Second harmonic generation microscopy of electromechanical reshaping on corneal collagen.

Refractive errors remain a global health concern, as a large proportion of the world's population is myopic. Current ablative approaches are costly, not without risks, and not all patients are candidates for these procedures. Electromechanical reshaping (EMR) has been explored as a viable cost-effective modality to directly shape tissues, including cartilage. In this study, stromal collagen structure and fibril orientation was examined before and after EMR with second-harmonic generation microscopy (SHG), a nonlinear multiphoton imaging method that has previously been used to study native corneal collagen with high spatial resolution. EMR, using a milled metal contact lens and potentiostat, was performed on the corneas of five extracted rabbit globes. SHG was performed using a confocal microscopy system and all images underwent collagen fibril orientation analysis. The collagen SHG signal in controls is uniform and is similarly seen in samples treated with pulsed potential, while continuous EMR specimens have reduced, nonhomogeneous signal. Collagen fibril orientation in native tissue demonstrates a broad distribution with suggestion of another peak evolving, while with EMR treated eyes a bimodal characteristic becomes readily evident. Pulsed EMR may be a means to correct refractive errors, as when comparing its SHG signal to negative control, preservation of collagen structures with little to no damage is observed. From collagen fiber orientation analysis, it can be inferred that simple DC application alters the structure of collagen. Future studies will involve histological assessment of these layers and multi-modal imaging analysis of dosimetry.

The Critical Role of Intracellular Bacterial Communities in Uncomplicated Recurrent Urinary Cystitis: A Comprehensive Review of Detection Methods and Diagnostic Potential.

Urinary tract infections (UTIs) are among the most common bacterial infections worldwide and are particularly prevalent in women. Recurrent UTIs significantly diminish quality of life due to their symptoms and frequent relapses. Patients often experience immediate relapse following slightly strenuous activities or intense psychological stress. In this review, we explore why infections persist despite the advent of various treatments and suggest strategies to manage recurrent cystitis by targeting the mechanisms of adhesion and infection. Vitamin D levels and the expression of neutrophil gelatinase-associated lipocalin are linked to the recurrence of UTIs. During a UTI, bacteria employ adhesins to invade the urinary tract, adhere to urothelial cells, and then penetrate these cells, where they rapidly multiply to establish intracellular bacterial communities. Bacteria can also form quiescent intracellular reservoirs that escape immune responses and antibiotic treatments, leading to recurrence under certain conditions. The surface proteins of bacteria and D-mannose are crucial in the adhesion of bacteria to the urothelium. Understanding these processes provides valuable insights into potential therapeutic approaches that focus on preventing bacterial attachment and cluster formation. By disrupting the ability of bacteria to adhere to and form clusters on cells, we can better manage recurrent UTIs and improve patient outcomes.

Inhibition of Granule Cell Dispersion and Seizure Development by Astrocyte Elevated Gene-1 in a Mouse Model of Temporal Lobe Epilepsy.

Although granule cell dispersion (GCD) in the hippocampus is known to be an important feature associated with epileptic seizures in temporal lobe epilepsy (TLE), the endogenous molecules that regulate GCD are largely unknown. In the present study, we have examined whether there is any change in AEG-1 expression in the hippocampus of a kainic acid (KA)-induced mouse model of TLE. In addition, we have investigated whether the modulation of astrocyte elevated gene-1 (AEG-1) expression in the dentate gyrus (DG) by intracranial injection of adeno-associated virus 1 (AAV1) influences pathological phenotypes such as GCD formation and seizure susceptibility in a KA-treated mouse. We have identified that the protein expression of AEG-1 is upregulated in the DG of a KA-induced mouse model of TLE. We further demonstrated that AEG-1 upregulation by AAV1 delivery in the DG-induced anticonvulsant activities such as the delay of seizure onset and inhibition of spontaneous recurrent seizures (SRS) through GCD suppression in the mouse model of TLE, while the inhibition of AEG-1 expression increased susceptibility to seizures. The present observations suggest that AEG-1 is a potent regulator of GCD formation and seizure development associated with TLE, and the significant induction of AEG-1 in the DG may have therapeutic potential against epilepsy.

Electrochemical Lipolysis Induces Adipocyte Death and Fat Necrosis: In Vivo Pilot Study in Pigs.

BACKGROUND: Current minimally invasive fat reduction modalities use equipment that can cost thousands of U.S. dollars. Electrochemical lipolysis (ECLL), using low-cost battery and electrodes (approximately $10), creates acid/base within fat (width, approximately 3 mm), damaging adipocytes. Longitudinal effects of ECLL have not been studied. In this pilot study, the authors hypothesize that in vivo ECLL induces fat necrosis, decreases adipocyte number/viability, and forms lipid droplets. METHODS: Two female Yorkshire pigs (50 to 60 kg) received ECLL. In pig 1, 10 sites received ECLL, and 10 sites were untreated. In pig 2, 12 sites received ECLL and 12 sites were untreated. For ECLL, two electrodes were inserted into dorsal subcutaneous fat and direct current was applied for 5 minutes. Adverse effects of excessive pain, bleeding, infection, and agitation were monitored. Histology, live-dead (calcein, Hoechst, ethidium homodimer-1), and morphology (Bodipy and Hoechst) assays were performed on day 0 and postprocedure days 1, 2, 7, 14 (pig 1 and pig 2), and 28 (pig 2). Average particle area, fluorescence signal areas, and adipocytes and lipid droplet numbers were compared. RESULTS: No adverse effects occurred. Live-dead assays showed adipocyte death on the anode on days 0 to 7 and the cathode on days 1 to 2 (not significant). Bodipy showed significant adipocyte loss at all sites ( P < 0.001) and lipid droplet formation at the cathode site on day 2 ( P = 0.0046). Histology revealed fat necrosis with significant increases in average particle area at the anode and cathode sites by day 14 (+277.3% change compared with untreated, P < 0.0001; +143.4%, P < 0.0001) and day 28 (+498.6%, P < 0.0001; +354.5%, P < 0.0001). CONCLUSIONS: In vivo ECLL induces fat necrosis in pigs. Further studies are needed to evaluate volumetric fat reduction. CLINICAL RELEVANCE STATEMENT: In vivo ECLL induces adipocyte death and fat necrosis. ECLL has the potential to be utilized in body fat contouring.

Hybrid Bladder Phantom to Validate Next-Generation Optical Wearables for Neurogenic Bladder Volume Monitoring.

PURPOSE: The development of optics-based wearables for bladder volume monitoring has emerged as a significant topic in recent years. Given the innovative nature of this technology, there is currently no bladder phantom available to effectively validate these devices against more established gold standards, such as ultrasound. In this study, we showcase and demonstrate the performance of our hybrid bladder phantom by using an optical device and making comparisons with ultrasound. METHODS: A series of validation tests, including phantom repeatability, ultrasound scanning, and an optical test, were performed. A near-infrared optical device was utilized to conduct diffuse optical spectroscopy (DOS). Machine learning models were employed to construct predictive models of volume using optical signals. RESULTS: The size and position of an embedded balloon, serving as an analog for the bladder, were shown to be consistent when infused with 100 mL to 350 mL of water during repeatability testing. For DOS data, we present 7 types of machine learningbased models based on different optical signals. The 2 best-performing models demonstrated an average absolute volume error ranging from 12.7 mL to 19.0 mL. CONCLUSION: In this study, we introduced a hybrid bladder phantom designed for the validation of near-infrared spectroscopy-based bladder monitoring devices in comparison with ultrasound techniques. By offering a reproducible and robust validation tool, we aim to support the advancement of next-generation optical wearables for bladder volume monitoring.

A narrative review on the use of near-infrared spectroscopy to monitor bladder volume and in vitro validation approaches.

Background and Objective: Current guidelines for patients with neurogenic bladder (NB) dysfunction suggest the use of self-intermittent catheterization with adherence to catheterization timers. Due to biorhythmic variability, unpredictable voiding times may occur. As a result, many patients abstain from extended social or work activities, turn to more secluded lifestyles, and generally experience a decrease in quality of life. Being able to know when to void is essential for patients with NB dysfunction. To solve the problem of variable void timings, wearable devices using near-infrared spectroscopy (NIRS) have been emergent and showed potential for bladder volume monitoring. Therefore, in this review, we provided a comprehensive overview of research which implemented NIRS for bladder volume monitoring, and discussed how the researchers validated their device by in-vitro methods and suggested a potential validation approach. Methods: A literature search using PubMed and Google Scholar was conducted on February 2023. Publications involving bladder volume monitoring incorporating NIRS technique with in-vitro validation was considered for review. Key Content and Findings: Due to the novelty of NIRS being applied to bladder monitoring, there are a few possibilities to effectively validate this technique through in-vitro methods. Ballistics gel, which has been proven to be a versatile material for applications involving ultrasound, could be a suitable material when constructing a bladder phantom for in-vitro validation of NIRS technology. Conclusions: By outlining a more standardized in-vitro validation model based on ballistics gel, we hope to facilitate development in this field towards a more accurate and robust NIRS-based bladder monitoring device.

Cognitive training based on functional near-infrared spectroscopy neurofeedback for the elderly with mild cognitive impairment: a preliminary study.

Introduction: Mild cognitive impairment (MCI) is often described as an intermediate stage of the normal cognitive decline associated with aging and dementia. There is a growing interest in various non-pharmacological interventions for MCI to delay the onset and inhibit the progressive deterioration of daily life functions. Previous studies suggest that cognitive training (CT) contributes to the restoration of working memory and that the brain-computer-interface technique can be applied to elicit a more effective treatment response. However, these techniques have certain limitations. Thus, in this preliminary study, we applied the neurofeedback paradigm during CT to increase the working memory function of patients with MCI. Methods: Near-infrared spectroscopy (NIRS) was used to provide neurofeedback by measuring the changes in oxygenated hemoglobin in the prefrontal cortex. Thirteen elderly MCI patients who received CT-neurofeedback sessions four times on the left dorsolateral prefrontal cortex (dlPFC) once a week were recruited as participants. Results: Compared with pre-intervention, the activity of the targeted brain region increased when the participants first engaged in the training; after 4 weeks of training, oxygen saturation was significantly decreased in the left dlPFC. The participants demonstrated significantly improved working memory compared with pre-intervention and decreased activity significantly correlated with improved cognitive performance. Conclusion: Our results suggest that the applications for evaluating brain-computer interfaces can aid in elucidation of the subjective mental workload that may create additional or decreased task workloads due to CT.

Gene Expression Profiles of Long-Chain Acyl-Coenzyme A Dehydrogenase, Nuclear Distribution C-Containing Protein 3, and Receptor Tyrosine Kinase Tie-1 in Swimming Larva of Sea Cucumber Apostichopus japonicus.

The sea cucumber, Apostichopus japonicus, is one of the most valuable aquatic species. The color of body wall and appearance are important for the value of sea cucumbers. To examine expression pattern of long-chain acyl-coenzyme A dehydrogenase (LCAD), nuclear distribution C-containing protein 3 (NUDCD3), and receptor tyrosine kinase Tie-1 (TIE1), previously reported as differently expressed genes during the pigmentation of sea cucumber, we analyzed the temporal profiles of LCAD, NUDCD3, and TIE1 mRNAs in LED-exposed and light-shielded A. japonicus. Real-time quantitative PCR revealed that the LCAD, NUDCD3, and TIE1 mRNAs from the juveniles at 40-60 days post-fertilization (dpf) exhibited increasing patterns as compared to those of an early developmental larva (6-dpf). At 60-dpf juveniles, the LCAD and TIE1 mRNA levels of LED-exposed individuals were higher than those of light-shielded ones, whereas at 40-dpf and 50-dpf juveniles, the NUDCD3 mRNA expression was higher in the light-shielded condition (p<0.05). In the pigmented juveniles (90-dpf), the LCAD and TIE1 mRNA levels tended to show higher levels in red individuals than those in green ones, but there was a conversely higher level of NUDCD3 mRNA in green larva. In situ examination of LCAD and NUDCD3 mRNAs in light-shielded 6-dpf larva revealed that both genes are mainly expressed in the internal organs compared to the body surface. Together, these results may provide insights into the differential gene expression of LCAD, NUDCD3, and TIE1 during pigmentation process of the sea cucumber.

Spectral correction of light emitting diodes enables accurate hydration ratio calculation using narrowband diffuse reflectance spectroscopy.

Significance: Light emitting diodes (LEDs) are commonly utilized for tissue spectroscopy due to their small size, low cost, and simplicity. However, LEDs are often approximated as single-wavelength devices despite having relatively broad spectral bandwidths. When paired with photodiodes, the wavelength information of detected light cannot be resolved. This can result in errors during chromophore concentration calculations. These errors are particularly apparent when analyzing water and fat in the 900 to 1000 nm window where the spectral bandwidth of LEDs can encompass much of the analysis region, resulting in intense crosstalk. Aim: We utilize and present a spectral correction (SC) algorithm to correct for the spectral bandwidth of LEDs. We show the efficacy using a narrowband technique of spectrally broad and overlapping LEDs. Approach: Narrowband diffuse reflectance spectroscopy (nb-DRS), a technique capable of quantifying the hydration ratio (RH2O) of turbid media, was utilized. nb-DRS typically requires a broadband light source and spectrometer. We reduce the hardware to just five LEDs and a photodiode detector, relying on SC to compensate for spectral crosstalk. The effectiveness of our SC approach was tested in simulations as well as in an emulsion phantom and limited selection of human tissue. Results: In simulations, we show that calculated RH2O errors increased with the spectral bandwidth of LEDs but could be corrected using SC. Likewise, in emulsions, we found an average error of 8.7% (maximum error 14%) if SC was not used. By contrast, applying SC reduced the average error to 2.2% (maximum error of 6.4%). We show that despite utilizing multiple, spectrally broad, and overlapping LEDs, SC was still able to restore the performance of our narrowband method, making it comparable to a much larger full broadband system.

Advancing Patient Care: Innovative Use of Near-Infrared Spectroscopy for Monitoring Urine Volume in Neurogenic Bladder.

PURPOSE: Current guidelines recommend clean intermittent catheterization (CIC) at regular time intervals for patients with spinal cord injuries; however, many patients experience difficulties. Performing time-based CIC outside the home is a significant burden for patients. In this study, we aimed to overcome the limitations of the current guidelines by developing a digital device to monitor bladder urine volume in real-time. METHODS: The optode sensor is a near-infrared spectroscopy (NIRS)-based wearable device intended to be attached to the skin of the lower abdomen where the bladder is located. The sensor's primary function is to detect changes in urine volume within the bladder. An in vitro study was conducted using a bladder phantom that mimicked the optical properties of the lower abdomen. To validate the data in the human body at the proof-of-concept level, one volunteer attached the device to the lower abdomen to measure the light intensity between the first voiding and immediately before the second voiding. RESULTS: The degree of attenuation at the maximum test volume was equivalent across experiments, and the optode sensor with multiplex measurements demonstrated robust performance for patient diversity. Moreover, the symmetric feature of the matrix was deemed a potential parameter for identifying the accuracy of sensor localization in a deep-learning model. The validated feasibility of the sensor showed almost the same results as an ultrasound scanner, which is routinely used in the clinical field. CONCLUSION: The optode sensor of the NIRS-based wearable device can measure the urine volume in the bladder in real-time.

Pathophysiological Role of Microglial Activation Induced by Blood-Borne Proteins in Alzheimer's Disease.

The blood-brain barrier (BBB) restricts entry of neurotoxic plasma components, blood cells, and pathogens into the brain, leading to proper neuronal functioning. BBB impairment leads to blood-borne protein infiltration such as prothrombin, thrombin, prothrombin kringle-2, fibrinogen, fibrin, and other harmful substances. Thus, microglial activation and release of pro-inflammatory mediators commence, resulting in neuronal damage and leading to impaired cognition via neuroinflammatory responses, which are important features observed in the brain of Alzheimer's disease (AD) patients. Moreover, these blood-borne proteins cluster with the amyloid beta plaque in the brain, exacerbating microglial activation, neuroinflammation, tau phosphorylation, and oxidative stress. These mechanisms work in concert and reinforce each other, contributing to the typical pathological changes in AD in the brain. Therefore, the identification of blood-borne proteins and the mechanisms involved in microglial activation and neuroinflammatory damage can be a promising therapeutic strategy for AD prevention. In this article, we review the current knowledge regarding the mechanisms of microglial activation-mediated neuroinflammation caused by the influx of blood-borne proteins into the brain via BBB disruption. Subsequently, the mechanisms of drugs that inhibit blood-borne proteins, as a potential therapeutic approach for AD, along with the limitations and potential challenges of these approaches, are also summarized.

Development of a Particle Filter-Based Path Tracking Algorithm of Autonomous Trucks with a Single Steering and Driving Module Using a Monocular Camera.

Recently, in various fields, research into the path tracking of autonomous vehicles and automated guided vehicles has been conducted to improve worker safety, convenience, and work efficiency. For path tracking of various systems applied to autonomous driving technology, it is necessary to recognize the surrounding environment, determine technology accordingly, and develop control methods. Various sensors and artificial-intelligence-based perception methods have limitations in that they must learn a large amount of data. Therefore, a particle-filter-based path tracking algorithm using a monocular camera was used for the recognition of target RGB. The path tracking errors were calculated and a linear-quadratic-regulator-based desired steering angle were derived. The autonomous trucks were steered and driven using a pulse-width-modulation-based steering and driving motor. Based on an autonomous truck with a single steering and driving module, it was verified that the path tracking could be used in three evaluation scenarios. To compare the LQR-based path tracking control performance proposed in this paper, an elliptical path tracking scenario using a conventional sliding mode control with robust control performance was performed. The results show that the RMS of the lateral preview error of the SMC was approximately 18% larger than that of the LQR-based method.

Mesenchymal Stem Cell Transplantation Ameliorates Ara-C-Induced Motor Deficits in a Mouse Model of Cerebellar Ataxia.

This study investigated the therapeutic effects of transplanting human mesenchymal stem cells (hMSCs) into wild-type mice that were intraperitoneally administered cytosine arabinoside (Ara-C) to develop cerebellar ataxia (CA) during the first three postnatal days. hMSCs were intrathecally injected into 10-week-old mice once or thrice at 4-week intervals. Compared to the nontreated mice, the hMSC-treated mice showed improved motor and balance coordination, as measured using the rotarod, open-field, and ataxic scoring assessments, and increased protein levels in Purkinje and cerebellar granule cells, as measured using calbindin and NeuN protein markers. Multiple hMSC injections preserved Ara-C-induced cerebellar neuronal loss and improved cerebellar weight. Furthermore, the hMSC implantation significantly elevated the levels of neurotrophic factors, including brain-derived and glial cell line-derived neurotrophic factors, and suppressed TNF-α-, IL-1ß-, and iNOS-mediated proinflammatory responses. Collectively, our results demonstrate that hMSCs exhibit therapeutic potential for Ara-C-induced CA by protecting neurons through the stimulation of neurotrophic factors and inhibition of cerebellar inflammatory responses, which can improve motor behavior and alleviate ataxia-related neuropathology. In summary, this study suggests that hMSC administration, particularly multiple treatments, can effectively treat ataxia-related symptoms with cerebellar toxicity.

pKr-2 induces neurodegeneration via upregulation of microglial TLR4 in the hippocampus of AD brain.

We recently demonstrated that prothrombin kringle-2 (pKr-2) derived from blood-brain barrier (BBB) disruption could induce hippocampal neurodegeneration and object recognition impairment through neurotoxic inflammatory responses in the five familial Alzheimer's disease mutation (5XFAD) mice. In the present study, we aimed to determine whether pKr-2 induces microglial activation by stimulating toll-like receptor 4 (TLR4) upregulation and examine whether this response contributes to pKr-2-induced neuroinflammatory damage in the hippocampi of mice models. We observed that inflammatory responses induced by pKr-2 administration in the hippocampi of wild-type mice were significantly abrogated in TLR4-deficient mice (TLR4-/-), and caffeine supply or rivaroxaban treatment that inhibits the overexpression of hippocampal pKr-2 reduced TLR4 upregulation in 5XFAD mice, resulting in the inhibition of neuroinflammatory responses. Similar to the expression patterns of pKr-2, TLR4, and the TLR4 transcription factors, PU.1 and p-c-Jun, seen in the postmortem hippocampal tissues of Alzheimer's disease (AD) patients, our results additionally showed the influence of transcriptional regulation on TLR4 expression following pKr-2 expression in triggering the production of neurotoxic inflammatory mediators. Therefore, we conclude that pKr-2 may play a role in initiating upregulation of microglial TLR4, consequently inducing hippocampal neurodegeneration. Furthermore, the control of pKr-2-induced microglial TLR4 could be a useful therapeutic strategy against hippocampal neurodegeneration in AD.

In vivo electrochemical lipolysis of fat in a Yucatan pig model: A proof of concept study.

OBJECTIVES: Traditional fat contouring is now regularly performed using numerous office- based less invasive techniques. However, some limitations of these minimally invasive techniques include high cost or limited selectivity with performing localized contouring and reduction of fat. These shortcomings may potentially be addressed by electrochemical lipolysis (ECLL), a novel approach that involves the insertion of electrodes into tissue followed by application of a direct current (DC) electrical potential. This results in the hydrolysis of tissue water creating active species that lead to fat necrosis and apoptosis. ECLL can be accomplished using a simple voltage-driven system (V-ECLL) or a potential-driven feedback cell (P-ECLL) both leading to water electrolysis and the creation of acid and base in situ. The aim of this study is to determine the long-lasting effects of targeted ECLL in a Yucatan pig model. METHODS: A 5-year-old Yucatan pig was treated with both V-ECLL and P-ECLL in the subcutaneous fat layer using 80:20 platinum:iridium needle electrodes along an 8 cm length. Dosimetry parameters included 5 V V-ECLL for 5, 10, and 20 minutes, and -1.5 V P-ECLL, -2.5 V P-ECLL, -3.5 V P-ECLL for 5 minutes. The pig was assessed for changes in fat reduction over 3 months with digital photography and ultrasound. After euthanasia, tissue sections were harvested and gross pathology and histology were examined. RESULTS: V-ECLL and P-ECLL treatments led to visible fat reduction (12.1%-27.7% and 9.4%-40.8%, respectively) and contour changes across several parameters. An increased reduction of the superficial fat layer occurred with increased dosimetry parameters with an average charge transfer of 12.5, 24.3, and 47.5 C transferred for 5 V V-ECLL for 5, 10, and 20 minutes, respectively, and 2.0, 11.5, and 24.0 C for -1.5 V P-ECLL, -2.5 V P-ECLL, -3.5 V P-ECLL for 5 minutes, respectively. These dose-dependent changes were also evidenced by digital photography, gross pathology, ultrasound imaging, and histology. CONCLUSIONS: ECLL results in selective damage and long-lasting changes to the adipose layer in vivo. These changes are dose-dependent, thus allowing for more precise contouring of target areas. P-ECLL has greater efficiency and control of total charge transfer compared to V-ECLL, suggesting that a low-voltage potentiostat treatment can result in fat apoptosis equivalent to a high-voltage DC system.

Electrochemical lipolysis of subcutaneous adipose tissue in a porcine animal model.

OBJECTIVES: There is a considerable demand for noninvasive low-cost fat reduction methods with fewer side effects and shorter recovery times. This study aims to develop a fat-reduction method through electrochemical lipolysis of subcutaneous adipocytes using needle-based electrodes, body tissue fluids, and electrical current application. METHODS: Electrochemical lipolysis was performed by inserting a 4-pin needle electrode connected to a DC power supply into the pig's abdomen. Applied electrical current (0.5 and 1 mA) and treatment time (5 or 10 minutes) were varied systematically. Ultrasound imaging was performed before and after treatment to determine changes in fat thickness. Tissue samples were collected at 0, 2, and 4 weeks posttreatment for histological evaluation to determine the mechanism of action and the procedure's efficacy. RESULTS: Electrochemical subcutaneous adipose tissue lipolysis in a porcine model was achieved through hydrolysis of physiologic fluid within the vicinity of the inserted electrode where an electric current is applied, leading to localized disruption of fat cell membranes and necrosis. Electric current configuration 1.0 mA showed more pronounced lipolysis effects applied for 10 minutes, significantly decreasing adipocyte content per treatment area. The electrochemical treatment method also stimulates collagen synthesis, which helps reduce fat. CONCLUSIONS: Electrochemical lipolysis is a potential new noninvasive localized technique to reduce fat. The treatment method induces fat cell necrosis via in situ reduction-oxidation reaction by the electrochemical activation of physiologic fluid in the surrounding tissue. Electrochemical lipolysis is a simple, low-cost, fat-reducing treatment method without harmful side effects.

Heliorhodopsin Helps Photolyase to Enhance the DNA Repair Capacity.

Light quality is a significant factor for living organisms that have photosensory systems, such as rhodopsin, a seven alpha-helical transmembrane protein with the retinal chromophore. Here, we report, for the first time, the function of new rhodopsin, which is an inverted 7-transmembrane protein, isolated from Trichococcus flocculiformis. T. flocculiformis heliorhodopsin (TfHeR) works as a regulatory helper rhodopsin that binds with class 2 cyclobutane pyrimidine dimer (CPDII) photolyase to broaden the spectrum and upregulate DNA repair activity. We have confirmed their interaction through isothermal titration calorimetry (dissociation constant of 21.7 µM) and identified the charged residues for the interaction. Based on in vivo and in vitro experiments, we showed that the binding of heliorhodopsin with photolyase improved photolyase activity by about 3-fold to repair UV-caused DNA damage. Also, the DNA repair activity of TfHeR/T. flocculiformis photolyase (TfPHR) was observed in the presence of green light. Our results suggested that heliorhodopsin directly controls the activity of photolyase and coevolves to broaden the activity spectrum by protein-protein interaction. IMPORTANCE This study reports a function for Heliorhodopsin working as a regulatory helper rhodopsin that with CPDII photolyase to broaden the spectrum and upregulating the DNA repair activity. Our results suggested that heliorhodopsin directly controls photolyase activity and coevolves to broaden the DNA repair capacity by protein-protein interaction.

Pattern Analysis of Laser Fiber Degradation According to the Laser Setting: In Vitro Study of the Double-Firing Phenomenon.

BACKGROUND: It is essential to understand the mechanism of the various causes of laser fiber damage and an ideal method of reducing endoscope damage induced by laser emission in multiple sites. This study classified the different patterns of laser fiber degradation according to laser settings and analyzed the role of cavitation bubbles to find a desirable way of minimizing endoscope damage. METHODS: A total of 118 laser fibers were analyzed after 1-,3-, and 5-min laser emission to artificial stones under the settings of 1 J-10 Hz, 1 J-20 Hz, 1 J-30 Hz, and 2 J-10 Hz. Every 3 cm from the fiber tip was marked and examined with a digital microscope and a high-speed camera. The images of the fibers and the movement of cavitation bubbles were taken with a distance of 1 to 5 mm from the gel. RESULTS: Seven types of fiber damage (charring, limited and extensive peeled-off, bumpy, whitish plaque, crack, and break-off) coincided during laser emission. Damages rapidly increased with emission time > 3 minutes regardless of the laser settings. The damaged lengths covered 5 mm on average, and the fibers at 5-min emission were significantly shorter than others. The fiber durability of 1J-10Hz setting was better than other settings after 3-min laser emission. Backward movement of the cavitation bubbles was found at the 1-mm distance from the gel, and the damaged lengths were longer than the diameters of the cavitation bubbles because of their proximal movement. CONCLUSION: The damage patterns of the laser fiber tips were classified into seven types. The heat damage around the surface of the laser fiber can be increased according to the high-energy or high-frequency laser setting, a short distance to the stone, a short distance from the tips of flexible ureteroscopes, no cutting laser fiber procedures, and the inappropriate use of irrigation fluid or laser fiber jacket.

Stochastic gradient Langevin dynamics with adaptive drifts.

We propose a class of adaptive stochastic gradient Markov chain Monte Carlo (SGMCMC) algorithms, where the drift function is adaptively adjusted according to the gradient of past samples to accelerate the convergence of the algorithm in simulations of the distributions with pathological curvatures. We establish the convergence of the proposed algorithms under mild conditions. The numerical examples indicate that the proposed algorithms can significantly outperform the popular SGMCMC algorithms, such as stochastic gradient Langevin dynamics (SGLD), stochastic gradient Hamiltonian Monte Carlo (SGHMC) and preconditioned SGLD, in both simulation and optimization tasks. In particular, the proposed algorithms can converge quickly for the distributions for which the energy landscape possesses pathological curvatures.