Distinct effects of CDK8 module subunits on cellular growth and proliferation in Drosophila.

The Mediator complex, composed of about 30 conserved subunits, plays a pivotal role in facilitating RNA polymerase II-dependent transcription in eukaryotes. Within this complex, the CDK8 kinase module (CKM), comprising Med12, Med13, CDK8, and CycC (Cyclin C), serves as a dissociable subcomplex that modulates the activity of the small Mediator complex. Genetic studies in Drosophila have revealed distinct phenotypes of CDK8-CycC and Med12-Med13 mutations, yet the underlying mechanism has remained unknown. Here, using Drosophila as a model organism, we show that depleting CDK8-CycC enhances E2F1 target gene expression and promotes cell-cycle progression. Conversely, depletion of Med12-Med13 affects the expression of ribosomal protein genes and fibrillarin, indicating a more severe reduction in ribosome biogenesis and cellular growth compared to the loss of CDK8-CycC. Moreover, we found that the stability of CDK8 and CycC relies on Med12 and Med13, with a mutually interdependent relationship between Med12 and Med13. Furthermore, CycC stability depends on the other three CKM subunits. These findings reveal distinct roles for CKM subunits in vivo , with Med12-Med13 disruption exerting a more pronounced impact on ribosome biogenesis and cellular growth compared to the loss of CDK8-CycC. Significance: The CDK8 kinase module (CKM), comprising CDK8, CycC, Med12, and Med13, is essential in the Mediator complex for RNA polymerase II-dependent transcription in eukaryotes. While expected to function jointly, CKM subunit mutations result in distinct phenotypes in Drosophila . This study investigates the mechanisms driving these differing effects. Our analysis reveals the role of Med12-Med13 pair in regulating ribosomal biogenesis and cellular growth, contrasting with the involvement of CDK8-CycC in E2F1-dependent cell-cycle progression. Additionally, an asymmetric interdependence in the stability of CDK8-CycC and Med12-Med13 was observed. CKM mutations or overexpression are associated with cancers and cardiovascular diseases. Our findings underscore the distinct impacts of CKM mutations on cellular growth and proliferation, advancing our understanding of their diverse consequences in vivo .

Preoperative glucose-to-lymphocyte ratio predicts survival in cancer.

Background: Systemic inflammation and glucose metabolism have been closely related to the survival of cancer patients. Therefore, we aimed to evaluate whether preoperative glucose-to-lymphocyte ratio (GLR) can be used to predict the survival of cancer patients. Methods: We retrospectively examined 2172 cancer patients who underwent surgery from January 1, 2014, to December 31, 2016. There were 240 patients with non-small cell lung cancer (NSCLC), 378 patients with colorectal cancer (CRC), 221 patients with breast cancer (BC), 335 patients with gastric cancer (GC), 270 patients with liver cancer, 233 patients with esophageal cancer (EC), 295 patients with renal cancer, and 200 patients with melanoma. The formula for preoperative GLR calculation was as follows: GLR=glucose/lymphocyte count. The overall survival (OS) was estimated using the Kaplan-Meier method. The predictive factors for OS were determined using multivariate analysis. Results: The Kaplan-Meier analysis showed that the median survival time in the high-GLR group was much shorter than that of those in the low-GLR group for different cancers. Cox multivariate regression analysis reveals that preoperative GLR was an independent factor for predicting overall survival in different tumor types. Conclusion: Elevated preoperative GLR was remarkably associated with a poorer prognosis in patients with NSCLC, CRC, breast cancer, gastric cancer, kidney cancer, liver cancer, esophageal cancer, and melanoma. Preoperative GLR promises to be an essential predictor of survival for cancer patients.

Red blood cell distribution width is associated with sarcopenia risk in early-stage non-small cell lung cancer.

BACKGROUND: Sarcopenia has received increasing attention in non-small cell lung cancer (NSCLC). Red blood cell distribution width (RDW) is a significant component of the complete blood count and indicates the heterogeneity of erythrocyte volume. Little information is known about RDW in relation to sarcopenia in early-stage (IA-IIIA) NSCLC. The purpose of the present study was to investigate the association between RDW and sarcopenia risk in early-stage NSCLC patients. METHODS: This study included 378 patients with pathologically confirmed stage IA-IIIA NSCLC. Sarcopenia was defined by measuring the skeletal muscle index (SMI) at the eleventh thoracic vertebra level. The maximum Youden index on the receiver operating characteristic (ROC) curve was used to estimate the cutoff value for RDW to predict sarcopenia. Logistic regression analyses were carried out to assess the independent risk factors for sarcopenia in NSCLC. RESULTS: The ROC curve indicated that the best cutoff point for RDW to predict sarcopenia was 12.9 (sensitivity of 43.80% and specificity of 76.76%, respectively). Moreover, there were significant differences in hemoglobin (p < 0.001), comorbidities (p = 0.001), histological type (p = 0.002), and cancer stage (p = 0.032) between the high RDW and low RDW groups. Logistic regression analyses revealed that high RDW is an independent risk factor for sarcopenia in early-stage NSCLC. CONCLUSION: RDW is associated with sarcopenia risk in early-stage NSCLC.

3D Bioprinting of Acellular Corneal Stromal Scaffolds with a Low Cost Modified 3D Printer: A Feasibility Study.

PURPOSE: Loss of corneal transparency is one of the major causes of visual loss, generating a considerable health and economic burden globally. Corneal transplantation is the leading treatment procedure, where the diseased cornea is replaced by donated corneal tissue. Despite the rise of cornea donations in the past decade, there is still a huge gap between cornea supply and demand worldwide. 3D bioprinting is an emerging technology that can be used to fabricate tissue equivalents that resemble the native tissue, which holds great potential for corneal tissue engineering application. This study evaluates the manufacturability of 3D bioprinted acellular corneal grafts using low-cost equipment and software, not necessarily designed for bioprinting applications. This approach allows access to 3D printed structures where commercial 3D bioprinters are cost prohibitive and not readily accessible to researchers and clinicians. METHODS: Two extrusion-based methods were used to 3D print acellular corneal stromal scaffolds with collagen, alginate, and alginate-gelatin composite bioinks from a digital corneal model. Compression testing was used to determine moduli. RESULTS: The printed model was visually transparent with tunable mechanical properties. The model had central radius of curvature of 7.4 mm, diameter of 13.2 mm, and central thickness of 0.4 mm. The compressive secant modulus of the material was 23.7 ± 1.7 kPa at 20% strain. 3D printing into a concave mold had reliability advantages over printing into a convex mold. CONCLUSIONS: The printed corneal models exhibited visible transparency and a dome shape, demonstrating the potential of this process for the preparation of acellular partial thickness corneal replacements. The modified printing process presented a low-cost option for corneal bioprinting.

Preoperative small airway dysfunction is associated with skeletal muscle loss in early-stage non-small cell lung cancer.

BACKGROUND: Postoperative skeletal muscle loss (SM loss) was reported to be associated with a poor prognosis in early-stage non-small cell lung cancer (NSCLC). Small airway dysfunction (SAD) is a common but neglected respiratory abnormality. Little information is known about the association between preoperative SAD and postoperative SM loss in early-stage NSCLC. Therefore, this study aimed to investigate the correlation between preoperative SAD and SM loss after surgery in early-stage NSCLC patients. METHODS: There were 348 NSCLC patients with stages I-IIIA in this study from January 2017 to December 2020. All CT images were contrast-enhanced scans, and the skeletal muscle index (SMI) was measured using CT images. A 10.0% decrease in SMI over 12 months was determined as the cut-off value to define excessive SM loss. Logistic regression analyses were used to examine the relationship between SAD and SM loss. RESULTS: This study included 348 subjects who underwent pulmonary operation (159 males and 189 females; mean age: 57.5 ± 8.8 years). 152 (43.7%) patients were identified as having SAD before surgery, and 179 patients (51.4%) were identified as having SM loss after 1 year. Moreover, a higher incidence of SAD was found in the SM loss group compared with that in the non-SM loss group (52.0% vs. 34.9%, p = 0.001). The patients with SAD were older, had larger tumor size, and had lower albumin levels. Furthermore, there were significant correlations between the lung function parameters manifesting SAD and the percentage change in SMI (for the forced expiratory flow when 75% of forced vital capacity has been exhaled (FEF75%), Pearson r=-0.107, p = 0.046; for FEF50%, r = -0.142, p = 0.008; and for FEF25-75%, r=-0.124, p = 0.021; respectively). However, no significant correlations were found between SMI and the lung function parameters reflecting proximal airway obstruction (p > 0.05). Logistic regression analysis revealed that preoperative SAD (HR, 2.465; 95% CI, 1.256-4.838; p = 0.009) was independent risk factor for postoperative SM loss in early-stage NSCLC. In addition, multivariable analysis revealed that SAD (HR, 1.816; 95% CI, 1.025-3.216, P = 0.041) were associated with postoperative complications. CONCLUSION: Preoperative SAD is significantly associated with postoperative complications and SM loss in early NSCLC patients. Our results suggest that preoperative assessment of SAD may be useful for risk stratification of surgical candidates with potential for targeted interventions.

Overview of the Circadian Clock in the Hair Follicle Cycle.

The circadian clock adapts to the light-dark cycle and autonomously generates physiological and metabolic rhythmicity. Its activity depends on the central suprachiasmatic pacemaker. However, it also has an independent function in peripheral tissues such as the liver, adipose tissue, and skin, which integrate environmental signals and energy homeostasis. Hair follicles (HFs) maintain homeostasis through the HF cycle, which depends heavily on HF stem cell self-renewal and the related metabolic reprogramming. Studies have shown that circadian clock dysregulation in HFs perturbs cell cycle progression. Moreover, there is increasing evidence that the circadian clock exerts a significant influence on glucose metabolism, feeding/fasting, stem cell differentiation, and senescence. This suggests that circadian metabolic crosstalk plays an essential role in regulating HF regeneration. An improved understanding of the role of the circadian clock in HFs may facilitate the discovery of new drug targets for hair loss. Therefore, the present review provides a discussion of the relationship between the circadian clock and HF regeneration, mainly from the perspective of HF metabolism, and summarizes the current understanding of the mechanisms by which HFs function.

L-Ascorbic Acid 2-Phosphate Attenuates Methylmercury-Induced Apoptosis by Inhibiting Reactive Oxygen Species Accumulation and DNA Damage in Human SH-SY5Y Cells.

Methylmercury (MeHg) is a toxin that causes severe neuronal oxidative damage. As vitamin C is an antioxidant well-known to protect neurons from oxidative damage, our goal was to elucidate its protective mechanism against MeHg-induced oxidative stress in human neuroblastomas (SHSY5Y). We treated cells with MeHg, L-ascorbic acid 2-phosphate (AA2P), or both, and used MTT, flow cytometry, and Western blot analyses to assess cell damage. We found that MeHg significantly decreased the survival rate of SH-SY5Y cells in a time- and dose-dependent manner, increased apoptosis, downregulated PAR and PARP1 expression, and upregulated AIF, Cyto C, and cleaved Caspase-3 expression. A time course study showed that MeHg increased reactive oxygen species (ROS) accumulation; enhanced apoptosis; increased DNA damage; upregulated expression ofγH2A.X, KU70, 67 and 57 kDa AIF, CytoC, and cleaved Caspase-3; and downregulated expression of 116 kDa PARP1, PAR, BRAC1, and Rad51. Supplementation with AA2P significantly increased cell viability and decreased intrinsic ROS accumulation. It also reduced ROS accumulation in cells treated with MeHg and decreased MeHg-induced apoptosis. Furthermore, AA2P conversely regulated gene expression compared to MeHg. Collectively, we demonstrate that AA2P attenuates MeHg-induced apoptosis by alleviating ROS-mediated DNA damage and is a potential treatment for MeHg neurotoxicity.

Research progress of PBX1 in developmental and regenerative medicine.

Pre-B-cell leukemia transcription factor 1 (PBX1) proteins are a subfamily of evolutionarily conserved atypical homeodomain transcription factors belonging to the superfamily of triple amino acid loop extension homeodomain proteins. PBX family members play crucial roles in the regulation of various pathophysiological processes. This article reviews the research progress on PBX1 in terms of structure, developmental function, and regenerative medicine. The potential mechanisms of development and research targets in regenerative medicine are also summarized. It also suggests a possible link between PBX1 in the two domains, which is expected to open up a new field for future exploration of cell homeostasis, as well as the regulation of endogenous danger signals. This would provide a new target for the study of diseases in various systems.

PBX1-SIRT1 Positive Feedback Loop Attenuates ROS-Mediated HF-MSC Senescence and Apoptosis.

Stem cell senescence and depletion are major causes of aging and aging-related diseases. The NAD (Nicotinamide adenine dinucleotide) - SIRT1 (Silent Information Regulator 1) - PARP1 (Poly (ADP-ribose) polymerase-1) axis has gained interest owing to its significant role in regulating stem cell senescence and organismal aging. A recent study from our lab showed that pre-B-cell leukemia transcription factor1 (PBX1) overexpression attenuates hair follicle-derived mesenchymal stem cells (HF-MSCs) senescence and apoptosis by regulating ROS-mediated DNA damage via PARP1 downregulation; thus, suggesting that PARP1 downregulation is a common manifestation of the roles of both PBX1 and SIRT1 in HF-MSCs senescence attenuation, and implying a potential link between PBX1 and SIRT1. To this end, HF-MSCs overexpressing PBX1, overexpressing both PBX1 and PARP1, downregulating SIRT1, and overexpressing PBX1 as well as downregulating SIRT1 were generated, and senescence, apoptosis, DNA damage, and repair biomarkers were analyzed. Our results showed that (1) PBX1 overexpression alleviated HF-MSCs senescence and apoptosis accompanied by SIRT1 upregulation, PARP1 downregulation, and increased intracellular NAD and ATP levels. (2) SIRT1 knockdown enhanced cellular senescence and apoptosis, accompanied by increased ROS accumulation, DNA damage aggravation, and decreased intracellular NAD and ATP levels. (3) PBX1 overexpression rescued HF-MSCs senescence and apoptosis induced by SIRT1 knockdown. (4) PBX1 rescued PARP1 overexpression-mediated ATP and NAD depletion, accompanied by increased SIRT1 expression. Collectively, our results revealed that a positive interaction feedback loop exists between PBX1 and SIRT1. To the best of our knowledge we are the first to report that there is a PBX1-SIRT1-PARP1 axis that plays a critical role in alleviating HF-MSCs senescence and apoptosis. We provide a new perspective on the mechanisms underlying stem cell senescence as well as age-related disease prevention and treatment.

Utility of mean platelet volume in differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are the most prevalent histologic types of primary liver cancer. HCC and ICC differ in treatment and prognosis, warranting an effective differential diagnosis between them. This study aimed to explore the clinical value of mean platelet volume (MPV) to discriminate between HCC and ICC. MATERIAL/METHODS: We performed a retrospective analysis of ICC and HCC patients who were from the Harbin Medical University Cancer Hospital, China. Logistic regression analysis was used to identify the independent factors for the differentiation of HCC and ICC. A receiver operating characteristic curve was built to evaluate the diagnostic performance of the potential model. An independent validation study was performed to validate the diagnostic ability. RESULTS: ICC patients were detected in 146 out of 348 patients in the primary cohort. MPV levels were decreased in ICC patients compared with those in HCC patients. Logistic regression analysis revealed that MPV was an independent factor in distinguishing HCC from ICC. A combination of sex, hepatitis B surface antigen, MPV, alpha-fetoprotein, and carbohydrate antigen 19-9 demonstrated a good capability to differentiate HCC from ICC. Similar results were achieved in the validation cohort. CONCLUSIONS: MPV may be a new marker to help distinguish ICC from HCC. Further validation studies are required.

Highly efficient solar photothermal conversion of graphene-coated conjugated microporous polymers hollow spheres.

Highly efficient harvesting, transfer, and storage of solar energy are of great significance for the sustainability of society Herein, we report the design and synthesis of conjugated microporous polymers hollow spheres (CMPs-HS) coated by graphene (GCMPs-HS) and compounded with the phase change material (PCM) octadecanol (GCMPs@ODA) for efficient solar photothermal conversion. The as-synthesized CMPs-HS shows a high specific surface (519.95 m2 g-1 and 309.26 m2 g-1), good thermostability, and lower thermal conductivity (0.33 W m-2h-1). By coating graphene, the light absorption remained about 90% in the visible light range, which allows light harvest for photothermal conversion. Taking the GCMPs-HS as a functional layer for the solar steam generation (SSG) system, a high evaporation efficiency of near 90% is obtained. After inhaling octadecanol, GCMPs@ODA are prepared and their latent heats are measured to about 217.4 J g-1 and 224.6 J g-1. Under 1 sun irradiation, the photothermal conversion efficiencies of GCMPs@ODA are measured to be 87.15% and 85.83%, the above merits applied in different conditions are superior to photothermal conversion materials reported in the literature. Thus, among the above merits, the fabricated materials are the competitive candidate which shows the great potential in the efficient application of solar energy.

A microfluidic approach for studying microcolonization of Escherichia coli O157:H7 on leaf trichome-mimicking surfaces under fluid shear stress.

Escherichia coli O157:H7 have previously been associated with disease outbreaks associated with leafy green vegetables. However, the physical mechanisms that determine the spatial organization of bacteria onto leafy greens are still not clear. Microfluidics with embedded trichome-mimicking microposts were employed to investigate the role of shear flow and configuration of trichomes on E. coli O157:H7 microcolonization. We characterized the three-dimensional microcolonization of green fluorescent protein (GFP)-tagged E. coli O157:H7 using multiphoton fluorescence microscopy and compared their differences under static (no flow; incubated for 36 h at 37°C) and fluid shear conditions (750 nl/min for 36 h at 37°C). For micropatterned trichome arrays, we demonstrated that natural wax-mixed polydimethylsiloxane retains similar topographies and contact angles to the surface of trichome-bearing leafy greens. Our results showed that E. coli O157:H7 under fluid shear stress aligned their colonization parallel to the direction of flow. In a static condition, their colonization had no preferential alignment, with statistically similar angular distributions in all directions. In addition, depending on dimensions of the trichome arrays and flow conditions, different bacterial microcolonization patterns grew radially from initial attachment; they formed into filamentous structures and developed into bridges by surface hydrophobicity and flow-induced shear with a nutrient-rich medium. Collectively, these results demonstrate how the consequences of bacterial colonization in response to shear flow can affect pathogenic bacterial contamination of leafy greens and biofilm architectures.

Efficacy and safety of acupuncture for patients with pseudomyopia: A protocol for systematic review and meta-analysis.

BACKGROUND: Myopia are common health problems that people experience in daily life. Pediatric myopia has become a major international public health concern that has a negative impact on physical, mental health of patients, and quality of life. Currently, there is no cure available. Press needle as an adjuvant therapy is currently undergoing clinical trials in different medical centers. However, no relevant systematic review or meta-analysis has been designed to evaluate the effects of press needle patching on early myopia. There is also a lack of systematic evaluation and analysis of acupoints and thumbtack needle. METHODS: We will electronically search Medline, Embase, PubMed, Web of Science, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, and Wan-Fang Database from their inception to October 2021. In addition, we will manually retrieve other resources including the reference lists of identified publications, conference articles, and gray literature. The clinical randomized controlled trials or quasi-randomized controlled trials related to press needle for the treatment of early myopia will be included in the study. The language is limited to Chinese and English. Research selection, data extraction, and research quality assessment will be independently completed by 2 researchers. Data were synthesized by using afixed effect model or random effect model depend on the heterogeneity test. The total effective rate was the primary outcomes. RevMan V.5.3 statistical software will be used for meta-analysis. If it is not appropriate for a meta-analysis, then a descriptive analysis will be conducted. Data synthesis will use the risk ratio and the standardized or weighted average difference of continuous data to represent the results. RESULTS: This study will analyze the clinical effective rate, pesudomyopia outcomes, quality of life, improvement of clinical symptoms of pesudomyopia, and validity of thumbtack needle for patients with pesudomyopia. CONCLUSION: This systematic review will provide evidence to judge whether thumbtack needle is an effective intervention for patients with early myopia. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42021243151.

Magnesium hydroxide coated hollow glass microspheres/chitosan composite aerogels with excellent thermal insulation and flame retardancy.

The development of an environmental-friendly thermal insulation and flame retardant material has attracted widespread attention in modern architecture. In this work, a kind of novel aerogel composites were prepared by incorporation of Mg(OH)2 coated hollow glass microspheres (HGM) into chitosan (CSA) matrix and then cross-linking by glutaraldehyde (abbreviated as CSA-HGM-Mg(OH)2). The as-prepared composite aerogel exhibits vertical directional channel with high porosity and excellent thermal insulation with a low thermal conductivity of 0.035 W m-1 k-1. Besides, it shows excellent flame retardancy with a high limit oxygen index (LOI) value up to 50.8, which is one of the highest values among the most of flame retardants reported previously. Also, a very low peak heat release rate (pHRR) of 24.12 kW m-2 was obtained which makes the aerogel composite reaching UL-94 V-0 rating. Such results may be attributed to a synergy effect by combination of its abundantly porous structure derived from HGM to give a better thermal insulation and excellent nonflammability of CSA and Mg(OH)2 to offer a superior flame retardancy. Taking advantages of its high mechanical strength, low cost materials, simple and scalable preparation method, CSA-HGM-Mg(OH)2 aerogel composites may hold great potential for future thermal insulation and flame retardant applications.

Preliminary Study on Reference Interval of Serum Pepsinogen in Healthy Subjects.

OBJECTIVE: This study determined the reference interval of pepsinogen (PG) of healthy people in the local region to provide a basis for early screening of gastric cancer. METHODS: Among the healthy people who underwent a physical examination in our hospital from January 2020 to December 2020, 2568 subjects were selected based on the relevant screening criteria. Their serum PG I and II levels and PG I:PG II ratio were determined by chemiluminescent microparticle immunoassay (CIMA), and the results were statistically analyzed. Finally, according to document CLSI-C28-A3, the PG reference interval of the local region was determined. RESULTS: The PG I and II levels of the males in all age groups were higher than those of the females in the corresponding age groups, and the differences were statistically significant (P < 0.05). However, the differences in the PG I:PG II ratio between the genders in the different age groups were not statistically significant (P > 0.05). The PG I and II levels increased with age in both men and women, while the PG I:PG II ratio was not correlated with age in either gender. CONCLUSION: The PG reference interval of the local region was initially determined as providing a reliable reference basis for clinical treatment.

Modified Hollow Glass Microspheres/Reduced Graphene Oxide Composite Aerogels with Low Thermal Conductivity for Highly Efficient Solar Steam Generation.

Solar steam generation (SSG) as a pollution-free and sustainable way for desalination or wastewater treatment has attracted great attention in recent years. Herein, we report the fabrication of novel aerogels GAHAS and GAHAF composed of 3-aminopropyltriethoxysilane (KH550)-modified hollow glass microspheres (HGM) and reduced graphene oxide (RGO) by a sol-gel method for highly efficient SSG. The RGO can well wrap on modified HGM and form an interpenetrated porous structure with an excellent mechanical property. In addition, benefiting from the hollow structure of HGM, GAHAS obtained by supercritical CO2 drying well maintains the original structure of the hydrogel and shows low thermal conductivity (0.0823 W m-1 K-1) in the wet state and self-floating ability. Combined with its superhydrophilic wettability and high light absorption (ca. 93%), the as-prepared GAHAS shows an outstanding photothermal conversion efficiency of 89.13% under 1 sun (1 kW m-2) illumination and excellent stability. Moreover, from the simulated seawater outdoor solar desalination experiment, it was found that the concentrations of the four primary ions K+, Ca2+, Na+, and Mg2+ in purified water are 1.65, 0.09, 1.42, and 0.32 mg L-1, respectively, and fully meet drinking water standards. Thus, our GAHAS aerogel shows great potential for practical application in SSG. This work enriches the photothermal materials and may provide a new idea for design and creation of HGM-based photothermal materials with low thermal conductivity, tunable porosity, high mechanical strength, self-floating ability, and high solar energy conversion efficiency for SSG.

Effects of dim artificial light at night on locomotor activity, cardiovascular physiology, and circadian clock genes in a diurnal songbird.

Artificial light is transforming the nighttime environment and quickly becoming one of the most pervasive pollutants on earth. Across taxa, light entrains endogenous circadian clocks that function to synchronize behavioral and physiological rhythms with natural photoperiod. Artificial light at night (ALAN) disrupts these photoperiodic cues and has consequences for humans and wildlife including sleep disruption, physiological stress and increased risk of cardiovascular disease. However, the mechanisms underlying organismal responses to dim ALAN, resembling light pollution, remain elusive. Light pollution exists in the environment at lower levels (<5 lux) than tested in many laboratory studies that link ALAN to circadian rhythm disruption. Few studies have linked dim ALAN to both the upstream regulators of circadian rhythms and downstream behavioral and physiological consequences. We exposed zebra finches (Taeniopygia gutatta) to dim ALAN (1.5 lux) and measured circadian expression of five pacemaker genes in central and peripheral tissues, plasma melatonin, locomotor activity, and biomarkers of cardiovascular health. ALAN caused an increase in nighttime activity and, for males, cardiac hypertrophy. Moreover, downstream effects were detectable after just short duration exposure (10 days) and at dim levels that mimic the intensity of environmental light pollution. However, ALAN did not affect circulating melatonin nor oscillations of circadian gene expression in the central clock (brain) or liver. These findings suggest that dim ALAN can alter behavior and physiology without strong shifts in the rhythmic expression of molecular circadian pacemakers. Approaches that focus on ecologically-relevant ALAN and link complex biological pathways are necessary to understand the mechanisms underlying vertebrate responses to light pollution.

Comparison of the transfer accuracy of two digital indirect bonding trays for labial bracket bonding.

OBJECTIVES: To compare the transfer accuracy of two digital transfer trays, the three-dimensional printed (3D printed) tray and the vacuum-formed tray, in the indirect bonding of labial brackets. MATERIALS AND METHODS: Ten digital dental models were constructed by oral scans using an optical scanning system. 3D printed trays and vacuum-formed trays were obtained through the 3Shape indirect bonding system and rapid prototyping technology (10 in each group). Then labial brackets were transferred to 3D printed models, and the models with final bracket positioning were scanned. Linear (mesiodistal, vertical, buccolingual) and angular (angulation, torque, rotation) transfer errors were measured using GOM Inspect software. The mean transfer errors and prevalence of clinically acceptable errors (linear errors of ≤0.5 mm and angular errors of ≤2°) of two digital trays were compared using the Mann-Whitney U-test and the Chi-square test, respectively. RESULTS: The 3D printed tray had a lower mean mesiodistal transfer error (P < .01) and a higher prevalence of rotation error within the limit of 2° (P = .03) than did the vacuum-formed tray. Linear errors within 0.5 mm were higher than 90% for both groups, while torque errors within 2° were lowest at 50.9% and 52.9% for the 3D printed tray and vacuum-formed tray, respectively. Both groups had a directional bias toward the occlusal, mesial, and buccal. CONCLUSIONS: The 3D printed tray generally scored better in terms of transfer accuracy than did the vacuum-formed tray. Both types of trays had better linear control than angular control of brackets.

Freeform reflector antenna design method to improve transmission efficiency and control output intensity distribution.

In this paper, a reflector antenna design method is proposed to improve transmission efficiency and control output intensity distribution. Primary and secondary mirrors are constructed segment by segment using a numerical method according to the law of energy conservation, the vector theory of reflection, and Fermat's principle that the optical path length of each ray must be equal. To verify the effectiveness and practicability of this method, an example of an antenna with the prescribed intensity distribution of the output beam is given. The transmission efficiency of the antenna system designed by this method reaches 100% in theory. The effects of output intensity distribution and deviation on transmission efficiency were also analyzed. We believe that the results show that the proposed method is a highly efficient approach to the design of a freeform reflector antenna to improve transmission efficiency and control the output intensity distribution.

Coaxial oblique interface shearing: tunable generation and sorting of double emulsions for spatial gradient drug release.

We propose a coaxial oblique interface shearing (COIS) process for one-step generation of double emulsions which are synchronously sorted with spatial gradient distributions. As a coaxial needle supplying the inner and outer liquids obliquely vibrates across an air-liquid interface, the pinch-off of the compound liquid neck arises and the resultant double emulsions moves with tunable lateral displacements in the receiving phase. In the COIS process, the morphology and size of the double emulsions are heavily dependent on the vibration frequency and the inner and outer liquid flow rates. The lateral droplet displacements changing with process parameters can be precisely controlled in experiments and predicted theoretically by the Stokes drift model. Furthermore, the feasibility of the COIS process in spatial gradient drug release is verified. The double emulsions sorted along a specific direction are available for spatial gradient release under thermal and chemical environments, respectively. The COIS technique has great potential in fields of sensors, spatial gradient materials, advanced drug delivery and biomedical applications.