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Lung nodule localization using conventional image-guided video-assisted thoracoscopic surgery involves lung puncture, which increases the risk of needle-related complications. We aimed to evaluate the feasibility and safety of a single-stage non-invasive laser-guided stamping localization technique followed by resection under general anesthesia in a hybrid operating room. We retrospectively reviewed consecutive patients who underwent thoracoscopic surgery for small pulmonary nodules using laser-guided dye-stamping localization methods in a hybrid operating room between June 2023 and October 2023. During the study period, 18 patients with 20 lesions underwent single-stage intraoperative image-guided stamping video-assisted thoracoscopic surgery in the hybrid operating room. The median size of the nodules was 7.4 mm (interquartile range [IQR] 5.7-9.8 mm), and median distance from the pleural surface was 9.8 mm (IQR 7.7-14.6 mm). The median localization time was 26 min (IQR 23-34 min), whereas median operation time was 69 min (IQR 62-87 min). The total median operating room time was 146 min (IQR 136-157 min). Twelve patients underwent less than two cone-beam computed tomography scans, while 6 underwent more than two scans. The total median dose area product, including cone-beam computed tomography scans, was 5731.4 uGym2. No localization-related complications were observed, and the postoperative length of stay was 1 day (IQR 1-2 days). The single-stage image-guided pleural stamping technique for localizing small pulmonary nodules in a hybrid operating room is feasible and safe. Future research with larger cohorts is required to further explore the benefits of this workflow.
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RATIONALE AND OBJECTIVES: Percutaneous lung tumor ablations are mostly performed in computed tomography (CT) rooms under local anesthesia with conscious sedation. However, maintaining the breath-hold phase during this can be challenging, affecting image quality and increasing complications. With the advent of hybrid operating rooms (HORs), this procedure can be performed with endotracheal tube (ETGA) intubation under general anesthesia with lung separation, ensuring precise imaging in a single-stage setting. Lung separation provides surgical exposure of one lung while ensuring ample gas exchange with the other. This study evaluated tumor ablations performed in an HOR equipped with cone beam CT and laser guidance. MATERIALS AND METHODS: This retrospective study included patients who underwent lung tumor ablation under general anesthesia with an ETGA in an HOR between July 2020 and May 2023. Anesthesia considerations, perioperative management, and postoperative follow-ups were evaluated. RESULTS: 65 patients (78 tumors) underwent ablation using two types of lung ventilation methods including a single-lumen tube with a blocker (SLT/BL) (n = 15) and double-lumen tube (DLT) (n = 50). Most patients experienced desaturation during the apnea phase of dynamic CT and needling. The average SpO2 value was significantly lower in the DLT group than in the SLT/BL group during the procedure (81.1% versus 88.7%, P = 0.033). Five, three, and two patients developed pneumothorax, subcutaneous emphysema, and pleural effusion, respectively. CONCLUSION: Percutaneous ablation under general anesthesia with endotracheal intubation and lung separation performed in HORs was feasible and safe. The setup minimized complication risks and maintained a balance between patient safety and successful procedures.
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In this article, the multidisciplinary team of the Taiwan Academy of Tumor Ablation, who have expertise in treating lung cancer, present their perspectives on percutaneous image-guided thermal ablation (IGTA) of lung tumors. The modified Delphi technique was applied to reach a consensus on clinical practice guidelines concerning ablation procedures, including a comprehensive literature review, selection of panelists, creation of a rating form and survey, and arrangement of an in-person meeting where panelists agreed or disagreed on various points. The conclusion was a final rating and written summary of the agreement. The multidisciplinary expert team agreed on 10 recommendations for the use of IGTA in the lungs. These recommendations include terms and definitions, line of treatment planning, modality, facility rooms, patient anesthesia settings, indications, margin determination, post-ablation image surveillance, qualified centers, and complication ranges. In summary, IGTA is a safe and feasible approach for treating primary and metastatic lung tumors, with a relatively low complication rate. However, decisions regarding the ablation technique should consider each patient's specific tumor characteristics.
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Consenso , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Taiwan , Técnicas de Ablação/métodos , Cirurgia Assistida por Computador/métodos , Ablação por Cateter/métodosRESUMO
PURPOSE: We developed a novel augmented fluoroscopy-guided intrathoracic stamping technique for localizing small pulmonary nodules in the hybrid operating room. We conducted an observational study to investigate the feasibility of this technique and retrospectively compared two augmented fluoroscopy-guided approaches: intrathoracic and transbronchial. METHODS: From August 2020 to March 2023, consecutive patients underwent single-stage augmented fluoroscopy-guided localization under general anaesthesia. This included intrathoracic stamping and bronchoscopic lung marking, followed by thoracoscopic resection in a hybrid operating room. Comparative analyses were performed between the two groups. RESULTS: The data of 50 patients in the intrathoracic stamping and 67 patients in the bronchoscopic lung marking groups were analysed. No significant difference was noted in demographic data between the groups, except a larger lesion depth in the bronchoscopic lung marking group (14.7 ± 11.7 vs 11.0 ± 5.8 mm, p = 0.029). Dye localization was successfully performed in 49 intrathoracic stamping group patients (98.0%) and 67 bronchoscopic lung marking group patients (100%). No major procedure-related complications occurred in either group; however, the time flow (total anaesthesia time/global operating room time) was longer, and the radiation exposure (fluoroscopy duration/total dose area product) was larger in the bronchoscopic lung marking group. CONCLUSIONS: Augmented fluoroscopic stamping localization under intubated general anaesthesia is feasible and safe, providing an alternative with less global operating room time and lower radiation exposure for image-guided thoracoscopic surgery in the hybrid operating room.
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We conducted pharmacokinetic research wherein salcaprozate sodium (SNAC) was utilized as a penetration enhancer by incorporating it into pancreatic kininogenase (PK) to improve the bioavailability of pancreatic kininogenase enteric-coated tablets. We conducted in vitro studies on PK using the Caco-2 cell model and quantified PK levels using the enzyme-linked immunosorbent assay (ELISA) method. We conducted methodological verification by blending SNAC and PK powders into enteric-coated capsules, and studied the pharmacokinetic characteristics. Based on the PK transport assay, the cumulative permeation rates of the test group that employed a SNAC to PK ratio of 32:1, 16:1, 8:1, 4:1, and 2:1 were 13.574%, 7.597%, 10.653%, 3.755%, and 2.523%, respectively. We conducted a uniformity test on the powder that contained a blend of SNAC and PK. The relative standard deviations (RSDs) for both the power containing SNAC and the power not containing SNAC were less than 10%. Based on the methodological verification, in vivo pharmacokinetic study of PK met the experimental requirements. As indicated by the results of in vivo pharmacokinetic research on rats, the test group (This group used SNAC) had a PK AUC0-12 h of 5679.747 ng/L*h and t1/2 of 4.569 h, while the control group (This group did not use SNAC) had a PK AUC0-12 h of 4639.665 ng/L*h and t1/2 of 3.13 h. This study has established a low-cost, environmentally friendly, and safe SNAC synthesis route with high process yield suitable for industrial production. SNAC demonstrates an absorption-enhancing effect on PK, and the optimal ratio of SNAC to PK is determined to be 32:1.
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Caprilatos , Calicreínas , Humanos , Ratos , Animais , Administração Oral , Células CACO-2RESUMO
The tomato is one of the most important vegetable crops grown worldwide. Tomato brown rugose fruit virus (ToBRFV), a seed-borne tobamovirus, poses a serious threat to tomato production due to its ability to break the resistant genes (Tm-1, Tm-2, Tm-22) in tomatoes. The objective of this work was to identify new resistant source(s) of tomato germplasm against ToBRFV. To achieve this aim, a total of 476 accessions from 12 Solanum species were tested with the ToBRFV US isolate for their resistance and susceptibility. As a result, a total of 44 asymptomatic accessions were identified as resistant/tolerant, including thirty-one accessions of S. pimpinellifolium, one accession of S. corneliomulleri, four accessions of S. habrochaites, three accessions of S. peruvianum, and five accessions of S. subsection lycopersicon hybrid. Further analyses using serological tests identified four highly resistant S. pimpinellifolium lines, PI 390713, PI 390714, PI 390716, and PI 390717. The inheritance of resistance in the selected lines was verified in the next generation and confirmed using RT-qPCR. To our knowledge, this is a first report of high resistance to ToBRFV in S. pimpinellifolium. These new genetic resources will expand the genetic pool available for breeders to develop new resistant cultivars of tomato against ToBRFV.
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Bottle gourd (Lagenaria siceraria (Mol.) Strandl.) is an economically important vegetable crop and one of the earliest domesticated crops. However, the population history and genomic diversification of bottle gourd have not been extensively studied. We generated a comprehensive bottle gourd genome variation map from genome sequences of 197 world-wide representative accessions, which enables a genome-wide association study for identifying genomic loci associated with resistance to zucchini yellow mosaic virus, and constructed a bottle gourd pangenome that harbors 1534 protein-coding genes absent in the reference genome. Demographic analyses uncover that domesticated bottle gourd originated in Southern Africa c. 12 000 yr ago, and subsequently radiated to the New World via the Atlantic drift and to Eurasia through the efforts of early farmers in the initial Holocene. The identified highly differentiated genomic regions among different bottle gourd populations harbor many genes contributing to their local adaptations such as those related to disease resistance and stress tolerance. Presence/absence variation analysis of genes in the pangenome reveals numerous genes including those involved in abiotic/biotic stress responses that have been under selection during the world-wide expansion of bottle gourds. The bottle gourd variation map and pangenome provide valuable resources for future functional studies and genomics-assisted breeding.
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Variação Genética , Genoma de Planta , Genômica , Genômica/métodos , Cucurbitaceae/genética , Filogenia , Genética Populacional , Resistência à Doença/genética , Genes de Plantas , Estudo de Associação Genômica Ampla , Doenças das Plantas/virologia , Doenças das Plantas/genéticaRESUMO
Nearly all glioblastoma (GBM) patients relapse following standard treatment and eventually succumb to disease. While large-scale, integrated multiomic studies have tremendously advanced the understanding of primary GBM at the cellular and molecular level, the posttherapeutic trajectory and biological properties of recurrent GBM remain poorly understood. This knowledge gap was addressed in a recent Cancer Cell article in which Kim and colleagues report on a highly integrative proteogenomic analysis performed on 123 matched primary and recurrent GBMs that uncovered a dramatic evolutionary shift from a proliferative state at initial diagnosis to the activation of neuronal and synaptogenic pathways at recurrence following therapy. Neuronal transition was characterized by posttranslational activation of WNT/PCP signaling and BRAF kinase, while many canonical oncogenic pathways, and EGFR in particular, were downregulated. Parallel multiomics analyses of patient-derived xenograft (PDX) models corroborated this evolutionary trajectory, allowing in vivo experiments for translational significance. Notably, targeting BRAF kinase disrupted both the neuronal transition and migration capabilities of recurrent gliomas, which were key characteristics of posttreatment progression. Furthermore, combining BRAF inhibitor vemurafenib with temozolomide prolonged survival in PDX models. Overall, the results reveal novel biological mechanisms of GBM evolution and therapy resistance, and suggest promising therapeutic intervention.
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Neoplasias Encefálicas , Glioblastoma , Proteogenômica , Humanos , Glioblastoma/genética , Glioblastoma/patologia , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Proteogenômica/métodos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Animais , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/metabolismo , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/tratamento farmacológico , Camundongos , Temozolomida/farmacologiaRESUMO
Manganese ions (Mn2+)-coordinated nanoparticles have emerged as a promising class of antitumor nanotherapeutics, capable of simultaneously disrupting the immunosuppressive tumor microenvironment (TME) and triggering the stimulator of interferon genes (STING) pathway-dependent antitumor immunity. However, the activation of STING signaling by Mn2+-based monotherapies is suboptimal for comprehensive stimulation of antigen presenting cells and reversal of immunosuppression in the TME. Here, we report the design of a Mn2+/CpG oligodeoxynucleotides (ODNs) codecorated black phosphorus nanosheet (BPNS@Mn2+/CpG) platform based on the Mn2+ modification of BPNS and subsequent adsorption of synthetic CpG ODNs. The coordination of Mn2+ significantly improved the stability of BPNS and the adsorption of CpG ODNs. The acidic TME and endosomal compartments can disrupt the Mn2+ coordination, triggering pH-responsive release of CpG ODNs and Mn2+ to effectively activate the Toll-like receptor 9 and STING pathways. As a result, M2-type macrophages and immature dendritic cells were strongly stimulated in the TME, thereby increasing T lymphocyte infiltration and reversing the immunosuppression within the TME. Phototherapy and chemodynamic therapy, utilizing the BPNS@Mn2+/CpG platform, have demonstrated efficacy in inducing immunogenic cell death upon 808 nm laser irradiation. Importantly, the treatment of BPNS@Mn2+/CpG with laser irradiation exhibited significant therapeutic efficacy against the irradiated primary tumor and effectively suppressed the growth of nonirradiated distant tumor. Moreover, it induced a robust immune memory, providing long-lasting protection against tumor recurrence. This study demonstrated the enhanced antitumor potency of BPNS@Mn2+/CpG in multimodal therapy, and its proof-of-concept application as a metal ion-modified BPNS material for effective DNA/drug delivery and immunotherapy.
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Nanopartículas , Neoplasias , Humanos , Oligodesoxirribonucleotídeos/farmacologia , Terapia Combinada , Imunoterapia , Neoplasias/tratamento farmacológico , Microambiente TumoralRESUMO
OBJECTIVES: Persistent growth of Mycobacterium abscessus complex (MABC) in the respiratory system is not uncommon and may indicate continuous infection of MABC lung disease (MABC-LD), but its prevalence, risk factors, and clinical impact have not been investigated. METHODS: The present study was conducted in two medical centers in northern Taiwan. We enrolled patients with MABC-LD and investigated the prevalence and predictors of persistent culture positivity (MABC-PP). Furthermore, we analyzed the association between MABC-PP and radiographic or clinical progression. RESULTS: Among 189 patients with MABC-LD, 58 were in the MABC-PP group. Independent predictors for MABC-PP included an increasing radiographic score and highest acid-fast stain (AFS) of strong positivity (3-4+) at initial diagnosis (compared with negative AFS). MABC-PP and highest AFS were independently associated with MABC-LD progression by the multivariable analysis model. The adjusted hazard ratio increased to 3.56 when the two independent factors existed. CONCLUSIONS: MABC-PP accounted for 30.7% and was predicted by initial AFS grade and radiographic score. Patients with MABC-PP, and highest AFS grade might have disease progression.
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Pneumopatias , Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Humanos , Infecções por Mycobacterium não Tuberculosas/microbiologia , Prevalência , Pneumopatias/microbiologia , Fatores de Risco , Antibacterianos/uso terapêuticoRESUMO
Extracellular vesicles (EVs) derived from human adipose mesenchymal stem cells (hADSCs) may exert a therapeutic benefit in alleviating sepsis-induced organ dysfunction by delivering cargos that include RNAs and proteins to target cells. The current study aims to explore the protective effect of miR-150-5p delivered by hADSC-EVs on sepsis-induced acute lung injury (ALI). We noted low expression of miR-150-5p in plasma and bronchoalveolar lavage fluid samples from patients with sepsis-induced ALI. The hADSC-EVs were isolated and subsequently cocultured with macrophages. It was established that hADSC-EVs transferred miR-150-5p to macrophages, where miR-150-5p targeted HMGA2 to inhibit its expression and, consequently, inactivated the MAPK pathway. This effect contributed to the promotion of M2 polarization of macrophages and the inhibition of proinflammatory cytokines. Further, mice were made septic by cecal ligation and puncture in vivo and treated with hADSC-EVs to elucidate the effect of hADSC-EVs on sepsis-induced ALI. The in vivo experimental results confirmed a suppressive role of hADSC-EVs in sepsis-induced ALI. Our findings suggest that hADSC-EV-mediated transfer of miR-150-5p may be a novel mechanism underlying the paracrine effects of hADSC-EVs on the M2 polarization of macrophages in sepsis-induced ALI.
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Lesão Pulmonar Aguda , Vesículas Extracelulares , Células-Tronco Mesenquimais , MicroRNAs , Sepse , Humanos , Animais , Camundongos , Sepse/complicações , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/terapia , MicroRNAs/genéticaRESUMO
OBJECTIVES: The experience of thermal ablation of lung lesions is limited, especially performing the procedure under localisation by cone-beam CT in the hybrid operation room (HOR). Here, we present the experience of microwave ablation (MWA) of lung nodules in the HOR. METHODS: We reviewed patients who underwent image-guide percutaneous MWA for lung nodules in the HOR under general anaesthesia between July 2020 and July 2022. The workflow in the HOR including the pre-procedure preparation, anaesthesia consideration, operation methods, and postoperative care was clearly described. RESULTS: Forty lesions in 33 patients who underwent MWA under general anaesthesia (GA) in the HOR were analysed. Twenty-seven patients had a single pulmonary nodule, and the remaining six patients had multiple nodules. The median procedure time was 41.0 min, and the median ablation time per lesion was 6.75 min. The median global operation room time was 115.0 min. The median total dose area product was 14881 µGym2. The median ablation volume was 111.6 cm3. All patients were discharged from the hospital with a median postoperative stay of 1 day. Four patients had pneumothorax, two patients had pleural effusion during the first month of outpatient follow-up, and one patient reported intercostal neuralgia during the 3-month follow-up. CONCLUSIONS: Thermal ablation of pulmonary nodules under GA in the HOR can be performed safely and efficiently if we follow the workflow provided. The procedure provides an alternative to managing pulmonary nodules in patients. CLINICAL RELEVANCE STATEMENT: Thermal ablation of pulmonary nodules under GA in the HOR can be performed safely and efficiently if the provided workflow is followed. KEY POINTS: ⢠We tested the feasibility of microwave ablation of lung lesions performed in a hybrid operating room. ⢠To this end, we provide a description of microwave ablation of the lung under cone-beam CT localisation. ⢠We describe a workflow by which ablation of the pulmonary nodule can be performed safely under general anaesthesia.
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Bottle gourd (Lagenaria siceraria L.) belongs to the cucurbit family and has a long history of cultivation in tropical and subtropical regions worldwide, both for food and medicine. Popularized by its unique fruit shapes, gourds are used to make ornaments and musical instruments. However, there is limited information on volatile organic compounds (VOCs) in the bottle gourd fruit. In the present study, we conducted a comparative analysis of VOCs profiled in two accessions (USVL5 and USVL10) with distinct fruit shapes: bottle and cylinder. While USVL5 only produced long cylinder fruits, USVL10 produced two fruit types, cylinder (USVL10CYN) and bottle (USVL10A and USVL10B). VOCs in each line were analyzed using headspace solid-phase microextraction-gas chromatography/mass spectrometry (HS-SPME-GC/MS). Aliphatic aldehydes and alcohols were the most abundant compounds found in these bottle gourd accessions. Based on the functional profile of the identified VOCs, our results reveal the suitability of our tested line (USVL10), enriched in functionally important VOCs such as hexanal (abundance = 381.07), nonanal (abundance = 9.85), 2-methoxy-2-methylpropane (abundance = 21.26) and D-limonene (abundance = 31.48). The VOCs profiling and functional analyses support the notion that the bottle gourd accession USVL10 can be a good candidate for its use in agriculture, the health care industry and domestic uses.
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Investigation on a competitive endogenous RNA (ceRNA) network attracted lots of attention due its function in cancer regulation. Here, we probed into the possible molecular mechanism of circSSPO/microRNA-6820-5p (miR-6820-5p)/kallikrein-related peptidase 8 (KLK8)/PKD1 network in the esophageal squamous cell carcinoma (ESCC). Following whole-transcriptome sequencing and differential analysis in collected ESCC tissue samples, circRNA-miRNA-mRNA regulatory network affecting ESCC was investigated. After interaction measurement among circSSPO/miR-6820-5p/KLK8/PKD1, their regulatory roles in ESCC cell functions in vitro and xenograft tumor growth and lung metastasis in vivo were analyzed. The bioinformatics prediction and sequencing results screened that circSSPO, miR-6820-5p, KLK8, and PKD1 were associated with ESCC development. In ESCC, miR-6820-5p was expressed at very low levels, while circSSPO, KLK8, and PKD1 were highly expressed. In vitro cell experiments further proved that circSSPO competitively inhibited miR-6820-5p to induce ESCC cell malignant properties. Moreover, knockdown of KLK8 or PKD1 inhibited ESCC cell malignant properties. circSSPO also promoted the tumorigenic and metastasis of ESCC through the upregulation of KLK8 and PKD1 expression in vivo. We found that circSSPO was an oncogenic circRNA that was significantly abundant in ESCC tissues and circSSPO exhibited an oncogenic activity in ESCC by elevating expression of KLK8 and PKD1 through suppressing miR-6820-5p expression.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , MicroRNAs , RNA Circular , Humanos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica , Calicreínas/genética , Calicreínas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , Regulação para Cima/genéticaRESUMO
The development and performance of a DNA probe adsorbing Mn2+-modified black phosphorus (BP@Mn2+/DNA) hybrid nanosensor is reported that enables rapid detection of cancer-derived exosomal microRNAs (miRNAs) and exosomes. This two-dimensional (2D) nanosensor can spontaneously penetrate the lipid bilayer of exosome membranes owing to its ultra-thin geometry. Subsequently, the adsorbed probe specifically hybridizes with the target miRNA and then dissociates from the nanosensor surface, generating fluorescent signals. Therefore, the BP@Mn2+/DNA nanosensor can differentiate between colorectal cancer (CRC) cell-derived exosomes and those derived from intestinal epithelial cells through sensing of exosomal miRNAs. Furthermore, when the epithelial cell adhesion molecule (EpCAM) aptamer is adsorbed onto BP@Mn2+ instead of the miRNA probe, the nanosensor is able to distinguish exosomes derived from the plasma of CRC patients from those of healthy controls by the recognition ability of the EpCAM aptamer. By utilizing this nanosensor, we were able to effectively differentiate cancer-derived exosomes through the direct detection of miRNA-21 within the exosomes, as well as the identification of specific exosomal membrane proteins. This nanosensor design paves the way for the development of rapid and efficient cancer-derived exosomal miRNA and exosome biosensing nanoplatforms.
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Exossomos , MicroRNAs , Neoplasias , Humanos , Exossomos/metabolismo , Molécula de Adesão da Célula Epitelial/metabolismo , Neoplasias/metabolismo , Oligonucleotídeos/metabolismoRESUMO
Lung cancer is the most lethal cancer type in Taiwan and worldwide. Early detection and treatment advancements have improved survival. However, small peripheral pulmonary nodules (PPN) biopsy is often challenging, relying solely on bronchoscopy with radial endobronchial ultrasound (EBUS). Augmented fluoroscopy overlays the intra-procedural cone-beam computed tomography (CBCT) images with fluoroscopy enabling real-time three-dimensional localization during bronchoscopic transbronchial biopsy. The hybrid operating room (HOR), equipped with various types of C-arm CBCT, is a perfect suite for PPN diagnosis and other interventional pulmonology. This study shares the single institute experience of EBUS transbronchial biopsy of PPN with the aid of augmented fluoroscopic bronchoscopy (AFB) and CBCT in an HOR. We retrospectively enrolled patients who underwent robotic CBCT, augmented fluoroscopy-guided, radial endobronchial ultrasound-confirmed transbronchial biopsy and cryobiopsy in a hybrid operating room. Patient demographic characteristics, computed tomography images, rapid on-site evaluation cytology, and final pathology reports were collected. Forty-one patients underwent transbronchial biopsy and 6 received additional percutaneous transthoracic core-needle biopsy during the same procedure. The overall diagnostic yield was 88%. The complications included three patients with pneumothorax after receiving subsequent CT-guided percutaneous transthoracic needle biopsy, and two patients with hemothorax who underwent transbronchial cryobiopsy. Overall, the bronchoscopic biopsy of PPN using AFB and CBCT as precise guidance in the hybrid operating room is feasible and can be performed safely with a high diagnostic yield.
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Tomato is an important vegetable in the United States and around the world. Recently, tomato brown rugose fruit virus (ToBRFV), an emerging tobamovirus, has impacted tomato crops worldwide and can result in fruit loss. ToBRFV causes severe symptoms, such as mosaic, puckering, and necrotic lesions on leaves; other symptoms include brown rugose and marbling on fruits. More importantly, ToBRFV can overcome resistance in tomato cultivars carrying the Tm-22 locus. In this study, we recovered ToBRFV sequences from tomato seeds, leaves, and fruits from the U.S., Mexico, and Peru. Samples were pre-screened using a real-time RT-PCR assay prior to high-throughput sequencing. Virus draft genomes from 22 samples were assembled and analyzed against more than 120 publicly available genomes. Overall, most sequenced isolates were similar to each other and did not form a distinct population. Phylogenetic analysis revealed three clades within the ToBRFV population. Most of the isolates (95%) clustered in clade 3. Genetic analysis revealed differentiation between the three clades indicating minor divergence occurring. Overall, pairwise identity showed limited genetic diversity among the isolates in this study with worldwide isolates, with a pairwise identity ranging from 99.36% and 99.97%. The overall population is undergoing high gene flow and population expansion with strong negative selection pressure at all ToBRFV genes. Based on the results of this study, it is likely that the limited ToBRFV diversity is associated with the rapid movement and eradication of ToBRFV-infected material between countries.
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Solanum lycopersicum , Tobamovirus , Frutas , Filogenia , Tobamovirus/genética , Variação GenéticaRESUMO
OBJECTIVES: Hybrid operating rooms (HOR) have been increasingly used for image-guided lung surgery, and most surgical teams have used percutaneous localization for small pulmonary nodules. We evaluated the feasibility and safety of augmented fluoroscopic bronchoscopy localization under endotracheal tube intubation general anaesthesia followed by thoracoscopic surgery as a single-stage procedure in ab HOR. METHODS: We retrospectively reviewed clinical records of patients who underwent single-stage augmented fluoroscopic bronchoscopy localization under general anaesthesia followed by thoracoscopic surgery in an HOR between August 2020 and March 2022. RESULTS: Single-stage localization and resection were performed for 85 nodules in 74 patients. The median nodule size was 8 mm [interquartile range (IQR), 6-9 mm], and the median distance from the pleural space was 10.9 mm (IQR, 8-20 mm). All nodules were identifiable on cone-beam computed tomography images and marked transbronchially with indigo carmine dye (median markers per lesion: 3); microcoils were placed for deep margins in 16 patients. The median localization time was 30 min (IQR 23-42 min), and the median fluoroscopy duration was 3.3 min (IQR 2.2-5.3 min). The median radiation exposure (expressed as the dose area product) was 4303.6 µGym2 (IQR 2879.5-6268.7 µGym2). All nodules were successfully marked and resected, and the median global operating room time was 178.5 min (IQR 153.5-204 min). There were no localization-related complications, and the median length of postoperative stay was 1 day (IQR, 1-2 days). CONCLUSIONS: Single-stage augmented fluoroscopic bronchoscopy localization under general anaesthesia followed by thoracoscopic surgery was feasible and safe.
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Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Nódulo Pulmonar Solitário , Humanos , Salas Cirúrgicas , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Estudos Retrospectivos , Broncoscopia , Cirurgia Torácica Vídeoassistida/métodos , Tomografia Computadorizada por Raios X/métodos , Nódulos Pulmonares Múltiplos/cirurgia , Fluoroscopia , Nódulo Pulmonar Solitário/cirurgiaRESUMO
To develop various biosensors, several 2D nanomaterials adsorb DNA probes (aptamers) via π-π stacking interactions. However, interference from DNA displacement by external non-targeted ligands has precluded their practical applications for specific detection and imaging at high protein concentrations. Metal coordination is an attractive strategy for biomolecular crosslinking and functional molecular self-assembly. Herein, a robust 2D biosensor nanoplatform was developed to enhance DNA adsorption and affinity using Mn2+-modified black phosphorus nanosheets (BPNS@Mn2+) via metal coordination. The Mn2+ can simultaneously coordinate with the lone pair electrons (π bonds) of the BPNS and nucleotide bases to provide binding sites for DNA nucleobases on the BPNS surface, which greatly enhances the stability of the inner BPNS and improves DNA adsorption and affinity. The DNA adsorption mechanism of BPNS@Mn2+ was also characterized, and is extensively discussed. Without any further modification, this BPNS@Mn2+/DNA biosensor specifically detected single-stranded DNA (linear range: 10-200 nM, detection limit: 5.76 nM) and thrombin (linear range: 20-180 nM, detection limit: 2.39 nM) in 100 nM bovine serum albumin solution. The nonspecific ligands in the environment did not affect the detection performance of the robust biosensor. In addition, the expression levels of microRNA-21 can be imaged and analyzed in living cells using this biosensor, which is consistent with the results of the polymerase chain reaction. This study highlights the potential of metal coordination in surface modification and provides new opportunities for biomedical applications of 2D nanomaterials with superior DNA-adsorption capacity, facilitating the development of biosensor design and nucleic acid/drug delivery.
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Técnicas Biossensoriais , MicroRNAs , Ácidos Nucleicos , Adsorção , Técnicas Biossensoriais/métodos , DNA/química , DNA de Cadeia Simples , Oligonucleotídeos , Fósforo , Soroalbumina Bovina , TrombinaRESUMO
Glioma stem cells (GSCs) are thought to drive growth and therapy resistance in glioblastoma (GBM) by "hijacking" at least a subset of signaling pathways active in normal neural stem cells (NSCs). Though the origins of GSCs still remain elusive, uncovering the mechanisms of self-renewing division and cell differentiation in normal NSCs has shed light on their dysfunction in GSCs. However, the distinction between self-renewing division pathways utilized by NSC and GSC becomes critical when considering options for therapeutically targeting signaling pathways that are specifically active or altered in GSCs. It is well-established that cyclin-dependent kinases (CDKs) regulate the cell cycle, yet more recent studies have shown that CDKs also play important roles in the regulation of neuronal survival, metabolism, differentiation, and self-renewal. The intimate relationship between cell cycle regulation and the cellular programs that determine self-renewing division versus cell differentiation is only beginning to be understood, yet seems to suggest potential differential vulnerabilities in GSCs. In this timely review, we focus on the role of CDKs in regulating the self-renewal properties of normal NSCs and GSCs, highlighting novel opportunities to therapeutically target self-renewing signaling pathways specifically in GBM.