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Ligand-modified nanocarriers can promote oral or inhalative administration of macromolecular drugs across the intestinal or pulmonary mucosa. However, enhancing the unidirectional transport of the nanocarriers through "apical uptake→intracellular transport→basolateral exocytosis" route remains a hot topic and challenge in current research. Forskolin is a naturally occurring diterpenoid compound extracted from the roots of C. forskohlii. In our studies, we found that forskolin could increase the transcellular transport of butyrate-modified nanoparticles by 1.67-fold and 1.20-fold in Caco-2 intestinal epithelial cell models and Calu-3 lung epithelial cell models, respectively. Further mechanistic studies revealed that forskolin, on the one hand, promoted the cellular uptake of butyrate-modified nanoparticles by upregulating the expression of monocarboxylic acid transporter-1 (MCT-1) on the apical membrane. On the other hand, forskolin facilitated the binding of MCT-1 to caveolae, thereby mediating butyrate-modified nanoparticles hijacking caveolae to promote the basolateral exocytosis of butyrate-modified nanoparticles. Studies in normal mice model showed that forskolin could promote the transmucosal absorption of butyrate-modified nanoparticles by >2-fold, regardless of oral or inhalative administration. Using semaglutide as the model drug, both oral and inhalation delivery approaches demonstrated significant hypoglycemic effects in type 2 diabetes mice model, in which inhalative administration was more effective than oral administration. This study optimized the strategies aimed at enhancing the transmucosal absorption of ligand-modified nanocarriers in the intestinal or pulmonary mucosa.

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The cytoskeleton facilitates tumor cells invasion into the bloodstream via vasculogenic mimicry (VM) for "attack", and protects cells against external threats through cytoskeletal remodeling and tunneling nanotubes (TNTs) for "defense". However, the existing strategies involving cytoskeleton are not sufficient to eliminate tumor metastasis due to mitochondrial energy supply, both within tumor cells and from outside microenvironment. Here, considering the close relationship between cytoskeleton and mitochondria both in location and function, we construct a nano-platform that combats the "attack" and "defense" of cytoskeleton in the cascading metastasis. The nano-platform is composed of KFCsk@LIP and KTMito@LIP for the cytoskeletal collapse and mitochondrial dysfunction. KFCsk@LIP prevents the initiation and circulation of cascading tumor metastasis, but arouses limited suppression in tumor cell proliferation. KTMito@LIP impairs mitochondria to trigger apoptosis and impede energy supply both from inside and outside, leading to an amplified effect for metastasis suppression. Further mechanisms studies reveal that the formation of VM and TNTs are seriously obstructed. Both in situ and circulating tumor cells are disabled. Subsequently, the broken metastasis cascade results in a remarkable anti-metastasis effect. Collectively, based on the nano-platform, the cytoskeletal collapse with synchronous mitochondrial dysfunction provides a potential therapeutic strategy for cascading tumor metastasis suppression.

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With the higher requirements of various tactical and technical indicators of the weapon systems, the current research on the ignition and combustion characteristics of different types of solid propellants is not comprehensive. In more complex and harsh environmental conditions, the pressure affects the ignition and combustion characteristics. Therefore, the paper studies the ignition and combustion characteristics of the modified double-base propellants (MDB propellants) and fuel-rich propellants (FR propellants) under low-pressure environment. Combining experiment and theory, the ignition delay time and burning rate of two kinds of solid propellants are compared and analyzed at low pressure by the laser ignition experimental device. The results displayed that the burning flames of the FR and MDB propellant presented evident V-shape and cylindrical, respectively. The flame brightness decreased with the decrease in pressure. With the increase of pressure and heat flux, the ignition delay time of the MDB propellant and the FR propellant decreased. By comparison, Model 2 of the ignition delay time was more effective for the estimation of the ignition delay time of the FR propellant. The experimental results are compared with the three burning rate models, which are the Vielle formula (Model 1), Summerfield formula (Model 2), and B-number burning rate formula (Model 3). The results showed the burning rate was more in accord with Model 3.

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Post-surgical efferocytosis of tumor associated macrophages (TAMs) originates an immunosuppressive tumor microenvironment and facilitates abscopal metastasis of residual tumor cells. Currently, few strategies could inhibit efferocytosis while recovering the tumor-eliminative phagocytosis of TAMs. Herein, we developed an in situ hydrogel that contains anti-CD47 antibody (aCD47) and apocynin (APO), an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase. This hydrogel amplifies the non-efferocytic phagocytosis of TAMs by (1) blocking the extracellular "Don't eat me" signal of efferocytosis with aCD47, which enhances the receptor-mediated recognition and engulfment of tumor cells by TAMs in the post-surgical tumor bed, and (2) by utilizing APO to dispose of tumor debris in a non-efferocytic manner, which prevents acidification and maturation of efferosomes and allows for M1-polarization of TAMs, leading to improved antigen presentation ability. With the complementary intervention of extracellular and intracellular, this hydrogel reverses the immunosuppressive effects of efferocytosis, and induces a potent M1-associated Th1 immune response against tumor recurrence. In addition, the in situ detachment and distal colonization of metastatic tumor cells were efficiently restrained due to the intervention of efferocytosis. Collectively, the hydrogel potentiates surgery treatment of tumor by recovering the tumor-elimination ability of post-surgical TAMs.

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We determined the prevalence of infection and genetic identity of Hepatozoon spp. harbored by Rhipicephalus sanguineus sensu lato ticks in Taiwan. A total of 1082 ticks were collected from dogs and DNA extraction was performed from individual tick specimens. Hepatozoon infection was detected by performing a nested-PCR assay based on the 18S small subunit ribosomal RNA (ssrRNA) gene. The genetic identity of detected Hepatozoon was identified by gene sequencing and phylogenetic analysis. Hepatozoon infection was detected in nymphs, males and females of R. sanguineus s. l. ticks with an infection rate of 20.8%, 22.8% and 29.4%, respectively. Sequence and phylogenetic analysis revealed that these Hepatozoon spp. of Taiwan were genetically affiliated to the same clade within the genospecies of H. canis and can be discriminated from other genospecies of H. americanum and H. felis. Intraspecies analysis based on the genetic distance (GD) values indicates a lower level (GD < 0.005) genetic divergence within the same genospecies of H. canis detected in Taiwan, Brazil and Spain. Interspecies analysis also reveals a higher heterogeneity of Taiwan strains distinguished from other genospecies of H. felis (GD > 0.040) and H. americanum (GD > 0.056). This study provides the first molecular evidence of H. canis detected and identified in various stages of R. sanguineus s. l. ticks in Taiwan. Detection of H. canis in unfed male ticks may imply the possible mechanism of transstadial survival in R. sanguineus s. l. ticks. Further investigations on Hepatozoon spp. harbored by various vector ticks in Taiwan may illustrate the epidemiological significance of this parasite.

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Abstract Anti-N-methyl-D-aspartate receptor encephalitis is a recently described neurological disorder and an increasingly recognized cause of psychosis, movement disorders and autonomic dysfunction. We report 20-year-old Chinese female who presented with generalized tonic-clonic seizures, recent memory loss, visual hallucinations and abnormal behavior. Anti-N-methyl-D-aspartate receptor encephalitis was diagnosed and a computed tomography scan of abdomen reviewed a left adnexal tumor. We describe the first such case report of a patient with anti-N-methyl-D-aspartate receptor encephalitis who was given a bilateral transversus abdominis plane block as the sole anesthetic for removal of ovarian tumor. We also discuss the anesthetic issues associated with anti-N-methyl-D-aspartate receptor encephalitis. As discovery of tumor and its removal is the focus of initial treatment in this group of patients, anesthetists will encounter more such cases in the near future.

Resumo A encefalite antirreceptor de N-metil-D-aspartato (NMDA) é um distúrbio neurológico recentemente descrito e uma causa cada vez mais reconhecida de psicose, distúrbios do movimento e disfunção autonômica. Relatamos o caso de uma paciente de origem chinesa, de 20 anos, que se apresentou com crises tônico-clônicas generalizadas, perda de memória recente, alucinações visuais e comportamento anormal. Encefalite antirreceptor de NMDA foi diagnosticada e uma tomografia computadorizada de abdome revelou um tumor anexial à esquerda. Descrevemos o primeiro relato de caso de paciente com encefalite antirreceptor de NMDA submetida ao bloqueio de plano transverso abdominal (PTA) bilateral como única anestesia para remoção de tumor ovariano. Também discutimos as questões anestésicas associadas à encefalite antirreceptor de NMDA. Como a descoberta e a remoção do tumor são o foco do tratamento inicial nesse grupo de pacientes, os anestesiologistas encontrarão mais desses casos no futuro próximo.

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Abstract Tension pneumocephalus is rare but has been well documented following trauma and neurosurgical procedures. It is a surgical emergency as it can lead to neurological deterioration, brainstem herniation and death. Unlike previous cases where tension pneumocephalus developed postoperatively, we describe a case of intraoperative tension pneumocephalus leading to sudden, massive open brain herniation out of the craniotomy site. The possible causative factors are outlined. It is imperative to rapidly identify possible causes of acute intraoperative brain herniation, including tension pneumocephalus, and institute appropriate measures to minimize neurological damage.

Resumo O pneumoencéfalo hipertensivo é raro, mas foi bem documentado após trauma e procedimentos neurocirúrgicos. Trata-se de uma emergência cirúrgica porque pode levar à deterioração neurológica, herniação do tronco cerebral e morte. Ao contrário de casos anteriores, nos quais o pneumoencéfalo hipertensivo se desenvolveu no pós-operatório, descrevemos um caso de pneumoencéfalo hipertensivo desenvolvido no período intraoperatório que levou a uma herniação cerebral súbita, maciça e aberta para fora do local da craniotomia. Os possíveis fatores causais são destacados. É imperativo identificar rapidamente as possíveis causas da herniação cerebral aguda no intraoperatório, incluindo o pneumoencéfalo hipertensivo, e instituir medidas apropriadas para minimizar os danos neurológicos.

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Tension pneumocephalus is rare but has been well documented following trauma and neurosurgical procedures. It is a surgical emergency as it can lead to neurological deterioration, brainstem herniation and death. Unlike previous cases where tension pneumocephalus developed postoperatively, we describe a case of intraoperative tension pneumocephalus leading to sudden, massive open brain herniation out of the craniotomy site. The possible causative factors are outlined. It is imperative to rapidly identify possible causes of acute intraoperative brain herniation, including tension pneumocephalus, and institute appropriate measures to minimize neurological damage.

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Anti-N-methyl-d-aspartate receptor encephalitis is a recently described neurological disorder and an increasingly recognized cause of psychosis, movement disorders and autonomic dysfunction. We report 20-year-old Chinese female who presented with generalized tonic-clonic seizures, recent memory loss, visual hallucinations and abnormal behavior. Anti-N-methyl-d-aspartate receptor encephalitis was diagnosed and a computed tomography scan of abdomen reviewed a left adnexal tumor. We describe the first such case report of a patient with anti-N-methyl-d-aspartate receptor encephalitis who was given a bilateral transversus abdominis plane block as the sole anesthetic for removal of ovarian tumor. We also discuss the anesthetic issues associated with anti-N-methyl-d-aspartate receptor encephalitis. As discovery of tumor and its removal is the focus of initial treatment in this group of patients, anesthetists will encounter more such cases in the near future.

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