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Objective Fibular length is important for ankle stability. Failure to adequately restore and stabilize fibula length may result in malunion, hindering postoperative functional exercises and recovery of ankle function. However, there is no unified and effective reduction method for fibular shortening in Maisonneuve fractures. In this study, we introduce the biplane reduction as an effective surgical technique for restoring the length of the fibula in Maisonneuve fractures. Methods This retrospective study enrolled 12 patients preoperatively diagnosed with Maisonneuve fractures between June 2019 and June 2022. All patients underwent our biplane reduction technique to restore the length of their fibula. Operation time, hospital stay, complications, FTA (the angle between the fibular tip and the superior articular surface of the talus), visual analog pain score, and the American Orthopaedic Foot and Ankle Society ankle‐hindfoot score were recorded. An independent sample t‐test was used for component comparisons, and a paired sample t‐test or one‐way analysis of variance was used for intra‐group comparisons. Results No patient was lost to follow‐up and no obvious postoperative complications were observed. After operation, FTA recovered from 37.52 ± 0.37 ° to 40.42 ± 0.43 °, which was significantly improved compared with that before operation (p

Abstract The investigation of triggers causing the onset and intensification of Northern Hemisphere Glaciation (NHG) during the late Pliocene is essential for understanding the global climate system, with important implications for projecting future climate changes. Despite their critical roles in the global climate system, influences of land-ocean interactions on high-latitude ice sheets remain largely unexplored. Here, we present a high-resolution Asian dust record from Ocean Drilling Program Site 1208 in the North Pacific, which lies along the main route of the westerlies. Our data indicate that atmosphere-land-ocean interactions affected aeolian dust emissions through modulating moisture and vegetation in dust source regions, highlighting a critical role of terrestrial systems in initiating the NHG as early as 3.6 Myr ago. Combined with additional multi-proxy and model results, we further show that westerly wind strength was enhanced, mainly at low-to-middle tropospheric levels, during major glacial events at about 3.3 and 2.7 Myr ago. We suggest that coupled responses of Earth’s surface dynamics and atmospheric circulation in the Plio-Pleistocene likely involved feedbacks related to changes in paleogeography, ocean circulation, and global climate.

Abstract Yangshan gold belt (YSGB) in Gansu Province is a super‐large orogenic gold deposit located in the middle section of the Mianxian‐Lueyang arcuate suture zone (Mian‐Lue suture zone). The YSGB is mainly divided into the Gejiaowan, Anba, and Gaoloushan mine sections. The ore veins are strictly controlled by strong strain zones in the fracture zone and secondary fractures superimposed on the inherited activity and are vein‐like in general and lenticular in localities. For a long time, there have been different understandings regarding its ore‐controlling factors and mineral genesis. By utilizing controlled‐source audio‐frequency magnetotellurics (CSAMT) technology to conduct electrical characteristic studies, the deep electrical structural characteristics of the Gaoloushan section are identified, and a tectonically‐controlled geoelectric model of the deposit is established, which provides geophysical evidence for the view that the Yangshan gold mine is a tectonically‐controlled low‐temperature hydrothermal deposit in altered rock, guiding the arrangement of exploration work and identifying prospective mining areas, and thereby providing a geophysical exploration paradigm for deep exploration of large orogenic gold deposits.

Abstract The present study investigates the efficacy of newly developed Zr-based metal–organic frameworks, specifically MIP-206, and its amine-modified counterpart, MIP-206-NH2, for the re-covery of antimony (Sb) from both synthetic and actual mining wastewater. Batch method studies were employed to examine the effect of waste media pH, Sb concentration, process kinetics, and the performance of the regeneration solution. MIP-206-NH2 exhibited impressive separation capabilities, achieving 102.18 mg/g and 63.23 mg/g for Sb (V) and Sb (III), respectively. In contrast, the pristine MIP-206 reached maximum values of 26.26 mg/g for Sb (V) and 16.95 mg/g for Sb (III). The separation process was well-described by the Langmuir equation, and the kinetics followed the pseudo-second-order model. Although the amine modification resulted in a decrease in the surface area of MIP-206 from 1345.21 to 1169.86 m2/g, SEM and XRD analyses confirmed that the structural integrity of MIP-206-NH2 remained unchanged. In terms of reusability, MIP-206-NH2 maintained up to 90% of its separation performance over 9 cycles, while MIP-206 demonstrated effectiveness for 7 cycles. The regeneration solution exhibited a capacity of approximately 0.63 mol/L for Sb (V) and 0.71 mol/L for Sb (III). Furthermore, MIP-206 and MIP-206-NH2 demonstrated successful application in selectively separating Sb from real mining wastewater.

Objective Faults are among the most prevalent geological structures in oil and gas basins. Because of their significant connection to oil and gas resources, they have consistently attracted the attention of experts and scholars in the field, making them a hot research topic. Although previous researchers delved tirelessly into the correlation between faults, oil, and gas, new theoretical breakthroughs have been steadily emerging and have been used to promote advancements in oil and gas exploration. Nonetheless, there continues to be a dearth of thorough investigations into the underlying links between faults and the formation and distribution of oil and gas reservoirs, as well as methods for comprehensively and quantitatively defining the connections between faults and oil and gas. Methods The formation of a fault from inception encompasses multiple stages of development, including implicit and explicit stages, and differentiating the diverse growth stages of a fault, ranging from the initial embryonic stage to the terminal stage, poses a significant challenge. To address this issue, the Dongying Sag in the Bohai Bay Basin was selected as the focal point of this study. By employing physical and numerical simulation techniques, the researchers sought to replicate the entire life cycle evolution of the Chennan Fault, a basin-controlling boundary fault, from its embryonic stage to its terminal stage while elucidating the distinct characteristics of each stage. Building upon this foundation, the relative ages of the primary faults in the Dongying Depression and the various modes of fault activity at different stages were qualitatively and quantitatively determined, leading to the establishment of a reservoir-control model. Results The research findings indicate that normal faults tend to grow in six distinct stages: the embryonic stage (0 < RA (relative age) ≤ 1), characterized by microfractures or induced fracture zones; juvenile stage (1 < RA ≤ 2), with an intermittent connection of fault geometry; mature stage (2 < RA ≤ 3), marked by the connection of plate-like fault geometry and clear fault throw; declining stage (3 < RA ≤ 4), in which induced fracture zones form on both sides of the fault core, resulting in a shovel-like fault geometry; terminal stage (4 < RA ≤ 5), ramp-flat fault geometry, which has complex derived structures; and death stage (5 < RA ≤ 6), in which fault movement stops or undergoes inversion. The activity pattern of a fault is intricately linked to the duration and intensity of its age. Stable continuous, and high-intensity fault activity promotes the evolution of faults into their terminal stage. Research on reservoir control traps indicates that faults can create reservoirs at all stages of their development. However, as faults age, their ability to control reservoir formation strengthens. The types of traps influenced by faults transition from individual, isolated structures to a variety of arrangements. Moreover, the diversity of oil and gas reservoirs evolves from singular to multifaceted, and the size of these reservoirs expands from small to large. The embryonic and juvenile stage faults primarily influence closure; the mature stage faults predominantly impact sand and reservoir; and the declining stage and terminal stage faults primarily govern the overall distribution range of source rocks, as well as the migration, accumulation, and dissipation of oil and gas. Conclusion The reservoir control potential of the Chennan Fault was assessed by considering factors such as reservoir control advantages, the degree of oil and gas enrichment, and the scale of oil and gas accumulation. The reservoir control capacity of the Chennan Fault was classified as “strong.” Reevaluation of the fault’s reservoir control potential from the perspective of its developmental and evolutionary stages significantly enhances and elevates theoretical research on fault reservoir control and also advances exploration efforts in established mature areas. [Significance] Identifying the formation age and evolutionary patterns of extensional faults has immense theoretical and practical importance for comprehending alterations in the fault’s reservoir control capabilities. Moreover, it offers crucial guidance for oil and gas exploration, particularly for enhancing the reserves in existing exploration areas.

Existing research suggests that elite clubs exist in venture capital markets, but a standard for determining their size and composition is lacking. This paper addresses this challenge by using the weighted k-means sorting algorithm to construct a research framework for elite clubs. Validating the framework with investment events data from China’s venture capital market (2001–2018), intriguing findings emerge. The ranking of Venture Capitalists (VCs) follows a power-law distribution, providing evidence for elite clubs’ existence. The analysis identifies a turning point in the score curve, serving as a valuable indicator for club boundaries. Elite clubs demonstrate relatively high stability, maintaining advantages and elite status in future competitions. Empirical validation confirms the proposed framework’s superior stability compared to existing methods. Importantly, elite club members outperform non-elites significantly. This paper effectively identifies elite clubs in the Chinese venture capital market, helping other VCs recognize potential partners, access high-quality information, and enhance investment performance.

Casimir interaction is an intriguing phenomenon that is induced by electromagnetic quantum fluctuations, which dominates the interaction between microstructures at small separations and is essential for micro- and nano-electromechanical systems (MEMS and NEMS). However, Casimir interaction driven by hyperbolic polaritons remains an unexplored frontier. In this work, we investigate the Casimir interaction between natural hyperbolic material hexagonal boron nitride from the perspective of force distribution with different optical axis orientations for the first time. The attractive Casimir force is remarkably enhanced due to the excitation of volume-confined hyperbolic polaritons (HPs). Furthermore, distinct repulsive contributions to the force are observed due to surface-confined HPs that only exist when the optical axis is in-plane. The HPs are associated with a striking thickness dependence of spectral force properties, suggesting that the discrete volume-confined HPs lead to the attractive-repulsive transition of Casimir force. This work sheds light on the relation between HPs and the vacuum fluctuation-induced force, which could offer new opportunities for the development of the MEMS and NEMS.

Abstract Chirality and luminescence are important for both chemistry and biology, which are highly influenced by aggregation. In this work, a pair of metalated tetraphenylethylene(TPE)‐based organic cage enantiomers are reported, which feature a quadrangular prismatic cage structure. These homochiral cages exhibit concentration‐dependent chiral behaviors alongside a propensity for thermodynamic aggregation. Aggregation caused quench effect is found for these cages accompanying the increasing of the concentrations. When a poor solvent is added to produce a kinetical aggregation, the aggregation‐annihilation circular dichroism and aggregation‐induced emission behaviors are observed for these enantiomeric cages. By comparing these observations with the photophysical behaviors of a pair of structurally similar organic molecular enantiomers, the unique photophysical properties observed are intricately linked to the metal‐integrated TPE‐functionalized cage structures.

There are few reports about primary intracranial granulomas without an identifiable infectious history. A 25-year-old male with intracranial granuloma. The patient presented with a history of tinnitus with intermittent headache for 1 week. Consequently, MRI showed pronounced and extensive enhancement lesions in the left frontal lobe involved in the cerebral longitudinal fissure cistern and the inside of the right frontal lobe, accompanied by a moderate degree of oedema; The lesion was a pilomyxoid astrocytoma preoperatively. Following a systemic examination, gross total resection of the lesion was performed, and postoperative pathological examination revealed the presence of inflammatory lesions. The patient exhibited notable symptom amelioration post-surgery, leading to discharge after the treatment. Subsequently, a sequential treatment involving steroid therapy was administered, resulting in successful patient recovery.

Abstract Efficient topical drug delivery remains a significant challenge in glaucoma management. Although nanoparticle formulations offer considerable promise, their complex preparation processes, co‐delivery issues, and batch consistency have hindered their potential. A scalable fabrication strategy is developed here for preparing solid drug nanoparticles (SDNs) with enhanced drug delivery efficiency. Utilizing hydrophobic antiglaucoma drugs brimonidine (BM) and betaxolol (BX), uniform fixed combination BM/BX SDNs are fabricated through a continuous process, improving batch‐to‐batch consistency for combined glaucoma treatment. With trehalose being used as a lyoprotectant, BM/BX SDNs can be stored as dry powder and easily reconstituted in phosphate buffered saline. Importantly, reconstituted BM/BX SDNs form clear, homogenous solutions, and exhibit negligible cytotoxicity and irritation, making them well‐suited for topical administration as eyedrops. Ex vivo and in vivo studies demonstrated that topically applied BM/BX SDNs permeate through the cornea significantly (about two fold to three fold) compared to their hydrophilic counterparts, i.e., brimonidine tartrate, and betaxolol hydrogen chloride. Notably, BM/BX SDNs displayed consistent intraocular pressure lowering effects in vivo in both normotensive rats and glaucoma mice. Collectively, this study demonstrates the potential of the scalable fabrication strategy and the resultant BM/BX SDNs for improving glaucoma management through eyedrops.

The value-added tax (VAT) in China is levied and allocated based on the origin principle. Under the background of the increasing substitution of online retail for traditional offline retail, this mechanism will exacerbate the disparity of regional tax revenue, and intensify tax competition among local governments. Therefore, reconsidering the allocation mechanism of value-added tax in China can be an important policy decision, and it is influenced by various economic and social factors. Firstly, we utilize large-scale retail transaction data from an e-commerce platform to measure regional disparities in retail and consumption among different regions and then reveals present tax policy results in revenue imbalance in different regions. Secondly, we establish a model based on game theory to illustrate how the origin principle leads to fierce tax competition among regions. Furthermore, by establishing and solving tax allocation models between local governments and the central government, this study simulates and calculates the degree of revenue imbalance under different scenarios and attempts to propose policy measures. The results indicate that implementing the destination principle will reduce regional tax imbalances. Moreover, adjusting the allocation ratio between the central government and local governments based on city levels is advantageous for further reducing regional tax revenue disparities.

The advanced technology microwave sounder (ATMS) is an important satellite instrument that provides vital data on atmosphere temperature and moisture for weather forecasting and climate research, and helps us plan for extreme weather. However, its coarse resolution and angular dependence have long been a challenge for improving image visualization. This article proposes a method to enhance the imagery visualization for ATMS, combining limb correction (LC) with artificial intelligence (AI) resolution enhancement (RE). Measurement data from the ATMS onboard NOAA-20 were utilized to train the LC method, which were then validated using newly acquired NOAA-21 ATMS data. The AI RE was performed using enhanced super-resolution generative adversarial networks, which increased the pixel resolution by a factor of four. The high-resolution (HR) Advanced Microwave Scanning Radiometer 2 data served as a reference to initially and quantitatively evaluate the RE method. The combined method of LC and AI RE produced an angular-dependence-free and HR ATMS image, resulting in a significant improvement in image visualization, including surface and atmosphere information, and allows for clear identification of severe weather events. For the swift identification and analysis of tropical cyclones in the upcoming season, as of this writing, this proposed method has been routinely employed to produce high-quality global ATMS images, and these images are showcased and tested in the NOAA internal HR imagery visualization system—JSTAR Mapper. Moreover, concentrated efforts are being made to further enhance these images in preparation for an official release.

We use actual pavement disease data, pavement performance data and pavement maintenance data to develop a data envelopment analysis (DEA) model to evaluate the effectiveness of repairing each type of pavement disease. Next, an optimization model is proposed to improve the pavement maintenance performance while reducing the pavement maintenance cost. Results indicate that repairing transverse cracking and rutting pavement diseases is more effective in improving the pavement maintenance performance. We also find that the pavement maintenance performance is enhanced prominently if the cost constraint increases from 0.1 to 0.2, while only slight improvements are observed if the maintenance cost keeps increasing. When the cost constraint is set to 0.2, the number of expressway sections with excellent condition increases by 71 and the average pavement condition index (PCI) increases by 0.27, implying that the generated pavement maintenance strategy can achieve a good performance while using much lower maintenance cost.

Abstract Objective: Inflammation plays a critical role in the progression of chronic liver diseases, and diet can modulate inflammation. Whether an inflammatory dietary pattern is associated with higher risk of hepatic steatosis or fibrosis remains unclear. We aimed to investigate the associations between inflammatory dietary pattern and the odds of hepatic steatosis and fibrosis. Design: In this nationwide cross-sectional study, diet was measured using two 24-h dietary recalls. Empirical dietary inflammatory pattern (EDIP) score was derived to assess the inflammatory potential of usual diet, which has been validated to highly predict inflammation markers in the study population. Controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) were derived from FibroScan to define steatosis and fibrosis, respectively. Setting: US National Health and Nutrition Examination Survey. Participants: 4171 participants aged ≥18 years. Results: A total of 1436 participants were diagnosed with S1 steatosis (CAP ≥ 274 dB/m), 255 with advanced fibrosis (LSM ≥ 9·7 kPa). Compared with those in the lowest tertile of EDIP-adherence scores, participants in the highest tertile had 74 % higher odds of steatosis (OR: 1·74, 95 % CI (1·26, 2·41)). Such positive association persisted among never drinkers, or participants who were free of hepatitis B and/or C. Similarly, EDIP was positively associated with CAP in multivariate linear model (P < 0·001). We found a non-significant association of EDIP score with advanced fibrosis or LSM (P = 0·837). Conclusions: Our findings suggest that a diet score that is associated with inflammatory markers is associated with hepatic steatosis. Reducing or avoiding pro-inflammatory diets intake might be an attractive strategy for fatty liver disease prevention.

Rare earth ion (Nd, Sm, La and Ce) doped CaTiO3-SmAlO3 ceramics were obtained from corresponding oxides by thermal decomposition method and sintering at different temperatures up to 1370°C. The microstructure, densification and dielectric properties were systematically studied. The relationship between microstructure and dielectric properties was also correlated to understand the key contributor which improves quality factor. Relative dielectric constant of εr ≈ 39.3 and the highest quality factor Q × f = 49430GHz with small temperature coefficient τf of −9.4 ppm/K were obtained for the CaTiO3-Sm0.85Nd0.15AlO3 sample doped with 1.5 at.% Ce.

In order to promote the application of diamond-like carbon (DLC) coatings in harsh marine environments, magnetron sputtering technology was used to deposit CrN-DLC coatings on 304 stainless steel. Subsequently, SEM, Raman spectrometer, XPS, EDS, nanoindentation instrument, friction testing machine, three-dimensional profilometer, and electrochemical workstation were utilized to analyze the surface and cross-sectional morphology, microscopic bonding structure, chemical bonding state, composition and element distribution, hardness, tribological properties and corrosion resistance of CrN-DLC films prepared under different nitrogen flow conditions. Results showed that the CrN-DLC coatings had a dense surface structure with no obvious defects, and the deposited coatings were all amorphous in structure. The coatings showed a 55% elastic recovery rate when 2 mL/min N2 was passed through, indicating that the CrN-DLC coatings had good toughness, and the wear rate of the coating prepared under this condition under simulated seawater rubbing against Si3N4 balls was only 8.63×10-10 m3/(N·m). In the electrochemical tests, the anodic polarization curves of all CrN-DLC coatings showed obvious passivation phenomenon. Among them, the corrosion current density of the coating through the 2 mL/min N2 was 2 orders of magnitude lower than that of 304 stainless steel, showing good corrosion resistance. Generally, the structural design and elemental doping of the CrN-DLC coatings could effectively improve the wear and corrosion resistance of 304 stainless steel, which enhanced the application of DLC coatings in the marine environment.

Objective: This study aimed to investigate the differences in enzymatic properties of endogenous transglutaminase （TGase） in silver carp and black carp. Methods: STG and BTG were purified from the muscle of silver carp and black carp, respectively, by 80% ammonium sulfate precipitation, Q-Sepharose FF, and Sephacryl S-200 HR chromatographies. Two enzymes were analyzed for relative molecular weights, peptide sequences, secondary structures, optimal reaction conditions, and thermal inactivation kinetics. Results: The purified STG and BTG showed similar relative molecular weights, of which the enzyme activities were 14.34 U/mg and 12.67 U/mg, respectively. Both enzymes showed differences in peptide sequences. The secondary structures of them were mainly the β-fold, though the content of β-fold in STG was slightly higher than that of BTG. The optimal temperatures for STG and BTG were both 50 ℃, and the optimal pH values were 8.0 and 7.5, respectively. The enzymes required Ca2+ up to 1 mmol/L for full activation. The activities of STG and BTG were enhanced by DTT, whereas PMSF, NH4Cl, NEM, EDTA, Cu2+, Ba2+, Zn2+, and Mg2+ showed inhibitory effects. When the temperature was 37~50 ℃, the passivations of STG and BTG by thermal treatment conformed to the first-order exponential decay kinetics with similar values of Ea. Conclusion: The primary and secondary structures of STG and BTG exhibited obvious differences, yet they still exhibited similar properties in terms of optimal reaction conditions and thermal inactivation kinetics.

The prescription of a course of oral antibiotics following bone grafting procedures is a common practice in clinical periodontics to reduce surgical site infections. The goal of this study is to characterize the release profile of antibiotics via local delivery using dendrimer hydrogels (DH) and to analyze the effect of two different particulate bone allografts on the release of the antibiotics in vitro. DH were synthesized from polyamidoamine (PAMAM) dendrimer G5 and polyethylene glycol diacrylate, and cefazolin was chosen as the antibiotic. The antibiotic-loaded samples were bathed in PBS and incubated at 37 °C; aliquots were taken (1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 12 h, 24 h, 48 h, 72 h) and analyzed using HPLC to determine the amounts of released cefazolin. In samples with DH, the estimated maximum concentration of cefazolin was 36.97 ± 2.39 μg/mL (95% CI: 34.58–39.36) with 50% released in 4.17 h (95%: 3.26–5.07) and an estimated growth rate of 0.27 (95% CI: 0.17–0.37). For samples without DH, the estimated maximum concentration of cefazolin was 167.4 ± 7.0 μg/mL (95% CI: 160.4–174.4) with 50% released in 2.36 h (95% CI: 2.05–2.67) and an estimated growth rate of 0.70 (95% CI: 0.54–0.87). We conclude that DH are a promising platform for sustained antibiotic release and that the presence of bone grafts did not significantly affect their release.

During the rolling process of profile ring, the design of the rolling cavity directly affects the forming quality of the final ring. In order to improve the cavity filling rate and reduce the production cycle time, this paper proposes a general evaluation method of the filling difficulty for profile ring rolling cavity by combining the response surface method(RSM) and the finite element method(FEM) with the step-type ring as the research object. Firstly, a universally applicable design method for profile ring rolling cavity is proposed, and based on the description of the rolling cavity, three design variables and a corresponding response objective are defined to achieve multi-objective optimization. Secondly, a finite element model of this step-type ring rolling process is established, and the response model is built and improved by significance analysis and analysis of variance(ANOVA) based on the forming simulation results. Then, the effects of different variables on the optimization objectives are comprehensively investigated by this response model. Finally, the evaluation method of the filling difficulty for profile ring rolling cavity is obtained by combining the contour plot of the response objective.

ObjectivesIn order to improve ship propulsion performance and efficiency, and overcome such obstacles as numerous propeller parameters, complicated modeling, slow convergence of hydrodynamic numerical calculations and turbulent wake field effects, this paper proposes an efficient propeller optimization method.MethodsA parameterized propeller constructed with non-uniform rational B-spline based free form deformation (NFFD) technology is used as the output. The CFD numerical simulation is applied to predict its performance characteristics and the Gaussian approximate prediction model of the propeller performance is established based on the simulation data. The optimization model aims to improve efficiency and reduce the torque coefficient by using the second-generation non-dominated sorting genetic algorithm (NSGA-II) method to obtain the optimal solution.ResultsThe results show that under the uniform flow field and wake field behind the ship, the optimization results of the propeller have similar laws; that is, the blade width and thickness of the propeller show a decreasing trend, while the inclination angle shows an increasing trend. The flow velocity decreases in the wake field behind the ship, so the reduction in width and thickness and increase in inclination angle of the propeller blade are smaller than those in the uniform flow field. ConclusionThe method proposed in this paper can be used to achieve the more efficient optimization design of propellers under uniform flow fields and wake fields behind ships.

Objective·To investigate the impact of complications on the prognosis and lung injury of patients with tuberculosis..Methods·A retrospective cohort study was used for analysis, to select a total of 450 smear-positive tuberculosis (TB) patients, 323 males (71.8%) and 127 females (28.2%), from January to December 2018 at Shanghai Pulmonary Hospital, Tongji University School of Medicine, which were divided into non-complication group and complication group (diabetes, hypertension, liver diseases, kidney diseases and gallbladder diseases). Overall treatment outcomes and lung injuries in TB patients with and without complications were analyzed by using χ2 test. Stratified analysis of the impact of each comorbidity on the prognosis and lung injury of TB patients was performed. Kaplan-Meier analysis was used to analyze the temporal correlation between complications and tuberculosis prognosis.Results·Four hundred and fifty patients with a median age of 33 years were included, 173 of whom had complications: diabetes in 49 cases, hypertension in 23 cases, liver diseases in 83 cases, kidney diseases in 35 cases, and gallbladder diseases in 17 cases. The cure rate of TB patients without complications was 80.5%, which was significantly higher than that of the group with complications (P

IntroductionThe ratio of Triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) is a crucial indicator for diabetes diagnosis.MethodsThis study utilizes the Copula function to model and fit the non-linear correlation among fasting blood glucose (Glu), glycosylated hemoglobin (HbA1C), and TG/HDL-C in patients with diabetes. The Copula function chosen for this study includes the two-dimensional Archimedes and Elliptical distribution family, as well as the multidimensional Vine Copula function, for fitting the data. The evaluation of the fitting effect is performed using the mean absolute error (MAE) and mean square error (MSE).ResultsThe results indicate that the Clayton Copula exhibits the highest effectiveness in fitting the pairwise relationship between Glu and TG/HDL-C, as well as HbA1C and TG/HDL-C, displaying the smallest fitting error. Additionally, the Vine Copula function produces a satisfactory fit for the relationship among all three indicators. Compared to linear analysis methods, the Copula function more accurately depicts the correlation among these three types of indicators.DiscussionMoreover, our findings indicate a stronger correlation in the lower tail between Glu and HbA1C, as well as TG/HDL-C, suggesting that the Copula function provides greater accuracy and applicability in depicting the relationship among these indicators. As a result, it can offer a more precise auxiliary diagnosis and serve as a valuable reference in clinical judgment.

Abstract Airborne mineral dust is sensitive to climatic changes, but its response to orbital forcing is still not fully understood. Here, we present a reconstruction of dust input to the Subarctic Pacific Ocean covering the past 190 kyr. The dust composition record is indicative of source moisture conditions, which were dominated by precessional variations. In contrast, the dust flux record is dominated by obliquity variations and displays an out‐of‐phase relationship with a dust record from the mid‐latitude North Pacific Ocean. Climate model simulations suggest precession likely drove changes in the aridity and extent of dust source regions. Additionally, the obliquity variations in dust flux can be explained by meridional shifts in the North Pacific westerly jet, driven by changes in the meridional atmospheric temperature gradient. Overall, our findings suggest that North Pacific dust input was primarily modulated by orbital‐controlled source aridity and the strength and position of the westerly winds.

Abstract Using a sample of 124 countries assisted by China from 2000 to 2019, this paper examines the impact of foreign aid on outward foreign direct investment (OFDI) and the mitigation mechanism of risk. The research finds that, first, foreign aid can significantly reduce the country risk of recipient countries, especially political risk and financial risk, and thus play a role in promoting the inflow of OFDI of donor countries, and there is a lagged effect of this role; Second, foreign aid from other countries has a negative impact on China's OFDI to recipient countries, indicating that foreign aid is nonaltruistic and exclusive; Third, the mitigation effect of foreign aid on country risk is achieved through five channels: compensation effect, synergistic effect, pioneer effect, assimilation effect, and redistribution effects.

Abstract Purpose The objective of this study was to investigate the effect of proximal fibular and/or posterolateral joint facet (PJF) fractures on early functional recovery after Schatzker type VI tibial plateau fractures (TPFs). Methods Seventy-nine patients with Schatzker type VI TPFs sustained from November 2016 to February 2021 were divided into three groups according to the integrity of the proximal fibula and PJF (groups A, B, and C). Details including demographics, duration of surgery, and complications were recorded. The Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) score, Hospital for Special Surgery (HSS) score, lateral knee pain and lateral hamstring tightness were ascertained at the final follow-up. The HSS and WOMAC scores have high reliability in evaluating knee function and osteoarthritis. Results There was a significant difference in the HSS score between groups A and C (P

Abstract Satellite observations covering the last four decades reveal an ocean warming pattern resembling the negative phase of the Pacific Decadal Oscillation. This pattern has therefore been widely interpreted as a manifestation of natural climate variability. Here, we re-examine the observed warming pattern and find that the predominant warming over the subtropical oceans, while mild warming or even cooling over the subpolar ocean, is dynamically consistent with the convergence and divergence of surface water. By comparison of observations, paleo-reconstructions, and model simulations, we propose that the observed warming pattern is likely a short-term transient response to the increased CO2 forcing, which only emerges during the early stage of anthropogenic warming. On centennial to millennial timescales, the subpolar ocean warming is expected to exceed the temporally dominant warming of the subtropical ocean. This delayed but amplified subpolar ocean warming has the potential to reshape the ocean-atmosphere circulation and threaten the stability of marine-terminating ice sheets.

Despite extensive investigations on urban metro passenger flows, their evolving spatiotemporal patterns with the extensions of urban metro networks have not been well understood. Using Shenzhen as a case study city, our study initiates an investigation into this matter by analyzing the evolving network topology of Shenzhen Metro. Subsequently, leveraging long-term smart card data, we analyze the evolving spatiotemporal patterns of passenger flows and develop an analytical approach to pinpoint the major passenger sources of urban metro congestion. While the passenger travel demand and the passenger flow volumes kept increasing with the extension of the urban metro network, the major passenger sources were very stable in space, highlighting the inherent invariance in the evolution of the urban metro system. Finally, we analyze the impact of population and land use factors on passenger flow contributions of passenger sources, obtaining useful clues to foresee future passenger flow conditions.

Most clinically non-functioning pituitary tumour arise from gonadotroph cells. However, clinically functional pituitary gonadotroph adenoma is rare. Here we report a female case who presented with menstrual disturbances, however further workup demonstrated a pituitary microadenoma with elevated FSH and oestradiol level. Transsphenoidal resection was performed and the surgical histopathology confirmed pituitary gonadotroph adenoma. Postoperatively, improvement in both symptoms and hormonal profile were observed. Interestingly, the initially enlarged and polycystic ovaries became within normal range around eight months after the surgery. We suggest functional gonadotroph adenoma should be considered in the presence of gynaecological disorder with persistently elevated oestradiol and FSH levels.

This paper employs a unique data set to analyze the trading behavior of wealthy individual investors across Mainland China and their impact on Chinese stock markets' tail risk. Results show that the wealthy individual investors' trading behavior can explain Chinese stock markets' tail risk, and the daily investment portfolios based on the network density of wealthy individual investors have significant excess returns. This paper also investigates the determinants of wealthy individual investors' trading behavior with the social network method and the spatial econometric model, and reveals that wealthy individuals benefit from the spillover effect of their trading behavior through the investor networks. The results of this paper not only reveal micro evidence for the formation mechanism of asset prices, but also provide insight into the behavior of wealthy individual investors.

In this paper, the fused graphical lasso (FGL) method is used to estimate multiple precision matrices from multiple populations simultaneously. The lasso penalty in the FGL model is a restraint on sparsity of precision matrices, and a moderate penalty on the two precision matrices from distinct groups restrains the similar structure across multiple groups. In high-dimensional settings, an oracle inequality is provided for FGL estimators, which is necessary to establish the central limit law. We not only focus on point estimation of a precision matrix, but also work on hypothesis testing for a linear combination of the entries of multiple precision matrices. We apply a de-biasing technology, which is used to obtain a new consistent estimator with known distribution for implementing the statistical inference, and extend the statistical inference problem to multiple populations. The corresponding de-biasing FGL estimator and its asymptotic theory are provided. A simulation study and an application of the diffuse large B-cell lymphoma data show that the proposed test works well in high-dimensional situation.

Abstract Although ordinary human mobility has been extensively studied, anomalous human mobility during emergencies or mass events is not sufficiently understood. The recently proposed vector field approach has shed light on human mobility studies. Here, the authors improve it to analyze anomalous human mobility in mass events. Specifically, the authors develop the anomalous field, the source field, and the dispersion field to identify the crowd gathering location, the start time, and the end time of anomalous human mobility. In addition, the authors propose the decay coefficient and the maximum distance to quantify the influence degree and scope of a mass event. The present approach can be used to capture the spatiotemporal characteristics of human mobility in mass events.

Abstract CMTR1, also called IFN-stimulated gene 95 kDa protein (ISG95), is elevated by viral infection in a variety of cells. However, the functions of CMTR1 in colorectal cancer (CRC), especially its roles in tumorigenesis and immune regulation, remain unclear. Here, we first identified CMTR1 as a novel oncogene in colorectal cancer. Based on The Cancer Genome Atlas (TCGA) database exploration and human tissue microarray (TMA) analysis, we found that CMTR1 expression was markedly higher in CRC tissues than in adjacent normal tissues. High CMTR1 expression was correlated with poor prognosis in CRC patients. Knockdown (KD) of CMTR1 significantly suppressed cell proliferation and tumorigenicity both in vitro and in vivo, whereas overexpression of CMTR1 resulted in the opposite effects. KEGG pathway analysis revealed differential enrichment in the JAK/STAT signaling pathway in colorectal cancer cells with CMTR1 KD. Mechanistically, suppression of CMTR1 expression inhibited RNAPII recruitment to the transcription start site (TSS) of STAT3 and suppressed STAT3 expression and activation. Furthermore, the efficacy of PD1 blockade immunotherapy was prominently enhanced in the presence of CMTR1 KD via increased infiltration of CD8 + T cells into the tumor microenvironment. Overall, it appears that CMTR1 plays a key role in regulating tumor cell proliferation and antitumor immunity.

Objective The distal tibiofibular syndesmosis (DTS) is a fretting joint and it is still a hot issue how to satisfy strong internal fixation while allowing fretting. This study described and evaluated a new method for elastic fixation of DTS injury with Nice Knot. Methods The study was designed as a retrospective study. Between June 2020 and June 2021, 31 patients who were diagnosed with ankle fracture and DTS injury without additional orthopedic injuries were enrolled in this case series. The study included 22 males and nine females, with an average age of 34.71 ± 14.66 years. All patients were treated with Nice Knot binding for DTS. Surgical time, length of stay, time of DTS fixation, total weight‐bearing time, complications, imaging parameters, and functional scores at follow‐up were recorded. Paired sample t‐tests or single factor analyses of variance were used at intra‐group comparison. Results All patients completed surgery with normal syndesmotic parameters. The recovery of DTS injury was verified by Hook and lateral malleolus rotation tests. The average follow‐up time was 15.97 ± 3.30 months. Only one case showed superficial infection after surgery, and the wound healed after symptomatic treatment. In terms of imaging, there were no significant differences in tibiofibular clear space (TFCS), tibiofibular overlap distance (TFOS), medial clear space (MCS), and superior clear space (SCS) immediately and at different follow‐up points after surgery. All obtained excellent and good outcomes according to the AOFAS score at least follow‐up after surgery. Conclusions Nice Knot elastic fixation of DTS injury is firm and stable while maintaining the physiological micromotion of the ankle joint.

Based on literature analysis, this paper reviews the evolution path of Japan's food education policy and analyzes the content and purpose of the basic law of food education. Based on the perspectives of multiple objectives and multi-subject role division, the author summarizes the experience of Japan's food education policy promotion. Their experiences mainly include: clear division of labor between the central and local governments, central unification and respect for local autonomy. Food breeding roots from a young age; Diversified feeding action plans; Planning food education courses with characteristics.

Abstract Background Pseudoaneurysm is a known complication of penetrating arterial injuries such as catheterization, gunshot wounds, and open fractures. Vaccination is an effective method for preventing multiple, serious, infectious diseases in children. Common adverse reactions related to vaccination include fever, swelling, redness, and pain. Brachial pseudoaneurysm after vaccination has not been previously reported. Case presentation Herein we describe a novel case of brachial pseudoaneurysm after vaccination in a child aged 1 year and 3 months. A pulsatile mass was formed in the medial left arm of the infant 10 days after vaccination at a community hospital and gradually grew larger. Preoperative images depicted an eccentric aneurysm in the brachial artery and a swirling flow pattern in the mass. The pseudoaneurysm was excised, and vein graft interpositioning was successfully performed. There were no short-term or long-term complications during the follow-up period. Conclusions Brachial pseudoaneurysm is a rare complication of vaccination via intramuscular injection. Medical staff should avoid puncture wounds to the brachial artery during vaccination, especially in infants.

Abstract Coagulation/flocculation is one of the most widely used and cost-effective pretreatment methods for improving the dewaterability of sludge. In this study, a cationic modified starch-based flocculant (St-CTA) in conjunction with a popular clay, attapulgite (ATP), was used for the conditioning of waste-activated sludge. The dewatering properties, including the filter cake moisture content, filtration specific resistance, capillary suction time, filtration rate and compressibility coefficient, were measured and compared by varying the doses of St-CTA and ATP. By combination of the apparent dewatering performance and the changes in the contents and distributions of the extracellular polymeric substance (EPS) fractions and components, sludge flocs, and microstructures of sludge cakes, the dewatering mechanisms were discussed in detail. St-CTA in conjunction with ATP can exhibit an enhanced dewaterability of sludge and the water content in final sludge cake can be stably reduced below 80% owing to the synergistic effects of St-CTA and ATP. In addition to the efficient charge neutralization of St-CTA, ATP not only acts as a skeleton builder in the sludge dewatering process which makes the sludge flocs more compact and improves the filterability and permeability, but also tightly interacts with the proteins in EPS of the sludge which reduces the protein content and further enhances the dewatering effect. This study provides an economical, green, and effective way to further improve the dewaterability of sludge.

Transthyretin(TTR) protein is a tetramer protein, synthesized mainly by the liver. TTR can be misfolded and deposited as amyloid fibrilae and deposited in the myocardial interstroma leading to transthyroxin amyloidosis cardiomyopathy (ATTR-CM). ATTR-CM was included in China's First List of Rare Diseases. Therapeutic strategies for ATTR-CM include blocking TTR synthesis in the liver, stabilizing TTR tetramers and destroying TTR fibra. Small molecule drugs such as tafamidis and diflunisal offer new treatment options for patients. Chlorobenzolic acid became the first drug approved by the U.S. Food and Drug Administration for the treatment of ATTR-CM. Small interfering RNA(siRNA)patisiran and antisense oligonucleotide (ASO)inotersen block TTR expression in the liver and have been approved for the treatment of ATTR variant polyneuropathy (ATTRv-PN)and are in phase Ⅲ trials for the treatment of ATTR-CM. Other siRNA drugs, vutrisiran, and ASO, eplontersen, are being evaluated for clinical efficacy. This article reviews the development of RNA-targeted therapeutics and gene-editing drugs using CRISPR-Cas9.

Nanoparticle-based therapeutics represent potential strategies for treating atherosclerosis; however, the complex plaque microenvironment poses a barrier for nanoparticles to target the dysfunctional cells. Here, we report reactive oxygen species (ROS)-responsive and size-reducible nanoassemblies, formed by multivalent host-guest interactions between β-cyclodextrins (β-CD)-anchored discoidal recombinant high-density lipoprotein (NP3ST) and hyaluronic acid-ferrocene (HA-Fc) conjugates. The HA-Fc/NP3ST nanoassemblies have extended blood circulation time, specifically accumulate in atherosclerotic plaque mediated by the HA receptors CD44 highly expressed in injured endothelium, rapidly disassemble in response to excess ROS in the intimal and release smaller NP3ST, allowing for further plaque penetration, macrophage-targeted cholesterol efflux and drug delivery. In vivo pharmacodynamicses in atherosclerotic mice shows that HA-Fc/NP3ST reduces plaque size by 53%, plaque lipid deposition by 63%, plaque macrophage content by 62% and local inflammatory factor level by 64% compared to the saline group. Meanwhile, HA-Fc/NP3ST alleviates systemic inflammation characterized by reduced serum inflammatory factor levels. Collectively, HA-Fc/NP3ST nanoassemblies with ROS-responsive and size-reducible properties exhibit a deeper penetration in atherosclerotic plaque and enhanced macrophage targeting ability, thus exerting effective cholesterol efflux and drug delivery for atherosclerosis therapy.

A shift in Central Asian dust supply with a reduced dominance of the Gobi Desert occurred during Pliocene global cooling, according to a combination of multi-proxy records from a Pacific ferromanganese crust and climate simulations.

Objective: This study aimed to improve the recrystallization yield and purity of flavonoid. Methods: Taking the crude flavonoids from pomelo peel extracted by ultrasonic-assisted ethanol extraction as raw materials, the process parameters of ethanol recrystallization and purification of flavonoids were optimized by response surface methodology. Results: The main factors affecting the recrystallization yield of flavonoids were ethanol concentration, crystallization time, pH value, and the interaction between ethanol concentration and pH value, among which, the ethanol concentration affacted most significantly. Conclusion: The optimal recrystallization conditions of flavonoids were as follows: ethanol volume fraction of 24%, liquid-solid ratio of 10∶1 (mL/g), pH 3.75, crystallization temperature of 4 ℃, and crystallization time of 24 h. The crystallization yield of flavonoids was 8.76%, and the main crystallization product was naringin with a purity of 83.38%.

BackgroundPreoperative anxiety often prevails in children at higher levels than adults, which is a common impediment for surgeons and anesthesiologists. It is of great necessity to explore an appropriate medication to improve this situation. Remimazolam, a type of benzodiazepine drug, has been indicated for the induction and maintenance of procedural sedation in adults since 2020. To date, rare studies were reported to investigate the effect of remimazolam on children. In this study, we investigated the safety and efficacy of intranasal drops of remimazolam and tried to determine the 95% effective dose (ED95) of remimazolam in single intranasal administration in attenuating preoperative anxiety in children.MethodsIn this study, 114 children were enrolled who underwent laparoscopic high-level inguinal hernia ligation between January 2021 and December 2022 and were divided into an early childhood children group and a pre-school children group. The biased coin design (BCD) was used to determine the target doses. A positive response was defined as the effective relief of preoperative anxiety (modified Yale Preoperative Anxiety Scale, mYPAS < 30). The initial nasal dose of remimazolam was 0.5 mg·kg−1 in the two groups. An increment or decrement of 0.1 mg·kg−1 was applied depending on the sedative responses. Isotonic regression and bootstrapping methods were used to calculate the ED95 and 95% confidence intervals (CIs), respectively.ResultsA total of 80 children completed the study, including 40 in the early childhood group and 40 in the pre-school children group. As statistical analysis indicated, the ED95 of a single intranasal infusion of remimazolam for the relief of preoperative anxiety is 1.57 mg·kg−1 (95% CI: 1.45–1.59 mg·kg−1) in early childhood children and 1.09 mg·kg−1 (95% CI: 0.99–1.11 mg·kg−1) in pre-school children, and the CIs did not overlap each other.ConclusionRemimazolam is an effective medication to relieve preoperative anxiety in children. Moreover, the ED95 of single nasal administration of remimazolam for effective relief of preoperative anxiety was 1.57 and 1.09 mg·kg−1 in early childhood children and pre-school children, respectively.

【Objective】In order to screen safe and effective fungicides to provide guidance for passion fruit production, seven biological fungicides were used as materials to study their control effects on the pathogen causing stem rot disease in passion fruits.【Method】Seven botanical and microbiological fungicides were used to determine their toxicity effects on the pathogen causing stem rot disease in passion fruits by mycelium growth rate method, the effects of fungicides on mycelium growth and spore morphology were observed, and their control effects were tested by in vivo inoculation method.【Result】All the selected fungicides showed inhibition effects on mycelium growth but had different effects on spore growth and morphology. Based on the indoor toxicity test results, among the botanical fungicides, Jinggangmycin showed the best inhibition effect with an EC50 of 7.79 mg/L, followed by Chunleimycin, ethylallicin and matrine, with the EC50 of 26.35 mg/L, 28.65 mg/L and 339.13 mg/L, respectively. Polyxins showed the lowest effect with an EC50 of 1 150.29 mg/L. Microbiological fungicide of Bacillus subtilis showed better effect than Trichoderma harzianum, with an EC50 of 3.2×106 CFU/g. The four screened fungicides of Jinggangmycin, Chunleimycin, ethylallicin and B. subtilis showed antifungal effects on different strains of fusarium pathogen. The in vivo inoculation test and field test showed that Jinggangmycin and B. subtilis had remarkable control effects on the pathogen causing stem rot disease in passion fruits, with in vivo inoculation control efficacy of 58.8% and 70.6%, respectively, and field control efficacy of 53.7% and 61.3%, respectively.【Conclusion】Two biological fungicides of B. subtilis and Jinggangmycin were screened out for their optimal control effects on the stem rot disease in passion fruits. It can provide alternatives or effective supplements for chemical fungicides for the control of stem rot disease, which could be promoted and applied.

Objective: To explore the effect of air frying pan treatment on the quality of arrowhead starch. Methods:Taking arrowhead starch as the research object, the effects of thermal cycle mode of air fryer （treated at 160 ℃ for 10 min） on the physical and chemical properties of arrowhead starch with different mesh numbers were investigated. Results: The properties of starch changed after treatment in air fryer, and the properties of starch with different particle sizes were also different after treatment. Under the treatment of air fryer, the viscosity of arrowhead starch with different mesh numbers was significantly different from that of the original starch, the light transmittance increased significantly and the transparency increased differently, and the transparency of starch decreased with the increase of mesh number; At the same time, the gelatinization properties such as freeze-thaw stability also decreased significantly, and the solubility and swelling degree increased. The modified Sagittaria starch particles have broken appearance, shrinkage, increased shape change, and obvious change of characteristic diffraction peak. Conclusion: The air fryer treatment destroyed the particle shape of arrowhead starch to a certain extent, changed the properties of starch itself, which was simpler than other modification methods.

Gasoline is the lifeblood of the national economy. The forecasting of gasoline prices is difficult because of frequent price fluctuations, its complex nature, diverse influencing factors, and low accuracy of prediction results. Previous studies mainly focus on forecasting gasoline prices in a single region by single time series analysis which ignores the daily price co-movement of different series from multiple regions. Because price co-movement may contain useful information for price forecasting, this paper proposes the Lasso-CNN ensemble model that combines statistical models and deep neural networks to forecast gasoline prices. In this model, the Least Absolute Shrinkage and Selection Operator (Lasso) screens and chooses the correlated time series to enhance the performance of forecasting and avoid overfitting, while Convolutional Neural Network (CNN) takes the selected multiple series as its input and then forecasts the gasoline prices in a certain region. Forecasting results of gasoline prices at the national level and regional levels by using the new method demonstrate that the new approach provides more accurate results for the predictions of gasoline prices than those results generated by alternative methods. Thus, the relevant series can enhance the performance of forecasting and help to gain better results.

Distributed Raman Fiber Amplifier (DRFA) is widely used in modern communication systems because it has a series of excellent features. Considering the existing problems of DRFA gain control, this paper studies and improves a method of Automatic Gain Control (AGC) of DRFA by Amplifying Spontaneous Emission (ASE) out of band. In view of the fact that DRFA gain is greatly affected by the performance of optical fiber link, this paper firstly theoretically analyzes the influence of the joint loss at the position 0 away from the pump source in the optical fiber link on the Raman gain control. Then the splice loss at different positions from the pump source is set to be equivalent to the splice loss at position 0. The relationship between Raman gain and out-of-band ASE power is modified so that the AGC of DRFA can be realized more accurately. The Optical Time Domain Reflectometer (OTDR) function is integrated in the DRFA module to detect the distance between the joint loss and the pump source and the loss value in the engineering optical fiber link. Experimental results show that the proposed AGC method can control the influence of joint loss on DRFA gain within 0.2 dB.

To study the effects of macro- and micro-fiber on the concrete beams, bending resistance tests were conducted on the polypropylene fiber-reinforced concrete beams. Stepwise loaded tests were carried out to obtain the load–deflection curves for different test pieces, cracking load values of the first inclined crack, recording and depicting crack development, changes in mid-span deflection of the test pieces, load–strain relationships of concrete, etc. The crack patterns and failure modes were observed. The research findings have shown that the ultimate load of the concrete beams doped with multi-size polypropylene fiber is 58.31 and 34.08% higher than that of ordinary concrete beams and concrete beams with single macro-fiber, respectively. Notably, the ultimate anti-bending bearing capacity of the beams significantly improves following the addition of macro-fiber. Polypropylene fiber can offset the defects caused by macro-fiber, remarkably suppress the development of cracks, and control the deformation of beams due to the effects of micro-fiber of different dimensions.

The use of nanoparticles in agrichemical formula and food products as additives has increased their chances of accumulation in humans via oral intake. Due to their potential toxicity, it is critical to understand their fate and distribution following oral intake. Cerium oxide nanoparticle (CeO2NP) is commonly used in agriculture and is highly stable in the environment. As such, it has been used as a model chemical to investigate nanoparticle's distribution and clearance. Based on their estimated human exposure levels, 0.15–0.75 ​mg/kg body weight/day of CeO2NPs with different sizes and surface charges (30–50 ​nm with negative charge and 25 ​nm are unlikely to accumulate in mouse organ after oral intake, indicating limited impacts on human health.

Abstract Since the first dendrimer was reported in 1978 by Fritz Vögtle, dendrimer research has grown exponentially, from synthesis to application in the past four decades. The distinct structure characteristics of dendrimers include nanoscopic size, multi-functionalized surface, high branching, cavernous interior, and so on, making dendrimers themselves ideal drug delivery vehicles. This mini review article provides a brief overview of dendrimer’s history and properties and the latest developments of dendrimers as drug delivery systems. This review focuses on the latest progress in the applications of dendrimers as drug and gene carriers, including 1) active drug release strategies to dissociate drug/gene from dendrimer in response to stimuli; 2) size-adaptive and charge reversal dendrimer delivery systems that can better take advantage of the size and surface properties of dendrimer; 3) bulk and micro/nano dendrimer gel delivery systems. The recent advances in dendrimer formulations may lead to the generation of new drug and gene products and enable the development of novel combination therapies.

Introduction: Although bone marrow-derived mesenchymal stem cells (BMSCs) have attracted increasing attention because of their pivotal functions in the process of wound healing and fibrosis alleviation, the underlying molecular mechanisms have been poorly understood. Moreover, transforming growth factor beta 1 (TGF-β1) is positively correlated with scar formation, whereas TGF-β3 inhibits the pathological scar formation process. However, the relation of TGF-β1, TGF-β3, and the TGF-β/Smad signaling pathway with BMSCs is unknown and requires further investigation. Methods: A cell co-culture platform was used to examine the relationship between BMSCs and dermal fibroblasts (DFs). EdU labelling and cell cycle detection were carried out to examine the viability of DF cells. Transwell and wound healing assays were used to test the cell migration of DFs. The expression of TGF-β pathway components and collagens were determined by RT-qPCR and western blotting. A damaged skin rat model was applied to test the effects of BMSC treatment on skin wound healing. Results: The results showed that BMSC secretion could inhibit the viability and migration of DFs. Moreover, we observed that the TGF-β-induced expression of TGF-β1, Smad2, Smad3, COLI and COLIII was attenuated upon BMSC treatment in DFs, while the decrease in TGF-β3 expression was enhanced by BMSCs. Furthermore, BMSC treatment accelerated wound healing and attenuated skin collagen deposition in a damaged skin rat model, leading to the mitigation of cell proliferation and enhancement of cell apoptosis. In addition, the expression of alpha-smooth muscle actin (α-SMA), COLI, and COLII was alleviated by BMSC treatment. Conclusions: Our results indicate that BMSCs can promote wound healing and inhibit skin collagen deposition, which is associated with the TGF-β/Smad signaling pathway.