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Development of new technologies with strong selectivity for target pollutants and low sensitivity toward a water matrix remains challenging. Herein, we introduced a novel strategy that used chlorite as an activator for Mn(VII) at pH 4.8, turning the inert reactivity of the pollutants toward Mn(VII) into a strong reactivity. This paved a new way for triggering reactions in water decontamination. By utilizing sulfamethoxazole (SMX) as a typical pollutant, we proposed coupled pathways involving electron transfer across hydrogen bonds (TEHB) and oxidation by reactive manganese species. The results indicated that a hydrogen bonding complex, SMX-ClO2-*, formed through chlorite binding the amino group of SMX initially in the TEHB route; such a complex exhibited a stronger reduction capability toward Mn(VII). Chlorite, in the hydrogen bonding complex SMX-ClO2-*, can then complex with Mn(VII). Consequently, a new reactive center (SMX-ClO2--Mn(VII)*) was formed, initiating the transfer of electrons across hydrogen bonds and the preliminary degradation of SMX. This is followed by the involvement of the generated Mn(V)-ClO2-/Mn(III) in the reduction process of Mn(VII). Such a process showed pH-dependent degradation, with a removal ratio ranging from 80% to near-stagnation as pH increased from 4.8 to 7. Combining with pKa analysis showed that the predominant forms of contaminants were crucial for the removal efficiency of pollutants by the Mn(VII)/chlorite process. The impact of the water matrix was demonstrated to have few adverse or even beneficial effects. With satisfactory performance against numerous contaminants, this study introduced a novel Mn(VII) synergistic strategy, and a new reactivity pattern focused on reducing the reduction potential of the contaminant, as opposed to increasing the oxidation potential of oxidants.
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Picrasma quassioides (D.Don) Benn is a member of the Simaroubaceae family, which has a long history of medicinal use in China, the composition of compounds is complex, mainly including alkaloids, lignin, triterpenoids, and other compounds. As a traditional Chinese medicine, P. quassioides has pharmacological effects such as anti-inflammatory, antipyretic, antiviral, blood pressure lowering and anticancer. Scholars at home and abroad have been studying P. quassioides for about 50 years. In the present review, the research status of the chemical composition, pharmacological activity and pharmacokinetics of P. quassioides was provided, as a reference for further developing the value of P. quassioides.
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OBJECTIVES: This study aims to evaluate the safety of a new inactivated poliomyelitis vaccine (Sabin strains) (sIPV) for large-scale use in primary and booster immunizations, whether simultaneously administered with other vaccines or not and to explore the persistence of all vaccines at approximately six months after vaccination. METHOD: A total of 3200 infants were recruited into this study, including 2000 infants aged 2-3 months randomly assigned (1:1) into the "sIPV basic" or the "sIPV+DTaP" group for primary immunization of sIPV. Another 1200 children aged 18 months old and above were randomly assigned (2:2:1:1) into the "sIPV booster," "sIPV+HepA-I," "sIPV+MMR", or "sIPV+HepA-L" group for booster immunization of sIPV. Adverse events within 30 days of each vaccination dose in all participants were self-reported by guardians using a WeChat mini-program. Approximately 200 blood samples were collected at 5-7 months after the final vaccination to test for antibodies against poliovirus and other viruses. RESULTS: 3198 participants in total were included in the safety study, including 1999 infants aged 2-3 months old and 1199 children aged 18-26 months old. For primary immunization, the incidence of adverse reactions in the "sIPV basic" and the "sIPV+DTaP" group were 3.19 and 6.21% (P = 0.001), respectively. For booster immunization, the incidences of adverse reaction for the "sIPV booster" group were 2.25%, while the incidence for the "sIPV +others" group in total was 2.50% (P = 0.788). Most adverse reactions were mild. Fever was the most common symptom in all groups. No vaccine-related serious adverse events (SAEs) were observed in this study. The seropositivity rates of antibodies in the "sIPV basic" and the "sIPV+DTaP" group were 92.31 and 100% against type 1 poliovirus (P = 0.031); 96.15% and 98.57% against type 2 poliovirus (P = 0.575); 98.08% and 91.43% against type 3 poliovirus (P = 0.237), respectively. Regarding booster vaccination with sIPV, whether co-administered with other vaccines or not, the seropositivity rates of antibodies against the three types of polioviruses were all 100%. Seropositivity rates of antibodies against hepatitis A, measles, mumps, and rubella were all no <77%, except for pertussis, which was <30%. CONCLUSION: sIPV demonstrated good safety and immune persistence for primary and booster vaccinations, whether administered singly or simultaneously. Antibodies against hepatitis A, measles, mumps and rubella were not disrupted by the co-vaccination. However, the seropositivity rates and geometric mean concentrations (GMCs) of antibodies against pertussis indicate the necessity for a booster dose.
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Anticuerpos Antivirales , Inmunización Secundaria , Poliomielitis , Vacuna Antipolio de Virus Inactivados , Humanos , Vacuna Antipolio de Virus Inactivados/inmunología , Vacuna Antipolio de Virus Inactivados/administración & dosificación , Vacuna Antipolio de Virus Inactivados/efectos adversos , Lactante , Inmunización Secundaria/métodos , Masculino , China , Femenino , Anticuerpos Antivirales/sangre , Poliomielitis/prevención & control , Poliomielitis/inmunología , Poliovirus/inmunología , Esquemas de Inmunización , Vacunación/métodos , Vacunas Combinadas/inmunología , Vacunas Combinadas/administración & dosificación , Vacunas Combinadas/efectos adversosRESUMEN
Wastewater treatment plants produce large amounts of sludge requiring stabilization before safe disposal. Traditional biological stabilization approaches are cost-effective but generally require either an extended retention time (10-40 days), or elevated temperatures (40-80 °C) for effective pathogens inactivation. This study overcomes these limitations via a novel acidic aerobic digestion process, leveraging an acid-tolerant ammonia-oxidizing bacterium (AOB) Candidatus Nitrosoglobus. To retain this novel but slowly growing AOB, we proposed the first-ever application of a classical wastewater configuration-moving bed biofilm reactor (MBBR)-for sludge treatment. The AOB in biofilm maintains acidic pH and high nitrite levels in sludge, generating free nitrous acid in situ to expedite sludge stabilization. This process was tested in two laboratory-scale aerobic digesters processing full-scale anaerobically digested sludge. At an ambient temperature of 20 °C, pathogens were reduced to levels well below the threshold specified for the highest stabilization level (Class A), within a retention time of 3.5 days. A high volatile solids reduction of 27.4 ± 5.2% was achieved. Through drastically accelerating stabilization and enhancing reduction, this process substantially saves capital and operational costs for sludge disposal.
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Purpose: Docetaxel (DTX) is a valuable anti-tumor chemotherapy drug with limited oral bioavailability. This study aims to develop an effective oral delivery system for DTX using natural nanoparticles (Nnps) derived from Coptidis Rhizoma extract. Methods: DTX-loaded self-assembled nanoparticles (Nnps-DTX) were created using an optimized heat-induction strategy. Nnps-DTX's shape, size, Zeta potential, and in vitro stability were all carefully examined. Additionally, the study investigated the encapsulation efficiency, loading capacity, crystal form, and intermolecular interactions of DTX in Nnps-DTX. Subsequently, the solubility, release, cellular uptake, metabolic stability, and preclinical pharmacokinetics of DTX in Nnps-DTX were systematically evaluated. Finally, the cytotoxicity of Nnps-DTX was assessed in three tumor cell lines. Results: Nnps-DTX was spherical in shape, 138.6 ± 8.2 nm in size, with a Zeta potential of -20.8 ± 0.6 mV, a DTX encapsulation efficiency of 77.6 ± 8.5%, and a DTX loading capacity of 6.8 ± 1.9%. Hydrogen bonds, hydrophobic interactions, and electrostatic interactions were involved in the formation of Nnps-DTX. DTX within Nnps-DTX was in an amorphous form, resulting in enhanced solubility (23.3 times) and release compared to free DTX. Following oral treatment, the mice in the Nnps-DTX group had DTX peak concentrations 8.8, 23.4, 44.6, and 5.7 times higher in their portal vein, systemic circulation, liver, and lungs than the mice in the DTX group. Experiments performed in Caco-2 cells demonstrated a significant increase in DTX uptake by Nnps-DTX compared to free DTX, which was significantly inhibited by indomethacin, an inhibitor of caveolae-mediated endocytosis. Furthermore, compared to DTX, DTX in Nnps-DTX demonstrated better metabolic stability in liver microsomes. Notably, Nnps-DTX significantly reduced the viability of MCF-7, HCT116, and HepG2 cells. Conclusion: The novel self-assembled nanoparticles considerably enhanced the cellular absorption, solubility, release, metabolic stability, and pharmacokinetics of oral DTX and demonstrated strong cytotoxicity against tumor cell lines.
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Docetaxel , Nanopartículas , Animales , Docetaxel/farmacocinética , Docetaxel/química , Docetaxel/farmacología , Docetaxel/administración & dosificación , Humanos , Administración Oral , Nanopartículas/química , Medicamentos Herbarios Chinos/farmacocinética , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Antineoplásicos/farmacocinética , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/administración & dosificación , Ratones , Línea Celular Tumoral , Coptis chinensis , Tamaño de la Partícula , Masculino , Liberación de Fármacos , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Supervivencia Celular/efectos de los fármacos , Disponibilidad Biológica , Solubilidad , Ratas Sprague-Dawley , Ratones Endogámicos BALB CRESUMEN
The third-generation aromatase inhibitors (AIs), represented by letrozole, anastrozole, and exemestane, have been used as a standard first-line adjuvant therapy for postmenopausal breast cancer patients with positive hormone receptor. However, their safety in the real world has not been systematically analyzed. We used the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) to investigate adverse event (AE) profiles of the three AIs, covering the period from Q1 2004 to Q3 2023. The time-to-event onset profiles and cumulative incidence were analyzed by Weibull shape parameter test and Kaplan-Meier method, respectively. The disproportionality analysis was utilized to assess drug toxicity risk. Based on the FAERS database, 18,035, 8242, and 7011 reports listing letrozole, anastrozole, and exemestane as primary suspected drugs were extracted, respectively. AEs associated with anastrozole displayed the latest onset (p < 0.0001); meanwhile, WSP test showed that all three AIs had early failure-type profiles. At the preferred term level, we acquired 95, 59, and 42 significant signals associated with letrozole, anastrozole, and exemestane, which involved 18, 13, and 15 system organ classes, respectively. The three AIs all reported that their strongest AE signal was trigger finger. Neutropenia was the most frequent AE for letrozole, while the highest occurrences of anastrozole and exemestane were arthralgia. We also found that interstitial lung disease, a rare but serious AE, showed strong signal intensity in all three AIs. Additionally, letrozole was also associated with lots of other rare but serious AEs in hematologic, respiratory, and hepatic systems, which were not recorded in the instructions. Our analysis of safety warning signals of the third-generation AIs from the FAERS database provided reference for clinical safe and rational drug use.
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Generalized pustular psoriasis (GPP) is a rare, chronic and potentially life-threatening autoinflammatory skin disease characterized by widespread eruption of sterile pustules, with or without systemic inflammation. GPP can significantly reduce patients' quality of life (QoL). Several therapeutic approaches have been described in the literature, but there is no consensus on optimal treatment. In this review, we summarize published literature on efficacy, safety and QoL outcomes associated with current treatment of GPP with both approved and non-approved products. Embase and MEDLINE databases were searched (1980-September 2023). A search protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered on the PROSPERO database (CRD42021215437). Details on publication, population, intervention, efficacy, safety and QoL were captured and checked by independent reviewers. In total, 118 publications were included, with only 19% of publications reporting on the results of clinical trials. Treatment modalities reported for GPP included non-biologic systemic therapies such as retinoids, cyclosporine and methotrexate, topical agents, biologics and small molecules, among others. Results were highly heterogeneous and methodological quality was very low, with only the interleukin-36R inhibitor spesolimab reporting results from placebo-controlled randomized trials; based on this, spesolimab is now approved for GPP treatment in regions including the USA, Japan, China, the EU and several other countries. Some other biologics are approved exclusively in Japan and Taiwan for the treatment of GPP based on open-label studies with small patient numbers in lieu of double-blind studies. Non-standardization of clinical outcomes across studies remains a major hurdle in reaching a consensus on optimal treatment. However, recently trials have been conducted using well-defined, disease-specific endpoints to evaluate GPP-targeted treatments, which will hopefully advance patient care. In conclusion, this review highlights the need for prospective randomized studies with GPP-specific endpoints to determine the optimal treatment strategy.
Generalized pustular psoriasis (GPP) is a rare, chronic skin condition characterized by painful, sterile pustules that can occur all over the body. These pustules may also be accompanied by systemic inflammation, which can lead to serious health complications. GPP significantly impacts patients' quality of life and can even be life-threatening. Because the disease is so rare, treatment guidelines have typically been based on those for plaque psoriasis. However, these guidelines do not specifically address the unique needs of GPP. In this review, we analysed the published literature on GPP management, focussing on treatment efficacy, safety and quality of life outcomes. We searched the literature databases Embase and MEDLINE for articles published between 1980 and September 2023. In total, we identified 118 publications on this topic, covering a wide range of therapies; only one of these therapies, spesolimab, reported results from placebo-controlled randomized trials. Based on these trials, spesolimab is now approved for GPP treatment in the USA, Japan, China, the EU and several other countries. Some other therapies are approved exclusively in Japan and Taiwan based on small, open-label studies in the absence of higher-quality data. To date, comparing treatments has been challenging because of different clinical outcomes used to measure effectiveness. However, well-defined endpoints specific to GPP have recently been developed and used in trials. In conclusion, our review highlights the need for prospective randomized studies with GPP-specific endpoints to determine the best treatment strategy.
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Circular RNA (circRNA) has been widely studied as a competitive endogenous RNA targeting microRNA (miRNA)/messenger RNA to regulate cancer progression. However, the regulatory mechanism of circ_0023179 in non-small cell lung cancer (NSCLC) remains unclear. The expression levels of circ_0023179, miR-615-5p and Cadherin 3 (CDH3) in NSCLC were detected using quantitative real-time polymerase chain reaction. The stability of circ_0023179 was verified using ribonuclease R enzyme, actinomycin D and agarose gel electrophoresis. Colony formation and thymidine analog 5-ethynyl-2'-deoxyuridine assays were performed to examine proliferation changes in NSCLC cells. Western blot was used to assess the levels of CDH3 and epithelial-mesenchymal transition (EMT)-related marker proteins to evaluate EMT. Dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays were performed to explore the potential mechanisms of circ_0023179 in regulating NSCLC progression. Finally, the effects of circ_0023179 on NSCLC tumour growth in vivo were explored using a nude mouse subcutaneous tumour model. The results showed that the expression of circ_0023179 was remarkably higher in NSCLC tissues and cells, and it had a significant effect on NSCLC cell proliferation. Additionally, the knockdown of circ_0023179 significantly inhibited tumour growth in NSCLC mice. Mechanistically, circ_0023179 alleviated its inhibition of downstream CDH3 through the sponge-like adsorption of miR-615-5p. The downregulation of miR-615-5p and the upregulation of CDH3 mitigated the inhibitory effect of silencing circ_0023179 on NSCLC cell proliferation. In conclusion, silencing circ_0023179 inhibited NSCLC cell proliferation by targeting the miR-615-5p/CDH3 axis involved in NSCLC progression.
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BACKGROUND: Internet hospitals (IHs) have rapidly developed as a promising strategy to address supply-demand imbalances in China's medical industry, with their capabilities directly dependent on information platform functionality. Moreover, a novel theory of "Trinity" smart hospital has provided advanced guidelines of IHs construction. OBJECTIVE: To explore the construction experience, construction models, and development prospects based on operational data from IHs. METHODS: Based on existing information systems and internet service functionalities, our hospital has built a "Smart Hospital Internet Information Platform (SHIIP)" for IHs operation, actively to expand online services, digitalize traditional healthcare, and explore healthcare services modes throughout the entire process and lifecycle. This article encompasses the platform architecture design, technological applications, patient service content and processes, healthcare professional support features, administrative management tools, and associated operational data. RESULTS: Our platform has presented a remarkable set of data, including 82,279,669 visits, 420,120 online medical consultations, 124,422 electronic prescriptions, 92,285 medication deliveries, 6,965,566 pre-diagnosis triages, 4,995,824 offline outpatient appointments, 2,025 medical education articles with a total of 15,148,310 views, and so on. These data demonstrate the significant role of IH as an indispensable component of our physical hospital services, with a deep integration between online and offline healthcare systems. CONCLUSIONS: Attributing to extreme convenience and improved efficiency, our IH has achieved a wide recognition and use from both the public and healthcare workers, and the upward trends in multiple data metrics suggest a promising outlook for its sustained and positive development in the future. Our pioneering exploration holds tremendous significance and serves as a valuable guiding reference for IHs construction and the progressive development of the internet healthcare sector.
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Abnormal levels of intracellular microviscosity have a close relationship with some diseases and pathologies. Therefore, quantitative imaging of viscosity at the cellular and organ levels is beneficial for disease diagnosis, curative effect evaluation, and anticancer drug screening. Herein, we synthesized viscosity-activated orange-red emitting carbon dots (named as LP-CDs) from lignin and p-phenylenediamine using a one-step method, whose fluorescence intensity, lifetime, and quantum yield significantly increase with rising viscosity. Meanwhile, the fluorescence intensity of LP-CDs also has a good linear relationship with the solution viscosity. Taking the advantages of high sensitivity, noninvasiveness, and rapid result output of fluorescence imaging, LP-CDs can visualize the cellular viscosity changes induced by inflammation and hyperglycemia, and image tumor evolution. More importantly, LP-CDs can be used as powerful sensors to screen anticancer drugs in vivo by evaluating therapeutic effects. This work provides a new scheme for constructing robust nanoprobes to achieve the diagnosis and imaging-guided surgery of viscosity related diseases.
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Antineoplásicos , Técnicas Biosensibles , Carbono , Imagen Óptica , Puntos Cuánticos , Viscosidad , Carbono/química , Humanos , Puntos Cuánticos/química , Antineoplásicos/uso terapéutico , Antineoplásicos/química , Antineoplásicos/farmacología , Técnicas Biosensibles/métodos , Animales , Imagen Óptica/métodos , Neoplasias/tratamiento farmacológico , Ratones , Ensayos de Selección de Medicamentos AntitumoralesRESUMEN
Chemicals are commonly dosed in sewer systems to reduce the emission of hydrogen sulfide (H2S) and methane (CH4), incurring high costs and environmental concerns. Nitrite dosing is a promising approach as nitrite can be produced from urine wastewater, which is a feasible integrated water management strategy. However, nitrite dosing usually requires strict conditions, e.g., relatively high nitrite concentration (e.g., â¼200 mg N/L) and acidic environment, to inhibit microorganisms. In contrast to "microbial inhibition", this study proposes "microbial utilization" concept, i.e., utilizing nitrite as a substrate for H2S and CH4 consumption in sewer. In a laboratory-scale sewer reactor, nitrite at a relatively low concentrations of 25-48 mg N/L was continuously dosed. Two nitrite-dependent microbial utilization processes, i.e., nitrite-dependent anaerobic methane oxidation (n-DAMO) and microbial sulfide oxidation, successfully occurred in conjunction with nitrite reduction. The occurrence of both processes achieved a 58 % reduction in dissolved methane and over 90 % sulfide removal in the sewer reactor, with microbial activities measured as 15.6 mg CH4/(L·h) and 29.4 mg S/(L·h), respectively. High copy numbers of n-DAMO bacteria and sulfide-oxidizing bacteria (SOB) were detected in both sewer biofilms and sediments. Mechanism analysis confirmed that the dosed nitrite at a relatively low level did not cause the inhibition of sulfidogenic process due to the downward migration of activity zones in sewer sediments. Therefore, the proposed "microbial utilization" concept offers a new alternative for simultaneous removal of sulfide and methane in sewers.
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OBJECTIVE: The objective of this study was to evaluate the clinical effect and safety of the postauricular infratemporal fossa approach (ITFA) in resecting jugular foramen lesions. METHODS: All 25 patients undergoing microsurgery via postauricular ITFA from March 2015 to May 2023 in the Department of Neurosurgery, Tangdu Hospital, Air Force Military Medical University were included. The clinical and radiological data were retrospectively analyzed. Regular follow-up was carried out. RESULTS: The mean age of all patients was 50.5±8.9 years, and 14 of them were female and 11 were male. Among the cases, lower cranial nerve schwannoma accounted for 60â¯% (15/25) of all tumors, jugular foramen paraganglioma accounted for 20â¯% (5/25), and the remaining 20â¯% included meningioma, chondrosarcoma, plasmacytoma, and salivary gland tumors. Total tumor resection was performed in 18 cases, subtotal tumor resection in 7 cases and partial resection in 1 case. Seven patients underwent gamma knife radiotherapy after surgery. Transient lower cranial nerve dysfunction occurred in 8 patients, and permanent lower cranial nerve dysfunction occurred in 2 patients after surgery. One patient developed facial paralysis, and one patient presented hearing loss. CONCLUSIONS: The postauricular ITFA achieved a relatively high total tumor resection rate and a lower incidence of neurological functional disorders. It is an alternative and suitable surgical approach for resecting jugular foramen lesions. Maximizing the preservation of neurological function is preferred, especially when radical resection cannot be achieved. Stereotactic radiotherapy could be used for residual tumors.
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Fosa Infratemporal , Foramina Yugular , Complicaciones Posoperatorias , Neoplasias de la Base del Cráneo , Humanos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Foramina Yugular/cirugía , Neoplasias de la Base del Cráneo/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Fosa Infratemporal/cirugía , Estudios Retrospectivos , Procedimientos Neuroquirúrgicos/métodos , Procedimientos Neuroquirúrgicos/efectos adversos , Neurilemoma/cirugía , Meningioma/cirugía , Resultado del Tratamiento , Neoplasias de los Nervios Craneales/cirugía , Anciano , Microcirugia/métodos , Paraganglioma/cirugía , Paraganglioma/diagnóstico por imagenRESUMEN
The advent of single cell transposase-accessible chromatin sequencing (scATAC-seq) technology enables us to explore the genomic characteristics and chromatin accessibility of blood cells at the single-cell level. To fully make sense of the roles and regulatory complexities of blood cells, it is critical to collect and analyze these rapidly accumulating scATAC-seq datasets at a system level. Here, we present scBlood (https://bio.liclab.net/scBlood/), a comprehensive single-cell accessible chromatin database of blood cells. The current version of scBlood catalogs 770,907 blood cells and 452,247 non-blood cells from â¼400 high-quality scATAC-seq samples covering 30 tissues and 21 disease types. All data hosted on scBlood have undergone preprocessing from raw fastq files and multiple standards of quality control. Furthermore, we conducted comprehensive downstream analyses, including multi-sample integration analysis, cell clustering and annotation, differential chromatin accessibility analysis, functional enrichment analysis, co-accessibility analysis, gene activity score calculation, and transcription factor (TF) enrichment analysis. In summary, scBlood provides a user-friendly interface for searching, browsing, analyzing, visualizing, and downloading scATAC-seq data of interest. This platform facilitates insights into the functions and regulatory mechanisms of blood cells, as well as their involvement in blood-related diseases.
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BACKGROUND: Canine circovirus (CanineCV), a non-enveloped virus with a circular DNA genome, has been identified in various avian and mammalian species, including domestic and wild canids. This study aimed to comprehensively analyze the prevalence of CanineCV across diverse animal species in 11 provinces of China. RESULTS: A total of 1,666 serum samples were collected, revealing a 5.82% prevalence of CanineCV in dogs, with the highest rates being observed in southern and eastern China. Phylogenetic analysis of 266 global CanineCV genomes sourced from the NCBI identified six distinct genotypes, elucidating the complex dynamics of their evolution. Evidence suggested a potential bat origin for CanineCV, with positive selection and high rates of evolution being observed. Recombination analysis revealed dynamic genetic exchange, highlighting the intricate nature of CanineCV evolution. Mutational analysis identified key amino acid substitutions likely to influence the virus's adaptation. Additionally, glycosylation, palmitoylation, and SUMOylation sites were predicted, shedding light on crucial functional properties of the virus. CONCLUSIONS: This study provides a global perspective on the origin, genetic diversity, and evolutionary dynamics of CanineCV. Understanding these factors is crucial for elucidating its epidemiology and potential health risks.
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Infecciones por Circoviridae , Circovirus , Enfermedades de los Perros , Filogenia , Animales , Circovirus/genética , Circovirus/clasificación , Perros , Enfermedades de los Perros/virología , Enfermedades de los Perros/epidemiología , China/epidemiología , Infecciones por Circoviridae/veterinaria , Infecciones por Circoviridae/epidemiología , Infecciones por Circoviridae/virología , Evolución Molecular , Genoma Viral , Variación Genética , Prevalencia , GenotipoRESUMEN
PROTACs, proteolysis targeting chimeras, are bifunctional molecules inducing protein degradation through a unique proximity-based mode of action. While offering several advantages unachievable by classical drugs, PROTACs have unfavorable physicochemical properties that pose challenges in application and formulation. In this study, we show the solubility enhancement of two PROTACs, ARV-110 and SelDeg51, using Poly(vinyl alcohol). Hereby, we apply a three-fluid nozzle spray drying set-up to generate an amorphous solid dispersion with a 30% w/w drug loading with the respective PROTACs and the hydrophilic polymer. Dissolution enhancement was achieved and demonstrated for t = 0 and t = 4 weeks at 5 °C using a phosphate buffer with a pH of 6.8. A pH shift study on ARV-110-PVA is shown, covering transfer from simulated gastric fluid (SGF) at pH 2.0 to fasted-state simulated intestinal fluid (FaSSIF) at pH 6.5. Additionally, activity studies and binding assays of the pure SelDeg51 versus the spray-dried SelDeg51-PVA indicate no difference between both samples. Our results show how modern enabling formulation technologies can partially alleviate challenging physicochemical properties, such as the poor solubility of increasingly large 'small' molecules.
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Hydrogen peroxide (H2O2) as a reactive oxygen species produced by cellular metabolism can be used in antitumor therapy. However, the concentration of intracellular H2O2 limits its application. Some materials could enhance the concentration of intracellular H2O2 to strengthen antitumor therapy. In this review, the recent advances in H2O2-supplying materials in terms of promoting intracellular H2O2 production and exogenous H2O2 supply are summarized. Then the mechanism of H2O2-supplying materials for tumor therapy is discussed from three aspects: reconstruction of the tumor hypoxia microenvironment, enhancement of oxidative stress, and the intrinsic anti-tumor ability of H2O2-supplying materials. In addition, the application of H2O2-supplying materials for tumor therapy is discussed. Finally, the future of H2O2-supplying materials is presented. This review aims to provide a novel idea for the application of H2O2-supplying materials in tumor therapy.
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Peróxido de Hidrógeno , Neoplasias , Microambiente Tumoral , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/metabolismo , Peróxido de Hidrógeno/farmacología , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Microambiente Tumoral/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Animales , Antineoplásicos/farmacología , Antineoplásicos/química , Especies Reactivas de Oxígeno/metabolismo , Hipoxia Tumoral/efectos de los fármacosRESUMEN
Based on some very recent results on Fe-catalyzed boron-source-dependent regiodivergent hydroborations of internal alkynes, we report here a boron-source-dependent but also ligand-dependent mechanistic trichotomy in borylative cyclizations. The choice of ligand plus boron source allows the synthesis of three isomeric borylative cyclization products starting from a common substrate and using the same precatalyst ((Ph3P)2Fe(CO)(NO)H) and sets the stage for the development of a unifying concept in Fe-catalyzed borylative cyclizations.
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The property of being stubborn and degradation resistant makes nanoplastic (NP) pollution a long-standing remaining challenge. Here, we apply a designed top-down strategy to leverage the natural hierarchical structure of waste crayfish shells with exposed functional groups for efficient NP capture. The crayfish shell-based organic skeleton with improved flexibility, strength (14.37 to 60.13 MPa), and toughness (24.61 to 278.98 MJ m-3) was prepared by purposefully removing the inorganic components of crayfish shells through a simple two-step acid-alkali treatment. Due to the activated functional groups (e.g., -NH2, -CONH-, and -OH) and ordered architectures with macropores and nanofibers, this porous crayfish shell exhibited effective removal capability of NPs (72.92 mg g-1) by physical interception and hydrogen bond/electrostatic interactions. Moreover, the sustainability and stability of this porous crayfish shell were demonstrated by the maintained high-capture performance after five cycles. Finally, we provided a postprocessing approach that could convert both porous crayfish shell and NPs into a tough flat sheet. Thus, our feasible top-down engineering strategy combined with promising posttreatment is a powerful contender for a recycling approach with broad application scenarios and clear economic advantages for simultaneously addressing both waste biomass and NP pollutants.