Search

Highlights We revealed a universal self-adaptive structural reconstruction from Cu2O to Cu@CuxO composites, ending with feeding gas-dependent microstructures and catalytic performances. We uncovered a CO2-induced passivation behavior by identifying a reduction-resistant but catalytic active Cu(I)-rich amorphous layer. We designed and fabricated hollow Cu2O nanospheres, demonstrating durable electrolysis at a partial current density of −200 mA cm−2 in producing C2H4 with an FE of up to 61% at −0.6 VRHE.

Abstract CT is crucial for diagnosing chest diseases, with image quality affected by spatial resolution. Thick-slice CT remains prevalent in practice due to cost considerations, yet its coarse spatial resolution may hinder accurate diagnoses. Our multicenter study develops a deep learning synthetic model with Convolutional-Transformer hybrid encoder-decoder architecture for generating thin-slice CT from thick-slice CT on a single center (1576 participants) and access the synthetic CT on three cross-regional centers (1228 participants). The qualitative image quality of synthetic and real thin-slice CT is comparable (p = 0.16). Four radiologists’ accuracy in diagnosing community-acquired pneumonia using synthetic thin-slice CT surpasses thick-slice CT (p 0.99). For lung nodule detection, sensitivity with thin-slice CT outperforms thick-slice CT (p 0.05). These findings indicate the potential of our model to generate high-quality synthetic thin-slice CT as a practical alternative when real thin-slice CT is preferred but unavailable.

IntroductionThe present study explores the effect of ginseng stem leaf (GSL) extract on the production performance, meat quality, antioxidant status, immune function, and lipid metabolism of white feathered broilers.MethodsThere were 6 replicates in each group, with 10 broilers in each replicate. In the 42 day trial, 300 AA broilers were randomly divided into five groups: control group (CON), 1.25% GSL extract group (GSL-L), 2.5% GSL group (GSL-M), 5% GSL group (GSL-H), and 45 mg/kg chlortetracycline group (CTC).ResultsThe results showed that different doses of GSL extract could improve the body weight, feed to gain ratio (F/G), average daily feed intake (ADFI), average daily gain (ADG), and meat quality of broilers. Compared with the control group, the addition of different doses of GSL improved the antioxidant and immune abilities of broilers to varying degrees, and the effect of GSL extract was significant in the GSL-H group (p

BackgroundCoronary artery disease (CAD) imposes a significant global health burden, necessitating a deeper comprehension of its genetic foundations to uncover innovative therapeutic targets. Employing a comprehensive Mendelian randomization (MR) approach, we aimed to explore the genetic associations between lipid profiles, immune cell phenotypes, and CAD risk.MethodsUtilizing data from recent large-scale genome-wide association studies (GWAS), we scrutinized 179 lipid and 731 immune cell phenotypes to delineate their genetic contributions to CAD pathogenesis, including coronary artery calcification (CAC). Moreover, specific immune cell phenotypes were examined as potential mediators of the lipid-CAD/CAC causal pathway.ResultsAmong the 162 lipid species with qualified instrumental variables (IVs) included in the analysis, we identified 36 lipids that exhibit a genetic causal relationship with CAD, with 29 being risk factors and 7 serving as protective factors. Phosphatidylethanolamine (18:0_20:4) with 8 IVs (OR, 95% CI, P-value: 1.04, 1.02-1.06, 1.50E-04) met the Bonferroni-corrected significance threshold (0.05/162 = 3.09E-04). Notably, all 18 shared lipids were determined to be risk factors for both CAD and CAC, including 16 triacylglycerol traits (15 of which had ≥ 3 IVs), with (50:1) exhibiting the highest risk [OR (95% CI) in CAC: 1.428 (1.129-1.807); OR (95% CI) in CAD: 1.119 (1.046-1.198)], and 2 diacylglycerol traits. Furthermore, we identified HLA DR+ natural killer cells (IVs = 3) as nominally significant with lipids and as potential mediators in the causal pathway between diacylglycerol (16:1_18:1) or various triacylglycerols and CAD (mediated effect: 0.007 to 0.013).ConclusionsThis study provides preliminary insights into the genetic correlations between lipid metabolism, immune cell dynamics, and CAD susceptibility, highlighting the potential involvement of natural killer cells in the lipid-CAD/CAC causal pathway and suggesting new targets for therapy. Further evidence is necessary to substantiate our findings.

Severe COVID-19 cases often progress to life-threatening conditions such as acute respiratory distress syndrome (ARDS), sepsis, and multiple organ dysfunction syndrome (MODS). Gelsolin (GSN), an actin-binding protein with anti-inflammatory and immunomodulatory properties, is a promising therapeutic target for severe COVID-19. Plasma GSN levels are significantly decreased in critical illnesses, including COVID-19, correlating with dysregulated immune responses and poor outcomes. GSN supplementation may mitigate acute lung injury, ARDS, and sepsis, which share pathophysiological features with severe COVID-19, by scavenging actin, modulating cytokine production, enhancing macrophage phagocytosis, and stabilizing the alveolar-capillary barrier. Preliminary data indicate that recombinant human plasma GSN improves oxygenation and lung function in severe COVID-19 patients with ARDS. Although further research is needed to optimize GSN therapy, current evidence supports its potential to mitigate severe consequences of COVID-19 and improve patient outcomes. This review provides a comprehensive analysis of the biological characteristics, mechanisms, and therapeutic value of GSN in severe COVID-19.

For the requirements of real-time services in autonomous driving systems, such as high-definition (HD) maps, based on the integration of sensing, communication, and computing, a multi-node cooperative sensing mechanism was proposed with the age of information (AoI) as the real-time indicator.Considering the constraints on communication and computing resources and vehicle energy consumption, the information collection, transmission and processing of sensing nodes were optimally scheduled to minimize the AoI averaged over time.A Lyapunov-based online scheduling algorithm was proposed to transform the long-term stochastic optimization problem into an online optimization problem, which could be solved with low complexity.Compared with the existing mechanism considering integrated communication and computing, the proposed mechanism can improve real-time performance by 9%～50%.

Abstract Mucopolysaccharidoses (MPS) screening is tedious and still performed by analysis of total glycosaminoglycans (GAG) using 1,9‐dimethylmethylene blue (DMB) photometric assay, although false positive and negative tests have been reported. Analysis of differentiated GAGs have been pursued classically by gel electrophoresis or more recently by quantitative LC–MS assays. Secondary elevations of GAGs have been reported in urinary tract infections (UTI). In this manuscript, we describe the diagnostic accuracy of urinary GAG measurements by LC–MS for MPS typing in 68 untreated MPS and mucolipidosis (ML) patients, 183 controls and 153 UTI samples. We report age‐dependent reference values and cut‐offs for chondroitin sulfate (CS), dermatan sulfate (DS), heparan sulfate (HS) and keratan sulfate (KS) and specific GAG ratios. The use of HS/DS ratio in combination to GAG concentrations normalized to creatinine improves the diagnostic accuracy in MPS type I, II, VI and VII. In total 15 samples classified to the wrong MPS type could be correctly assigned using HS/DS ratio. Increased KS/HS ratio in addition to increased KS improves discrimination of MPS type IV by excluding false positives. Some samples of UTI patients showed elevation of specific GAGs, mainly CS, KS and KS/HS ratio and could be misclassified as MPS type IV. Finally, DMB photometric assay performed in MPS and ML samples reveal four false negative tests (sensitivity of 94%). In conclusion, specific GAG ratios in complement to quantitative GAG values obtained by LC–MS enhance discrimination of MPS types. Exclusion of patients with UTI improve diagnostic accuracy in MPS IV but not in other types.

Objectives: This study aimed to investigate the association between drug exposure and adverse events (AEs) during the standardized multidrug-resistant tuberculosis (MDR-TB) treatment, as well as to identify predictive drug exposure thresholds. Methods: We conducted a prospective, observational multicenter study among participants receiving standardized MDR-TB treatment between 2016 and 2019 in China. AEs were monitored throughout the treatment and their relationships to drug exposure (e.g., the area under the drug concentration-time curve from 0 to 24 h, AUC0-24 h) were analyzed. The thresholds of pharmacokinetic predictors of observed AEs were identified by boosted classification and regression tree (CART) and further evaluated by external validation. Results: Of 197 study participants, 124 (62.9%) had at least one AE, and 15 (7.6%) experienced serious AEs. The association between drug exposure and AEs was observed including bedaquiline, its metabolite M2, moxifloxacin and QTcF prolongation (QTcF >450 ms), linezolid and mitochondrial toxicity, cycloserine and psychiatric AEs. The CART-derived thresholds of AUC0-24 h predictive of the respective AEs were 3.2 mg·h/l (bedaquiline M2); 49.3 mg·h/l (moxifloxacin); 119.3 mg·h/l (linezolid); 718.7 mg·h/l (cycloserine). Conclusions: This study demonstrated the drug exposure thresholds predictive of AEs for key drugs against MDR-TB treatment. Using the derived thresholds will provide the knowledge base for further randomized clinical trials of dose adjustment to minimize the risk of AEs.

Three-dimensional (3D) microstructure reconstruction is a key approach to exploring the relationship between pore characteristics and physical properties. Viewing the training image as a prior model, multiple-point statistics (MPS) focus on reproducing spatial patterns in the simulation grid. However, it is challenging to efficiently generate 3D nonstationary models with varying microstructures. In this work, we propose column-oriented simulation (ColSIM) to achieve the stochastic reconstruction of 3D porous media. A heterogeneous system is understood as a spatially evolving process that consists of frequent transitions of small magnitude and abrupt changes of large magnitude. First, a training image selection step is suggested to find representative microstructures. Our program applies modified Hausdorff distance, t-distributed stochastic neighboring embedding, and spectral clustering to organize two-dimensional (2D) candidate images. The medoid of each group is applied to guide the following programs. Second, we introduce column-oriented searching into MPS. To save simulation time, a subset of conditioning points is checked to find desired instances. Our program suggests an early stopping strategy to address complex microstructures. Third, a contrastive loss term is designed to create 3D models from 2D slice. To automatically calibrate the volume fraction and simplify parameter specification, the computer consistently monitors the difference between the present model and the target. The performance of ColSIM is examined by 3D multiphase material modeling and 3D heterogeneous shale simulation. To achieve quantitative evaluation, we compute various statistical functions and physical descriptors on simulated realizations. The proposed ColSIM exhibits competitive performance in terms of calculation efficiency, microstructure reproduction, and spatial uncertainty.

Silent information regulator two homolog 1 (SIRT1), an NAD + -dependent histone deacetylase, plays a pivotal regulatory role in a myriad of physiological processes. A growing body of evidence suggests that SIRT1 can exert protective effects in metabolic disorders and neurodegenerative diseases by inhibiting endoplasmic reticulum (ER) stress and the nuclear factor-κB (NF-κB) inflammatory signaling pathway. This review systematically elucidates the molecular mechanisms and biological significance of SIRT1 in regulating ER stress and the NF-κB pathway. On one hand, SIRT1 can deacetylate key molecules in the ER stress pathway, such as glucose-regulated protein 78 (GRP78), X-box binding protein 1 (XBP1), PKR-like ER kinase (PERK), inositol-requiring enzyme 1α (IRE1α), and activating transcription factor 6 (ATF6), thereby alleviating ER stress. On the other hand, SIRT1 can directly or indirectly remove the acetylation modification of the NF-κB p65 subunit, inhibiting its transcriptional activity and thus attenuating inflammatory responses. Through these mechanisms, SIRT1 can ameliorate insulin resistance in metabolic diseases, exert cardioprotective effects in ischemia-reperfusion injury, and reduce neuronal damage in neurodegenerative diseases. However, it is important to note that while these findings are promising, the complex nature of the biological systems involved warrants further investigation to fully unravel the intricacies of SIRT1’s regulatory mechanisms. Nevertheless, understanding the regulatory mechanisms of SIRT1 on ER stress and the NF-κB pathway is of great significance for expanding our knowledge of the pathogenesis of related diseases and exploring new preventive and therapeutic strategies targeting SIRT1.

Abstract Iron is an extraordinary promoter to impose nickel/cobalt (hydr)oxides as the most active oxygen evolution reaction catalysts, whereas the synergistic effect is actively debated. Here, we unveil that active oxygen species mediate a strong electrochemical interaction between iron oxides (FeOxHy) and the supporting metal oxyhydroxides. Our survey on the electrochemical behavior of nine supporting metal oxyhydroxides (M(O)OH) uncovers that FeOxHy synergistically promotes substrates that can produce active oxygen species exclusively. Tafel slopes correlate with the presence and kind of oxygen species. Moreover, the oxygen evolution reaction onset potentials of FeOxHy@M(O)OH coincide with the emerging potentials of active oxygen species, whereas large potential gaps are present for intact M(O)OH. Chemical probe experiments suggest that active oxygen species could act as proton acceptors and/or mediators for proton transfer and/or diffusion in cooperative catalysis. This discovery offers a new insight to understand the synergistic catalysis of Fe-based oxygen evolution reaction electrocatalysts.

Abstract Conventional manufacturing techniques to fabricate microfluidic chips, such as soft lithography and hot embossing process, have limitations that include difficulty in preparing multiple-layered structures, cost- and labor-consuming fabrication process, and low productivity. Digital light processing (DLP) technology has recently emerged as a cost-efficient microfabrication approach for the 3D printing of microfluidic chips; however, the fabrication resolution for microchannels is still limited to sub-100 microns at best. Here, we developed an innovative DLP printing strategy for high resolution and scalable microchannel fabrication by dosing- and zoning-controlled vat photopolymerization (DZC-VPP). Specifically, we proposed a modified mathematical model to precisely predict the accumulated UV irradiance for resin photopolymerization, thereby providing guidance for the fabrication of microchannels with enhanced resolution. By fine-tuning the printing parameters, including optical irradiance, exposure time, projection region, and step distance, we can precisely tailor the penetration irradiance stemming from the photopolymerization of the neighboring resin layers, thereby preventing channel blockage due to UV overexposure or compromised bonding stability owing to insufficient resin curing. Remarkably, this strategy can allow the preparation of microchannels with cross-sectional dimensions of 20 μm × 20 μm using a commercial printer with a pixel size of 10 μm × 10 μm; this is significantly higher resolution than previous reports. In addition, this method can enable the scalable and biocompatible fabrication of microfluidic drop-maker units that can be used for cell encapsulation. In general, the current DZC-VPP method can enable major advances in precise and scalable microchannel fabrication and represents a significant step forward for widespread applications of microfluidics-based techniques in biomedical fields.

The detection of two-line element (TLE) outliers and space events play a crucial role in enhancing spatial situational awareness. Therefore, this paper addresses the issue of TLE outlier detection methods that often overlook the mutual influence of multiple factors. Hence, a Multivariate Gaussian Mixture Model (MGMM) is introduced to consider the interdependencies among various indicators. Additionally, a Multi-strategy Genetic Algorithm (MGA) is employed to adjust the complexity of the MGMM, allowing it to accurately learn the actual distribution of TLE data. Initially, the proposed method applies probabilistic fits to the predicted error rate changes for both the TLE semi-major axis and the orbital inclination. Chaos initialization, a posterior probability penalty, and local optimization iterations are subsequently integrated into the genetic algorithm. These enhancements aim to estimate the MGMM parameters, addressing issues related to poor robustness and the susceptibility of the MGMM to converge to local optima. The algorithm’s effectiveness is validated using TLE data from typical space targets. The results demonstrate that the optimized algorithm can efficiently detect outliers and maneuver events within complex TLE data. Notably, the comprehensive detection performance index, measured, using the F1 score, improved by 15.9% compared to the Gaussian mixture model. This significant improvement underscores the importance of the proposed method in bolstering the security of complex space environments.

Temperature fluctuations affect the performance of high-precision gravitational reference sensors. Due to the limited space and the complex interrelations among sensors, it is not feasible to directly measure the temperatures of sensor heads using temperature sensors. Hence, a high-accuracy interpolation method is essential for reconstructing the surface temperature of sensor heads. In this study, we utilized XGBoost-LSTM for sensor head temperature reconstruction, and we analyzed the performance of this method under two simulation scenarios: ground-based and on-orbit. The findings demonstrate that our method achieves a precision that is two orders of magnitude higher than that of conventional interpolation methods and one order of magnitude higher than that of a BP neural network. Additionally, it exhibits remarkable stability and robustness. The reconstruction accuracy of this method meets the requirements for the key payload temperature control precision specified by the Taiji Program, providing data support for subsequent tasks in thermal noise modeling and subtraction.

Deficiencies of lysosomal enzymes responsible for the degradation of glycosaminoglycans (GAG) cause pathologies commonly known as the mucopolysaccharidoses (MPS). Each type of MPS is caused by a deficiency in a specific GAG-degrading enzyme and is characterized by an accumulation of disease-specific GAG species. Previously, we have shown the potential of the beta-D-xyloside, odiparcil, as an oral GAG clearance therapy for Maroteaux-Lamy syndrome (MPS VI), an MPS characterized by an accumulation of chondroitin sulphate (CS) and dermatan sulphate (DS). This work suggested that odiparcil acts via diverting the synthesis of CS and DS into odiparcil-bound excretable GAG. Here, we investigated the effect of odiparcil on lysosomal abundance in fibroblasts from patients with MPS I and MPS VI. In MPS VI fibroblasts, odiparcil reduced the accumulation of a lysosomal-specific lysotracker dye. Interestingly, a reduction of the lysotracker dye was also observed in odiparcil-treated fibroblasts from patients with MPS I, a disorder characterized by an accumulation of DS and heparan sulphate (HS). Furthermore, odiparcil was shown to be effective in reducing CS, DS, and HS concentrations in liver and eye, as representative organs, in MPS VI and MPS I mice treated with 3 doses of odiparcil over 3 and 9 months, respectively. In conclusion, our data demonstrates odiparcil efficiently reduced lysosome abundance and tissue GAG concentrations in in vitro and in vivo models of MPS VI and MPS I and has potential as a treatment for these disorders.

Abstract Crystal transformation of metal compound cathodes during charge/discharge processes in alkali metal‐ion batteries usually generates profound impact on structural stability and electrochemical performance, while the theme in anode materials, which always occurs and completes during the first redox cycle, is rarely explored probably due to the fast transformation dynamics. Herein, for the first time, a unique crystal transformation behavior with slow dynamics in anode of sodium‐ion batteries (SIBs) is reported, which further promotes electrochemical performance. Specifically, irreversible γ → β crystal transformation of In2Se3 is observed, induced by the persistent size degradation of In2Se3 particles during repeated sodiation/desodiation, supported by a series of ex situ characterizations, such as HRTEM, XRD, and XPS of γ‐In2Se3/reduced graphene oxide (γ‐In2Se3@rGO) nanocomposite. The hybrid electrode shows ultrahigh long‐term cycling stability (378 mA h g−1 at 1.0 A g−1 after 1000 cycles) and excellent rate capability (272 mA h g−1 at 20.0 A g−1). Full battery with Na3V2(PO4)3 cathode also manifests superior performance, promising β‐In2Se3 dominated electrode materials in high‐power and long‐life SIBs. The first‐principle calculations suggest the crystal transformation enhances electric conductivity of β‐In2Se3 and facilitates its accessibility to sodium. In combination with the synergistic effect between rGO matrix, substantially enhanced electrochemical performance is realized.

Supply chain financing provides important funding channels for micro and small enterprises (MSEs), but effectively evaluating their creditworthiness remains challenging. Past methods overly rely on static financial indicators and subjective judgment in determining credit evaluation weights. This study proposes a dynamic credit evaluation approach that uses sensitivity analysis to optimize the weighting scheme. An indicator system is constructed based on the unique characteristics of e-commerce MSEs. The weight optimization integrates subjective, objective, and sensitivity-based methods to reflect specific financing scenarios. A system dynamics model simulates the credit evaluation mechanism and identifies the sensitivity of each influencing factor. The resultant comprehensive weights are applied in a TOPSIS-GRA dynamic evaluation model to assess MSE credit levels over time. An empirical analysis of 20 online stores demonstrates the proposed model's advantages in accurately revealing credit rankings relative to conventional static models. This research provides an effective data-driven weighting technique and dynamic evaluation framework for supply chain finance credit assessment.

In power lines, the proportion of parallel cables is gradually increasing, but the uneven current distribution and sheath circulation affect the safe and stable operation of parallel cables. Existing studies show that cable current and sheath circulation are obviously affected by cable laying mode. At present, the designed cable laying mode is as “pin” laying and horizontal “I” laying. Combined with the above engineering difficulties, this paper focuses on the parameter optimization scheme of 220 kV two circuit parallel cables in the same direction when the metal sheath is cross connected and grounded. Firstly, the operation model of 220kV two circuits in-phase two parallel cables is established. The numerical differences between the current distribution non-uniformity coefficient and sheath circulating current of the cables are analyzed and calculated under the condition of “pin” laying and horizontal “I” laying. Meanwhile, the influence of different phase sequence arrangement on the current distribution non-uniformity coefficient and sheath circulating current of the cables is compared. Secondly, the cable laying mode of “symmetrical pin” is designed, and the improvement effect of uneven coefficient of cable current distribution and metal sheath circulating current under “symmetrical pin” laying is compared and analyzed. Finally, the differences of the above parameters in different phase sequence arrangements are compared and analyzed. The research results show that the symmetrical pin laying can improve the uneven distribution of current and sheath circulating current, which has important engineering practical value.

We consider a hypersonic vehicle optimal flight control problem. The problem is modeled as an optimal control problem of switched systems (OCPSS), which can become a parameter optimization problem (POP). Following that, to achieve the globally optimal solution of the POP, an improved continuous filled function (CFF) algorithm including one adjusting parameter is proposed based on a penalty function, in which the CFF is differentiable, excludes logarithmic terms or exponential terms, and does not require to minimize the cost function. Numerical results show that the proposed algorithm is effective.

Abstract Background No consensus has been reached on an optimal blood lactate evaluation system although several approaches have been reported in the literature in recent years. A group-based trajectory modeling (GBTM) method could better stratify patients with acute respiratory distress syndrome (ARDS) complicated with sepsis in the intensive care unit (ICU). Patients and methods 760 patients from the comprehensive ICU of Tianjin Medical University General Hospital with ARDS complicated with sepsis were eligible for analysis. Serial serum lactate levels were measured within 48 h of admission. In addition to the GBTM lactate groups, the initial lactate, peak lactate level, the area under the curve of serial lactate (lactate AUC), and lactate clearance were also considered for comparison. The short- and long-term outcomes were the 30- and 90-day mortality, respectively. Results Three lactate groups were identified based on GBTM, with group 3 exhibiting the worse short- [hazard ratio (HR) for 30-day mortality: 2.96, 95% confidence interval (CI) 1.79–4.87, P

Background: The pharmacokinetic/pharmacodynamics (PK/PD) target derived from the hollow-fiber system model for linezolid for treatment of the multidrug-resistant tuberculosis (MDR-TB) requires clinical validation. Therefore, this study aimed to develop a population PK model for linezolid when administered as part of a standardized treatment regimen, to identify the PK/PD threshold associated with successful treatment outcomes and to evaluate currently recommended linezolid doses.Method: This prospective multi-center cohort study of participants with laboratory-confirmed MDR-TB was conducted in five TB designated hospitals. The population PK model for linezolid was built using nonlinear mixed-effects modeling using data from 168 participants. Boosted classification and regression tree analyses (CART) were used to identify the ratio of 0- to 24-h area under the concentration-time curve (AUC0-24h) to the minimal inhibitory concentration (MIC) threshold using the BACTEC MGIT 960 method associated with successful treatment outcome and validated in multivariate analysis using data from a different and prospective cohort of 159 participants with MDR-TB. Furthermore, based on the identified thresholds, the recommended doses were evaluated by the probability of target attainment (PTA) analysis.Result: Linezolid plasma concentrations (1008 samples) from 168 subjects treated with linezolid, were best described by a 2-compartment model with first-order absorption and elimination. An AUC0–24h/MIC > 125 was identified as a threshold for successful treatment outcome. Median time to sputum culture conversion between the group with AUC0-24h/MIC above and below 125 was 2 versus 24 months; adjusted hazard ratio (aHR), 21.7; 95% confidence interval (CI), (6.4, 72.8). The boosted CART-derived threshold and its relevance to the final treatment outcome was comparable to the previously suggested target of AUC0–24h/MIC (119) using MGIT MICs in a hollow fiber infection model. Based on the threshold from the present study, at a standard linezolid dose of 600 mg daily, PTA was simulated to achieve 100% at MGIT MICs of ≤ .25 mg which included the majority (81.1%) of isolates in the study.Conclusion: We validated an AUC0–24h/MIC threshold which may serve as a target for dose adjustment to improve efficacy of linezolid in a bedaquiline-containing treatment. Linezolid exposures with the WHO-recommended dose (600 mg daily) was sufficient for all the M. tb isolates with MIC ≤ .25 mg/L.

Recycling reinjection of CO2 captured and purified from the produced gas of CO2 flooding can not only enhance oil recovery, but also realize the geological storage of CO2, so as to provide good social and economic benefit. With the operation and advancement of CO2 flooding development mode, one single CO2 capture and purification process can hardly deal with the yearly increase and large-scale variation of CO2 content in the produced gas. In order to provide support for the promotion of CO2-EOR technology oil and gas fields, to this end, this paper puts forward four schemes of multi-method CO2 capture and purification process. It includes two-stage hydramine method, one-stage membrane separation + one-stage hydramine method, two-stage membrane separation + one-stage hydramine method, one-stage membrane separation + two-stage hydramine method. And based on the working condition data of CO2 flooding in one certain oilfield, simulation was carried out by using HYSYS software. In addition, the enrichment degree of the CO2 captured and purified by means of different schemes and its energy consumption and economy were analyzed mainly. And the following research results were obtained. First, when the CO2 concentration of the produced gas is low, it is necessary to put the two-stage alcohol amine circulation process into production firstly to realize the deacidification of natural gas while purchasing some pure CO2 to mix at a certain proportion, so as to reach the required CO2 purity of reinjected gas. Second, as the CO2 concentration of the produced gas increases, it is better to use the membrane separation technology before the two-stage alcohol amine circulation process, so that the enriched and purified gas can reach the required CO2 purity of direction reinjection. In conclusion, the research results can provide engineering practical guidance for the formulation of the scheme to enrich and purify CO2 from the produced gas of CO2 flooding.

Microfluidics-based fabrication of cell-laden microgels has shown great potential for applications in cell therapy and tissue engineering, however, the difficulty in chip operation and compromised cell viability due to cell sedimentation and channel blockage remain a major challenge for functional cell-laden microgels preparation. Herein, we presented the design and optimization of integrated microfluidic chip for large-scale preparation of cell-laden microgels with controllable size and complex microstructure. Specifically, to avoid severe cell sedimentation and uneven distribution in the parallelized microchannel, we simulated cell movement state using computational fluid dynamics simulation. It was found that higher laminar flow velocity gradient and higher precursor viscosity can significantly improve the uniform cell distribution in parallelized channels and reduce the product difference between channels. Moreover, we designed multiple-layered microfluidic chips allowing multiple inputting liquids for the fabrication of microgels with complex structures. This integrated chip facilitated cell encapsulation at a maximum production rate of 240 ml/h of cell suspension with retained cell viability and functionality. Therefore, our study provided a biocompatible and high-throughput strategy for large-scale preparation of cell-laden microgels, which can enable significant advances for clinical-relevant applications of cell-laden microgels, including cell therapy, tissue regeneration and 3D bioprinting.

Menthol is an important flavoring additive that triggers a cooling sensation. Under physiological condition, low to moderate concentrations of menthol activate transient receptor potential cation channel subfamily M member 8 (TRPM8) in the primary nociceptors, such as dorsal root ganglion (DRG) and trigeminal ganglion, generating a cooling sensation, whereas menthol at higher concentration could induce cold allodynia, and cold hyperalgesia mediated by TRPM8 sensitization. In addition, the paradoxical irritating properties of high concentrations of menthol is associated with its activation of transient receptor potential cation channel subfamily A member 1 (TRPA1). Under pathological situation, menthol activates TRPM8 to attenuate mechanical allodynia and thermal hyperalgesia following nerve injury or chemical stimuli. Recent reports have recapitulated the requirement of central group II/III metabotropic glutamate receptors (mGluR) with endogenous κ-opioid signaling pathways for menthol analgesia. Additionally, blockage of sodium channels and calcium influx is a determinant step after menthol exposure, suggesting the possibility of menthol for pain management. In this review, we will also discuss and summarize the advances in menthol-related drugs for pathological pain treatment in clinical trials, especially in neuropathic pain, musculoskeletal pain, cancer pain and postoperative pain, with the aim to find the promising therapeutic candidates for the resolution of pain to better manage patients with pain in clinics.

High-precision inertial sensors or accelerometers can provide references for free-falling motion in gravitational fields in space. They serve as the key payloads for gravity recovery missions such as CHAMP, the GRACE-type missions, and the planned Next-Generation Gravity Missions. In this work, a systematic method for electrostatic inertial sensor calibration of gravity recovery satellites is suggested, which is applied to and verified with the Taiji-1 mission. With this method, the complete operating parameters including the scale factors, the center of mass offset vector, and the intrinsic biased acceleration can be precisely calibrated with only two sets of short-term in-orbit experiments. This could reduce the gaps in data that are caused by necessary in-orbit calibrations during the lifetime of related missions. Taiji-1 is the first technology-demonstration satellite of the “Taiji Program in Space”, which, in its final extended phase in 2022, could be viewed as operating in the mode of a high–low satellite-to-satellite tracking gravity mission. Based on the principles of calibration, swing maneuvers with time spans of approximately 200 s and rolling maneuvers for 19 days were conducted by Taiji-1 in 2022. Given the data of the actuation voltages of the inertial sensor, satellite attitude variations, precision orbit determinations, the inertial sensor’s operating parameters are precisely re-calibrated with Kalman filters and are relayed to the Taiji-1 science team. The relative errors of the calibrations are

Higher-order chromatin structure is temporarily disrupted during mitosis. Here the authors show that loss of the architectural factor CTCF results in failure to form structural loops and leads to inappropriate cis-regulatory contacts and alterations of compartmental interactions after mitosis. Furthermore, they show global 3D architecture is set up without transcription, but that transcription contributes to proper gene domain formation.

Onboard electrostatic suspension inertial sensors are important applications for gravity satellites and space gravitational-wave detection missions, and it is important to suppress noise in the measurement signal. Due to the complex coupling between the working space environment and the satellite platform, the process of noise generation is extremely complex, and traditional noise modeling and subtraction methods have certain limitations. With the development of deep learning, applying it to high-precision inertial sensors to improve the signal-to-noise ratio is a practically meaningful task. Since there is a single noise sample and unknown true value in the measured data in orbit, odd–even sub-samplers and periodic sub-samplers are designed to process general signals and periodic signals, and adds reconstruction layers consisting of fully connected layers to the model. Experimental analysis and comparison are conducted based on simulation data, GRACE-FO acceleration data, and Taiji-1 acceleration data. The results show that the deep learning method is superior to traditional data smoothing processing solutions.

Chronic pain after bone fracture and orthopedic surgery is often refractory to most analgesics currently in use, thus emphasizing the urgent need for improved therapeutic medications. Chemokine-dependent neuroinflammation is critical for excitatory synaptic plasticity and central nociception sensitization. Recent studies have focused on the inhibition of inflammatory responses by artesunate, the first anti-malaria drug extracted from artemisinin. The present study investigated the analgesic effects and potential targets of artesunate in a mouse model of chronic pain induced by tibial fracture and orthopedic surgery. Three injections of artesunate were intrathecally administered on a daily basis from days 4 to 6 after fracture. We reported that repetitive exposure to artesunate (10 and 100 μg but not 1 μg) dose-dependently prevented fracture-induced mechanical and cold allodynia. Moreover, single intrathecal injection of artesunate (100 μg) alleviated the established chronic pain on day 14 after fracture surgery. Intraperitoneal artesunate (10 and 50 mg kg−1) therapy was effective against chronic fracture pain. Intriguingly, artesunate inhibited the upregulation of spinal chemokine CCL21, triggering receptor expressed on myeloid cells 2 (TREM2) and DNAX-activating protein of 12 kDa (DAP12) expressions and microglia activation in fracture mice. Furthermore, spinal CCL21 neutralization attenuated the severity of fracture-associated post-surgical pain. Exogenous CCL21-induced acute inflammatory pain was impaired by artesunate therapy. Additionally, the pharmacological blockage of TREM2 reduced recombinant CCL21-elicited behavioral hypernociception. The present findings demonstrate that artesunate therapy reduces the initiation and maintenance of fracture-associated chronic postoperative pain by inhibiting CCL21-dependent TREM2/DAP12 inflammatory signaling and microglia activation, thus suggesting that artesunate could emerge as a therapeutic strategy for fracture pain management.

Chronic pain is a common, complex and unpleasant sensation following nerve injury, tissue trauma, inflammatory diseases, infection and cancer. It affects up to 25% of adults and is increasingly recognized as the leading cause of distress, disability and disease burden globally. Chronic pain is often refractory to most current analgesics, thus emphasizing the requirement for improved therapeutic medications. It is of great importance to elucidate the specific pathogenesis of chronic pain with different etiologies. Recent progress has advanced our understanding in the contribution of neuroinflammation and glial cells (microglia and astrocyte) activation in the plasticity of excitatory nociceptive synapses and the development of chronic pain phenotypes. Oxidative stress-associated neuronal apoptosis is also identified to be a pivotal step for central pain sensitization. The family of cysteine aspartate specific proteases (Caspases) has been well known to be key signaling molecules for inflammation and apoptosis in several neurological conditions. Recent studies have highlighted the unconventional and emerging role of caspases in microgliosis, astrocytes morphogenesis, chemokines release, cytokines secretion and neuronal apoptosis in initiating and maintaining synaptogenesis, synaptic strength and signal transduction in persistent pain hypersensitivity, suggesting the possibility of targeting caspases pathway for prevention and treatment of chronic pain. In this review, we will discuss and summarize the advances in the distinctive properties of caspases family in the pathophysiology of chronic pain, especially in neuropathic pain, inflammatory pain, cancer pain and musculoskeletal pain, with the aim to find the promising therapeutic candidates for the resolution of chronic pain to better manage patients undergoing chronic pain in clinics.

Pompe disease is caused by the deficiency of lysosomal acid α-glucosidase (GAA). It is expected that gene therapy to replace GAA with adeno-associated virus (AAV) vectors will be less effective early in life because of the rapid loss of vector genomes. AAV2/8-LSPhGAA (3 × 1010 vector genomes [vg]/mouse) was administered to infant (2-week-old) or adult (2-month-old) GAA knockout mice. AAV vector transduction in adult mice significantly corrected GAA deficiency in the heart (p 50 weeks. However, in infant mice, the same treatment only partially corrected GAA deficiency in the heart (p < 0.05), diaphragm (p < 0.05), and quadriceps (p < 0.05). The clearance of glycogen was much more efficient in adult mice compared with infant mice. Improved wire hang test latency was observed for treated adults (p < 0.05), but not for infant mice. Abnormal ventilation was corrected in both infant and adult mice. Vector-treated female mice demonstrated functional improvement, despite a lower degree of biochemical correction compared with male mice. The relative vector dose for infants was approximately 3-fold higher than adults, when normalized to body weight at the time of vector administration. Given these data, the dose requirement to achieve similar efficacy will be higher for the treatment of young patients.

Bufalin (Buf), an active ingredient of the traditional Chinese medicine Chansu, is known to have anticancer effects for breast cancer. However, its poor solubility, high toxicity, and extensive side effects limit its use. Metal-organic frameworks (MOFs) are a class of promising drug delivery systems known for their high porosity. Here, we designed and constructed pH-sensitive and redox-responsive folic acid–modified MOFs as drug carriers of Buf (FA-MOF/Buf). Moreover, the anticancer activity of nanomedicines was also explored in vitro and in vivo. Compared to free Buf, the FA-MOF/Buf nanoparticles demonstrated improved water solubility and stability, higher intracellular uptake, and enhanced cytotoxicity in breast cancer cells in vitro. Furthermore, it displayed improved accumulation in the tumor site, enhanced anticancer activity, and reduced side effects in vivo. Our results demonstrated that FA-MOF could be developed as a potential delivery system for Buf to improve its antitumor activity for breast cancer treatment.

At present, polyurethane (PU) has been extensively used as a grouting material in civil engineering. The mechanical properties of PU are the key to achieving the desirable grouting effect. This study presents the research results of the mechanical behavior of PU matrix under tensile, successive cyclic tensile, and stress relaxation at the nanoscale, using the coarse-grained molecular dynamics simulation method. The influences of the number of molecule chains and strain rate on the tensile mechanical properties are discussed, and the tensile deformation mechanism of PU matrix is revealed. The tensile strength of PU matrix is independent of loading path, and after yielding, the strain of PU matrix contains the elastic strain, plastic strain, and viscous strain. In the stress relaxation process, the evolution of the axial stress is mainly caused by the varied van der Waals interactions. The stress relaxation behavior of PU matrix can be described by the viscoelastic model consisting of one elastic element in parallel with one Maxwell element.

Bone fracture following traumatic injury or due to osteoporosis is characterized by severe pain and motor impairment and is a major cause of global mortality and disability. Fracture pain often originates from mechanical distortion of somatosensory nerve terminals innervating bones and muscles and is maintained by central sensitization. Chronic fracture pain (CFP) after orthopedic repairs is considered one of the most critical contributors to interference with the physical rehabilitation and musculoskeletal functional recovery. Analgesics available for CFP in clinics not only have poor curative potency but also have considerable side effects; therefore, it is important to further explore the pathogenesis of CFP and identify safe and effective therapies. The typical physiopathological characteristics of CFP are a neuroinflammatory response and excitatory synaptic plasticity, but the specific molecular mechanisms involved remain poorly elucidated. Recent progress has deepened our understanding of the emerging properties of chemokine production, proinflammatory mediator secretion, caspase activation, neurotransmitter release, and neuron-glia interaction in initiating and sustaining synaptogenesis, synaptic strength, and signal transduction in central pain sensitization, indicating the possibility of targeting neuroinflammation to prevent and treat CFP. This review summarizes current literature on the excitatory synaptic plasticity, microgliosis, and microglial activation-associated signaling molecules and discusses the unconventional modulation of caspases and stimulator of interferon genes (STING) in the pathophysiology of CFP. We also review the mechanisms of action of analgesics in the clinic and their side effects as well as promising therapeutic candidates (e.g., specialized pro-resolving mediators, a caspase-6 inhibitor, and a STING agonist) for pain relief by the attenuation of neuroinflammation with the aim of better managing patients undergoing CFP in the clinical setting.

As methicillin-resistant Staphylococcus aureus (MRSA) is becoming a serious pathogenic threaten to human health worldwide, there is an urgent need to discover new antibiotics for the treatment of MRSA infections. Alboflavusins (AFNs) are a group of halogenated cyclohexapeptides with anti-MRSA activities. In this study, two novel brominated AFN congeners (compounds 1 and 2) were isolated from the wild-type strain Streptomyces alboflavus sp. 313 that was fermented in the production medium supplemented with NaBr; two new (compounds 3 and 5) and a known (compound 4) dehelogenated AFN congeners were isolated from S. alboflavus ΔafnX, in which the tryptophan halogenase gene afnX was inactivated. The structures of these compounds were assigned by careful NMR and MS analyses. The anti-MRSA activities of varied AFN congeners were assessed against different MRSA strains, which revealed that compounds 1 and 2 with bromine displayed effective activities against the tested MRSA strains. Especially, compound 2 showed good anti-MRSA activity, while compounds 3, 4, and 5 without halogen exhibited weak anti-MRSA activities, outlining the influence of halogen substitution to the bioactivities of AFNs.

Summary: CCCTC-binding factor (CTCF) is a conserved zinc finger transcription factor implicated in a wide range of functions, including genome organization, transcription activation, and elongation. To explore the basis for CTCF functional diversity, we coupled an auxin-induced degron system with precision nuclear run-on. Unexpectedly, oriented CTCF motifs in gene bodies are associated with transcriptional stalling in a manner independent of bound CTCF. Moreover, CTCF at different binding sites (CBSs) displays highly variable resistance to degradation. Motif sequence does not significantly predict degradation behavior, but location at chromatin boundaries and chromatin loop anchors, as well as co-occupancy with cohesin, are associated with delayed degradation. Single-molecule tracking experiments link chromatin residence time to CTCF degradation kinetics, which has ramifications regarding architectural CTCF functions. Our study highlights the heterogeneity of CBSs, uncovers properties specific to architecturally important CBSs, and provides insights into the basic processes of genome organization and transcription regulation.

Hetao Plain is one of the most serious area of local arsenic poisoning in China.Based on shallow groundwater arsenic samples, the paper used the semivariogram to reveal the spatial distribution and heterogeneity of groundwater arsenic concentration, and further discussed the influencing factors.The results show that the arsenic concentration in groundwater generally increases from south to north in the Hetao Plain.The residual groundwater arsenic concentration is fitted to the pure nugget effect model under the assumption of isotropic conditions, which means it is random on the measured scale, so there is no spatial autocorrelation and the variance is great in short distances.The fractal dimension value is large(D=1.999), further indicating the distinct variation of groundwater arsenic concentration within the measured scale.Groundwater arsenic is closely related to organic matters in sediments.Since the Late Quaternary, the tectonic movements of the northern mountains and changes in the sedimentary environment of the basin has caused multiple sedimentary facies, resulting in a high degree of spatial variability in burial conditions of organic matters.The high spatial variability of organic matters characteristics further leads to high spatial variability of groundwater arsenic concentration.The slow groundwater flow plays an important role in maintaining this pattern.This article focuses on the spatial heterogeneity of groundwater arsenic in the Hetao area, which has scientific significance for effectively predicting the potential risk of arsenic exposure in drinking water in unknown areas, accurately preventing endemic diseases and ensuring water supply safety.

To explore the electronic warehouse receipt pledge financing cooperation mechanism in the alliance formed between loan enterprises, commercial banks, e-commerce platforms, and logistics enterprises, by constructing a tripartite evolutionary game model, the game equilibrium strategy is then obtained, and the influencing factors of the cooperation mechanism are further simulated. It was found that in this tripartite evolutionary game, the stable strategy combination occurs when the loan enterprise chooses to repay on time, the platform alliance chooses to provide services, and the commercial bank chooses to continue to cooperate. However, heterogeneity exists in the influencing factors for the three-party selection strategy in the game, which is manifested in the fact that the higher the realization rate of the pledge, the more evolution is required in the selection strategy for loan enterprises to continue cooperating. The higher the information service fee, the higher the enthusiasm of the platform alliance in choosing to provide services. Credit levels, loan interest rates, and pledge realization rates are all important factors that affect the choice strategy of commercial banks.

Microfluidics-based alginate microgels have shown great potential to encapsulate cells in a high-throughput and controllable manner. However, cell viability and biological functions are substantially compromised due to the harsh conditions for gelation, which remains a major challenge for cell encapsulation. Herein, we presented an efficient and biocompatible method by on-chip triggered gelation to generate microfluidic alginate microgels for single-cell encapsulation. Two calcium complexes of calcium–ethylenediaminetetraacetic acid (Ca-EDTA) and calcium–nitrilotriacetic (Ca-NTA) as crosslinkers for triggered gelation of alginate were compared and investigated for feasible application. By triggered release of Ca2+ ions from the calcium complex via adding acetic acid in the oil phase, the alginate precursor in the aqueous droplets can be crosslinked to form alginate microgels. Although using Ca-EDTA and Ca-NTA both achieved on-chip gelation, Ca-NTA led to significantly higher cell viability since the dissociation of Ca2+ ions from Ca-NTA can be obtained using less concentration of acid compared to Ca-EDTA. We further demonstrated the functionality of encapsulated mesenchymal stem cells (MSCs) in alginate microgels prepared using Ca-NTA, as evidenced by the osteogenesis of encapsulated MSCs upon inductive culture. In summary, our study provided a biocompatible strategy to prepare alginate microgels for single-cell encapsulation which can be further used for applications in tissue engineering and cell therapies.

Abstract Hutchison-Gilford Progeria Syndrome (HGPS) is a rare, accelerated aging disorder caused by nuclear accumulation of progerin, an altered form of the Lamin A gene. The primary cause of death is cardiovascular disease at about 14 years. Loss and dysfunction of smooth muscle cells (SMCs) in the vasculature may cause defects associated with HGPS. Due to limitations of 2D cell culture and mouse models, there is a need to develop improved models to discover novel therapeutics. To address this need, we produced a functional three-dimensional model of HGPS that replicates an arteriole-scale tissue engineered blood vessel (TEBV) using induced pluripotent stem cell (iPSC)-derived SMCs from an HGPS patient. To isolate the effect of the HGPS iSMCs, the endothelial layer consisted of human cord blood-derived endothelial progenitor cells (hCB-EPCs) from a separate, healthy donor. TEBVs fabricated from HGPS iSMCs and hCB-EPCs show reduced vasoactivity, increased medial wall thickness, increased calcification and apoptosis relative to TEBVs fabricated from normal iSMCs or primary MSCs. Additionally, treatment of HGPS TEBVs with the proposed therapeutic Everolimus, increases HGPS TEBV vasoactivity and increases iSMC differentiation in the TEBVs. These results show the ability of this iPSC-derived TEBV to reproduce key features of HGPS and respond to drugs.

Compelling evidence suggests that defective DNA damage response (DDR) plays a key role in the premature aging phenotypes in Hutchinson-Gilford progeria syndrome (HGPS). Studies document widespread alterations in histone modifications in HGPS cells, especially, the global loss of histone H3 trimethylated on lysine 9 (H3K9me3). In this study, we explore the potential connection(s) between H3K9me3 loss and the impaired DDR in HGPS. When cells are exposed to a DNA-damaging agent Doxorubicin (Dox), double strand breaks (DSBs) are generated that result in the phosphorylation of histone H2A variant H2AX (gammaH2AX) within an hour. We find that the intensities of gammaH2AX foci appear significantly weaker in the G0/G1 phase HGPS cells compared to control cells. This reduction is associated with a delay in the recruitment of essential DDR factors. We further demonstrate that ataxia-telangiectasia mutated (ATM) is responsible for the amplification of gammaH2AX signals at DSBs during G0/G1 phase, and its activation is inhibited in the HGPS cells that display significant loss of H3K9me3. Moreover, methylene (MB) blue treatment, which is known to save heterochromatin loss in HGPS, restores H3K9me3, stimulates ATM activity, increases gammaH2AX signals and rescues deficient DDR. In summary, this study demonstrates an early DDR defect of attenuated gammaH2AX signals in G0/G1 phase HGPS cells and provides a plausible connection between H3K9me3 loss and DDR deficiency.

This study investigated the possible enhancement of berberine’s (BB) hypoglycemic activity by oligomeric proanthocyanidins (OPCs) and its underlying mechanism. The hypoglycemic activity of the studied compounds was evaluated in diabetic db/db mice. The cellular uptake and efflux of BB with or without OPCs were investigated using Caco-2 intestinal cells. A pharmacokinetic study of BB and OPCs was performed in Sprague Dawley (SD) mice by oral administration of the study compounds. Liquid chromatography⁻tandem mass spectrometry (LC⁻MS/MS) was employed to determine the cellular efflux, retention, and the serum concentrations of the compounds. The results revealed that OPCs considerably potentiated the hypoglycemic efficacy of BB in diabetic db/db mice. In the in vitro experiments, OPCs significantly inhibited the efflux and increased the uptake of the P-glycoprotein (P-gp) substrate rhodamine-123 (R123) and BB in Caco-2 intestinal cells. Moreover, OPCs substantially reduced the expression of P-gp in Caco-2 cells. The inhibition of BB efflux by OPCs was translated into the improved pharmacokinetics in vivo. When co-administered, OPCs obviously increased the average maximum concentration of BB in mice. In summary, this study demonstrated that combination of BB with OPCs could significantly improve the pharmacokinetics and hypoglycemic efficacy of BB, which is valuable for future exploration of the combination of BB and OPCs as oral hypoglycemic agents.