City acupuncture: the sustainable development of the balanced city in post-industrial age

After the Franco dictatorship, a new chapter occurred in Barcelona’s Democracy. As having fully understood the spirit of Cerda’s planning, the participants in Barcelona urban planning creatively started to use a treatment called acupuncture in the city, which has the same spirit as traditional Chinese medical science, and revived the ruined city, gradually gain back the balanced and sustainable management of the city. The thesis introduces the problems Barcelona met in the post-industrial age and the corresponding solutions, mainly focuses on Barcelona city renewal in the 80s, and tries to explain the relationship between traditional Chinese medical science and city acupuncture, which will be the clue of the thesis. The thesis will be described in three chapters, human body and city under the view of traditional Chinese medical science, acupuncture therapy and the Barcelona model and sustainable development of the balanced city.Peer Reviewe

Perception of Misalignment States for Sky Survey Telescopes with the Digital Twin and the Deep Neural Networks

Sky survey telescopes play a critical role in modern astronomy, but misalignment of their optical elements can introduce significant variations in point spread functions, leading to reduced data quality. To address this, we need a method to obtain misalignment states, aiding in the reconstruction of accurate point spread functions for data processing methods or facilitating adjustments of optical components for improved image quality. Since sky survey telescopes consist of many optical elements, they result in a vast array of potential misalignment states, some of which are intricately coupled, posing detection challenges. However, by continuously adjusting the misalignment states of optical elements, we can disentangle coupled states. Based on this principle, we propose a deep neural network to extract misalignment states from continuously varying point spread functions in different field of views. To ensure sufficient and diverse training data, we recommend employing a digital twin to obtain data for neural network training. Additionally, we introduce the state graph to store misalignment data and explore complex relationships between misalignment states and corresponding point spread functions, guiding the generation of training data from experiments. Once trained, the neural network estimates misalignment states from observation data, regardless of the impacts caused by atmospheric turbulence, noise, and limited spatial sampling rates in the detector. The method proposed in this paper could be used to provide prior information for the active optics system and the optical system alignment.Comment: The aforementioned submission has been accepted by Optics Express. We kindly request any feedback or comments to be directed to the corresponding author, Peng Jia ([email protected]), or the second corresponding author, Zhengyang Li ([email protected]). Please note that Zhengyang is currently stationed in the South Antarctica and will not be available until after February 1st, 202

Glycyrrhizin arginine salt protects against cisplation-induced acute liver injury by repressing BECN1-mediated ferroptosis

The study aimed to investigate the protective effects and biological mechanisms of glycyrrhizin arginine salt (Gly-Arg) against cisplatin (Cis)-induced liver injury. Our data showed that Gly-Arg improved Cis-induced liver injury. Further study showed that BECN1 (beclin1) and LC3-II/LC3-I protein expression was significantly increased in primary hepatocytes and mouse liver tissues after Cis treatment, but Gly-Arg reduced the protein levels of BECN1 and LC3-II/LC3-I in primary hepatocytes and mouse liver tissues. Also, Gly-Arg improved indicators related to Cis-induced ferroptosis. Furthermore, Cis increased colocalization of lysosomal membrane-associated protein 1A (LAMP1) with ferritin heavy chain 1 (FTH1) in primary mouse hepatocytes, while Gly-Arg intervention attenuated this colocalization in primary hepatocytes. More improtantly, Cis enhanced the formation of the BECN1-xCT complex, thus inhibiting solute carrier family 7 member 11 (SLC7A11, xCT) and glutathione peroxidase-4 (GPX4) activity. In contrast, Gly-Arg intervention disrupted the formation of this complex. However, Gly-Arg alleviated Cis-induced liver injury in mice by preventing autophagic death and ferroptosis through the inhibition of BECN1-xCT complex formation

Investigation into the dynamic change pattern of the stress field during integral fracturing in deep reservoirs

Deep reservoirs have high temperature, high pressure, and high stress. The development of such resources is high cost. Integral fracturing applies one-time well displacement, batch drilling, and batch fracturing. Multiple wells are stimulated with zipper fracturing. It can avoid the interference of the well drilling and fracturing. In this way, the spatial stresses can be utilized to generate the complex fracture network. The dynamic change pattern of the stress field is of great value for the design of integral fracturing. Based on the displacement discontinuity method (DDM) and the fracture mechanics criteria, a whole fracture propagation program is developed to calculate the spatial stress distribution and the whole fracture geometry. The reliability of the program is verified against the classical analytical solutions. Based on the program, this work systematically investigates the effects of the fracture length, the fracturing sequence, the fracture distribution mode, and the injection pressure on the stress field. The main conclusions are as follows: 1) When the fracture half-length is 150 m and the well spacing is 300 m, the staggered fracture distribution mode can ensure uniform fracture propagation and realize the active utilization of inter-well stress field; 2) Compared with the relative fracture distribution mode, the staggered fracture distribution mode is less susceptible to the stress field induced by the adjacent hydraulic fractures, hydraulic fractures tend to propagate along the direction of the maximum horizontal principal stress; 3) The stress field is highly influenced by the in-fracture fluid pressure. The stress interference is stronger with a greater fluid injection pressure and a higher fracture deflection angle will be obtained. It can enhance the fracture propagation resistance and increase the stress value. This work discovers the stress change pattern and lays out a solid foundation for the optimization of the integral fracturing

The Characteristics, Long-Term Outcomes, Risk Factors, and Antithrombotic Therapy in Chinese Patients With Atrial Fibrillation and Bioprosthetic Valves

Introduction: There were few data about the clinical profiles and long-term outcomes in Chinese patients with atrial fibrillation (AF) and bioprosthetic valves.Methods: The retrospective study enrolled 903 patients with bioprosthetic valve replacement at our hospital and discharged with a diagnosis of AF from January 2010 to December 2018.Results: The median age was 65.6 (61.9–69.1) years, and 548 (60.7%) patients were women. During a follow-up period of 3.84 (2.64–5.51) years, 68 (1.8 per 100 person-years) patients died, 81 (2.1 per 100 person-years) patients developed thromboembolism, and 23 (0.6 per 100 person-years) patients experienced major bleeding. The CHA2DS2-VASc score, as a categorical variable (low, moderate, or high risk), predicted the risk of thromboembolism with the C-statistic of 0.6 (95% CI: 0.511–0.689, p = 0.046). The incidence of the CHA2DS2-VASc score increment was 11.6 per 100 person-years, and the annual reclassification rate of stroke risk (from a low or moderate group to a higher group) was 12.7%. The current proportion of oral anticoagulants was 52.3, 59, and 63.2%, respectively, in the low, moderate, and high stroke risk groups. Age (OR: 1.04, 95% CI: 1.01–1.06, p = 0.01), left atrial size (OR: 1.05, 95% CI: 1.03–1.08, p < 0.001), and rheumatic heart disease (OR: 1.49, 95% CI: 1.05–2.10, p = 0.025) were positively associated with the use of oral anticoagulants. The history of chronic kidney disease (OR: 0.20, 95% CI: 0.05–0.76, p = 0.018), prior surgical ablation (OR: 0.33, 95% CI: 0.24–0.47, p < 0.001), and antiplatelet agent use (OR: 0.08, 95% CI: 0.05–0.13, p < 0.001) were inversely related to the use of oral anticoagulants. Higher admission estimated glomerular filtration rate (HR: 0.515, 95% CI: 0.311–0.853, p = 0.01), left ventricular ejection fraction (HR: 0.961, 95% CI: 0.931–0.992, p = 0.014), concomitant surgical ablation (HR: 0.348, 95% CI: 0.171–0.711, p = 0.004), and rheumatic heart disease history (HR: 0.515, 95% CI: 0.311–0.853, p = 0.01) were associated with a lower risk of death. Surgical ablation (HR: 0.263, 95% CI: 0.133–0.519, p < 0.001) and oral anticoagulants (HR: 0.587, 95% CI: 0.375–0.918, p = 0.019) were related to a lower risk of thromboembolism.Conclusion: Chinese patients with AF and bioprosthetic valve(s) were relatively young and had a high prevalence of rheumatic heart disease with few comorbidities. The percentage of mitral bioprosthetic valve replacement was high. The proportion of concomitant surgical ablation or surgical left atrial appendage occlusion or exclusion was relatively low. The thromboembolic events were the major long-term adverse events. The anticoagulation therapy was underused in patients at moderate or high stroke risk. The CHA2DS2-VASc score was verified to be used for predicting stroke risk in this population. The stroke risk dynamically changed; it needed to be reestimated once the risk factor changed

Recent Progress in Phage Therapy to Modulate Multidrug-Resistant Acinetobacter baumannii, Including in Human and Poultry

Acinetobacter baumannii is a multidrug-resistant and invasive pathogen associated with the etiopathology of both an increasing number of nosocomial infections and is of relevance to poultry production systems. Multidrug-resistant Acinetobacter baumannii has been reported in connection to severe challenges to clinical treatment, mostly due to an increased rate of resistance to carbapenems. Amid the possible strategies aiming to reduce the insurgence of antimicrobial resistance, phage therapy has gained particular importance for the treatment of bacterial infections. This review summarizes the different phage-therapy approaches currently in use for multiple-drug resistant Acinetobacter baumannii, including single phage therapy, phage cocktails, phage–antibiotic combination therapy, phage-derived enzymes active on Acinetobacter baumannii and some novel technologies based on phage interventions. Although phage therapy represents a potential treatment solution for multidrug-resistant Acinetobacter baumannii, further research is needed to unravel some unanswered questions, especially in regard to its in vivo applications, before possible routine clinical use

Pharmacodynamics, metabolomics and pathological studies on mechanisms of traditional benefits of Angelica sinensis in blood circulation

Angelica sinensis is a rich source of medically important active molecules that need in-depth understanding on its action mechanisms. Therefore, through pharmacodynamics, metabolomics, and network pharmacology, the traditional benefits of A. sinensis in blood circulation was studied using 24 randomly selected Sprague-Dawley (SD) rats. Measurement of the blood rheological parameters for whole blood viscosity (WBV) and plasma viscosity (PV), and inspection of the heart and lung tissues pathological changes were undertaken using molecular and bioinformatic techniques. Multivariate statistical analysis and establishment of the model of the relationship between metabolite expression and sample categories to test the prediction of sample categories were performed. Screening was undertaken to find the potential metabolites for A. sinensis to treat blood stasis syndrome and find related metabolic pathways. Active ingredients of A. sinensis and targets and building of an “effect component-target” network was undertaken, A. sinensis was confirmed to improve blood stasis syndrome in rats and improve heart and lung pathology to varying degrees. Compared with the blood stasis model group, A. sinensis significantly reduced WBV and PV in hemorheology (p<0.05, p<0.01) and regulated blood stasis-induced changes in 22 metabolites including alpha-D-glucose, L-isoleucine, creatine and acetylcarnitine, which are involved in the metabolism of linoleic acid, linolenic acid, phenylalanine, ascorbic acid and uronic acid. Using the network pharmacology to build a "component-target-pathway" network of A. sinensis, 62 active ingredients, 169 active proteins and 18 metabolic pathways were obtained, among which linoleic acid metabolism, ascorbic acid and uronic acid metabolism were consistent with the metabolic pathways obtained by metabolomics

The tetraspanin transmembrane protein CD53 mediates dyslipidemia and integrates inflammatory and metabolic signaling in hepatocytes

Tetraspanins are transmembrane signaling and proinflammatory proteins. Prior work demonstrates that the tetraspanin, CD53/TSPAN25/MOX44, mediates B-cell development and lymphocyte migration to lymph nodes and is implicated in various inflammatory diseases. However, CD53 is also expressed in highly metabolic tissues, including adipose and liver; yet its function outside the lymphoid compartment is not defined. Here, we show that CD53 demarcates the nutritional and inflammatory status of hepatocytes. High-fat exposure and inflammatory stimuli induced CD53 in vivo in liver and isolated primary hepatocytes. In contrast, restricting hepatocyte glucose flux through hepatocyte glucose transporter 8 deletion or through trehalose treatment blocked CD53 induction in fat- and fructose-exposed contexts. Furthermore, germline CD53 deletion in vivo blocked Western diet-induced dyslipidemia and hepatic inflammatory transcriptomic activation. Surprisingly, metabolic protection in CD53 KO mice was more pronounced in the presence of an inciting inflammatory event. CD53 deletion attenuated tumor necrosis factor alpha-induced and fatty acid + lipopolysaccharide-induced cytokine gene expression and hepatocyte triglyceride accumulation in isolated murine hepatocytes. In vivo, CD53 deletion in nonalcoholic steatohepatitis diet-fed mice blocked peripheral adipose accumulation and adipose inflammation, insulin tolerance, and liver lipid accumulation. We then defined a stabilized and trehalase-resistant trehalose polymer that blocks hepatocyte CD53 expression in basal and over-fed contexts. The data suggest that CD53 integrates inflammatory and metabolic signals in response to hepatocyte nutritional status and that CD53 blockade may provide a means by which to attenuate pathophysiology in diseases that integrate overnutrition and inflammation, such as nonalcoholic steatohepatitis and type 2 diabetes

Lomerizine attenuates LPS-induced acute lung injury by inhibiting the macrophage activation through reducing Ca2+ influx

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening lung diseases with high mortality rates, predominantly attributable to acute and severe pulmonary inflammation. Lomerizine (LMZ) is a calcium channel blocker previously used in preventing and treating migraine. Here, we found that LMZ inhibited inflammatory responses and lung pathological injury by reducing pulmonary edema, neutrophil infiltration and pro-inflammatory cytokine production in lipopolysaccharide (LPS)-induced ALI mice. In vitro experiments, upon treating with LMZ, the expression of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α was attenuated in macrophages. The phosphorylation of p38 MAPK, ERK1/2, JNK, and NF-κB p65 was inhibited after LMZ treatment. Furthermore, LPS-induced Ca2+ influx was reduced by treating with LMZ, which correlated with inhibition of pro-inflammatory cytokine production. And L-type Ca2+ channel agonist Bay K8644 (BK) could restore cytokine generation. In conclusion, our study demonstrated that LMZ alleviates LPS-induced ALI and is a potential agent for treating ALI/ARDS

Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials: RISE and RIDE.

PURPOSE: To report 36-month outcomes of RIDE (NCT00473382) and RISE (NCT00473330), trials of ranibizumab in diabetic macular edema (DME). DESIGN: Phase III, randomized, multicenter, double-masked, 3-year trials, sham injection-controlled for 2 years. PARTICIPANTS: Adults with DME (n=759), baseline best-corrected visual acuity (BCVA) 20/40 to 20/320 Snellen equivalent, and central foveal thickness (CFT) ≥ 275 μm on optical coherence tomography. METHODS: Patients were randomized equally (1 eye per patient) to monthly 0.5 mg or 0.3 mg ranibizumab or sham injection. In the third year, sham patients, while still masked, were eligible to cross over to monthly 0.5 mg ranibizumab. Macular laser was available to all patients starting at month 3; panretinal laser was available as necessary. MAIN OUTCOME MEASURES: The proportion of patients gaining ≥15 Early Treatment Diabetic Retinopathy Study letters in BCVA from baseline at month 24. RESULTS: Visual acuity (VA) outcomes seen at month 24 in ranibizumab groups were consistent through month 36; the proportions of patients who gained ≥15 letters from baseline at month 36 in the sham/0.5 mg, 0.3 mg, and 0.5 mg ranibizumab groups were 19.2%, 36.8%, and 40.2%, respectively, in RIDE and 22.0%, 51.2%, and 41.6%, respectively, in RISE. In the ranibizumab arms, reductions in CFT seen at 24 months were, on average, sustained through month 36. After crossover to 1 year of treatment with ranibizumab, average VA gains in the sham/0.5 mg group were lower compared with gains seen in the ranibizumab patients after 1 year of treatment (2.8 vs. 10.6 and 11.1 letters). Per-injection rates of endophthalmitis remained low over time (∼0.06% per injection). The incidence of serious adverse events potentially related to systemic vascular endothelial growth factor inhibition was 19.7% in patients who received 0.5 mg ranibizumab compared with 16.8% in the 0.3 mg group. CONCLUSIONS: The strong VA gains and improvement in retinal anatomy achieved with ranibizumab at month 24 were sustained through month 36. Delayed treatment in patients receiving sham treatment did not seem to result in the same extent of VA improvement observed in patients originally randomized to ranibizumab. Ocular and systemic safety was generally consistent with the results seen at month 24. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references