RESUMO
Zeolite nanosheets with an extremely thin thickness featuring both unique pore systems and low diffusion resistance have the potential to achieve enhanced catalytic performance in the conversion of bulky molecular biomass. The preparation of unit-cell level nanosheets generally requires complex and costly multifunctional surfactants or an organic structure-directing agent (OSDA). Commercially available and environmentally friendly ionic liquids can also direct the structure of zeolite nanosheets by π-π stacking when these kinds of OSDA are used in large amount. Herein, we first report unit-cell-sized silicogermanate nanosheets of NS-IM-20 (UWY topology), 5 nm in thickness, which were synthesized at a relatively low ionic liquid concentration with the assistance of halide ion (Cl-). The Pd-loaded NS-IM-20 nanosheets with a hierarchical porosity and moderate acidity act as promising bifunctional catalysts for selective biomass conversion.
RESUMO
BACKGROUND: Hepatectomy combined with hepatic artery reconstruction in the operation for hilar cholangiocarcinoma (Klatskin tumor) is a challenging procedure. We present a video of left hepatectomy combined with right hepatic artery reconstruction for hilar cholangiocarcinoma. PATIENT AND METHODS: The patient was a 60-year-old male who presented with obstructive jaundice. The imaging examination showed that the confluence of left and right hepatic ducts and the wall of common hepatic duct were thickened, the local lumen was narrowed, the intrahepatic bile duct was dilated, and the right hepatic artery was invaded by tumors nearly 2.3 centimeters. Left hepatectomy with total caudate lobectomy, resection with reconstruction of right hepatic artery, hilar lymphadenectomy, and Roux-en-Y hepaticojejunostomy were performed. RESULTS: The operation time was 345 min, and the amount of bleeding was about 400 ml. There was no blood transfusion. The pathology showed poorly differentiated adenocarcinoma, with negative margins of common bile duct and right hepatic duct, and negative results of all lymph nodes. The patient's recovery was uneventful and he was discharged on postoperative day 14. The patient was disease free at 12-month follow-up evaluation. CONCLUSIONS: Hepatic artery resection and reconstruction procedure is safe and feasible for hilar cholangiocarcinoma in a highly tertiary hepatobiliary center.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Masculino , Humanos , Pessoa de Meia-Idade , Tumor de Klatskin/cirurgia , Tumor de Klatskin/patologia , Hepatectomia/métodos , Artéria Hepática/cirurgia , Artéria Hepática/patologia , Fígado/cirurgia , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/cirurgiaRESUMO
As one of the significant challenges to human health, cancer has long been a focal point in medical treatment. With ongoing advancements in the field of medicine, numerous methodologies for cancer therapy have emerged, among which oncolytic virus therapy has gained considerable attention. However, oncolytic viruses still exhibit limitations. Combining them with various therapies can further enhance the efficacy of cancer treatment, offering renewed hope for patients. In recent research, scientists have recognized the promising prospect of amalgamating oncolytic virus therapy with diverse treatments, potentially surmounting the restrictions of singular approaches. The central concept of this combined therapy revolves around leveraging oncolytic virus to incite localized tumor inflammation, augmenting the immune response for immunotherapeutic efficacy. Through this approach, the patient's immune system can better recognize and eliminate cancer cells, simultaneously reducing tumor evasion mechanisms against the immune system. This review delves deeply into the latest research progress concerning the integration of oncolytic virus with diverse treatments and its role in various types of cancer therapy. We aim to analyze the mechanisms, advantages, potential challenges, and future research directions of this combination therapy. By extensively exploring this field, we aim to instill renewed hope in the fight against cancer.
RESUMO
The utilization of extracellular vesicles (EV) in immunotherapy, aiming at suppressing peripheral immune cells responsible for inflammation, has demonstrated significant efficacy in treating various inflammatory diseases. However, the clinical application of EV has faced challenges due to their inadequate targeting ability. In addition, most of the circulating EV would be cleared by the liver, resulting in a short biological half-life after systemic administration. Inspired by the natural microvesicles (MV, as a subset of large size EV) are originated and shed from the plasma membrane, we developed the immunosuppressive MV-mimetic (MVM) from endotoxin tolerant dendritic cells (DC) by a straightforward and effective extrusion approach, in which DC surface proteins were inherited for providing the homing ability to the spleen, while αCD3 antibodies were conjugated to the MVM membranes for specific targeting of T cells. The engineered MVM carried a large number of bioactive cargos from the parental cells, which exhibited a remarkable ability to promote the induction of regulatory T cells (Treg) and polarization of anti-inflammatory M2 macrophages. Mechanistically, the elevated Treg level by MVM was mediated due to the upregulation of miR-155-3p. Furthermore, it was observed that systemic and local immunosuppression was induced by MVM in models of sepsis and rheumatoid arthritis through the improvement of Treg and M2 macrophages. These findings reveal a promising cell-free strategy for managing inflammatory responses to infections or tissue injury, thereby maintaining immune homeostasis.
Assuntos
Micropartículas Derivadas de Células , Células Dendríticas , Inflamação , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Animais , Camundongos , Inflamação/tratamento farmacológico , Micropartículas Derivadas de Células/metabolismo , Camundongos Endogâmicos C57BL , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Vesículas Extracelulares , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/imunologia , Sepse/imunologia , Sepse/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacos , Humanos , Imunoterapia/métodosRESUMO
BACKGROUND: Rheumatoid arthritis (RA) is a prevalent inflammatory autoimmune disease characterised by persistent inflammation and joint damage with elevated levels of reactive oxygen species (ROS). Current treatment modalities for RA have significant limitations, including poor bioavailability, severe side effects, and inadequate targeting of inflamed joints. Herein, we synthesised cerium/manganese oxide nanoparticles (NPs) as efficient drug carriers with antioxidant and catalytic-like functions that can eliminate ROS to facilitate the polarization of macrophages phenotype from M1 to M2 and alleviate inflammation. Methotrexate (MTX), a first-line RA medication, was loaded into the NPs, which were further modified with bovine serum albumin (BSA) and integrated into dissolving hyaluronic acid-based microneedles (MNs) for transdermal delivery. RESULT: This innovative approach significantly enhanced drug delivery efficiency, reduced RA inflammation, and successfully modulated macrophage polarization toward an anti-inflammatory phenotype. CONCLUSION: This research not only presents a promising drug delivery strategy for RA but also contributes broadly to the field of immune disease treatment by offering an advanced approach for macrophage phenotypic reprogramming.
Assuntos
Artrite Reumatoide , Cério , Compostos de Manganês , Nanopartículas , Óxidos , Humanos , Manganês/farmacologia , Espécies Reativas de Oxigênio/farmacologia , Artrite Reumatoide/tratamento farmacológico , Macrófagos , Inflamação , Cério/farmacologiaRESUMO
Self-transcribing active regulatory region sequencing (STARR-seq) is a high-throughput sequencing method capable of simultaneously discovering and validating all enhancers within the genome. In this method, candidate sequences are inserted into plasmid vectors and electroporated into cells. Acting as both enhancers and target genes, the self-transcription of these sequences will also be enhanced by themselves. By sequencing the transcriptome and comparing the results with the non-inserted control, the locations and activity of enhancers can be determined. In traditional enhancer discovery strategies, the chromatin open regions and transcription active regions were sequenced and predicted as enhancers. However, the activity of these putative enhancers could only be validated one by one without a high-throughput method. STARR-seq solved this limitation, allowing simultaneous enhancers discovery and activity validation in a high-throughput manner. Since the introduction of STARR-seq, it has been widely used to discover enhancers and validate enhancer activity in a number of organisms and cells. In this review, we present the traditional enhancer prediction methods and the basic principles, development history, specific applications of STARR-seq, and its future prospects, aiming to provide a reference for researchers in related fields conducting enhancer studies.
Assuntos
Elementos Facilitadores Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Animais , Análise de Sequência de DNA/métodosRESUMO
A multidimensional extra-large pore zeolite with highly hydrothermal stability, denoted as -IRT-HS, has been developed successfully, starting from Ge-rich germanosilicate precursor hydrothermally directed by a small and commercially available piperidinium-type organic structure-directing agent (OSDA). -IRT-HS, with the supermicropores, is structurally analogues to 28-membered ring -IRT topology as confirmed by various spectroscopic techniques. And it is the high-silica (Si/Ge=58) zeolite with the largest pore size as well. Notably, using acid-washed as-made Ge-rich -IRT precursor as the silicon source is crucial to restore partially collapsed structure into a stable framework by OSDA-assisted recrystallization. The calcined -IRT-HS maintains a high crystallinity, even when stored in a humid environment for extended periods or directly exposed to water. Additionally, high silica Al-containing analogue is also readily synthesized, serving as an active solid-acid catalyst in 1,3,5-triisopropylbenzene cracking reaction, yielding an impressive initial conversion up to 76.1 % much higher than conventional large-pore Beta zeolite (30.4 %). This work will pave the way for the designed synthesis of targeted high-silica zeolites with stable and extra-large pore frameworks, mimicking the structures of existing Ge-rich counterparts.
RESUMO
Osteoarthritis (OA) is a common degenerative joint disease characterized by progressive cartilage degradation and inflammation. In recent years, mesenchymal stem cells (MSCs) derived exosomes (MSCs-Exo) have attracted widespread attention for their potential role in modulating OA pathology. However, the unpredictable therapeutic effects of exosomes have been a significant barrier to their extensive clinical application. In this study, we investigated whether fucoidan-pretreated MSC-derived exosomes (F-MSCs-Exo) could better protect chondrocytes in osteoarthritic joints and elucidate its underlying mechanisms. In order to evaluate the role of F-MSCs-Exo in osteoarthritis, both in vitro and in vivo studies were conducted. MiRNA sequencing was employed to analyze MSCs-Exo and F-MSCs-Exo, enabling the identification of differentially expressed genes and the exploration of the underlying mechanisms behind the protective effects of F-MSCs-Exo in osteoarthritis. Compared to MSCs-Exo, F-MSCs-Exo demonstrated superior effectiveness in inhibiting inflammatory responses and extracellular matrix degradation in rat chondrocytes. Moreover, F-MSCs-Exo exhibited enhanced activation of autophagy in chondrocytes. MiRNA sequencing of both MSCs-Exo and F-MSCs-Exo revealed that miR-146b-5p emerged as a promising candidate mediator for the chondroprotective function of F-MSCs-Exo, with TRAF6 identified as its downstream target. In conclusion, our research results demonstrate that miR-146b-5p encapsulated in F-MSCs-Exo effectively inhibits TRAF6 activation, thereby suppressing inflammatory responses and extracellular matrix degradation, while promoting chondrocyte autophagy for the protection of osteoarthritic cartilage cells. Consequently, the development of a therapeutic approach combining fucoidan with MSC-derived exosomes provides a promising strategy for the clinical treatment of osteoarthritis.
Assuntos
Condrócitos , Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Osteoartrite , Animais , Ratos , Condrócitos/metabolismo , Exossomos/metabolismo , MicroRNAs/metabolismo , Osteoartrite/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , Fator 6 Associado a Receptor de TNF/farmacologiaRESUMO
Glioma is the most common malignant tumor in the brain, accounting for over 80% of all primary intracranial tumors. The current clinical treatment has shown certain limitations. Although M1 type microglia can secrete various pro-inflammatory cytokines and are expected to be used for glioma treatment, direct use of microglia may lead to overactivation and trigger immune storms. Therefore, we first found that serum starvation can stimulate the transformation of microglia into M1 type. Subsequently, we found through comparative experiments that the inhibitory effect of microglial cell lysis medium on glioma cells was stronger than that of microglial cell culture medium. Finally, we successfully prepared sodium alginate hydrogel loaded with microglia lysis solution to achieve sustained inhibitory effect on the growth of glioma and avoid its proliferation.
RESUMO
BALKGROUND: Gobio huanghensis is a small economic fish endemic to the Yellow River at the junction of the Tibetan Plateau and the Huangtu Plateau in China. To understand the impact of environmental changes and human activities on the ecological structure of the G. huanghensis population, a comparative study was conducted on the age composition, growth characteristics, mortality rate, and exploitation rate of the G. huanghensis populations in the Gansu and Ningxia sections of the upper Yellow River. RESULTS: During the investigation, a total of 1147 individuals were collected, with 427 individuals collected from the Gansu section and 720 individuals from the Ningxia section. The results showed that G. huanghensis in the Gansu section exhibited a total length ranging from 5.00 to 22.80 cm, with an average of 12.68 ± 4.03 cm. In the Ningxia section, the total length of G. huanghensis ranged from 2.15 to 20.65 cm, with an average of 9.48 ± 3.56 cm. The age composition of G. huanghensis in the Gansu section ranged from 1 to 7 years, where female fish were observed between 1 and 7 years old, and male fish between 1 and 6 years old. In the Ningxia section, both female and male fish ranged from 1 to 5 years old. The relationships between total length and body weight were (Gansu section, R2 = 0.9738) and (Ningxia section, R2 = 0.9686), indicating that fish in the Gansu section exhibit positive allometric growth, while fish in the Ningxia section exhibit negative allometric growth. The von Bertalanffy growth equation revealed that G. huanghensis in the Gansu section exhibited an asymptotic total length L∞ of 27.426 cm with a growth coefficient K of 0.225 yr-1, while in the Ningxia section, the asymptotic total length L∞ was 26.945 cm with a growth coefficient K of 0.263 yr-1. The total mortality rate (Z) values of G. huanghensis were 0.7592 yr and 1.1529 yr in the Gansu section and Ningxia section, respectively. The average natural mortality rate (M), estimated by three different methods, in the Gansu section was 0.4432 yr, while it was 0.5366 yr in the Ningxia section. The exploitation rate (E) of G. huanghensis was 0.4163 in the Gansu section and 0.5345 in the Ningxia section, indicating that the population in the Ningxia section may have been overexploited. CONCLUSION: Prolonged fishing pressures and environmental changes may have led to variations in the ecological parameters of the G. huanghensis population between the Gansu and Ningxia sections.
Assuntos
Cipriniformes , Rios , Animais , Humanos , Feminino , Masculino , Lactente , Pré-Escolar , Criança , China/epidemiologia , Peso Corporal , CaçaRESUMO
To investigate various population biological parameters of Xenocypris argentea in the lower reaches of the Tangwang River (China), a comprehensive study was conducted for the first time. A total of 1,003 samples were collected from April to November 2022. The collected samples revealed that female X. argentea had total lengths ranging from 12.4 cm to 25.7 cm (weighing 15.86 g to 159.55 g), and male X. argentea had total lengths ranging from 10.8 cm to 23.9 cm (weighing 9.27 g to 121.06 g). The age of the samples was determined using otolith analysis, indicating that the ages ranged from 1 to 5 years old in both females and males. The length-weight relationships were further analyzed, uncovering the allometric growth index (b) was 3.1296 for females, indicating a positive allometric growth pattern. Differently, males exhibited a b value of 3.0274, suggesting an isometric growth pattern. Furthermore, the von Bertalanffy growth formula provided insights into the growth characteristics of X. argentea, revealing an asymptotic total length (L∞) of 36.096 cm and a growth coefficient (K) of 0.121. The analysis of the gonadal somatic index (GSI) and ovarian development period indicated that the spawning period occurred from April to July, with peak spawning in June. The study also explored fecundity-related traits, finding that individual absolute fecundity (FA) ranged from 11,364 eggs to 56,377 eggs, while eviscerated body weight relative fecundity (FW) ranged from 209 eggs/g to 823 eggs/g. The exploitation rate (E) for X. argentea was calculated as 0.574, suggesting that the population of X. argentea has been overexploited. By revealing previously unknown data on the key life history traits of X. argentea, this study has provided valuable insights that are crucial for the development of conservation strategies and policies.
Assuntos
Cipriniformes , Rios , Animais , Feminino , Masculino , Reprodução , Fertilidade , GônadasRESUMO
A high sensitivity and ultra-low concentration range photoacoustic spectroscopy (PAS) gas detection system, which was based on a novel trapezoid compound ellipsoid resonant photoacoustic cell (TCER-PAC) and partial least square (PLS), was proposed to detect acetylene (C2H2) gas. In the concentration range of 0.5 ppm â¼ 10.0 ppm, the limit of detection (LOD) values of TCER-PAC-based PAS system without data processing was 66.4 ppb, which was lower than that of the traditional trapezoid compound cylindrical resonant photoacoustic cell (TCCR-PAC). The experimental results indicated that the TCER-PAC had higher sensitivity than of TCCR-PAC. Within the concentration range of 12.5 ppb â¼ 125.0 ppb, the LOD and limit of quantification (LOQ) of TCER-PAC-based PAS system combined with PLS regression algorithm were 1.1 ppb and 3.7 ppb, respectively. The results showed that higher detection sensitivity and lower LOD were obtained by PAS system with TCER-PAC and PLS than that of TCCR-PAC-based PAS system.
RESUMO
To investigate the age structure, growth pattern, mortality and exploitation rates of Leuciscus chuanchicus in the upstream Ningxia section of the Yellow River, four sampling surveys were conducted between 2022 and 2023. A total of 472 individuals were measured for their total length (TL) and body weight (W). Age determination was performed using otoliths. The collected samples had a range of total lengths from 4.52 to 37.45 cm, body weights ranging from 0.68 to 552.43 g, and ages ranging from 1 to 7 years old. The relationship between total length and body weight was expressed as W = 0.0052 L3.19 for all samples, which indicates that the growth of L. chuanchicus adheres to allometry. The Von Bertalanffy growth equation revealed that the fish had an asymptotic total length (L∞) of approximately 37.9 cm with a growth coefficient (K) value of approximately 0.461 yr-1. Using the age-based catch curve method, the calculated total instantaneous mortality rate (Z) for all samples was determined as being equal to approximately 1.1302 yr-1. Additionally, three methods were used to estimate the average instantaneous rate of natural mortality (M), resulting in an approximate value of 0.7167 yr-1 for all samples. Furthermore, the instantaneous rate of fishing mortality (F) for all samples was calculated as 0.4134 yr-1, leading us to determine that the exploitation rate (E) is 0.3658. It was concluded that the growth rate of L. chuanchicus in the upstream of the Yellow River is relatively fast, and L. chuanchicus has not been subjected to excessive exploitation, yet its relatively high natural mortality rate underscores the need for targeted management measures aimed at preserving its habitat.
Assuntos
Rios , Animais , China/epidemiologia , Cyprinidae/crescimento & desenvolvimento , Mortalidade/tendências , PesqueirosRESUMO
Proteins play a vital role in various biological processes and achieve their functions through protein-protein interactions (PPIs). Thus, accurate identification of PPI sites is essential. Traditional biological methods for identifying PPIs are costly, labor-intensive, and time-consuming. The development of computational prediction methods for PPI sites offers promising alternatives. Most known deep learning (DL) methods employ layer-wise multi-scale CNNs to extract features from protein sequences. But, these methods usually neglect the spatial positions and hierarchical information embedded within protein sequences, which are actually crucial for PPI site prediction. In this paper, we propose MR2CPPIS, a novel sequence-based DL model that utilizes the multi-scale Res2Net with coordinate attention mechanism to exploit multi-scale features and enhance PPI site prediction capability. We leverage the multi-scale Res2Net to expand the receptive field for each network layer, thus capturing multi-scale information of protein sequences at a granular level. To further explore the local contextual features of each target residue, we employ a coordinate attention block to characterize the precise spatial position information, enabling the network to effectively extract long-range dependencies. We evaluate our MR2CPPIS on three public benchmark datasets (Dset 72, Dset 186, and PDBset 164), achieving state-of-the-art performance. The source codes are available at https://github.com/YyinGong/MR2CPPIS.
Assuntos
Aprendizado Profundo , Proteínas/metabolismo , Proteínas/química , Mapeamento de Interação de Proteínas/métodos , Biologia Computacional/métodos , Humanos , Bases de Dados de ProteínasRESUMO
Photoacoustic spectroscopy (PAS) has been rapidly developed and applied to different detection scenarios. The acoustic pressure detection is an important part in the PAS system. In this paper, an ultrahigh sensitivity Fabry-Perot acoustic sensor with a T-shaped cantilever was proposed. To achieve the best acoustic pressure effect, the dimension of the cantilever structure was designed and optimized by finite element analysis using COMSOL Multiphysics. Simulation results showed that the sensitivity of such T-shaped cantilever was 1.5 times higher than that based on a rectangular cantilever, and the resonance frequency of T-shaped cantilever were able to modulate from 800â¯Hz to 1500â¯Hz by adjusting the multi-parameter characteristics. Experimental sensing results showed that the resonance frequency of T-shaped Fabry-Perot acoustic sensor was 1080â¯Hz, yielding a high sensitivity of 1.428 µm/Pa, with a signal-to-noise ratio (SNR) of 84.8â¯dB and a detectable pressure limit of 1.9 µPa/Hz1/2@1â¯kHz. We successfully used such acoustic sensor to measure acetylene (C2H2) concentration in the PAS. The sensitivity of PAS for C2H2 gas was 3.22â¯pm/ppm with a concentration range of 50â¯ppm â¼100â¯ppm, and the minimum detection limit was 24.91ppb.
RESUMO
Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic inflammation of the synovial joints and the dysfunction of regulatory T cells (Tregs) in the peripheral blood. Therefore, an optimal treatment strategy should aim to eliminate the inflammatory response in the joints and simultaneously restore the immune tolerance of Tregs in peripheral blood. Accordingly, we developed an efferocytosis-mimicking nanovesicle that contains three functional factors for immunomodulating of efferocytosis, including "find me" and "eat me" signals for professional (macrophage) or non-professional phagocytes (T lymphocyte), and "apoptotic metabolite" for metabolite digestion. We showed that efferocytosis-mimicking nanovesicles targeted the inflamed joints and spleen of mice with collagen-induced arthritis, further recruiting and selectively binding to macrophages and T lymphocytes to induce M2 macrophage polarization and Treg differentiation and T helper cell 17 (Th17) recession. Under systemic administration, the efferocytosis-mimicking nanovesicles effectively maintained the pro-inflammatory M1/anti-inflammatory M2 macrophage balance in joints and the Treg/Th17 imbalance in peripheral blood to prevent RA progression. This study demonstrates the potential of efferocytosis-mimicking nanovesicles for RA immunotherapy.
Assuntos
Artrite Reumatoide , Eferocitose , Nanopartículas , Animais , Camundongos , Artrite Experimental/imunologia , Artrite Reumatoide/imunologia , Modelos Animais de Doenças , Terapia de Imunossupressão/métodos , Inflamação/imunologia , Macrófagos/imunologia , Nanopartículas/química , Linfócitos T Reguladores/imunologiaRESUMO
The aim of this study was to investigate the effects of ensiled agricultural byproducts from Qinghai-Tibet plateau on growth performance, rumen microbiota, ruminal epithelium morphology, and nutrient transport-related gene expression in Tibetan sheep. Fourteen male Tibetan sheep were randomly assigned to one of two diets: an untreated diet (without silage inoculum, CON, nâ =â 7) or an ensiled diet (with silage inoculum, ESD, nâ =â 7). The total experimental period lasted for 84 d, including early 14 d as adaption period and remaining 70 d for data collection. The ESD increased average daily gain (Pâ =â 0.046), dry matter intake (Pâ <â 0.001), ammonia nitrogen (Pâ =â 0.045), microbial crude protein (Pâ =â 0.034), and total volatile fatty acids concentration (Pâ <â 0.001), and decreased ruminal pH value (Pâ =â 0.014). The proportion of propionate (Pâ =â 0.006) and the copy numbers of bacteria (Pâ =â 0.01) and protozoa (Pâ =â 0.002) were higher, while the proportion of acetate (Pâ =â 0.028) was lower in the sheep fed ESD compared to CON. Pyrosequencing of the 16S ribosomal RNA gene revealed that ESD increased the relative abundance of Firmicutes, Ruminococcus, Lachnospiraceae_AC2044_group, Lachnospiraceae_XPB1014_group, and Christensenellaceae_R-7_group in the rumen (Pâ <â 0.05), while decreased the relative abundance of Bacteroidota, Prevotellaceae_UCG-003, and Veillonellaceae_UCG-001 (Pâ <â 0.05). Analyses with PICRUSt2 and STAMP indicated that the propionate metabolism pathway was enriched in the sheep fed ESD (Pâ =â 0.026). The ESD increased the rumen papillae height (Pâ =â 0.012), density (Pâ =â 0.036), and surface area (Pâ =â 0.001), and improved the thickness of the total epithelia (Pâ =â 0.018), stratum corneum (Pâ =â 0.040), stratum granulosum (Pâ =â 0.042), and stratum spinosum and basale (Pâ =â 0.004). The relative mRNA expression of cyclin-dependent Kinase 2, CyclinA2, CyclinD2, zonula occludens-1, Occludin, monocarboxylate transporter isoform 1 (MCT1), MCT4, sodium/potassium pump, and sodium/hydrogen antiporter 3 were higher in the rumen epithelial of sheep fed ESD than CON (Pâ <â 0.05). Conversely, the relative mRNA expressions of Caspase 3 and B-cell lymphoma-2 were lower in the sheep fed ESD than CON (Pâ <â 0.05). In conclusion, compared with an untreated diet, feeding an ensiled diet altered the rumen microbial community, enhanced nutrient transport through rumen epithelium, and improved the growth performance of Tibetan sheep.
Tibetan sheep on the Qinghai-Tibet Plateau experience significant nutrient stress while a substantial amount of agricultural byproducts in the region go discarded and wasted. In this study, agricultural byproducts were ensiled and fed to the Tibetan sheep to investigate their effects on growth performance, rumen microorganisms, and nutrient transport through rumen epithelial tissues. Fourteen male Tibetan sheep were randomly assigned to one of two diets: untreated diet (without silage inoculum, CON, nâ =â 7) or ensiled diet (with silage inoculum, ESD, nâ =â 7). After 70 d of feeding, the ESD-fed sheep had a higher body weight than CON. The ensiled diet changed the rumen microbial community and increased the relative abundance of cellulolytic bacteria in the rumen. In addition, the ensiled diet also promoted the development of rumen epithelia and improved the relative expression of gene related to nutrient transport. Overall, the ensiled diet optimized the use of agricultural byproducts and significantly contributed to the production of Tibetan sheep.
Assuntos
Ração Animal , Dieta , Rúmen , Silagem , Animais , Rúmen/microbiologia , Ovinos/fisiologia , Ovinos/crescimento & desenvolvimento , Masculino , Dieta/veterinária , Ração Animal/análise , Silagem/análise , Tibet , Microbioma Gastrointestinal/efeitos dos fármacos , Epitélio , Fenômenos Fisiológicos da Nutrição Animal , Distribuição Aleatória , Bactérias/classificaçãoRESUMO
BACKGROUND: Associating liver partition with portal vein ligation for staged liver resection (ALPPS) has been used in the treatment of patients with advanced or massive liver cancer without sufficient future liver remnant, but concerns remain regarding tumor outcomes and surgical safety. This study aims to evaluate the efficacy and safety of a new procedure, Hepatic artery restriction operation combined with ALPPS (HARO-ALPPS), in the treatment of HCC patients especially with severe fibrosis. METHODS: This retrospective study analyzed 8 patients who underwent HARO-ALPPS for HCC and compared their outcomes with 64 patients who underwent conventional ALPPS. The primary outcomes assessed were liver regeneration ability (measured by relative and absolute kinetic growth rates), postoperative complications, and mortality. The secondary outcomes included overall survival and disease-free survival. RESULTS: HARO-ALPPS significantly restricted the blood supply of the hepatic artery. One week after surgery, the blood flow of the right hepatic artery dropped to 62.1%. At the same time, HARO-ALPPS shows superior liver regeneration ability, which is particularly prominent in the background of liver fibrosis. No serious complications occurred after HARO-ALPPS. The overall survival rate of HARO-ALPPS was 75%, which was higher than that of ALPPS (64%, P=0.816). CONCLUSION: Compared to conventional ALPPS, HARO-ALPPS exhibits a better liver regeneration ability, and favorable long-term outcomes. Further prospective studies are needed to validate these findings and evaluate the long-term oncologic outcomes of this novel procedure.
RESUMO
Immunogenic cell death (ICD) of tumor cells serves as a crucial initial signal in the activation of anti-tumor immune responses, holding marked promise in the field of tumor immunotherapy. However, low immunogenicity tumors pose challenges in achieving complete induction of ICD, thereby limiting the response rates of immunotherapy in clinical patients. The emergence of cuproptosis as a new form of regulated cell death has presented a promising strategy for enhanced immunotherapy of low immunogenic tumors. To trigger cuproptosis, copper-ionophore elesclomol (ES) had to be employed for the copper-transporting-mediated process. Herein, we proposed a copper(II)-based metal-organic framework nanoplatform (Cu-MOF) to facilitate a cooperative delivery of encapsulated ES and copper (ES-Cu-MOF) to induce cuproptosis burst and enhance ICD of fibrosarcoma. Our results showed that the ES-Cu-MOF nano-regulator could effectively release Cu2+ and ES in response to the intracellular environment, resulting in elevated mitochondrial ROS generation and initiated cuproptosis of tumor cells. Furthermore, sequential ICDs were significantly triggered via the ES-Cu-MOF nano-regulator to activate the anti-tumor immune response. The results of tumor inhibition experiment indicated that the nano-regulator of ES-Cu-MOF obviously accumulated in the tumor site, inducing ICD for dendritic cell activation. This enabled an increased infiltration of cytotoxic CD8+ T cells and consequently enhanced antitumor immune responses for successfully suppressing fibrosarcoma growth. Thus, the copper(II)-based metal-organic framework nano-regulator offered a promising approach for inducing cuproptosis and cuproptosis-stimulated ICD for cancer immunotherapy.
RESUMO
Pro-inflammatory M1 macrophages possess the ability to change the immunosuppressive tumor microenvironment by releasing various inflammatory factors simultaneously, which can effectively inhibit tumor progression and relapse. Promoting macrophage polarization towards M1 may be an effective way to treat Melanoma. However, the risk of cytokine storm caused by the proliferation and excessive activation of M1 macrophages greatly limits it as a biosafety therapeutic strategy in anti-tumor immunotherapy. Therefore, how to engineer natural M1 macrophage to a biocompatible biomaterial that maintains the duration time of tumor suppressive property duration time still remains a huge challenge. To achieve this goal, we developed an injectable macroporous hydrogel (M1LMHA) using natural M1 macrophage lysates and alginate as raw materials. M1LMHA had excellent biocompatibility, adjustable degradation rate and could sustainably release varieties of natural inflammatory factors, such as tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ), and interleukin-12 (IL-12), etc. M1LMHA could repolarize anti-inflammatory M2 macrophages to M1 macrophages by the synergistic effect of released tiny inflammatory factors via the NF-κB pathway. This study supported that M1LMHA might be an effective and safe tool to activate tumor-associated immune cells, improving the efficiency of anti-tumor immunotherapy.