Systemic Circulation Research Articles

Measurement of ocean currents by seafloor distributed optical-fiber acoustic sensing.

Ocean current measurements play a crucial role in aiding our understanding of ocean dynamics and circulation systems. Traditional methods, such as drifters and ocean buoys, are sparsely distributed and of limited effectiveness due to the nature of the marine environment and high operating expenses. Distributed acoustic sensing (DAS) is an emerging technology using submarine optical-fiber (OF) cables as dense seismo-acoustic arrays, offering a new perspective for ocean observations. Here, in situ observations of ocean surface gravity waves (OSGWs) and ocean currents by DAS were made along a pre-existing 33.6 km seafloor OF cable. The average current velocity and water depth along the cable were determined from observed OSGW-induced seafloor noise (0.05-0.2 Hz) using ambient-noise interferometry and frequency-domain beamforming. Variations in current velocity were derived at high spatiotemporal resolution using the frequency-domain waveform-stretching method. The inverted current velocity was verified by nearby ocean buoy observations and forecasting results. The observations demonstrate the effectiveness of DAS-instrumented OF cables in monitoring ocean currents.

Mof-derived carbon aerogel for rapid on-site extraction of chlorophenols based on drone-liquid circulation system

Mof-derived carbon aerogel for rapid on-site extraction of chlorophenols based on drone-liquid circulation system

Rapid estimation of left ventricular contractility with a physics-informed neural network inverse modeling approach

Physics-based computer models based on numerical solutions of the governing equations generally cannot make rapid predictions, which in turn limits their applications in the clinic. To address this issue, we developed a physics-informed neural network (PINN) model that encodes the physics of a closed-loop blood circulation system embedding a left ventricle (LV). The PINN model is trained to satisfy a system of ordinary differential equations (ODEs) associated with a lumped parameter description of the circulatory system. The model predictions have a maximum error of less than 5% when compared to those obtained by solving the ODEs numerically. An inverse modeling approach using the PINN model is also developed to rapidly estimate model parameters (in ∼ 3 min) from single-beat LV pressure and volume waveforms. Using synthetic LV pressure and volume waveforms generated by the PINN model with different model parameter values, we show that the inverse modeling approach can recover the corresponding ground truth values for LV contractility indexed by the end-systolic elastance Ees with a 1% error, which suggests that this parameter is unique. The PINN inverse modeling approach is then applied to estimate Ees using waveforms acquired from 11 swine models, including waveforms acquired before and after administration of dobutamine (an inotropic agent) in 3 animals. The estimated Ees is about 58% to 284% higher for the data associated with dobutamine compared to those without, which implies that this approach can be used to estimate LV contractility using single-beat measurements. The PINN inverse modeling can potentially be used in the clinic to simultaneously estimate LV contractility and other physiological parameters from single-beat measurements.

Self‐Oxygenated Biomimetic Nanozyme for Tumor Catalytic Immunotherapy

AbstractThe treatment of solid tumors remains a significant challenge due to the complex, immunosuppressive tumor microenvironment (TME). This manuscript introduces the self‐oxygenated biomimetic nanozyme system, SS‐MSN@Au‐BOM, which innovatively combines catalytic therapy with immunotherapy to modulate the TME for enhanced therapeutic efficacy. Employing mesoporous silicon nanoparticles doped with disulfide bonds, the system integrates gold nanozymes that exhibit glucose oxidase (GOx)‐like and peroxidase (POD)‐like activities, along with a catalase (CAT) function derived from bacterial outer membrane (BOM) coatings. SS‐MSN@Au‐BOM significantly disrupted tumor growth by catalyzing endogenous hydrogen peroxide to generate cytotoxic ROS and essential oxygen, enhancing intratumoral ROS levels while alleviating hypoxia. This catalytic action facilitates immunogenic cell death, enhances dendritic cell maturation, and T‐cell activation. Notably, the system shows excellent biocompatibility, effective tumor targeting, and prolonged systemic circulation. SS‐MSN@Au‐BOM offers a dual‐functional approach that effectively disrupts the TME and promotes robust antitumor immunity. This study paves the way for further clinical investigation and the development of enzyme‐based therapeutics, potentially transforming the landscape of cancer treatment.

Skin Structure, Physiology, and Pathology in Topical and Transdermal Drug Delivery

Several industries are increasingly focused on enhancing the delivery of active ingredients through the skin to optimize therapeutic outcomes. By facilitating the penetration of active ingredients through the skin barrier, these enhancers can significantly improve the efficacy of various formulations, ranging from skincare products to therapeutic agents targeting systemic circulation. As the understanding of skin physiology and the mechanisms of drug absorption deepen, these industries are adopting permeation enhancers more widely, ultimately leading to better patient outcomes and expanded treatment options. However, the structure and physiological function of the skin can vary according to different factors, such as the area of the body and between individuals. These variations, along with external environmental exposures, aging and pathological conditions, introduce complexities that must be carefully considered when designing effective delivery systems. Considering the intricacies of skin structure and physiology, tailoring systems to account for regional differences, individual variability, and changes induced by environmental factors or disease is critical to optimizing therapeutic outcomes. This review discusses the features of skin structure, physiology, and pathologies, as well as the application of permeation enhancers in these contexts. Furthermore, it addresses the use of animal skin models in transdermal delivery and dermatological studies, along with the latest developments in this field.

Circulating metabolites of Borneolum syntheticum (Bingpian) ameliorate atherosclerosis in ApoE-/- mice via inhibiting macrophage foam-cell formation.

Translational pharmacological research on traditional medicines lays the foundation for precisely understanding how the medicines function in the body to deliver therapeutic benefits. Borneolum syntheticum (Bingpian) is commonly used in Chinese herbal medicines for coronary heart disease, but its specific cardiovascular impact remains poorly understood. Isoborneol, a constituent of Bingpian, has been found to reduce lipid accumulation in macrophages in vitro, but its oral bioavailability is limited. This investigation aimed to evaluate anti-atherosclerotic effects of Bingpian, based on understanding its first-pass metabolism. Human subjects orally received an herbal medicine containing Bingpian and their plasma samples were analyzed to identify the major circulating compounds of Bingpian, with the metabolism that was also characterized in vitro and in mice. The identified compounds were evaluated for their ability to inhibit macrophage foam-cell formation induced by oxidized low-density lipoprotein. Furthermore, the anti-atherosclerotic effect of repeatedly dosed Bingpian was assessed in ApoE-/- mice fed a high-fat diet. In human subjects, the major circulating compounds of Bingpian were metabolites, rather than their precursor constituents borneol and isoborneol. These constituents were efficiently absorbed in the intestinal tract but underwent significant first-pass metabolism, involving UGT2B7-mediated glucuronidation into borneol-2-O-glucuronide and isoborneol-2-O-glucuronide, respectively, and CYP2A6/2B6/3A-mediated oxidation both into camphor. Despite their poor membrane permeability, hepatic efflux of borneol-2-O-glucuronide and isoborneol-2-O-glucuronide into the systemic circulation was enhanced by MRP3/4. The circulating metabolites, particularly their combinations, markedly inhibited macrophage foam-cell formation induced by oxidized low-density lipoprotein in vitro. Sub-chronic administration of Bingpian (30 mg·kg-1·d-1, i.g.) for 12 weeks significantly decreased atherosclerotic lesion size and enhanced plaque stability in ApoE-/- mice. Systemic exposure to Bingpian metabolites in mice closely resembles that in humans, suggesting that the pharmacodynamic effects of Bingpian in mice are likely applicable to humans. Overall, the cardiovascular benefits of Bingpian involve reducing atherosclerosis by inhibiting foam-cell formation through its metabolites. This investigation supports that oral Bingpian could be a druggable agent for reducing atherosclerosis.

Early coronary artery atherosclerosis in humans is associated with attenuated coronary retention of klotho

Abstract Background Vascular aging is a key feature of cardiovascular disease. α-klotho (klotho) is a protein inversely associated with aging and may contribute to vascular repair. Lower levels of systemic klotho have been identified in humans with features of early and advanced coronary atherosclerosis. It remains unknown if circulating klotho is present within human coronary circulation and whether cardiovascular klotho retention correlates with atherosclerosis. Purpose The current study aimed to assess the presence of klotho within coronary circulation compared to systemic circulation and hypothesized that net coronary klotho retention is attenuated in patients with early age-related features of coronary artery disease (CAD). Methods A total of 42 patients that underwent clinically indicated coronary angiogram for chest pain that had no obstructive CAD underwent intravascular ultrasound (IVUS) assessment were retrospectively examined. Virtual histology assessed coronary plaque characteristics. Blood samples simultaneously collected from the proximal aorta and coronary sinus were used for klotho detection using enzyme-linked immunosorbent assay. The net gradient of klotho across cardiovascular circulation was calculated by multiplying the arteriovenous klotho gradient by basal coronary blood flow. A net positive gradient indicated less cardiovascular klotho retention; a net negative gradient indicated greater cardiovascular klotho retention. Results Overall, participants were age 54±10 years old and 76% were female. There were overall higher levels of klotho within the coronary sinus (median 0.49 ng/mL [0.15; 1.69]) compared to systemic circulation (median 0.30 ng/mL [0.16; 1.14]). Participant groups were determined by those with positive (n = 20) or negative (n = 22) cardiovascular retention of klotho. Both groups were similar in age (56 ±2 vs. 51 ±2 years old, p = 0.080), gender (72% vs. 80% female, p = 0.580), and had similar occurrences of traditional cardiovascular comorbidities. Those with less cardiovascular klotho retention in the coronary vascular bed had significantly greater degree of non-obstructive coronary artery plaque (Gensini score 3.5 vs. 0, p < 0.001) and had higher percent plaque burden (46% [35; 53] vs. 34% [28; 46], p = 0.044) than those with greater cardiovascular klotho retention. Conclusions Patients with early coronary atherosclerosis may be characterized by attenuated retention of klotho within coronary circulation. Moreover, humans appear to have higher circulating klotho in coronary circulation than in systemic circulation. The current study may support a role for mechanism or potential therapeutic target for klotho in coronary atherosclerosis in humans.

Analysis of Spatial Agglomeration Characteristics of Logistics Enterprises in Henan Province based on Poi

As an important industry connecting urban and rural areas and serving production and life, logistics enterprises, as the micro-foundation of the development of logistics industry, have a profound impact on the spatial reconstruction of regional economic and social development. National Development and Reform Commission issued the "Fourteenth Five-Year Plan" modern logistics development and "Fourteenth Five-Year Plan" modern circulation system construction planning "put forward new requirements for the development of logistics industry, emphasizing the optimization of logistics spatial layout and speed up the construction of national logistics hub, especially pointed out that to make up for the shortcomings of the central and western regions. As an important base for the development of China's logistics industry, the spatial layout of logistics enterprises in Henan province not only affects the high-quality development of the logistics industry in the province, but also plays an important role in the improvement of the national logistics network. In this paper, based on POI data, the mean nearest neighbor method, local Moran scatter plot analysis and kernel density visualization technology are used to analyze the spatial agglomeration characteristics of logistics enterprises in 157 counties in Henan Province. It is found that the spatial distribution of logistics enterprises in Henan Province has gradually evolved from multi-point dispersion to a single-core and multi-core collaborative model with Zhengzhou as the core, and presents a significant spatial positive correlation and agglomeration trend. This change has improved the logistics efficiency and promoted the strengthening of regional economic ties. At the same time, the agglomeration trend of logistics enterprises in Henan Province continues to strengthen, from the initial agglomeration in the core area to the diversified diffusion pattern, showing the continuous optimization and reconstruction of logistics network in the province.

Toxicokinetics and Tissue Distribution of the Hepatotoxic Triterpenoid Saponin Pterocephin A in Rats Using the Ultra-Performance Liquid Chromatography–Tandem Mass Spectrometry (UPLC-MS/MS) Method

Pterocephin A is a natural triterpenoid saponin isolated from Pterocephalus hookeri, a traditional Tibetan medicine with slight toxicity, which can induce liver injury in rats. This study aimed to establish a sensitive and reliable UPLC-MS/MS method for exploring the toxicokinetics and tissue distribution of pterocephin A following single intravenous and intragastric administration. Pterocephin A and prosapogenin 1C (internal standard, IS) were extracted using a simple protein precipitation technique with methanol as the precipitant for plasma samples and methanol/acetonitrile = 1:1 (v/v) for tissue samples. UPLC separation was achieved by gradient elution with 0.3 mL/min and a mobile phase consisting of 5 mM ammonium formate (A) and acetonitrile (B) (0–2 min 30% B; 2–4 min: 30–80% B; 4–5 min: 80–98% B; 5–6.5 min: 98% B; 6.5–7 min: 98–30% B; and 7–8 min: 30% B, v/v) with a column temperature of 35 °C. MS spectrometry adopted negative ion scanning mode, primary MS spectrometry adopted full scan monitoring mode, and secondary MS spectrometry adopted targeted MS2 scan monitoring mode. The assay exhibited a linear dynamic range of 0.02–15 μg/mL for pterocephin A in biological samples, with the low limit of quantification set at 0.02 μg/mL. Non-compartmental toxicokinetic parameters indicated that pterocephin A was well absorbed into the systemic circulation and had a long residual time after intravenous (10 mg/kg) and intragastric (60 mg/kg) administration, as it could still be detected after 72 h. Tissue distribution analysis revealed detectable levels of pterocephin A in various tissues, and a high concentration was maintained in the liver after intravenous (10 mg/kg) administration, with the highest concentration being 610.95 ± 25.73 ng/mL and a specific distribution pattern of liver > lung > kidney > intestine > spleen > testes > heart > stomach. The toxicokinetic process and tissue distribution characteristics of pterocephin A were expounded in this study, which can provide relevant data support for further research and clinical application of pterocephin A with its slight toxicity.

The Development of LKPD Based on a Scientific Approach to Improve Students' Science Process Skills in Material on the Human Circulatory System and Digestive System Class XI SMA

The development of Student Worksheets (LKPD) based on a scientific approach to material on the human circulation system and digestive system is based on the teaching materials used at SMA Negeri 16 Padang in the form of Student Worksheets (LKPD). The LKPD is not complete in terms of components or in terms of LKPD elements. The LKPD used only takes the form of sheets containing questions, and does not use an approach that contains activities or learning steps so that it cannot train students' science process skills. This research aims to produce LKPD based on a scientific approach to material on the human circulation system and digestive system that is valid, practical and effective to improve students' science process skills. This research is development research using the Plomp model which consists of three stages, namely preliminary research phase, development or prototyping phase and assessment phase. The results of the LKPD validity test by the validator obtained a value of 84.67% with very valid criteria. The results of the LKPD practicality test obtained a score of 90.74% by teachers and 88.30% by students with very practical criteria. The results of the T-test showed differences in values between the experimental and control classes with a significance of 0.000 each in the circulatory system and digestive system material. It can be concluded that LKPD based on a scientific approach is very valid, very practical and effective in improving science process skills.

Treatment of chronic sinus tract leakage at rectal anastomosis with anal fistula endoscopy

Objective: To introduce the method of using anal fistula endoscope to treat chronic sinus tract leakage at rectal anastomosis site. Methods: We used anal fistula endoscopy to treat a patient with chronic sinus tract leakage after radical resection of rectal cancer, mainly including the following 5 steps: (1) establishing a water injection circulation system through the anus; (2) scraping off purulent coating and mucosa on the surface of the sinus tract with the brush; (3) hemostasis and removal of necrotic tissue with electrocoagulation rods; (4) filling the sinus tract with bioprotein gel; (5) compressing the sinus tract with transanal drainage tube. Results: The patient is a 70 year old male with rectal cancer. After undergoing 3D laparoscopic assisted radical resection of rectal cancer via abdominal anterior resection (Dixon's procedure) and diverting ileostomy surgery for more than 3 months, leakage of the rectal anastomosis was found through colonoscopy and anal iodine water contrast imaging .The patient started eating and flowing juice 6 hours after surgery, got out of bed 24 hours after surgery, and was discharged 48 hours after the removal of the anal canal. Three months after surgery, colonoscopy and transanal iodine hydrography showed that the sinus repair was intact. The diverting ileostomy was reduced 4 months after surgery. Conclusion: Anal fistula endoscope is safe and feasible for the treatment of chronic sinus tract anastomotic leakage in selected patients.

Overview of Ventilation and Lighting of Tuberculosis Patients' Homes in Sumenep, Indonesia

Tuberculosis is an infectious disease caused by the mycobacterium tuberculosis germ by causing respiratory disorders and is known as MOTT (Mycobacterium Other Than Tubercoluss). In Indonesia, tuberculosis is one of the public health problems that still has a high incidence rate. Tuberculosis can be affected by unqualified lighting, ventilation of the house. The purpose of this study is to find out the Overview of Ventilation and Lighting of Houses of Tuberculosis Patients in the Working Area of the Arjasa Health Center, Sumenep Regency. This study is an analytical research, with a cross sectional approach. The population of Tuberculosis patients in the Working Area of the Arjasa Health Center, Sumenep Regency is 65 people, with a sample of 56 people. The sampling technique uses Simple Random Sampling. Data collection will be carried out from May to June 2024. Data were collected by observation and interviews. The results of the study showed that the condition of the houses of Tuberculosis patients in the Working Area of the Arjasa Health Center, Sumenep Regency who did not meet the requirements was mostly influenced by house lighting (62.5%) and ventilation (67.9%). To reduce the transmission of Tuberculosis, it is sought to open windows when residents are in the house so that sunlight can kill tuberculosis germs, in addition to modifying the design of the house so that the air circulation system in the house remains fresh and comparing the floor area of the house with the number of residents in accordance with health requirements so as to minimize the transmission of Tuberculosis.

Candida albicans Induces Oral Microbial Dysbiosis and Promotes Oral Diseases

Candida albicans are ubiquitous fungal organisms that colonize the oral cavity of healthy individuals without causing disease. C. albicans is an opportunistic microorganism with several virulent factors that influence the inflammatory process and allow it to invade tissues, evade host defense mechanisms, and release toxins, facilitating proliferation and degradation. At present, increasing emphasis is placed on polymicrobial interactions between C. albicans and various bacterial pathogens. Such interaction is mutually beneficial for both parties: it is competitive and antagonistic. Their complex interaction and colonization in the oral cavity serve as the basis for several oral diseases. The dispersion of C. albicans in saliva and the systemic circulation is noted in association with other bacterial populations, suggesting their virulence in causing disease. Hence, it is necessary to understand fungal–bacterial interactions for early detection and the development of novel therapeutic strategies to treat oral diseases. In this paper, we review the mutualistic interaction of C. albicans in oral biofilm formation and polymicrobial interactions in oral diseases. In addition, C. albicans virulence in causing biofilm-related oral diseases and its presence in saliva are discussed.

Development of Minodronic Acid-Loaded Dissolving Microneedles for Enhanced Osteoporosis Therapy: Influence of Drug Loading on the Bioavailability of Minodronic Acid.

Osteoporosis is a metabolic bone disorder with impaired bone microstructure and increased bone fractures, seriously affecting the quality of life of patients. Among various bisphosphonates prescribed for managing osteoporosis, minodronic acid (MA) is the most potent inhibitor of bone context resorption. However, oral MA tablet is the only commercialized dosage form that has extremely low bioavailability, severe adverse reactions, and poor patient compliance. To tackle these issues, we developed MA-loaded dissolving microneedles (MA-MNs) with significantly improved bioavailability for osteoporosis therapy. We investigated the influence of drug loading on the physicochemical properties, transdermal permeation behavior, and pharmacokinetics of MA-MNs. The drug loading of MA-MNs exerted almost no effect on their morphology, mechanical property, and skin insertion ability, but it compromised the transdermal permeability and bioavailability of MA-MNs. Compared with oral MA, MA-MNs with the lowest drug loading (224.9μg/patch) showed a 9-fold and 25.8-fold increase in peak concentration and bioavailability, respectively. This may be ascribed to the reason that the increased drug loading can generate higher burst release, higher drug residual rate, and drug supersaturation effect in skin tissues, eventually limiting drug absorption into the systemic circulation. Moreover, MA-MNs prolonged the half-life of MA and provided more steady plasma drug concentrations than intravenously injected MA, which helps to reduce dosing frequency and side effects. Therefore, dissolving MNs with optimized drug loading provides a promising alternative for bisphosphonate drug delivery.

Metabolic Effects of Medium-Chain Triacylglycerol Consumption are Preserved in Obesity.

Several health beneficial effects are associated with intake of medium-chain triacylglycerol (MCT), however, the underlying mechanisms are unknown. Furthermore, it remains uncertain whether the acute metabolic effects of MCT differ between lean individuals and individuals with obesity - and whether these effects are sustained following chronic intake. This study aimed to elucidate the postprandial physiological and metabolic effects of MCT before and after eight days intake compared to intake of energy-matched triacylglycerol consisting of long-chain fatty acids (LCT) using a randomized cross-over design in lean individuals (n=8) and individuals with obesity (n=8). The study revealed that consumption of MCT increased ketogenesis and metabolic rate, while lowering blood glucose levels over five hours. The hypoglycemic action of MCT intake was accompanied by a concomitant transient increase in plasma insulin and glucagon levels. Interestingly, the effects on ketogenesis, metabolic rate, and glycemia were preserved in individuals with obesity and sustained after eight days of daily supplementation. Lipidomic plasma analysis in lean individuals (n=4) showed that a part of the ingested MCT bypasses the liver and entered the systemic circulation as medium-chain fatty acids (MCFA). The findings suggest that MCFA, along with ketone bodies from the liver, may act as signaling molecules and/or substrates in the peripheral tissues, thereby contributing to the effects of MCT intake. In summary, these findings underscore the health benefits of MCT in metabolically compromised individuals after daily supplementation. Moreover, we uncover novel aspects of MCFA biology, providing insights into how these fatty acids orchestrate physiological effects in humans.

Assessment of metabolic indicators of the cardiovascular system in children with nephrotic syndrome

Objective: to evaluate the metabolic parameters of the cardiovascular system in nephrotic syndrome in children Material and methods: 110 children hospitalized with nephrotic syndrome in the nephrology department of the Samarkand Regional Children’s Multidisciplinary Medical Center were examined. Results: Renocardial syndrome with nephrotic syndrome develops in 64.8% of cases, the majority of patients are children 3-6 years of age (44.1%), with a predominance of boys (58.8%). In a cardiometric study in patients with nephrotic syndrome, renocardial syndrome is manifested by significant changes in metabolic and adaptation parameters: oxygen and lactate content - by 1.5 times, creatine phosphate - by 20%, tension index - by 4.8 times and vascular stiffness index - by 5.2 times. Conclusion: Deviation of cardiometry indicators in different age groups indicates a decrease in the intensity of blood circulation in organs and systems, indicating a significant load on the cardiovascular system in nephrotic syndrome.

Appraisal of partial anomalous pulmonary venous drainage through a lumped-parameter mathematical model: a new pathophysiological proof of concept.

Haemodynamic determinants of the ratio between pulmonary and systemic flow (Qp/Qs) in partial anomalous pulmonary venous return (PAPVR) are still not fully understood. Indeed, among patients with the same number of lung segments draining anomalously, a great variability is observed in terms of right ventricular overload. The aim of this study was to test the hypothesis that the anatomic site of drainage, affecting the total circuit impedance, independently influences the magnitude of shunt estimated by Qp/Qs. A zero-dimensional (0D) lumped parameter mathematical model was developed and validated on a sample of patients. We developed a 0D lumped parameter model, using time varying elastances for heart chambers, RLC Windkessel circuits for the systemic and pulmonary circulations. Patients, were categorized into vena cava (VC) type (including left drainage to anomimous vein) and right atrium type (RA). The mathematical model is a system of ordinary differential equations that are numerically solved by means of the ode15s solver in the Matlab environment. The model showed an increase of Qp/Qs with the increase of the number of anomalous veins. With the same number of anomalous veins, Qp/Qs was lower in patients with anomalous drainage to the vena cava (VC) as compared with right atrium (RA) The validation sample consisted of 49 patients (27, 55% females). As predicted by the model, patients with PAPVR with VC type displayed a lower invasive and CMR Qp/Qs as compared with drainage to RA: 1.4 (1.2-1.7) and 1.45 (1.25-1.6) versus 2 (1.75-2.1) and 1.9 (1.6-2) p < 0.05. After stratifying for number of lung territories a lower Qp/Qs was measured in patients with VC PAPVR as compared with RA. In patients with PAPVR, the site of anomalous drainage modulates the Qp/Qs. According to the model, this effect is mediated by the post-capillary impedance of the circuit and significantly decreases with the increase of pulmonary vascular resistances.

Research on New Spatial Data Infrastructure Supports the Circulation of Geographic Information Data Elements

Abstract. Data is an important factor of production in the digital economy era and an important support for building a new development pattern. As an important part of data resources, geographic information data is also an important new factor of production, which plays a unique role in the construction of digital China and economic and social development. From the perspective of releasing the value of data elements, data infrastructure is a new type of infrastructure that provides integrated data aggregation, processing,circulation, application, operation, and security services for society under the support of network, computing power and other facilities. It is an organic whole covering hardware, software, open source protocols, standards, and mechanism design. Spatial data infrastructure (SDI) is a collection of technologies, policies and systems that realize the access and access of spatial data. Through the construction of new spatial data infrastructure (NSDI), it supports the circulation of geographic information data elements,making it an important part of data infrastructure. Firstly, this paper gives the connotation of geographic information data elements circulation. Secondly, it proposed to construct the circulation system of geographic information data elements on the basis of enumerating and summarizing the spatial data infrastructure, in order to better support the construction of digital China and economic and social development. Thirdly, the basic requirements, technical indicators and overall architecture of NSDI are designed. Finally, the opportunities and challenges faced by the circulation of geographic information data elements were summarized, mainly focusing on the aspects of policy mechanisms and security systems. At the end of the paper is a summary and acknowledgments.

Factors Influencing the Central Nervous System (CNS) Distribution of the Ataxia Telangiectasia Mutated and Rad3-Related Inhibitor Elimusertib (BAY1895344): Implications for the Treatment of CNS Tumors.

Glioblastoma (GBM) is a disease of the whole brain, with infiltrative tumor cells protected by an intact blood-brain barrier (BBB). GBM has a poor prognosis despite aggressive treatment, in part due to the lack of adequate drug permeability at the BBB. Standard of care GBM therapies include radiation and cytotoxic chemotherapy that lead to DNA damage. Subsequent activation of DNA damage response (DDR) pathways can induce resistance. Various DDR inhibitors, targeting the key regulators of these pathways such as ataxia telangiectasia mutated and Rad3-related (ATR), are being explored as radio- and chemosensitizers. Elimusertib, a novel ATR kinase inhibitor, can prevent repair of damaged DNA, increasing efficacy of DNA-damaging cytotoxic therapies. Robust synergy was observed in vitro when elimusertib was combined with the DNA-damaging agent temozolomide; however, we did not observe improvement with this combination in in vivo efficacy studies in GBM orthotopic tumor-bearing mice. This in vitro-in vivo disconnect was explored to understand factors influencing central nervous system (CNS) distribution of elimusertib and reasons for lack of efficacy. We observed that elimusertib is rapidly cleared from systemic circulation in mice and would not maintain adequate exposure in the CNS for efficacious combination therapy with temozolomide. CNS distribution of elimusertib is partially limited by P-glycoprotein efflux at the BBB, and high binding to CNS tissues leads to low levels of pharmacologically active (unbound) drug in the brain. Acknowledging the potential for interspecies differences in pharmacokinetics, these data suggest that clinical translation of elimusertib in combination with temozolomide for treatment of GBM may be limited. SIGNIFICANCE STATEMENT: This study examined the disconnect between the in vitro synergy and in vivo efficacy of elimusertib/temozolomide combination therapy by exploring systemic and central nervous system (CNS) distributional pharmacokinetics. Results indicate that the lack of improvement in in vivo efficacy in glioblastoma (GBM) patient-derived xenograft (PDX) models could be attributed to inadequate exposure of pharmacologically active drug concentrations in the CNS. These observations can guide further exploration of elimusertib for the treatment of GBM or other CNS tumors.

Peculiarities of the regional hemodynamics in patients with mono- and bilateral herpes simplex virus stromal keratitis

Background. Herpes simplex virus keratitis (HSVK) is the main cause of blindness in the world resulted from corneal pathology. The blood circulation system of the eye plays an important role in the effective implementation of the immune response. The purpose of the study: to determine the influence of the factor of laterality of the stromal HSVK on the ocular hemodynamics and the frequency of complications. Material and methods. Primary stromal HSVK (was registered for the first time and lasted no more than 3 months) was diagnosed in 32 people (35 eyes), 205 patients (226 eyes) had recurrent stromal HSVK. Among these patients, stromal HSVK was detected both in one eye — unilateral, and in two eyes — bilateral. Complications of stromal HSVK includes: the presence of a transparent graft — in 23 eyes and its opacity — in 10 eyes, secondary glaucoma — in 6 eyes, condition after corneal ulcer — in 16 eyes. The average age of the patients (M ± SD) is 42.2 ± 15.0 years. The control group consisted of 16 healthy volunteers (32 eyes) of similar age. The standard technique of rheoophthalmogram on the ReoCom computer rheograph (Kharkiv, Ukraine) was used. The following indicators were analyzed: rheographic quotient (RQ, ‰) (pulse volumetric blood filling); α1/T (%) — the tone of the large vessels of the eye; velocity of blood filling V (Ohm/s). Results. Patients with stromal HSVK had mainly monolateral eye lesion — 89.8 %, and bilateral lesion was present in 10.2 % of cases. There were no significant differences in the frequency of laterality between primary and recurrent stromal HSVK. In case of recurrence of complicated unilateral and bilateral stromal HSVK, the volumetric pulse blood filling was 17.6 and 30.3 % lower, respectively, than in uncomplicated course, which determines the insufficiency of blood supply to the eye. The rate of blood filling in complicated stromal HSVK was lower than in uncomplicated one by 23 %. At the recurrence of bilateral stromal HSVK, the RQ was higher by 26.4 %, and the rate of blood filling was higher by 36.3 % compared to unilateral one. There were no differences in remission. The tone of the large vessels of the eye with bilateral stromal HSVK is 14 % lower than with unilateral course. Conclusions. In case of recurrent stromal HSVK, the volume pulse blood filling of the eye and its velocity are higher, and the vascular tone is lower than in case of unilateral one, both uncomplicated and complicated. It is assumed that such a significant activation of the ocular hemodynamics is compensatory and contributes to a greater local immune response and improvement of trophism.