The role of macrophage polarization in vascular calcification.

Vascular calcification is an important factor in the high morbidity and mortality of Cardiovascular and cerebrovascular diseases. Vascular damage caused by calcification of the intima or media impairs the physiological function of the vascular wall. Inflammation is a central factor in the development of vascular calcification. Macrophages are the main inflammatory cells. Dynamic changes of macrophages with different phenotypes play an important role in the occurrence, progression and stability of calcification. This review focuses on macrophage polarization and the relationship between macrophages of different phenotypes and calcification environment, as well as the mechanism of interaction, it is considered that macrophages can promote vascular calcification by releasing inflammatory mediators and promoting the osteogenic transdifferentiation of smooth muscle cells and so on. In addition, several therapeutic strategies aimed at macrophage polarization for vascular calcification are described, which are of great significance for targeted treatment of vascular calcification.

A Single-Cell Landscape of Spermioteleosis in Mice and Pigs.

(1) Background: Spermatozoa acquired motility and matured in epididymis after production in the testis. However, there is still limited understanding of the specific characteristics of sperm development across different species. In this study, we employed a comprehensive approach to analyze cell compositions in both testicular and epididymal tissues, providing valuable insights into the changes occurring during meiosis and spermiogenesis in mouse and pig models. Additionally, we identified distinct gene expression signatures associated with various spermatogenic cell types. (2) Methods: To investigate the differences in spermatogenesis between mice and pigs, we constructed a single-cell RNA dataset. (3) Results: Our findings revealed notable differences in testicular cell clusters between these two species. Furthermore, distinct gene expression patterns were observed among epithelial cells from different regions of the epididymis. Interestingly, regional gene expression patterns were also identified within principal cell clusters of the mouse epididymis. Moreover, through analysing differentially expressed genes related to the epididymis in both mouse and pig models, we successfully identified potential marker genes associated with sperm development and maturation for each species studied. (4) Conclusions: This research presented a comprehensive single-cell landscape analysis of both testicular and epididymal tissues, shedding light on the intricate processes involved in spermatogenesis and sperm maturation, specifically within mouse and pig models.

Triglyceride-glucose index is associated with poor prognosis in acute coronary syndrome patients with prior coronary artery bypass grafting undergoing percutaneous coronary intervention.

BACKGROUND: The triglyceride-glucose (TyG) index, which is a reliable substitute indicator for insulin resistance, has been considered an independent risk factor for long-term outcomes in patients with cardiovascular disease. However, it remains unknown whether the TyG index is associated with poor prognosis in acute coronary syndrome (ACS) patients with prior coronary artery bypass grafting (CABG) undergoing percutaneous coronary intervention (PCI). METHODS: A total of 1158 ACS patients with prior CABG undergoing PCI were retrospectively studied. The TyG index was calculated by ln[fasting triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2]. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), a composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke, and unplanned repeat revascularization. RESULTS: During a median of 42-month follow-up, 350 patients (30.2%) experienced at least one endpoint event. Based on the optimal cut-off value of the TyG index, patients were divided into the high TyG index group and the low TyG index group. Patients in the high TyG index group had higher risks of MACCE (35.3% vs. 25.3%, p < 0.001), major adverse cardiovascular events (MACE) (31.1% vs. 23.4%, p = 0.003), nonfatal stroke (4.2% vs. 1.9%, p = 0.022) and unplanned repeat revascularization (19.4% vs. 11.3%, p < 0.001) than those in the low TyG index group. Cox regression analysis demonstrated that there was an independent association between the TyG index and MACCE regardless of whether the TyG index was a continuous or categorical variable (HR 1.42, 95% CI 1.09-1.86, p = 0.009; HR 1.53, 95% CI 1.16-2.01, p = 0.003, respectively). Restricted cubic spline curve exhibited that the relationship between the TyG index and MACCE was linear (p for non-linear = 0.595, p for overall = 0.005). By incorporating the TyG index groups into baseline risk model, the accuracy of predicting MACCE was improved [AUC: baseline risk model, 0.618 vs. baseline risk model + TyG index groups, 0.636, p for comparison = 0.042]. CONCLUSIONS: The TyG index is independently associated with MACCE, suggesting that the TyG index may serve as a valid indicator for predicting poor prognosis in ACS patients with prior CABG undergoing PCI.

MiR-449a downregulation alleviates the progression of renal interstitial fibrosis by mediating the KLF4/MFN2 axis.

BACKGROUND: Renal interstitial fibrosis (RIF) seriously threatens the health of individuals. MiRNAs regulate the progression of fibrosis. Nevertheless, the detailed function of miR-449a in RIF is largely unknown. METHODS: In vitro and in vivo models of RIF were developed to evaluate the function of miR-449a. The relationship among miR-449a, KLF4, and MFN2 was explored using a dual-luciferase reporter assay and chromatin immunoprecipitation. Additionally, the pathological changes in the mice were detected using Masson staining. The mRNA and protein expressions were assessed using quantitative reverse transcription polymerase chain reaction and western blot, respectively. RESULTS: TGF-ß1 downregulated the expressions of KLF4 and MFN2 in TCMK-1 cells, but upregulated the level of miR-449a. The downregulation of miR-449a significantly inhibited TGF-ß1-induced upregulation of fibrotic proteins in TCMK-1 cells. Meanwhile, miR-449a directly targeted KLF4. Moreover, KLF4 overexpression activated MFN2 transcription and reversed TGF-ß1-induced fibrosis by positively regulating MFN2. Furthermore, the downregulation of miR-449a could obviously alleviate the symptoms of RIF in mice with unilateral ureteral obstruction. CONCLUSION: MiR-449a downregulation attenuated the development of RIF by mediating the KLF4/MFN2 axis. Therefore, miR-449a might act as a target in treating RIF.

Dynamic prevalence of sleep disturbance among critically ill patients in intensive care units and after hospitalisation: A systematic review and meta-analysis.

BACKGROUND: Sleep disturbance is a common complaint among critically ill patients in intensive care units and after hospitalisation. However, the prevalence of sleep disturbance among critically ill patients varies widely. OBJECTIVE: To estimate the prevalence of sleep disturbance among critically ill patients in the intensive care unit and after hospitalisation. METHODS: Electronic databases were searched from their inception until 15 August 2022. Only observational studies with cross-sectional, prospective, and retrospective designs investigating sleep disturbance prevalence among critically ill adults (aged ≥ 18 years) during intensive care unit stay and after hospitalisation were included. RESULTS: We found 13 studies investigating sleep disturbance prevalence in intensive care units and 14 investigating sleep disturbance prevalence after hospitalisation, with 1,228 and 3,065 participants, respectively. The prevalence of sleep disturbance during an ICU stay was 66 %, and at two, three, six and ≥ 12 months after hospitalisation was 64 %, 49 %, 40 %, and 28 %, respectively. Studies using the Richards-Campbell Sleep Questionnaire detected a higher prevalence of sleep disturbance among patients in intensive care units than non-intensive care unit specific questionnaires; studies reported comparable sleep disturbance prevalence during intensive care stays for patients with and without mechanical ventilation. CONCLUSION: Sleep disturbance is prevalent in critically ill patients admitted to an intensive care unit and persists for up to one year after hospitalisation, with prevalence ranging from 28 % to 66 %. The study results highlight the importance of implementing effective interventions as early as possible to improve intensive care unit sleep quality.

Design and synthesis of novel orally selective and type II pan-TRK inhibitors to overcome mutations by property-driven optimization.

Rare oncogenic NTRK gene fusions result in uncontrolled TRK signaling leading to various adult and pediatric solid tumors. Based on the architecture of our multi-targeted clinical candidate BPR1K871 (10), we designed and synthesized a series of quinazoline compounds as selective and orally bioavailable type II TRK inhibitors. Property-driven and lead optimization strategies informed by structure-activity relationship studies led to the identification of 39, which showed higher (about 15-fold) selectivity for TRKA over AURA and AURB, as well as potent cellular activity (IC50 = 56.4 nM) against the KM12 human colorectal cancer cell line. 39 also displayed good AUC and oral bioavailability (F = 27%), excellent in vivo efficacy (TGI = 64%) in a KM12 xenograft model, and broad-spectrum anti-TRK mutant potency (IC50 = 3.74-151.4 nM), especially in the double-mutant TRKA enzymatic assays. 39 is therefore proposed for further development as a next-generation, selective, and orally-administered type II TRK inhibitor.

The Role of Leisure Satisfaction in Serious Leisure and Subjective Well-Being: Evidence From Chinese Marathon Runners.

The topics of serious leisure and subjective well-being have been discussed extensively in previous research. It is generally acknowledged that people prefer to experience deeper satisfaction and happiness through serious participation in leisure-time physical activities. However, it is essential to examine the relationship between serious leisure and subjective well-being in an urban setting as well as the mediating effect of leisure satisfaction. Data were collected from 447 recreational runners at the 2018 Wuxi International Marathon event in China. The study results showed that serious leisure was positively associated with leisure satisfaction and subjective well-being, that leisure satisfaction was positively associated with subjective well-being, and that leisure satisfaction completely mediated the relationship between serious leisure and subjective well-being. Running group membership significantly affected the path from serious leisure to leisure satisfaction, while other demographic variables (e.g., gender and education) did not moderate any paths. These results help explain the intricate relationship between serious leisure and subjective well-being and offer theoretical and managerial implications for serious leisure.

In-phase and anti-phase entanglement dynamics of Rydberg atomic pairs.

We study the correlated evolutions of two far-spaced Rydberg atomic pairs with different resonant frequencies, interacting via van der Waals (vdW) potentials and driven by a common laser field. They are found to exhibit in-phase (anti-phase) beating dynamics characterized by identical (complementary) intra-pair entanglements under a specific condition in regard of inter-pair vdW potentials and driving field detunings. This occurs when each atomic pair just oscillates between its ground state and symmetric entangled state because its doubly excited state and asymmetric entangled state are forbidden due to rigid dipole blockade and perfect destructive interference, respectively. More importantly, optimal inter-pair overall entanglement can be attained at each beating node corresponding to semi-optimal intra-pair entanglements, and inevitable dissipation processes just result in a slow decay of intra-pair and inter-pair entanglements yet without destroying in-phase and anti-phase beating dynamics.

MENDA: a comprehensive curated resource of metabolic characterization in depression.

Depression is a seriously disabling psychiatric disorder with a significant burden of disease. Metabolic abnormalities have been widely reported in depressed patients and animal models. However, there are few systematic efforts that integrate meaningful biological insights from these studies. Herein, available metabolic knowledge in the context of depression was integrated to provide a systematic and panoramic view of metabolic characterization. After screening more than 10 000 citations from five electronic literature databases and five metabolomics databases, we manually curated 5675 metabolite entries from 464 studies, including human, rat, mouse and non-human primate, to develop a new metabolite-disease association database, called MENDA (http://menda.cqmu.edu.cn:8080/index.php). The standardized data extraction process was used for data collection, a multi-faceted annotation scheme was developed, and a user-friendly search engine and web interface were integrated for database access. To facilitate data analysis and interpretation based on MENDA, we also proposed a systematic analytical framework, including data integration and biological function analysis. Case studies were provided that identified the consistently altered metabolites using the vote-counting method, and that captured the underlying molecular mechanism using pathway and network analyses. Collectively, we provided a comprehensive curation of metabolic characterization in depression. Our model of a specific psychiatry disorder may be replicated to study other complex diseases.

A new model for predicting intravenous immunoglobin-resistant Kawasaki disease in Chongqing: a retrospective study on 5277 patients.

Accurate evaluation of individual risk of intravenous immunoglobin (IVIG)-resistance is critical for adopting regimens for the first treatment and prevention of coronary artery lesions (CALs) in patients with Kawasaki disease (KD). METHODS: The KD patients hospitalized in Chongqing Children's Hospital, in west China, from October 2007 to December 2017 were retrospectively reviewed. Data were collected and compared between IVIG-resistant group and IVIG-responsive group. The independent risk factors were determined using multivariate regression analysis. A new prediction model was built and compared with the previous models. RESULTS: A total of 5277 subjects were studied and eight independent risk factors were identified including higher red blood cell distribution width (RDW), lower platelet count (PLT), lower percentage of lymphocyte (P-LYM), higher total bile acid (TBA), lower albumin, lower serum sodium level, higher degree of CALs (D-CALs) and younger age. The new predictive model showed an AUC of 0.74, sensitivity of 76% and specificity of 59%. For individual's risk probability of IVIG-resistance, an equation was given. CONCLUSIONS: IVIG-resistance could be predicted by RDW, PLT, P-LYM, TBA, albumin, serum sodium level, D-CALs and age. The new model appeared to be superior to those previous models for KD population in Chongqing city.

Anaerobic degradation of sulfamethoxazole by mixed cultures from swine and sewage sludge.

The objective of this study was to evaluate the anaerobic degradation of sulfamethoxazole (SMX) and the associated bacterial community changes in swine and sewage sludges. The degradation rate of SMX was higher in swine sludge than in sewage sludge. The addition of lactate, citrate, and sucrose had significant effects on SMX degradation, and sucrose addition yielded a higher SMX degradation rate than the other additives. At concentrations of 0.1-10 g/l sucrose, the SMX degradation rates increased in the sludge. The bacterial genera from swine sludge with sucrose exhibited the highest SMX degrading efficiency. Seventeen bacterial genera were found to be the major bacterial community members involved in SMX degradation in the sludge.

All-optical transistor based on Rydberg atom-assisted optomechanical system.

We study the optical response of a double optomechanical cavity system assisted by two Rydberg atoms. The target atom is only coupled with one side cavity by a single cavity mode, and gate one is outside the cavities. It has been realized that a long-range manipulation of optical properties of a hybrid system, by controlling the Rydberg atom decoupled with the optomechanical cavity. Switching on the coupling between atoms and cavity mode, the original spatial inversion symmetry of the double cavity structure has been broken. Combining the controllable optical non-reciprocity with the coherent perfect absorption/transmission/synthesis effect (CPA/CPT/CPS reported by [ X.-B.Yan Opt. Express 22, 4886 (2014)], we put forward the theoretical schemes of an all-optical transistor which contains functions such as a controllable diode, rectifier, and amplifier by controlling a single gate photon.

Worldwide Experience of a Durable Centrifugal Flow Pump in Pediatric Patients.

The primary objectives of this study were to describe the characteristics and survival outcomes for children supported with the HeartWare HVAD® system from the global community. This was a retrospective survey of patients <18 years of age with an HVAD® system. Questionnaires were sent to sites worldwide in April 2015 and collected between May 2015 and 2016. Information on 205 patients was collected. The median age at implantation was 13.1 years (interquartile range [IQR] 9.8-15.8 years) and the weight was 42 kg (IQR 28-60 kg). Over half of the implants occurred in males (61%), with the most common diagnosis being cardiomyopathy (n = 168, 82%). The majority of HVAD® systems implanted were left ventricular assist device (n = 189, 92.2%). Temporary right ventricular support was utilized in 24 patients (12%) with a median duration of 12 days (6-32 days). Fifty-five percent (n = 111) of the patients were discharged home after implantation after a median (IQR) duration of hospital stay of 40 days (28-71 days). By 12 months, the proportion of patients who underwent heart transplant was 65.4%, 10.7% had died, 3.2% were explanted for recovery, and 20.8% remained on the device. Death on the device on multivariable analysis was associated with the need for temporary RV support (hazard ratio [HR] 10.65 (95% CI 12.53-44.81), P = 0.001) and pump exchange (HR 7.9 (95% CI 1.8-34.2], P = 0.006). The use of the HeartWare HVAD system in the pediatric population is associated with mortality with the majority of patients supported to heart transplant by 1 year post implant. These positive results are independent of geographic location. The need for a temporary right heart support and pump exchange is associated with a higher risk of poor outcomes, and further work is required to predict these patients to allow for optimization. Although survival results are promising, further studies are needed to delineate the associated morbidities with this technology in the pediatric population.

Enhanced nonlinear characteristics with the assistance of a [Formula: see text]-symmetric trimer system.

We study the parity-time (PT) symmetry characteristics and the applications to nonlinear optics in an optical trimer system consisting of two indirectly coupled standing-mode micro-cavities and a two-level quantum emitter (QE) placed at the intersection of two cavities. We find this trimer system can exhibit analogical phenomena as those in typical [Formula: see text]-symmetric dimer systems composed of a passive cavity directly coupled to an active cavity. This system, whose [Formula: see text] symmetry is demonstrated by our analytic results, can be transformed between the [Formula: see text]-symmetric phase and the [Formula: see text]-broken phase by adjusting relevant system parameters. Then, with this system, we observe both the linear and nonlinear parts of the transmission field become remarkably enhanced and can further reach peak values around the [Formula: see text] breaking point. In addition, we show the negative correlation between the gain degree of the linear (nonlinear) transmission part and decay rate of the QE. This trimer proposal is feasible for experiments and may provide a promising platform for [Formula: see text]-symmetric optics of low-light levels. Moreover, novel phenomena arising from the QE-cavity-coupling induced nonlinearity gain could be explored to fabricate photonic devices and controllable nonlinear optical media for quantum information process and communication of photons.

Asymmetric light diffraction of an atomic grating with PT symmetry.

Cold atoms trapped in one-dimensional optical lattices and driven to the four-level N configuration are exploited for achieving an electromagnetically induced grating with parity-time-symmetry. This nontrivial grating exhibits unidirectional diffraction patterns, e.g., with incident probe photons diffracted into either negative or positive angles, depending on the sign relation between spatially modulated absorption and dispersion coefficients. Such asymmetric light diffraction is a result of the out-of-phase interplay of amplitude and phase modulations of transmission function and can be easily tuned via optical depth, probe detuning, pump Rabi frequencies, etc.

Synchronization enhancement of indirectly coupled oscillators via periodic modulation in an optomechanical system.

We study the synchronization behaviors of two indirectly coupled mechanical oscillators of different frequencies in a doublecavity optomechanical system. It is found that quantum synchronization is roughly vanishing though classical synchronization seems rather good when each cavity mode is driven by an external field in the absence of temporal modulations. By periodically modulating cavity detunings or driving amplitudes, however, it is possible to observe greatly enhanced quantum synchronization accompanied with nearly perfect classical synchronization. The level of quantum synchronization observed here is, in particular, much higher than that for two directly coupled mechanical oscillators. Note also that the modulation on cavity detunings is more appealing than that on driving amplitudes when the robustness of quantum synchronization is examined against the bath's mean temperature or the oscillators' frequency difference.

[Assessment of skin aging grading based on computer vision].

Skin aging is the most intuitive and obvious sign of the human aging processes. Qualitative and quantitative determination of skin aging is of particular importance for the evaluation of human aging and anti-aging treatment effects. To solve the problem of subjectivity of conventional skin aging grading methods, the self-organizing map (SOM) network was used to explore an automatic method for skin aging grading. First, the ventral forearm skin images were obtained by a portable digital microscope and two texture parameters, i.e., mean width of skin furrows and the number of intersections were extracted by image processing algorithm. Then, the values of texture parameters were taken as inputs of SOM network to train the network. The experimental results showed that the network achieved an overall accuracy of 80.8%, compared with the aging grading results by human graders. The designed method appeared to be rapid and objective, which can be used for quantitative analysis of skin images, and automatic assessment of skin aging grading.

Bacterial communities associated with sulfonamide antibiotics degradation in sludge-amended soil.

This study investigated the degradation of sulfonamide antibiotics (SAs) and microbial community changes in sludge-amended soil. In batch experiments, SA degradation was enhanced by addition of spent mushroom compost (SMC), SMC extract, and extract-containing microcapsule, with SMC showing higher SA degradation rate than the other additives in soil-sludge mixtures. In bioreactor experiments, the degradation of SAs in soil-sludge mixtures was in the order of sulfamethoxazole > sulfadimethoxine > sulfamethazine during four times of SA addition. SA removal was higher in soil-sludge mixtures than in soil alone. The bacterial composition differed in soil-sludge mixtures with and without SMC. In total, 44 differentially distributed bacterial genera were identified from different experimental settings and stages. Four bacterial genera, Acinetobacter, Alcaligenes, Brevundimonas, and Pseudomonas, were previously found involved in SA degradation, and 20 of the 44 bacterial genera were previously found in aromatic hydrocarbon degradation. Therefore, these bacteria have high potential to be SA degradation bacteria in this study.

Intervention timing and effect of PJ34 on astrocytes during oxygen-glucose deprivation/reperfusion and cell death pathways / 华中科技大学学报（医学）（英德文版）

Poly (ADP-ribose) polymerase-1 (PARP-1) plays as a double edged sword in cerebral ischemia-reperfusion, hinging on its effect on the intracellular energy storage and injury severity, and the prognosis has relationship with intervention timing. During ischemia injury, apoptosis and oncosis are the two main cell death pathway sin the ischemic core. The participation of astrocytes in ischemia-reperfusion induced cell death has triggered more and more attention. Here, we examined the protective effects and intervention timing of the PARP-1 inhibitor PJ34, by using a mixed oxygen-glucose deprivation/reperfusion (OGDR) model of primary rat astrocytes in vitro, which could mimic the ischemia-reperfusion damage in the "ischemic core". Meanwhile, cell death pathways of various PJ34 treated astrocytes were also investigated. Our results showed that PJ34 incubation (10 μmol/L) did not affect release of lactate dehydrogenase (LDH) from astrocytes and cell viability or survival 1 h after OGDR. Interestingly, after 3 or 5 h OGDR, PJ34 significantly reduced LDH release and percentage of PI-positive cells and increased cell viability, and simultaneously increased the caspase-dependent apoptotic rate. The intervention timing study demonstrated that an earlier and longer PJ34 intervention during reperfusion was associated with more apparent protective effects. In conclusion, earlier and longer PJ34 intervention provides remarkable protective effects for astrocytes in the "ischaemic core" mainly by reducing oncosis of the astrocytes, especially following serious OGDR damage.