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Study of PEG-rhG-CSF for the prevention of neutropenia in concurrent chemoradiotherapy for nasopharyngeal carcinoma
Background To study the efficacy and safety of Polyethylene glycolated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in the prevention of neutropenia during concurrent chemoradiotherapy for nasopharyngeal carcinoma (NPC). Methods This is a single-center, prospective, randomized controlled study conducted from June 1, 2021, to October 31, 2022 on patients diagnosed with locally advanced NPC. Participants were divided into an experimental group and a control group. The experimental group received PEG-rhG-CSF injections post-chemotherapy cycles, whereas the control group received standard care without additional intervention. Outcomes assessed included grade 3/4 neutropenia incidence, blood cell count changes, febrile neutropenia rates, delays or interruptions in chemotherapy/radiotherapy due to hematological toxicity, oral mucositis incidents, and bone pain occurrences, comparing these between both groups. Results 1. 88 patients with locally advanced NPC were included, the incidence of grade 3 neutropenia in the experimental group was lower than that in the control group (P = 0.026); 2. The white blood cell count and neutrophil count in D7, D10, D14, and D21 in the experimental group were higher than those in the control group (P<0.01); 3. The rate of delayed chemotherapy in the experimental group was lower than that in the control group (2.3% vs. 29.5%), P = 0.001; the rate of interruption of radiotherapy in the experimental group was lower than that in the control group (2.3% vs.27.3%), P = 0.003; 4. The incidence of bone pain in the experimental group was 34.1%, of which most were mild bone pain, and no severe bone pain occurred. The leukocyte and neutrophil counts of the patients in the bone pain group were significantly higher than those of the patients in the no bone pain group, P(WBC) = 0.001, P(ANC) = 0.002. Conclusions The preventive use of PEG-rhG-CSF decreases the incidence of neutropenia in patients undergoing concurrent chemoradiotherapy for NPC, thereby reducing rates of chemotherapy delays and radiotherapy interruptions, with mild adverse reactions that are tolerable by patients.
Effects of Temperature Fluctuations on Surface Mobility of Atomic Steps and Oxidation Dynamics in High-Temperature Alloys
Determination of optimal gamma radiation dose for mutation breeding in ’Sabz’ fig (Ficus carica L.) cuttings based on radiosensitivity and phenotypic changes
The dried fig cv. Sabz of Iran, distinguishes out among the several fig cultivars for its unique characteristics and excellent properties. The aims to this study were 1) Carefully monitoring the resulting phenotypic changes in growth patterns, leaf morphology, shoot traits, root characteristics, and other relevant traits after irradiated with different gamma rays; 2) Investigating the LD25, 50, 75 and GR25, 50, 75 values at different gamma radiation doses for chose optimum dose. According to our results, the LD50 was 70 Gy, while the LD25 and LD75 were approximately 48 and 95 Gy, respectively. Data analysis revealed that higher doses, ranging from 50 to 90 Gy, led to a reduction in leaf area for fig hardwood cuttings compared to those exposed to lower doses of gamma irradiation (10, 20, 30, and 40 Gy). In fig cuttings, the plant height gradually decreased in line with increasing irradiation doses up to 60 Gy. Among the root traits, root number was particularly influenced by higher radiation doses. On other hand, when fig cuttings were exposed to a 40 Gy radiation dosage, the average root count dropped by 50%. However, when fig cuttings were subjected to a 90 Gy radiation dose, the average root count surged by 90.7% in comparison to the control treatment. Additionally, the GR50 values were 63 Gy for internode length, 67 Gy for leaf area and 56 Gy for plant height and aerial biomass. However, the GR50 values for root number, root volume, and root biomass were 46 Gy, 57 Gy, and 51 Gy, respectively. An analysis based on the GR25, GR50, and GR75 values indicated that plant height, aerial biomass and root biomass exhibited greater sensitivity to radioactivity in comparison to other plant portions of the fig. According to the biological responses in the ‘Sabz’ fig, 60 Gy of gamma radiation is a suitable dose for initial mutagenesis studies.
DNA Tetrahedron-Driven Multivalent Proteolysis-Targeting Chimeras: Enhancing Protein Degradation Efficiency and Tumor Targeting
Engineering dimer mutants of human geranylgeranyl pyrophosphate synthase
Geranylgeranyl pyrophosphate synthase (GGPPS), a key enzyme in protein prenylation, plays a critical role in cellular signal transduction and is a promising target for cancer therapy. However, the enzyme’s native hexameric quaternary structure presents challenges for crystallographic studies. The primary objective of this study was to engineer dimeric forms of human GGPPS to facilitate high-resolution crystallographic analysis of its ligand binding interactions. Through site-directed mutagenesis, we disrupted the inter-dimer interactions required for hexamer assembly, generating three stable double-site mutants: Y246D/C247L, Y246D/C205A, and Y246K/C247L. Enzyme assays confirmed that all mutants retained wild-type catalytic activity under both saturating and subsaturating substrate conditions. Differential scanning fluorimetry showed that the mutant proteins had a ~10°C lower melting temperature than the wild-type enzyme but exhibited similar shifts in melting temperature in the presence of the known inhibitors risedronate and zoledronate. Crystallographic analysis of the Y246D/C247L mutant yielded a 2.1 Å resolution structure, providing detailed insights into the binding of isopentenyl pyrophosphate. Closer inspection also revealed the unexpected formation of intermolecular disulfide bonds connecting neighboring dimers, which may explain the enhanced crystallizability of the Y246D/C247L mutant compared to the wild-type and other mutants. These findings highlight the potential of the dimeric mutants as substitutes for wild-type GGPPS in future studies. Optimized dimeric mutants could serve as valuable molecular tools to further our understanding of the enzyme’s structural and functional properties and aid in the rational design of novel therapeutic agents targeting GGPPS.
Dissecting the Molecular Structure of the Air/Ice Interface from Quantum Simulations of the Sum-Frequency Generation Spectrum
Gene expression analysis reveals mir-29 as a linker regulatory molecule among rheumatoid arthritis, inflammatory bowel disease, and dementia: Insights from systems biology approach
Background Rheumatoid arthritis (RA) is a degenerative autoimmune disease, often managed through symptomatic treatment. The co-occurrence of the reported extra-articular comorbidities such as inflammatory bowel disease (IBD), and dementia may complicate the pathology of the disease as well as the treatment strategies. Therefore, in our study, we aim to elucidate the key genes, and regulatory elements implicated in the progression and association of these diseases, thereby highlighting the linked potential therapeutic targets. Methodology Ten microarray datasets each for RA, and IBD, and nine datasets for dementia were obtained from Gene Expression Omnibus. We identified common differentially expressed genes (DEGs) and constructed a gene-gene interaction network. Subsequently, topology analysis for hub gene identification, cluster and functional enrichment, and regulatory network analysis were performed. The hub genes were then validated using independent microarray datasets from Gene Expression Omnibus. Results A total of 198 common DEGs were identified from which CD44, FN1, IGF1, COL1A2, and POSTN were identified as the hub genes in our study. These hub genes were mostly enriched in significant processes and pathways like tissue development, collagen binding, cell adhesion, regulation of ERK1/2 cascade, PI3K-AKT signaling, and cell surface receptor signaling. Key transcription factors TWIST2, CEBPA, EP300, HDAC1, HDAC2, NFKB1, RELA, TWIST1, and YY1 along with the miRNA hsa-miR-29 were found to regulate the expression of the hub genes significantly. Among these regulatory molecules, miR-29 emerged as a significant linker molecule, bridging the molecular mechanisms of RA, IBD, and dementia. Validation of our hub genes demonstrated a similar expression trend in the independent datasets used for our study. Conclusion Our study underscores the significant role of miR-29 in modulating the expression of hub genes and the associated transcription factors, which are crucial in the comorbidity status of RA, dementia, and IBD. This regulatory mechanism highlights miR-29 as a key player in the pathogenesis of these comorbid diseases.
Mechanistic Investigation of the Ce(III) Chloride Photoredox Catalysis System: Understanding the Role of Alcohols as Additives
Aligned membranes regulate wound healing via MMP12 secreted by macrophages
Aligned electrospinning membranes (Align) have demonstrated the potential to enhance wound healing by establishing a regenerative microenvironment surrounding the wound; However, the precise mechanism underlying its facilitation of healing remains unclear. To elucidate aligned electrospun fiber membrane’s role in accelerating wound healing and improving its quality, we conducted a comprehensive analysis. Firstly, in vivo experiments confirmed that Align promotes wound healing. Through combined bulk RNA sequencing and single-cell RNA sequencing, we identified that MMP12+ macrophages exhibit high expression of MMP12 during the early stage of wound remodeling, thereby inhibiting fibroblast migration and reducing scar formation after wound closure. Finally, both in vitro and in vivo experiments further validated the role of MMP12 in promoting wound healing and suppressing fibroblast migration. Our findings reveal that Align effectively enhances skin wound healing by upregulating MMP12 expression while inhibiting fibroblast migration. These insights provide valuable knowledge on how Align promotes efficient scar-free wound healing and serve as a theoretical foundation for developing more effective biological dressings.
Site-Selective Copper(I)-Catalyzed Hydrogenation of Amides
Prevalence and features of allergic bronchopulmonary aspergillosis, United States, 2016–2022
The epidemiology of allergic bronchopulmonary aspergillosis (ABPA) in the United States is not well-described. To estimate national ABPA prevalence among patients with asthma or cystic fibrosis, characterize ABPA testing practices, and describe ABPA clinical features, treatment, and 6-month outcomes. We used the 2016–2022 Merative™ MarketScan® Commercial/Medicare and Multi-State Medicaid Databases to identify cohorts of patients with 1) asthma, 2) cystic fibrosis (CF), and 3) ABPA. We calculated ABPA prevalence per 10,000 patients with asthma or CF, assessed diagnostic testing for ABPA among patients with severe asthma, and described features of patients with ABPA using diagnosis and procedure codes. The overall ABPA prevalence among patients with asthma was 2.8/10,000 (Commercial/Medicare) and 1.0/10,000 (Medicaid). ABPA prevalence increased with asthma severity (Commercial/Medicare: mild 1.3, moderate 9.3, severe 70.6, Medicaid: mild 0.3, moderate 2.4, severe 32.4). Among patients with CF, ABPA prevalence was 183.7/10,000 (Commercial/Medicare) and 134.6/10,000 (Medicaid). Among patients with severe asthma, 10.3% (Commercial/Medicare) and 7.4% (Medicaid) received total immunoglobulin E testing, which is recommended for ABPA diagnosis. Among all patients with ABPA (Commercial/Medicare: n = 1,564, Medicaid: n = 410), ABPA treatments included inhaled corticosteroids (>70%), systemic corticosteroids (>62%), and antifungals (>18%). Patients with ABPA and Medicaid were more likely to experience hospitalization (45.1% vs. 22.5% of patients with Commercial/Medicare insurance) and respiratory failure (18.5% vs. 10.9%). This analysis provides initial estimates of national ABPA prevalence. Further studies could identify potential barriers to ABPA testing and investigate potential factors affecting payer-related differences in ABPA burden.
Controlling the Spatiotemporal Self-Organization of Stimuli-Responsive Nanocrystals under Out-of-Equilibrium Conditions
Assessing changing baleen whale distributions and reported incidents relative to vessel activity in the Northwest Atlantic
Baleen whales are among the largest marine megafauna, and while mostly well-protected from direct exploitation, they are increasingly affected by vessel traffic, interactions with fisheries, and climate change. Adverse interactions, notably vessel strikes and fishing gear entanglement, often result in distress, injury, or death for these animals. In Atlantic Canadian waters, such negative interactions or ‘incidents’ are consistently reported to marine animal response organizations but have not yet been analyzed relative to the spatial distribution of whales and vessels. Using a database of 483,003 whale sightings, 1,110 incident reports, and 82 million hours of maritime vessel activity, we conducted a spatiotemporal vulnerability analysis for all six baleen whale species occurring in the Northwest Atlantic Ocean by developing an ensemble of habitat-suitability models. The relative spatial risk of vessel-induced incidents was assessed for present (1985–2015) and projected near-future (2035–2055) distributions of baleen whales. Areas of high habitat suitability for multiple baleen whale species were intrinsically linked to sea surface temperature and salinity, with multispecies hotspots identified in the Bay of Fundy, Scotian Shelf, Laurentian Channel, Flemish Cap, and Gulf of St. Lawrence. Present-day model projections were independently evaluated using a separate database of acoustic detections and found to align well. Regions of high relative incident risk were projected close to densely inhabited regions, principal maritime routes, and major fishing grounds, in general coinciding with reported incident hotspots. While some high-risk regions already benefit from mitigation strategies aimed at protecting North Atlantic Right Whales, our analysis highlights the importance of considering risks to multiple species, both in the present day and under continued environmental change.
Improving early prediction of crop yield in Spanish olive groves using satellite imagery and machine learning
In the production sector, the usefulness of predictive systems as a tool for management and decision-making is well known. In the agricultural sector, a correct economic balance of the farm depends on making the right decisions. For this purpose, having information in advance on crop yields is an extraordinary help. Numerous predictive models infer accurate crop yield data from aerobiological variables and pollen analysis; this is around spring, in the middle stage of the crop year, when planning and investments are already done. The aim of this study is to anticipate accurate crop yield data at an early stage of the cropping season. In the case of olive groves in Spain, this period is in February. This work is developed for an entire province, Jaen, belonging to the region of Andalusia, in Southern Spain. The methodology uses Machine Learning algorithms together with an exhaustive analysis of predictor variables. Temporal data come from public web services, such as spatial data infrastructures of some state agencies. The processing of the satellite imagery is carried out by the geospatial processing service Google Earth Engine. The result is the early prediction of kilograms of both olive crop and olive oil, eight months prior to the beginning of the first harvesting campaigns of the year, with an average absolute error of prediction better than 26%. The relevance of this work is the early availability of predicted crop yield data together with the multi-scale applicability of the predictive models. This makes this model a useful tool for all the agents involved in olive grove management. From farmers, to agricultural technicians, researchers and scientists dedicated to the study of the olive tree, to governmental institutions and agricultural associations that provide technical support, advice and regulation to ensure responsible practices and the long-term viability of the olive industry.
Unlocking Chiral Sulfinimidoyl Electrophiles: Asymmetric Synthesis of Sulfinamides Catalyzed by Anionic Stereogenic-at-Cobalt(III) Complexes
Analyzing robust dividend payout policy with dynamic panel regression: Application of speed of adjustment to half-life
This study aims to observe the effects of financial metrics, free float shareholders, GDP growth and firm age on dividend payout policy in both the short- and long-term scenarios. The study introduces the dynamic panel regression models, i.e. Autoregressive Integrated Moving Average (ARIMA) for time series data and Weighted Least Squares (WLS) to account for autocorrelation and heteroscedasticity limitation. The dataset includes all companies listed on the Stock Exchange of Thailand during the years 2013–2023. The study finds that in the long-term, GDP growth negatively relates to dividend payout policy in all industrial sectors. Financial metrics, free float shareholders, GDP growth and firm age affect a mixed picture of industrial sectors on dividend payout policy. In the short-term, previous dividend payments significantly influence dividend payment policy. Furthermore, a higher debt-to-equity ratio, firm age, and free cashflows influence dividend payout policy in various industrial sectors. Also shown by the analysis is that factors influence short-run adjustment to half-life analysis.
Colloidal Germanium Quantum Dots with Broadly Tunable Size and Light Emission
The value co-creation mechanism of Public Cultural Services ecosystem in China based on "public value" theory
The establishment of China’s public cultural service system has been explored for nearly two decades, but there is still a significant gap in achieving the goal of equalising and eliminating differences in public value, and it is urgent to systematically explore the public value governance issues contained in it. This paper presents a localised theoretical analysis framework based on the strategic triangle model of public value, with the objective of exploring the endogenous mechanism of China’s public cultural services ecosystem (PCSE). Furthermore, it constructs a panel vector autoregression (PVAR) model from a dynamic endogenous perspective, employing the STATA 16.0 software package to conduct empirical tests. The empirical testing of the interactions between government attention (GA), cultural needs (CN) and public cultural services (PCS), as well as the regional heterogeneity, is based on data from 31 provinces and municipalities in mainland China for the period of 2008–2022. The findings are as follows: (1) The unified analysis framework reveals a significant positive mutual promotion relationship between GA and PCS. In contrast, the two-way promotion relationship between CN and PCS is weak, while the relationship between GA and PCS is unstable. (2) The results of the dynamic response analysis demonstrate significant regional disparities in the value co-creation path of public cultural services. The circular transfer of CN and PCS is more pronounced in the eastern region, while the central-western regions rely more on the circular transfer of GA and PCS. This study offers insights for central and local governments to reinforce the value co-creation foundation of a service-oriented government, explore a value co-creation pathway tailored to local conditions, and construct a contemporary public cultural services ecosystem guided by the value of common prosperity in spiritual life.