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Abstract Natural products encompass a diverse range of compounds with high impact applications in consumer care, agriculture and most notably, therapeutics. However, despite the expansive chemical repertoire indicated in genomic information of microbes, only a small subset can be obtained under laboratory conditions. To increase accessible chemical space and realize Nature’s full chemical potential, a multi-pronged genetic- and cultivation-based strategy has been employed to activate and upregulate natural product biosyntheses in native and heterologous strains. This data descriptor documents a characterized collection of 2,138 liquid chromatography-tandem mass spectrometry (LC/MS-MS) spectra of fermentation extracts from 54 native actinobacterial strains collected from soil and marine environments in Singapore, and their 459 activated mutants in 3 to 5 media. A total of 743 unique metabolites have been identified, with the activated mutants demonstrating an approximately 2-fold expansion in accessible chemical space over wild type strains. Interrogating this expanded chemical diversity with cheminformatic tools can provide direction for the discovery of novel natural products with desirable functional activity.

Abstract Information and Communication Technologies (ICTs) can provide rich learning opportunities in classroom teaching, which requires teachers’ effective instrumental orchestrations. However, there is a lack of research regarding the development of teachers’ instrumental orchestrations. In this study, we designed and implemented a professional development course, aiming to explore whether the course could change preservice mathematics teachers’ instrumental orchestrations. To this end, an analytical framework of instrumental orchestrations within a GeoGebra environment was established. Data were collected from Chinese preservice mathematics teachers, including the videotapes of their simulated lessons, GeoGebra files, written documents, self-reflections, online speaking, etc. In the results, three participants’ changes in instrumental orchestrations were presented as main cases. It was found that the three preservice mathematics teachers’ types of instrumental orchestrations did not change, but the frequencies of those increased significantly. The changes in didactical configurations were mainly reflected in the layout of GeoGebra, and the changes in exploitation modes were mainly manifested in the techniques teachers use and the management of mathematics tasks. In addition, it was revealed that theoretical support (instrumental approach), technical support (knowledge about using GeoGebra), and community support (“Same Content Different Designs” activity and communicating and discussing with others) were useful course elements inviting changes in instrumental orchestrations. In this regard, this study contributes to providing a promising professional development course that can be used in teacher training so as to improve teachers’ instrumental orchestrations.

The World Health Organization’s end TB strategy promotes the use of symptom and chest radiograph screening for tuberculosis (TB) disease. However, asymptomatic early states of TB beyond latent TB infection and active disease can go unrecognized using current screening criteria. We conducted a longitudinal cohort study enrolling household contacts initially free of TB disease and followed them for the occurrence of incident TB over 1 year. Among 1,747 screened contacts, 27 (52%) of the 52 persons in whom TB subsequently developed during follow-up had a baseline abnormal radiograph. Of contacts without TB symptoms, persons with an abnormal radiograph were at higher risk for subsequent TB than persons with an unremarkable radiograph (adjusted hazard ratio 15.62 [95% CI 7.74–31.54]). In young adults, we found a strong linear relationship between radiograph severity and time to TB diagnosis. Our findings suggest chest radiograph screening can extend to detecting early TB states, thereby enabling timely intervention.

Abstract Background Venous thromboembolism (VTE), is a noteworthy complication in individuals with gastric cancer, but the current diagnosis and treatment methods lack accuracy. In this study, we developed a t-PAIC chemiluminescence kit and employed chemiluminescence to detect the tissue plasminogen activator inhibitor complex (t-PAIC), thrombin-antithrombin III complex (TAT), plasmin-α2-plasmin inhibitor complex (PIC) and thrombomodulin (TM), combined with D-dimer and fibrin degradation products (FDP), to investigate their diagnostic potential for venous thrombosis in gastric cancer patients. The study assessed variations in six indicators among gastric cancer patients at different stages. Results The t-PAIC reagent showed LOD is 1.2 ng/mL and a linear factor R greater than 0.99. The reagents demonstrated accurate results, with all accuracy deviations being within 5%. The intra-batch and inter-batch CVs for the t-PAIC reagent were both within 8%. The correlation coefficient R between this method and Sysmex was 0.979. Gastric cancer patients exhibited elevated levels of TAT, PIC, TM, D-D, FDP compared to the healthy population, while no significant difference was observed in t-PAIC. In the staging of gastric cancer, patients in III-IV stages exhibit higher levels of the six markers compared to those in I-II stages. The ROC curve indicates an enhancement in sensitivity and specificity of the combined diagnosis of four or six indicators. Conclusion Our chemiluminescence assay performs comparably to Sysmex’s method and at a reduced cost. The use of multiple markers, including t-PAIC, TM, TAT, PIC, D-D, and FDP, is superior to the use of single markers for diagnosing VTE in patients with malignant tumors. Gastric cancer patients should be screened for the six markers to facilitate proactive prophylaxis, determine the most appropriate treatment timing, ameliorate their prognosis, decrease the occurrence of venous thrombosis and mortality, and extend their survival.

The research status of operational management for research vessels is reviewed in this paper. The reviewed literature are analyzed from four topics, i.e., operation and management, evaluation of research vessel, voyage sharing and coordination, and others. By investigating four national organizations, research vessel owner, we summarized the operational management experience from five aspects, i.e., scientific survey, ship and research equipment asset, ship operation, ship and equipment safety, and the crew. Taking “ZHUHAIYUN” as an example, this paper uncovers that a ship with characteristic of research vessel and intelligent ship may face three challenges, i.e., without operational management experience for intelligent ships, lack of professional human resources, unestablished organization. To overcome these challenges, the current operational management practice of “ZHUHAIYUN” is introduced from five points, i.e., building the prototype of operational management center, establishing the ship management system, constructing professional team, and developing oceanic culture in the South China Sea. The results provide reference for operational management of both new-building research vessels and intelligent ships.

Background and purpose: Despite the superior dose conformity of proton therapy, the dose distribution is sensitive to daily anatomical changes, which can affect treatment accuracy. This study evaluated the dose recalculation accuracy of two synthetic computed tomography (sCT) generation algorithms in a commercial treatment planning system. Materials and methods: The evaluation was conducted for head-and-neck, thorax-and-abdomen, and pelvis sites treated with proton therapy. Thirty patients with two cone-beam computed tomography (CBCT) scans each were selected. The sCT images were generated from CBCT scans using two algorithms, Corrected CBCT (corrCBCT) and Virtual CT (vCT). Dose recalculations were performed based on these images for comparison with “ground truth” deformed CTs. Results: The choice of algorithm influenced dose recalculation accuracy, particularly in high dose regions. For head-and-neck cases, the corrCBCT method showed closer agreement with the “ground truth”, while for thorax-and-abdomen and pelvis cases, the vCT algorithm yielded better results (mean percentage dose discrepancy of 0.6 %, 1.3 % and 0.5 % for the three sites, respectively, in the high dose region). Head-and-neck and pelvis cases exhibited excellent agreement in high dose regions (2 %/2 mm gamma passing rate >98 %), while thorax-and-abdomen cases exhibited the largest differences, suggesting caution in sCT algorithm usage for this site. Significant systematic differences were observed in the clinical target volume and organ-at-risk doses in head-and-neck and pelvis cases, highlighting the importance of using the correct algorithm. Conclusions: This study provided treatment site-specific recommendations for sCT algorithm selection in proton therapy. The findings offered insights for proton beam centers implementing adaptive radiotherapy workflows.

Abstract Pulmonary fibrosis is characterized by pathological accumulation of scar tissue in the lung parenchyma. Many of the processes that are implicated in fibrosis, including increased extracellular matrix synthesis, also occur following pneumonectomy (PNX), but PNX instead results in regenerative compensatory growth of the lung. As fibroblasts are the major cell type responsible for extracellular matrix production, we hypothesized that comparing fibroblast responses to PNX and bleomycin (BLM) would unveil key differences in the role they play during regenerative versus fibrotic lung responses. RNA‐sequencing was performed on flow‐sorted fibroblasts freshly isolated from mouse lungs 14 days after BLM, PNX, or sham controls. RNA‐sequencing analysis revealed highly similar biological processes to be involved in fibroblast responses to both BLM and PNX, including TGF‐β1 and TNF‐α. Interestingly, we observed smaller changes in gene expression after PNX than BLM at Day 14, suggesting that the fibroblast response to PNX may be muted by expression of transcripts that moderate pro‐fibrotic pathways. Itpkc, encoding inositol triphosphate kinase C, was a gene uniquely up‐regulated by PNX and not BLM. ITPKC overexpression in lung fibroblasts antagonized the pro‐fibrotic effect of TGF‐β1. RNA‐sequencing analysis has identified considerable overlap in transcriptional changes between fibroblasts following PNX and those overexpressing ITPKC.

Abstract Background Type 2 diabetes mellitus (T2DM) is closely linked to metabolic syndrome, characterised by insulin resistance, hyperglycaemia, abnormal lipid metabolism, and chronic inflammation. Diabetic ulcers (DUs) comprise consequential complications that arise as a result of T2DM. To investigate, db/db mice were used for the disease model. The findings demonstrated that a scaffold made from a combination of rhubarb charcoal-crosslinked chitosan and silk fibroin, designated as RCS/SF, was able to improve the healing process of diabetic wounds in db/db mice. However, previous studies have primarily concentrated on investigating the impacts of the RSC/SF scaffold on wound healing only, while its influence on the entire body has not been fully elucidated. Material and methods The silk fibroin/chitosan sponge scaffold containing rhubarb charcoal was fabricated in the present study using a freeze-drying approach. Subsequently, an incision with a diameter of 8 mm was made on the dorsal skin of the mice, and the RCS/SF scaffold was applied directly to the wound for 14 days. Subsequently, the impact of RCS/SF scaffold therapy on hepatic lipid metabolism was assessed through analysis of serum and liver biochemistry, histopathology, quantitative real-time PCR (qRT-PCR), immunohistochemistry, and Western blotting. Results The use of the RCS/SF scaffold led to an enhancement in the conditions associated with serum glucolipid metabolism in db/db mice. An assessment of hepatic histopathology further confirmed this enhancement. Additionally, the qRT-PCR analysis revealed that treatment with RCS/SF scaffold resulted in the downregulation of genes associated with fatty acid synthesis, fatty acid uptake, triglyceride (TG) synthesis, gluconeogenesis, and inflammatory factors. Moreover, the beneficial effect of the RCS/SF scaffold on oxidative stress was shown by assessing antioxidant enzymes and lipid peroxidation. Additionally, the network pharmacology analysis verified that the adenosine monophosphate-activated protein kinase (AMPK) signalling pathway had a vital function in mitigating non-alcoholic fatty liver disease (NAFLD) by utilizing R. officinale. The measurement of AMPK, sterol regulatory element binding protein 1 (SREBP1), fatty acid synthase (FASN), and acetyl CoA carboxylase (ACC) gene and protein expression provided support for this discovery. Furthermore, the molecular docking investigations revealed a robust affinity between the active components of rhubarb and the downstream targets of AMPK (SREBP1 and FASN). Conclusion By regulating the AMPK signalling pathway, the RCS/SF scaffold applied topically effectively mitigated hepatic lipid accumulation, decreased inflammation, and attenuated oxidative stress. The present study, therefore, emphasises the crucial role of the topical RCS/SF scaffold in regulating hepatic lipid metabolism, thereby confirming the concept of "external and internal reshaping".

Abstract Natural products possess significant therapeutic potential but remain underutilized despite advances in genomics and bioinformatics. While there are approaches to activate and upregulate natural product biosynthesis in both native and heterologous microbial strains, a comprehensive strategy to elicit production of natural products as well as a generalizable and efficient method to interrogate diverse native strains collection, remains lacking. Here, we explore a flexible and robust integrase-mediated multi-pronged activation approach to reliably perturb and globally trigger antibiotics production in actinobacteria. Across 54 actinobacterial strains, our approach yielded 124 distinct activator-strain combinations which consistently outperform wild type. Our approach expands accessible metabolite space by nearly two-fold and increases selected metabolite yields by up to >200-fold, enabling discovery of Gram-negative bioactivity in tetramic acid analogs. We envision these findings as a gateway towards a more streamlined, accelerated, and scalable strategy to unlock the full potential of Nature’s chemical repertoire.

Background: To delve into the precise mechanisms by which 6-gingerol ameliorates lipid metabolism disorders in skeletal muscle. Methods: The level of triglycerides (TG) was used to evaluate lipid deposition. In skeletal muscle, transmission electron microscopy (TEM) was employed to observe mitochondrial morphology. Additionally, PCR was applied to detect mitochondrial biogenesis, and levels of malondialdehyde (MDA), catalase (CAT), glutathione, r-glutamyl cysteingl+glycine (GSH) and nicotinamide adenine dinucleotide (NADH) were measured to assess mitochondrial oxidative stress levels. In vivo, flow cytometry and immunofluorescence assays were conducted to quantify reactive oxygen species (ROS) and mitochondrial membrane potential (MMP). Furthermore, the Seahorse XF assays was utilized to assess mitochondrial respiratory capacity. Fluorescence confocal microscopy and molecular docking were applied to analyze the binding of 6-gingerol and adiponectin receptor 1 (AdipoR1). The expression of AdipoR1, AMPK, PGC-1α and SIRT1 were detected by Western Blot. Results: In vivo, 6-gingerol could reduce body weight in mice induced by a high-fat diet, enhance metabolic profiles in plasma, decrease lipid accumulation in skeletal muscle and liver, and elevate adiponectin levels. In skeletal muscle, it could restore mitochondrial morphology, boost mitochondrial copy number and biogenesis, and mitigate oxidative stress. In vitro, 6-gingerol may directly interact with AdipoR1 to upregulate the expression of downstream proteins p-AMPK, SIRT1, and PGC-1α, leading to a reduction in lipid deposition, a decrease in ROS production, an increase in mitochondrial membrane potential, and an enhancement of mitochondrial respiratory capacity in C2C12 myotubes. Conclusion: 6-Gingerol ameliorated lipid metabolism in skeletal muscle by regulating the AdipoR1/AMPK signaling pathway.

BackgroundEmerging infectious diseases pose a significant threat to global public health. Timely detection and response are crucial in mitigating the spread of such epidemics. Inferring the onset time and epidemiological characteristics is vital for accelerating early interventions, but accurately predicting these parameters in the early stages remains challenging.MethodsWe introduce a Bayesian inference method to fit epidemic models to time series data based on state-space modeling, employing a stochastic Susceptible-Exposed-Infectious-Removed (SEIR) model for transmission dynamics analysis. Our approach uses the particle Markov chain Monte Carlo (PMCMC) method to estimate key epidemiological parameters, including the onset time, the transmission rate, and the recovery rate. The PMCMC algorithm integrates the advantageous aspects of both MCMC and particle filtering methodologies to yield a computationally feasible and effective means of approximating the likelihood function, especially when it is computationally intractable.ResultsTo validate the proposed method, we conduct case studies on COVID-19 outbreaks in Wuhan, Shanghai and Nanjing, China, respectively. Using early-stage case reports, the PMCMC algorithm accurately predicted the onset time, key epidemiological parameters, and the basic reproduction number. These findings are consistent with empirical studies and the literature.ConclusionThis study presents a robust Bayesian inference method for the timely investigation of emerging infectious diseases. By accurately estimating the onset time and essential epidemiological parameters, our approach is versatile and efficient, extending its utility beyond COVID-19.

Abstract Background There are limited real-world data regarding the use of droperidol for antiemetic prophylaxis in intravenous patient-controlled analgesia (IV-PCA). This study aimed to evaluate the antiemetic benefits and sedation effects of droperidol in morphine-based IV-PCA. Methods Patients who underwent major surgery and used morphine-based IV-PCA at a medical center from January 2020 to November 2022 were retrospectively analyzed. The primary outcome was the rate of any postoperative nausea and/or vomiting (PONV) within 72 h after surgery. Propensity score matching was used to match patients with and without the addition of droperidol to IV-PCA infusate in a 1:1 ratio. Multivariable conditional logistic regression models were used to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Results After matching, 1,104 subjects were included for analysis. The addition of droperidol to IV-PCA reduced the risk of PONV (aOR: 0.49, 95% CI: 0.35–0.67, p

Deserts play a significant role in terrestrial ecosystems, but their importance is often underestimated in research due to the undervaluation of ecosystem services (ES), particularly the absence of environmental stakeholder perspectives. This study utilized the social science research methodology to investigate the identification and perceptions of desert ES, and the perceived changes in the significance and accessibility of these services following land use alteration among two groups with distinct livelihood strategies in the arid desert region of Northwest China. The study identified 28 ES; with water being the top priority for all; herbs, water and fodder were considered significantly reduced by 78.69 %, 55.74 % and 50.82 % of the PPG, while 62.69 %, 37.31 % and 32.84 % of the APG considered herbs, sense of belonging and link to ancestors to be significantly decreased. The research also explored the potential of social science research methods for assessing ES and contributing to understanding environmental stakeholders' needs and perceptions. It is recommended that future ecological conservation and land project development prioritizes the livelihoods, emotional well-being, and cultural needs of residents. This approach will contribute to the long-term sustainability of both the environment and the project, while also safeguarding the well-being of residents.

Background and purpose: High-density dental fillings pose a non-negligible impact on head and neck cancer treatment. For proton therapy, stopping power ratio (SPR) prediction will be significantly impaired by the associated image artifacts. Dose perturbation is also inevitable, compromising the treatment plan quality. While plenty of work has been done on metal or amalgam fillings, none has touched on composite resin (CR) and glass ionomer cement (GIC) which have seen an increasing usage. Hence, this work aims to provide a detailed characterisation of SPR and dose perturbation in proton therapy caused by CR and GIC. Materials and methods: Four types of fillings were used: CR, Fuji Bulk (FB), Fuji II (FII) and Fuji IX (FIX). The latter three belong to GIC category. Measured SPR were compared with SPR predicted using single-energy computed tomography (SECT) and dual-energy computed tomography (DECT). Dose perturbation of proton beams with lower- and higher-energy levels was also quantified using Gafchromic films. Results: The measured SPR for CR, FB, FII and FIX were 1.68, 1.77, 1.77 and 1.76, respectively. Overall, DECT could predict SPR better than SECT. The lowest percentage error achieved by DECT was 19.7 %, demonstrating the challenge in estimating SPR, even for fillings with relatively lower densities. For both proton beam energies and all four fillings of about 4.5 mm thickness, the maximum dose perturbation was 3 %. Conclusion: This study showed that dose perturbation by CR and GIC was comparatively small. We have measured and recommended the SPR values for overriding the fillings in TPS.

The lack of reliable near-surface wind data products in lake district regions significantly limits the efficiency of meteorological models, forecasts, services, and wind resource development. This is primarily due to a shortage of observation data and related studies, as well as insufficient validation and promotion of existing data products, which further hinders the comprehension and monitoring of local wind fields. In this study, comprehensive verification research was conducted on mainstream wind field products, namely, ERA5-Land (EC), GLDAS (GL), and HRCLDAS (HR) in the Dongting Lake area of China. This was achieved by utilizing a large volume of measured data and a triple collocation analysis (TCA) method. Additionally, an exploration into the optimal wind field data fusion method was undertaken. HR products demonstrate superior performance in capturing wind speed at the in situ measured scale, while GL outperforms at the grid scale, and EC products show relatively stable performance with minimal outliers. The long short-term memory (LSTM) neural network model, combined with time-series features, emerges as the most optimal data fusion model. LSTM fusion product is superior to the original product (except for HR products at the in situ measured scale), TCA-based weighted fusion products, and multi-layer fully connected neural network (MFCNN) on various parameters. This study quantifies the performance of mainstream wind products in lake areas and provides a benchmark for further application of these products. Furthermore, the successful implementation of an optimal wind data fusion method can provide valuable insights for related research, and the resulting wind fusion products can offer superior basic data support for local terminal applications.

Dynamic mathematics software, such as GeoGebra, is a kind of subject-specific digital tool used for enabling users to create mathematical objects and operate them dynamically and interactively, which is very suitable for mathematics teaching and learning at all school levels, especially at the secondary school level. However, limited research has focused on how multiple influencing factors of secondary school teachers' usage behavior of dynamic mathematics software work together. Based on the unified theory of acceptance and use of technology (UTAUT) model, combined with the concept of self-efficacy, this study proposed a conceptual model used to analyze the factors influencing secondary school teachers' usage behavior of dynamic mathematics software. Valid questionnaire data were provided by 393 secondary school mathematics teachers in the Hunan province of China and analyzed using a partial least squares structural equation modeling (PLS-SEM) method. The results showed that social influence, performance expectancy and effort expectancy significantly and positively affected secondary school teachers' behavioral intentions of dynamic mathematics software, and social influence was the greatest influential factor. In the meantime, facilitating conditions, self-efficacy and behavioral intention had significant and positive effects on secondary school teachers' usage behavior of dynamic mathematics software, and facilitating conditions were the greatest influential factor. Results from the multi-group analysis indicated that gender and teaching experience did not have significant moderating effects on all relationships in the dynamic mathematics software usage conceptual model. However, major had a moderating effect on the relationship between self-efficacy and usage behavior, as well as the relationship between behavioral intention and usage behavior. In addition, training had a moderating effect on the relationship between social influence and behavioral intention. This study has made a significant contribution to the development of a conceptual model that could be used to explore how multiple factors affected secondary school teachers' usage behavior of dynamic mathematics software. It also benefits the government, schools and universities in enhancing teachers' digital teaching competencies.

The sampling technique is commonly used in research investigations to more accurately estimate data with greater precision, at a lower cost and in less time. In plant DUS (distinctness, uniformity, and stability) testing, many quantitative characteristic data usually need to be obtained through individual measurements. However, there is currently no scientific method for determining the appropriate sampling size. The minimum number of testing samples for DUS testing was calculated based on the theory of sample size in descriptive studies and was validated through simple random sampling. The results show that the quantitative characteristics for the edible mushroom Shiitake (Lentinula edodes) in DUS testing were uniform. The calculated results show that 10 fruiting bodies for a single measurement were sufficient. Furthermore, the outcomes of the random sampling revealed that the mean of 10 samples did not significantly differ from the mean of all data. When the sample size exceeded 10, Cohen’s kappa statistic suggested that the conclusion of distinctness was very close to the near-perfect agreement. Reducing the number of samples did not affect the uniform assessment. This study suggests that the theory of sample size in descriptive studies could be applied to calculate the minimum sample size in DUS testing, and for Shiitake DUS testing, measuring 10 fruiting bodies was sufficient.

Abstract Background The retinal image quality derived from lower-order (LOA) and higher-order aberrations (HOA) for fixed 3-mm and photopic pupil diameters, in children undergoing combined 0.01% atropine and orthokeratology (AOK) versus those receiving orthokeratology alone (OK) over two years was evaluated. Methods The visual Strehl ratio based on the optical transfer function (VSOTF), derived from 2nd- to 4th-order terms (LOA and HOA combined), 2nd-order terms (LOA only), and 3rd- to 4th-order terms (HOA only) for fixed 3-mm and natural photopic pupil diameters, was compared between the two treatment groups. The individual Zernike coefficients for a fixed 3-mm pupil size of 2nd- to 4th-orders, root mean square (RMS) of LOA ( $${Z}_{2}^{0}$$ Z 2 0 , $${Z}_{2}^{-2}$$ Z 2 - 2 , and $${Z}_{2}^{2}$$ Z 2 2 combined), HOA (3rd to 4th orders inclusive), and Coma ( $${Z}_{3}^{-1}{\mathrm{and }Z}_{3}^{1}$$ Z 3 - 1 and Z 3 1 combined) were also compared between the two groups. Results Right eye data of 33 AOK and 35 OK participants were analysed. Under photopic conditions, significantly lower VSOTF based on HOA only was observed in the AOK group compared with that in the OK group at all post-treatment visits (all P 0.05). For a fixed 3-mm pupil size, the VSOTF based on HOA only, LOA only, or HOA and LOA combined, were not different between the two groups (all P > 0.05). AOK participants had slower axial elongation (mean ± SD, 0.17 ± 0.19 mm vs. 0.35 ± 0.20 mm, P

Abstract Background Ambient air pollutants can be hazardous to human health, especially for vulnerable children. The impact of ambient air pollutant exposure before and during intensive care unit (ICU) stays on the development of ventilator-associated pneumonia (VAP) in critically ill children has not been established. We aimed to determine the correlations between short-term exposures to ambient fine particulate matter (PM2.5) and VAP in pediatric cardiac surgery patients in the ICU, and explore the effect of delayed exposure. Methods The medical record of 1755 child patients requiring artificial ventilation in the ICU between December 2013 to December 2020, were analyzed. The daily average concentrations of particulate matters (PM2.5 and PM10), sulfur dioxide (SO2), and ozone (O3) were calculated from public data. Interactions between these pollutants and VAP were simulated with the distributed lag non-linear model. Results Three hundred forty-eight cases (19.829%) of VAP were identified in this study, while the average concentrations of PM2.5, PM10, O3 and SO2 were 58, 118, 98 and 26 μg/m3, respectively. Exposure to increased levels of PM2.5 two days prior (lag 2-day) to VAP diagnosis is significantly correlated with an enhanced risk for VAP development. Even a slight increase of 10 μg/m3 in PM2.5 can translate to a 5.4% increase in VAP incidence (95% CI: 1.4%-9.5%) while the VAP incidence increased to 11.1% (95%CI: 4.5–19.5%) when PM2.5 concentration is well below the National Ambient Air Quality standard (NAAQS) of 50 μg/m3. The association was more pronounced in those aged below 3-months, with low body mass index or suffered from pulmonary arterial hypertension. Conclusion Short-term PM2.5 exposure is a significant risk for development of VAP in pediatric patients. This risk is present even with PM2.5 levels below the NAAQS. Ambient PM2.5 may represent a previously unrecognized risk factor for pneumonia and the current environmental pollution standards need to be reevaluated to consider susceptible populations. Trial registration The trial was registered with the National Clinical Trial Center: The correlation between ambient air pollution and the complications in ICU underwent cardiac surgery. Trial registration number: ChiCTR2000030507. Date of registration: March 5, 2020. URL of trial registry record: http://www.chictr.org.cn/index.aspx .

Background and purposeThis study aimed to investigate the feasibility of safe-dose escalation to dominant intraprostatic lesions (DILs) and assess the clinical impact using dose-volume (DV) and biological metrics in photon and proton therapy. Biological parameters defined as late grade ≥ 2 gastrointestinal (GI) and genitourinary (GU) derived from planned (DP) and accumulated dose (DA) were utilized.Materials and methodsIn total, 10 patients with high-risk prostate cancer with multiparametric MRI-defined DILs were investigated. Each patient had two plans with a focal boost to the DILs using intensity-modulated proton therapy (IMPT) and volumetric-modulated arc therapy (VMAT). Plans were optimized to obtain DIL coverage while respecting the mandatory organ-at-risk constraints. For the planning evaluation, DV metrics, tumor control probability (TCP) for the DILs and whole prostate excluding the DILs (prostate-DILs), and normal tissue complication probability (NTCP) for the rectum and bladder were calculated. Wilcoxon signed-rank test was used for analyzing TCP and NTCP data.ResultsIMPT achieved a higher Dmean for the DILs compared to VMAT (IMPT: 68.1 GyRBE vs. VMAT: 66.6 Gy, p < 0.05). Intermediate–high rectal and bladder doses were lower for IMPT (p < 0.05), while the high-dose region (V60 Gy) remained comparable. IMPT-TCP for prostate-DIL were higher compared to VMAT (IMPT: 86%; α/β = 3, 94.3%; α/β = 1.5 vs. VMAT: 84.7%; α/β = 3, 93.9%; α/β = 1.5, p < 0.05). Likewise, IMPT obtained a moderately higher DIL TCP (IMPT: 97%; α/β = 3, 99.3%; α/β = 1.5 vs. VMAT: 95.9%; α/β = 3, 98.9%; α/β = 1.5, p < 0.05). Rectal DA-NTCP displayed the highest GI toxicity risk at 5.6%, and IMPT has a lower GI toxicity risk compared to VMAT-predicted Quantec-NTCP (p < 0.05). Bladder DP-NTCP projected a higher GU toxicity than DA-NTCP, with VMAT having the highest risk (p < 0.05).ConclusionDose escalation using IMPT is able to achieve a high TCP for the DILs, with the lowest rectal and bladder DV doses at the intermediate–high-dose range. The reduction in physical dose was translated into a lower NTCP (p < 0.05) for the bladder, although rectal toxicity remained equivalent.

BackgroundThe growing global burden of visual impairment necessitates better population eye screening for early detection of eye diseases. However, accessibility to testing is often limited and centralized at in-hospital settings. Furthermore, many eye screening programs were disrupted by the COVID-19 pandemic, presenting an urgent need for out-of-hospital solutions. ObjectiveThis study investigates the performance of a novel remote perimetry application designed in a virtual reality metaverse environment to enable functional testing in community-based and primary care settings. MethodsThis was a prospective observational study investigating the performance of a novel remote perimetry solution in comparison with the gold standard Humphrey visual field (HVF) perimeter. Subjects received a comprehensive ophthalmologic assessment, HVF perimetry, and remote perimetry testing. The primary outcome measure was the agreement in the classification of overall perimetry result normality by the HVF (Swedish interactive threshold algorithm–fast) and testing with the novel algorithm. Secondary outcome measures included concordance of individual testing points and perimetry topographic maps. ResultsWe recruited 10 subjects with an average age of 59.6 (range 28-81) years. Of these, 7 (70%) were male and 3 (30%) were female. The agreement in the classification of overall perimetry results was high (9/10, 90%). The pointwise concordance in the automated classification of individual test points was 83.3% (8.2%; range 75%-100%). In addition, there was good perimetry topographic concordance with the HVF in all subjects. ConclusionsRemote perimetry in a metaverse environment had good concordance with gold standard perimetry using the HVF and could potentially avail functional eye screening in out-of-hospital settings.

Abstract Background Minimally invasive modifications of inguinal lymphadenectomy (IL), including laparoscopic IL (LIL) and robotic-assisted IL (RAIL), have been utilized for penile cancer. Comparative study is necessary to guide the decision about which minimally invasive technique to select for IL. Therefore we compared RAIL with LIL performed via an antegrade approach in terms of perioperative outcomes. Methods We conducted a retrospective study of 43 patients who underwent RAIL (n = 20) or LIL (n = 23) for penile cancer from 2016 to 2020. The key surgical procedures and techniques are described. Complications were graded by the Clavien-Dindo classification, and operative time, estimated blood loss (EBL), lymph nodal yield, nodal positivity, postoperative drain duration, and disease recurrence during follow-up were assessed. Categorical variables were compared using chi-squared whereas continuous variables were compared by t-tests. Results The operative time for RAIL was significantly shorter than that of LIL (median 83 vs 95 min). Significantly less blood loss was reported with RAIL than with LIL (median 10 vs 35 ml). Lymph node yield, pathological positive nodes, the hospital stay, postoperative drain duration, postoperative complications and recurrence were similar for RAIL and LIL. Conclusions For patients with penile cancer, perioperative outcomes of RAIL and LIL were similar, but there was less blood loss, a shorter operative time for robotic cases.

Purpose Strokes are challenging to diagnose in pediatric emergency departments (EDs) as level of suspicion is low and atypical presentations are common. We analyzed clinical features, epidemiology and factors of delayed identification in arterial ischemic strokes (AIS) and hemorrhagic strokes (HS). Methods Single-center retrospective cohort study of children aged between 29 days and 18 years old diagnosed with stroke between July 2016 to June 2021. Results Among 36 children, 11 (30.5%) had AIS, 25 (69.4%) had HS. Median age for AIS was 9 years (interquartile range [IQR], 2 to 9) and HS 9 years (IQR, 1 to 11.5) (P=0.715). Focal neurological deficit was seen in 72.7% of AIS and 20% of HS (P=0.006). Only 18.2% of AIS and 52.0% of HS presented within 6 hours of symptoms. Median time from symptom onset to ED presentation was 24 hours (IQR, 12 to 28) for AIS and 7 hours (IQR, 1.8 to 48) for HS (P=0.595). Most (85.6%) arrived by own transport. Median time from presentation to neuroimaging was 7 hours (IQR, 0.9 to 7) for AIS and 4.8 (IQR, 1.3 to 16.8) hours for HS (P=0.376). Eleven patients, 9/25 (36.0%) HS and 2/11 (18.2%) AIS, did not have stroke as differential diagnosis at ED (P=0.714). Common initial diagnoses were viral illness or headaches. On univariate analysis, age

Abstract Background The N6‐methyladenosine (m6A) can modify long non‐coding RNAs (lncRNAs), thereby influencing a wide array of biological functions. However, the prognosis of m6A‐related lncRNAs (m6ARLncRNAs) in non‐small cell lung cancer (NSCLC) remains largely unknown. Methods Pearson correlation analysis was used to identify m6ARLncRNAs in 1835 NSCLC patients and with the condition (|Pearson R| > 0.4 and p

Abstract Objective This study aims to decode the proteomic signature of cardiomyocytes in response to lncRNA Ftx knockdown and overexpression via proteomic analysis, and to study the biological role of lncRNA Ftx in cardiomyocytes. Methods The expression level of the lncRNA Ftx in cardiomyocytes cultured in vitro was intervened, and the changes in protein levels in cardiomyocytes were quantitatively detected by liquid chromatography-mass spectrometry. The key molecules and pathways of the lncRNA-Ftx response were further examined by GO, KEGG, and protein interaction analysis. Results A total of 2828 proteins are quantified. With a 1.5-fold change threshold, 32 upregulated proteins and 49 downregulated proteins are identified in the lncRNA Ftx overexpression group, while 67 up-regulated proteins and 54 down-regulated proteins are identified in the lncRNA Ftx knockdown group. Functional clustering analysis of differential genes revealed that the lncRNA Ftx is involved in regulating cardiomyocyte apoptosis and ferroptosis and improving cellular energy metabolism. In addition, Hub genes such as ITGB1, HMGA2, STAT3, GSS, and LPCAT3 are regulated downstream by lncRNA Ftx. Conclusion This study demonstrates that lncRNA Ftx plays a vital role in cardiomyocytes and may be involved in the occurrence and development of various myocardial diseases. It provides a potential target for clinical protection of the myocardium and reversal of myocardial fibrosis.

Medical imaging is crucial for the detection and diagnosis of breast cancer. Artificial intelligence and computer vision have rapidly become popular in medical image analyses thanks to technological advancements. To improve the effectiveness and efficiency of medical diagnosis and treatment, significant efforts have been made in the literature on medical image processing, segmentation, volumetric analysis, and prediction. This paper is interested in the development of a prediction pipeline for breast cancer studies based on 3D computed tomography (CT) scans. Several algorithms were designed and integrated to classify the suitability of the CT slices. The selected slices from patients were then further processed in the pipeline. This was followed by data generalization and volume segmentation to reduce the computation complexity. The selected input data were fed into a 3D U-Net architecture in the pipeline for analysis and volumetric predictions of cancer tumors. Three types of U-Net models were designed and compared. The experimental results show that Model 1 of U-Net obtained the highest accuracy at 91.44% with the highest memory usage; Model 2 had the lowest memory usage with the lowest accuracy at 85.18%; and Model 3 achieved a balanced performance in accuracy and memory usage, which is a more suitable configuration for the developed pipeline.

Introduction:. Erythropoietic protoporphyria (EPP) is a rare photodermatosis mainly caused by deficiency of the enzyme ferrochelatase (FECH). We herein report a case of EPP associated with 2 novel mutations in FECH. Case presentation:. A 15-year-old boy experienced pain and pruritus after sunlight exposure. He had occasional claret-red urine, hepatomegaly with increased alanine aminotransferase and aspartate aminotransferase levels, and an elevated free erythrocyte protoporphyrin level. He was treated with oral β-carotene and cholestyramine and avoidance of sunlight as much as possible. Discussion:. Genome sequencing revealed 2 novel FECH mutations that had been inherited from his healthy parents. Pathogenicity analysis involving prediction using PolyPhen-2, SIFT, and Mutation Taster revealed that the 2 novel mutations were likely pathogenic. Although the patient’s parents were healthy, they each had one of these 2 mutations. This finding is consistent with previous reports stating that individuals carrying low-expression alleles can be asymptomatic. The pathogenesis of the disease caused by these 2 mutations requires verification by larger and more detailed studies. Conclusion:. Although the precise role of these mutations in EPP is not clear, the findings in the present case expand the genotypic spectrum of the disease.

ABSTRACT Lentinula edodes is one of the most widely cultivated edible mushrooms in the world. When cultivated in sawdust, the surface mycelium of L. edodes needs a long postripening stage wherein it forms a brown film (BF) by secreting and accumulating pigments. BF formation is critical for the high quality and yield of fruiting bodies. Protein lysine acetylation (KAC) is an important post-translational modification that regulates growth and development. Previous studies have shown that deacetylase levels are significantly increased during BF formation in the postripening stage of L. edodes. The aim of this study was to assess the role of protein acetylation during BF formation. To this end, we compared the acetylome of L. edodes mycelia before and after BF formation using anti-acetyl antibody-based label-free quantitative proteomics. We identified 5,613 acetylation sites in 1,991 proteins, and quantitative information was available for 4,848 of these sites in 1,815 proteins. Comparative acetylome analysis showed that the modification of 699 sites increased and that of 562 sites decreased during BF formation. Bioinformatics analysis of the differentially acetylated proteins showed significant enrichment in the tricarboxylic acid (TCA) cycle and proteasome pathways. Furthermore, functional assays showed that BF formation is associated with significant changes in the activities of proteasome, citrate synthase, and isocitrate dehydrogenase. Consistent with this hypothesis, the lysine deacetylase inhibitor trichostatin (TSA) delayed autophagy and BF formation in L. edodes. Taken together, KAC and autophagy play important roles in the mycelial BF formation and postripening stage of L. edodes. IMPORTANCE Mycelial BF formation and postripening of L. edodes affects the quality and quantity of its edible fruiting bodies. In this study, we explored the role of protein KAC in this biological process, with the aim of optimizing the cultivation and yield of L. edodes.

Abstract The brown planthopper (BPH) is the leading cause of insect damage to rice plants and BPH infestations have caused profound losses in rice production since the 1970’s. There is an urgent need to discover new BPH resistance genes to ensure the successful production of rice. Here, a new BPH resistance source provided by SeedWorks International Pvt. Ltd., SWD10, was used for this purpose. QTL mapping using 232 F2 progenies and 216 polymorphic markers revealed two dominant BPH resistance QTLs, BPH41 and BPH42, located on chromosome 4. BPH resistance mechanism test revealed that antibiosis and antixenosis mechanisms both play a role in BPH resistance conferred by these two QTLs. The QTLs were delimited between markers SWRm_01617 and SWRm_01522 for BPH41, and SWRm_01695 and SWRm_00328 for BPH42. Additionally, using RNA-seq data of lines containing the resistant QTLs, we shortlisted four and three gene candidates for BPH41 and BPH42, respectively. Differential gene expression analysis of lines containing the QTLs suggested that SWD10 BPH resistance is contributed by the plant’s innate immunity and the candidate genes may be part of the rice innate immunity pathway. Currently, the newly identified QTLs are being utilized for breeding BPH resistant rice varieties and hybrids.

Abstract A first-line chemotherapeutic drug for non-small cell lung cancer (NSCLC), cisplatin (CDDP), fails to induce immunogenic cell death (ICD) because it fails to induce calreticulin (CRT) exposure on the cell surface. We investigated the potential of ischemia and reperfusion injury (I/R) combined with CDDP to induce ICD in lung cancer cells. The in vitro model of I/R, oxygen-glucose deprivation and reperfusion (OGD/R), effectively induced CRT exposure, ATP secretion, high mobility group box 1 (HMGB1) release and eIF2α phosphorylation in both Lewis lung carcinoma (LLC) and A549 cells when combined with CDDP. By using a vaccine assay and coculture with bone marrow-derived dendritic cells (BMDCs), we showed that OGD/R restored the immunogenicity of CDDP by phosphorylating eIF2α and demonstrated that OGD/R + CDDP (O + C) is an ICD inducer. Using the inguinal tumor model, we found that I/R significantly enhanced the tumor-killing effect of CDDP and Mitomycin C, and this effect relied on adaptive antitumor immunity. Consistently, I + C altered the ratio of interferon-gamma-secreting T lymphocytes, thus overcoming the immunosuppressive effect induced by CDDP. In conclusion, our research presents a new combination strategy and indicates that I/R is a potential anticancer immunogenic modality when combined with nonimmunogenic chemotherapy.