Synchronously Sensitive Immunoassay and Efficient Inactivation of Living Zika Virus via DNAzyme Catalytic Amplification and In Situ Aggregation-Induced Emission Photosensitizer Generation.

Sensitive identification and effective inactivation of the virus are paramount for the early diagnosis and treatment of viral infections to prevent the risk of secondary transmission of viruses in the environment. Herein, we developed a novel two-step fluorescence immunoassay using antibody/streptavidin dual-labeled polystyrene nanobeads and biotin-labeled G-quadruplex/hemin DNAzymes with peroxidase-mimicking activity for sensitive quantitation and efficient inactivation of living Zika virus (ZIKV). The dual-labeled nanobeads can specifically bind ZIKV through E protein targeting and simultaneously accumulate DNAzymes, leading to the catalytic oxidation of Amplex Red indicators and generation of intensified aggregation-induced emission fluorescence signals, with a detection limit down to 66.3 PFU/mL and 100% accuracy. Furthermore, robust reactive oxygen species generated in situ by oxidized Amplex Red upon irradiation can completely kill the virus. This sensitive and efficient detection-inactivation integrated system will expand the viral diagnostic tools and reduce the risk of virus transmission in the environment.

Current research progress, opportunities, and challenges of Limosillactobacillus reuteri-based probiotic dietary strategies.

Limosillactobacillus reuteri (L. reuteri), a type of Lactobacillus spp., stands out as the most extensively researched probiotic. Its remarkable intestinal adhesion has led to widespread applications in both the food and medical sectors. Notably, recent research highlights the probiotic efficacy of L. reuteri sourced from breast milk, particularly in influencing social behavior and mitigating atopic dermatitis. In this review, our emphasis is on surveying recent literature regarding the promotion of host's health by L. reuteri. We aim to provide a concise summary of the latest regulatory effects and potential mechanisms attributed to L. reuteri in the realms of metabolism, brain- and immune-related functions. The mechanism through which L. reuteri promotes host health by modulating the intestinal microenvironment primarily involves promoting intestinal epithelial renewal, bolstering intestinal barrier function, regulating gut microbiota and its metabolites, and suppressing inflammation and immune responses. Additionally, this review delves into new technologies, identifies shortcomings, and addresses challenges in current L. reuteri research. Finally, the application prospects of L. reuteri are provided. Therefore, a better understanding of the role and mechanisms of L. reuteri will contribute significantly to the development of new probiotic functional foods and enable precise, targeted interventions for various diseases.

A diagnostic strategy for pulmonary fat embolism based on routine H&E staining using computational pathology.

Pulmonary fat embolism (PFE) as a cause of death often occurs in trauma cases such as fractures and soft tissue contusions. Traditional PFE diagnosis relies on subjective methods and special stains like oil red O. This study utilizes computational pathology, combining digital pathology and deep learning algorithms, to precisely quantify fat emboli in whole slide images using conventional hematoxylin-eosin (H&E) staining. The results demonstrate deep learning's ability to identify fat droplet morphology in lung microvessels, achieving an area under the receiver operating characteristic (ROC) curve (AUC) of 0.98. The AI-quantified fat globules generally matched the Falzi scoring system with oil red O staining. The relative quantity of fat emboli against lung area was calculated by the algorithm, determining a diagnostic threshold of 8.275% for fatal PFE. A diagnostic strategy based on this threshold achieved a high AUC of 0.984, similar to manual identification with special stains but surpassing H&E staining. This demonstrates computational pathology's potential as an affordable, rapid, and precise method for fatal PFE diagnosis in forensic practice.

Cardiac-specific deletion of BRG1 ameliorates ventricular arrhythmia in mice with myocardial infarction.

Malignant ventricular arrhythmia (VA) after myocardial infarction (MI) is mainly caused by myocardial electrophysiological remodeling. Brahma-related gene 1 (BRG1) is an ATPase catalytic subunit that belongs to a family of chromatin remodeling complexes called Switch/Sucrose Non-Fermentable Chromatin (SWI/SNF). BRG1 has been reported as a molecular chaperone, interacting with various transcription factors or proteins to regulate transcription in cardiac diseases. In this study, we investigated the potential role of BRG1 in ion channel remodeling and VA after ischemic infarction. Myocardial infarction (MI) mice were established by ligating the left anterior descending (LAD) coronary artery, and electrocardiogram (ECG) was monitored. Epicardial conduction of MI mouse heart was characterized in Langendorff-perfused hearts using epicardial optical voltage mapping. Patch-clamping analysis was conducted in single ventricular cardiomyocytes isolated from the mice. We showed that BRG1 expression in the border zone was progressively increased in the first week following MI. Cardiac-specific deletion of BRG1 by tail vein injection of AAV9-BRG1-shRNA significantly ameliorated susceptibility to electrical-induced VA and shortened QTc intervals in MI mice. BRG1 knockdown significantly enhanced conduction velocity (CV) and reversed the prolonged action potential duration in MI mouse heart. Moreover, BRG1 knockdown improved the decreased densities of Na+ current (INa) and transient outward potassium current (Ito), as well as the expression of Nav1.5 and Kv4.3 in the border zone of MI mouse hearts and in hypoxia-treated neonatal mouse ventricular cardiomyocytes. We revealed that MI increased the binding among BRG1, T-cell factor 4 (TCF4) and ß-catenin, forming a transcription complex, which suppressed the transcription activity of SCN5A and KCND3, thereby influencing the incidence of VA post-MI.

Assessing and decoupling ecosystem services evolution in karst areas: A multi-model approach to support land management decision-making.

Incorporating Ecosystem Service Value (ESV) into land use planning provides a fresh perspective for informed land management decisions. ESV, influenced by socio-economic and natural factors, has complex driving mechanisms, particularly in China's southwestern karst regions. Studying mediating variables helps elucidate these mechanisms. Further research into ecosystem services interactions and effective land use policies in karst areas is needed. This study evaluates the ESV of Guizhou Province, located in southern China's karst region, using the benefit transfer approach. Combining the Guizhou Provincial Land Use Planning Outline (2006-2020) with the multi-objective programming (MOP) model optimized by genetic algorithm and the patch-generating land use simulation (PLUS) model, four future development scenarios were designed. The response of ESV to land use and land cover (LULC) changes at the county scale under four different development scenarios from 2000 to 2020 and in the future was analyzed. A partial least squares structural equation model (PLS-SEM) was used to decouple the driving mechanism affecting ESV. The results show that over the past two decades, with the implementation of various ecological restoration projects, the total ESV has increased. The ESV for natural development scenarios, ecological conservation scenarios, economic development scenarios, and sustainable development scenarios are CNY 238.278 billion, CNY 400.514 billion, CNY 283.201 billion, and CNY 323.615 billion, respectively. The direct impacts of karst surface characteristic factors (KSCF), meteorological factors (MF), socio-economic factors (SEF) and transportation location factors (TLF) on ESV are positive (0.098), negative (-0.098), positive (0.336), and positive (0.109) respectively. The total effect of KSCF on ESV through influencing socio-economic factors and LULC is (-0.738), with SEF playing a complete mediating role. MF indirectly affect ESV by influencing LULC, with LULC playing a complete mediating role in this process. The PLS-SEM model shows that under the dominant position of LULC, the interaction between natural environmental factors and socio-economic factors on ESV is very complex. This study offers valuable insights that can guide managers in this region, as well as in other karst regions globally, in the development of sustainable land use policies.

Oxygen concentration titration guided by oxygen reserve index during pediatric laryngeal surgery with high-flow nasal cannula oxygen: a randomized controlled trial.

PURPOSE: The objective of this study was to evaluate whether adjusting the oxygen concentration guided by the Oxygen Reserve Index (ORI) during pediatric laryngeal surgery with High Flow Nasal Cannula Oxygen (HFNO) could achieve postoperative PaO2 close to physiological levels while ensuring adequate oxygenation in surgery. METHODS: Sixty pediatric patients undergoing laryngeal surgery or examination were randomly assigned to two groups. The ORI group received oxygen concentration adjustments every 5 min to maintain a target ORI value of 0.21, whereas the control group did not undergo any adjustments. Postoperative PaO2, time weighted average fraction of inspired oxygen (FiO2), and mean Peripheral Oxygen Saturation (SpO2) were compared between groups. Finally, some analyses were conducted to examine the relationship of ORI with PaO2. RESULTS: In general, the postoperative PaO2 was 164.9 ± 48.8 mmHg in ORI group and 323.0 ± 87.7 mmHg in control group (P < 0.01). The time weighted average FiO2 in the ORI group was 85.9 [81.8-92.7] %. There was no significant difference in mean SpO2 between the two groups (ORI vs. control: 98.4 [97.7-99.2] vs. 98.8 [97.7-99.5]; P = 0.36). According to the analyses, the optimal cut value for ORI was determined to be 0.195 when PaO2 was 150 mmHg. CONCLUSIONS: In pediatric laryngeal surgery with HFNO, reducing oxygen concentration guided by ORI helped achieve postoperative PaO2 levels closer to physiological norms without compromising intra-operative oxygenation.

A nexus of dietary restriction and gut microbiota: Recent insights into metabolic health.

In recent times, dietary restriction (DR) has received considerable attention for its promising effects on metabolism and longevity. Previous studies on DR have mainly focused on the health benefits produced by different restriction patterns, whereas comprehensive reviews of the role of gut microbiota during DR are limited. In this review, we discuss the effects of caloric restriction, fasting, protein restriction, and amino acid restriction from a microbiome perspective. Furthermore, the underlying mechanisms by which DR affects metabolic health by regulating intestinal homeostasis are summarized. Specifically, we reviewed the impacts of different DRs on specific gut microbiota. Additionally, we put forward the limitations of the current research and suggest the development of personalized microbes-directed DR for different populations and corresponding next-generation sequencing technologies for accurate microbiological analysis. DR effectively modulates the composition of the gut microbiota and microbial metabolites. In particular, DR markedly affects the rhythmic oscillation of microbes which may be related to the circadian clock system. Moreover, increasing evidence supports that DR profoundly improves metabolic syndrome, inflammatory bowel disease, and cognitive impairment. To summarize, DR may be an effective and executable dietary manipulation strategy for maintaining metabolic health, however, further investigation is needed to elucidate the underlying mechanisms.

A review on processing methods and functions of wheat germ-derived bioactive peptides.

Wheat germ protein is a potential resource to produce bioactive peptides. As a cheap, safe, and healthy nutritional factor, wheat germ-derived bioactive peptides (WGBPs) provide benefits and great potential for biomedical applications. The objective of this review is to reveal the current research status of WGBPs, including their preparation methods and biological functions, such as antibacterial, anti-tumor, immune regulation, antioxidant, and anti-inflammatory properties, etc. We also reviewed the information in terms of the preventive ability of WGBPs to treat serious infectious diseases, to offer their reference to further research and application. Opinions on future research directions are also discussed. Through the review of previous research, we find that there are still some scientific issues in the basic research and industrialization process of WGBPs that deserve further exploration. Firstly, based on current complex enzymolysis, the preparation and production of WGBPs need to be combined with other advanced technology to achieve efficient and large-scale production. Secondly, studies on the bioavailability, biosafety, and mechanism against different diseases of WGBPs need to be carried out in different in vitro and in vivo models. More human experimental evidence is also required to support its industrial application as a functional food and nutritional supplement.HighlightsThe purification and identification of wheat germ-derived bioactive peptides.The main biological activities and potential mechanisms of wheat germ hydrolysates/peptides.Possible absorption and transport pathways of wheat germ hydrolysate/peptide.Wheat germ peptide shows a variety of health benefits according to its amino acid sequence.Current food applications and future perspectives of wheat germ protein hydrolysates/peptide.

Frequencies and patterns of symptoms in Chinese adults with accommodative and binocular dysfunctions.

PURPOSE: Recent studies have found that children with convergence insufficiency experience higher frequencies of performance-related symptoms (e.g., losing concentration), but data on performance-related symptoms among adults with accommodative dysfunctions (ADs) and/or binocular dysfunctions (BDs) are lacking, which might cause misdiagnosis, diagnostic confusion, or exacerbation of attention deficits. We aimed to describe frequencies and symptom patterns in adults with ADs and/or BDs who were treated at optometric clinics and explore any correlations between visual symptoms and clinical findings. METHODS: This cross-sectional study divided 235 participants (age: 23.7 ± 2.9 years) into three groups: ADs, BDs, and normal binocular vision (NBV) groups. Convergence Insufficiency Symptom Survey (CISS), refractive examinations, and binocular tests were administered to all participants. After 1-to-1 propensity score matching, outcomes were assessed using Mann‒Whitney U test and Pearson's correlation analysis among three groups. RESULTS: In this sample, the number (frequency) of individuals with ADs and/or BDs was 117 (49.8%). ADs and BDs groups experienced significantly more performance-related symptoms (feeling sleepy, losing concentration, trouble remembering, reading slowly, losing place, and having to re-read; all P < 0.05) than the NBV group. Significant correlations were observed between performance-related symptoms and clinical findings, including accommodative amplitude (r = - 0.294), accommodative facility (r = - 0.452), near phoria (r = - 0.261), near point of convergence (r = 0.482), and positive fusional vergence (r = - 0.331) (all P < 0.001). CONCLUSION: ADs and/or BDs are commonly present in adults treated at optometric clinics, and adults diagnosed with ADs and/or BDs exhibit more performance-related symptoms than participants with NBV.

A Blockchain-Based Authentication and Authorization Scheme for Distributed Mobile Cloud Computing Services.

Authentication and authorization constitute the essential security component, access control, for preventing unauthorized access to cloud services in mobile cloud computing (MCC) environments. Traditional centralized access control models relying on third party trust face a critical challenge due to a high trust cost and single point of failure. Blockchain can achieve the distributed trust for access control designs in a mutual untrustworthy scenario, but it also leads to expensive storage overhead. Considering the above issues, this work constructed an authentication and authorization scheme based on blockchain that can provide a dynamic update of access permissions by utilizing the smart contract. Compared with the conventional authentication scheme, the proposed scheme integrates an extra authorization function without additional computation and communication costs in the authentication phase. To improve the storage efficiency and system scalability, only one transaction is required to be stored in blockchain to record a user's access privileges on different service providers (SPs). In addition, mobile users in the proposed scheme are able to register with an arbitrary SP once and then utilize the same credential to access different SPs with different access levels. The security analysis indicates that the proposed scheme is secure under the random oracle model. The performance analysis clearly shows that the proposed scheme possesses superior computation and communication efficiencies and requires a low blockchain storage capacity for accomplishing user registration and updates.

Raman Spectroscopy Profiling of Splenic T-Cells in Sepsis and Endotoxemia in Mice.

Sepsis is a life-threatening condition that results from an overwhelming and disproportionate host response to an infection. Currently, the quality and extent of the immune response are evaluated based on clinical symptoms and the concentration of inflammatory biomarkers released or expressed by the immune cells. However, the host response toward sepsis is heterogeneous, and the roles of the individual immune cell types have not been fully conceptualized. During sepsis, the spleen plays a vital role in pathogen clearance, such as bacteria by an antibody response, macrophage bactericidal capacity, and bacterial endotoxin detoxification. This study uses Raman spectroscopy to understand the splenic T-lymphocyte compartment profile changes during bona fide bacterial sepsis versus hyperinflammatory endotoxemia. The Raman spectral analysis showed marked changes in splenocytes of mice subjected to septic peritonitis principally in the DNA region, with minor changes in the amino acids and lipoprotein areas, indicating significant transcriptomic activity during sepsis. Furthermore, splenocytes from mice exposed to endotoxic shock by injection of a high dose of lipopolysaccharide showed significant changes in the protein and lipid profiles, albeit with interindividual variations in inflammation severity. In summary, this study provided experimental evidence for the applicability and informative value of Raman spectroscopy for profiling the immune response in a complex, systemic infection scenario. Importantly, changes within the acute phase of inflammation onset (24 h) were reliably detected, lending support to the concept of early treatment and severity control by extracorporeal Raman profiling of immunocyte signatures.

[Systematic review and Meta-analysis of efficacy and safety of Kushen Gelatum combined with antibiotics in treatment of bacterial vaginosis].

This study aims to systematically evaluate the clinical efficacy and safety of Kushen Gelatum combined with antibiotics for treating bacterial vaginosis. The randomized controlled trial(RCT) of Kushen Gelatum for treating bacterial vaginosis were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, and Cochrane Library with the time interval from inception to January 2023. Data were extracted from the included RCT by 2 investigators, including the sample size, characteristics of patients, interventions and controls, outcome indicators, and adverse effects. The Cochrane collaboration network's bias risk assessment tool was used for methodolo-gical quality evaluation of the included trials. RevMan 5.4 was employed to perform the Meta-analysis. A total of 19 RCTs were inclu-ded, involving 1 980 patients with bacterial vaginosis. Meta-analysis showed that, compared with nitroimidazoles alone, Kushen Gelatum + nitroimidazoles improved the total response rates in terms of clinical symptoms and laboratory tests(RR=1.24, 95%CI[1.13, 1.36], P<0.000 01), laboratory tests(RR=1.16, 95%CI[1.06, 1.26], P=0.000 9), and clinical symptoms(RR=1.26, 95%CI[1.08, 1.46], P=0.003), and reduced the leukocyte esterase positive rate(RR=0.29, 95%CI[0.17, 0.48], P<0.000 01) and the recurrence rate(RR=0.37, 95%CI[0.23, 0.58], P<0.000 1). Compared with lincomycin antibiotics(clindamycin) alone, Kushen Gelatum + lincomycin antibiotics(clindamycin) improved the total response rates in terms of clinical symptoms and laboratory tests(RR=1.18, 95%CI[1.06, 1.31], P=0.003) and laboratory tests(RR=1.27, 95%CI[1.04, 1.54], P=0.02), reduced the recurrence rate(RR=0.20, 95%CI[0.05, 0.75], P=0.02), and shortened the time to relief of burning sensation(MD=-1.70, 95%CI[-2.15,-1.26], P<0.000 01), vaginal itching(MD=-0.82, 95%CI[-1.30,-0.34], P=0.000 8), and abnormal leucorrhea(MD=-1.52, 95%CI[-1.98,-1.06], P<0.000 01). Compared with nitroimidazoles + probiotics, Kushen Gelatum + nitroimidazoles + probiotics improved the total response rate in terms of clinical symptoms and laboratory tests(RR=1.18, 95%CI[1.02, 1.36], P=0.03) and reduced the recurrence rate(RR=0.27, 95%CI[0.09, 0.76], P=0.01). Kushen Gelatum combined with antibiotics demonstrates a potential therapeutic effect on bacterial vaginosis, whereas the number and quality of the relevant clinical studies remain to be improved. The process of clinical trial should be standardized to improve the quality of evidence, so as to provide strong evidence to guide the application of Kushen Gelatum in clinical practice.

Evaluating Subtle Pathological Changes in Early Myocardial Ischemia Using Spectral Histopathology.

Early myocardial ischemia (EMI) is morphologically challenging, and the results from conventional histological staining may be subjective, imprecise, or even silent. The size of myocardial necrosis determines the acute and long-term mortality of EMI. The precise diagnosis of myocardial ischemia is critical for both clinical management and forensic investigation. Fourier transform infrared (FTIR) spectroscopic imaging is a highly sensitive tool for detecting protein conformations and imaging protein profiles. The aim of this study was to evaluate the application of FTIR imaging with multivariate analysis to detect biochemical changes in the protein conformation in the early phase of myocardial ischemia and to visually classify different disease states. The spectra and curve fitting results revealed that the total protein content decreased significantly in the EMI group and that the α-helix content of the secondary protein structure continuously decreased as ischemia progressed, while the ß-sheet content increased. Differences in the control and EMI groups and perfused and ischemic myocardium were confirmed using principal component analysis and partial least squares discriminant analysis. Next, two support vector machine classifiers were effectively created. The accuracy, recall, and precision were 99.98, 99.96, and 100.00%, respectively, to differentiate the EMI group from the control group and 99.25, 98.95, and 99.54%, respectively, to differentiate perfused and ischemic myocardium. Ultimately, high EMI diagnostic accuracy was achieved with 100.00% recall and 100.00% precision, and ischemic myocardium diagnostic accuracy was achieved with 99.30% recall and 99.53% precision for the test set. This pilot study demonstrated that FTIR imaging is a powerful automated quantitative analysis tool to detect EMI without morphological changes and will improve diagnostic accuracy and patient prognosis.

Preparation of Novel Chiral Stationary Phases Based on the Chiral Porous Organic Cage by Thiol-ene Click Chemistry for Enantioseparation in HPLC.

Porous organic cages (POCs) are an emerging class of porous materials that have aroused considerable research interest because of their unique characteristics, including good solubility and a well-defined intrinsic cavity. However, there have so far been no reports of chiral POCs as chiral stationary phases (CSPs) for enantioseparation by high-performance liquid chromatography (HPLC). Herein, we report the first immobilization of a chiral POC, NC1-R, on thiol-functionalized silica using a mild thiol-ene click reaction to prepare novel CSPs for HPLC. Two CSPs (CSP-1 and CSP-2) with different spacers have been prepared. CSP-1, with a cationic imidazolium spacer, exhibited excellent enantioselectivity for the resolution of various racemates. Twenty-three and 12 racemic compounds or chiral drugs were well enantioseparated on the CSP-1-packed column under normal-phase and reversed-phase conditions, respectively, including alcohols, diols, esters, ethers, ketones, epoxides, organic acids, and amines. In contrast, chiral resolution using CSP-2 (without a cationic imidazolium spacer)-packed column B was inferior to that of column A, demonstrating the important role of the cationic imidazolium spacer for chiral separation. The chiral separation capability of column A was also compared with that of two most popular commercial chiral columns, Chiralpak AD-H and Chiralcel OD-H, which exhibits good chiral recognition complementarity with the two commercial chiral columns. In addition, five positional isomers dinitrobenzene, nitroaniline, chloroaniline, bromoaniline, and iodoaniline were also well separated on column A. The effects of temperature, mobile phase composition, and injected analyte mass for separation on column A were investigated. Column A also showed good stability and reproducibility after repeated injections. This work demonstrates that chiral POCs are promising chiral materials for HPLC enantioseparation.

Comprehensive profiling of Sanguisorba officinalis using offline two-dimensional mixed-mode liquid chromatography × reversed-phase liquid chromatography, tandem high-resolution mass spectrometry, and molecular network.

The profiling of natural products is important in modern biological sciences and new drug development. However, the separation and characterization of complex herbal extracts are significantly challenging for researchers in the biochemical field. Herein, an offline two-dimensional mixed-mode liquid chromatography × reversed-phase liquid chromatography system is developed. Our system exhibits high orthogonality and is composed of a newly prepared stationary phase in the first dimension and a traditional C18 phase in the second dimension, and is operated in combination with a high-resolution mass spectrometry and molecular network. Sanguisorba officinalis L. is studied using the proposed method owing to its bioactivity. With the aid of orthogonal separation, the ionization of the individual components is improved. The number of detected compounds and separated peaks are significantly increased when one-dimensional liquid chromatography is upgraded to two-dimensional liquid chromatography. In addition, 270 compounds (127 of which are tentatively characterized as new compounds, and further confirmation is needed) are successfully characterized based on their fragmentation patterns under the guidance of molecular network, while only 95 compounds are characterized using one-dimensional liquid chromatography and high-resolution mass spectrometry. The results indicate that the developed offline two-dimensional mixed-mode liquid chromatography × reversed-phase liquid chromatography, tandem high-resolution mass spectrometry, and molecular network method are effective for profiling complex samples.

A Hierarchical Blockchain-Assisted Conditional Privacy-Preserving Authentication Scheme for Vehicular Ad Hoc Networks.

Through information sharing, vehicles can know the surrounding road condition information timely in Vehicular Adhoc Networks. To ensure the validity of these messages and the security of vehicles, the message authentication, privacy-preserving, and delay problems are three important issues. Although many conditional privacy-preserving authentication schemes have been proposed to ensure secure communication, there still exist some imperfections such as frequent interactions or unlinkability. From this, our paper proposes a novel hierarchical blockchain-assisted authentication scheme to solve these existing issues comprehensively. First, unlinkability is achieved by a dynamic key derivation algorithm. Second, the proposed scheme can reduce correlation processing delay, queuing delay, and deployment costs by adopting hierarchical Vehicle Fog Computing. Third, cross-region authentication is achieved by taking advantage of the properties of blockchain. In addition, we demonstrate our scheme can fulfill the security criteria of the Vehicular Adhoc Network by security analysis. Furthermore, the simulations are carried out to show its availability by using JAVA and NS-3. The findings reveal that the suggested method outperforms earlier schemes in terms of computation cost and communication cost. All in all, making the authentication scheme more efficient and concise is the focus of our future research.

UHPLC/MS-Based Serum Metabolomics Reveals the Mechanism of Radiation-Induced Thrombocytopenia in Mice.

Radiation-induced thrombocytopenia is a common and life-threatening side effect of ionizing radiation (IR) therapy. However, the underlying pathological mechanisms remain unclear. In the present study, irradiation was demonstrated to significantly reduce platelet levels, inhibit megakaryocyte differentiation, and promote the apoptosis of bone marrow (BM) cells. A metabolomics approach and a UHPLC-QTOF MS system were subsequently employed for the comprehensive analysis of serum metabolic profiles of normal and irradiated mice. A total of 66 metabolites were significantly altered, of which 56 were up-regulated and 10 were down-regulated in irradiated mice compared to normal mice on day 11 after irradiation. Pathway analysis revealed that disorders in glycerophospholipid metabolism, nicotinate and nicotinamide metabolism, sphingolipid metabolism, inositol phosphate metabolism, and tryptophan metabolism were involved in radiation-induced thrombocytopenia. In addition, three important differential metabolites, namely L-tryptophan, LysoPC (17:0), and D-sphinganine, which were up-regulated in irradiated mice, significantly induced the apoptosis of K562 cells. L-tryptophan inhibited megakaryocyte differentiation of K562 cells. Finally, serum metabolomics was performed on day 30 (i.e., when the platelet levels in irradiated mice recovered to normal levels). The contents of L-tryptophan, LysoPC (17:0), and D-sphinganine in normal and irradiated mice did not significantly differ on day 30 after irradiation. In conclusion, radiation can cause metabolic disorders, which are highly correlated with the apoptosis of hematopoietic cells and inhibition of megakaryocyte differentiation, ultimately resulting in thrombocytopenia. Further, the metabolites, L-tryptophan, LysoPC (17:0), and D-sphinganine can serve as biomarkers for radiation-induced thrombocytopenia.

Cost-effectiveness analyses of sacubitril-valsartan for heart failure.

The objective of this study was to evaluate the pharmacoeconomic value of sacubitril-valsartan for the treatment of heart failure (HF). PubMed, Embase, Cochrane Library, ScienceDirect, Scopus, CNKI, Wanfang, and VIP databases were searched systematically and the retrieval time ended in August 2019. According to the criteria of inclusion and exclusion, the quality of studies included was evaluated as per the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) scale, and the results were extracted and analyzed systematically. The total of 11 cost-effectiveness studies was identified, 10 were performed in the developed countries and 1 in Thailand. All the patients in the studies had chronic heart failure with reduced ejection fraction (HFrEF). Totally, the quality of all the 11 studies was reported to be of an average score of 20.5. Study perspective and time horizons were described in the 11 studies. All included studies discounted the cost or effectiveness. Only 1 study estimated direct and indirect costs; 10 studies evaluated direct cost. The incremental cost-effectiveness ratio (ICER) of sacubitril-valsartan treating HFrEF was $13,150 per quality-adjusted life-years (QALY) in Thailand and $86,735 in Singapore. In European countries, the ICER was from $21,786 to $34,576 per QALY and mean value was $25,410.6 per QALY. In the USA, ICER values ranged from $47,099 to $143,891 per QALY, and mean value was $73,383.5 per QALY; ICER was $30,090 per QALY in Colombia. With the exception of Thailand and Singapore, the ICER of other countries in the included literature was below the implemented country-specific thresholds. Based on existing literatures, with the exception of Thailand and Singapore, sacubitril-valsartan for the treatment of HFrEF is a better cost-effective therapy with ICER basically below the implemented country-specific thresholds. Sacubitril-valsartan was not considered a cost-effective treatment for heart failure with reduced ejection fraction in Thailand and Singapore with the current economic evaluation evidences, but with the willingness-to-pay (WTP) of other counties, sacubitril-valsartan was found to be a cost-effective treatment compared with comparator. Drug cost, time horizon, and hospitalization were the most influential variables across studies. Four studies indicated that with the longer time horizon, the lower ICER value would gain. Further studies are warranted to better evaluate comprehensive utility value of sacubitril-valsartan on heart failure.

Pose-varied swing arm profilometer test for off-axis aspheric surfaces with strong asphericity.

The swing arm profilometer (SAP) has been widely used to test large aspheric optics by measuring the asphericity from its best-fitting sphere (BFS). To further improve the test accuracy, we propose a pose-varied test mode for the SAP with a shorter-range probe to measure off-axis aspheric surfaces with stronger asphericity. In contrast to the classical SAP mode in which the air-table is fixed in a stationary position during measurement, we adjust the pose of each scan arc to match the local BFS and the measurement range of the probe decreases to half that of the global asphericity. To verify the effectiveness, we conduct experiments on an off-axis asphere with a diameter of 3 and 2 m. Compared with a classical SAP mode, it achieved an improved performance of 50% higher repeatability and 32% higher accuracy.

Local and Systemic Expression Profile of IL-10, IL-17, IL-27, IL-35, and IL-37 in Periodontal Diseases: A Cross-sectional Study.

AIM: This study aimed to compare the level of interleukin (IL)-10, IL-17, IL-27, IL-35, and IL-37 in the gingival crevicular fluid (GCF) and human plasma of subjects with periodontal disease. MATERIALS AND METHODS: In this cross-sectional study conducted over a 3-month period at a primary dental clinic in Malaysia, 45 participants were recruited via consecutive sampling and assigned into three groups, namely healthy periodontium group (n = 15), gingivitis group (n = 15), and periodontitis group (n = 15). Gingival crevicular fluid and plasma samples were collected from each participant. Enzyme-linked immunosorbent assay test was conducted to measure the concentration of IL-10, IL-17, IL-27, IL-35, and IL-37. Kruskal-Wallis H test was used to compare the interleukin levels between patient groups. RESULTS: In GCF samples, IL-17 level was the highest in the periodontitis group (p <0.05), while IL-27 was the lowest (p <0.05). Meanwhile, plasma levels of IL-27 and IL-37 were significantly lower (p <0.05) in the periodontitis group, but plasma IL-35 levels were observed to rise with increasing disease severity. CONCLUSION: There are reduced local and systemic levels of IL-27 in periodontitis patients. CLINICAL SIGNIFICANCE: Periodontal diseases exert both local and systemic effects, resulting in the destruction of the tooth-supporting structures and contributing to the systemic inflammatory burden. Some of the cytokines that were investigated in the current study, IL-17, IL-27, IL-35, and IL-37, can be potential biomarkers that warrant further longitudinal clinical studies to determine their usefulness as prognostic/diagnostic markers.