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Abstract Background The impact of the etiology of rotator cuff injury (RCI) on outcomes after rotator cuff repair remains unclear. This study aimed to evaluate the postoperative outcomes of patients with RCIs of different etiologies and identify the risk factors affecting prognosis. Methods This study included 73 patients with RCI who underwent arthroscopic rotator cuff repair. The patients were categorized into either a traumatic group or a non-traumatic group based on their history of trauma. Preoperative and postoperative assessments included shoulder range of motion, muscle strength, and physical examination findings specific to the shoulder for both groups. Clinical differences between arthroscopic repair of traumatic and non-traumatic RCIs were evaluated using univariate analysis. Logistic regression analysis determined independent risk factors for rotator cuff repair prognosis. Results Among the 73 patients, 31 were in the traumatic group and 42 in the non-traumatic group, with a minimum postoperative follow-up of 12 months and a mean follow-up of 13.8 months. The duration of the disease was significantly longer in the non-traumatic group compared with the traumatic group (P

Abstract Pectobacterium carotovorum and Pectobacterium aroidearum represent the primary pathogens causing variable soft rot disease. However, the fundamental defense responses of Pinellia ternata to pathogens remain unclear. Our investigation demonstrated that the disease produced by P. carotovorum is more serious than P. aroidearum. RNA-seq analysis indicated that many cell wall-related genes, receptor-like kinase genes, and resistance-related genes were induced by P. aroidearum and P. carotovorum similarly. But many different regulatory pathways exert a crucial function in plant immunity against P. aroidearum and P. carotovorum, including hormone signaling, whereas more auxin-responsive genes were responsive to P. carotovorum, while more ethylene and gibberellin-responsive genes were responsive to P. aroidearum. 12 GDSL esterase/lipase genes and 3 fasciclin-like arabinogalactan protein genes were specifically upregulated by P. carotovorum, whereas 11 receptor-like kinase genes and 8 disease resistance genes were up-regulated only by P. aroidearum. Among them, a lectin gene (part1transcript/39001) was induced by P. carotovorum and P. aroidearum simultaneously. Transient expression in N. benthamiana demonstrated that the lectin gene improves plant resistance to P. carotovorum. This study offers a comprehensive perspective on P. ternata immunity produced by different soft rot pathogens and reveals the importance of lectin in anti-soft rot of P. ternata for the first time.

Tislelizumab, as a PD-1 inhibitor, has demonstrated significant efficacy in cancer treatment. However, it may also induce immune-related adverse events (irAEs). This case report describes a patient who developed oral ulcers and dysphagia following treatment with tislelizumab, which was diagnosed as exfoliative esophagitis through endoscopic examination. The condition improved after corticosteroid pulse therapy. A review of the relevant literature revealed no prior reports of immune checkpoint inhibitor (ICI)-related esophagitis cases, prompting an exploration of the potential pathophysiological mechanisms and therapeutic strategies. This report emphasizes the importance of vigilance for rare irAEs during ICI therapy, advocating for early detection and timely intervention.

Chlorophyll content is a vital indicator for evaluating vegetation health and estimating productivity. This study addresses the issue of Global Ecosystem Dynamics Investigation (GEDI) data discreteness and explores its potential in estimating chlorophyll content. This study used the empirical Bayesian Kriging regression prediction (EBKRP) method to obtain the continuous distribution of GEDI spot parameters in an unknown space. Initially, 52 measured sample data were employed to screen the modeling parameters with the Pearson and RF methods. Next, the Bayesian optimization (BO) algorithm was applied to optimize the KNN regression model, RFR model, and Gradient Boosting Regression Tree (GBRT) model. These steps were taken to establish the most effective RS estimation model for chlorophyll content in Dendrocalamus giganteus (D. giganteus). The results showed that: (1) The R2 of the EBKRP method was 0.34~0.99, RMSE was 0.012~3,134.005, rRMSE was 0.011~0.854, and CRPS was 965.492~1,626.887. (2) The Pearson method selects five parameters (cover, pai, fhd_normal, rv, and rx_energy_a3) with a correlation greater than 0.37. The RF method opts for five parameters (cover, fhd_normal, sensitivity, rh100, and modis_nonvegetated) with a contribution threshold greater than 5.5%. (3) The BO-GBRT model in the RF method was used as the best estimation model (R2 = 0.86, RMSE = 0.219 g/m2, rRMSE = 0.167 g/m2, p = 84.13%) to estimate and map the chlorophyll content of D. giganteus in the study area. The distribution range is 0.20~2.50 g/m2. The findings aligned with the distribution of D. giganteus in the experimental area, indicating the reliability of estimating forest biochemical parameters using GEDI data.

Abstract Background The effects of the timing of surgical repair on the outcomes of traumatic and non-traumatic rotator cuff injuries (RCI) remain elusive. Thus, this study aimed to compare differences in outcomes following the repair of traumatic and non-traumatic RCI at varying time points. Methods The study population comprised 87 patients with traumatic and non-traumatic RCI who underwent arthroscopic rotator cuff repair and were followed up for a minimum of 6 months. Next, the trauma and the non-trauma groups were stratified into subgroups according to the time of injury (early repair: occurring within 3 months; delayed repair: occurring after 3 months). Measurements before and after surgical interventions were compared to evaluate the effect of the duration of RCI on the functional status of patients in the trauma and non-trauma groups. Primary evaluation indices included the Visual Analog Scale (VAS) pain score, American Shoulder and Elbow Surgeons (ASES) score, Constant shoulder function score, and the University of California, Los Angeles (UCLA) shoulder score. Secondary evaluation indices consisted of shoulder range of motion (ROM), postoperative rotator cuff retear rate, and incidence of joint stiffness. Results Among the 40 patients in the trauma group, 22 underwent early repair, whereas the remaining 18 underwent delayed repair. In the non-trauma group consisting of 47 patients, 18 underwent early repair, whereas the remaining 29 underwent delayed repair. The minimum clinical follow-up time was 6 months, with an average follow-up time of 10.2 months. During postoperative follow-up, 1 and 6 patients who underwent early and delayed repair experienced re-tear in the trauma group, respectively. Contrastingly, 3 and 8 patients who underwent early and delayed repair presented with re-tear in the non-trauma group, respectively. Conclusion Early repair of traumatic RCI yielded superior outcomes, including improved range of motion, lower pain symptoms, and lower risk of postoperative re-tears compared to delayed repair. Additionally, non-surgical treatment is recommended as the preferred approach for patients with non-traumatic RCI.

Abstract Pinellia ternata (Thunb.) Breit is a traditional Chinese medicine with important pharmacological effects. However, its cultivation is challenged by soil degradation following excessive use of chemical fertilizer. We conducted an experiment exploring the effects of replacing chemical fertilizers with organic fertilizers (OF) on the growth and yield of P. ternata, as well as on the soil physicochemical properties and microbial community composition using containerized plants. Six fertilization treatments were evaluated, including control (CK), chemical fertilizer (CF), different proportions of replacing chemical fertilizer with organic fertilizer (OM1−4). Containerized P. ternata plants in each OF treatment had greater growth and yield than the CK and CF treatments while maintaining alkaloid content. The OM3 treatment had the greatest yield among all treatments, with an increase of 42.35% and 44.93% compared to the CK and CF treatments, respectively. OF treatments improved soil quality and fertility by enhancing the activities of soil urease (S-UE) and sucrase (S-SC) enzymes while increasing soil organic matter and trace mineral elements. OF treatments increased bacterial abundance and changed soil community structure. In comparison to the CK microbial groups enriched in OM3 were OLB13, Vicinamibacteraceae, and Blrii41. There were also changes in the abundance of gene transcripts among treatments. The abundance of genes involved in the nitrogen cycle in the OM3 has increased, specifically promoting the transformation of N-NO3 − into N-NH4 +, a type of nitrogen more easily absorbed by P. ternata. Also, genes involved in "starch and sucrose metabolism" and "plant hormone signal transduction" pathways were positively correlated to P. ternata yield and were upregulated in the OM3 treatment. Overall, OF in P. ternata cultivation is a feasible practice in advancing sustainable agriculture and is potentially profitable in commercial production.

Abstract The change of fracture propagation direction caused by stress interference between fractures is one of the main reasons that affect shale gas productivity. Natural fractures will be damaged by the induced stress, and the induced stress field produced by natural fracture damage will in turn affect the propagation of hydraulic fractures. Previous studies usually ignored the impact of stress field variation caused by natural fracture damage, leading to inaccurate fracture propagation simulation results. A new model for simulating hydraulic fracturing-induced stress field is established with consideration of the influence of natural fracture damage. Then, the natural fracture-induced stress is analyzed in open and closed fracture states. Through superposition of stress fields of natural fractures and hydraulic fractures, the interaction among open and closed natural fractures, reservoir and hydraulic fracture, and the corresponding fracture property evolution are studied. The results demonstrate that induced stress is not affected by elastic modulus and Poisson's ratio of the rock. The induced stress difference at the fracture tip is proportional to the net pressure and the length of hydraulic fractures. The results provide guidance for the optimal design of fracturing. When the deflection angle of hydraulic fracture is less than 90°, the maximum induced stress difference at the fracture tip decreases with the reduction in the deflection angle. When the deflection angle of hydraulic fracture is smaller than 90° or the deflection angle of natural fracture is smaller than 45°, the steering of hydraulic fracture is less hindered, which is beneficial to the formation of complex fracture network.

Abstract Root-associated microbiomes contribute to plant growth and health, and are dynamically affected by plant development and changes in the soil environment. However, how different fertilizer regimes affect quantitative changes in microbial assembly to effect plant growth remains obscure. Here, we explore the temporal dynamics of the root-associated bacteria of soybean using quantitative microbiome profiling (QMP) to examine its response to unbalanced fertilizer treatments (i.e., lacking either N, P or K) and its role in sustaining plant growth after four decades of unbalanced fertilization. We show that the root-associated bacteria exhibit strong succession during plant development, and bacterial loads largely increase at later stages, particularly for Bacteroidetes. Unbalanced fertilization has a significant effect on the assembly of the soybean rhizosphere bacteria, and in the absence of N fertilizer the bacterial community diverges from that of fertilized plants, while lacking P fertilizer impedes the total load and turnover of rhizosphere bacteria. Importantly, a SynCom derived from the low-nitrogen-enriched cluster is capable of stimulating plant growth, corresponding with the stabilized soybean productivity in the absence of N fertilizer. These findings provide new insights in the quantitative dynamics of the root-associated microbiome and highlight a key ecological cluster with prospects for sustainable agricultural management.

Objectives: Amid the challenges posed by the global COVID-19 pandemic, understanding how the crisis shapes people' environmental behaviours and consciousness becomes paramount. This study aimed to unravel the implications of the global pandemic on individuals' environmental protection activities, environmentally prioritized attitudes, and confidence in future environmental protection movements. Methods: By combing detailed COVID-19 surveillance data from the World Health Organization and the Integrated Values Surveys, this study analysed information from 54,951 participants aged 15 years and above across 18 countries spanning 6 continents. Utilizing the global pandemic as a natural experiment, Logistic regressions with Difference-in-Difference (DID) models were employed for a robust estimation of the pandemic's effects on environmental outcomes. Results: The findings revealed a notable reduction in the likelihood of environmental protection activities among individuals (adjusted OR: 0.34, 95% CI: 0.23–0.51). However, pandemic exposure was linked to an increased environmentally prioritized attitude (1.35, 1.18–1.54) and enhanced confidence in environmental protection movements (1.16, 1.01–1.32). Notably, the beneficial effects of the pandemic on environmental attitudes (1.42, 1.21–1.67) and confidence (1.19, 1.01–1.39) were significantly observed exclusively among younger individuals and women exhibited heightened sensitivity to the pandemic's positive impact on environmental attitudes (1.55, 1.30–1.86), while men displayed increased sensitivity in confidence regarding future environmental movements (1.23, 1.00–1.50). Conclusions: This study contributes valuable insights to the existing literature by elucidating the intricate relationship between global crises and individual environmental protection. The evidence generated provides policymakers with essential information for formulating comprehensive post-pandemic strategies aimed at jointly promoting and achieving high-quality development of the population and the environmental dimension of SDGs.

BackgroundOwing to the long penetration depth of gamma (γ)-rays, individuals working in ionizing radiation environments are chronically exposed to low-dose γ-radiation, resulting in cognitive changes. Dose rate significantly affects radiation-induced biological effects; however, its role in chronic low-dose γ-irradiation-induced cognitive impairment remains unclear. We aimed to investigate whether chronic low-dose γ-irradiation at low-dose-rate (LDR) could induce cognitive impairment and to compare the cognitive alteration caused by chronic low-dose γ-irradiation at LDR and high-dose-rate (HDR).MethodsThe rats were exposed to γ-irradiation at a LDR of 6 mGy/h and a HDR of 20 mGy/h for 30 days (5 h/day). Functional imaging was performed to assess the brain inflammation and blood–brain barrier (BBB) destruction of rats. Histological and immunofluorescence analyses were used to reveal the neuron damage and the activation of microglia and astrocytes in the hippocampus. RNA sequencing was conducted to investigate changes in gene expression in hippocampus.ResultsThe rats in the LDR group exhibited more persistent cognitive impairment than those in the HDR group. Furthermore, irradiated rats showed brain inflammation and a compromised BBB. Histologically, the number of hippocampal neurons were comparable in the LDR group but were markedly decreased in the HDR. Additionally, activated M1-like microglia and A1-like astrocytes were observed in the hippocampus of rats in the LDR group; however, only M1-like microglia were activated in the HDR group. Mechanistically, the PI3K–Akt signaling pathway contributed to the different cognitive function change between the LDR group and HDR group.ConclusionCompared with chronic low-dose γ-irradiation at HDR, LDR induced more severe cognitive impairment which might involve PI3K/Akt signaling pathway.

Abstract Most terrestrial plants establish a symbiosis with arbuscular mycorrhizal fungi (AMF), which provide them with lipids and sugars in exchange for phosphorus and nitrogen. Nutrient exchange must be dynamically controlled to maintain a mutually beneficial relationship between the two symbiotic partners. The WRI5a and its homologues play a conserved role in lipid supply to AMF. Here, we demonstrate that the AP2/ERF transcription factor MtERM1 binds directly to AW-box and AW-box-like cis-elements in the promoters of MtSTR2 and MtSTR, which are required for host lipid efflux and arbuscule development. The EAR domain-containing transcription factor MtERF12 is also directly activated by MtERM1/MtWRI5a to negatively regulate arbuscule development, and the TOPLESS co-repressor is further recruited by MtERF12 through EAR motif to oppose MtERM1/MtWRI5a function, thereby suppressing arbuscule development. We therefore reveal an ERM1/WRI5a–ERF12–TOPLESS negative feedback loop that enables plants to flexibly control nutrient exchange and ensure a mutually beneficial symbiosis.

Abstract Background The application of virtual reality (VR) in gastroscopic operation teaching can be safe and effective, but the advantages can be realized only when students accept and use it. This study aims to identify the factors influencing Chinese clinical medical postgraduates on their intention to use the 3D gastroscopic model constructed based on VR technology using Unified Theory of Acceptance and Use of Technology (UTAUT) model. Students’ demographic factors are also taken into consideration. Methods All methods were carried out in accordance with relevant guidelines. Data were collected from clinical medical postgraduates students in China using stratified sampling. A total of 292 questionnaires including valid responses were used in this study. Data were processed using Amos 24.0 and SPSS 26.0 software and the statistical analysis technique was based on structural equation modeling (SEM). Results The results showed that different from the mediator of home location and year of clinical learning, mediator of gender, university kind and graduate degree did not affect the behavioral intention. In addition, performance expectancy, facilitating condition, and social influence directly and indirectly have effect on behavioral intention. Also, the significance between social influence and performance expectancy, social influence and effort expectancy were verified. Conclusions This study manifested that the proposed framework based on the UTAUT had explanatory power to identify the factors influencing the students’ behavioral intention to use the 3D gastroscopic model constructed based on VR technology. Whereas, an important variable of effort expectancy in the frame of the SEM were not certified, thereby indicating that particular attention should be paid to this variable by universities and teachers before applying 3D gastroscopic model constructed based on VR technology in teaching. Added preparatory work is required such as explaining the basic knowledge of the operating steps of VR model and make students adequately understand its accessibility, which can probably improve the intentions of them to use it. The positive effects of social influence on performance expectancy and effort expectancy we proposed was also verified in this study, which provided a direction for future research.

Abstract At ASIACRYPT 2019, Zhang proposed a near collision attack on A5/1 claiming to recover the 64‐bit A5/1 state with a time complexity around 232 cipher ticks with negligible memory requirements. Soon after its proposal, Zhang's near collision attack was severely challenged by Derbez et al. who claimed that Zhang's attack cannot have a time complexity lower than Golic's memoryless guess‐and‐determine attack dating back to EUROCRYPT 1997. In this article, both the guess‐and‐determine and the near collision attacks for recovering A5/1 states with negligible memory complexities are studied. Firstly, a new guessing technique called the move guessing technique that can construct linear equation filters in a more efficient manner is proposed. Such a technique can be applied to both guess‐and‐determine and collision attacks for efficiency improvements. Secondly, the filtering strength of the linear equation systems is taken into account for complexity analysis. Such filtering strength are evaluated with practical experiments making the complexities more convincing. Based on such new techniques, the authors are able to give 2 new guess‐and‐determine attacks on A5/1: the 1st attack recovers the internal state s0 ${oldsymbol{s}}^{0}$ with time complexity 243.92; the 2nd one recovers a different state s1 ${oldsymbol{s}}^{1}$ with complexity 243.25. Golic's guess‐and‐determine attack and Zhang's near collision attacks are revisited. According to our detailed analysis, the complexity of Golic's s1 ${oldsymbol{s}}^{1}$ recovery attack is no lower than 246.04, higher than the previously believed 243. On the other hand, Zhang's near collision attack recovers s0 ${oldsymbol{s}}^{0}$ with the time complexity 253.19: such a complexity can be further lowered to 250.78 with our move guessing technique.

Summary: Antibody inhibitors of the interleukin-6 (IL-6) signaling pathway, such as tocilizumab and sarilumab, have been used to treat rheumatoid arthritis, chimeric antigen receptor T cell-induced cytokine storm, and severe COVID-19 pneumonia. Here, we solve the cryogenic electron microscopy structures of sarilumab and tocilizumab in complex with IL-6R to resolutions of 3.2 and 3.3 Å, respectively. These structures reveal that both tocilizumab and sarilumab bind to the D3 domain of IL-6R. The binding surfaces of the two antibodies largely overlap, but the detailed interactions are different. Functional studies of various mutants show results consistent with our structural analysis of the antibodies and IL-6R interactions. Structural comparisons with the IL-6/IL-6R/gp130 complex indicate that sarilumab and tocilizumab probably inhibit IL-6/IL-6R signaling by competing for the IL-6 binding site. In summary, this work reveals the antibody-blocking mechanism of the IL-6 signaling pathway and paves the way for future antibody discovery.

The severe global warming issue currently threatens humans' existence and development. Countries and international organizations have effectively implemented policies to reduce carbon emissions and investigate low-carbon growth strategies. Reducing carbon emissions is a hot topic that academics and government policy-making departments are concerned about.Through necessary condition analysis (NCA) and fuzzy set qualitative comparative analysis(fsQCA), this paper investigates local governments' configuration linkage effect and path choice to improve carbon emission performance from six dimensions: energy consumption, industrial structure, technological innovation, government support, economic development, and demographic factors. The research findings include the following: (1) Individual condition does not represent necessary conditions for the government's carbon performance. Among the two sets of second-order equivalence configurations(S and Q) (five high-level carbon performance configurations), those dominated by economic development or low energy consumption can produce high-level carbon performance. Therefore, the six antecedent conditions dimensions work together to explain how the government can create high levels of carbon performance. (2)According to the regional comparison, China's eastern, central, and western regions exhibit similarities and differences in the driving forces behind high carbon emission performance. All three regions can demonstrate carbon emission performance when all the factors are combined. However, when constrained by the conditions of each region's resource endowment, the eastern region emphasizes the advantage of economic and technological innovation, the central region favors government support and demographic factors, and the western region prefers upgrading industrial structure based on a specific level of economic development.

As China continues to implement its progressive fertility promotion policy, there has been a drastic decline in the fertility rate. Given that the migrant population constitutes more than a quarter of China's total population, enhancing the willingness of this demographic to have additional children through policy-guided urban public services is pivotal for optimizing China's population development strategy. This study analyzes the influence of urban public services on the reproductive intentions of the migrant population, utilizing data from 110,667 migrant families with one child, drawn from China's Migrant Population Dynamic Monitoring data in 2016 and 2018. The data analysis reveals several key findings: (1) Urban public services, overall, exhibit a notable positive effect on the willingness of the migrant population to have more children, albeit with limitations and a declining trend. (2) Among urban public services, primary basic education significantly impacts the willingness of the migrant population to expand their families. (3) Large cities have created a 'reverse screening' effect on the migrant population, leading to differential access to public services. This scenario caters effectively to the high human capital migrant individuals while reducing accessibility to livelihood public services for the low human capital migrant population. This paper critically evaluates China's progressively adjusted fertility policy from the perspective of the migrant population. It underscores the necessity of establishing a comprehensive fertility support policy system across China.

Redox mediators (RMs) are reported to effectually encourage the inactive decomposition of discharge products in lithium–oxygen batteries (LOBs); however, oxidized RMs and other injurious species still attack the Li anodes. An ionic liquid (IL)‐modified PVDF single‐lithium‐ion conducting composite membrane that can permit Li+ only but blocks anions and other molecules is prepared. The PVDF is combined with the strong‐acid cation styrene exchange resin with cation exchange characteristics to make a heterogeneous composite single‐ionic conductor membrane and the IL modification causes the formation of a more‐dense groove inside the PVDF membrane apparently strengthening the conductivity of the membrane without losing its impermeability to cations and discharge intermediates. The utility of the modified composite PVDF (MCP) separator greatly extends the cycle life of the LOB from 66 to 347 cycles at 1000 mAg−1 and 1000 mAhg−1 compared to cells using glass fiber separators. Rate performance is significantly enhanced at 3000 and 5000 mAg−1, increasing from 33 and 21 cycles to 171 and 137 cycles. The full discharge capacity also expands from 3702 to 51 205 mAhg−1. The MCP separator enables iodide‐assisted cathode processes and improves lithium anode stripping/plating, which is essential to improve the performance of nonelectrolytic LOBs.

Sodium-dependent vitamin C transporters are responsible for vitamin C uptake and tissue distribution in mammals. Here, authors present cryo-EM structures of mouse SVCT1 in both the apo and substrate-bound states, revealing the structural basis of substrate recognition and transport.

Pinellia ternata (Thunb.) Breit. is a traditional Chinese medicinal plant that has been widely used in China, Japan and Korea to relieve cough, vomiting, and inflammation. This review summarizes the recent research focus on germplasm resources, genetic diversity, functional genes, genetic breeding and prospects of P. ternata. The impact of germplasm resources and biogeography are the key factors of the effects of traditional Chinese medicinal materials, avoiding the medical negligence caused by using the confused medicine. Genetic diversity and genetic breeding are the basis of germplasm improvement. A virus-free technique of tissue culture is used to rapid propagation of P. ternata, promoting the production of seedlings without season restrictions. Functional gene research is the theoretical basis and target of germplasm improvement. Many genes, such as PtsHSP17.2 and PtSAD have been confirmed to play an important role in heat stress, guiding the selection and breeding of heat-resistant and drought-resistant P. ternata resources. Still, some problems exist in the production of P. ternata, presenting a challenge in breeding and cultivation. We summarize previous studies here and propose directions for further study to advance the research in the production of P. ternata.

Mechanical forces in the tumor microenvironment (TME) are associated with tumor growth, proliferation, and drug resistance. Strong mechanical forces in tumors alter the metabolism and behavior of cancer cells, thus promoting tumor progression and metastasis. Mechanical signals are transformed into biochemical signals, which activate tumorigenic signaling pathways through mechanical transduction. Cancer immunotherapy has recently made exciting progress, ushering in a new era of “chemo-free” treatments. However, immunotherapy has not achieved satisfactory results in a variety of tumors, because of the complex tumor microenvironment. Herein, we discuss the effects of mechanical forces on the tumor immune microenvironment and highlight emerging therapeutic strategies for targeting mechanical forces in immunotherapy.

Background: Panax ginseng Meyer (P. ginseng) is a traditional natural/herbal medicine. The amelioration on inflammatory bowel disease (IBD) activity rely mainly on its main active ingredients that are referred to as ginsenosides. However, the current literature on gut microbiota, gut microbiota-host co-metabolites, and systems pharmacology has no studies investigating the effects of ginsenoside on IBD. Methods: The present study was aimed to investigate the role of ginsenosides and the possible underlying mechanisms in the treatment of IBD in an acetic acid-induced rat model by integrating metagenomics, metabolomics, and complex biological networks analysis. In the study ten ginsenosides in the ginsenoside fraction (GS) were identified using Q-Orbitrap LC-MS. Results: The results demonstrated the improvement effect of GS on IBD and the regulation effect of ginsenosides on gut microbiota and its co-metabolites. It was revealed that 7 endogenous metabolites, including acetic acid, butyric acid, citric acid, tryptophan, histidine, alanine, and glutathione, could be utilized as significant biomarkers of GS in the treatment of IBD. Furthermore, the biological network studies revealed EGFR, STAT3, and AKT1, which belong mainly to the glycolysis and pentose phosphate pathways, as the potential targets for GS for intervening in IBD. Conclusion: These findings indicated that the combination of genomics, metabolomics, and biological network analysis could assist in elucidating the possible mechanism underlying the role of ginsenosides in alleviating inflammatory bowel disease and thereby reveal the pathological process of ginsenosides in IBD treatment through the regulation of the disordered host–flora co-metabolism pathway.

Fracture mouth temporary plugging and diverting fracturing (TPDF) technology refers to plugging the previously created fractures by use of the degradable diverters and enhancing the wellbore pressure. In this way, the subsequent injection fluids can be diverted into the under-stimulated zone and the overall stimulation effects can be improved. Influenced by downhole temperature, pressure, and fracture mouth morphology, the reported slot plugging test at room temperature cannot effectively guide the field operation of the fracture mouth TPDF, and the success rate can be significantly influenced. In this work, a high-pressure evaluation system for fracture mouth temporary plugging is designed, the effects of the reservoir temperature and the real fracture morphology can be considered effectively. The key factors and their influencing pattern are systematically investigated. Moreover, the optimal temporary plugging condition and the key factors affecting the plugging effect were determined by orthogonal experiments. The results show that the diverter bridging speed at 150 °C increases by 33% compared with that at room temperature, and the corresponding diverter dosage reduces by 34%. If the diverter concentration is too high, the diverter bridging speed will be reduced and the diverter dosage will be increased. The higher the fluid injection rate and the carrier fluid viscosity, the faster the diverter bridging speed (DBS), and the less the diverter dosage. The factors influencing the diverter dosage rank (from strong to weak): the viscosity of the carrying fluid, the reservoir temperature, the fluid injection speed, the concentration of the 1 mm particulate-shaped diverter (PSD), and the concentration of the 3 mm PSD.

Organic acids are a key active component of Pinellia ternata (Thunb.) Breit, and their concentration is closely associated with the quality of P. ternata. Developing an efficient and rapid method for detecting organic acids can offer a valuable technology for real-time assessment of P. ternata quality. In this work, a high-performance liquid chromatography coupled to triple quadrupole mass spectrometry (HPLC-QqQ-MS/MS) approach, combining the optimization of extraction conditions using response surface methodology (RSM), was developed for the simultaneous quantitative analysis of six organic acids in P. ternata. The optimal extraction conditions for organic acids in P. ternata were ultrasonic extraction with a solid–liquid ratio of 1:50, ultrasonic time of 60 min, and extraction temperature of 55 °C. Multiple-reaction monitoring (MRM) scanning was employed for quantification using HPLC-QqQ-MS/MS in negative ionization mode through a single run of 10 min, and the limit of detection (LLOD) and limit of quantification (LLOQ) for organic acids were as low as 0.138 ng/mL and 0.614 ng/mL, respectively. The relative standard deviations (RSDs) of reproducibility, precision, and stability were all lower than 5.0%, and recovery rates were 97.75–107.14%, with RSDs < 5.0%. Finally, this method was successfully applied to determine the investigated organic acids in 12 production regions of P. ternata, revealing significant differences between different production areas. This indicates that the optimized method is suitable for further accurate investigations of organic acids of P. ternata.

In order to investigate the effects of plasticizers on the binding energy, solubility parameter and mechanical properties of pBAMO-b-GAP copolymer (the copolymer of 3,3′-bis(azidomethy) oxetane and glycidyl azide polymer), the related copolymer/plasticizer mixed systems were established by molecular dynamics simulations. Besides, the mechanical properties of the formulas based on pBAMO-b-GAP containing the three energetic plasticizers were also studied experimentally. The results showed that all involved energetic plasticizers could be miscible with the pBAMO-b-GAP. The order of binding energy was theoretically found to be pBAMO-b-GAP / BuNENA > pBAMO-b-GAP/ TMETN > pBAMO-b-GAP/ DIANP which was consistent with the trends of the experimental tensile strength values of three mixed materials. Excitedly, the DIANP showed strongest effects among the three plasticizers on improving the toughness of the copolymer according to the calculation of Cauchy pressure and experimental value of elongation. For the pBAMO-b-GAP copolymer, the DIANP could be a promising plasticizer and compolymer/plasticizer mixed system was suitable used as binder in azido polyether-based propellants.

Abstract Temporary plugging and diverting fracturing (TPDF) technique shows great advantages in stimulating unconventional oil and gas reserves. Revealing the fracture plugging mechanism and establishing the evaluation method are beneficial for revealing the mechanism of forming multiple fractures during TPDF. This work revealed the processes of plugging the fractures based on the typical injection pressure curve of hydraulic fracturing operation and then applied the stress cage model, the fracture closure stress model, and the fracture propagation resistance model to reveal the fracture plugging mechanisms. Moreover, this paper establishes a 2D XFEM model to evaluate the fracture plugging effect, and the reliability of the model is verified against the finite element model. Based on the XFEM model, this work investigates the fracture plugging effects influenced by the uneven distribution of net pressure within the fracture. The results prove that fracture mouth plugging of TPF mainly enhances the wellbore circumferential stress, in‐fracture plugging mainly enhances fracture closure pressure, fracture tip plugging mainly hinders fracturing fluids flowing toward fracture tips, all of them aim at enhancing the reopen pressure of the existing fractures and prevent the propagation of the existing fracture. Diverter bridging and plugging can change the distribution of fracture net pressure and dramatically reduce the fracture tip stress factor, and thus, the existing fracture propagation can be efficiently stopped.

A desorption-tailoring strategy is demonstrated to steadily prepare self-assembled p-AlGaN superlattices with sub-nanometer ultrathin barriers by MOCVD, which juggle the hole concentration and transport.

Abstract Background Ovarian cancer (OC) is one of the serious threats to the health of women worldwide, and accurate biomarkers are urgently demanded for early diagnosis of OC. We have previously confirmed that miR-205 promotes the invasion and metastasis of OC cells by inhibiting the expression of the tumor suppressor gene TCF21. In this study, we used liquid biopsy technology to detect the expression levels of the four genes, miR-205, CA125, HE4 and TCF21, in the exosomes of plasma of OC patients. Combined with analysis of clinicopathological parameters of OC patients, we aimed to provide efficient and non-invasive laboratory biomarkers for early diagnosis of OC. Methods 36 OC patients who were diagnosed in local hospitals from September 2020 to July 2021 were selected as OC group, 31 cases of surgically diagnosed with ovarian benign lesions were selected as benign group, and 32 healthy people who underwent physical examination during the same period were selected as a control group. We employed transmission electron microscope (TEM), Western blotting (WB), and nanoparticle tracking analysis (NTA) to identify biomarkers in the exosomes extracted from plasma of the three groups. The RNA levels of miR-205, CA125, HE4 and TCF21 genes in plasma exosomes were detected by real-time quantitative PCR (qRT-PCR) method. We used clinical pathological parameters and the Receiver Operating Characteristic (ROC) curves to evaluate the diagnostic efficacy for the genes detected in plasma exosomes. Results We found that the expression level of miR-205 in plasma exosomes of the OC group was significantly higher than that of the benign and control groups (P

In order to clarify the gas-water two-phase flow law in horizontal wells and study the gas-water two-phase flow characteristics in horizontal wells, firstly, the gas-water two-phase in a horizontal well is numerically simulated and analyzed, and the flow pattern distribution under different well inclination angles and different phase separation flow rates is obtained. Secondly, a series of production logging instruments including CAT instrument was used to conduct experimental research on gas-water two-phase flow under different flow conditions, and the measured values of each CAT probe were extracted to reflect the local holdup under different flow patterns. Finally, SSA-BP neural network algorithm is used to identify a gas-water two-phase flow pattern in a wellbore by using experimental parameters such as center holdup, well inclination angle, spinner revolution, and CAT probe measurements. The recognition accuracy of the neural network was improved from 83.75% to 91.66%, and the operation speed was accelerated. It provides a research idea to explore the flow characteristics of gas-water two-phase flow in horizontal wells.

Deterministic and stochastic processes can simultaneously construct plant community assemblages. However, how they shape herbaceous plants’ phylogeny and functional structure in alpine meadows is unclear, hindering the understanding of species’ coexistence processes and diversity maintenance in herbaceous communities. We established a permanent research sample plot of 3.76 × 105 m2 in alpine meadows on the northeastern Qinghai-Tibet Plateau of China, investigated the flora, measured nine functional traits, analyzed inter- and intraspecific variation, and visualized phylogenetic signals. The results show that: (1) The phylogenetic structure based on DNA barcode sequences exhibits a range from competitive exclusion (NRI 0, NTI > 0) along an altitude gradient. (2) The interspecific functional structure varied with altitude, reflecting different survival strategies of plants. In contrast, intraspecific trait variation was associated with environmental screening processes. (3) Except for PH and LPC, none of the functional traits showed a phylogenetic signal (K 0.05), suggesting that they are more influenced by environmental heterogeneity; with increasing altitude, enhanced environmental filtering favors species with conservative strategies of selection. These results suggest that deterministic processes (interspecific competition, habitat filtering) may be the main mechanisms of species coexistence in alpine meadows. Low altitude drives niche differentiation of coexisting species through competitive exclusion to reduce competition for resources. In contrast, high altitude species lead to the coexistence of functionally similar species through habitat filtering.

Dust emissions are likely to increase significantly when land vegetation is absent, such as during the Precambrian period. Here, the authors use climate simulations to find that high dust emissions in the Precambrian could have cooled the global climate by ~10 °C.

Abstract Background The polymer-based drug/gene delivery is promising for the treatment of inherent or acquire disease, because of the polymer’s structural flexibility, larger capacity for therapeutic agent, low host immunogenicity and less cost. Antisense therapy is an approach to fighting genetic disorders or infections using antisense oligonucleotides (AOs). Unfortunately, the naked AOs showed low therapeutic efficacy in vivo and in clinical trial due to their poor cellular uptake and fast clearance in bloodstream. In this study, a series of triazine-cored amphiphilic polymers (TAPs) were investigated for their potential to enhance delivery of AOs, 2′-O-methyl phosphorothioate RNA (2′-OMePS) and phosphorodiamidate morpholino oligomer (PMO) both in vitro and in vivo. Results TAPs significantly enhanced AO-induced exon-skipping in a GFP reporter-based myoblast and myotube culture system, and observed cytotoxicity of the TAPs were lower than Endoporter, Lipofectamine-2000 or PEI 25K. Application of optimized formulations of TAPs with AO targeted to dystrophin exon 23 demonstrated a significant increase in exon-skipping efficiency in dystrophic mdx mice. The best ones for PMO and 2′-OMePS delivery have reached to 11-, 15-fold compared with the AO only in mdx mice, respectively. Conclusion The study of triazine-cored amphiphilic polymers for AO delivery in vitro and in mdx mice indicated that the carrier’s performances are related to the molecular size, compositions and hydrophilic-lipophilic balance (HLB) of the polymers, as well as the AO’s structure. Improved exon-skipping efficiency of AOs observed in vitro and in mdx mice accompanied with low cytotoxicity demonstrated TAP polymers are potentials as safe and effective delivery carrier for gene/drug delivery.

As an important energy replacement block in China, the tight conglomerate oilfields in the Mahu area are difficult to develop and are characterized by strong heterogeneity, large horizontal stress differences, and undeveloped natural fractures. However, new development processes including temporary blocking diversion and large section-multiple clusters have been implemented on the oilfields in the past few years. In 2020, two adjacent horizontal wells in the MD well area experienced a poor fracturing development effect compared with the earlier wells in this area. Analysis suggests that the main reasons are water sensitivity of the reservoir, insufficient fracturing scale, and/or interference from the adjacent old wells. To ameliorate the problem, this study presents an experimental study of multiple temporary plugging and refracturing technology in long horizontal well sections, in combination with electromagnetic and microseismic monitoring. Results from the study show a great difference between the two monitoring techniques, which is attributed to their different detection principles. Interestingly, the combination of the two approaches provides a greater performance than either approach alone. As the fracturing fluid flow diversion is based on temporary plugging diversion and electromagnetic monitoring of fracturing fluid is advantageous in temporary plugging diversion monitoring, both approaches require further research and development to address complex situations such as multiple temporary plugging and refracturing in long intervals of adjacent older wells.

A new method for the determination of oil and water flow rates in vertical upward oil-water two-phase pipe flows has been proposed. This method consists of an application of machine learning techniques on the probability density function (PDF) and the power spectral density (PSD) of the power spectrum output of an ultrasonic Doppler sensor in the pipe. The power spectrum characteristic parameters of the two-phase flow are first determined by the probability density function (PDF) method. Then, the transducer signal is preprocessed by distance correlation analysis (DCA), and independent features are extracted by principal component analysis (PCA). The extracted features are used as input to a least-squares fit, which gave the oil flow rates as output. In the same way, the transducer signal is also preprocessed by partial correlation analysis (PCA), and independent features were extracted using independent component analysis (ICA). The extracted features were used as inputs to multilayer back-propagation neural networks, which water cuts as output. The present method was used to calibrate an ultrasonic Doppler sensor to estimate the flow rates of both phases in oil–water flow in a vertical pipe of diameter 159 mm. Predictions of the present method were in good agreement with direct flow rate measurements. Compared to previously used methods of feature extraction from the ultrasonic Doppler power spectrum signals, the present method provides a theoretical basis for the interpretation of ultrasonic multiphase flow logging data. Ultrasonic multiphase flow logging has potential application value in the production profile logging and interpretation evaluation of production wells with low fluid production and high water cut.

Air temperature (Ta) is an essential parameter for science research and engineering practice. While the traditional site-based approach is only able to obtain observations in limited and discrete locations, satellite remote sensing is promising to retrieve some environmental variables with spatially continuous coverage. Nowadays, land surface temperature (Ts) measurements can be obtained from some satellite sensors (e.g., MODIS), further enabling us to estimate Ta in view of the relationship between Ta and Ts. In this article, we proposed a two-phase integrated framework to estimate daily mean Ta nationwide. In the first phase, multivariate linear regression models were fitted between site-based observations of daily mean air temperature (Ta-mean) and MODIS land surface temperature products (including Terra day: TMOD-day, Terra night: TMOD-night, Aqua day: TMYD-day, and Aqua night: TMYD-night) conditional on some covariates of environmental factors. The fitted models were then used to predict Ta-mean from those covariates at unobserved locations. The predicted Ta-mean were looked on as stochastic variables, and their distributions were also obtained. In the second phase, Bayesian maximum entropy (BME) methods were used to produce spatially continuous maps of Ta-mean taking the meteorological station observations as hard data and the predicted Ta-mean in the first phase as soft data. It is shown that the proposed approach is promising to improve the interpolation accuracy significantly, comprehensively considering the prior knowledge and the context of space variability and correlation, which will enable it to compile spatially continuous air temperature products with higher accuracy.

Poor vitamin D status is a widespread problem regardless of age and sex, emphasizing the necessity of new food sources to improve vitamin D levels. Currently, approximately 60% of dietary vitamin D consumption occurs via fortified foods. Vitamin D insufficiency (50–90%) is widespread according to age and region, despite different levels of sunlight exposure. The food industry must identify more effective strategies to increase normal dietary vitamin D intake and improve overall health. Strategies for vitamin D fortification include bioaddition, wherein a vitamin D-rich food source is added to staple foods during processes. These bioadditive strategies expand the range of vitamin D-containing foods and appeal to different preferences, cultures, and economic statuses. In several countries, vitamin D deficiency places athletes at a high risk of disease susceptibility. Due to low sun exposure, athletes in countries with higher and lower levels of sunlight have similar risks of vitamin D deficiency. In this review, we summarize recent technical advances to promote vitamin D utilization by humans during sports activities and in relation to the normal practices of athletes.

BackgroundsAs a new oral chemotherapy drug, TAS-102 is currently recommended as the third-line treatment for metastatic colorectal cancer (mCRC). Recently, studies have reported the efficacy of TAS-102 combined with bevacizumab in colon cancer patients after standard treatment fails. Here, we evaluated the efficacy and safety of TAS-102 combined with bevacizumab versus TAS-102 as a single agent by a systematic review and a meta-analysis.MethodsPubMed, Web of Science and Cochrane libraries were searched. Studies involving bevacizumab combined with TAS-102 in mCRC were included. Study characteristics (author, year of publication, country et al.), efficacy (disease control rate(DCR), progression-free survival(PFS), overall survival(OS)) and adverse effects were extract from studies. Forest plots were created based on Cox model analysis.ResultsAfter screening 550 studies, a total of 3 studies were included, which compared the safety and effectiveness of TAS-102 with or without bevacizumab. Analysis based on Cox regression showed that the combined treatment group had advantages in 6-month (OR= 2.93, 95% CI: 1.72 to 5.00, P

Polysaccharides from Panax ginseng C. A. Meyer (P. ginseng) are the main active component of P. ginseng and exhibit significant intestinal anti-inflammatory activity. However, the therapeutic mechanism of the ginseng polysaccharide is unclear, and this hinders the application for medicine or functional food. In this study, a polysaccharide was isolated from P. ginseng (GP). The primary structure and morphology of the GP were studied by HPLC, FT-IR spectroscopy, and scanning electron microscopy (SEM). Further, its intestinal anti-inflammatory activity and its mechanism of function were evaluated in experimental systems using DSS-induced rats, fecal microbiota transplantation (FMT), and LPS-stimulated HT-29 cells. Results showed that GP modulated the structure of gut microbiota and restored mTOR-dependent autophagic dysfunction. Consequently, active autophagy suppressed inflammation through the inhibition of NF-κB, oxidative stress, and the release of cytokines. Therefore, our research provides a rationale for future investigations into the relationship between microbiota and autophagy and revealed the therapeutic potential of GP for inflammatory bowel disease.

Book Review

Antisense oligonucleotide (AO) therapy has been the specific treatment for Duchenne muscular dystrophy, with ongoing clinical trials. However, therapeutic applications of AOs remain limited, particularly because of the lack of efficient cellular delivery methods imperative for achieving efficacy. In this study, we investigated a few aminoglycosides (AGs) for their potential to improve the delivery of antisense phosphorodiamidate morpholino oligomer (PMO) both in vitro and in vivo. AGs had lower cytotoxicity compared with Endoporter, the currently most effective delivery reagent for PMO in vitro, and improved efficiency in PMO delivery 9- to 15-fold over PMO alone. Significant enhancement in systemic PMO-targeted dystrophin exon 23 skipping was observed in mdx mice, up to a 6-fold increase with AG3 (kanamycin) and AG7 (sisomicin) compared with PMO only. No muscle damage could be detected clearly with the test dosages. These results establish AGs as PMO delivery-enhancing agents for treating muscular dystrophy or other diseases. Keywords: aminoglycoside, antisense delivery, exon skipping, PMO, muscular dystrophy

BackgroundPancreatic cancer has a high incidence and mortality. Most patients are in an advanced stage at the time of initial diagnosis and cannot be cured by a single surgery. The ASCO clinical practice guideline emphasized the overall management and multidisciplinary comprehensive treatment which put forward the concept of conversion therapy. In this paper, the real-world observation and study were carried out to explore the conversion effect of chemotherapy in patients with advanced pancreatic cancer and their long-term survival.MethodsThe subjects of this study are advanced pancreatic cancer patients who visited the oncology department of Zhejiang Provincial People’s Hospital from 2015 to 2019. Collected and summarized the cases, and selected 5 representative patients for analysis, all of them received standard treatment (FOLFIRINOX, AS, AG, or GS). The progress, clinical evaluation, adverse reactions, and prognosis of these patients after conversion therapy were analyzed and discussed in conjunction with relevant literature.ResultsFive patients with advanced pancreatic cancer received conversion therapy with an average survival time of 29.8 months, two of them received surgical treatment, and postoperative evaluations were pathological complete response (pCR). The tolerance of chemotherapy was good in five patients, and no serious adverse reactions of grade 3 or 4 occurred.ConclusionConversion therapy for patients with advanced pancreatic cancer strives for surgical opportunities of radical resection, prolongs survival and improves quality of life.

This article reviews Tong-king Lee's book on Singapore's multilingualism/

This article is an interview with the leading French translator, Prof. Noel Dutrait, about his translation of translation of modern Chinese literature in France

This article is an interview with Gao Xingjian, the Nobel Prize laureate of 2000.

Gastric cancer is a common digestive tract tumor and the second most prevalent cancer. The prognosis of advanced gastric cancer is poor. Conversion therapy can reduce tumor burden, downgrade tumor, and increase the possibility of complete resection, thus prolonging the survival time of patients with gastric cancer. In conversion therapy, chemotherapy and targeted therapy are the main methods of medical treatment, which can control tumor growth and recurrence. As an antiangiogenic targeted drug, apatinib is widely used in the third-line treatment of advanced gastric cancer. Recent studies have shown that it may be of great help in rapid reduction of tumor stage and improvement of prognosis in conversion therapy. This study reported three cases of gastric cancer complicated with multiple abdominal and retroperitoneal lymph node metastases. After receiving apatinib combined with SOX regimen for four cycles, computed tomography showed that the focus and lymph node metastasis were reduced after treatment, and primary tumors were resected. Postoperative pathology result showed that the patients got R0 resection. After radical surgery, the maintenance therapy including apatinib was given. The progression-free survival time was more than 10 months. Apatinib combined with SOX regimen as a conversion therapy for advanced gastric adenocarcinoma increases the possibility of successful surgical resection, which might prolong the survival time of patients.

Antisense oligonucleotide (AON) therapy for Duchenne muscular dystrophy has drawn great attention in preclinical and clinical trials, but its therapeutic applications are still limited due to inefficient delivery. In this study, we investigated a few saponins for their potential to improve delivery performance of an antisense phosphorodiamidate morpholino oligomer (PMO) both in vitro and in vivo. The results showed that these saponins, especially digitonin and tomatine, improve the delivery efficiency of PMO comparable to Endo-Porter-mediated PMO delivery in vitro. The significant enhancement of PMO targeting to dystrophin exon 23 delivery was further observed in mdx mice up to 7-fold with the digitonin as compared to PMO alone. Cytotoxicity of the digitonin and glycyrrhizin was lower than Endo-Porter in vitro and not clearly detected in vivo under the tested concentrations. These results demonstrate that optimization of saponins in molecular size and composition are key factors to achieve enhanced PMO exon-skipping efficiency. The higher efficiency and lower toxicity endow saponins as gene/AON delivery enhancing agents for treating muscular dystrophy or other diseases.

Panax spp. (Araliaceae family) are widely used medicinal plants and they mainly include Panax ginseng C.A. Meyer, Panax quinquefolium L. (American ginseng), and Panax notoginseng (notoginseng). Polysaccharides are the main active ingredients in these plants and have demonstrated diverse pharmacological functions, but comparisons of isolation methods, structural features, and bioactivities of these polysaccharides have not yet been reported. This review summarizes recent advances associated with 112 polysaccharides from ginseng, 25 polysaccharides from American ginseng, and 36 polysaccharides from notoginseng and it compares the differences in extraction, purification, structural features, and bioactivities. Most studies focus on ginseng polysaccharides and comparisons are typically made with the polysaccharides from American ginseng and notoginseng. For the extraction, purification, and structural analysis, the processes are similar for the polysaccharides from the three Panax species. Previous studies determined that 55 polysaccharides from ginseng, 18 polysaccharides from American ginseng, and 9 polysaccharides from notoginseng exhibited anti-tumor activity, immunoregulatory effects, anti-oxidant activity, and other pharmacological functions, which are mediated by multiple signaling pathways, including mitogen-activated protein kinase, nuclear factor kappa B, or redox balance pathways. This review can provide new insights into the similarities and differences among the polysaccharides from the three Panax species, which can facilitate and guide further studies to explore the medicinal properties of the Araliaceae family used in traditional Chinese medicine.

We investigated a series of Tween 85 modified low molecular weight polyethylenimine (LPEI, 0.8k/1.2k/2.0k)-copolymers (Zs) through simple formulation and covalent conjugation with phosphorodiamidate morpholino oligomer (PMO) for their potential to enhance delivery in vitro and in dystrophic mdx mice. Z polymers significantly enhanced PMO-induced exon-skipping in a GFP reporter-based cell culture system. Application of optimized formulations of Zs with PMO targeted to dystrophin exon 23 demonstrated a significant increase in exon-skipping efficiency in mdx mice. Consistent with our observations in vitro, optimization of molecular size and hydropholic-lipopholic balance (HLB) of polymers are important factors to achieve enhanced PMO delivery in vivo. The best formulation of Zs enhanced PMO delivery with 20- and 6-fold over PMO alone in vitro and in vivo, respectively. Further, chemical conjugation of the polymer and PMO exhibits greater benefit than polymer/PMO simple formulation in PMO delivery efficiency. Observed cytotoxicity of the Zs was lower than Endo-porter and PEI 25k in vitro, and no tissue toxicity was clearly detected with the Zs at the dosage tested. These results indicate the potential of the Zs as effective and safe PMO delivery carriers for treating diseases such as muscular dystrophy.

Entretien avec Noel Dutrait sur sa traduction de La Montagne de l’âme de Gao Xingjian. Interview with Noel Dutrait on his translation of La Montagne de l'âme by Gao Xingjian

Antisense oligonucleotide therapy for Duchenne muscular dystrophy has shown great potential in preclinical and clinical trials, but its therapeutic applications are still limited due to inefficient delivery. In this study, we investigated a few polyquaterniums (PQs) with different size and composition for their potential to improve delivery performance of an antisense phosphorodiamidate morpholino oligomer (PMO) both in vitro and in vivo. The results showed that LuviquatTM series, especially PQ-1 and PQ-3, promoted the exon-skipping efficiency comparable to Endoporter-mediated PMO delivery in vitro. Significant enhancement in skipping dystrophin exon 23 has also been achieved with PQ-3 up to seven-fold when compared to PMO alone in mdx mice. Cytotoxicity of the PQs was lower than Endoporter and PEI 25 K in vitro and muscle damage not clearly detected in vivo under the tested concentrations. These results together demonstrate that the optimization of PQ in molecular size, composition and distribution of positive charges is the key factor to achieve enhanced PMO exon-skipping efficiency. The higher efficiency and lower toxicity endow polyquaternium series as AO delivery enhancing agents for treating muscular dystrophy and other diseases.

The paper presents a new type of material—foamed concrete—adopted for expansion subgrade of the expressway. Intriguingly, the irregular through shakes appear on its top. The method combining the engineering case, theoretical analysis, and numerical simulation is employed to analyze its T-shaped and tree-shaped through shake. The research indicates that when the underground water table is high, cracks are easily seen on the top of step-shape foamed concrete due to buoyancy force. Under the concentrated load effect, the maximum displacement of 27.09 mm is observed on the top of the simply supported beam when elastic modulus is 200 MPa. The maximum principle tensile stress of 0.34 MPa also occurs on the top of the simply supported beam when elastic modulus is 200 MPa and 400 MPa, which is greater than tensile strength of foamed concrete of 0.31 MPa and 0.26 MPa at 7 d and 28 d, respectively. Thus, the adoption of a simply supported beam structure fits site through crack. To avert cracks on the top of foamed concrete in high groundwater table, the antibuoyancy measures should be adopted prior to construction of the upper bearing stratum. The study has expanded the application scope of subgrade and enriched theory of foamed concrete filled in high groundwater table, providing a significant reference to similar projects.