ABSTRACT
While HC2 and GP5+/6+ PCR-EIA were pivotal in test validation of new HPV assays, they represent the first generation of comparator tests based upon technologies that are not in widespread use anymore. In the current guideline, criteria for second-generation comparator tests are presented that include more detailed resolution of HPV genotypes. Second-generation comparator tests should preferentially target only the 12 genotypes classified as carcinogenic (IARC-group I), and show consistent non-inferior sensitivity for CIN2+ and CIN3+ and specificity for ≤CIN1 compared to one of the first-generations comparators, in at least three validation studies using benchmarks of 0.95 for relative sensitivity and 0.98 for relative specificity. Validation should take into account used storage media and other sample handling procedures. Meta-analyses were conducted to identify the assays that fulfill these stringent criteria. Four tests fulfilled the new criteria: (1) RealTime High-Risk HPV Test (Abbott), (2) Cobas-4800 HPV test (Roche Molecular System), (3) Onclarity HPV Assay (BD Diagnostics), and (4) Anyplex II HPV HR Detection (Seegene), each evaluated in three to six studies. Whereas the four assays target 14 carcinogenic genotypes, the first two identify separately HPV16 and 18, the third assay identifies five types separately and the fourth identifies all the types separately.
Subject(s)
Early Detection of Cancer , Papillomaviridae , Papillomavirus Infections , Sensitivity and Specificity , Uterine Cervical Neoplasms , Female , Humans , DNA, Viral/genetics , Early Detection of Cancer/methods , Genotype , Human Papillomavirus DNA Tests/methods , Human Papillomavirus DNA Tests/standards , Molecular Diagnostic Techniques/methods , Molecular Diagnostic Techniques/standards , Papillomaviridae/genetics , Papillomaviridae/classification , Papillomaviridae/isolation & purification , Papillomavirus Infections/diagnosis , Papillomavirus Infections/virology , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/virologyABSTRACT
Background: China exited strict Zero-COVID policy with a surge in Omicron variant infections in December 2022. Given China's pandemic policy and population immunity, employing Baidu Index (BDI) to analyze the evolving disease landscape and estimate the nationwide pneumonia hospitalizations in the post Zero COVID period, validated by hospital data, holds informative potential for future outbreaks. Methods: Retrospective observational analyses were conducted at the conclusion of the Zero-COVID policy, integrating internet search data alongside offline records. Methodologies employed were multidimensional, encompassing lagged Spearman correlation analysis, growth rate assessments, independent sample T-tests, Granger causality examinations, and Bayesian structural time series (BSTS) models for comprehensive data scrutiny. Results: Various diseases exhibited a notable upsurge in the BDI after the policy change, consistent with the broader trajectory of the COVID-19 pandemic. Robust connections emerged between COVID-19 and diverse health conditions, predominantly impacting the respiratory, circulatory, ophthalmological, and neurological domains. Notably, 34 diseases displayed a relatively high correlation (r > 0.5) with COVID-19. Among these, 12 exhibited a growth rate exceeding 50% post-policy transition, with myocarditis escalating by 1,708% and pneumonia by 1,332%. In these 34 diseases, causal relationships have been confirmed for 23 of them, while 28 garnered validation from hospital-based evidence. Notably, 19 diseases obtained concurrent validation from both Granger causality and hospital-based data. Finally, the BSTS models approximated approximately 4,332,655 inpatients diagnosed with pneumonia nationwide during the 2 months subsequent to the policy relaxation. Conclusion: This investigation elucidated substantial associations between COVID-19 and respiratory, circulatory, ophthalmological, and neurological disorders. The outcomes from comprehensive multi-dimensional cross-over studies notably augmented the robustness of our comprehension of COVID-19's disease spectrum, advocating for the prospective utility of internet-derived data. Our research highlights the potential of Internet behavior in predicting pandemic-related syndromes, emphasizing its importance for public health strategies, resource allocation, and preparedness for future outbreaks.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/epidemiology , China/epidemiology , Retrospective Studies , Hospitalization/statistics & numerical data , Bayes Theorem , Health Policy , PandemicsABSTRACT
Methylated arsenicals, including highly toxic species, such as methylarsenite [MAs(III)], are pervasive in the environment. Certain microorganisms possess the ability to detoxify MAs(III) by ArsI-catalyzed demethylation. Here, we characterize a bifunctional enzyme encoded by the arsI gene from Acidovorax sp. ST3, which can detoxify MAs(III) through both the demethylation and oxidation pathways. Deletion of the 22 C-terminal amino acids of ArsI increased its demethylation activity while reducing the oxidation activity. Further deletion of 44 C-terminal residues enhanced the MAs(III) demethylation activity. ArsI has four vicinal cysteine pairs, with the first pair being necessary for MAs(III) demethylation, while at least one of the other three pairs contributes to MAs(III) oxidation. Molecular modeling and site-directed mutagenesis indicated that one of the C-terminal vicinal cysteine pairs is involved in modulating the switch between oxidase and demethylase activity. These findings underscore the critical role of the C-terminal region in modulating the enzymatic activities of ArsI, particularly in MAs(III) demethylation. This research reveals the structure-function relationship of the ArsI enzyme and advances our understanding of the MAs(III) metabolism in bacteria.
ABSTRACT
BACKGROUND: Traditional Chinese medicine formulations often contain hydrophobic components with limited solubility and stability, leading to low oral bioavailability. Self-assembled nanoparticles (SANs) have shown promise in enhancing oral bioavailability of these components. However, whether un-decocted Chinese herbal pellets can generate SANs and the impact of SANs formed by multiple components on pharmacokinetic parameters remains unexplored. METHODS: In this study, single-factor approach was employed to determine the optimal separation method of nano-emulsion phase of XiaoYao pill (N-XY). Morphological and particle size analyses confirmed the nanoscale nature of N-XY. High-performance liquid chromatography (HPLC) fingerprint analysis was conducted to compare the distribution of active ingredients among three different phases of XiaoYao pill (XY pill). In vitro release studies were performed to evaluate the release mechanism of four ingredients from N-XY. Additionally, in vivo pharmacokinetics and tissue distribution behaviors were investigated in rats. RESULTS: N-XY exhibited uniform and stable characteristics as a water-in-oil (O/W) nano-emulsion. Fingerprint analysis identified 25 characteristic peaks and 8 key ingredients in N-XY, with the highest peak areas. In vitro release studies showed a sustained release behavior of N-XY. The pharmacokinetics study showed that the ferulic acid of N-XY had a 1.37-fold higher AUC, 1.44-fold lower Vd/F, 1.39-fold lower CL/F, and a prolonged t1/2 than A-XY, indicating enhanced bioavailability due to reduced elimination. Furthermore, the tissue distribution revealed that the levels of paeoniflorin and ferulic acid from N-XY significantly increased in liver, spleen, lungs, uterus and ovaries, exhibiting targeting characteristics. CONCLUSION: This study comprehensively explored the formation, characterization, and pharmacokinetics of nano-emulsion in XY pill, introducing novel perspectives and initiating preliminary research on potential SANs in un-decocted traditional Chinese medicine formulations. It also emphasized the importance of enhancing pharmacokinetics of hydrophobic components in Chinese herbal formulations and laid the foundation for future nano-formulation research for XY pill.
ABSTRACT
Respiratory Burst Oxidase Homologues (RBOHs) are involved in plant growth, development, and stress adaptation. How OsRBOHs affect root hair formation and consequently nutrient acquisition and drought resistance in rice is not well understood. We knocked out six OsRBOH genes in rice that were expressed in roots and identified OsRBOHE as the only one affecting root hair formation. OsRBOHE was strongly expressed in the root epidermis, root hairs and tiller buds. OsRBOHE is localised at the plasma membrane. Knockout of OsRBOHE decreased reactive oxygen species generation in the root hairs and tiller buds, downregulated genes involved in cell wall biogenesis, and decreased root hair length and tillering by 90% and 30%, respectively. Knockout of OsRBOHE decreased phosphorus acquisition only in low available P soil under aerobic conditions, but not in high P soil or under flooded conditions when P was likely not limited by diffusion. Knockout of OsRBOHE markedly decreased drought resistance of rice plants through the effect on root hair formation and the associated rhizosheath. Taken together, OsRBOHE is crucial for root hair formation and tillering and consequently on drought resistance in rice. The contribution of root hairs to P acquisition in rice is limited to aerobic soil.
ABSTRACT
Electrochemical ammonia synthesis presents a sustainable alternative, offering the potential for enhanced energy efficiency and environmental benefits compared to the conventional Haber-Bosch process. In recent years, the electrocatalytic reduction of nitrate to ammonia (NO3-RR) has emerged as a crucial approach for achieving sustainable NH3 production. To enhance energy efficiency and successfully convert NO3- to NH3, it is essential to investigate cost-effective electrocatalysts that provide high Faraday efficiency and demonstrate adequate stability. Ti-based materials are considered ideal candidates as catalysts due to their environmental friendliness and robust stability. This review initially summarizes the nitrate reduction reaction pathway and concisely discusses the impact of the potential intermediates and reaction steps on the overall reaction efficiency and product selectivity. Subsequently, an overview of the fundamental characteristics of Ti and TiO2 is presented. Additionally, the research process on Ti-based electrocatalysts in the electrochemical reduction of nitrate for ammonia synthesis is summarized. Finally, the design strategies, such as heteroatom doping and the introduction of oxygen vacancies, to enhance catalytic efficiency and selectivity are presented. Through this comprehensive review, we endeavor to furnish researchers with the most recent insights into the application of titanium-based electrocatalysts in nitrate reduction reactions and to stimulate innovative thought processes on the electrocatalytic synthesis of ammonia.
ABSTRACT
A comprehensive understanding of the evolution of soybean climate potential productivity and its response to climate change in Heilongjiang Province can offer reference and basis for further tapping soybean production potential and realizing stable and high yield of soybean in the frigid region. Based on meteorological data from 80 meteorological stations in Heilongjiang Province from 1961 to 2020, we estimated photosynthesis, light temperature, and climate potential productivity of soybean by the stepwise correction method, examined the spatiotemporal variations by spatial interpolation and statistical analysis methods, and analyzed the impact of changes in climate factors such as radiation, temperature, and precipitation on climate potential productivity. The results showed that during the study period, the average values of photosynthesis potential productivity (YQ), light-temperature potential productivity (YT), and climate potential productivity (YW) of soybean in Heilongjiang Province were 7533, 6444, and 3515 kg·hm-2, respectively. The temporal changes of those variables showed significant increasing trends, with increases of 125.9, 182.9, and 116.1 kg·hm-2·(10 a)-1, respectively. For the spatial distribution, YQ, YT, YW were characterized by high values in plains and lower in the mountains, and gradually decreased from southwest to northeast. Compared with that during 1961-1990, the high value zone of YW in period 1991-2020 expanded by 7.1%, and the low value zone decreased by 5.1%. YW showed a significant response to climate change. The potential temperature growth period was extended due to climate warming. The continuous increase in thermal resources, combined with relatively sufficient precipitation, effectively alleviated the negative impact of the decline in light resources on soybean production in Heilongjiang Province. The projected "warm and humid" climate would comprehensively boost climate potential productivity of soybean in Heilongjiang Province.
Subject(s)
Climate Change , Glycine max , Glycine max/growth & development , China , Photosynthesis , Biomass , Ecosystem , TemperatureABSTRACT
The past two decades has witnessed a remarkable increase in the number of microbial genomes retrieved from marine systems1,2. However, it has remained challenging to translate this marine genomic diversity into biotechnological and biomedical applications3,4. Here we recovered 43,191 bacterial and archaeal genomes from publicly available marine metagenomes, encompassing a wide range of diversity with 138 distinct phyla, redefining the upper limit of marine bacterial genome size and revealing complex trade-offs between the occurrence of CRISPR-Cas systems and antibiotic resistance genes. In silico bioprospecting of these marine genomes led to the discovery of a novel CRISPR-Cas9 system, ten antimicrobial peptides, and three enzymes that degrade polyethylene terephthalate. In vitro experiments confirmed their effectiveness and efficacy. This work provides evidence that global-scale sequencing initiatives advance our understanding of how microbial diversity has evolved in the oceans and is maintained, and demonstrates how such initiatives can be sustainably exploited to advance biotechnology and biomedicine.
Subject(s)
Aquatic Organisms , Biodiversity , Bioprospecting , CRISPR-Cas Systems , CRISPR-Cas Systems/genetics , Aquatic Organisms/genetics , Bacteria/genetics , Bacteria/classification , Archaea/genetics , Archaea/classification , Genome, Bacterial/genetics , Metagenome , Genome, Archaeal/genetics , Seawater/microbiology , Phylogeny , Oceans and SeasABSTRACT
An abnormal capacity increase stage has been observed in nanostructured SiO2 after the initial capacity drop stage. To investigate the Li+ storage kinetic mechanism for each stage, SiO2@C core-shell nanospheres with a total diameter of â¼108 to 170 nm but an adjustable C shell thickness of â¼4 to 31 nm have been fabricated. First, the existence form and specific content of SiO2 nanoparticles with a size of â¼6-10 nm, which are embedded in the outer C shell of SiO2@C core-shell nanospheres, were confirmed by SEM, TEM, BET, and TGA, respectively. It was found that the initial stage for capacity drop happens at 15-43 cycles and is followed by an enhancement stage, which presents an increase of â¼120 to 180% in capacity relative to the lowest capacity value during cycling. Among them, the sample of P-1 with a diameter of 109 nm for the SiO2 core and thickness of 31 nm for the C shell delivers the highest specific capacity of 1060 mAh/g at 100 mA/g and a capacity increase rate of â¼180% through 300 cycles. XPS analysis for the delithiation process indicates that the capacity drop and increase stage involves the partial oxidation of Li silicate, which is correlated to the formation of Li2Si2O5. Our study can be used to explain the mechanism of the abnormal capacity increase phenomenon for the SiO2 anode and provide a high-capacity anode material for LIB application.
ABSTRACT
The outbreak of highly pathogenic influenza virus subtypes, such as H7 and H5, presents a significant global health challenge, necessitating the development of rapid and sensitive diagnostic methods. In this study, we have developed a novel dual-component biosensor assembly, each component of which incorporates an antibody fused with a nano-luciferase subunit. Our results demonstrate the effectiveness of this biosensor in enabling the rapid and sensitive detection of influenza H7 and other subtypes. Additionally, we successfully applied the biosensor in paper-based assay and lateral flow assay formats, expanding its versatility and potential for field-deployable applications. Notably, we achieved effective detection of the H7N9 virus using this biosensor. Furthermore, we designed and optimized a dedicated biosensor to the sensitive detection of the influenza H5 subtype. Collectively, our findings underscore the significant potential of this dual-component biosensor assembly as a valuable and versatile tool for accurate and timely diagnosis of influenza virus infections, promising to advance the field of influenza diagnostics and contribute to outbreak management and surveillance efforts.
ABSTRACT
The benzofuran core inhibitors HCV-796, BMS-929075, MK-8876, compound 2, and compound 9B exhibit good pan-genotypic activity against various genotypes of NS5B polymerase. To elucidate their mechanism of action, multiple molecular simulation methods were used to investigate the complex systems of these inhibitors binding to GT1a, 1b, 2a, and 2b NS5B polymerases. The calculation results indicated that these five inhibitors can not only interact with the residues in the palm II subdomain of NS5B polymerase, but also with the residues in the palm I subdomain or the palm I/III overlap region. Interestingly, the binding of inhibitors with longer substituents at the C5 position (BMS-929075, MK-8876, compound 2, and compound 9B) to the GT1a and 2b NS5B polymerases exhibits different binding patterns compared to the binding to the GT1b and 2a NS5B polymerases. The interactions between the para-fluorophenyl groups at the C2 positions of the inhibitors and the residues at the binding pockets, together with the interactions between the substituents at the C5 positions and the residues at the reverse ß-fold (residues 441-456), play a key role in recognition and the induction of the binding. The relevant studies could provide valuable information for further research and development of novel anti-HCV benzofuran core pan-genotypic inhibitors.
Subject(s)
Antiviral Agents , Benzofurans , Genotype , Hepacivirus , Viral Nonstructural Proteins , Viral Nonstructural Proteins/antagonists & inhibitors , Viral Nonstructural Proteins/metabolism , Viral Nonstructural Proteins/chemistry , Benzofurans/chemistry , Benzofurans/pharmacology , Hepacivirus/drug effects , Hepacivirus/enzymology , Hepacivirus/genetics , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Molecular Dynamics Simulation , Molecular Docking Simulation , Binding Sites , Protein Binding , Humans , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , RNA-Dependent RNA PolymeraseABSTRACT
Bacillus velezensis is a promising candidate for biocontrol applications. A common second messenger molecule, bis-(3,5)-cyclic-dimeric-guanosine monophosphate (c-di-GMP), has the ability to regulate a range of physiological functions that impact the effectiveness of biocontrol. However, the status of the c-di-GMP signaling pathway in biocontrol strain LQ-3 remains unknown. Strain LQ-3, which was isolated from wheat rhizosphere soil, has shown effective control of wheat sharp eyespot and has been identified as B. velezensis through whole-genome sequencing analyses. In this study, we investigated the intracellular c-di-GMP signaling pathway of LQ-3 and further performed a comparative genomic analysis of LQ-3 and 29 other B. velezensis strains. The results revealed the presence of four proteins containing the GGDEF domain, which is the conserved domain for c-di-GMP synthesis enzymes. Additionally, two proteins were identified with the EAL domain, which represents the conserved domain for c-di-GMP degradation enzymes. Furthermore, one protein was found to possess a PilZ domain, indicative of the conserved domain for c-di-GMP receptors in LQ-3. These proteins are called DgcK, DgcP, YybT, YdaK, PdeH, YkuI, and DgrA, respectively; they are distributed in a similar manner across the strains and belong to the signal transduction family. We selected five genes from the aforementioned seven genes for further study, excluding YybT and DgrA. They all play a role in regulating the motility, biofilm formation, and colonization of LQ-3. This study reveals the c-di-GMP signaling pathway associated with biocontrol features in B. velezensis LQ-3, providing guidance for the prevention and control of wheat sharp eyespot by LQ-3.
ABSTRACT
Intestinal dysmotility syndromes have been epidemiologically associated with several antecedent bacterial and viral infections. To model this phenotype, we previously infected mice with the neurotropic flavivirus, West Nile Virus (WNV) and demonstrated intestinal transit defects. Here, we find that within one week of WNV infection, enteric neurons and glia become damaged, resulting in sustained reductions of neuronal cells and their networks of connecting fibers. Using cell-depleting antibodies, adoptive transfer experiments, and mice lacking specific immune cells or immune functions, we show that infiltrating WNV-specific CD4+ and CD8+ T cells damage the enteric nervous system (ENS) and glia, which leads to intestinal dysmotility; these T cells use multiple and redundant effector functions including perforin and Fas ligand. In comparison, WNV-triggered ENS injury and intestinal dysmotility appears to not require infiltrating monocytes and damage may be limited by resident muscularis macrophages. Overall, our experiments support a model whereby antigen specific T cell subsets and their effector molecules responding to WNV infection direct immune pathology against enteric neurons and supporting glia that results in intestinal dysmotility.
ABSTRACT
High-power laser diodes with a stable wavelength and narrow linewidth are crucial for many applications. In this study, we introduce a first-order distributed feedback (DFB) grating into an asymmetric large-cavity laser diode operating around 940â nm. This design maintains high output power and offers a wide temperature locking range. The nearly sinusoidal shape first-order grating is fabricated by ultraviolet (UV) nanoimprint lithography, inductively coupled plasma (ICP) dry etching, and wet polishing. At a heat sink temperature of 25°C, the DFB laser diode, with a 200â µm stripe width and 4â mm cavity length, achieves a maximum output power of 24.8â W and a full width at half maximum (FWHM) of 0.4â nm under continuous-wave (CW) conditions. The maximum slope efficiency is calculated to be 1.04â W/A. At an output power of 10.7â W, the device reaches a peak wall-plug efficiency of 56%. Under quasi-continuous operation at 20â A, the laser output spectrum remains locked to the DFB grating over a temperature range from -10°C to 110°C, with a temperature coefficient of 0.062â nm/°C.
ABSTRACT
BACKGROUND: Immune checkpoint inhibition (ICI) currently is the most effective treatment to induce durable responses in metastatic melanoma. The aims of this study are the characterization of patients with early, late and non-response to ICI and analysis of survival outcomes in a real-world patient cohort. METHODS: Patients who received PD-1-based immunotherapy for non-resectable stage-IV melanoma in any therapy line were selected from the prospective multicenter real-world DeCOG study ADOREG-TRIM (NCT05750511). Patients showing complete (CR) or partial (PR) response already during the first 3 months of treatment (Early Responders, EarlyR) were compared to patients showing CR/PR at a later time (Late Responders, LateR), a stable disease (SD) and to patients showing progressive disease (Non-Responders, NonR). RESULTS: Of 522 patients, 8.2 % were EarlyR (n = 43), 19.0 % were LateR (n = 99), 37.0 % had a SD (n = 193) and 35.8 % were NonR (n = 187). EarlyR, LateR and SD patients had comparable baseline characteristics. Multivariate logbinomial regression analyses adjusted for age and sex revealed positive tumor PD-L1 (RR=1.99, 95 %-CI=1.14-3.46, p = 0.015), and normal serum CRP (RR=1.59, 95 %-CI=0.93-2.70, p = 0.036) as independently associated with the achievement of an early response compared to NonR. The median progression-free and overall survival was 46.0 months (95 % CI 19.1; NR) and 47.8 months (95 %-CI 36.9; NR) for EarlyR, NR (95 %-CI NR; NR) for LateR, 8.1 months (7.0; 10.4) and 35.4 months (29.2; NR) for SD, and 2.0 months (95 %-CI 1.9; 2.1) and 6.1 months (95 %-CI 4.6; 8.8) for NonR patients. CONCLUSION: Less than 10 % of metastatic melanoma patients achieved an early response during the first 3 months of PD-1-based immunotherapy. Early responders were not superior to late responders in terms of response durability and survival.
ABSTRACT
BACKGROUND: The impact of acrylamide (ACR) on learning and memory has garnered considerable attention. However, the targets and mechanisms are still unclear. RESULTS: Elongation factor 2 (eEF2) was significantly upregulated in the results of serum proteomics. Results from in vitro and in vivo experiments indicated a notable upregulation of Eukaryotic elongation factor 2 kinase (eEF2K), the sole kinase responsible for eEF2 phosphorylation, following exposure to ACR (P < 0.05). Subsequent in vitro experiments using eEF2K siRNA and in vivo experiments with eEF2K-knockout mice demonstrated significant improvements in abnormal indicators related to ACR-induced learning and memory deficits (P < 0.05). Proteomic analysis of the hippocampus revealed Lpcat1 as a crucial downstream protein regulated by eEF2K. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that eEF2K may play a role in the process of ACR-induced learning and memory impairment by affecting ether lipid metabolism. CONCLUSIONS: In summary, eEF2K as a pivotal treatment target in the mechanisms underlying ACR-induced learning and memory impairment, and studies have shown that it provides robust evidence for potential clinical interventions targeting ACR-induced impairments.
ABSTRACT
AIM: To assess and compare the variations and agreements across different ocular biometric parameters using swept-source optical coherence tomography (SS-OCT) and Scheimpflug tomography in patients diagnosed with cataract. METHODS: This prospective case series was conducted at Tianjin Medical University Eye Hospital. In total, 212 eyes from 212 patients scheduled for phacoemulsification were included. Eyes were evaluated preoperatively using two SS-OCT devices (IOLMaster700 and CASIA2) and Scheimpflug tomography (Pentacam). Central corneal thickness (CCT), anterior chamber depth (ACD), aqueous depth (AQD), white-to-white distance (WTW), flat simulated keratometry (Kf), steep simulated keratometry (Ks), mean keratometry (Km), and total corneal keratometry (TKm) were measured. Intraclass correlation coefficient (ICC), 95% confidence intervals (CI) and limits of agreement (LoA) widths were conducted to assess differences and correlations between devices. RESULTS: All parameters, except for Ks, were significantly different. Pairwise comparison revealed no significant differences between keratometry obtained by IOLMaster 700 and Pentacam. LoA widths of all paired comparisons for Ks were >0.80 D. Except for WTW between IOLMaster 700 and CASIA2 and between CASIA2 and Pentacam, other Pearson's coefficients between devices showed a strong correlation (all r>0.95). The ICC of WTW (ICC=0.438, 95%CI 0.167-0.625) showed poor reliability. The reliability of CCT, ACD, and AQD was excellent (all ICC>0.95), whereas that of TKm was good (ICC=0.827, 95%CI 0.221-0.939). A significant linear correlation was also observed among devices. CONCLUSION: The ocular parameters derived from the use of IOLMaster700, CASIA2, and Pentacam exhibit significant discrepancies; as such, measurements from these devices should not be deemed as interchangeable.
ABSTRACT
RATIONALE, AIMS AND OBJECTIVES: Psychometrics of the Chinese Life Attitude Self-rating Questionnaire for Breast Cancer (LASQ-BC) has not yet been conducted in a larger sample of women with breast cancer. This study aimed to examine the reliability, validity, and sensitivity of the LASQ-BC in Chinese mainland female breast cancer patients. METHOD: This is a cross-sectional study. Reliability was determined by Cronbach's α and Guttman split-half coefficient. Convergent and discriminant validity were evaluated via item-subscale and item-total score correlations. Factorial validity was estimated using a principal component analysis with varimax rotation. Sensitivity was identified via Cohen's effect size (ES) and an independent sample t-test between the new and recurrent cases. Multiple linear regression analysis was used to further examine sensitivity of the LASQ-BC under the influence of newly diagnosed breast cancer (yes vs. no). RESULTS: A total of 429 patients completed the questionnaire. Cronbach's α of the LASQ-BC was 0.96, ranging from 0.86 to 0.92 for the four subscales (i.e., choice and responsibility, life meaning, benevolence, and life experiences). The Guttman split-half coefficient was 0.90. The hypothesised item-subscale and item-total score correlations were higher than the critical value of 0.50. Four factors were extracted from the 23 items, explaining 69.29% of the total variance. Eligible ES (range: 0.38-0.48) was found in the four subscales and total score between the new and recurrent cases (independent sample t-test), and under the influence of newly diagnosed breast cancer (yes vs. no; multiple linear regression analysis). CONCLUSION: The Chinese LASQ-BC has acceptable reliability, validity, and sensitivity in women with breast cancer of mainland China. It can be used to female breast cancer patients as an invaluable metric and a crucial instrument for assessing and discerning those grappling with a suboptimal life attitude, and in gauging the efficacy of psychological interventions tailored to enhance this perspective.
ABSTRACT
The aim of this study was to investigated the effects of forsythiaside A (FA) on acute lung injury (ALI). The lung tissue pathological was detected by hematoxylin-eosin staining (HE) staining. Wet weight/dry weight (w/d) of the lung in mice was measured. Cytokine such as interleukin 1ß (IL-1ß), IL-6 and tumor necrosis factor-α (TNF-α) were also detected. Compared with the vector group, the protein expression levels of TRAF6 and TAK1 the RNF99 group were significantly reduced. Ubiquitinated TRAF6 protein was increased after knockdown of RNF99. Finally, it was found that FA significantly ameliorated ALI via regulation of RNF99/TRAF6/NF-κB signal pathway. In conclusion, RNF99 was an important biomarker in ALI and FA alleviated ALI via RNF99/ TRAF6/NF-κB signal pathway.
Subject(s)
Acute Lung Injury , Signal Transduction , Animals , Humans , Male , Mice , Acute Lung Injury/drug therapy , Acute Lung Injury/pathology , Acute Lung Injury/metabolism , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/pharmacology , Cytokines/metabolism , Glycosides/pharmacology , Glycosides/therapeutic use , Lung/pathology , Lung/drug effects , Lung/metabolism , Mice, Inbred C57BL , NF-kappa B/metabolism , Signal Transduction/drug effects , TNF Receptor-Associated Factor 6/metabolism , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/geneticsABSTRACT
Tissue-clearing techniques have revolutionized the field of biological imaging by rendering biological specimens transparent and enabling inside optical detection. Light-sheet fluorescence microscopy (LSFM) is a powerful tool for three-dimensional imaging of large biological samples. Combining tissue-clearing techniques with LSFM has advanced the efficient 3D visualization of these samples. A crucial challenge with LSFM is the requirement for the objective to operate within the clearing reagent, which can cause aberrations. To address this issue, we introduce a novel, to our knowledge, approach for the flexible design of the solid immersion refractive meniscus lens (SIMlens), facilitating the use of air objectives with cleared samples. Compared to the previous SIMlens, this method not only eliminates aberrations but also offers customized options for enhancing the numerical aperture and working distance of the objective lens, achieving at least a 10% improvement. We have demonstrated the feasibility of this new method using mouse brain samples.