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Surgical resection, the mainstay for melanoma treatment, faces challenges due to high tumor recurrence rates and complex postoperative wound healing. Chronic inflammation from residual disease and the risk of secondary infections impede healing. We introduce an innovative, injectable hydrogel system that integrates a multifaceted therapeutic approach. The hydrogel, crosslinked by calcium ions with sodium alginate, encapsulates a blood clot rich in dendritic cells (DCs) chemoattractants and melanoma cell-derived nanovesicles (NVs), functioning as a potent immunostimulant. This in situ recruitment strategy overcomes the limitations of subcutaneous tumor vaccine injections and more effectively achieves antitumor immunity. Additionally, the hydrogel incorporates Chlorella extracts, enhancing its antimicrobial properties to prevent wound infections and promote healing. One of the key findings of our research is the dual functionality of Chlorella extracts; they not only expedite the healing process of infected wounds but also increase the hydrogel's ability to stimulate an antitumor immune response. Given the patient-specific nature of the blood clot and NVs, our hydrogel system offers customizable solutions for individual postoperative requirements. This personalized approach is highlighted by our study, which demonstrates the synergistic impact of the composite hydrogel on preventing melanoma recurrence and hastening wound healing, potentially transforming postsurgical melanoma management.

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Células Dendríticas , Hidrogeles , Melanoma , Cicatrización de Heridas , Hidrogeles/química , Animales , Células Dendríticas/inmunología , Células Dendríticas/efectos de los fármacos , Melanoma/terapia , Melanoma/patología , Cicatrización de Heridas/efectos de los fármacos , Humanos , Recurrencia Local de Neoplasia/prevención & control , Ratones Endogámicos C57BL , Antiinfecciosos/uso terapéutico , Antiinfecciosos/farmacología , Ratones , Línea Celular Tumoral , Femenino

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ETHNOPHARMACOLOGICAL RELEVANCE: Huachansu Capsule (HCSc) is a simple enteric-coated capsule refined from the skin of the dried toad, a traditional medicinal herb. It has been used clinically for many years to treat a variety of malignant tumors with remarkable efficacy. To date, a number of main components of HCSc have been reported to be cardiotoxic, but the specific mechanism of cardiotoxicity is still unknown. AIM OF THE STUDY: The aim of this study was to elucidate the possible cardiotoxic symptoms caused by high-doses of HCSc and to further reveal the complex mechanisms by which it causes cardiotoxicity. MATERIALS AND METHODS: UPLC-Q-Exactive Orbitrap MS and network toxicology were used to identify and predict the potential toxic components, related signaling pathways. Then, we used acute and sub-acute toxicity experiments to reveal the apparent phenomenon of HCSc-induced cardiotoxicity. Finally, we combined transcriptomics and metabolomics to elucidate the potential mechanism of action, and verified the putative mechanism by molecular docking, RT-qPCR, and Western blot. RESULTS: We found 8 toad bufadienolides components may be induced cardiac toxicity HCSc main toxic components. Through toxicity experiments, we found that high dose of HCSc could increase a variety of blood routine indexes, five cardiac enzymes, heart failure indexes (BNP), troponin (cTnI and cTnT), heart rate and the degree of heart tissue damage, while low-dose of HCSc had no such changes. In addition, by molecular docking, found that 8 kinds of main toxic components and cAMP, AMPK, IL1ß, mTOR all can be a very good combination, especially in the cAMP. Meanwhile, RT-qPCR and Western blot results showed that HCSc could induce cardiotoxicity by regulating a variety of heart-related differential genes and activating the cAMP signaling pathway. CONCLUSIONS: In this study, network toxicology, transcriptomics and metabolomics were used to elucidate the complex mechanism of possible cardiotoxicity induced by high-dose HCSc. Animal experiments, molecular docking, Western blot and RT-qPCR experiments were also used to verify the above mechanism. These findings will inform further mechanistic studies and provide theoretical support for its safe clinical application.

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Cardiotoxicidad , Metabolómica , Transcriptoma , Animales , Metabolómica/métodos , Masculino , Transcriptoma/efectos de los fármacos , Ratas , Bufanólidos/toxicidad , Simulación del Acoplamiento Molecular , Ratas Sprague-Dawley , Farmacología en Red , Cápsulas , Transducción de Señal/efectos de los fármacos , Perfilación de la Expresión Génica/métodos , Anuros

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BACKGROUND: Although progress has been made in accurate diagnosis and targeted treatments, breast cancer (BC) patients with metastasis still present a grim prognosis. With the continuous emergence and development of new personalized and precision medicine targeting specific tumor biomarkers, there is an urgent need to find new metastatic and prognostic biomarkers for BC patients. METHODS: We were dedicated to identifying genes linked to metastasis and prognosis in breast cancer through a combination of in silico analysis and experimental validation. RESULTS: A total of 25 overlap differentially expressed genes were identified. Ten hub genes (namely MRPL13, CTR9, TCEB1, RPLP0, TIMM8B, METTL1, GOLT1B, PLK2, PARL and MANBA) were identified and confirmed. MRPL13, TCEB1 and GOLT1B were shown to be associated with the worse overall survival (OS) and were optionally chosen for further verification by western blot. Only MRPL13 was found associated with cell invasion, and the expression of MRPL13 in metastatic BC was significantly higher than in primary BC. CONCLUSION: We proposed MRPL13 could be a potential novel biomarker for the metastasis and prognosis of breast cancer.

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Biomarcadores de Tumor , Neoplasias de la Mama , Simulación por Computador , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Femenino , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Pronóstico , Regulación Neoplásica de la Expresión Génica , Metástasis de la Neoplasia , Perfilación de la Expresión Génica/métodos , Línea Celular Tumoral , Persona de Mediana Edad

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VOCs (Volatile organic compounds) exert a vital role in ozone and secondary organic aerosol production, necessitating investigations into their concentration, chemical characteristics, and source apportionment for the effective implementation of measures aimed at preventing and controlling atmospheric pollution. From July to October 2020, online monitoring was conducted in the main urban area of Shijiazhuang to collect data on VOCs and analyze their concentrations and reactivity. Additionally, the PMF (positive matrix factorization) method was utilized to identify the VOCs sources. Results indicated that the TVOCs (total VOCs) concentration was (96.7 ± 63.4 µg/m3), with alkanes exhibiting the highest concentration of (36.1 ± 26.4 µg/m3), followed by OVOCs (16.4 ± 14.4 µg/m3). The key active components were alkenes and aromatics, among which xylene, propylene, toluene, propionaldehyde, acetaldehyde, ethylene, and styrene played crucial roles as reactive species. The sources derived from PMF analysis encompassed vehicle emissions, solvent and coating sources, combustion sources, industrial emissions sources, as well as plant sources, the contribution of which were 37.80%, 27.93%, 16.57%, 15.24%, and 2.46%, respectively. Hence, reducing vehicular exhaust emissions and encouraging neighboring industries to adopt low-volatile organic solvents and coatings should be prioritized to mitigate VOCs levels.

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Contaminantes Atmosféricos , Monitoreo del Ambiente , Compuestos Orgánicos Volátiles , Compuestos Orgánicos Volátiles/análisis , Contaminantes Atmosféricos/análisis , China , Emisiones de Vehículos/análisis , Ciudades , Contaminación del Aire/estadística & datos numéricos , Contaminación del Aire/prevención & control , Contaminación del Aire/análisis

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In this work, an ingenious dual-circle DNA walker (DCDW) with pretty fast walking speed and high amplification efficiency was developed for rapid and ultrasensitive electrochemical detection of microRNA-221 (miRNA-221) related to liver cancer, combined with the toehold-mediated strand-displacement reactions (TSDRs). Impressively, compared with the traditional DNA walker, the DCDW with unique double-stranded interlocked DNA nanostructure not only possesses higher stability, flexibility, and anti-entanglement ability, but also enables more functional domain in a smaller area, thereby enhancing the local concentration, which can greatly improve the working efficiency. As a validation, the electrochemical biosensor realized rapid and ultrasensitive detection of miRNA-221 with a reaction time of 15 min and detection limit down to 1.9 aM, and had been applied in MHCC97L and HeLa cancer cell lysates, thus providing an innovative insight to design intelligent functional interlocked DNA walkers for ultimate application in the construction of biosensing platform and miRNA detection in biological sample.

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INTRODUCTION: Brain organoids are believed to be able to regenerate impaired neural circuits and reinstate brain functionality. The neuronal activity of organoids is considered a crucial factor for restoring host function after implantation. However, the optimal stage of brain organoid post-transplantation has not yet been established. External electrical signal plays a crucial role in the physiology and development of a majority of human tissues. However, whether electrical input modulates the development of brain organoids, making them ideal transplant donors, is elusive. METHODS: Bioelectricity was input into cortical organoids by electrical stimulation (ES) with a multi-electrode array (MEA) to obtain a better-transplanted candidate with better viability and maturity, realizing structural-functional integration with the host brain. RESULTS: We found that electrical stimulation facilitated the differentiation and maturation of organoids, displaying well-defined cortical plates and robust functional electrophysiology, which was probably mediated via the pathway of calcium-calmodulin (CaM) dependent protein kinase II (CAMK II)-protein kinase A (PKA)-cyclic-AMP response binding protein (pCREB). The ES-pretreated D40 organoids displayed superior cell viability and higher cell maturity, and were selected to transplant into the damaged primary sensory cortex (S1) of host. The enhanced maturation was exhibited within grafts after transplantation, including synapses and complex functional activities. Moreover, structural-functional integration between grafts and host was observed, conducive to strengthening functional connectivity and restoring the function of the host injury. CONCLUSION: Our findings supported that electrical stimulation could promote the development of cortical organoids. ES-pretreated organoids were better transplanted donors for strengthening connectivity between grafts and host. Our work presented a new physical approach to regulating organoids, potentially providing a novel translational strategy for functional recovery after brain injury. In the future, the development of 3D flexible electrodes is anticipated to overcome the drawbacks of 2D planar MEA, promisingly achieving multimodal stimulation and long-term recordings of brain organoids.

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Postoperative cognitive dysfunction (POCD) is a prevalent neurological complication that can impair learning and memory for days, months, or even years after anesthesia/surgery. POCD is strongly associated with an altered composition of the gut microbiota (dysbiosis), but the accompanying metabolic changes and their role in gut-brain communication and POCD pathogenesis remain unclear. Here, the present study reports that anesthesia/surgery in aged mice induces elevated intestinal indoleamine 2,3-dioxygenase (IDO) activity, which shiftes intestinal tryptophan (TRP) metabolism toward more IDO-catalyzed kynurenine (KYN) and less gut bacteria-catabolized indoleacetic acid (IAA). Both anesthesia/surgery and intraperitoneal KYN administration induce increased KYN levels that correlate with impaired spatial learning and memory, whereas dietary IAA supplementation attenuates the anesthesia/surgery-induced cognitive impairment. Mechanistically, anesthesia/surgery increases the proportion of interferon-γ (IFN-γ)-producing group 1 innate lymphoid cells (ILC1) in the small intestine lamina propria and elevates intestinal IDO expression and activity, as indicated by the higher ratio of KYN to TRP. The IDO inhibitor 1-MT and antibodies targeting IFN-γ or ILCs mitigate anesthesia/surgery-induced cognitive dysfunction, suggesting that intestinal ILC1 expansion and the ensuing IFN-γ-induced IDO upregulation may be the primary pathway mediating the shift to the KYN pathway in POCD. The ILC1-KYN pathway in the intestine could be a promising therapeutic target for POCD.

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Synchronous fluorescence spectroscopy (SFS) technology exhibits significant advantages in identifying target fluorescence signals within complex mixtures of multiple fluorescent compounds, owing to their closely overlapping spectra. In this study, a SFS method is reported for the first time for the direct analysis of leonurine in drugs containing concurrent natural products. By setting the wavelength interval (Δλ) to 30 nm, the characteristic emission peak of leonurine is observed at 307 nm, which increases proportionally with the concentration of leonurine without spectral overlap from other fluorescent species. The limit of detection (LOD) is estimated to be about 0.22 µM, and a low linear range of 0 to 20 µM is obtained. The common cations, anions and concomitant compounds display no interference with the SFS signal of leonurine, supporting the practical application of this method. Thus, we successfully applied this SFS method to detect leonurine in several real samples (leonurus granules, capsules, ointment and pills), in which the good relative standard deviation (RSD) values (0.04-4.24%) and recoveries (95.63-113%) were obtained. As a result, this work provides an efficient and convenient method to identify the target active compound from natural products without complex pre-treatment to diminish the fluorescent chaos that might be serving a potential role in the study of traditional Chinese medicine.

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MOTIVATION: Genes function in networks are typically correlated due to their functional connectivity. Variable selection methods have been developed to select important genes associated with a trait while incorporating network graphical information. However, no method has been proposed to quantify the uncertainty of individual genes under such settings. RESULTS: In this paper, we construct confidence intervals and provide p-values for parameters of a high-dimensional linear model incorporating graphical structures where the number of variables p diverges with the number of observations. For combining the graphical information, we propose a graph-constrained desparsified LASSO (GCDL) estimator, which reduces dramatically the influence of high correlation of predictors and enjoys the advantage of faster computation and higher accuracy compared with the desparsified LASSO. Theoretical results show that the GCDL estimator achieves asymptotic normality. The asymptotic property of the uniform convergence is established, with which an explicit expression of the uniform confidence interval can be derived. Extensive numerical results indicate that the GCDL estimator and its (uniform) confidence interval performs well even when predictors are highly correlated. AVAILABILITY AND IMPLEMENTATION: An R package implementing the proposed method is available at https://github.com/XiaoZhangryy/gcdl. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

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Pneumonia involves complex immunological and pathological processes leading to pulmonary dysfunction, which can be life-threatening yet lacks effective specialized medications. Natural enzymes can be used as biological agents for the treatment of oxidative stress-related diseases, but limiting to catalytic and environmental stability as well as high cost. Herein, an artificial enzyme, gold nanoclusters (Au NCs) with excellent stability, bioactivity, and renal clearance can be used as the next-generation biological agents for acute lung injury (ALI) and allergic lung disease (ALD). The Au25 clusters can mimic catalase (CAT) and glutathione peroxidase (GPx), and the Km of Au24Er1 with H2O2 reaches 1.28 mM, about 22 times higher than natural CAT (≈28.8 mM). The clusters inhibit the oxidative stress in the mitochondria and promote the synthesis of adenosine triphosphate (ATP). The molecular mechanism shows that the TLR4/MyD88/NF-κB pathway and M1 macrophage-mediated inflammatory response are suppressed in ALI and the Th1/Th2 imbalance in ovalbumin (OVA)-induced ALD is rescued. Further, the clusters can notably improve lung function in both ALI and ALD models which paves the way for immunomodulation and intervention for lung injury and can be used as a substitute for natural enzymes and potential biopharmaceuticals in the treatment of various types of pneumonia.

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OBJECTIVES: This study aimed to compare the accuracy of digital complete-arch implant impressions with prefabricated aids using three intraoral scanners (IOSs) and explore the correlation between virtual deviation measurement and physical framework misfit. MATERIALS AND METHODS: Four edentulous maxillary master models with four and six parallel and angular implants were fabricated and scanned by a laboratory scanner as reference scans. Ten scans of each master model were acquired using three IOSs (IOS-T, IOS-M, and IOS-A) with and without prefabricated aids. Trueness and precision of root mean square (RMS) errors were measured. Ten aluminum alloy frameworks were fabricated, and the misfit was measured with a micro-computed tomography scan with one screw tightened. RESULTS: Trueness and precision showed significant improvement when prefabricated aids were used for all three IOSs (p < 0.010). Median (interquartile range) RMS errors of trueness reduced from 67.5 (30.4) to 61.8 (30.3) µm, from 100.6 (35.4) to 45.9 (15.1) µm, and from 52.7 (33.2) to 41.1 (22.5) µm for scanner IOS-T, IOS-M, and IOS-A, respectively (p < 0.010). The precision of IOS-A and IOS-M was significantly better than IOS-T when using prefabricated aid (p < 0.001). RMS errors and the maximum marginal misfit of the framework were significantly correlated (p < 0.001, R2 = 0.845). CONCLUSIONS: With the prefabricated aids, the accuracy of IOSs enhanced significantly in digital complete-arch implant impressions. Three IOSs showed different levels of improvement in accuracy. Virtual RMS errors <62.2 µm could be the clinically acceptable threshold (150 µm) for framework passive fit.

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We analyzed age structure and dynamics, spatial distribution patterns, and reproductive capabilities of four Rosa persica populations in Xinjiang, to evaluate the survival status of the species and explore the reasons behind its endangerment. The results showed that the populations had fewer individuals in the youngest (Ⅰ) and oldest (Ⅵ-Ⅷ) age classes, with a predominance of middle-aged individuals, resulting in an irregular pyramid-shaped distribution, described as "high in the middle, low on both sides". The populations were generally growing, but were susceptible to external environmental disturbances (Vpi'＞0, Pmax＞0). The mortality rate (qx) and vanish rate (Kx) peaked at age Ⅴ, leading to a sharp decline in plant abundance. The life expectancy (ex) decreased progressively with the increases of age class, reaching its lowest at age Ⅷ, which indicated minimal vitality at this stage. A time sequence analysis predicted a future dominance of individuals at age Ⅴ-Ⅷ, suggesting an aging trend. Spatially, the four populations were predominantly clumped, with the intensity of clumping ranked from highest to lowest as P4, P3, P1, and P2. P3 and P4 exhibited better reproductive capabilities than P1 and P2. There was a significant positive correlation between hundred-fruit weight and plant height and crown width, and between total seed number and crown width and hundred-fruit weight.

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Dinámica Poblacional , Rosa , Rosa/crecimiento & desarrollo , China , Frutas/crecimiento & desarrollo , Reproducción , Ecosistema , Conservación de los Recursos Naturales

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To date, it remains challenging to precisely and efficiently construct structurally intriguing polycarbocycles with densely packed stereocenters in organic synthesis. Niduterpenoid B, a naturally occurring ERα inhibitor, exemplifies this complexity with its intricate polycyclic network comprising 5 cyclopentane and 1 cyclopropane rings, featuring 13 contiguous stereocenters, including 4 all-carbon quaternary centers. In this work, we describe the first total synthesis of niduterpenoid B using a structural reorganization strategy. Key features include the following: (1) an efficient methoxy-controlled cascade reaction that precisely forges a highly functionalized tetraquinane (A-D rings) bearing sterically hindered contiguous quaternary stereocenters; (2) a rhodium-catalyzed [1 + 2] cycloaddition that facilitates the construction of a strained 3/5 bicycle (E-F rings) angularly fused with ring D.

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BACKGROUND: In June 2019, a patient presented with persistent fever and multiple organ dysfunction after a tick bite at a wetland park in Inner Mongolia. Next-generation sequencing in this patient revealed an infection with a previously unknown orthonairovirus, which we designated Wetland virus (WELV). METHODS: We conducted active hospital-based surveillance to determine the prevalence of WELV infection among febrile patients with a history of tick bites. Epidemiologic investigation was performed. The virus was isolated, and its infectivity and pathogenicity were investigated in animal models. RESULTS: WELV is a member of the orthonairovirus genus in the Nairoviridae family and is most closely related to the tickborne Hazara orthonairovirus genogroup. Acute WELV infection was identified in 17 patients from Inner Mongolia, Heilongjiang, Jilin, and Liaoning, China, by means of reverse-transcriptase-polymerase-chain-reaction assay. These patients presented with nonspecific symptoms, including fever, dizziness, headache, malaise, myalgia, arthritis, and back pain and less frequently with petechiae and localized lymphadenopathy. One patient had neurologic symptoms. Common laboratory findings were leukopenia, thrombocytopenia, and elevated d-dimer and lactate dehydrogenase levels. Serologic assessment of convalescent-stage samples obtained from 8 patients showed WELV-specific antibody titers that were 4 times as high as those in acute-phase samples. WELV RNA was detected in five tick species and in sheep, horses, pigs, and Transbaikal zokors (Myospalax psilurus) sampled in northeastern China. The virus that was isolated from the index patient and ticks showed cytopathic effects in human umbilical-vein endothelial cells. Intraperitoneal injection of the virus resulted in lethal infections in BALB/c, C57BL/6, and Kunming mice. The Haemaphysalis concinna tick is a possible vector that can transovarially transmit WELV. CONCLUSIONS: A newly discovered orthonairovirus was identified and shown to be associated with human febrile illnesses in northeastern China. (Funded by the National Natural Science Foundation of China and the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences.).

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Fiebre , Nairovirus , Mordeduras de Garrapatas , Adulto , Anciano , Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Adulto Joven , Anticuerpos Antivirales/sangre , China/epidemiología , Fiebre/diagnóstico , Fiebre/epidemiología , Fiebre/virología , Nairovirus/genética , Nairovirus/aislamiento & purificación , Nairovirus/patogenicidad , Filogenia , Mordeduras de Garrapatas/complicaciones , Mordeduras de Garrapatas/virología , Prevalencia , Modelos Animales de Enfermedad , Ovinos , Caballos , Porcinos , Lactante , Preescolar , Niño , Adolescente , Anciano de 80 o más Años

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Background: Hyperuricemia elevates gut permeability; however, the risk of its influence on the compromised intestinal barrier is poorly understood. Aims: This study was carried out, aiming to elucidate the orchestrators and disruptors of intestinal barrier in hyperuricemia. Methods: A mouse model of hyperuricemia was induced by administering adenine and oteracil potassium to mice. Allopurinol was used to decrease uric acid level, and antibiotics were administered to mice to deplete gut microbiota. Intestinal permeability was assessed using FITC-labeled dextran. Changes in gut microbial community were analyzed through 16S rRNA sequencing. IL-1ß and TNF-α levels were quantified using ELISA. The expression of tight junction protein genes, TLR4, p65 and IL-1ß, was determined with Q-PCR and Western blotting. Results: Allopurinol treatment effectively reduced intestinal permeability and serum TNF-α levels. Antibiotic treatment alleviated but not abolished intestinal permeability. Uric acid alone was insufficient to increase Coca2 monolayer permeability. Allopurinol treatment altered microbial composition and suppressed opportunistic infections. Re-establishing hyperuricemia in a germfree mouse model protected mice from intestinal injury. Allopurinol and antibiotic treatments reduced TLR4 and IL-1ß expressions, increased occludin and claudin-1 expressions but suppressed NF-ĸB p65 signaling. However, removing gut microbiota aggravated lipid metabolic dysfunction. Conclusion: Gut microbiota is a direct and specific cause for intestinal barrier dysfunction.

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Separation/conversion disorders in functional coma with pseudocataplexy are rare.On December 9,2021,a young female patient with separation/conversion disorders was treated in the Department of Neurology in the First Affiliated Hospital of Shandong First Medical University.The main symptoms were episodic consciousness disorders,sudden fainting,and urinary incontinence.Complete laboratory tests and cranial magnetic resonance imaging showed no obvious abnormalities.Standard multi-channel sleep monitoring and multiple sleep latency tests were performed.The patient was unable to wake up during nap and underwent stimulation tests.There was no response to orbital pressure,loud calls,or tapping,while the α rhythm in all electroencephalogram leads and the increased muscular tone in the mandibular electromyography indicated a period of wakefulness.The results of 24-hour sleep monitoring suggested that the patient had sufficient sleep at night and thus was easy to wake up in the morning.The results of daytime unrestricted sleep and wake-up test showed that the patient took one nap in the morning and one nap in the afternoon.When the lead indicated the transition from N3 to N2 sleep,a wake-up test was performed on the patient.At this time,the patient reacted to the surrounding environment and answered questions correctly.Because the level of orexin in the cerebrospinal fluid was over 110 pg/mL,episodic sleep disorder was excluded and the case was diagnosed as functional coma accompanied by pseudocataplexy.The patient did not present obvious symptom remission after taking oral medication,and thus medication withdrawl was recommended.Meanwhile,the patient was introduced to adjust the daily routine and mood.The follow-up was conducted six months later,and the patient reported that she did not experience similar symptoms after adjusting lifestyle.Up to now,no similar symptoms have appeared in multiple follow-up visits for three years.Functional coma with pseudocataplexy is prone to misdiagnosis and needs to be distinguished from true coma and episodic sleep disorders.

Asunto(s)

Coma , Humanos , Femenino , Coma/etiología , Trastornos de Conversión/complicaciones , Trastornos de Conversión/diagnóstico , Electroencefalografía , Cataplejía/diagnóstico , Cataplejía/complicaciones , Orexinas/líquido cefalorraquídeo

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Background: The government-led community-based Chinese National Integrated Demonstration Areas for the Prevention and Control of Noncommunicable Diseases programme was launched in 2011, but no rigorous impact evaluation has been conducted to date. We aimed to evaluate the causal effects of this programme on behavioural risk factors. Methods: We used data from the latest five waves of the China Chronic Disease and Risk Factor Surveillance. The primary outcome is a behavioural risk score combining current smoking, passive smoking, drinking in last month, regular exercise, body mass index, and waist circumference. We applied the synthetic difference-in-differences method and constructed synthetic controls from the non-demonstration areas with the outcome. The average treatment effects on the treated were estimated for overall effect and by short- (1-2), medium- (3-4), and long-term (6-7 years) effects. Findings: We identified 26 demonstration areas (N = 72,193) and 100 non-demonstration areas (N = 275,397). Participants in the demonstration areas had higher education and income levels and different pre-implementation trends than non-demonstration areas. Using synthetic controls instead of non-demonstration areas reduced these pre-implementation differences. Compared to the synthetic controls, declines were observed in current smoking (-1.78% [-4.51%, 0.96%]), passive smoking (-8.09% [-14.27%, -1.90%]), and drinking in last month (-4.04% [-8.75%, 0.67%]) but not in the other factors. Behavioural risk score declined by 1.05 short-term (95% CI: -1.84, -0.26), 1.15 medium-term (95% CI: -2.08, -0.22), 2.82 long-term (95% CI: -4.79, -0.85), and 1.54 overall (95% CI: -2.51, -0.56). Interpretation: The programme improved behavioural risk scores, primarily through reductions in the prevalence of smoking and drinking, and the effect was long-lasting. Our findings provided empirical evidence for utilizing an integrated prevention and control strategy to fight against NCD in China and other countries facing similar challenges. Funding: The China National Key Research and Development Program (2018YFC1315304 and 2017YFC1310902); National Natural Science Foundation of China (81872721).

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In the past decades, various methods, such as chemical sensing, X-ray screening, and spectroscopy, have been employed to detect explosives for environmental protection and national public security. However, achieving ultrahigh sensitivity for detection, which is crucial for some practical applications, remains challenging. This study employs scanning transmission electron microscopy and electron energy loss spectroscopy (STEM-EELS) to detect individual ∼200 nm explosive nanoparticles of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX). The vibrational modes of HMX were acquired for each single nanoparticle under the aloof STEM-EELS mode, which ensures damage-free detection. Detailed comparisons with Raman and infrared spectra validate the acquired data's origin. This work highlights STEM-EELS as an effective tool in explosives detection, offering ultrahigh sensitivity, damage-free, and nanometer spatial resolution, with potential applications in environmental protection, public security, and criminal investigations.

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CRISPR-Cas9 editing triggers activation of the TP53-p21 pathway, but the impacts of different editing components and delivery methods have not been fully explored. In this study, we introduce a p21-mNeonGreen reporter iPSC line to monitor TP53-p21 pathway activation. This reporter enables dynamic tracking of p21 expression via flow cytometry, revealing a strong correlation between p21 expression and indel frequencies, and highlighting its utility in guide RNA screening. Our findings show that p21 activation is significantly more pronounced with double-stranded oligodeoxynucleotides (ODNs) or adeno-associated viral vectors (AAVs) compared to their single-stranded counterparts. Lentiviral vectors (LVs) and integrase-defective lentiviral vectors (IDLVs) induce notably lower p21 expression than AAVs, suggesting their suitability for gene therapy in sensitive cells such as hematopoietic stem cells or immune cells. Additionally, specific viral promoters like SFFV significantly amplify p21 activation, emphasizing the critical role of promoter selection in vector development. Thus, the p21-mNeonGreen reporter iPSC line is a valuable tool for assessing the potential adverse effects of gene editing methodologies and vectors.