The role of HPV11 E7 in modulating STING-dependent interferon ß response in recurrent respiratory papillomatosis.

Recurrent respiratory papillomatosis (RRP) is a rare benign tumor caused mainly by the infection of the respiratory tract epithelial cells by the human papillomavirus (HPV) type 6/11. However, the specific mechanisms underlying the inhibition of the host's innate immune response by HPV remain unclear. For this purpose, we employed single-cell RNA sequencing to analyze the states of various immune cells in RRP samples post-HPV infection and utilized a cellular model of HPV infection to elucidate the mechanisms by which HPV evades the innate immune system in RRP. The results revealed distinct immune cell heterogeneity in RRP and demonstrated that HPV11 E7 can inhibit the phosphorylation of the stimulator of interferon genes protein, thereby circumventing the body's antiviral response. In vitro co-culture experiments demonstrated that stimulation of macrophages to produce interferon-beta induced the death of HPV-infected epithelial cells, also reducing HPV viral levels. In summary, our study preliminarily identifies the potential mechanisms by which HPV evades the host's antiviral immune response, as well as the latent antiviral functions exhibited by activated macrophages. This research serves as an initial exploration of antiviral immune evasion in RRP, laying a solid foundation for investigating immunotherapeutic approaches for the disease.IMPORTANCESurgical tumor reduction is the most common treatment for recurrent respiratory papillomatosis (RRP). One of the characteristics of RRP is its persistent recurrence, and multiple surgeries are usually required to control the symptoms. Recently, some adjuvant therapies have shown effectiveness, but none of them can completely clear human papillomavirus (HPV) infection, and thus, a localized antiviral immune response is significant for disease control; after all, HPV infection is limited to the epithelium. Inhibition of interferon-beta (IFN-ß) secretion by HPV11 E7 viral proteins in epithelial cells by affecting stimulator of interferon genes phosphorylation may account for the persistence of low-risk HPV replication in the RRP. Moreover, suppression of the IFN-I pathway in RRP cell types might provide clues regarding the hyporeactive function of local immune cells. However, activation of macrophage groups to produce IFN-ß can still destroy HPV-infected cells.

A hybrid deep learning framework for gene regulatory network inference from single-cell transcriptomic data.

Inferring gene regulatory networks (GRNs) based on gene expression profiles is able to provide an insight into a number of cellular phenotypes from the genomic level and reveal the essential laws underlying various life phenomena. Different from the bulk expression data, single-cell transcriptomic data embody cell-to-cell variance and diverse biological information, such as tissue characteristics, transformation of cell types, etc. Inferring GRNs based on such data offers unprecedented advantages for making a profound study of cell phenotypes, revealing gene functions and exploring potential interactions. However, the high sparsity, noise and dropout events of single-cell transcriptomic data pose new challenges for regulation identification. We develop a hybrid deep learning framework for GRN inference from single-cell transcriptomic data, DGRNS, which encodes the raw data and fuses recurrent neural network and convolutional neural network (CNN) to train a model capable of distinguishing related gene pairs from unrelated gene pairs. To overcome the limitations of such datasets, it applies sliding windows to extract valuable features while preserving the direction of regulation. DGRNS is constructed as a deep learning model containing gated recurrent unit network for exploring time-dependent information and CNN for learning spatially related information. Our comprehensive and detailed comparative analysis on the dataset of mouse hematopoietic stem cells illustrates that DGRNS outperforms state-of-the-art methods. The networks inferred by DGRNS are about 16% higher than the area under the receiver operating characteristic curve of other unsupervised methods and 10% higher than the area under the precision recall curve of other supervised methods. Experiments on human datasets show the strong robustness and excellent generalization of DGRNS. By comparing the predictions with standard network, we discover a series of novel interactions which are proved to be true in some specific cell types. Importantly, DGRNS identifies a series of regulatory relationships with high confidence and functional consistency, which have not yet been experimentally confirmed and merit further research.

Promote lipolysis in white adipocytes by magnetic hyperthermia therapy with Fe3O4microsphere-doped hydrogel.

Obesity has become an ongoing global crisis, since it increases the risks of cardiovascular disease, type 2 diabetes, fatty liver, cognitive decline, and some cancers. Adipose tissue is closely associated with the disorder of lipid metabolism. Several efforts have been made toward the modulation of lipid accumulation, but have been hindered by poor efficiency of cellular uptake, low safety, and uncertain effective dosage. Herein, we design an Fe3O4microsphere-doped composite hydrogel (Fe3O4microspheres @chitosan/ß-glycerophosphate/collagen), termed as Fe3O4@Gel, as the magnetocaloric agent for magnetic hyperthermia therapy (MHT), aiming to promote lipolysis in white adipocytes. The experimental results show that the obtained Fe3O4@Gel displays a series of advantages, such as fast sol-gel transition, high biocompatibility, and excellent magneto-thermal performance. MHT, which is realized by Fe3O4@Gel subjected to an alternating magnetic field, leads to reduced lipid accumulation, lower triglyceride content, and increased mitochondrial activity in white adipocytes. This work shows that Fe3O4@Gel-mediated MHT can effectively promote lipolysis in white adipocytesin vitro, which provides a potential approach to treat obesity and associated metabolic disorders.

Catalytic PMS oxidation universality of CuFe2O4/MnO2 heterojunctions at multiple application scenarios.

The magnetic CuFe2O4/MnO2 heterojunctions were prepared by hydrothermal method, and the effect of different reaction temperature on the physicochemical properties and catalytic activity was investigated. The CuFe2O4/MnO2 heterojunctions prepared at 100 °C can effectively activate peroxymonosulfate (PMS) at multiple application scenarios for degradation and mineralization of tetracycline, o-nitrophenol and ceftriaxone sodium under indoor light, visible light and dark condition. Additionally, the CuFe2O4/MnO2-PMS system showed high catalytic activity and anti-interference ability for degradation of pharmaceutical pollutants in natural water bodies and industrial wastewater. The TC removal efficiency in Qianhu Lake water, Ganjiang River water and tap water was about 88%, 92% and 89%, respectively. The CuFe2O4/MnO2-PMS system is also effective for actual pharmaceutical wastewater treatment with 77.9% of COD removal efficiency. Interestingly, the reactive species of CuFe2O4/MnO2-PMS system under visible light are different from those in dark condition, and the different catalytic mechanisms at multiple application scenarios were proposed. This work provides new insights into mechanism exploration of heterojunction catalyst for PMS activation.

A comprehensive overview and critical evaluation of gene regulatory network inference technologies.

Gene regulatory network (GRN) is the important mechanism of maintaining life process, controlling biochemical reaction and regulating compound level, which plays an important role in various organisms and systems. Reconstructing GRN can help us to understand the molecular mechanism of organisms and to reveal the essential rules of a large number of biological processes and reactions in organisms. Various outstanding network reconstruction algorithms use specific assumptions that affect prediction accuracy, in order to deal with the uncertainty of processing. In order to study why a certain method is more suitable for specific research problem or experimental data, we conduct research from model-based, information-based and machine learning-based method classifications. There are obviously different types of computational tools that can be generated to distinguish GRNs. Furthermore, we discuss several classical, representative and latest methods in each category to analyze core ideas, general steps, characteristics, etc. We compare the performance of state-of-the-art GRN reconstruction technologies on simulated networks and real networks under different scaling conditions. Through standardized performance metrics and common benchmarks, we quantitatively evaluate the stability of various methods and the sensitivity of the same algorithm applying to different scaling networks. The aim of this study is to explore the most appropriate method for a specific GRN, which helps biologists and medical scientists in discovering potential drug targets and identifying cancer biomarkers.

Double helix point spread function with variable spacing for precise 3D particle localization.

To extend the axial depth of nanoscale 3D-localization microscopy, we propose here a splicing-type vortex singularities (SVS) phase mask, which has been meticulously optimized with a Fresnel approximation imaging inverse operation. The optimized SVS DH-PSF has proven to have high transfer function efficiency with adjustable performance in its axial range. The axial position of the particle was computed by using both the main lobes' spacing and the rotation angle, an improvement of the localization precision of the particle. Concretely, the proposed optimized SVS DH-PSF, with a smaller spatial extent, can effectively reduce the overlap of nanoparticle images and realize the 3D localization of multiple nanoparticles with small spacing, with respect to PSFs for large axial 3D localization. Finally, we successfully conducted extensive experiments on 3D localization for tracking dense nanoparticles at 8µm depth with a numerical aperture of 1.4, demonstrating its great potential.

Laser frequency noise correction in LFM-based interferometric fiber-optic hydrophone array.

In this paper, we propose a novel time-division multiplexed (TDM) array for a large-scale interferometric fiber-optic hydrophone system, in which we introduce a power-optimized reference probe and effectively reduce the additional white noise while correcting for light source frequency noise. Laser frequency noise usually introduces appreciable phase noise during demodulation of interferometric fiber-optic hydrophones. In the previous means, one would introduce an additional probe isolated from the environment in sensor array, and use it as a reference to calibrate the demodulation results of the other actual sensors. However, while correcting, the reference probe also introduces a large white noise. In our array, the echo of the reference probe is higher than the other sensors, thus solving this problem. The novel array design is applied to our previously proposed fiber-optic hydrophone based on a linear frequency modulated (LFM) light source. Experiments show that the deterioration of phase noise floor caused by additional white noise is improved from at least 3 dB originally to within 1 dB. This paper analyzes the factors that need to be concerned for the successful implementation of correction algorithms in hydrophone systems based on LFM sources. Particular focus is given to the impact of the power optimization of reference probe on the white noise and the corrected phase noise. Our proposal allows a significant relaxation of the demanding linewidth requirement for interferometric hydrophone. It is shown that laser with linewidth of 338.06 MHz can replace that with 1.417 kHz in our new system, while achieves the same demodulation noise floor.

Engineering Escherichia coli native metabolism for efficient biosynthesis of orotate.

Orotate (OA) is a precursor of pyrimidine nucleotides and is widely used in food, pharmaceutical, and cosmetic industries. Although various microorganisms have been used for OA production, the production efficiency needs to be further improved for industrial application. In this study, we engineered Escherichia coli native metabolism for efficient OA production. The entire pathway was divided into the downstream OA synthesis, the midstream aspartate/glutamine supply, and the upstream glycolysis modules. First, the downstream module was optimized by disrupting pyrE to block OA consumption and release the feedback inhibition, and tuning expression of the biosynthetic genes. Second, the midstream pathway was enhanced by increasing the supply of the precursors and the cofactor nicotinamide adenine dinucleotide phosphate (NADPH). More importantly, we observed that pyrE disruption may lead to metabolic disorder as indicated by the accumulation of large amount of acetate. This problem was solved by reducing the flux of glycolysis. With these efforts, the final strain produced 80.3 g/L OA with a yield of 0.56 g/g glucose in fed-batch fermentation, which are the highest titer and yield reported so far. This work paves the way for industrial production of OA and represents as a good example of modulating cell metabolism for efficient chemical production.

Exploring the role of PMEPA1 in gastric cancer.

Although there are several treatments available for gastric cancer (GC), the prognosis of the disease is still poor due to many factors, such as late diagnosis and tumor heterogeneity. To identify potential therapeutic targets, bioinformatics techniques and clinical sample validation were employed and prostate transmembrane protein androgen induced 1 (PMEPA1) was selected for further study. In the present study, we found that elevated PMEPA1 expression correlates with a worse prognosis and weaker anti-tumor immunity in GC patients. Moreover, our study showed that PMEPA1 not only influences cell proliferation, clone formation, invasion, and migration in vitro, but also plays an important role in GC progression in vivo. Mechanically, PMEPA1 exerts its oncogenic effects through activating the Wnt/ß-catenin signaling pathway. Therefore, PMEPA1 is a potential target for treating GC effectively.

Aptamer-modified atomically precise gold nanoclusters as targeted nanozymes to scavenge reactive oxygen species in white adipocytes.

Oxidative stress caused by excessive reactive oxygen species (ROS) leads to the dysfunction of white adipocytes and white fat, and also promotes triglyceride storage by inhibiting the respiration of adipocytes directly. Nanozymes, as a new generation of artificial enzymes, have exhibited attractive potential in scavenging ROS and treatment of ROS-related diseases. Herein, aptamer-modified atomically precise gold Au25nanoclusters (Apt-Au25NCs), are employed as targeted nanozymes to scavenge ROS in white adipocytes. Our results show that Apt-Au25NCs have high targeting capability toward white adipocytes with low cytotoxicity. Furthermore, Apt-Au25NCs show high superoxide dismutase (SOD)-like and catalase (CAT)-like activity in a concentration-dependent manner, and also good thermal and pH stability compared with natural SOD and CAT. Finally, the efficiency of ROS scavenging by Apt-Au25NCs in white adipocytes is evaluated. This work demonstrates that Apt-Au25NCs, as targeted nanozymes, are efficient in scavenging ROS in white adipocytes, exhibiting promising potential for the treatment of obesity and related diseases.

Advanced inter-spacecraft offset frequency setting strategy for the Taiji program based on a two-stage optimization algorithm.

For space-based gravitational wave (GW) detection, the continuity of detection data acquisition is crucial to the inversion of wave sources and the realization of scientific goals. To control the inter-spacecraft beat-note frequency in an appropriate range for continuous gravitational wave detection and to reduce the upper bound of the beat-note frequency for improving the detection capability, a two-stage optimization algorithm is proposed to solve the offset frequency setting strategy in the Taiji program. The optimization objectives are the maximum offset frequency duration and minimum upper bound of the beat-note frequency. Considering all feasible phase-locked schemes, Doppler frequency shift, and the bandwidth of the phasemeter, a series of offset frequency setting strategies satisfying the conditions was obtained. The solution results show that the upper bound can be reduced to 16 MHz and, in this case, the offset frequency changes nine times with a minimum and maximum offset frequency duration of 90 days and 713 days, respectively. If the Doppler frequency shift is constrained, the minimum upper bound can be reduced to 14 MHz. When the minimum duration is increased, the minimum upper bound is increased. These results show that, by varying the offset frequency a limited number of times, the data continuity requirements of the Taiji program can be satisfied, and the phasemeter development difficulty and detection capability can be balanced, and may provide a reference for the phasemeter design, the setting of phase-locking schemes, and inter-spacecraft offset frequency in the Taiji program.

Enhanced Detection Precision of the Taiji Program by Frequency Setting Strategy Based on a Hierarchical Optimization Algorithm.

For space-based gravitational wave detection, a laser interferometric measurement system composed of a three-spacecraft formation offers the most rewarding bandwidth of astrophysical sources. There are no oscillators available that are stable enough so that each spacecraft could use its own reference frequency. The conversion between reference frequencies and their distribution between all spacecrafts for the synchronization of the different metrology systems is the job of the inter-spacecraft frequency setting strategy, which is important for continuously acquiring scientific data and suppressing measurement noise. We propose a hierarchical optimization algorithm to solve the frequency setting strategy. The optimization objectives are minimum total readout displacement noise and maximum beat-note frequency feasible range. Multiple feasible parameter combinations were obtained for the Taiji program. These optimized parameters include lower and upper bounds of the beat note, sampling frequency, pilot tone signal frequency, ultrastable clock frequencies, and modulation depth. Among the 20 Pareto optimal solutions, the minimum total readout displacement noise was 4.12 pm/Hz, and the maximum feasible beat-note frequency range was 23 MHz. By adjusting the upper bound of beat-note frequency and laser power transmitted by the telescope, we explored the effects of these parameters on the minimum total readout displacement noise and optimal local laser power in greater depth. Our results may serve as a reference for the optimal design of laser interferometry system instrument parameters and may ultimately improve the detection performance and continuous detection time of the Taiji program.

Method Comparison for Simulating Non-Gaussian Beams and Diffraction for Precision Interferometry.

In the context of simulating precision laser interferometers, we use several examples to compare two wavefront decomposition methods-the Mode Expansion Method (MEM) and the Gaussian Beam Decomposition (GBD) method-for their precision and applicability. To assess the performance of these methods, we define different types of errors and study their properties. We specify how the two methods can be fairly compared and based on that, compare the quality of the MEM and GBD through several examples. Here, we test cases for which analytic results are available, i.e., non-clipped circular and general astigmatic Gaussian beams, as well as clipped circular Gaussian beams, in the near, far, and extremely far fields of millions of kilometers occurring in space-gravitational wave detectors. Additionally, we compare the methods for aberrated wavefronts and their interaction with optical components by testing reflections from differently curved mirrors. We find that both methods can generally be used for decomposing non-Gaussian beams. However, which method is more accurate depends on the optical system and simulation settings. In the given examples, the MEM more accurately describes non-clipped Gaussian beams, whereas for clipped Gaussian beams and the interaction with surfaces, the GBD is more precise.

Phase optimization algorithm for 3D particle localization with large axial depth.

We propose an optimization algorithm based on Fresnel approximation (FA) imaging to optimize an extended-axial-depth point spread function (PSF) for 3D particle localization. The transfer function efficiency of the PSF is improved by repeatedly imposing constraints in the object plane, the spatial domain, and the Fourier domain. During the iterative calculation, the effective photon number or Cramer-Rao lower bound is used as the termination condition of the iteration. The algorithm allows flexible adjustment of the peak intensity ratio of the two main lobes. Moreover, the transfer function efficiency can be balanced by increasing the weight of the modulation function of the expected PSF at each axial position. The twin-Airy (TA) PSF optimized by the FA optimization algorithm does not require complex post-processing, whereas post-processing is an essential step for the unoptimized TA-PSF. The optimization algorithm is significant for extended-axial-depth PSFs used for 3D particle localization, as it improves localization precision and temporal resolution.

Different Bonding Defects on Dual-Metal Single-Atom Electrocatalyst CoZnN6 (OH) for Oxygen Reduction Reaction.

Since dual-metal single-atom catalyst (CoZnN/C) has been experimentally synthesized by atomically arching CoZn on N-doped carbon nanofibers and exhibited potential electrocatalysis activity towards oxygen reduction reaction (ORR), we perform first-principles calculations to identify the highly active sites at different defects by comparing the four-step ORR processes on the constructed four CoZnN6 models on graphene. The corresponding N-edge effect, dopant effect, and C-edge ring-closing effect are evaluated with the ORR evolution on different bonding environments, including pristine CoZnN6 (OH), nanoribbon (NR) along zigzag direction, substitution of carbon/oxygen (C/O substitution), and C-edge ring-closing configurations. OH-ligand is shown to significantly improve the ORR activities for all the considered structures. Especially, C-substituted CoZnN6 (OH), NR-CoZnN5 O(OH) and CoZnN6 (OH) with C-edge-effect exhibit obviously reduced overpotentials (ηlim =0.28, 0.48 and 0.41 V) of rate-determining steps among all the considered nine candidates. By plotting the relationship between the limiting potentials (Ulim ) and free energies of intermediate *OH (ΔGOH* ), two prior catalysts of pristine-CoZnN5 C(OH) and defect-CoZnN6 CH(OH) are located near the top of the volcano curve with higher Ulim =0.95 and 0.82 V than Pt(111) (Ulim =0.80 V), implying that C-substitution could facilitate ORR performance in pristine- and defect-CoZnN6 (OH) bonding situation.

Inter-spacecraft offset frequency setting strategy in the Taiji program.

For controlling the beat frequency of heterodyne interferometry so that the Taiji program can detect gravitational waves in space, an offset frequency setting strategy based on a linear programming algorithm is proposed. Considering factors such as Doppler frequency shift, phase-locking scheme, laser relative intensity noise, and phase detector bandwidth, inter-spacecraft offset frequency setting results suitable for the Taiji program are obtained. During the six years of running the detection process, the use of frequency bounds in the range of [5 MHz, 25 MHz] showed that offset frequencies will remain unchanged for a maximum of 1931 days. If the upper and lower bounds are adjusted, and the relative motion between spacecraft is further constrained, the offset frequencies do not need to change during the time of the mission. These results may provide insights into selecting the phase detector and designing operation parameters such as orbit and laser modulation frequency in the Taiji program.

Online Health Information Seeking Behaviors Among Older Adults: Systematic Scoping Review.

BACKGROUND: With the world's population aging, more health-conscious older adults are seeking health information to make better-informed health decisions. The rapid growth of the internet has empowered older adults to access web-based health information sources. However, research explicitly exploring older adults' online health information seeking (OHIS) behavior is still underway. OBJECTIVE: This systematic scoping review aims to understand older adults' OHIS and answer four research questions: (1) What types of health information do older adults seek and where do they seek health information on the internet? (2) What are the factors that influence older adults' OHIS? (3) What are the barriers to older adults' OHIS? (4) How can we intervene and support older adults' OHIS? METHODS: A comprehensive literature search was performed in November 2020, involving the following academic databases: Web of Science; Cochrane Library database; PubMed; MEDLINE; CINAHL Plus; APA PsycINFO; Library and Information Science Source; Library, Information Science and Technology Abstracts; Psychology and Behavioral Sciences Collection; Communication & Mass Media Complete; ABI/INFORM; and ACM Digital Library. The initial search identified 8047 publications through database search strategies. After the removal of duplicates, a data set consisting of 5949 publications was obtained for screening. Among these, 75 articles met the inclusion criteria. Qualitative content analysis was performed to identify themes related to the research questions. RESULTS: The results suggest that older adults seek 10 types of health information from 6 types of internet-based information sources and that 2 main categories of influencing factors, individual-related and source-related, impact older adults' OHIS. Moreover, the results reveal that in their OHIS, older adults confront 3 types of barriers, namely individual, social, and those related to information and communication technologies. Some intervention programs based on educational training workshops have been created to intervene and support older adults' OHIS. CONCLUSIONS: Although OHIS has become increasingly common among older adults, the review reveals that older adults' OHIS behavior is not adequately investigated. The findings suggest that more studies are needed to understand older adults' OHIS behaviors and better support their medical and health decisions in OHIS. Based on the results, the review proposes multiple objectives for future studies, including (1) more investigations on the OHIS behavior of older adults above 85 years; (2) conducting more longitudinal, action research, and mixed methods studies; (3) elaboration of the mobile context and cross-platform scenario of older adults' OHIS; (4) facilitating older adults' OHIS by explicating technology affordance; and (5) promoting and measuring the performance of OHIS interventions for older adults.

Online Health Information Seeking Among Patients With Chronic Conditions: Integrating the Health Belief Model and Social Support Theory.

BACKGROUND: Chronic diseases are the leading causes of death and disability. With the growing patient population and climbing health care expenditures, researchers and policy makers are seeking new approaches to improve the accessibility of health information on chronic diseases while lowering costs. Online health information sources can play a substantial role in effective patient education and health communication. However, some contradictory evidence suggests that patients with chronic conditions may not necessarily seek online health information. OBJECTIVE: This study aims to integrate 2 theories (ie, the health belief model and social support theory) and a critical health literacy perspective to understand online health information seeking (OHIS) among patients with chronic conditions. METHODS: We used the survey method to collect data from online chronic disease communities and groups on social media platforms. Eligible participants were consumers with at least 1 chronic condition and those who have experience with OHIS. A total of 390 valid questionnaires were collected. The partial least squares approach to structural equation modeling was employed to analyze the data. RESULTS: The results suggested that perceived risk (t=3.989, P<.001) and perceived benefits (t=3.632, P<.001) significantly affected patients' OHIS. Perceived susceptibility (t=7.743, P<.001) and perceived severity (t=8.852, P<.001) were found to influence the perceived risk of chronic diseases significantly. Informational support (t=5.761, P<.001) and emotional support (t=5.748, P<.001) also impacted the perceived benefits of online sources for patients. In addition, moderation analysis showed that critical health literacy significantly moderated the link between perceived risk and OHIS (t=3.097, P=.002) but not the relationship between perceived benefits and OHIS (t=0.288, P=.774). CONCLUSIONS: This study shows that the health belief model, when combined with social support theory, can predict patients' OHIS. The perceived susceptibility and severity can effectively explain perceived risk, further predicting patients' OHIS. Informational support and emotional support can contribute to perceived benefits, thereby positively affecting patients' OHIS. This study also demonstrated the important negative moderating effects of critical health literacy on the association between perceived risk and OHIS.

Three-dimensional diffusion coefficient measurement by a large depth-of-field rotating point spread function.

A prominent challenge in single-molecule localization microscopy is the real-time, fast, and accurate localization of nano-objects moving in three-dimensional (3D) samples. A well-established method for 3D single-molecule localization is the double-helix pointspread-function (DH-PSF) engineering, which uses additional optical elements to make the PSF exhibit different rotation angles with different nanoparticle depths. However, the compact main lobe size, effective detection depth, and precise conversion between rotation angle and depth are necessary, posing challenges to the DH-PSF generation method. Here we generate a more compact DH-PSF using Fresnel-zone-based spiral phases, and the pure phase mask achieves high transmission efficiency. The final generated DH-PSFs have a linear rotation rate at each axial position, showing a more accurate rotation angle and depth conversion. The Cramer-Rao lower limit calculation results show that the axial depth of DH-PSF extends to ∼11µm with an axial localization precision of ∼45nm at 3000 photons and average background noise of 15. We measured the diffusion coefficient of nanospheres in different concentrations of glycerol using the generated DH-PSF. The measured results are within 6% error from the theoretical values, indicating the superior performance of the DH-PSF for nanoparticle diffusion coefficient measurements.

Diagnostic and treatment protocol for a patient with temporomandibular disorder using a stabilization splint and temporary anchorage devices.

Treatment of orthodontic patients with temporomandibular disorder (TMD) is challenging for orthodontists because of the TMD signs and symptoms and unstable mandible position, which may lead to improper diagnosis and treatment design. This case report presents a 22-year-old woman with proclined maxillary incisors and TMD. First, stabilization splint therapy was implemented to eliminate temporomandibular joint pain and to obtain the stable adapted centric posture. Subsequently, orthodontic treatment was initiated on the basis of a definitive diagnosis made from the postsplint records. Temporary anchorage devices were used to intrude maxillary molars and distalize the maxillary dental arch. Favorable soft tissue, skeletal, and dental relationship were accomplished after 12 months of comprehensive orthodontic treatment. Functional occlusion was established with teeth as well as vacuum-formed retainers. Excellent posttreatment stability was maintained after a 20-month retention.