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The oxygen isotope composition of phosphate is a useful tool for studying biogeochemical phosphorus cycling. However, the current Ag3PO4 method is not only tedious in PO43- extraction and purification but also requires a large-sized sample at the micromole level, thereby limiting its application. Here, we present an approach to measuring the oxygen isotope composition, δ18O, of dissolved phosphate at the nanomole level using electrospray ionization Orbitrap mass spectrometry (ESI-Orbitrap-MS). We compared the reproducibility of δ18O measurements using the H2PO4- ions (m/z = 97 and 99 for H2P16O4- and H2P18O16O3-, respectively) and using the PO3- fragment ions (m/z = 79 and 81 for P16O3- and P18O16O2-, respectively) generated by source fragmentation and by higher-energy collisional dissociation, respectively. The results demonstrate that phosphate δ18O can be more reliably measured by the PO3- ions than by the H2PO4- ions. PO3- generated by source fragmentation at 40 V achieved the highest reproducibility for δ18O based on precision tests. Furthermore, the mass spectrum for a 50:50 µM mixed solution of phosphate and sulfate revealed that PO3- ions resulting from source fragmentation at 40 V are the predominant species in the Orbitrap analyzer. Notably, P16O3- ions (m/z: 79) are not interfered with by 32S16O3- (m/z: 80) ions. This is in contrast to the case for 1H2P16O4- ions, which share the same m/z value with 1H32S16O4- ions and exhibit much lower signal intensity than HSO4- ions. Using the PO3- fragment method and six phosphate standards with a wide range of δ18O values, we obtained a calibration line with a slope of 0.94 (R2 = 0.98). The overall uncertainty for ESI-Orbitrap-MS phosphate δ18O measurement was 0.8 (n = 30; 1 SD). With much room for improvement, the PO3- fragment method presents a better approach to measuring the phosphate oxygen isotope composition, applicable to nanomole sample sizes in a liquid phase.
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IMPORTANCE: Clade 2.3.4.4 H5Nx avian influenza viruses (AIVs) have circulated globally and caused substantial economic loss. Increasing numbers of humans have been infected with Clade 2.3.4.4 H5N6 AIVs in recent years. Only a few human influenza vaccines have been licensed to date. However, the licensed live attenuated influenza virus vaccine exhibited the potential of being recombinant with the wild-type influenza A virus (IAV). Therefore, we developed a chimeric cold-adapted attenuated influenza vaccine based on the Clade 2.3.4.4 H5 AIVs. These H5 vaccines demonstrate the advantage of being non-recombinant with circulated IAVs in the future influenza vaccine study. The findings of our current study reveal that these H5 vaccines can induce cross-reactive protective efficacy in mice and ferrets. Our H5 vaccines may provide a novel option for developing human-infected Clade 2.3.4.4 H5 AIV vaccines.
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Proteção Cruzada , Vírus da Influenza A , Vacinas contra Influenza , Infecções por Orthomyxoviridae , Animais , Camundongos , Anticorpos Antivirais , Furões , Influenza Aviária , Vacinas contra Influenza/genética , Vacinas Atenuadas , Infecções por Orthomyxoviridae/prevenção & controleRESUMO
The emerging evidence of human infections with emerging viruses suggests their potential public health importance. A novel taxon of viruses named Statoviruses (for stool-associated Tombus-like viruses) was recently identified in the gastrointestinal tracts of multiple mammals. Here we report the discovery of respiratory Statovirus-like viruses (provisionally named Restviruses) from the respiratory tracts of five patients experiencing acute respiratory disease with Human coronavirus OC43 infection through the retrospective analysis of meta-transcriptomic data. Restviruses shared 53.1%-98.8% identities of genomic sequences with each other and 39.9%-44.3% identities with Statoviruses. The phylogenetic analysis revealed that Restviruses together with a Stato-like virus from nasal-throat swabs of Vietnamese patients with acute respiratory disease, formed a well-supported clade distinct from the taxon of Statoviruses. However, the consistent genome characteristics of Restviruses and Statoviruses suggested that they might share similar evolutionary trajectories. These findings warrant further studies to elucidate the etiological and epidemiological significance of the emerging Restviruses.
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Genoma Viral , Filogenia , Infecções Respiratórias , Humanos , China/epidemiologia , Genoma Viral/genética , Infecções Respiratórias/virologia , Infecções Respiratórias/epidemiologia , Masculino , Feminino , Estudos Retrospectivos , Sistema Respiratório/virologia , Pré-Escolar , Adulto , Criança , RNA Viral/genética , Pessoa de Meia-IdadeRESUMO
Ibuprofen (IBU) and naproxen (NPX), as widely prescribed non-steroidal anti-inflammatory drugs (NSAIDs), are largely produced and consumed globally, leading to frequent and ubiquitous detection in various aqueous environments. Previously, the microbial transformation of them has been given a little attention, especially with the isolated fungus. A yeast-like Apiotrichum sp. IB-1 has been isolated and identified, which could simultaneously transform IBU (5 mg/L) and NPX (2.5 mg/L) with maximum efficiencies of 95.77% and 88.31%, respectively. For mono-substrate, the transformation efficiency of IB-1 was comparable to that of co-removal conditions, higher than most of isolates so far. IBU was oxidized mainly through hydroxylation (m/z of 221, 253) and NPX was detoxified mainly via demethylation (m/z of 215) as shown by UPLC-MS/MS results. Based on transcriptome analysis, the addition of IBU stimulated the basic metabolism like TCA cycle. The transporters and respiration related genes were also up-regulated accompanied with higher expression of several dehydrogenase, carboxylesterase, dioxygenase and oxidoreductase encoding genes, which may be involved in the transformation of IBU. The main functional genes responsible for IBU and NPX transformation for IB-1 should be similar in view of previous studies, which needs further confirmation. This fungus would be useful for potential bioremediation of NSAIDs pollution and accelerate the discovery of functional oxidative genes and enzymes different from those of bacteria.
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Anti-Inflamatórios não Esteroides , Biotransformação , Ibuprofeno , Naproxeno , Ibuprofeno/metabolismo , Naproxeno/metabolismo , Anti-Inflamatórios não Esteroides/metabolismo , Biodegradação AmbientalRESUMO
Underwater optical imaging for information acquisition has always been an innovative and crucial research direction. Unlike imaging in the air medium, the underwater optical environment is more intricate. From an optical perspective, natural factors such as turbulence and suspended particles in the water cause issues like light scattering and attenuation, leading to color distortion, loss of details, decreased contrast, and overall blurriness. These challenges significantly impact the acquisition of underwater image information, rendering subsequent algorithms reliant on such data unable to function properly. Therefore, this paper proposes a method for underwater image restoration using Stokes linearly polarized light, specifically tailored to the challenges of underwater complex optical imaging environments. This method effectively utilizes linear polarization information and designs a system that uses the information of the first few frames to calculate the enhanced images of the later frames. By doing so, it achieves real-time underwater Stokes linear polarized imaging while minimizing human interference during the imaging process. Furthermore, the paper provides a comprehensive analysis of the deficiencies observed during the testing of the method and proposes improvement perspectives, along with offering insights into potential future research directions.
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BACKGROUND: Limited studies have focused on the risk assessment of stroke in rural regions. Moreover, the application of artificial intelligence in stroke risk scoring system is still insufficient. This study aims to develop a simplified and visualized risk score with good performance and convenience for rural stroke risk assessment, which is combined with a machine learning (ML) algorithm. METHODS: Participants of the Henan Rural Cohort were enrolled in this study. The total participants (n = 38,322) were randomly split into a train set and a test set in the ratio of 7:3. An ML algorithm was used to select variables and the logistic regression was then applied to construct the scoring system. The C-statistic and the Brier score (BS) were used to evaluate the discrimination and calibration. The Framingham stroke risk profile (FSRP) and the self-reported stroke risk function (SRSRF) were chosen to be compared. RESULTS: The Rural Stroke Risk Score (RSRS) was produced in this study, including age, drinking status, triglyceride, type 2 diabetes mellitus, hypertension, waist circumference, and family history of stroke. On validation, the C-statistic was 0.757 (95% CI 0.749-0.765) and the BS was 0.058 in the test set. In addition, the discrimination of RSRS was 6.02% and 7.34% higher than that of the FSRP and SRSRF, respectively. CONCLUSIONS: A well-performed scoring system for assessing stroke risk in rural residents was developed in this study. This risk score would facilitate stroke screening and the prevention of cardiovascular disease in economically underdeveloped areas.
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Diabetes Mellitus Tipo 2 , Acidente Vascular Cerebral , Humanos , Inteligência Artificial , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controleRESUMO
OBJECTIVES: Carbapenem-resistant Bacteroides fragilis has emerged globally and cfiA is the key underlying factor. However, the prevalence of cfiA-positive carbapenem-resistant B. fragilis varies among countries. Therefore, we investigated the prevalence of cfiA-positive B. fragilis clinical isolates in a tertiary hospital in China. METHODS: Carbapenem-resistant cfiA-positive B. fragilis isolates were identified using polymerase chain reaction. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to identify the characteristic mass spectra of cfiA-positive B. fragilis. RESULTS: The prevalence of cfiA among 153 B. fragilis isolates was 22.2% (34/153), when 20.6% (7/34) cfiA-positive B. fragilis strains were isolated from pediatric patients. Twenty-one carbapenem-resistant B. fragilis isolates were identified and were all positive with cfiA gene. Two characteristic peaks (4825 and 9642 Da) were identified using MALDI-TOF MS, and the sensitivity, specificity, and both the positive and negative predictive values of these two peaks were 100%. A new peak shift from 9627 Da for cfiA-negative isolates to 9642 Da for cfiA-positive isolates was observed. CONCLUSIONS: A high prevalence of cfiA was observed among B.fragilis isolates in this study, especially those isolated from pediatric patients. Characteristic MS spectra can accurately discriminate cfiA-positive and -negative B. fragilis isolates and can contribute to the rapid screening of cfiA-positive B. fragilis isolates in clinical laboratories.
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Infecções Bacterianas , Infecções por Bacteroides , Humanos , Criança , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/análise , beta-Lactamases/genética , Bacteroides fragilis , Prevalência , Carbapenêmicos/farmacologia , Hospitais de Ensino , China/epidemiologia , Infecções por Bacteroides/epidemiologia , Testes de Sensibilidade MicrobianaRESUMO
The current study aimed to investigate the sagittal morphology of the spinopelvic complex and the components of the lumbar spine in the normal population. In total, 132 adult volunteers were retrospectively evaluated and divided into four groups according to the Roussouly classification. Statistical analysis of radiological parameters, including lumbar lordosis (LL), thoracic kyphosis (TK), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), PI-LL, LL-TK, lumbar vertebral lordosis from L1 to L5 (L1L-L5L), the intervertebral angle from L1-L2 to L5-S1 (IVA1-2-IVA5-1), segmental lordosis from L1 to L5 (S1L-S5L), the proportion of L1-L5 (L1%-L5%), the proportion of the intervertebral angle from L1-L2 to L5-S1 (IVA1-2%-IVA5-1%), and proportion of segmental lordosis from L1 to L5 (S1L%-S5L%), was performed. Based on the classification, type II (n = 46) was the most common, followed by type I (n = 39), type III (n = 36), and type IV (n = 11). The quantitative values of the sagittal parameters of the four groups were obtained. Results showed a significant difference in terms of LL, PI, SS, and LL-TK. Further, L1%, L2%, L3%, IVA1-2%, IVA2-3%, S1L%, S2L%, and S3L% had an increasing trend. PI was positively correlated with LL, S1L, S2L, S3L, S4L, S1L%, and S2L%, but not with S5L%. In conclusion, pelvic parameters had a significant effect on lumbar curvature and lordosis distribution. Further, the abovementioned results were beneficial for individual surgical decision-making regarding targeted intervertebral angle, screw-insertion dimension, and rod contouring.
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Cifose , Lordose , Adulto , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Lordose/diagnóstico por imagem , Estudos Retrospectivos , Corpo Vertebral , Cifose/diagnóstico por imagemRESUMO
Methane production through anaerobic digestion (AD) of municipal sludge is economic and eco-friendly, which is commonly affected by temperature and pollutants residues. However, little is known about methanogenesis in psychrophilic AD (PAD) with temperature variations that simulating seasonal variations and with antibiotic stress. Here, two groups of AD systems with oxytetracycline (OTC) were operated with temperature maintained at 35 °C and 15 °C or variation to explore the influence to methanogenesis. The acetic acid was noticeably accumulated in OTC groups initially (P < 0.001). Methane production was noticeably inhibited initially in PAD with OTC, but had been stimulated later at 35 °C. The dominant acetoclastic methanogens Methanosaeta gradually decreased to 15.48% and was replaced by methylotrophic Methanomethylovorans (73.43%) in PAD with OTC. Correspondingly, the abundances of functional genes related to methylotrophic methanogenesis were also higher in these groups. Besides, genes involving in methane oxidation had over 50 times higher abundances in PAD with OTC groups in the second phase. Further investigation is essential to understand the main dynamics of methanogenesis in PAD and to clear the related molecular mechanism for future methane production regulation in sludge systems.
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Oxitetraciclina , Esgotos , Esgotos/química , Antibacterianos , Anaerobiose , Reatores Biológicos , MetanoRESUMO
BACKGROUND: In 2011, a new influenza virus, named Influenza D Virus (IDV), was isolated from pigs, and then cattle, presenting influenza-like symptoms. IDV is one of the causative agents of Bovine Respiratory Disease (BRD), which causes high morbidity and mortality in feedlot cattle worldwide. To date, the molecular mechanisms of IDV pathogenicity are unknown. Recent IDV outbreaks in cattle, along with serological and genetic evidence of IDV infection in humans, have raised concerns regarding the zoonotic potential of this virus. Influenza virus polymerase is a determining factor of viral pathogenicity to mammals. METHODS: Here we take a prospective approach to this question by creating a random mutation library about PB2 subunit of the IDV viral polymerase to test which amino acid point mutations will increase viral polymerase activity, leading to increased pathogenicity of the virus. RESULTS: Our work shows some exact sites that could affect polymerase activities in influenza D viruses. For example, two single-site mutations, PB2-D533S and PB2-G603Y, can independently increase polymerase activity. The PB2-D533S mutation alone can increase the polymerase activity by 9.92 times, while the PB2-G603Y mutation increments the activity by 8.22 times. CONCLUSION: Taken together, our findings provide important insight into IDV replication fitness mediated by the PB2 protein, increasing our understanding of IDV replication and pathogenicity and facilitating future studies.
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Infecções por Orthomyxoviridae , Orthomyxoviridae , Thogotovirus , Aminoácidos/genética , Animais , Bovinos , Mutação , Suínos , Thogotovirus/genética , Replicação ViralRESUMO
BACKGROUND: Few studies have developed risk models for dyslipidaemia, especially for rural populations. Furthermore, the performance of genetic factors in predicting dyslipidaemia has not been explored. The purpose of this study is to develop and evaluate prediction models with and without genetic factors for dyslipidaemia in rural populations. METHODS: A total of 3596 individuals from the Henan Rural Cohort Study were included in this study. According to the ratio of 7:3, all individuals were divided into a training set and a testing set. The conventional models and conventional+GRS (genetic risk score) models were developed with Cox regression, artificial neural network (ANN), random forest (RF), and gradient boosting machine (GBM) classifiers in the training set. The area under the receiver operating characteristic curve (AUC), net reclassification index (NRI), and integrated discrimination index (IDI) were used to assess the discrimination ability of the models, and the calibration curve was used to show calibration ability in the testing set. RESULTS: Compared to the lowest quartile of GRS, the hazard ratio (HR) (95% confidence interval (CI)) of individuals in the highest quartile of GRS was 1.23(1.07, 1.41) in the total population. Age, family history of diabetes, physical activity, body mass index (BMI), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were used to develop the conventional models, and the AUCs of the Cox, ANN, RF, and GBM classifiers were 0.702(0.673, 0.729), 0.736(0.708, 0.762), 0.787 (0.762, 0.811), and 0.816(0.792, 0.839), respectively. After adding GRS, the AUCs increased by 0.005, 0.018, 0.023, and 0.015 with the Cox, ANN, RF, and GBM classifiers, respectively. The corresponding NRI and IDI were 25.6, 7.8, 14.1, and 18.1% and 2.3, 1.0, 2.5, and 1.8%, respectively. CONCLUSION: Genetic factors could improve the predictive ability of the dyslipidaemia risk model, suggesting that genetic information could be provided as a potential predictor to screen for clinical dyslipidaemia. TRIAL REGISTRATION: The Henan Rural Cohort Study has been registered at the Chinese Clinical Trial Register. (Trial registration: ChiCTR-OOC-15006699 . Registered 6 July 2015 - Retrospectively registered).
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Dislipidemias/genética , Predisposição Genética para Doença , Modelos Biológicos , Calibragem , Estudos de Coortes , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Curva ROC , Fatores de RiscoRESUMO
The tumour suppressor gene silencing and proto-oncogene activation caused by epigenetic alterations plays an important role in the initiation and progression of cancer. Re-establishing the balance between the expression of tumour suppressor genes and proto-oncogenes by epigenetic modulation is a promising strategy for cancer treatment. In this study, we investigated whether cancer cells can be epigenetically reprogrammed by oocyte extract. H460 human lung cancer cells were reversibly permeabilized and incubated with the extract of bovine parthenogenetic oocytes. Bisulphite sequencing showed that bovine parthenogenetic oocyte extract induced significant demethylation at the promoters of the tumour suppressor genes RUNX3 and CDH1, but not at the promoter of the oncogenic pluripotency gene SOX2. Chromatin immunoprecipitation showed that the histone modifications at RUNX3 and CDH1 promoters were modulated towards a transcriptionally activating state, while those at SOX2 promoter towards a transcriptionally repressive state. Correspondingly, bovine parthenogenetic oocyte extract reversed the epigenetic silencing of RUNX3 and CDH1, and repressed the expression of SOX2. At the functional level, proliferation, anchorage-independent growth, migration and invasion of H460 cells was strongly inhibited. These results indicate that bovine parthenogenetic oocyte extract changes the expression patterns of tumour suppressor and oncogenic genes in cancer cells by remodelling the epigenetic modifications at their promoters. Bovine parthenogenetic oocyte extract may provide a useful tool for epigenetically reprogramming cancer cells and for dissecting the epigenetic mechanisms involved in tumorigenesis.
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Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Oócitos/química , Animais , Antígenos CD , Caderinas/genética , Caderinas/metabolismo , Bovinos , Extratos Celulares/química , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Subunidade alfa 3 de Fator de Ligação ao Core/genética , Subunidade alfa 3 de Fator de Ligação ao Core/metabolismo , Metilação de DNA , Genes Supressores de Tumor , Histonas/metabolismo , Humanos , Partenogênese , Regiões Promotoras Genéticas , Processamento de Proteína Pós-Traducional , Proto-Oncogene Mas , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Ativação TranscricionalRESUMO
Hydrogels possess inherent characteristics that render them promising for the prevention of peri-implantitis. Nonetheless, hydrogels with singular network structures are incapable of concurrently achieving the desired adhesion and mechanical properties. In this work, a carboxymethyl resistant starch/polyacrylic acid semi-interpenetrating (CMRS/PAA semi-IPN) hydrogel was successfully prepared in one step. Its morphology, structure, mechanical properties, and adhesion properties were systematically assessed, which revealed a homogeneously porous structure with a commendable mechanical strength of 67.317 kPa and an adhesion strength of 63 kPa. Ciprofloxacin (Cip) was loaded in the CMRS/PAA hydrogel via in situ compounding. The in vitro kinetic study of drug release shows that the slow drug release efficiency exceeds 90â¯% in the weakly acidic microenvironment at the infection site after 72â¯h, indicating enhanced antimicrobial properties. The Cip-loaded hydrogel also exhibits a remarkable bacterial inhibition rate exceeding 99â¯% against the pathogenic bacterium P. gingivalis and good cytocompatibility and hemocompatibility in vitro. In summary, the current work explored a novel solution and direction for the development of anti-infective medical materials applicable to dental implants.
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Although 3D reconstruction has been widely used in many fields as a key component of environment perception, existing technologies still have the potential for further improvement in 3D scene reconstruction. We propose an improved reconstruction algorithm based on the MVSNet network architecture. To glean richer pixel details from images, we suggest deploying a DE module integrated with a residual framework, which supplants the prevailing feature extraction mechanism. The DE module uses ECA-Net and dilated convolution to expand the receptive field range, performing feature splicing and fusion through the residual structure to retain the global information of the original image. Moreover, harnessing attention mechanisms refines the 3D cost volume's regularization process, bolstering the integration of information across multi-scale feature volumes, consequently enhancing depth estimation precision. When assessed our model using the DTU dataset, findings highlight the network's 3D reconstruction scoring a completeness (comp) of 0.411 mm and an overall quality of 0.418 mm. This performance is higher than that of traditional methods and other deep learning-based methods. Additionally, the visual representation of the point cloud model exhibits marked advancements. Trials on the Blended MVS dataset signify that our network exhibits commendable generalization prowess.
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In recent years, negative pressure wound dressings have garnered widespread attentions. However, it is challenging to drain the accumulated fluid under negative pressures for hydrogel dressings. To address this issue, this study prepared a chemical/physical duel-network PEG-CMCS/AG/MXene hydrogel composed by chemical disulfide crosslinked network of four-arm polyethylene glycol/carboxymethyl chitosan (4-Arm-PEG-SH/CMCS), and the physical network of hydrogen bond of agar (AG). Under near-infrared light (NIR) irradiation, the PEG-CMCS/AG/MXene hydrogel undergoes photothermal heating due to integrate of MXene, which destructs the hydrogen bond network and allows the removal of exudate through a mechanism mimicking the sweat gland-like effect of skin pores. The photothermal heating effect also enables the antimicrobial activity to prevent wound infections. The excellent electrical conductivity of PEG-CMCS/AG/MXene can promote cell proliferation under the external electrical stimulation (ES) in vitro. The animal experiments of full-thickness skin defect model further demonstrate its ability to accelerate wound healing. The conversion between thioester and thiol achieved with L-cysteine methyl ester hydrochloride (L-CME) can provides the on-demand dissolution of the dressing in situ. This study holds promises to provide a novel solution to the issue of fluid accumulations under hydrogel dressings and offers new approaches to alleviating or avoiding the significant secondary injuries caused by frequent dressing changes.
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Multi-view stereo based on learning is a critical task in three-dimensional reconstruction, enabling the effective inference of depth maps and the reconstruction of fine-grained scene geometry. However, the results obtained by current popular 3D reconstruction methods are not precise, and achieving high-accuracy scene reconstruction remains challenging due to the pervasive impact of feature extraction and the poor correlation between cost and volume. In addressing these issues, we propose a cascade deep residual inference network to enhance the efficiency and accuracy of multi-view stereo depth estimation. This approach builds a cost-volume pyramid from coarse to fine, generating a lightweight, compact network to improve reconstruction results. Specifically, we introduce the omni-dimensional dynamic atrous spatial pyramid pooling (OSPP), a multiscale feature extraction module capable of generating dense feature maps with multiscale contextual information. The feature maps encoded by the OSPP module can generate dense point clouds without consuming significant memory. Furthermore, to alleviate the issue of feature mismatch in cost volume regularization, we propose a normalization-based 3D attention module. The 3D attention module aggregates crucial information within the cost volume across the dimensions of channel, spatial, and depth. Through extensive experiments on benchmark datasets, notably DTU, we found that the OD-MVSNet model outperforms the baseline model by approximately 1.4% in accuracy loss, 0.9% in completeness loss, and 1.2% in overall loss, demonstrating the effectiveness of our module.
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Imageamento Tridimensional , Imageamento Tridimensional/métodos , Algoritmos , Redes Neurais de Computação , Processamento de Imagem Assistida por Computador/métodos , HumanosRESUMO
Long noncoding RNA small nucleolar RNA host gene 1 (lncRNA SNHG1) plays a crucial role in the occurrence and progression of various tumors. This study investigates the function of lncRNA SNHG1 in hepatocellular carcinoma (HCC). We discovered that lncRNA SNHG1 is significantly upregulated in HCC and markedly enhances cell proliferation, migration, and invasion, while simultaneously suppressing apoptosis in HCC cells. Furthermore, lncRNA SNHG1 was found to downregulate miR-7-5p expression. Overexpression of lncRNA SNHG1 counteracted the suppression of HCC cell migration, proliferation, and invasion caused by miR-7-5p mimics, and reversed the miR-7-5p mimics' enhancement of apoptosis in HCC cells. Additionally, miR-7-5p was shown to negatively regulate IGF2BP2, with the silencing of IGF2BP2 diminishing the abilities of HCC cells to proliferate, migrate, and invade, and increasing their propensity for apoptosis. Overexpression of lncRNA SNHG1 negated these effects. Thus, lncRNA SNHG1 fosters HCC progression by upregulating IGF2BP2 expression through targeting miR-7-5p.
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In osteosarcoma, immunotherapy often faces hurdles posed by cancer-associated fibroblasts (CAFs) that secrete dense extracellular matrix components and cytokines. Directly removing CAFs may prove ineffective and even promote tumor metastasis. To address this challenge, a sequential nanocomposite hydrogel that reshapes CAF behavior is developed, enhancing tumor-infiltrating T-cells in osteosarcoma. The approach utilizes an injectable blend of carboxymethyl chitosan and tetrabasic polyethylene glycol, forming a hydrogel for controlled release of a potent CAF suppressor (Nox4 inhibitor, Nox4i) and liposomal Doxorubicin (L-Dox) to induce immunogenic cell death (ICD) upon in situ administration. Nox4i effectively counters CAF activation, overcoming T-cell exclusion mechanisms, followed by programmed L-Dox release for ICD induction in stroma-rich osteosarcoma models. Combining the co-delivery gel with αPD-1 checkpoint inhibitor further enhances its effectiveness in an orthotopic osteosarcoma model. Immunophenotyping data underscore a significant boost in tumor T-cell infiltration and favorable anti-tumor immunity at the whole-animal level.
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Neoplasias Ósseas , Fibroblastos Associados a Câncer , Doxorrubicina/análogos & derivados , Osteossarcoma , Animais , Nanogéis , Fibroblastos Associados a Câncer/patologia , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Hidrogéis/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Imunoterapia , Linhagem Celular Tumoral , Microambiente Tumoral , PolietilenoglicóisRESUMO
Objective: To validate whether a residual mass demonstrated on early postoperative MR after percutaneous endoscopic lumbar discectomy (PELD) is indeed an intraoperatively retained annulus fibrosus, and explore the correlation between imaging changes in the residual mass and clinical prognosis of patients. Methods: A prospective study of 118 patients were included. During surgery, a contrast medium, Gadopentetate Dimeglumine, was injected around the ruptured annulus fibrosus. The intensity of the T2 signal, the size of the remaining mass (SR), and the cross-sectional area of the spinal canal (SCSA), VAS, and ODI were assessed at preoperative, 1-h (7-day), 6-month, and 12-month postoperative intervals. Based on VAS at 7 days post-surgery, patients were classified into either a non-remission group (Group A, VAS > 3) or a remission group (Group B, VAS ≤ 3). Results: Six patients who developed recurrent LDH were excluded. A residual mass was detected on MRI 1 h after surgery in 94.6% (106/112). During one year of follow-up, 90.1% (101/112) of the patients displayed fibrous annulus remodeling, although 68.7% (77/112) still exhibited herniation. Significant differences were found in the ODI between Groups A and B one week after surgery (p < 0.001). However, no significant differences were observed in T2 signal intensity, SR, and SCSA at 1-h, 6-month and 12-month post-surgery (p > 0.05) between the two groups. In a multiple linear regression analysis, early postoperative ODI changes were associated with T2 signal (B = -10.22, sig < 0.05), long-term changes were associated with alterations in SR (B = 5.63, sig < 0.05) and SCSA (B = -0.13, sig < 0.05). Conclusion: The residual mass observed in early postoperative MR images after PELD was the retained annulus fibrosus intraoperatively. Short-term changes in clinical symptoms after PELD were linked to T2 signal intensity, while long-term changes were associated with changes in SR and SCSA.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant threat to human health globally. It is crucial to develop a vaccine to reduce the effect of the virus on public health, economy, and society and regulate the transmission of SARS-CoV-2. Influenza B virus (IBV) can be used as a vector that does not rely on the current circulating influenza A strains. In this study, we constructed an IBV-based vector vaccine by inserting a receptor-binding domain (RBD) into a non-structural protein 1 (NS1)-truncated gene (rIBV-NS110-RBD). Subsequently, we assessed its safety, immunogenicity, and protective efficacy against SARS-CoV-2 in mice, and observed that it was safe in a mouse model. Intranasal administration of a recombinant rIBV-NS110-RBD vaccine induced high levels of SARS-CoV-2-specific IgA and IgG antibodies and T cell-mediated immunity in mice. Administering two doses of the intranasal rIBV-NS110-RBD vaccine significantly reduced the viral load and lung damage in mice. This novel IBV-based vaccine offers a novel approach for controlling the SARS-CoV-2 pandemic.