ABSTRACT
High-capacity storage technologies are needed to meet our ever-growing data demands1,2. However, data centres based on major storage technologies such as semiconductor flash devices and hard disk drives have high energy burdens, high operation costs and short lifespans2,3. Optical data storage (ODS) presents a promising solution for cost-effective long-term archival data storage. Nonetheless, ODS has been limited by its low capacity and the challenge of increasing its areal density4,5. Here, to address these issues, we increase the capacity of ODS to the petabit level by extending the planar recording architecture to three dimensions with hundreds of layers, meanwhile breaking the optical diffraction limit barrier of the recorded spots. We develop an optical recording medium based on a photoresist film doped with aggregation-induced emission dye, which can be optically stimulated by femtosecond laser beams. This film is highly transparent and uniform, and the aggregation-induced emission phenomenon provides the storage mechanism. It can also be inhibited by another deactivating beam, resulting in a recording spot with a super-resolution scale. This technology makes it possible to achieve exabit-level storage by stacking nanoscale disks into arrays, which is essential in big data centres with limited space.
ABSTRACT
LiMn1-yFeyPO4 (LMFP) is a significant and cost-effective cathode material for Li-ion batteries, with a higher working voltage than LiFePO4 (LFP) and improved safety features compared to layered oxide cathodes. However, its commercial application faces challenges due to a need for a synthesis process to overcome the low Li-ion diffusion kinetics and complex phase transitions. Herein, a solid-state synthesis process using LFP and nano LiMn0.7Fe0.3PO4 (MF73) is proposed. The larger LFP acts as a structural framework fused with nano-MF73, preserving the morphology and high performance of LFP. These results demonstrate that the solid-state reaction occurs quickly, even at a low sintering temperature of 500 °C, and completes at 700 °C. However, contrary to the expectations, the larger LFP particles disappeared and fused into the nano-MF73 particles, revealing that Fe ions diffuse more easily than Mn ions in the olivine framework. This discovery provides valuable insights into understanding ion diffusion in LMFP. Notably, the obtained LMFP can still deliver an initial capacity of 142.3 mAh g-1, and the phase separation during the electrochemical process is significantly suppressed, resulting in good cycling stability (91.1% capacity retention after 300 cycles). These findings offer a promising approach for synthesizing LMFP with improved performance and stability.
ABSTRACT
Cuproptosis is a novel form of regulated cell death which guarantees to increase the efficacy of existing anticancer treatments that employ traditional apoptotic therapeutics. However, reducing the amount of undesirable Cu ions released in normal tissue and maximizing Cu-induced cuproptosis therapeutic effects at tumor sites are the major challenges. In this study, exploiting the chemical properties of copper ionophores and the tumor microenvironment, a novel method is developed for controlling the valence of copper ions that cause photoinduced cuproptosis in tumor cells. CJS-Cu nanoparticles (NPs) can selectively induce cuproptosis after cascade reactions through H2 O2 -triggered Cu2+ release, photoirradiation-induced superoxide radical (âO2 - ) generation, and reduction of Cu2+ to Cu+ by âO2 - . The generated reactive oxygen species can result in glutathione depletion and iron-sulfur cluster protein damage and further augmented cuproptosis. CJS-Cu NPs effectively suppressed tumor growth and downregulated the expression of metastasis-related proteins, contributing to the complete inhibition of lung metastasis. Ultimately, this study suggests novel avenues for the manipulation of cellular cuproptosis through photochemical reactions.
Subject(s)
Lung Neoplasms , Nanoparticles , Humans , Copper , Glutathione , Superoxides , Apoptosis , Tumor MicroenvironmentABSTRACT
In ovo vaccination is an attractive immunization approach for chickens. However, most live Newcastle disease virus (NDV) vaccine strains used safely after hatching are unsafe as in ovo vaccines due to their high pathogenicity for chicken embryos. The mechanism for viral pathogenicity in chicken embryos is poorly understood. Our previous studies reported that NDV strain TS09-C was a safe in ovo vaccine, and the F protein cleavage site (FCS) containing three basic amino acids (3B-FCS) was the crucial determinant of the attenuation of TS09-C in chicken embryos. Here, five trypsin-like proteases that activated NDV in chicken embryos were identified. The F protein with 3B-FCS was sensitive to the proteases Tmprss4, Tmprss9, and F7, was present in fewer tissue cells of chicken embryos, which limited the viral tropism, and was responsible for the attenuation of NDV with 3B-FCS, while the F protein with FCS containing two basic amino acids could be cleaved not only by Tmprss4, Tmprss9, and F7 but also by Prss23 and Cfd, was present in most tissue cells, and thereby was responsible for broad tissue tropism and high pathogenicity of virus in chicken embryos. Furthermore, when mixed with the protease inhibitors aprotinin and camostat, NDV with 2B-FCS exhibited greatly weakened pathogenicity in chicken embryos. Thus, our results extend the understanding of the molecular mechanism of NDV pathogenicity in chicken embryos and provide a novel molecular target for the rational design of in ovo vaccines, ensuring uniform and effective vaccine delivery and earlier induction of immune protection by the time of hatching. IMPORTANCE As an attractive immunization approach for chickens, in ovo vaccination can induce a considerable degree of protection by the time of hatching, provide support in closing the window in which birds are susceptible to infection, facilitate fast and uniform vaccine delivery, and reduce labor costs by the use of mechanized injectors. The commercial live Newcastle disease virus (NDV) vaccine strains are not safe for in ovo vaccination and cause the death of chicken embryos. The mechanism for viral pathogenicity in chicken embryos is poorly understood. In the present study, we identified five trypsin-like proteases that activate NDV in chicken embryos and elucidated their roles in the tissue tropism and pathogenicity of NDV used as in ovo vaccine. Finally, we revealed the molecular basis for the pathogenicity of NDV in chicken embryos and provided a novel strategy for the rational design of in ovo ND vaccines.
Subject(s)
Newcastle Disease , Peptide Hydrolases , Poultry Diseases , Viral Vaccines , Animals , Chick Embryo , Antibodies, Viral , Chickens , Newcastle Disease/immunology , Newcastle Disease/virology , Newcastle disease virus/physiology , Peptide Hydrolases/metabolism , Poultry Diseases/immunology , Poultry Diseases/virology , Vaccines, Attenuated , Viral Vaccines/administration & dosage , VirulenceABSTRACT
Colorectal cancer (CRC) is the second most common cause of cancer-related mortality and lies third in terms of morbidity due to the limited number of effective druggable targets. Since cancer stem cells (CSCs) are considered to be one of the roots of tumorigenesis, outgrowth and metastasis, targeting CSCs may be a promising strategy to reverse the malignant phenotypes of CRC. Cyclin-dependent kinase 12 (CDK12) has been reported to be involved in the self-renewal of CSCs in various cancers, rendering it an attractive potential target against CSCs to consequently limit the malignant phenotypes in CRC. In the present study, we aimed to investigate whether CDK12 can be a potential therapeutic target for patients with CRC and clarify its underlying mechanism. We found that CDK12, but not CDK13 is required for CRC survival. CDK12 was found to drive tumor initiation according to the colitis-associated colorectal cancer mouse model. In addition, CDK12 promoted CRC outgrowth and hepatic metastasis in the subcutaneous allograft and liver metastasis mouse models, respectively. In particular, CDK12 was able to induce the self-renewal of CRC CSCs. Mechanistically, the activation of Wnt/ß-catenin signaling mediated by CDK12 was implicated in stemness regulation and malignant phenotype maintenance. These findings indicate that CDK12 is a candidate druggable target in CRC. Therefore, the CDK12 inhibitor SR-4835 warrants clinical trial testing in patients with CRC.
Subject(s)
Colorectal Neoplasms , Wnt Signaling Pathway , Animals , Mice , beta Catenin/metabolism , Carcinogenesis/genetics , Cell Line, Tumor , Cell Proliferation , Cell Transformation, Neoplastic/genetics , Colorectal Neoplasms/pathology , Cyclin-Dependent Kinases/metabolism , Disease Models, Animal , Gene Expression Regulation, Neoplastic , Neoplastic Stem Cells/metabolism , Phenotype , Wnt Signaling Pathway/geneticsABSTRACT
Objective: The objective of this study was to integrate metabolomics and transcriptomics data to identify key diagnostic and prognostic markers for esophageal squamous cell carcinoma (ESCC). Plasma samples were collected from 85 ESCC patients at different stages and 50 healthy volunteers for non-targeted metabolomic analysis. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for non-targeted metabolomic analysis. Subsequently, we integrated the metabolomic data with transcriptomic data from the Gene Expression Omnibus (GEO) and prognosis data from The Cancer Genome Atlas Program (TCGA) to perform pathway analysis. Our focus was on pathways that involve both metabolites and upstream genes, as they often exhibit higher accuracy. Results: Through the integration of metabolomics and transcriptomics, we identified significant alterations in the platelet activation pathway in ESCC. This pathway involves the participation of both metabolites and genes, making it a more accurate reflection of pathological changes associated with the disease. Notably, metabolite arachidonic acid (AA) and chemokine receptor type 2(CXCR2) were significantly downregulated in ESCC, while genes collagen type I alpha 1(COL1A1), collagen type I alpha 2(COL1A2), collagen type III alpha 1(COL3A1), type 3 inositol 1,4,5-trisphosphate receptor (ITPR3), and insulin-like growth factor II mRNA binding protein 3(IGF2BP3) were significantly upregulated, indicating the presence of tumor-induced platelet activation in ESCC. Further analysis of prognosis data revealed that high expression of COL1A1, IGF2BP3, and ITPR3 was associated with a favorable prognosis for ESCC, while high CXCR2 expression was linked to an adverse prognosis. In addition, we combined COL1A1, ITPR3, IGF2BP3, CXCR2, and AA to form a diagnostic biomarker panel. The receiver operating characteristic curve (ROC) demonstrated excellent diagnostic capability (AUC=0.987). Conclusion: Our study underscores the significant role of platelet activation pathways and related genes in the diagnosis and prognosis of ESCC patients. These findings offer promising insights for improving the clinical management of ESCC.
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Layered transition-metal (TM) oxides have drawn ever-growing interest as positive electrode materials in potassium-ion batteries (PIBs). Nevertheless, the practical implementation of these positive electrode materials is seriously hampered by their inferior cyclic property and rate performance. Reported here is a self-templating strategy to prepare homogeneous P2-K0.6CoO2 (KCO) microcubes. Benefiting from the unusual microcube architecture, the interface between the electrolyte and the active material is considerably diminished. As a result, the KCO microcubes manifest boosted electrochemical properties for potassium storage including large reversible capacity (87.2 mAh g-1 under 20 mA g-1), superior rate performance, and ultralong cyclic steady (an improved capacity retention of 86.9% under 40 mA g-1 after 1000 cycles). More importantly, the fabrication approach can be effectively extended to prepare other layered TM oxide (P3-K0.5MnO2, P3-K0.5Mn0.8Fe0.2O2, P2-K0.6Co0.67Mn0.33O2, and P2-K0.6Co0.66Mn0.17Ni0.17O2) microcubes and nonlayered TM oxide (KFeO2) microcubes.
ABSTRACT
Metal hexacyanoferrates (HCFs) are regarded as promising cathode materials for potassium-ion batteries (PIBs) on account of their low cost and high energy density. However, the difficult-to-remove [Fe(CN)6] vacancies and crystal water lead to structural instability and capacity deterioration as well as the stereotype of poor thermostability of conventional HCFs. Herein, we report (100) face-oriented potassium magnesium hexacyanoferrate (KMgHCF) nanoplates with low [Fe(CN)6] vacancies and high crystallinity, enabling thermostability up to 550 °C, high-temperature carbon coating and crystal water elimination. The as-obtained KMgHCF/C nanoplates exhibit superior potassium storage properties, including a large reversible capacity of 84.6â mAh g-1, a high voltage plateau of 3.87â V, excellent long-term cycling performance over 15000â cycles and high rate capability at 5â A g-1. The unprecedented cycling stability of KMgHCF/C is attributed to the synergistic effect of a highly reversible two-phase reaction, low [Fe(CN)6] vacancies and no crystal water, a specially exposed steady (100) surface, and a protective carbon coating. This work provides a new material selection and modification strategy for the practical application of HCFs in PIBs.
ABSTRACT
OBJECTIVES: To assess the safety and efficacy of ultrasound-guided thermal ablation for low-risk papillary thyroid microcarcinoma (PTMC) via a prospective multicenter study. METHODS: From January 2017 through June 2021, low-risk PTMC patients were screened. The management details of active surveillance (AS), surgery, and thermal ablation were discussed. Among patients who accepted thermal ablation, microwave ablation (MWA) was performed. The main outcome was disease-free survival (DFS). The secondary outcomes were tumor size and volume changes, local tumor progression (LTP), lymph node metastasis (LNM), and complication rate. RESULTS: A total of 1278 patients were included in the study. The operation time of ablation was 30.21 ± 5.14 min with local anesthesia. The mean follow-up time was 34.57 ± 28.98 months. Six patients exhibited LTP at 36 months, of whom 5 patients underwent a second ablation, and 1 patient received surgery. The central LNM rate was 0.39% at 6 months, 0.63% at 12 months, and 0.78% at 36 months. Of the 10 patients with central LNM at 36 months, 5 patients chose ablation, 3 patients chose surgery and the other 2 patients chose AS. The overall complication rate was 1.41%, and 1.10% of patients developed hoarseness of the voice. All of the patients recovered within 6 months. CONCLUSIONS: Thermal ablation of low-risk PTMC was observed to be safe and efficacious with few minor complications. This technique may help to bridge the gap between surgery and AS as treatment options for patients wishing to have their PTMC managed in a minimally invasive manner. CLINICAL RELEVANCE STATEMENT: This study proved that microwave ablation is a safe and effective treatment method for papillary thyroid microcarcinoma. KEY POINTS: Percutaneous US-guided microwave ablation of papillary thyroid microcarcinoma is a very minimally invasive treatment under local anesthesia during a short time period. The local tumor progression and complication rate of microwave ablation in the treatment of papillary thyroid microcarcinoma are very low.
Subject(s)
Radiofrequency Ablation , Thyroid Neoplasms , Humans , Microwaves/therapeutic use , Prospective Studies , Thyroid Neoplasms/surgery , Thyroid Neoplasms/pathology , Radiofrequency Ablation/methods , Treatment Outcome , Retrospective StudiesABSTRACT
Target double-stranded DNA (dsDNA) or single-stranded DNA (ssDNA) can activate the trans-cleavage activity of the CRISPR/Cas12a, cutting the surrounding non-target ssDNA arbitrarily. In a typical CRISPR/Cas12a system, this non-target ssDNA, with a fluorescent tag and its quencher incorporated at both ends (ssDNA-FQ), is usually used as the reporter. Here, a 2-aminopurine probe (T-pro 4), made by inserting four 2-APs in non-target ssDNA, was screened for using as a reporter in the CRISPR/Cas12a system. Compared with ssDNA-FQ, each 2-AP probe is cleaved by the activated CRISPR/Cas12a system, multi-unit signals are generated. Therefore, the CRISPR/Cas12a system using the 2-AP probe as a reporter may be more sensitive than the CRISPR/Cas12a system which uses ssDNA-FQ as the reporter. We achieved ssDNA detection at as little as 10-11 M using the 2-AP probe as the reporter in the CRISPR/Cas12a system. Compared to the CRISPR/Cas12a system using ssDNA-FQ as the reporter, its sensitivity increased by an order of magnitude. Furthermore, the method that combines PCR and the 2-AP-probe-mediated CRISPR/Cas12a system can detect goat pox virus (GTPV) down to 8.35 × 10-2 copies per µL, 10 times lower than the method that combines PCR and the ssDNA-FQ-mediated CRISPR/Cas12a system. These results indicate that the CRISPR/Cas12a system using the screened 2-AP probe as a reporter has potential in highly sensitive detection of viruses.
Subject(s)
2-Aminopurine , Biosensing Techniques , CRISPR-Cas Systems/genetics , DNA, Single-Stranded/genetics , Coloring Agents , Polymerase Chain ReactionABSTRACT
Image-defined risk factors (IDRF) in neuroblastoma have been developed to predict tumor resectability and surgical complications; however, the potential prognostic value of IDRF in neuroblastoma has been variably reported. Previous studies did not report the IDRF status separately from the International Neuroblastoma Risk Group (INRG) stage. Moreover, the association between IDRF and clinical and pathological factors has not been discussed further. In this retrospective study, we investigated the clinical and biological features of neuroblastoma at different INRG stages based on IDRF. Event-free survival (EFS) and overall survival (OS) related to the INRG stage were analyzed using log-rank tests, and the prognostic value of the IDRF number and type was also evaluated. Among 72 patients, 182 IDRF at diagnosis were found in 79.2%. The distribution of the INRG stages was 10 L1 (13.9.0%), 25 L2 (34.7%), and 37 M/MS (51.4%). Patients with stage M/Ms had a larger tumor volume, a higher percentage of age ≥ 18 months, elevated lactate dehydrogenase (LDH) level, elevated ferritin level, and a higher percentage of COG high-risk compared with stage L1 and L2 patients. EFS and OS were similar for stage L1 and L2 tumors but were significantly poorer for metastatic disease. However, EFS (P = 0.06) and OS (P = 0.07) were similar for IDRF-negative and positive neuroblastomas. Patients with stage M/Ms with IDRF-positive had poorer EFS (P = 0.001) and OS (P < 0.001) compared with patients in stage L2. An IDRF ≥ 4, vascular IDRF, and infiltrative IDRF of the tumor were significant indicators of poor prognosis. Conclusion: Our study indicates that increasing the INRG stages based on IDRF is associated with various unfavorable clinical features of neuroblastoma. The principal determinant of survival in neuroblastoma is the presence of metastatic disease more than IDRF alone at diagnosis. Both the number and type of IDRF have important clinical significance in the protocol planning of neuroblastoma, rather than just considering the absence or presence of IDRF. What is Known: ⢠The International Neuroblastoma Risk Group Staging System (INRGSS) now employs image-defined risk factors (IDRFs) to stratify and stage disease. ⢠The presence of IDRF at diagnosis are associated with higher rates of operative complications and incomplete surgical resection. What is New: ⢠The principal determinant of survival from neuroblastoma is the presence of metastatic disease at diagnosis, more than IDRF alone. ⢠IDRF number and type should also be considered during the diagnosis and treatment planning of neuroblastoma, rather than just considering the absence or presence of IDRF.
Subject(s)
Neuroblastoma , Humans , Infant , Retrospective Studies , Neoplasm Staging , Neuroblastoma/diagnosis , Neuroblastoma/pathology , Risk Factors , Prognosis , BiologyABSTRACT
OBJECTIVES: The objective of our study was to assess the ability of contrast-enhanced ultrasound (CEUS) in evaluating renal microperfusion in an animal model. METHODS: Twenty Sprague-Dawley rats were subdivided into two groups: the normal and chronic intermittent hypoxia (CIH) groups. In the CIH model, 10 Sprague-Dawley rats were exposed to CIH for 8 weeks to mimic obstructive sleep apnea (OSA). The CEUS parameters of the renal cortex and medulla were obtained and compared between groups. The pathological changes of the kidney tissues were examined by histological staining such as hematoxylin and eosin (H&E) and Masson's trichrome. RESULTS: CIH caused morphological damage to kidneys. In the cortex, the peak intensity (PI) (P = .009) was significantly lower and time to peak (Ttop) (P = .019) was significantly prolonged in the CIH group compared with the controls. The area under ascending curve (WiAUC) in the medulla and cortex were both significantly lower in the CIH group than those in the control group (P both <.05). CEUS parameters (including PI and WiAUC of the cortex and WiAUC of the medulla) were negatively correlated with serum creatinine (P all <.05). In the medulla, the area under descending curve (WoAUC) was positively correlated with serum creatinine (P = .027), PI was negatively correlated with uric acid (P = .034). CONCLUSION: CEUS parameters (including Ttop, PI, WoAUC, and WiAUC) reflect renal microvascular changes in CIH. CEUS could be a safe and accurate imaging method to assess renal microvascular damage in CIH rats.
Subject(s)
Hypoxia , Kidney , Rats , Animals , Rats, Sprague-Dawley , Creatinine , Kidney/pathology , Hypoxia/diagnostic imaging , Hypoxia/pathology , Ultrasonography , Disease Models, AnimalABSTRACT
With high theoretical capacity and operating voltage, KVPO4F is a potential high energy density cathode material for potassium-ion batteries. However, its performance is usually limited by F loss, poor electronic conductivity, and unsteady electrode/electrolyte interface. Herein, a simple one-step sintering process is developed, where vanadium-oxalate-phosphite/phosphate frameworks and fluorinated polymer are used to synthesize carbon-coated KVPO4F nanoplates. It is found that the V-F-C bond generated by fluorinated-polymer-derived carbon at the interface of KVPO4F/C nanoplates diminishes the F loss, as well as enhances K-ions migration ability and the electronic conductivity of KVPO4F. The as-synthesized KVPO4F/C cathode delivers a reversible capacity of 106.5 mAh g-1 at 0.2 C, a high working voltage of 4.28 V, and a rate capability with capacity of 73.8 mAh g-1 at the ultrahigh current density of 100 C. In addition, a KVPO4F/C//soft carbon full cell exhibits a high energy density of 235.5 Wh kg-1.
ABSTRACT
1,7-Di-tert-butyl-substituted aza-BODIPYs (tBu-azaBDP) were successfully obtained for the first time. The structures of tBu-azaBDP and Ph-azaBDP were confirmed by X-ray crystal analysis, and tBu-azaBDP 2 is more twisted than Ph-azaBDP 5. tBu-azaBDPs have significant photo-stability and enhanced water solubility. tBu-azaBDPs possess excellent optical properties, such as high molar extinction coefficients, broad full width half maxima, and large Stokes shifts, which is comparable to those of the parent dye Ph-azaBDP. Although the low-barrier rotation of the distal -tBu groups in tBu-azaBDPs results in low quantum yield, photothermal conversion efficiency and singlet oxygen generation ability of tBu-azaBDPs are more effective than those of Ph-azaBDP, which is highly desirable for a photothermal-photodynamic therapy agent.
Subject(s)
Boron Compounds , Photochemotherapy , Singlet OxygenABSTRACT
Ischemic stroke leads to high mortality and disability rates in humans. Cerebral ischemic injury has a severe complex pathophysiological mechanism. The abnormal release of inflammatory cytokines will cause brain tissue damage and destroy the blood-brain barrier integrity, which aggravates the process of brain injury. Therefore, attenuating the level of inflammatory response is critical for the therapy of cerebral ischemia injury. This study examined the rule of SIP treatment to support neuron protective effect after cerebral injury in an animal model of middle cerebral artery occlusion (MCAO). After ischemia/reperfusion, neurological function, neuroglia cells activation, infarction volume, brain water content, brain tissue apoptosis ratio, and inflammatory response were assessed, and quantitative PCR and western blot were also detected, respectively. Treatment of SIP ameliorated neurological dysfunction, brain infarction, brain edema, and brain cell apoptosis after MCAO operation. Overexpression SIP also suppressed pro-inflammatory cytokines release. Furthermore, the protective effect of SIP on brain injury occurs through reduced neuroglia cells activation through downregulation of the NF-κB pathway. In summary, the present work indicated that SIP prevents ischemic cerebral infarction-induced inflammation and apoptosis by blocking inflammasome activation via NF-κB signaling pathway. Those results suggest that SIP treatment is an attractive strategy for prevention of ischemic cerebral infarction.
Subject(s)
Brain Injuries , Brain Ischemia , Receptors, Steroid , Reperfusion Injury , Animals , Brain Injuries/complications , Brain Injuries/metabolism , Cytokines/metabolism , Humans , Infarction, Middle Cerebral Artery/complications , Infarction, Middle Cerebral Artery/metabolism , Inflammasomes , NF-kappa B/metabolism , Reperfusion Injury/etiology , Reperfusion Injury/metabolism , Reperfusion Injury/prevention & control , WaterABSTRACT
AIM: Antimicrobial resistance (AMR) has become a global concern. Developing novel antimicrobials is one of the most effective approaches in tackling AMR. Considering its relatively low cost and risk, drug repurposing has been proposed as a valuable approach for novel antimicrobial discovery. The aim of this study was to screen for antimicrobial compounds against Streptococcus suis, an important zoonotic bacterial pathogen, from an Food and Drug Administration (FDA)-approved drug library. METHODS AND RESULTS: In this study, we tested the antimicrobial activity of 1815 FDA-approved drugs against S. suis. Sixty-seven hits were obtained that showed a growth inhibition of more than 98%. After excluding already known antibiotics and antiseptics, 12 compounds were subjected to minimal inhibition concentration (MIC) assessment against S. suis. This showed that pralatrexate, daunorubicin (hydrochloride), teniposide, aclacinomycin A hydrochloride and floxuridine gave a relatively low MIC, ranging from 0.85 to 5.25 µg/ml. Apart from pralatrexate, the remaining four drugs could also inhibit the growth of antimicrobial-resistant S. suis. It was also demonstrated that these four drugs had better efficacy against Gram-positive bacteria than Gram-negative bacteria. Cytotoxicity assays showed that floxuridine and teniposide had a relatively high 50% cytotoxic concentration (CC50 ). The in vivo efficacy of floxuridine was analysed using a Galleria mellonella larvae infection model, and the results showed that floxuridine was effective in treating S. suis infection in vivo. CONCLUSIONS: Five compounds from the FDA-approved drug library showed high antimicrobial activity against S. suis, among which floxuridine displayed potent in vivo efficacy that is worth further development. SIGNIFICANCE AND IMPACT OF STUDY: Our study identified several antimicrobial compounds that are effective against S. suis, which provides a valuable starting point for further antimicrobial development.
Subject(s)
Anti-Infective Agents , Pharmaceutical Preparations , Streptococcal Infections , Streptococcus suis , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents/pharmacology , Anti-Infective Agents/therapeutic use , Humans , Microbial Sensitivity Tests , Streptococcal Infections/drug therapy , Streptococcal Infections/microbiology , United States , United States Food and Drug AdministrationABSTRACT
OBJECTIVE: To investigate the efficacy of radiofrequency ablation (RFA) as a treatment option for primary hyperparathyroidism (pHPT) and risk factors for postablative eucalcemic parathyroid hormone elevation (ePTH). METHODS: This retrospective study included 51 patients with pHPT who underwent RFA. The patients were divided into the ePTH and normal PTH groups, based on the serum intact parathyroid hormone (iPTH) level one month after ablation. Serum iPTH, calcium, and phosphorus levels, and the volume reduction rates (VRR) of the parathyroid glands were compared between the groups at each follow-up point. Risk factors for ePTH at one month after ablation were examined. RESULTS: After RFA, one (2%) patient had persistent pHPT, and 50 (98%) patients were cured. The incidence rates of ePTH at 1, 3, 6, and 12 months were 48%, 30%, 20%, and 16%, respectively. Serum iPTH levels in the ePTH group were higher than those in the normal PTH group at each follow-up point (all p < 0.05), except 1 day after ablation (p > 0.05). Serum calcium and phosphorus levels, and the VRR of the glands were comparable in both groups at each follow-up point (all p > 0.05), except for calcium levels 3 days after RFA (p < 0.05). Baseline iPTH (odds ratio, 1.067; p = 0.045) and calcium (odds ratio, 3.923; p = 0.038) levels were independent risk factors for ePTH 1 month after RFA. CONCLUSIONS: RFA is safe and effective for the treatment of pHPT. Moreover, ePTH occurrence after RFA was associated with baseline iPTH and calcium levels and did not increase the risk of recurrent pHPT.
Subject(s)
Hyperparathyroidism, Primary , Radiofrequency Ablation , Calcium , Humans , Hyperparathyroidism, Primary/surgery , Parathyroid Hormone , Parathyroidectomy , Radiofrequency Ablation/adverse effects , Retrospective Studies , Risk FactorsABSTRACT
BACKGROUND: The majority of patients may experience atelectasis under general anesthesia, and the Trendelenburg position and pneumoperitoneum can aggravate atelectasis during laparoscopic surgery, which promotes postoperative pulmonary complications. Lung recruitment manoeuvres have been proven to reduce perioperative atelectasis, but it remains controversial which method is optimal. Ultrasonic imaging can be conducive to confirming the effect of lung recruitment manoeuvres. The purpose of our study was to assess the effects of ultrasound-guided alveolar recruitment manoeuvres by ultrasonography on reducing perioperative atelectasis and to check whether the effects of recruitment manoeuvres under ultrasound guidance (visual and semiquantitative) on atelectasis are superior to sustained inflation recruitment manoeuvres (classical and widely used) in laparoscopic gynaecological surgery. METHODS: In this randomized, controlled, double-blinded study, women undergoing laparoscopic gynecological surgery were enrolled. Patients were randomly assigned to receive either lung ultrasound-guided alveolar recruitment manoeuvres (UD group), sustained inflation alveolar recruitment manoeuvres (SI group), or no RMs (C group) using a computer-generated table of random numbers. Lung ultrasonography was performed at four predefined time points. The primary outcome was the difference in lung ultrasound score (LUS) among groups at the end of surgery. RESULTS: Lung ultrasound scores in the UD group were significantly lower than those in both the SI group and the C group immediately after the end of surgery (7.67 ± 1.15 versus 9.70 ± 102, difference, -2.03 [95% confidence interval, -2.77 to -1.29], P < 0.001; 7.67 ± 1.15 versus 11.73 ± 1.96, difference, -4.07 [95% confidence interval, -4.81 to -3.33], P < 0.001;, respectively). The intergroup differences were sustained until 30 min after tracheal extubation (9.33 ± 0.96 versus 11.13 ± 0.97, difference, -1.80 [95% confidence interval, -2.42 to -1.18], P < 0.001; 9.33 ± 0.96 versus 10.77 ± 1.57, difference, -1.43 [95% confidence interval, -2.05 to -0.82], P < 0.001;, respectively). The SI group had a significantly lower LUS than the C group at the end of surgery (9.70 ± 1.02 versus 11.73 ± 1.96, difference, -2.03 [95% confidence interval, -2.77 to -1.29] P < 0.001), but the benefit did not persist 30 min after tracheal extubation. CONCLUSIONS: During general anesthesia, ultrasound-guided recruitment manoeuvres can reduce perioperative aeration loss and improve oxygenation. Furthermore, these effects of ultrasound-guided recruitment manoeuvres on atelectasis are superior to sustained inflation recruitment manoeuvres. TRIAL REGISTRATION: Chictr.org.cn, ChiCTR2100042731, Registered 27 January 2021, www.chictr.org.cn .
Subject(s)
Laparoscopy , Pulmonary Atelectasis , Female , Gynecologic Surgical Procedures/adverse effects , Humans , Laparoscopy/adverse effects , Laparoscopy/methods , Lung/diagnostic imaging , Positive-Pressure Respiration/methods , Postoperative Complications , Pulmonary Atelectasis/diagnostic imaging , Pulmonary Atelectasis/etiology , Pulmonary Atelectasis/prevention & control , Ultrasonography , Ultrasonography, InterventionalABSTRACT
Aiming at the task allocation problem of heterogeneous unmanned underwater vehicle (UUV) swarms, this paper proposes a dynamic extended consensus-based bundle algorithm (DECBBA) based on consistency algorithm. Our algorithm considers the multi-UUV task allocation problem that each UUV can individually complete multiple tasks, constructs a "UUV-task" matching matrix and designs new marginal utility, reward and cost functions for the influence of time, path and UUV voyage. Furthermore, in view of the unfavorable factors that restrict the underwater acoustic communication range between UUVs in the real environment, our algorithm complete dynamic task allocation of UUV swarms with optimization in load balance indicator by the update of the UUV individual and the task completion status in the discrete time stage. The performance indicators (including global utility and task completion rate) of the dynamic task allocation algorithm in the scenario with communication constraints can be well close to the static algorithm in the ideal scenario without communication constraints. The simulation experiment results show that the algorithm proposed in this paper can quickly and efficiently obtain the dynamic and conflict-free task allocation assignment of UUV swarms with great performance.
Subject(s)
Algorithms , Computer SimulationABSTRACT
Nebraska's eastern saline wetlands are globally unique and highly vulnerable inland salt marsh ecosystems. This research aims to evaluate the status of the saline wetlands in eastern Nebraska to discover the conditions of saline wetland hydrology, hydrophytes, and hydraulic soil. The research adopts machine learning and Google Earth Engine to classify Sentinel-2 imagery for water and vegetation classification and the National Agriculture Imagery Program imagery for salinity conditions. Six machine learning models are applied in water, soil, and vegetation detection in the study area. The optimal model (linear kernel SVM) generates an overall accuracy of 99.95% for water classification. For saline vegetation classification, the optimal model is the gradient tree boost with an overall accuracy of 94.07%. The overall accuracy values of saline soil classification using the optimal model (linear kernel SVM) varied among different years. The results of this study show the possibility of an observation approach for continuously monitoring Nebraska's eastern saline wetlands. The water classification results show that the saline wetlands in this area all have a similar temporal water cover pattern within each year. For saline vegetation, the peak season in this area is between June and July. The years 2019 (19.00%) and 2018 (17.69%) had higher saline vegetation cover rates than 2017 (10.54%). The saline soil classification shows that the saline soil area is highly variable in response to changes in the water and vegetation conditions. The research findings provide solid scientific evidence for conservation decision-making in these saline wetland areas.