Search

Background: Endometrial injury is considered the major cause of female infertility. Traditional therapies such as estrogen substitution therapy are not satisfactory due to individual variation in response to treatment, thereby warranting the use of alternative strategies such as stem cell therapy. Transplantation of stem cells, such as umbilical cord mesenchymal stem cells (UCMSCs), has been shown to improve endometrial healing. However, due to the effect of the intrauterine environment, the therapeutic effect of UCMSCs is limited, and its efficacy is unstable. HOXA10, encoded by the HOXA10 gene, plays an important role in endometrium morphology maintenance, proliferation, differentiation, and embryo implantation. Moreover, UCMSCs do not show HOXA10 expression. Objective: Our study aimed to evaluate the therapeutic effects of HOXA10-transfected UCMSCs on endometrial injury repair in vivo. Method: First, we established T10-UCMSCs (UCMSCs transfected with HOXA10) for transplantation. To establish the endometrial injury model, we injected 95% ethanol into the uterine cavity and transplanted T10-UCMSCs into the uterine cavity from the cornua uteri. Fourteen days later, uteri were collected for histological and biochemical analysis of endometrial growth and receptivity. Result: Our results showed the endometrial receptivity was better in T10-UCMSCs group than in UCMSCs group, suggesting that HOXA10 could enhance the repairing ability of UCMSCs in the endometrium injury repair. More importantly, the fertility test showed that more embryos were implanted in the T10-UCMSCs group. Conclusion: Our results suggest that UCMSCs with HOXA10 expressing could improve the therapeutic effects on endometrial injury repairing.

Heart rate is one of the most important physiological data of basic signs in human activities. By daily monitoring of heart rate data, it is helpful to know the running condition and state of the body in time. For some people with heart disease, timely heart rate monitoring can help to launch a daily warning. With the development of information technology, smart health wearable products represented by smart watches are widely popular, and heart rate detection function has been added to the products. This paper introduces the principle of heart rate detection, studies and discusses two detection schemes for the heart rate detection function on smartwatches, and compares the two schemes to obtain the advantages and disadvantages of the existing heart rate detection schemes, so as to provide people with a better choice of smartwatches.

For vaccine companies, the announcements of beginning and ending of COVID-19 vaccine development are milestones of vaccine companies. Few studies have explored how announcements of COVID-19 vaccine affect stock market returns of vaccine companies. In this work, we match the announcements of beginning and ending of COVID-19 vaccine development with three leading vaccine companies and adopt the event study methodology to examine the relationship between COVID-19 vaccine development events and changes in stock returns. We identify the 6 public announcements related to 3 begging and 3 ending as well as 3 vaccine companies. The majority events were associated with stock prices increases when those events happened. Our study shows that Covid-19 vaccine R&D have material economic implications and the result shows that investors can use biological company announcements as a solution for determining when to invest in the company and its competitors.

In order to study the prevention of roadway roof bending, sinking, and breaking and the prevention of dynamic disasters such as the appearance of rock bursts, three-point bending experiments of sandstone under different spans were carried out. By using stress loading system and acoustic emission technology, the acoustic emission characteristic parameters of the sandstone fracture process were analyzed, the precursory information of rock bending fracture was explored, and the evolution law of sandstone damage based on acoustic emission characteristics was obtained. The results showed that according to the variation of acoustic emission ringing count, the load-time curve was divided into four typical stages: the first stage showed an overall increasing trend; the second stage showed an obvious increasing trend; the third stage showed obvious accelerated growth and the acoustic emission ringing count reached the maximum at the moment of rupture. In the fourth stage, the amplitude and frequency of the ringing count are large and high. With the increase in span, the cumulative ringing counts of AE decreased, and the rate of change gradually decreased. The fracture process of three-point bending sandstone can reflect the precursor information of rock fracture from time domain, frequency domain, and R value (ratio of cumulative acoustic emission ringing count to cumulative energy count). In time domain, the evolution characteristics of AE cumulative ringing count stage II can be used to predict the three-point bending fracture of sandstone. The peak frequency shows a linear increase after a spike and then an accelerated increase to a rupture, and the boundary point between the spike and the linear and nonlinear can be obtained. The decrease in R value can indicate that the main crack is growing in the specimen. According to the damage rate, the characteristics of the damage variables can be divided into five stages: stationary and low, gradually increasing, gradually decreasing, main crack coalescence, and complete fracture. With the increase in span, the fracture damage shows a decreasing trend. The residual damage fluctuates between 0.38 and 0.40 due to the difference in crack propagation trajectory. It has theoretical research value for revealing the internal mechanism of rock bending and fracture and has engineering guiding significance for mine pressure and rock strata control and dynamic disaster prevention.

Diabetic wounds have been a serious concern for human health owing to their long chronic inflammation and reduced vascularization. Herein, we report novel oil-in-water (o/w) nanoemulsions (NEs) containing Poria cocos triterpenes extract (PTE) to fabricate hyaluronic acid hydrogels (PTE-NEs) for the treatment of diabetic wounds. The size and morphology of NEs are analyzed by transmission electron microscope (TEM) and Zeta potential, respectively. Furthermore, the rheological behavior and morphology of synthesized hydrogels are also determined. It is found that PTE-NEs gel has a homogeneous and porous structure with good elastic properties. In addition, in vitro experiments show that the cell viability of PTE-NEs gel is85 % without cytotoxicity. In vivo experiments of diabetic rats demonstrate that the PTE-NEs gel can not only significantly accelerate diabetic wound healing, collagen deposition, M2 macrophage polarization, and angiogenesis, but also inhibit inflammation. In conclusion, PTE plays a significant role in wound healing and exhibits anti-inflammatory effects, demonstrating its great potential in treating diabetic wounds.

During the postoperative management of urinary diseases, oral or intravenous administration of drugs and implanting ureteral stents are usually required, making localized drug delivery by ureteral stent a precise and effective medication strategy. In the traditional drug loading method, the drug was premixed in the implants in production lines and the versatility of drugs was restricted. However, the complex situation in the urinary system fails the possibility of finding a "one fits all" medication plan, and the intraoperative drug-loading of implants is highly desired to support customized therapy. Here, we designed an ultrathin (8 μm), elastic, and self-adhesive nanofiber bio-tape (NFBT) that can easily encapsulate drugs on the stent surface for controllable localized drug delivery. The NFBT exhibited high binding strength to a ureteral stent, a sustained release over 7 d in PBS for hydrophilic drug, and a zero-order release curve over 28 days for the hydrophobic drug nitrofurantoin (NFT). Further in vivo experiments using a porcine ureteral tract infection model demonstrated that NFBT loaded with NFT could significantly reduce the bacterial concentration in urine. The total amount of NFT delivered by the NFBT was about 2.68 wt% of the recommended dose for the systemic administration.

In this paper, power-sizing equations of rotor-permanent-magnet flux-switching (RPM-FS) machines are proposed and implemented, where the main decisive factors of the electromagnetic torque, namely electric loading and magnetic loading, are deduced, respectively. Although the topologies of RPM-FS machines are evolved from traditional stator-PM flux-switching machines, there are still seriously flux leakages between poles, and it is hard to derive the peak value of the air-gap flux density directly. Hence, a local simplified magnetic equivalent circuit is utilized to calculate the magnetic loading, which is crucial for the power-sizing equation. The influences of the pole-to-pole flux-leakages and harmonics in back-EMF are considered to improve the calculated accuracy of the power-sizing equation. Consequently, the electromagnetic torque can be predicted with acceptable accuracy. The feasibility of the power-sizing equation is verified by the finite element analysis and experimental results.

At the end of the Qing Dynasty, the national crisis was unprecedentedly serious, and people of insight began to explore ways to save and survive. During this period, Yen Fu's translation of English biologist Huxley's Evolution and Ethics, published in 1897, had a great impact on the Chinese society in the late Qing Dynasty. This paper aimes to study the translation means and philosophy of Yen Fu's version of Evolution and Ethics in the context of the late Qing Dynasty and the contemporary social background, to explore the country sentiments and the characteristics of Yen Fu’s country sentiments and the reasons for its formation, and further point out its contemporary value.

The Russia-Ukraine crisis is expected to have a considerable impact on the global economy. By applying the event study approach, we examine the effect of the war on the UK, the US, and China across ten major industries over different lengths of the event window around 22 February 2022. The observed significant cumulative abnormal returns (CAR) in specific industries, along with the differences between nations, are comprehensively analyzed with actual situations faced by each country. Through comparisons, the UK is concluded to be mainly more affected by the crisis than the US and China, especially in the material, information technology, and consumer staples industries. Notably, all three countries are observed to have positive and significant CARs across the event window, which provides strong evidence of the adverse impact of the Russia-Ukraine war on the global energy supply. In other industries, the harmful effects of the crisis vary from countries. This study could provide a new, broad inspection of the ongoing crisis at a macro level and a substantial information reference for policymakers.

Enhancements in the echo intensity and mechanical index (MI) tolerance of ideal ultrasound contrast agents (UCAs) are urgently needed to realize precise clinical ultrasound (US). Solid cellulose nanocrystals (CNCs) have the advantages of imparting strong sound wave propagation and echo intensity when irradiated by US. This study aimed to fabricate improved UCAs via CNC-modified SonoVue ultrasound microbubbles (MBs), characterize the resulting SonoVue@CNC MBs, and evaluate the performance of the SonoVue@CNC MBs in US imaging in vitro and in vivo. SonoVue@CNC MBs were successfully prepared by incorporating CNCs into SonoVue MBs via self-assembly. The SonoVue@CNC MBs were spherical in shape with mean particle sizes of (5.50 ± 1.60) μm. The CNCs were mainly distributed on the polymeric shells of the SonoVue@CNC MBs. When the MI was 0.4, the echo intensity of the SonoVue@CNC MBs was 1.5-fold greater than that of the SonoVue MBs in vitro. The CNC concentration regulated the quality of SonoVue@CNC-promoted contrast-enhanced ultrasound (CEUS) images. Enhanced US images of both the livers and kidneys of Sprague–Dawley (SD) rats showed that the CNC-loaded UCA led to a higher echo intensity than SonoVue. In CCK-8 assays using MCF-10A cells, both SonoVue@CNC MBs and CNCs exhibited weak toxicities against MCF-10A cells. Ultimately, the spherical SonoVue@CNC MBs with a uniform particle size displayed an enhanced safety profile and improved the imaging quality of US in vivo and in vitro. Next, drugs and targeting moieties will be loaded onto the SonoVue@CNC MBs via the CNCs to develop UCA-based selective ultrasonic theranostic methods. Graphical abstract As shown in the graphical abstract, the white bubble in the left-middle position symbolized SonoVue microbubble (MB), the green rod-like particle signified CNC nanorod. The big white bubble decorated with green rod-like nanorod next to the mouse was SonoVue@CNC MB which was successfully prepared by incorporating CNCs into SonoVue MB via self-assembly. The purple square frame on the upper left displayed CNC, SonoVue MB, SonoVue@CNC MB and their relative diagrammatic drawings. Picture (I) displayed the transmission electron microscopy results for CNCs (a) and SonoVue@CNC MBs (b, c and d) of morphological study. Picture (II) displayed the in vitro ultrasound (US) imaging of SonoVue (a) MB and SonoVue@CNC (b, c and d) MBs with different CNCs concentrations. Picture (III and IV) displayed the in vivo US imaging of SonoVue (a) and SonoVue@CNC (b, c and d) MBs with different CNCs concentrations for SD mouse liver and kidney, respectively.

Problem definition: This paper empirically investigates how customer email engagement affects the profitability of subscription service providers and retailers. They have been using email engagement to increase customer retention. However, it is unclear whether email engagement improves their profitability. The existing literature focuses on email engagement’s benefit of customer retention but ignores its associated operating cost to serve retained customers. Methodology/results: We analyze the outcome of a field experiment conducted by a large U.S. car wash chain that offers tiered subscription services to consumers and employs an radiofrequency identification-based technology to track subscriber service events. We apply survival analysis and difference-in-differences methods to estimate the effects of email engagement on subscribers’ retention and service consumption. We find that a one-month engagement with two emails separated by a half-month interval increased the likelihood of subscriber retention by 7.4% five months after the experiment started and decreased the subscriber churn odds by 26.3% for the entire five-month duration. Meanwhile, we find that the same engagement increased a subscriber’s per-period service consumption by 7.0%. We provide suggestive evidence for two behavioral mechanisms that explain the effect of email engagement on subscribers’ service consumption. First, the engagement effect decays over time and exhibits fatigue after the second email, suggesting that emails act as reminders to subscribers. Second, the engagement effect persists after engagement ends but weakens over time, suggesting the habit formation of subscribers. By computing subscriber lifetime value and the operating cost of service, we find that email engagement increases profit when deployed on mid-level infrequent-use subscribers and top-level subscribers but decreases profit when deployed on mid-level frequent-use subscribers and basic-level subscribers. Therefore, we recommend that the company use a selective strategy by sending engagement emails to only profitable subscribers. Managerial implications: Our study highlights that email engagement is a double-edged sword; it increases both customer retention and service consumption, and it may decrease profitability when the increased operating cost to serve retained customers outweighs the benefit of customer retention. We recommend that subscription service providers and retailers adopt a data-driven approach to optimize their email engagement strategies.

Establishing a suitable animal model of growth plate injury is necessary to evaluate the effect of tissue engineering scaffolds on repairing the injured growth plate. However, the currently used animal models have limitations. Therefore in this study, we reported and evaluated a new modeling method termed the longitudinal disruption method, which is to make a longitudinal defect in the region of growth plate. To compare this new method with the traditional transverse disruption method, we constructed the models by both methods, respectively. To observe whether bone bridges were formed, histological sections were analyzed by hematoxylin-eosin (HE) and Masson staining at 3 weeks after modeling. The HE and Masson staining results showed the formation of bone bridges in both groups, implying that the two methods successfully injured the growth plate. However, it was unclear whether the exact injury to growth plate caused by both methods was consistent. Therefore, to evaluate the accuracy and precision of modeling method, the X-ray and micro-computed tomography (CT) were performed immediately after modeling. The percentages of accurate defect position in the longitudinal and transverse modeling groups were 88.89% and 55.56%, respectively. The micro-CT results revealed irregularly shaped defect cross sections in the transverse modeling group, whereas the defects in the longitudinal modeling group had regular shapes. The mean defect areas were 10.06 ± 0.86 and 12.30 ± 2.13 mm

The Maoming basin in south China is rich in oil shale resources, whereas the Youganwo formation is a potential area for large-scale in situ exploration because of its relatively large thickness, high oil content, and good continuity. Based on previous geologic studies on the Maoming basin and the laboratory experimental data, in situ pyrolysis models for shale oil are established using the CMG-STARS software to simulate the in situ heating and reactions. To analyze the major influencing factors, the CMOST module is employed to conduct the sensitivity analysis with accumulated oil and gas production as the target functions. The initial kerogen concentration, formation permeability, activation energy of pyrolysis reaction, frequency factor, heating rate, heating power, heat loss, heat conductivity, heat capacity, and bottom-hole pressure are chosen to be the controlling parameters. A total of 128 cases are calculated for each target function with the fractional factorial sampling method. The sensitivity analysis results demonstrate that the heating power, initial kerogen concentration, and reaction activation energy are the major influencing factors for oil and gas production. The simulation results also reveal that high non-uniformity of the temperature field will cause the light oil to convert to gas and char at the high-temperature zone near the heater well. It is suggested that proper control of formation temperature, such as increasing permeability to promote oil and gas flow and form a more uniform temperature field, will help to prevent oil production loss caused by secondary reactions.

Sap flow is widely used to estimate the transpiration and water consumption of canopies and to manage water resources. In this paper, an improved time series prediction model was proposed by integrating three basic networks—CNN, GRU and BiLSTM—to assess sap flow with historical environment variables. A dataset with 17,569 records of each, including 9 environment variables and 1 sap flow, was applied from a public database of SAPFLUXNET. After normalization, the environment variables were analyzed and composed with the factor analysis method. After the CNN-GRU-BiLSTM structure was designed, N records of three main factors were computed from environment variables, which were measured at N previous moments, and the sap flow was measured at the current moment, and they were applied for each training, validation, and testing cycle. To improve and compare the CNN-GRU-BiLSTM-based model, nine other models, using the methods of multiple linear regression, support vector regression, random forest, LSTM, GRU, BiLSTM, CNN-GRU, CNN-BiLSTM, and CNN-GRU-LSTM, were constructed in this study, respectively. Results show that the performance of the CNN-GRU-BiLSTM-based model has more accuracy than the other nine models we built in this paper, with the mean absolute error, mean squared error, mean absolute percentage error, and coefficient of determination (R2) being 0.0410, 0.0029, 0.2708 and 0.9329, respectively. Furthermore, for a comparison of the descending dimension method of factor analysis, principal component analysis (PCA) and singular value decomposition (SVD) methods were applied and compared, respectively. Results show that the performance of the factor analysis-based model is better than the PCA- or SVD-based model, with the R2 results of the factor analysis-based model being higher than the PCA- and SVD-based models by 5.06% and 10.63%, respectively. This study indicates that the CNN-GRU-BiLSTM-based sap flow prediction model established with a factor analysis of historical environmental variables has optimistic applications for analyzing the transpiration of trees and evaluating water consumption.

The novel wheat powdery mildew and stripe rust resistance genes Pm5V/Yr5V are introgressed from Dasypyrum villosum and fine mapped to a narrowed region in 5VS, and their effects on yield-related traits were characterized. The powdery mildew and stripe rust seriously threaten wheat production worldwide. Dasypyrum villosum (2n = 2x = 14, VV), a relative of wheat, is a valuable resource of resistance genes for wheat improvement. Here, we describe a platform for rapid introgression of the resistance genes from D. villosum into the wheat D genome. A complete set of new wheat-D. villosum V (D) disomic substitution lines and 11 D/V Robertsonian translocation lines are developed and characterized by molecular cytogenetic method. A new T5DL·5V#5S line NAU1908 shows resistance to both powdery mildew and stripe rust, and the resistances associated with 5VS are confirmed to be conferred by seedling resistance gene Pm5V and adult-plant resistance gene Yr5V, respectively. We flow-sort chromosome arm 5VS and sequence it using the Illumina NovaSeq 6000 system that allows us to generate 5VS-specific markers for genetic mapping of Pm5V/Yr5V. Fine mapping shows that Pm5V and Yr5V are closely linked and the location is narrowed to an approximately 0.9 Mb region referencing the sequence of Chinese Spring 5DS. In this region, a NLR gene in scaffold 24,874 of 5VS orthologous to TraesCS5D02G044300 is the most likely candidate gene for Pm5V. Soft- and hard-grained T5DL·5V#5S introgressions confer resistance to both powdery mildew and stripe rust in diverse wheat genetic backgrounds without yield penalty. Meanwhile, significant decrease in plant height and increase in yield were observed in NIL-5DL·5V#5S compared with that in NIL-5DL·5DS. These results indicate that Pm5V/Yr5V lines might have the potential value to facilitate wheat breeding for disease resistance.

In this paper, hydrothermal treatment was used to treat river sediment. The physicochemical properties, chemical speciation, bioavailability, ecotoxicity, and leaching toxicity of heavy metals (Zn, Cu, Cr, Cd, Ni, Pb) in sediment under different hydrothermal treatment conditions were studied, and stabilization mechanisms of heavy metals were explained. The results showed that hydrothermal temperature and time had a huge impact on sediment reduction and heavy metal stabilization. The best reduction and stabilization of sediments were achieved at a hydrothermal temperature of 260°C and a hydrothermal period of 3 h. The hydrothermal treatment caused the sediment to undergo dehydration, dihydroxylation, decarboxylation, deamination, and aromatization with a gradual decrease in its H/C ratio, O/C ratio, and pH; a gradual increase in porosity and surface area; and a decrease in particle size. This facilitates the dehydration, reduction, and stabilization of the sediment. The bioavailable components of heavy metals in sediment were dramatically reduced following hydrothermal treatment, but the fraction of stable components rose significantly. This resulted in a marked decrease in the environmental bioavailability, ecotoxicity, and leaching toxicity of the heavy metals. Therefore, hydrothermal treatment might be an effective ex situ repairment way for reducing, stabilizing, and making river sediment harmless.

A second-order accurate in time, positivity-preserving, and unconditionally energy stable operator splitting numerical scheme is proposed and analyzed for the system of reaction-diffusion equations with detailed balance. The scheme is designed based on an energetic variational formulation, in which the reaction part is reformulated in terms of the reaction trajectory, and both the reaction and diffusion parts dissipate the same free energy. At the reaction stage, the reaction trajectory equation is approximated by a second-order Crank-Nicolson type method. The unique solvability, positivity-preserving, and energy-stability are established based on a convexity analysis. In the diffusion stage, an exact integrator is applied if the diffusion coefficients are constant, and a Crank-Nicolson type scheme is applied if the diffusion process becomes nonlinear. In either case, both the positivity-preserving property and energy stability could be theoretically established. Moreover, a combination of the numerical algorithms at both stages by the Strang splitting approach leads to a second-order accurate, structure-preserving scheme for the original reaction-diffusion system. Numerical experiments are presented, which demonstrate the accuracy of the proposed scheme., 23 pages, 2 figures

B7-H4, a sibling to PD-L1 in B7 family, has been reported to be a novel immune checkpoint that is prevalent among non-inflamed tumors. Herein, we attempt to explore the potential of B7-H4 in survival prediction and therapeutic guidance in muscle-invasive bladder cancer (MIBC) patients.This study included 391 patients from The Cancer Genome Atlas (TCGA) database and 122 patients from Zhongshan (ZS) Hospital. The evaluation of response to PD-L1 inhibitors was based on 270 patients in IMvigor210 cohort. Kaplan-Meier survival and multivariate analyses were performed to assess clinical outcomes in three cohorts. The correlation of B7-H4 expression with immune contexture and genomic alterations was analyzed based on immunohistochemistry, Microenvironment Cell Populations-counter (MCP-counter) tool, and whole-exome sequencing.MIBC patients with the high level of B7-H4 expression (B7-H4Despite adverse clinical outcomes, B7-H4

The ion transport properties across the membrane under conditions of different membrane types, solution concentrations, flow rates and temperatures were investigated in a four-compartment reactor. By combining linear sweep voltammetry and chronopotentiometry, the limiting current density (I lim), the ion transition time (τ) and the difference between ion transport numbers in the membrane and the solution (t m–t s) were determined. And the diffusion boundary layer thickness (δ) of the membrane-solution system at steady-state conditions was measured by electrochemical impedance spectroscopy. The results show that the use of Selemion membrane and the increase of solution concentration, flow rate and temperature, I lim and τ increase, t m–t s and δ decrease. This means the concentration polarization of the system is weaker and complete concentration polarization is more difficult to occur. At the same time, I lim, τ and t m–t s are strongly related to solution concentration and temperature, while the diffusion boundary layer thickness is mainly affected by solution concentration and flow rate. Additionally, I lim of anion exchange membranes is larger than that of cation exchange membranes due to the difference in migration rates of anion and cation.

In underground engineering, the deformation and failure process of the surrounding rock of the roadway is always accompanied by the occurrence of energy. The study of the energy distribution law of the surrounding rock of the roadway plays an important role in its stability. This paper first theoretically analyzes the stress and energy distribution law of the surrounding rock of the roadway, then with the help of numerical simulation method, combined with the existing physical and mechanical parameters, based on the existing support parameters of Dongrong No. 2 Mine, gradually compares and analyzes the distribution of vertical stress and energy under the three support methods of no support, original support, and combined support, and the results found that the vertical stress distribution law under the three support methods is basically the same. High-stress areas appear on the two ribs of the roadway, and low-stress areas appear on the roof and floor. The range of high-stress areas from no support to combined support continues to decrease and becomes more evenly distributed. The energy distribution pattern is basically the same. The overall energy of the coal seam is high. There are high-energy areas at 2 m left and right of the roadway, and the roof and floor energy of the roadway is the smallest. The low energy area extends 5 m up and down, respectively. The range of high-energy areas from no support to combined support is shrinking, and the energy distribution is more uniform.

Cancer is still ranked as a leading cause of death according to estimates from the World Health Organization (WHO) and the strong link between tumor viruses and human cancers have been proved for almost six decades. Cell-free DNA (cfDNA) has drawn enormous attention for its dynamic, instant, and noninvasive advantages as one popular type of cancer biomarker. cfDNAs are mainly released from apoptotic cells and exosomes released from cancer cells, including those infected with viruses. Although cfDNAs are present at low concentrations in peripheral blood, they can reflect tumor load with high sensitivity. Considering the relevance of the tumor viruses to the associated cancers, cfDNAs derived from viruses may serve as good biomarkers for the early screening, diagnosis, and treatment monitoring. In this review, we summarize the methods and newly developed analytic techniques for the detection of cfDNAs from different body fluids, and discuss the implications of cfDNAs derived from different tumor viruses in the detection and treatment monitoring of virus-associated cancers. A better understanding of cfDNAs derived from tumor viruses may help formulate novel antitumoral strategies to decrease the burden of cancers that attributed to viruses.

Introduction: Growth plate injury is a significant challenge in clinical practice, as it could severely affect the limb development of children, leading to limb deformity. Tissue engineering and 3D bioprinting technology have great potential in the repair and regeneration of injured growth plate, but there are still challenges associated with achieving successful repair outcomes.Methods: In this study, GelMA hydrogel containing PLGA microspheres loaded with chondrogenic factor PTH(1–34) was combined with BMSCs and Polycaprolactone (PCL) to develop the PTH(1–34)@PLGA/BMSCs/GelMA-PCL scaffold using bio-3D printing technology.Results: The scaffold exhibited a three-dimensional interconnected porous network structure, good mechanical properties, biocompatibility, and was suitable for cellchondrogenic differentiation. And a rabbit model of growth plate injury was appliedto validate the effect of scaffold on the repair of injured growth plate. The resultsshowed that the scaffold was more effective than injectable hydrogel in promotingcartilage regeneration and reducing bone bridge formation. Moreover, the addition ofPCL to the scaffold provided good mechanical support, significantly reducing limbdeformities after growth plate injury compared with directly injected hydrogel.Discussion: Accordingly, our study demonstrates the feasibility of using 3D printed scaffolds for treating growth plate injuries and could offer a new strategy for the development of growth plate tissue engineering therapy.

Transition metal selenides (TMSs) have been extensively explored as the most attractive battery-type supercapacitor cathodes. However, TMSs usually exhibit elusive active sites, sluggish reaction/diffusion kinetics, and poor conductivity, which severely degrade their capacity and rate performance. To overcome these shortcomings of TMSs, herein, we employ a synchronous strategy of Mn donor doping and Se vacancy in a flower-like Ni3Se4 cathode and optimize the dopant/vacancy concentration (VSe(M)–Mn(M)–Ni3Se4) to maximize electron release from Mn and effectively accumulate the electrons around the vacancy, resulting in maximum electron transfer during the charge–discharge process. Moreover, the proposed strategy can intrinsically tune electronic structure, increase electroactive sites, accelerate OH− diffusion kinetics, and pledge the ion chemisorption–desorption equilibrium verified based on first-principle calculations. Thus, the fabricated cathode exhibits ultrahigh capacity and rate capability (357 and 275 mAh g−1 at 1 and 100 A g−1, respectively), and a hybrid supercapacitor with the cathode exhibits sufficient energy density of 118 Wh kg−1 at 0.8 kW kg−1 and exceptional durability, which is considerably greater than that exhibited by supercapacitors comprising other cathodes. Moreover, the charge–discharge mechanism is elaborated in detail via ex situ techniques. This study provides fundamental guidelines for constructing high-performance battery-type cathodes, which can be used in next-generation supercapacitors.

Introduction: The repair and regeneration of growth plate injuries using tissue engineering techniques remains a challenge due to large bone bridge formation and low chondrogenic efficiency.Methods: In this study, a bilayer drug-loaded microspheres was developed that contains the vascular endothelial growth factor (VEGF) inhibitor, Bevacizumab, on the outer layer and insulin-like growth factor-1 (IGF-1), a cartilage repair factor, on the inner layer. The microspheres were then combined with bone marrow mesenchymal stem cells (BMSCs) in the gelatin methacryloyl (GelMA) hydrogel to create a composite hydrogel with good injectability and biocompatibility.Results: The in vitro drug-release profile of bilayer microspheres showed a sequential release, with Bevacizumab released first followed by IGF-1. And this hydrogel simultaneously inhibited angiogenesis and promoted cartilage regeneration. Finally, in vivo studies indicated that the composite hydrogel reduced bone bridge formation and improved cartilage regeneration in the rabbit model of proximal tibial growth plate injury.Conclusion: This bilayer microsphere-based composite hydrogel with sequential controlled release of Bevacizumab and IGF-1 has promising potential for growth plate injury repair.

BackgroundDue to the effectiveness and safety, acupuncture, one of the traditional therapies of Chinese medicine, has been widely used in clinical practice globally. A few systematic review or meta-analyses have proved its effectiveness and safety towards patients with cancer pain, while there are no syntheses among those evidence. The aim of this scoping review is to summarize the evidence from systematic reviews of acupuncture for the treatment of cancer pain and evaluate the breadth and methodological quality of these evidence as well.MethodsThe scoping review process was guided by the methodology framework of Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA ScR) and “Arkseyand O’Malley six-stage framework”. Electronic searches were carried out in several online databases from inception to Jan 2022. Systematic reviews and meta-analyses that involve any type of acupuncture for patients with cancer pain will be included. A pair of reviewers independently screened full texts. Moreover, review characteristics were extracted, and methodological quality was assessed using the AMSTAR 2 tool.ResultsTwenty-five systematic reviews and meta-analyses were included. Manual acupuncture is the most frequently included types of test group intervention (48%), followed by acupuncture + medicine (28%), and auricular acupuncture (12%). All the reviews have declared that acupuncture is an effective method for cancer pain treatment. Eleven reviews (44%) aiming at evaluating the safety also have confirmed that acupuncture is safe for treating cancer pain. However, most included studies were conducted in China. With certain geographical limitations, the findings were not representative within the region. The results of our review may owe to the synthesis of all kinds of cancer pain, and only 2 reviews described the type of cancer pain in detail.ConclusionsThis scoping review synthesizes and evaluates existing evidence of acupuncture for cancer pain. From this scoping review of systematic reviews and meta-analyses, there are clear recommendations for future studies: expanding the region of research in the world and trying to conduct the study of different types of cancer pain in details as much as possible. Evidences of acupuncture for cancer pain can inform clinical decision-making. Systematic review registrationhttps://inplasy.com/inplasy-2022-1-0073/, identifier INPLASY202210073.

Synchrotron small-angle X-ray diffraction is the method of choice for nm-scale structural studies of striated muscle under physiological conditions and on millisecond time scales. The lack of generally applicable computational tools for modeling X-ray diffraction patterns from intact muscles has been a significant barrier to exploiting the full potential of this technique. Here, we report a novel “forward problem” approach using the spatially explicit computational simulation platform MUSICO to predict equatorial small-angle X-ray diffraction patterns and the force output simultaneously from resting and isometrically contracting rat skeletal muscle that can be compared to experimental data. The simulation generates families of thick–thin filament repeating units, each with their individually predicted occupancies of different populations of active and inactive myosin heads that can be used to generate 2D-projected electron density models based on known Protein Data Bank structures. We show how, by adjusting only a few selected parameters, we can achieve a good correspondence between experimental and predicted X-ray intensities. The developments presented here demonstrate the feasibility of combining X-ray diffraction and spatially explicit modeling to form a powerful hypothesis-generating tool that can be used to motivate experiments that can reveal emergent properties of muscle.

Background Infertility is associated with the alteration of the seminal microbiome. However, how the onset of dysbiosis remains controversial and the involvement of host factors remains elusive. This study investigates the alterations of the seminal microbiome in male infertility and examines the association and function of DEFB119, a reproductive-tract-specific host antimicrobial peptide, on the seminal microbiome and male fertility. Results We analyzed the seminal microbiome by 16S rRNA sequencing in 30 individuals with normal sperm parameters and 58 male-factor infertile patients. While we observed comparable genera, diversity and evenness of bacterial communities, a marked decrease in the modularity of the metacommunities was observed in patients with abnormal spermiogram. Analysis of the protein level of DEFB119 by ELISA revealed a marked elevation of DEFB119 in a subpopulation of male-infertile patients. Elevated seminal DEFB119 was associated with a decrease in the observed genera, diversity and evenness of bacterial communities and further distortion of the metacommunities. Mediation analysis suggests the involvement of elevated DEFB119 and dysbiosis of the seminal microbiome in mediating the abnormalities in the spermiogram. Functional experiments showed that recombinant DEFB119 significantly decrease the progressive motility of sperm in patients with abnormal spermiogram. Moreover, DEFB119 demonstrated species-specific antimicrobial activity against common seminal and non-seminal species. Conclusions Male infertility is associated with distorted bacterial networks. Elevation of the DEFB119 level in seminal plasma stratifies male infertile patients with dysbiosis of the seminal microbiome. Both elevated DEFB119 and dysbiosis contribute to the abnormal spermiogram. Our work identifies an important host factor that mediates the host-microbiome interaction and stratifies the seminal microbiome associated with male infertility. These results may lead to a new diagnostic method for male infertility and regimens for formulating the microbiome in the reproductive tract and other organ systems.

Background Respiratory diseases are the 2nd leading cause of death globally. The current treatments for chronic lung diseases are only supportive. Very few new classes of therapeutics have been introduced for lung diseases in the last 40 years, due to the lack of reliable lung models that enable rapid, cost-effective, and high-throughput testing. To accelerate the development of new therapeutics for lung diseases, we established two classes of lung-mimicking models: (i) healthy, and (ii) diseased lungs – COPD. Methods To establish models that mimic the lung complexity to different extents, we used five design components: (i) cell type, (ii) membrane structure/constitution, (iii) environmental conditions, (iv) cellular arrangement, (v) substrate, matrix structure and composition. To determine whether the lung models are reproducible and reliable, we developed a quality control (QC) strategy, which integrated the real-time and end-point quantitative and qualitative measurements of cellular barrier function, permeability, tight junctions, tissue structure, tissue composition, and cytokine secretion. Results The healthy model is characterised by (i) continuous tight junctions, (ii) physiological cellular barrier function, (iii) a full thickness epithelium composed of multiple cell layers, and (iv) the presence of ciliated cells and goblet cells. Meanwhile, the disease model emulates human COPD disease: (i) dysfunctional cellular barrier function, (ii) depletion of ciliated cells, and (ii) overproduction of goblet cells. The models developed here have multiple competitive advantages when compared with existing in vitro lung models: (i) the macroscale enables multimodal and correlative characterisation of the same model system, (ii) the use of cells derived from patients that enables the creation of individual models for each patient for personalised medicine, (iii) the use of an extracellular matrix proteins interface, which promotes physiological cell adhesion and differentiation, (iv) media microcirculation that mimics the dynamic conditions in human lungs. Conclusion Our model can be utilised to test safety, efficacy, and superiority of new therapeutics as well as to test toxicity and injury induced by inhaled pollution or pathogens. It is envisaged that these models can also be used to test the protective function of new therapeutics for high-risk patients or workers exposed to occupational hazards. Graphical Abstract