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Intracellular pathogens can survive inside the macrophages to protect themselves from eradication by the innate immune system and conventional antibiotics, resulting in severe bacterial infections. In this work, an antibiotic-free nanocomplex (HA/GA-Fe@NO-DON), exhibiting macrophage-targeted synergistic gas therapy (nitric oxide, NO)/chemodynamic therapy/immunotherapy, was reported. HA/GA-Fe nanoparticles were synthesized by the strong coordination interactions among carboxyl groups of hyaluronic acid (HA), polyphenol groups of gallic acid (GA), and Fe(II) ions. The hydrophobic glutathione (GSH)-responsive NO donor (NO-DON) was encapsulated in HA/GA-Fe nanoparticles to form the final nanocomplexes (HA/GA-Fe@NO-DON). HA on the nanocomplexes guides the macrophage-specific uptake and intracellular accumulation. After the uptake, HA/GA-Fe@NO-DON nanocomplexes could not only generate highly toxic hydroxyl radicals (â¢OH) by the Fenton reaction and GSH depletion but also release NO when stimulated by intracellular GSH. Meanwhile, the nanocomplexes could trigger an efficient proinflammation immune response to reinforce the antibacterial activity. This work presents the development of antibiotic-free macrophage-targeted HA/GA-Fe@NO-DON nanocomplexes as an effective adjuvant nanomedicine with synergistic gas therapy/chemodynamic therapy/immunotherapy for eliminating intracellular bacterial infection.
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Long noncoding RNAs (lncRNAs) are strongly associated with glucose homeostasis, but their roles remain largely unknown. In this study, the potential role of lncRNA-Snhg3 in glucose metabolism was evaluated both in vitro and in vivo. Here, we found a positive relationship between Snhg3 and hepatic glycogenesis. Glucose tolerance improved in hepatocyte-specific Snhg3 knock-in (Snhg3-HKI) mice, while it worsened in hepatocyte-specific Snhg3 knockout (Snhg3-HKO) mice. Furthermore, hepatic glycogenesis had shown remarkable increase in Snhg3-HKI mice and reduction in Snhg3-HKO mice, respectively. Mechanistically, Snhg3 increased mRNA and protein expression levels of PPP1R3B through inducing chromatin remodeling and promoting the phosphorylation of protein kinase B. Collectively, these results suggested that lncRNA-Snhg3 plays a critical role in hepatic glycogenesis.
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Hígado , ARN Largo no Codificante , Animales , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Ratones , Hígado/metabolismo , Ratones Noqueados , Glucosa/metabolismo , Masculino , Hepatocitos/metabolismo , Ratones Endogámicos C57BL , Glucógeno Hepático/metabolismoRESUMEN
OBJECTIVE: To explore the clinical, imaging, and genetic characteristics of an adult patient with sporadic Neuronal intranuclear inclusion disease (NIID). METHODS: A patient who had visited the First People's Hospital of Chenzhou on August 6, 2023 was selected as the study subject. Results of clinical examination, neuroimaging, and genetic testing were retrospectively analyzed along with a literature review. The number of GGC trinucleotide repeats in the 5'-untranslated region of the NOTCH2NLC gene was determined by GC-PCR. RESULTS: The patient had presented with episodic encephalopathy, with enhanced magnetic resonance imaging showing enhancement features of the posterior cerebral cortex during the period of acute episode. Genetic testing revealed an increased number of GGC repeats (n = 97) in the 5'- untranslated region of the NOTCH2NLC gene, which confirmed the diagnosis of NIID. CONCLUSION: Clinical attention should be paid to the enhanced MRI findings of patients with adult-onset NIID, for whom posterior cortical enhancement may be characteristic manifestation during the acute phase of encephalopathy-like episode.
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Cuerpos de Inclusión Intranucleares , Enfermedades Neurodegenerativas , Humanos , Cuerpos de Inclusión Intranucleares/genética , Enfermedades Neurodegenerativas/genética , Imagen por Resonancia Magnética , Masculino , Pruebas Genéticas , Femenino , Persona de Mediana Edad , Receptor Notch2/genética , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , AdultoRESUMEN
Acute lung injury (ALI) including acute respiratory distress syndrome (ARDS) is a major complication and increase the mortality of patients with cardiac surgery. We previously found that the protein cargoes enriched in circulating extracellular vesicles (EVs) are closely associated with cardiopulmonary disease. We aimed to evaluate the implication of EVs on cardiac surgery-associated ALI/ARDS. The correlations between "oncoprotein-induced transcript 3 protein (OIT3) positive" circulating EVs and postoperative ARDS were assessed. The effects of OIT3-overexpressed EVs on the cardiopulmonary bypass (CPB) -induced ALI in vivo and inflammation of human bronchial epithelial cells (BEAS-2B) were detected. OIT3 enriched in circulating EVs is reduced after cardiac surgery with CPB, especially with postoperative ARDS. The "OIT3 positive" EVs negatively correlate with lung edema, hypoxemia and CPB time. The OIT3-overexpressed EVs can be absorbed by pulmonary epithelial cells and OIT3 transferred by EVs triggered K48- and K63-linked polyubiquitination to inactivate NOD-like receptor protein 3 (NLRP3) inflammasome, and restrains pro-inflammatory cytokines releasing and immune cells infiltration in lung tissues, contributing to the alleviation of CPB-induced ALI. Overexpression of OIT3 in human bronchial epithelial cells have similar results. OIT3 promotes the E3 ligase Cbl proto-oncogene B associated with NLRP3 to induce the ubiquitination of NLRP3. Immunofluorescence tests reveal that OIT3 is reduced in the generation from the liver sinusoids endothelial cells (LSECs) and secretion in liver-derived EVs after CPB. In conclusion, OIT3 enriched in EVs is a promising biomarker of postoperative ARDS and a therapeutic target for ALI after cardiac surgery.
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Optical frequency comb in the vacuum ultraviolet (VUV)/extreme ultraviolet (XUV) region has attracted a great deal of attention, as it provides coherent VUV/XUV radiation source with a rather narrow bandwidth, facilitating precise spectroscopic measurements in the short wavelength regime. In this study, we report on the linewidth measurement of a home-built VUV comb centered at 148 nm using direct frequency comb spectroscopy with NO2. The measurement reveals that the upper bound of our comb linewidth is less than 28 MHz. Fitting the whole trace with different repetition rates shows that the center frequency of the excitation is 2 021.25 ± 0.24 THz (â¼148.32 nm). Thus, we assigned this excitation to the transition from the 6a1 orbital (ν1'=0, ν2'=0) to the 3pσu orbital (ν1'=3, ν2'=8) in NO2. Our work demonstrates that VUV combs are potentially powerful tools for precision spectroscopic measurements in the short wavelength regime.
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Laser-arc hybrid additive manufacturing (LAHAM) holds substantial potential in industrial applications, yet ensuring dimensional accuracy remains a major challenge. Accurate prediction and effective control of the geometrical dimensions of the deposited layers are crucial for achieving this accuracy. The width and height of the deposited layers, key indicators of geometric dimensions, directly affect the forming precision. This study conducted experiments and in-depth analysis to investigate the influence of various process parameters on these dimensions and proposed a predictive model for accurate forecasting. It was found that the width of the deposited layers was positively correlated with laser power and arc current and negatively correlated with scanning speed, while the height was negatively correlated with laser power and scanning speed and positively with arc current. Quantitative analysis using the Taguchi method revealed that the arc current had the most significant impact on the dimensions of the deposited layers, followed by scanning speed, with laser power having the least effect. A predictive model based on extreme gradient boosting (XGBoost) was developed and optimized using particle swarm optimization (PSO) for tuning the number of leaf nodes, learning rate, and regularization coefficients, resulting in the PSO-XGBoost model. Compared to models enhanced with PSO-optimized support vector regression (SVR) and XGBoost, the PSO-XGBoost model exhibited higher accuracy, the smallest relative error, and performed better in terms of Mean Relative Error (MRE), Mean Square Error (MSE), and Coefficient of Determination R2 metrics. The high predictive accuracy and minimal error variability of the PSO-XGBoost model demonstrate its effectiveness in capturing the complex nonlinear relationships between process parameters and layer dimensions. This study provides valuable insights for controlling the geometric dimensions of the deposited layers in LAHAM.
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Perineural invasion (PNI), the neoplastic invasion of nerves, is an often overlooked pathological phenomenon in cervical cancer that is associated with poor clinical outcomes. The occurrence of PNI in cervical cancer patients has limited the promotion of Type C1 surgery. Preoperative prediction of the PNI can help identify suitable patients for Type C1 surgery. However, there is a lack of appropriate preoperative diagnostic methods for PNI, and its pathogenesis remains largely unknown. Here, we dissect the neural innervation of the cervix, analyze the molecular mechanisms underlying the occurrence of PNI, and explore suitable preoperative diagnostic methods for PNI to advance the identification and treatment of this ominous cancer phenotype.
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In this study, we examined how surface topography and particle medium interact to affect the tribological performance of rubber sliding interfaces, uncovering the mechanisms of particle lubrication under various conditions. We found that microtextured surfaces, created using a mold transfer method, modestly reduced the friction coefficient of rubber under both dry and lubricated states, primarily by altering the real contact area. Additionally, the presence of different microconvex textures on the surface topography significantly influenced rubber's tribological properties. Our three-dimensional morphological analysis revealed that microtextured rubber surfaces with higher Sa, Sku, and Sal and lower Str values consistently showed lower friction coefficients during sliding. The friction mechanism was attributed to the combined effects of the material properties, surface topography, and contact area. With the addition of a particle medium, the dry friction coefficient of the rubber interface decreased but exhibited an initial increase, followed by a decrease with increasing particle diameter. When particles were mixed with a water-based cutting fluid, the concentration, diameter, and wettability of the particles significantly impacted the tribological properties due to the synergistic effects of surface topography and particle lubrication. This work enhances our understanding of tribological control for viscoelastic materials through surface design, providing a theoretical basis for the tribological optimization of rubber surfaces.
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To gain a better understanding of the factors that contribute to anxiety among PhD students and the reasons for poor regulation in the current situation, this paper analyses the existing literature on anxiety among PhD students using Green's model. It also compares and evaluates various methods of regulating anxiety. The literature review to extract information on the causes and levels of anxiety, methods and outcomes of anxiety intervention and regulation, and to make comparisons. The study reveals that the phenomenon of PhD students' anxiety has intensified globally in recent years, especially after the end of the epidemic. PhD students experience anxiety due to research pressure, economic pressure, future development, and interpersonal pressure. The main influencing factors are currently the relationship with the supervisor, development prospects, social support, and peer comparison. Among the stress relief methods, the regulation of self-relaxation was found to have better effects on mild anxiety, such as positive thinking, meditation, yoga and physical exercise can be helpful for emotion release then help focus on problem solved. Whereas severe anxiety may require institutional and pharmacological support, also including using psychological therapy such as behavioral cognitive therapy and systematic desensitization methods. For university, competence to provide course-assisted guidance, such as writing groups, peer support, and time management, is also important. Academic communities should pay attention to the guidance on academic fairness. However, PhD students are often unaware of the resources available to them for coping with stress and may not take the initiative to seek psychological counseling or institutional assistance. Therefore, PhD students should receive support from various sources, be guided to express their thoughts, and receive additional education and academic assistance to manage stress. This will enhance their confidence and aid in improving their scientific research.
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Cardiac signaling pathways functionally important in the heart's response to exercise often protect the heart against pathological stress, potentially providing novel therapeutic targets. However, it is important to determine which of these pathways can be feasibly targeted in vivo. Transgenic overexpression of exercise-induced CITED4 has been shown to protect against adverse remodeling after ischemia/reperfusion injury (IRI). Here we investigated whether somatic gene transfer of CITED4 in a clinically relevant time frame could promote recovery after IRI. Cardiac CITED4 gene delivery via intravenous AAV9 injections in wild type mice led to an approximately 3-fold increase in cardiac CITED4 expression. After 4 weeks, CITED4-treated animals developed physiological cardiac hypertrophy without adverse remodeling. In IRI, delivery of AAV9-CITED4 after reperfusion resulted in a 6-fold increase in CITED4 expression 1 week after surgery, as well as decreased apoptosis, fibrosis, and inflammatory markers, culminating in a smaller scar and improved cardiac function 8 weeks after IRI, compared with control mice receiving AAV9-GFP. Somatic gene transfer of CITED4 induced a phenotype suggestive of physiological cardiac growth and mitigated adverse remodeling after ischemic injury. These studies support the feasibility of CITED4 gene therapy delivered in a clinically relevant time frame to mitigate adverse ventricular remodeling after ischemic injury.
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Long noncoding RNAs (lncRNAs) participate in regulating skeletal muscle development. However, little is known about their role in regulating chicken myogenesis. In this study, we identified a novel lncRNA, lncMPD2, through transcriptome sequencing of chicken myoblasts at different developmental stages. Functionally, gain- and loss-of-function experiments showed that lncMPD2 inhibited myoblast proliferation and differentiation. Mechanistically, lncMPD2 directly bound to miR-34a-5p, and miR-34a-5p promoted myoblasts proliferation and differentiation and inhibited the mRNA and protein expression of its target gene THBS1. THBS1 inhibited myoblast proliferation and differentiation in vitro and delayed muscle regeneration in vivo. Furthermore, rescue experiments showed that lncMPD2 counteracted the inhibitory effects of miR-34a-5p on THBS1 and myogenesis-related gene mRNA and protein expression. In conclusion, lncMPD2 regulates the miR-34a-5p/THBS1 axis to inhibit the proliferation and differentiation of myoblasts and skeletal muscle regeneration. This study provides more insight into the molecular regulatory network of skeletal muscle development, identifying novel potential biomarkers for improving chicken quality and increasing chicken yield. In addition, this study provides a potential goal for breeding strategies that minimize muscle damage in chickens.
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Diferenciación Celular , Proliferación Celular , Pollos , MicroARNs , Desarrollo de Músculos , Mioblastos , ARN Largo no Codificante , Desarrollo de Músculos/genética , ARN Largo no Codificante/genética , Animales , MicroARNs/genética , Diferenciación Celular/genética , Mioblastos/metabolismo , Mioblastos/citología , Músculo Esquelético/metabolismo , Regeneración/genéticaRESUMEN
Alpha-foetoprotein (AFP) is taken as a diagnostic tumor marker for the screening and diagnosis of cancer. Nucleic acid-based isothermal amplification strategies are emerging as a potential technology in early screening and clinical diagnosis of AFP. The leakages between hairpins dramatically increase the background and reduce the sensitivity. Thus, it is necessary to develop some strategies to reduce the leakage for isothermal amplification strategies. A DNAzyme-locked leakless enzyme-free amplification system was developed for AFP detection in liver cancer and breast cancer. AFP could open the apt-hairpin and initiate the catalytic hairpin assembly (CHA) reaction to produce a Y-shaped duplex. Two tails of a Y-shaped duplex cleaved the two kinds of leakless hairpins. Then, the third tail of the Y-shaped duplex catalyzed the second CHA between the cleaved leakless hairpins to recover the fluorescent intensity. The limit of detection reached 5 fg/mL by the two levels of signal amplifications. Importantly, the leakless hairpin design effectively reduced leakage between hairpins and weakened the background. In addition, it also showed a great promising potential for AFP detection in early screening and clinical diagnosis.
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Neoplasias de la Mama , ADN Catalítico , Límite de Detección , Neoplasias Hepáticas , Técnicas de Amplificación de Ácido Nucleico , alfa-Fetoproteínas , ADN Catalítico/química , ADN Catalítico/metabolismo , alfa-Fetoproteínas/análisis , Humanos , Técnicas de Amplificación de Ácido Nucleico/métodos , Neoplasias de la Mama/diagnóstico , Neoplasias Hepáticas/diagnóstico , Femenino , Biomarcadores de Tumor/sangre , Técnicas Biosensibles/métodosRESUMEN
The frequent occurrence of viral infections poses a serious threat to human life. Identifying effective antiviral components is urgent. In China, pearls have been important traditional medicinal ingredients since ancient times, exhibiting various therapeutic properties, including detoxification properties. In this study, a peptide, KKCH, which acts against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was derived from Pinctada fucata pearls. Molecular docking showed that it bound to the same pocket of the SARS-CoV-2 S protein and cell surface target angiotensin-converting enzyme II (ACE2). The function of KKCH was analyzed through surface plasmon resonance (SPR), Enzyme-Linked Immunosorbent Assays, immunofluorescence, and simulation methods using the SARS-CoV-2 pseudovirus and live virus. The results showed that KKCH had a good affinity for ACE2 (KD = 6.24 × 10-7 M) and could inhibit the binding of the S1 protein to ACE2 via competitive binding. As a natural peptide, KKCH inhibited the binding of the SARS-CoV-2 S1 protein to the surface of human BEAS-2B and HEK293T cells. Moreover, viral experiments confirmed the antiviral activity of KKCH against both the SARS-CoV-2 spike pseudovirus and SARS-CoV-2 live virus, with half-maximal inhibitory concentration (IC50) values of 398.1 µM and 462.4 µM, respectively. This study provides new insights and potential avenues for the prevention and treatment of SARS-CoV-2 infections.
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Enzima Convertidora de Angiotensina 2 , Antivirales , Tratamiento Farmacológico de COVID-19 , Péptidos , Pinctada , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Animales , Humanos , Enzima Convertidora de Angiotensina 2/metabolismo , Enzima Convertidora de Angiotensina 2/química , Antivirales/farmacología , Antivirales/química , COVID-19/virología , Células HEK293 , Simulación del Acoplamiento Molecular , Péptidos/farmacología , Péptidos/química , Unión Proteica , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/metabolismo , Glicoproteína de la Espiga del Coronavirus/metabolismo , Glicoproteína de la Espiga del Coronavirus/químicaRESUMEN
BACKGROUND: Toxoplasma gondii is an opportunistic pathogenic protozoan that infects all warm-blooded animals, including humans, and causes zoonotic toxoplasmosis. The bradyzoite antigen 1 (BAG1), known as heat-shock protein (HSP)30, is a specific antigen expressed during the early stage of T. gondii tachyzoite-bradyzoite conversion. METHODS: A bag1 gene knockout strain based on the T. gondii type II ME49 was constructed and designated as ME49Δbag1. The invasion, proliferation, and cyst formation efficiency in the cell model and survival in the mouse model were compared between the ME49 and ME49Δbag1 strains after infection. Quantitative polymerase chain reaction (qPCR) was used to detect the transcriptional level of important genes, and western-blot was used to detect protein levels. RESULTS: ME49Δbag1 displayed significantly inhibited cyst formation, although it was not completely blocked. During early differentiation induced by alkaline and starvation conditions in vitro, the proliferation of ME49Δbag1 was significantly accelerated relative to the ME49 strain. Meanwhile, the transcription of the HSP family and bradyzoite formation deficient 1 (bfd1) were significantly enhanced. The observed upregulation suggests a compensatory mechanism to counterbalance the impaired stress responses of T. gondii following bag1 knockout. On the other hand, the elevated transcription levels of several HSP family members, including HSP20, HSP21, HSP40, HSP60, HSP70, and HSP90, along with BFD1, implied the involvement of alternative regulatory factors in bradyzoite differentiation aside from BAG1. CONCLUSIONS: The data suggested that when bag1 was absent, the stress response of T. gondii was partially compensated by increased levels of other HSPs, resulting in the formation of fewer cysts. This highlighted a complex regulatory network beyond BAG1 influencing the parasite's transformation into bradyzoites, emphasizing the vital compensatory function of HSPs in the T. gondii life cycle adaptation.
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Proteínas de Choque Térmico , Proteínas Protozoarias , Toxoplasma , Toxoplasma/genética , Toxoplasma/metabolismo , Animales , Ratones , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Técnicas de Inactivación de Genes , Toxoplasmosis Animal/parasitología , Femenino , Humanos , Proteínas de Unión al ADN , Factores de TranscripciónRESUMEN
Breast muscle growth rate and intramuscular fat (IMF) content show apparent differences between fast-growing broilers and slow-growing indigenous chickens. However, the underlying genetic basis of these phenotypic characteristics remains elusive. In this study, we investigate the dynamic alterations of three-dimensional genome architecture and chromatin accessibility in breast muscle across four key developmental stages from embryo to starter chick in Arbor Acres (AA) broilers and Yufen (YF) indigenous chickens. The limited breed-specifically up-regulated genes (Bup-DEGs) are embedded in breed-specific A compartment, while a majority of the Bup-DEGs involving myogenesis and adipogenesis are regulated by the breed-specific TAD reprogramming. Chromatin loops allow distal accessible regions to interact with myogenic genes, and those loops share an extremely low similarity between chicken with different growth rate. Moreover, AA-specific loop interactions promote the expression of 40 Bup-DEGs, such as IGF1, which contributes to myofiber hypertrophy. YF-specific loop interactions or distal accessible regions lead to increased expression of 5 Bup-DEGs, including PIGO, PEMT, DHCR7, TMEM38B, and DHDH, which contribute to IMF deposition. These results help elucidate the regulation of breast muscle growth and IMF deposition in chickens.
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Pollos , Cromatina , Desarrollo de Músculos , Fenotipo , Animales , Pollos/genética , Pollos/crecimiento & desarrollo , Cromatina/metabolismo , Cromatina/genética , Desarrollo de Músculos/genética , Músculo Esquelético/metabolismo , Músculo Esquelético/crecimiento & desarrollo , Músculos Pectorales/metabolismo , Músculos Pectorales/crecimiento & desarrollo , Embrión de Pollo , Regulación del Desarrollo de la Expresión GénicaRESUMEN
Despite limited research on refractory and/or endocrine therapy failure in elderly metastatic breast cancer (MBC) patients, a prior study showed that low-dose oral cyclophosphamide (CY) can improve the overall survival rate of MBC patients, possibly through the immunoregulation of regulatory T cells (Tregs). We preliminarily investigated the combination of endocrine therapy (ET) with oral low-dose CY as salvage therapy in elderly patients via peripheral blood regulatory T-cell analyses. In addition, we evaluated the associations of tumor tertiary lymphoid structures (TLSs) with therapeutic outcomes. HR+/HER2- advanced breast cancer patients who received low-dose CY combined with ET or ET only from April 2015 to August 2021 were enrolled in this retrospective study. The primary outcome was the clinical control rate (CCR), and the secondary outcome was progression-free survival (PFS). Circulating T lymphocyte subpopulations represented by Tregs were monitored during treatment by flow cytometry methods. TLSs wereconfirmed by hematoxylin-eosin staining of pretreatment specimens, and CD3, CD4, and Foxp3 were detected using Opal multicolor immunofluorescence. A total of 85 patients who received CY + ET and 50 patients who received ET only were enrolled, the percentage of patients who received CCR was 73% (62/85) vs. 70% (45/50), and the objective response rate (ORR) was 28% (24/85) vs. 24% (12/50). No deaths occurred during the study period. The mean PFS time was 13 vs. 11 months (P = 0.03). In the CY + ET group, decreases in CD4+/CD25+/Foxp3+ T cells (P < 0.001) were favorable for both clinical control and prolonged PFS (P < 0.001). Compared with patients without TLSs, those with TLSs were more likely to have better clinical control and PFS (mean time = 6 months), and a greater number of Treg cells during TLS pretreatment correlated with longer PFS (P = 0.043). Oral low-dose CY combined with standard ET exerts immunological effects by decreasing Treg levels to achieve improved clinical responses. Moreover, patients with TLSs might benefit more from such therapy than those without TLSs, and a high Treg cell count in TLSs before treatment predicts better therapeutic efficacy.
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Neoplasias de la Mama , Ciclofosfamida , Linfocitos T Reguladores , Humanos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/uso terapéutico , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/efectos de los fármacos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/mortalidad , Anciano , Estudios Retrospectivos , Administración Oral , Persona de Mediana Edad , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Metástasis de la Neoplasia , Resultado del TratamientoRESUMEN
Fiber-bundle-based endoscopy, with its ultrathin probe and micrometer-level resolution, has become a widely adopted imaging modality for in vivo imaging. However, the fiber bundles introduce a significant honeycomb effect, primarily due to the multi-core structure and crosstalk of adjacent fiber cores, which superposes the honeycomb pattern image on the original image. To tackle this issue, we propose an iterative-free spatial pixel shifting (SPS) algorithm, designed to suppress the honeycomb effect and enhance real-time imaging performance. The process involves the creation of three additional sub-images by shifting the original image by one pixel at 0, 45, and 90 degree angles. These four sub-images are then used to compute differential maps in the x and y directions. By performing spiral integration on these differential maps, we reconstruct a honeycomb-free image with improved details. Our simulations and experimental results, conducted on a self-built fiber bundle-based endoscopy system, demonstrate the effectiveness of the SPS algorithm. SPS significantly improves the image quality of reflective objects and unlabeled transparent scattered objects, laying a solid foundation for biomedical endoscopic applications.
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OBJECTIVE: To investigate the risk of developing diabetes and ketoacidosis in clinical patients with immune checkpoint inhibitors (ICIs). METHODS: We looked in the FDA Adverse Event Reporting System for reports of ICIs-associated diabetes mellitus (DM) and ketoacidosis between January 2004 and March 2022. We explored the signals using fourfold table-based proportional imbalance algorithms. Patient characteristics, country distribution, and outcomes of adverse reactions were described. Kruskal-Wallis test was used to compare the time of onset and prognosis of adverse reactions. RESULTS: A total of 2110 reports of ICIs-related DM were included in the study. The largest number of reports was from Japan (752, 35.64%), followed by the United States and France (624, 29.57%; 183, 8.67%). Seven drugs detected signals of DM and ketoacidosis according to 4 proportional imbalance algorithms: nivolumab, pembrolizumab, cemiplimab, dostarlimab, atezolizumab, avelumab, and durvalumab. Diabetes and ketoacidosis generally occurred early in the course of ICIs treatment, the median time to event onset was 144.5 (interquartile range 27-199) days. ICIs-related diabetes and ketoacidosis events resulted in 934 major medical events (44.3%), 524 hospitalizations (24.8%), 60 life-threatening events (2.8%), 42 deaths (2.0%), and 39 disability events (1.8%). CONCLUSION: The study reveals the risk and characteristics of diabetes and ketoacidosis associated with ICIs, which may provide evidence for postmarketing evaluation. Careful consideration should be given to the possibility of an increased risk of diabetes and ketoacidosis after using ICIs, and careful monitoring for diabetes and ketoacidosis is recommended.
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Small extracellular vesicles were shown to have similar functional roles to their parent cells without the defect of potential tumorigenicity, which made them a great candidate for regenerative medicine. The last twenty years have witnessed the rapid development of research on small extracellular vesicles. In this paper, we employed a scientometric synthesis method to conduct a retrospective analysis of small extracellular vesicles in the field of bone-related diseases. The overall background analysis consisted the visualization of the countries, institutions, journals, and authors involved in research. The current status of the research direction and future trends were presented through the analysis of references and keywords, which showed that engineering strategies, mesenchymal stem cell derived exosomes, and cartilage damage were the most concerning topics, and scaffold, osteoarthritis, platelet-rich plasma, and senescence were the future trends. We also discussed the current problems and challenges in practical applications, including the in-sight mechanisms, the building of relevant animal models, and the problems in clinical trials. By using CiteSpace, VOSviewer, and Bibliometrix, the presented data avoided subjective selectivity and tendency well, which made the conclusion more reliable and comprehensive. We hope that the findings can provide new perspectives for researchers to understand the evolution of this field over time and to search for novel research directions.