Network pharmacology-based exploration of molecular mechanisms underlying therapeutic effects of Jianpi Huatan Quyu recipe on chronic heart failure with spleen Qi deficiency syndrome.

BACKGROUND: Chronic heart failure is a complex clinical syndrome. The Chinese herbal compound preparation Jianpi Huatan Quyu recipe has been used to treat chronic heart failure; however, the underlying molecular mechanism is still not clear. AIM: To identify the effective active ingredients of Jianpi Huatan Quyu recipe and explore its molecular mechanism in the treatment of chronic heart failure. METHODS: The effective active ingredients of eight herbs composing Jianpi Huatan Quyu recipe were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The target genes of chronic heart failure were searched in the Genecards database. The target proteins of active ingredients were mapped to chronic heart failure target genes to obtain the common drug-disease targets, which were then used to construct a key chemical component-target network using Cytoscape 3.7.2 software. The protein-protein interaction network was constructed using the String database. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed through the Metascape database. Finally, our previously published relevant articles were searched to verify the results obtained via network pharmacology. RESULTS: A total of 227 effective active ingredients for Jianpi Huatan Quyu recipe were identified, of which quercetin, kaempferol, 7-methoxy-2-methyl isoflavone, formononetin, and isorhamnetin may be key active ingredients and involved in the therapeutic effects of TCM by acting on STAT3, MAPK3, AKT1, JUN, MAPK1, TP53, TNF, HSP90AA1, p65, MAPK8, MAPK14, IL6, EGFR, EDN1, FOS, and other proteins. The pathways identified by KEGG enrichment analysis include pathways in cancer, IL-17 signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, calcium signaling pathway, cAMP signaling pathway, NF-kappaB signaling pathway, AMPK signaling pathway, etc. Previous studies on Jianpi Huatan Quyu recipe suggested that this Chinese compound preparation can regulate the TNF-α, IL-6, MAPK, cAMP, and AMPK pathways to affect the mitochondrial structure of myocardial cells, oxidative stress, and energy metabolism, thus achieving the therapeutic effects on chronic heart failure. CONCLUSION: The Chinese medicine compound preparation Jianpi Huatan Quyu recipe exerts therapeutic effects on chronic heart failure possibly by influencing the mitochondrial structure of cardiomyocytes, oxidative stress, energy metabolism, and other processes. Future studies are warranted to investigate the role of the IL-17 signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, and other pathways in mediating the therapeutic effects of Jianpi Huatan Quyu recipe on chronic heart failure.

Trends and Disparities in Diet Quality and Nutrient Intake among US Adults by Bodyweight Status.

The prevalence of obesity has been increasing in the US. Among the multifactorial contributors to obesity, dietary factors stand out as primary drivers. Using data from NHANES, we investigated the trends and disparities in diet quality and nutrient intake among US adults with different bodyweight statuses. Participants were divided into normal weight, overweight, and obese groups based on BMI. Diet quality was examined using HEI-2020. Nutrient intake was estimated based on the USDA Food and Nutrient Database for Dietary Studies. From 1999 to 2020, Despite an overall improvement in diet quality among overweight and obese US adults, disparities persisted for most HEI-2020 components, and worsened for whole grains, seafood and plant proteins, and fatty acids between normal weight and obese participants. Overweight and obese participants tended to consume less energy from total carbohydrates and more from total fat. The estimated total energy intake increased among obese participants over the past two decades, while no significant changes were observed among normal weight and overweight participants. In the 2017-2020 period, obese participants had lower HEI-2020 scores than both normal weight and overweight participants. However, no significant differences in total energy intake were observed among normal weight, overweight, and obese populations.

Particle arc therapy: Status and potential.

There is a rising interest in developing and utilizing arc delivery techniques with charged particle beams, e.g., proton, carbon or other ions, for clinical implementation. In this work, perspectives from the European Society for Radiotherapy and Oncology (ESTRO) 2022 physics workshop on particle arc therapy are reported. This outlook provides an outline and prospective vision for the path forward to clinically deliverable proton, carbon, and other ion arc treatments. Through the collaboration among industry, academic, and clinical research and development, the scientific landscape and outlook for particle arc therapy are presented here to help our community understand the physics, radiobiology, and clinical principles. The work is presented in three main sections: (i) treatment planning, (ii) treatment delivery, and (iii) clinical outlook.

Advantages of unilateral percutaneous kyphoplasty for osteoporotic vertebral compression fractures-a systematic review and meta-analysis.

Data from English randomized controlled trials comparing unilateral versus bilateral PKP for the treatment of OVCFs were retrieved and analyzed, and the results showed that unilateral PKP is a better choice for the treatment of patients with OVCFs, which will provide a reliable clinical rationale for the treatment of OVCFs. PURPOSE: To investigate the advantages of unilateral percutaneous kyphoplasty (PKP) for the treatment of osteoporotic vertebral compression fractures(OVCFs). METHODS: The systematic evaluation program met all program requirements (CRD 42023422383) by successfully passing the PROSPERO International Prospective Systematic Evaluation Registry. Researchers searched the references of English-language randomized controlled trials comparing unilateral and bilateral PKP for the treatment of osteoporotic vertebral compression fractures published between 2010 and 2023 and manually searched for known primary and review articles. The study statistically analyzed data from all the included literature, which primarily included time to surgery, visual pain score(VAS) and Oswestry disability index(ODI) at postoperative follow-up time points, polymethylmethacrylate (PMMA, bone cement) injection dose, cement leakage, radiation dose, and improvement in kyphotic angle. RESULTS: This meta-analysis searched 416 articles published from 2010 to 2023 based on keywords, and 18 articles were finally included in this study. The results of the forest plot showed that unilateral PKP operative time, amount of bone cement used, and radiation dose to the patient were significantly reduced (p < 0.01, p < 0.01, and p < 0.01, respectively), and unilateral and bilateral PKP had comparable cement leakage (p = 0.49, 95% CI = 0.58-1.30), and there was no significant difference in the kyphotic angle between unilateral and bilateral PKP (p = 0.42, 95% CI = - 2.29-0.96). During follow-up, there was no significant difference in pain relief between unilateral and bilateral PKP (p = 0.70, 95% CI = - 0.09-0.06), nor was there a significant difference in ODI (p = 0.27, 95% CI = - 0.35-1.24). CONCLUSIONS: There is no difference in clinical efficacy between unilateral PKP and bilateral PKP, but unilateral PKP has a shorter operative time, a lower incidence of cement leakage, a lower amount of cement, and a lower radiation dose to the patient and operator. Unilateral PKP is a better option for patients with OVCFs.

Correction: Detection of obstructive sleep apnea using Belun Sleep Platform wearable with neural network-based algorithm and its combined use with STOP-Bang questionnaire.

[This corrects the article DOI: 10.1371/journal.pone.0258040.].

Robust treatment planning for small animal radio-neuromodulation using focused kV x-ray beams.

BACKGROUND: In preclinical radio-neuromodulation research, small animal experiments are pivotal for unraveling radiobiological mechanism, investigating prescription and planning techniques, and assessing treatment effects and toxicities. However, the target size inside a rat brain is typically in the order of sub-millimeters. The small target inside the visual cortex neural region in rat brain with a diameter of around 1 mm was focused in this work to observe the physiological change of this region. Delivering uniform doses to the small target while sparing health tissues is challenging. Focused kV x-ray technique based on modern x-ray polycapillary focusing lens is a promising modality for small animal radio-neuromodulation. PURPOSE: The current manual planning method could lead to sub-optimal plans, and the positioning uncertainties due to mechanical accuracy limitations, animal immobilization, and robotic arm motion are not considered. This work aims to design a robust inverse planning method to optimize the intensities of focused kV x-ray beams located in beam trajectories to irradiate small mm-sized targets in rat brains for radio-neuromodulation. METHODS: Focused kV x-ray beams were generated through polycapillary x-ray focusing lenses on achieving small (≤0.3 mm) focus perpendicular to the beam. The beam trajectories were manually designed in 3D space in scanning-while-rotating mode. Geant4 Monte Carlo (MC) simulation generated a dose calculation matrix for each focused kV x-ray beam located in beam trajectories. In the proposed robust inverse planning method, an objective function combining a voxel-wise stochastic programming approach and L1 norm regularization was established to overcome the positioning uncertainties and obtain a high-quality plan. The fast iterative shrinkage thresholding algorithm (FISTA) was utilized to solve the objective function and obtain the optimal intensities. Four cases were employed to validate the feasibility and effectiveness of the proposed method. The manual and non-robust inverse planning methods were also implemented for comparison. RESULTS: The proposed robust inverse planning method achieved superior dose homogeneity and higher robustness against positioning uncertainties. On average, the clinical target volume (CTV) homogeneity index (HI) of robust inverse plan improved to 13.3 from 22.9 in non-robust inverse plan and 53.8 in manual plan if positioning uncertainties were also present. The average bandwidth at D90 was reduced by 6.5 Gy in the robust inverse plan, compared to 9.6 Gy in non-robust inverse plan and 12.5 Gy in manual plan. The average bandwidth at D80 was reduced by 3.4 Gy in robust inverse plan, compared to 5.5 Gy in non-robust inverse plan and 8.5 Gy in manual plan. Moreover, the dose delivery time of manual plan was reduced by an average reduction of 54.7% with robust inverse plan and 29.0% with non-robust inverse plan. CONCLUSION: Compared to manual and non-robust inverse planning methods, the robust inverse planning method improved the dose homogeneity and delivery efficiency and was resistant to the uncertainties, which are crucial for radio-neuromodulation utilizing focused kV x-rays.

MiR-182/Sestrin2 affects the function of asthmatic airway smooth muscle cells by the AMPK/mTOR pathway.

Background and Objectives: Asthma is a chronic inflammatory airway disease and brings heavy economic and spiritual burdens to patients' families and the society. Airway smooth muscle cells (ASMCs) afect the development of asthma by secreting cytokines, growth factors, and prostates. The stress-inducing protein, Sestrin2, plays a vital role in antioxidant defense. The aim of this study is to investigate the role of Sestrin2 in asthma and its corresponding molecular mechanism. Materials and Methods: Airway remodeling was induced by construction of asthma rat model. Primary ASMCs were isolated through combining tissue block adherence and enzymatic digestion and identified by immunofluorescence staining. Gene expression was measured by quantitative real-time PCR (qPCR) and western blot (WB) experiments. Cell viability, proliferation, migration, and calcium flow of ASMCs were measured by Cell Counting Kit-8 (CCK-8), 5-ethynyl-deoxyuridine (EdU), Transwell, and Fluo-3AM, respectively. The binding of miR-182 and Sestrin2 3'-untranslated region (3'-UTR) was measured by luciferase reporter system and RNA-binding protein immunoprecipitation (RIP) analysis. Results: Sestrin2 expression was upregulated in asthma rat model and cell model. Overexpression of Sestrin2 enhanced the growth, migration, and calcium flow, and inversely, repression of Sestrin2 was reduced in ASMCs from the asthma group. MiR-182, one of the microRNAs (miRNAs) that possesses the potential to regulate Sestrin2, was downregulated in ASMCs from the asthma group. Further experiments revealed that Sestrin2 was inhibited by miR-182 and that overexpression of Sestrin2 reversed the miR-182-induced inhibition of the cellular progression of ASMCs from the asthma group. This study further investigated the downstream signaling pathway of Sestrin2 and found that increased expression of Sestrin2 activated 5'-adenosine monophosphate-activated protein kinase (AMPK), leading to the inactivation of mammalian target of rapamycin (mTOR) and thus promoting the growth, migration, and calcium flow of ASMCs from the asthma group. Conclusion: This study investigated the role of Sestrin2 for the first time and further dissected the regulatory factor of Sestrin2, ultimately elucidating the downstream signaling pathway of Sestrin2 in asthma, providing a novel pathway, and improving the understanding of the development and progression of asthma.

The rest-activity rhythm, genetic susceptibility and risk of type 2 diabetes: A prospective study in UK Biobank.

AIMS: This study aims to examine the association between the rest-activity rhythm (RAR) and the incidence of type 2 diabetes (T2D). MATERIALS AND METHODS: In total, 97 503 participants without diabetes in the UK Biobank cohort were recruited. Wearable accelerometry was used to monitor circadian behaviour. The parameters of RAR including inter-daily stability, intra-daily variability, relative amplitude (RA), most active continuous 10 h period (M10), and least active continuous 5 h period (L5) were calculated to evaluate the robustness and regularity of the RAR. The weighted polygenic risk score for T2D (T2D-PRS) was calculated. Cox proportion hazards models were used to evaluate the survival relationship and the joint and interaction effects of RAR parameters and T2D-PRS on the occurrence of T2D. RESULTS: During 692 257 person-years follow-ups, a total of 2434 participants were documented. After adjustment for potential confounders, compared with participants in the highest quartile of RA and M10, the participants in the lowest quartile had a greater risk of T2D (HRRA = 2.06, 95% CI: 1.76-2.41; HRM10 = 1.33, 95% CI: 1.19-1.49). Meanwhile, the highest quartile of L5 was related to a higher risk of T2D (HR = 1.78, 95% CI: 1.55-2.24). The joint analysis showed that the high T2D-PRS with the lowest quartile of RA and M10, or highest quartile of L5 jointly increased the risk of T2D (HRRA = 4.46, 95% CI: 3.36-6.42; HRM10 = 3.15, 95% CI: 2.29-4.32; HRL5 = 3.09, 95% CI: 2.40-3.99). No modification effects of T2D-PRS on the association between the RAR parameters and risk of T2D were observed (p > .05). CONCLUSION: The unbalanced RAR are associated with a greater risk of T2D, which are independent of known risk factors of T2D.

Ion-Diode-Like Heterojunction for Improving Electricity Generation from Water Droplets by Capillary Infiltration.

Water-droplet-based electricity generators are emerging hydrovoltaic technologies that harvest energy from water circulation through strong interactions between water and nanomaterials. However, such devices exhibit poor current performance owing to their unclear driving force (evaporation or infiltration) and undesirable reverse diffusion current. Herein, a water-droplet-based hydrovoltaic electricity generator induced by capillary infiltration with an asymmetric structure composed of a diode-like heterojunction formed by negatively and positively charged materials is fabricated. This device can generate current densities of 160 and 450 µA cm-2 at room temperature and 65 °C, respectively. The heterojunction achieves a rectification ratio of 12, which effectively suppresses the reverse current caused by concentration differences. This results in an improved charge accumulation of ≈60 mC cm-2 in 1000 s, which is three times the value observed in the control device. When the area of the device is increased to 6 cm2 , the current increases linearly to 1 mA, thus demonstrating the scale-up potential of the generator. It has been proven that the streaming potential originates from capillary infiltration, and the presence of ion rectification. The proposed method of constructing ion-diode-like structures provides a new strategy for improving generator performance.

Association of 24 h Behavior Rhythm with Non-Alcoholic Fatty Liver Disease among American Adults with Overweight/Obesity.

Emerging evidence suggests that in addition to metabolic, genetic and environmental factors, circadian rhythm also plays a role in non-alcoholic fatty liver disease (NAFLD). This study aimed to explore the association of 24 h behavior rhythm (activity-rest and feeding-fasting rhythm) with NAFLD. A total of 4502 adult participants with overweight/obesity from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 were included in the current study. The behavior rhythm indices were calculated and divided into quintiles for logistic regression models. Compared to those in the lowest quintile, participants in the highest quintile of relative amplitude (RA) had a lower risk of NAFLD (OR = 0.71, 95% CI, 0.55-0.91); participants in the highest quintile of the average activity of the least active continuous 5 h period (L5) were associated with a higher risk of NAFLD (OR = 1.35, 95% CI, 1.07-1.71). Additionally, participants in the highest quintile of fasting duration and feeding rhythm score were associated with a lower risk of NAFLD relative to those in the lowest quintile (OR = 0.76, 95% CI, 0.59-0.98 for fasting duration, OR = 0.74, 95% CI, 0.58-0.95 for feeding rhythm score). The associations were stronger among participants with obesity. No significant associations were found in the relationship of other behavior rhythm indices with NAFLD. This study indicated a significant association of 24 h behavior rhythm with NAFLD among American adults with overweight/obesity.

Identification of Bone Morphometric Protein-Related Hub Genes and Construction of a Transcriptional Regulatory Network in Patients With Ossification of the Ligamentum Flavum.

STUDY DESIGN: Basic science laboratory study. OBJECTIVE: To identify hub genes related to bone morphogenetic proteins (BMPs) in the ossification of the ligamentum flavum (OLF) and analyze their functional characteristics. SUMMARY OF BACKGROUND DATA: The exact etiology and pathologic mechanism of OLF remain unclear. BMPs are pleiotropic osteoinductive proteins that may play a critical role in this condition. MATERIALS AND METHODS: The GSE106253 and GSE106256 data sets were downloaded from the Gene Expression Omnibus database. The messenger RNA (mRNA) and long noncoding RNA expression profiles were obtained from GSE106253. The microRNA expression profiles were obtained from GSE106256. Differentially expressed genes were identified between OLF and non-OLF groups and then intersected with BMP-related genes to obtain differentially expressed BMP-related genes. The least absolute shrinkage selection operator and support vector machine recursive feature elimination were used to screen hub genes. Furthermore, a competing endogenous RNA network was constructed to explain the expression regulation of the hub genes in OLF. Finally, the protein and mRNA expression levels of the hub genes were verified using Western blot and real-time polymerase chain reaction, respectively. RESULTS: We identified 671 Differentially expressed genes and 32 differentially expressed BMP-related genes. Hub genes ADIPOQ , SCD , SCX , RPS18 , WDR82 , and SPON1 , identified through the least absolute shrinkage selection operator and support vector machine recursive feature elimination analyses, showed high diagnostic values for OLF. Furthermore, the competing endogenous RNA network revealed the regulatory mechanisms of the hub genes. Real-time polymerase chain reaction showed that the mRNA expression of the hub genes was significantly downregulated in the OLF group compared with the non-OLF group. Western blot showed that the protein levels of ADIPOQ, SCD, WDR82 , and SPON1 were significantly downregulated, whereas those of SCX and RPS18 were significantly upregulated in the OLF group compared with the non-OLF group. CONCLUSION: This study is the first to identify BMP-related genes in OLF pathogenesis through bioinformatics analysis. ADIPOQ , SCD , SCX , RPS18 , WDR82 , and SPON1 were identified as hub genes for OLF. The identified genes may serve as potential therapeutic targets for treating patients with OLF.

Belun Ring (Belun Sleep System BLS-100): Deep learning-facilitated wearable enables obstructive sleep apnea detection, apnea severity categorization, and sleep stage classification in patients suspected of obstructive sleep apnea.

GOAL AND AIMS: Our objective was to evaluate the performance of Belun Ring with second-generation deep learning algorithms in obstructive sleep apnea (OSA) detection, OSA severity categorization, and sleep stage classification. FOCUS TECHNOLOGY: Belun Ring with second-generation deep learning algorithms REFERENCE TECHNOLOGY: In-lab polysomnography (PSG) SAMPLE: Eighty-four subjects (M: F = 1:1) referred for an overnight sleep study were eligible. Of these, 26% had PSG-AHI<5; 24% had PSG-AHI 5-15; 23% had PSG-AHI 15-30; 27% had PSG-AHI ≥ 30. DESIGN: Rigorous performance evaluation by comparing Belun Ring to concurrent in-lab PSG using the 4% rule. CORE ANALYTICS: Pearson's correlation coefficient, Student's paired t-test, diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, Cohen's kappa coefficient (kappa), Bland-Altman plots with bias and limits of agreement, receiver operating characteristics curves with area under the curve, and confusion matrix. CORE OUTCOMES: The accuracy, sensitivity, specificity, and kappa in categorizing AHI ≥ 5 were 0.85, 0.92, 0.64, and 0.58, respectively. The accuracy, sensitivity, specificity, and Kappa in categorizing AHI ≥ 15 were 0.89, 0.91, 0.88, and 0.79, respectively. The accuracy, sensitivity, specificity, and Kappa in categorizing AHI ≥ 30 were 0.91, 0.83, 0.93, and 0.76, respectively. BSP2 also achieved an accuracy of 0.88 in detecting wake, 0.82 in detecting NREM, and 0.90 in detecting REM sleep. CORE CONCLUSION: Belun Ring with second-generation algorithms detected OSA with good accuracy and demonstrated a moderate-to-substantial agreement in categorizing OSA severity and classifying sleep stages.

Association of rest-activity circadian rhythm with chronic respiratory diseases, a cross-section survey from NHANES 2011-2014.

OBJECTIVE: A growing number of studies have examined the 24-h rest-activity characteristics in relation to health outcomes. Up to now, few studies have paid attention to the role of rest-activity circadian rhythm in chronic respiratory diseases (CRDs); therefore, to fill this gap, our study innovatively explored the association of rest-activity circadian rhythm indices with CRDs. METHODS: A total of 7412 participants from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 were included in this study. The rest-activity circadian rhythm indices were calculated using accelerometer data and were divided into quartiles to perform logistic regression. RESULTS: Participants in the highest quartile of Relative amplitude (RA) had a lower prevalence of emphysema, chronic bronchitis and asthma, compared to those in the lowest quartile. Participants in the highest quartile of Intradaily variability (IV) was associated with a higher prevalence of emphysema relative to those in the lowest quartile. Compared to those in the lowest quartile, participants in the highest quartile of the average activity of the most active continuous 10-h period (M10) had a lower prevalence of emphysema. Additionally, compared to those in the lowest quartile of the average activity of the least active continuous 5-h period (L5) and L5 start time, participants in the highest quartile had a higher prevalence of asthma. CONCLUSIONS: This study demonstrated that in general US adult population, disrupted rest-activity circadian rhythm was associated with a higher prevalence of CRDs.

The association between biomarkers of acrylamide and cancer mortality in U.S. adult population: Evidence from NHANES 2003-2014.

The association between acrylamide (AA) and the development of cancer has been extensively discussed but the results remained controversial, especially in population studies. Large prospective epidemiological studies on the relationship of AA exposure with cancer mortality were still lacking. Therefore, we aimed to assess the association between AA biomarkers and cancer mortality in adult population from National Health and Nutrition Examination Survey (NHANES) 2003-2014. We followed 3717 participants for an average of 10.3 years. Cox regression models with multivariable adjustments were performed to determine the relationship of acrylamide hemoglobin adduct (HbAA) and glycidamide hemoglobin adduct (HbGA) with cancer mortality. Mediation analysis was conducted to demonstrate the mediated role of low-grade inflammation score (INFLA-score) in this correlation. Compared with the lowest quintile, participants with the highest quintile of HbAA, HbGA and HbAA+HbGA had increased cancer mortality risk, and the hazard ratios(HRs) were 2.07 (95%CI:1.04-4.14) for HbAA, 2.39 (95%CI:1.29-4.43) for HbGA and 2.48 (95%CI:1.28-4.80) for HbAA+HbGA, respectively. And there was a considerable non-linearity association between HbAA and cancer mortality (p for non-linearity = 0.0139). We further found that increased INFLA-score significantly mediated 71.67% in the effect of HbGA exposure on increased cancer mortality risk. This study demonstrates that hemoglobin biomarkers of AA are positively associated with cancer mortality in adult American population and INFLA-score plays a mediated role in this process. Our findings can raise public awareness of environmental and dietary exposure to acrylamide and remind people to refrain from smoking or having acrylamide-rich foods.

Dose and dose rate objectives in Bragg peak and shoot-through beam orientation optimization for FLASH proton therapy.

PURPOSE: The combined use of Bragg peak (BP) and shoot-through (ST) beams has previously been shown to increase the normal tissue volume receiving FLASH dose rates while maintaining dose conformality compared to conventional intensity-modulated proton therapy (IMPT) methods. However, the fixed beam optimization method has not considered the effects of beam orientation on the dose and dose rates. To maximize the proton FLASH effect, here, we incorporate dose rate objectives into our beam orientation optimization framework. METHODS: From our previously developed group-sparsity dose objectives, we add upper and lower dose rate terms using a surrogate dose-averaged dose rate definition and solve using the fast-iterative shrinking threshold algorithm. We compare the dosimetry for three head-and-neck cases between four techniques: (1) spread-out BP IMPT (BP), (2) dose rate optimization using BP beams only (BP-DR), (3) dose rate optimization using ST beams only (ST-DR), and (4) dose rate optimization using combined BP and ST (BPST-DR), with the goal of sparing organs at risk without loss of tumor coverage and maintaining high dose rate within a 10 mm region of interest (ROI) surrounding the clinical target volume (CTV). RESULTS: For BP, BP-DR, ST-DR, and BPST-DR, CTV homogeneity index and Dmax were found to be on average 0.886, 0.867, 0.687, and 0.936 and 107%, 109%, 135%, and 101% of prescription, respectively. Although ST-DR plans were not able to meet dosimetric standards, BPST-DR was able to match or improve either maximum or mean dose in the right submandibular gland, left and right parotids, constrictors, larynx, and spinal cord compared to BP plans. Volume of ROIs receiving greater than 40 Gy/s ( V γ 0 ) ${V_{\gamma 0}})$ was 51.0%, 91.4%, 95.5%, and 92.1% on average. CONCLUSIONS: The dose rate techniques, particularly BPST-DR, were able to significantly increase dose rate without compromising physical dose compared with BP. Our algorithm efficiently selects beams that are optimal for both dose and dose rate.

Fixed Beamline Optimization for Intensity Modulated Carbon-Ion Therapy.

A major obstacle for the adoption of heavy ion therapy is the cost and technical difficulties to construct and maintain a rotational gantry. Many heavy ion treatment facilities instead choose to construct fixed beamlines as a compromise, which we propose to mitigate with optimized treatment couch angle. We formulate the integrated beam orientation and scanning spot optimization problem as a quadratic cost function with a group sparsity regularization term. The optimization problem is efficiently solved using fast iterative shrinkage-thresholding algorithm (FISTA). To test the method, we created the fixed beamline plans with couch rotation (FBCR) and without couch rotation (FB) for intensity modulated carbon-ion therapy (IMCT) and compared with the ideal scenario where both the couch and gantry have 360 degrees of freedom (GCR). FB, FBCR, and GCR IMCT plans were compared for ten pancreas cases. The FBCR plans show comparable PTV coverage and OAR doses for each pancreas case. In conclusion, the dosimetric limitation of fixed beams in heavy ion radiotherapy may be largely mitigated with integrated beam orientation optimization of the couch rotation.

Effect of the BMPR-II-SMAD3/MRTF pathway on proliferation and migration of ASMCs and the mechanism in asthma.

BACKGROUND: A variety of smooth muscle-specific genes and proteins, including SMAD3, BMPR-II, and MRTF, are involved in airway remodeling in asthma. As a receptor of bone morphogenetic protein (BMP) signaling, BMPR-II has important roles in airway remodeling in asthma. However, the underlying mechanism of BMPR-II in airway smooth muscle cells (ASMCs) in asthma remains incomplete. METHODS: Wistar rats were intraperitoneally injected with ovalbumin antigen suspension and aluminium hydroxide and, stimulated with ovalbumin nebulized inhalation to constructed asthma model. Primary ASMCs were isolated with collagenase I and identified by testing the α-SMA expression. Quantitative polymerase chain reaction (qPCR) and western blot assay were employed to detect the gene expression. CCK8, Transwell and Fluo-4 A assays were introduced to measure the cell viability, migration and intracellular Ca2+. Co-Immunoprecipitation (Co-IP) assay was applied to test the interaction among proteins. RESULTS: First, we observed significant increases in BMPR-II in asthmatic rat model and ASMCs at both the mRNA and protein levels. Second, we observed that silencing of siBMPR-II inhibited proliferation, migratory capacity and intracellular Ca2+ concentration in ASMCs. Furthermore, our study demonstrated that siBMPR-II inhibited the Smad3 expression and overexpression promoted the bioactivity of ASMCs. In addition, this study showed that p-Smad3 could interacted with MRTF and siMRTF inhibits the bioactivity of ASMCs. Finally, our results revealed BMPR-II-SMAD3/MRTF pathway affected the bioactivity of ASMCs. CONCLUSIONS: This study indicates that the BMPR-II-SMAD3/MRTF signaling pathway is involved in the process of ASMCs remodeling, providing novel avenues for the identification of new therapeutic modalities.

High-Efficiency, Mass-Producible, and Colored Solar Photovoltaics Enabled by Self-Assembled Photonic Glass.

Building-integrated photovoltaics is a crucial technology for developing zero-energy buildings and sustainable cities, while great efforts are required to make photovoltaic (PV) panels aesthetically pleasing. This places an urgent demand on PV colorization technology that has a low impact on power conversion efficiency (PCE) and is simultaneously mass-producible at a low cost. To address this challenge, this study contributes a colorization strategy for solar PVs based on short-range correlated dielectric microspheres, i.e., photonic glass. Through theoretical studies, first we demonstrate that the photonic glass self-assembled by high-index microspheres could enable both colored solar cells and modules, with easily variable colors and negligible parasitic absorption. By a fast spray coating process of colloidal monodisperse ZnS microspheres, we show the photonic glass layer could be easily deposited on silicon solar cells, enabling them to have structural colors. Through varying microsphere sizes, solar cells with different colors are achieved, showing low PCE loss compared to normal black cells. These colored solar cells are also encapsulated with a general lamination process to produce PV modules with various colors and patterns at a stunning PCE approaching 21%. Moreover, the long-term stability is subsequently verified by aging tests including an outdoor exposure for 10 days and a damp-heat test for 1000 h, and the mass producibility is demonstrated by presenting a colored PV panel with an output power over 108 W. These results confirm photonic glass as a promising strategy for colored PVs possessing high efficiency and practical applicability.

The Association of Dietary Vitamin Intake Time Across a Day With Cardiovascular Disease and All-Cause Mortality.

Background: Chrono-nutrition emphasized the importance of the intake time; however, less is known about the impact of dietary vitamin intake time on health. This study aimed to examine our hypothesis about which vitamin intake time could influence the natural course of cardiovascular disease (CVD). Methods: A total of 27,455 adults enrolled in the National Health and Nutrition Examination Survey (NHANES) during 2003-2014 were recruited. The 12 dietary vitamin intakes in the morning, afternoon, and evening were categorized into tertiles or quartiles. Cox-proportional hazard regression models were developed to evaluate the association of vitamin intake time with CVD and all-cause mortalities. Results: Compared with participants in the lowest quartile, participants in the highest quartile of dietary VB2 intake in the morning had significantly lowest mortality risk of CVD [hazard ratio (HR)VB2 = 0.75, 95% CI: 0.60-0.94, p = 0.017]; whereas, participants in the highest quartile of dietary-vitamin B6 (VB6), vitamin C (VC), vitamin E (VE), and folate-equivalent consumed in the evening showed the lowest risks of CVD (HRVB6 = 0.77, 95% CI: 0.60-0.99, p = 0.103; HRVC = 0.80, 95% CI: 0.65-0.98, p = 0.050; HRVE = 0.75, 95% CI: 0.56-0.99, p = 0.032; HRfolate-equivalent = 0.78, 95% CI: 0.63-0.97, p = 0.116) and all-cause mortalities (HRVB6 = 0.81, 95% CI: 0.71-0.93, p = 0.006; HRVC = 0.85, 95% CI: 0.76-0.95, p = 0.004; HRVE = 0.84, 95% CI: 0.72-0.97, p = 0.011; HRfolate-equivalent = 0.80, 95% CI: 0.71-0.90, p = 0.001). Moreover, equivalently replacing 10% intake of dietary VB6, VC, VE, and folate-equivalent in the morning with evening were associated with 4% (HRVB6 = 0.96, 95% CI: 0.92-0.99), 5% (HRVC = 0.95, 95% CI: 0.92-0.99), 4% (HRVE = 0.96, 95% CI: 0.91-0.99), and 5% (HRfolate-equivalent = 0.95, 95% CI: 0.92-0.99) lower risk of CVD mortality. Conclusion: This study found that the optimal intake time of dietary VB2 was in the morning, and the optimal intake times of dietary VB6, VC, VE, and folate-equivalent were in the evening.

Reformulated McNamara RBE-weighted beam orientation optimization for intensity modulated proton therapy.

PURPOSE: Empirical relative biological effectiveness (RBE) models have been used to estimate the biological dose in proton therapy but do not adequately capture the factors influencing RBE values for treatment planning. We reformulate the McNamara RBE model such that it can be added as a linear biological dose fidelity term within our previously developed sensitivity-regularized and heterogeneity-weighted beam orientation optimization (SHBOO) framework. METHODS: Based on our SHBOO framework, we formulated the biological optimization problem to minimize total McNamara RBE dose to OARs. We solve this problem using two optimization algorithms: FISTA (McNam-FISTA) and Chambolle-Pock (McNam-CP). We compare their performances with a physical dose optimizer assuming RBE = 1.1 in all structures (PHYS-FISTA) and an LET-weighted dose model (LET-FISTA). Three head and neck patients were planned with the four techniques and compared on dosimetry and robustness. RESULTS: Compared to Phys-FISTA, McNam-CP was able to match CTV [HI, Dmax, D95%, D98%] by [0.00, 0.05%, 1.4%, 0.8%]. McNam-FISTA and McNam-CP were able to significantly improve overall OAR [Dmean, Dmax] by an average of [36.1%,26.4%] and [29.6%, 20.3%], respectively. Regarding CTV robustness, worst [Dmax, V95%, D95%, D98%] improvement of [-6.6%, 6.2%, 6.0%, 4.8%] was reported for McNam-FISTA and [2.7%, 2.7%, 5.3%, -4.3%] for McNam-CP under combinations of range and setup uncertainties. For OARs, worst [Dmax, Dmean] were improved by McNam-FISTA and McNam-CP by an average of [25.0%, 19.2%] and [29.5%, 36.5%], respectively. McNam-FISTA considerably improved dosimetry and CTV robustness compared to LET-FISTA, which achieved better worst-case OAR doses. CONCLUSION: The four optimization techniques deliver comparable biological doses for the head and neck cases. Besides modest CTV coverage and robustness improvement, OAR biological dose and robustness were substantially improved with both McNam-FISTA and McNam-CP, showing potential benefit for directly incorporating McNamara RBE in proton treatment planning.