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Abstract Background Lung cancer is the most common cause of cancer death worldwide and poses an immediate health threat. Despite decades of basic and clinical research, the 5-year survival rate for lung cancer patients is less than 10%.The most important drawbacks in efficient treatment of lung cancer are delayed diagnosis and absence of effective screening. Detection and study of precancerous lesions of the bronchial mucosa might be one of the turning points in understanding of neoplastic transformation. Therefore, it would be the most effective prevention and early treatment modality. We report a case of high-grade intraepithelial neoplasia of the bronchial mucosa in which a neoplastic growth in the lumen of intrinsic segment in the upper lobe of the left lung was detected on electronic bronchoscopy, and biopsy confirmed squamous papillary hyperplasia with high-grade intraepithelial neoplasia. Case presentation A 74-year-old male was admitted to the hospital due to a mass lesion in his left lung. After admission, computed tomography scan of the chest showed an intraluminal mass in the intrinsic segment of the upper lobe of the left lung and an enlarged left hilum. Conclusions High-grade intraepithelial neoplasia of the bronchial mucosa is rare in the respiratory system. We report a case that can provide useful information for early diagnosis and treatment of the disease.

Abstract Evolution of SARS-CoV-2 variants emphasizes the need for multivalent vaccines capable of simultaneously targeting multiple strains. SCTV01E is a tetravalent COVID-19 vaccine derived from the spike protein of SARS-CoV-2 variants Alpha, Beta, Delta, and Omicron BA.1. In this double-blinded placebo-controlled pivotal efficacy trial (NCT05308576), the primary endpoint was vaccine efficacy (VE) against COVID-19 seven days post-vaccination in individuals without recent infection. Other endpoints included evaluating safety, immunogenicity, and the VE against all SARS-CoV-2 infections in individuals meeting the study criteria. Between December 26, 2022, and January 15, 2023, 9,223 individuals were randomized at a 1:1 ratio to receive SCTV01E or a placebo. SCTV01E showed a VE of 69.4% (95% CI: 50.6, 81.0) 7 days post-vaccination, with 75 cases in the placebo group and 23 in the SCTV01E group for the primary endpoint. VEs were 79.7% (95% CI: 51.0, 91.6) and 82.4% (95% CI: 57.9, 92.6), respectively, for preventing symptomatic infection and all SARS-CoV-2 infections 14 days post-vaccination. SCTV01E elicited a 25.0-fold higher neutralizing antibody response against Omicron BA.5 28 days post-vaccination compared to placebo. Reactogenicity was generally mild and transient, with no reported vaccine-related SAE, adverse events of special interest (AESI), or deaths. The trial aligned with the shift from dominant variants BA.5 and BF.7 to XBB, suggesting SCTV01E as a potential vaccine alternative effective against present and future variants.

Objective: Effects of low-temperature plasma pretreatment assisted by ultrasound on the extraction of total flavonoids from ginger powder were studied, and its mechanism was preliminary discussed, and provided a new method for the extraction of total flavonoids from ginger powder. Methods: The single-factor tests and three-factor three-level response surface optimization tests were carried out with the yield of total flavonoids in ginger powder as the index and discharge power, treatment time and air intake volume of low-temperature plasma as factors. Meanwhile, the contents of 21 kinds of polyphenols in ginger powder were determined by HPLC before and after low-temperature plasma treatment, and the structure of ginger powder were characterized by scanning electron microscope (SEM) and Fourier transform infrared spectroscopy (FTIR). Results: The optimum extraction conditions for total flavonoids from ginger powder were as follows: Vacuum degree less than 100 Pa, discharge power of 295 W, treatment time of 60 s, air intake volume of 150 cm3/min, and the yield of total flavonoids was 26.9 mg/g. Chromatographic results showed that 21 kinds of polyphenols were separated with high precision (relative standard deviation，RSD≤3.75%), good stability (RSD≤4.25%), good repeatability (RSD≤4.75%) and accurate and reliable recovery rate (average recovery rate of 84.11%~100.86%). After low-temperature plasma treatment, total flavonoids content in ginger was increased, and phenolic acids content was decreased. Etching effect of low-temperature plasma increased the surface roughness of starch particles and cell wall fragments in ginger powder and led to the decomposition of lignin, which increased the contact area between solvent and ginger powder, and it was conducive to solvent penetration. Conclusion: Ultrasound-assisted low-temperature plasma treatment is an effective method to extract total flavonoids from ginger powder.

Abstract Background The aim of this study was to investigate whether a causal relationship exists between serum uric acid (SUA) and diabetic microvascular complications using a two-sample Mendelian randomization (MR) method. Methods We used the MR approach, utilizing genome-wide association study (GWAS) summary statistics, to estimate the causal effect of SUA on diabetic microvascular complications in European individuals. The summary statistical data of SUA were obtained from the open database (IEU OPEN GWAS PROJECT) (p

Abstract Background Polypharmacy is common in older adults with psychiatric disorders, but no consensus has reached about the reliable indicators evaluating the benefits and risks of drug-drug interactions (DDIs) in polypharmacy. We aimed to identify indicators suitable for evaluating the clinical significance of DDIs in polypharmacy in older adults with psychiatric disorders. Methods The online tools were used to distribute and collect the questionnaires. The Delphi method was applied to analyze experts’ opinions. The degree of authority and coordination of experts were analyzed using the coefficient of variation, coefficient of coordination, expert’s judgment factor, familiarity with the study content factor, and Kendall coordination coefficient. Statistical analysis was conducted using the IBM SPSS® Statistics Package version 26.0. Results After three rounds of expert consultation, five primary and eleven secondary indicators were identified. The primary “pharmacodynamic indicator” included “severity of adverse drug reactions”, “duration of adverse drug reaction”, “symptom relief”, “time to onset of symptomatic relief”, “number of days in hospital”, and “duration of medication”. The secondary “pharmacokinetic indicator” contained “dosage administered” and “dosing intervals”. The primary “patient tolerance indicator” contained one secondary indicator of “patient tolerability”. The primary indicator “patient adherence” contained one secondary indicator of “patient adherence to medication”. The primary indicator “cost of drug combination” contained one secondary indicator of “readmission”. These indicators were used to determine the clinical significance of DDIs during polypharmacy. Conclusions The clinical significance of drug combinations should be taken into account when polypharmacy is used in the elderly. The five primary indicators and eleven secondary indicators might be preferred to evaluate their risks and benefits. Medication management in this population requires a multidisciplinary team, in which nurses play a key role. Future research should focus on how to establish efficient multidisciplinary team workflows and use functional factors to assess DDIs in polypharmacy for psychiatric disorders.

Abstract Copper mineralization in the Pulang (PL) porphyry deposit, Langdu (LD) porphyry-skarn deposit and Songnuo (SN) porphyry prospect in northwestern Yunnan, China, is closely related to the emplacement of quartz monzonite porphyries. The chemical compositions of biotite and apatite from those porphyries were analyzed to calculate the halogen fugacity and to constrain mineralized and barren porphyries. Our data show that biotites from the PL deposit have higher MgO, SiO2, TiO2 and F contents than those from the LD deposit or SN prospect. Compared to those in the LD deposit and SN prospect, the Mg (atoms per formula unit (apfu)) and AlVI (apfu) value in biotite is greater, and the F content is greater and the SO3 and Ce2O3/Y2O3 ratio in apatite are lower in the PL deposit. Ti-biotite thermometry and apatite-biotite geothermometry show that the crystallization temperature of biotite from the PL deposit is higher than that from the SN prospect or LD deposit. The results suggest that oxygen fugacity, magmatic sulfur, and H2O contents cannot be used to efficiently distinguish the PL deposit from the LD deposit and SN prospect. However, the halogen chemistry of biotite from the PL deposit is distinctly different from that of the LD deposit or SN prospect according to the lower IV (F), indicating that mineralized quartz monzonite porphyries in the PL deposit formed during the late magmatic stage, which is in contrast to those in the LD deposit and SN prospect. The mineralized porphyries display a remarkable negative linear relationship (r = − 0.96) with the log (f HF/f HCl) and log (f H2O/f HF) ratio, which can be used to distinguish the mineralized and barren porphyries. Compared with other typical porphyry Cu systems, there is a remarkable positive linear relationship between IV (Cl) and log (f H2O/f HCl). In addition, the linear slope and intercept for log (f H2O/f HCl) ratios and the IV (Cl) of biotite from the potassic and phyllic alteration zones are significantly greater than those from other porphyries.

Repair of large bone defects caused by severe trauma, non-union fractures, or tumor resection remains challenging because of limited regenerative ability. Typically, these defects heal through mixed routines, including intramembranous ossification (IMO) and endochondral ossification (ECO), with ECO considered more efficient. Current strategies to promote large bone healing via ECO are unstable and require high-dose growth factors or complex cell therapy that cause side effects and raise expense while providing only limited benefit. Herein, we report a bio-integrated scaffold capable of initiating an early hypoxia microenvironment with controllable release of low-dose recombinant bone morphogenetic protein-2 (rhBMP-2), aiming to induce ECO-dominated repair. Specifically, we apply a mesoporous structure to accelerate iron chelation, this promoting early chondrogenesis via deferoxamine (DFO)-induced hypoxia-inducible factor-1α (HIF-1α). Through the delicate segmentation of click-crosslinked PEGylated Poly (glycerol sebacate) (PEGS) layers, we achieve programmed release of low-dose rhBMP-2, which can facilitate cartilage-to-bone transformation while reducing side effect risks. We demonstrate this system can strengthen the ECO healing and convert mixed or mixed or IMO-guided routes to ECO-dominated approach in large-size models with clinical relevance. Collectively, these findings demonstrate a biomaterial-based strategy for driving ECO-dominated healing, paving a promising pave towards its clinical use in addressing large bone defects.

Abstract The stress paths of the cylindrical specimen in the p–q stress space by controlling the ratio of the axial and the radial loading is guaranteed to be consistent with the cuboid specimen, a novel method for imitating true-triaxial stress path by conventional triaxial apparatus was presented. Under the condition that p and q were variables and b was constant, the true-triaxial stress paths were realized by conventional triaxial apparatus strictly and easily. Under the condition that b and p were invariants, the b was used to control the ratio of axial and radial loading to ensure p constant, the method can be used to measure the strength on the π plane. If the tests were conducted at the different p with the same b, the critical state line of different b could be obtained. Under the condition that p and q were constant, the proposed method of nonlinear loading with b as a parameter could be used to design the various stress paths of true-triaxial under the condition of deviatoric stress consolidation, and which could be used to determine the deformation and the plastic flow of soil in 3D space. The proposed method could be used to achieve the equivalent stress path in the p–q stress space to obtain the 3D mechanical properties, and the stress path controlled by stress, strain, and a hybrid of stress and strain. Once the software of conventional triaxial apparatus was developed by the novel method, the measuring range of stress paths could be expanded greatly.

Abstract With the coming of the post‐antibiotic era, there is an increasingly urgent need for safe and efficient antibacterial vaccines. Bacterial outer membrane vesicles (OMVs) have received increased attention recently as a potential subunit vaccine. OMVs are non‐replicative and contain the principle immunogenic bacterial antigen, which circumvents the safety concerns of live‐attenuated vaccines. Here, we developed a novel nano‐vaccine by coating OMVs onto PEGylated nano‐Rehmannia glutinosa polysaccharide (pRL) in a structure consisting of concentric circles, resulting in a more stable vaccine with improved immunogenicity. The immunological function of the pRL‐OMV formulation was evaluated in vivo and in vitro, and the underlying mechanism was studied though transcriptomic analysis. The pRL‐OMV formulation significantly increased dendritic cell (DC) proliferation and cytokine secretion. Efficient phagocytosis of the formulation by DCs was accompanied by DC maturation. Further, the formulation demonstrated superior lymph node targeting, contributing to a potent mixed cellular response and bacterial‐specific antibody response against Bordetella bronchiseptica infection. Specifically, transcriptomic analysis revealed that the immune protection function correlated with T‐cell receptor signalling and Th1/Th2/Th17 differentiation, among other markers of enhanced immunological activity. These findings have implications for the future application of OMV‐coated nano‐carriers in antimicrobial immunotherapy.

ObjectiveTo investigate the relationship between circulating receptor activator of nuclear factor-kappa B ligand (RANKL) levels and marrow adipose tissue in postmenopausal females.MethodsA total of 164 postmenopausal females were included in the study. Serum levels of osteoprotegerin (OPG) and RANKL were measured using ELISA kits. Body composition and bone mineral density (BMD) were assessed using dual-energy X-ray absorptiometry. Complex-based chemical shift imaging-based MRI was employed to evaluate the vertebral marrow proton density fat fraction (PDFF). A multivariate linear regression model was utilized to analyze the predictive effects of PDFF and BMD on circulating levels of OPG and RANKL.ResultsSimple regression analysis showed significant associations among the marrow PDFF, BMD at either site, serum RANKL, and the RANKL/OPG ratio. In multivariate linear regression models, marrow PDFF was found to have a positive correlation (β = 3.15, 95% CI 2.60 to 3.70) and BMD had negative correlations (β = −0.200, 95% CI −0.348 to −0.051 for vertebral BMD; β = −0.383, 95% CI −0.589 to −0.177 for total hip BMD; and β =−0.393, 95% CI −0.598 to −0.188 for femoral neck BMD, all p < 0.01) with circulating soluble RANKL levels after adjusting for age, body mass index, physical activity, total fat mass, android/gynoid ratio, and lean mass. Similar results were observed for the RANKL/OPG ratio. Additionally, multivariate linear regression analyses revealed that marrow PDFF was a significant independent contributor of circulating soluble RANKL (β = 1.34, 95% CI 1.10 to 1.58, p < 0.001) after further controlling for BMD. However, marrow PDFF or BMD had no associations with circulating levels of OPG after adjusting for all potential confounders mentioned above.ConclusionsVertebral marrow fat fraction is independently associated with circulating soluble RANKL levels in postmenopausal females.

Capsaicinoids are produced uniquely in pepper fruits, and its level determines the commercial quality and health-promoting properties of pepper. So, it is particularly important to increase capsaicinoids content in pepper. Rhizosphere microbiota is critical to plant growth and performance, and affected by plant varieties. However, the impact of pepper varieties with different capsaicinoids yields on the rhizosphere microbiota is poorly understood. Using high-throughput sequencing of the 16S rRNA and internal transcribed spacer (ITS) region, we investigated the rhizosphere microbial community among five pepper varieties containing different capsaicinoids. Our results demonstrated that pepper variety significantly influenced the diversity and structure of rhizosphere microbial community. Bacterial diversity in varieties with high capsaicinoids content was significantly higher than in varieties with low capsaicinoids content, while fungal diversity was opposite to bacterial diversity. The correlation analysis revealed that 19 dominant bacterial genera (e.g., Chujaibacter, Rhodanobacter, and Gemmatimonas) were significantly correlated with capsaicinoids content, and nine of them were also significantly associated with soil nutrients, whereas only one fungal genus (Podospora) was significantly correlated with capsaicinoids content. Additionally, almost all genera which significantly correlated to capsaicinoids content were biomarkers of the five pepper varieties and the correlation was well corresponding to the capsaicinoids content. Overall, our results confirmed that the variety of pepper significantly affected the rhizosphere microbial community in the fields, and bacteria and fungi responded differently to capsaicinoids, which may affect the biosynthesis of capsaicinoids and contribute to further improvement of capsaicinoids production in pepper fruits.

ABSTRACT The tumor suppressor p53, primarily functioning as a transcription factor, has exhibited antiviral capabilities against various viruses in chickens, including infectious bursal disease virus (IBDV), avian leukosis virus subgroup J (ALV-J), and avian infectious laryngotracheitis virus (ILTV). Nevertheless, the existence of a universal antiviral mechanism employed by chicken p53 (chp53) against these viruses remains uncertain. This study conducted a comprehensive comparison of molecular networks involved in chp53’s antiviral function against IBDV, ALV-J, and ILTV. This was achieved through an integrated analysis of ChIP-seq data, examining chp53’s genome-wide chromatin occupancy, and RNA-seq data from chicken cells infected with these viruses. The consistent observation of chp53 target gene enrichment in metabolic pathways, confirmed via ChIP-qPCR, suggests a ubiquitous regulation of host cellular metabolism by chp53 across different viruses. Further genome binding motif conservation analysis and transcriptional co-factor prediction suggest conserved transcriptional regulation mechanism by which chp53 regulates host cellular metabolism during viral infection. These findings offer novel insights into the antiviral role of chp53 and propose that targeting the virus-host metabolic interaction through regulating p53 could serve as a universal strategy for antiviral therapies in chickens.IMPORTANCEThe current study conducted a comprehensive analysis, comparing molecular networks underlying chp53’s antiviral role against infectious bursal disease virus (IBDV), avian leukosis virus subgroup J (ALV-J), and avian infectious laryngotracheitis virus (ILTV). This was achieved through a combined assessment of ChIP-seq and RNA-seq data obtained from infected chicken cells. Notably, enrichment of chp53 target genes in metabolic pathways was consistently observed across viral infections, indicating a universal role of chp53 in regulating cellular metabolism during diverse viral infections. These findings offer novel insights into the antiviral capabilities of chicken p53, laying a foundation for the potential development of broad-spectrum antiviral therapies in chickens.

NUAK2 is a member of the AMP-activated protein kinase (AMPK) family, which plays an essential role in cellular processes such as apoptosis, proliferation, and cell fate. Recent studies have already shown that silencing of NUAK2 blocks proliferation and promotes apoptosis of human melanoma cells and liver cancer cells. In addition, NUAK2 is involved in the development of glioblastoma via regulating the expression of cancer stem cell-related genes, and it promotes the cell cycle entry in the glioblastoma cells. However, the expression and the role of NUAK2 in the progress of peripheral nerve regeneration after injury are yet to be elucidated. We observed that NUAK2 was upregulated following distal sciatic nerve crush (SNC). Interestingly, we discovered that NUAK2 showed co-localization with S100 (Schwann cell marker). Furthermore, we found that the NUAK2 had a spatiotemporal protein expression, which was consistent with proliferating cell nuclear-antigen (PCNA). The protein level of NUAK2 and YAP was upregulated in the model of TNF-α-induced Schwann cell (SC) proliferation. Furthermore, flow cytometry analysis, CCK-8, transwell assays, and wound healing assays were all performed with the purpose of exploring the role of NUAK2 in the regulation of SC proliferation and migration. More importantly, we found that NUAK2-deficient SCs showed significantly reduced expression of Yes-associated protein (YAP). Bioinformatic analysis identified upstream regulators of NUAK2 and NUAK2-associated genes (e.g., YAP1). Finally, we investigated the recovery changes during regeneration progress through the walking track analysis. Thus, we speculated that NUAK2 was involved in biochemical and physiological responses of SCs after SNC via YAP-driven proliferation and migration, and this study determined the importance of NUAK2 as a potential target in peripheral nerve regeneration.

Abstract The effective exploitation of infeasible solutions plays a crucial role in addressing constrained multiobjective optimization problems (CMOPs). However, existing constrained multiobjective optimization evolutionary algorithms (CMOEAs) encounter challenges in effectively balancing objective optimization and constraint satisfaction, particularly when tackling problems with complex infeasible regions. Subsequent to the prior exploration, this paper proposes a novel tri-stage with reward-switching mechanism framework (TSRSM), including the push, pull, and repush stages. Each stage consists of two coevolutionary populations, namely $${\text {Pop}}_1$$ Pop 1 and $${\text {Pop}}_2$$ Pop 2 . Throughout the three stages, $${\text {Pop}}_1$$ Pop 1 is tasked with converging to the constrained Pareto front (CPF). However, $${\text {Pop}}_2$$ Pop 2 is assigned with distinct tasks: (i) converging to the unconstrained Pareto front (UPF) in the push stage; (ii) utilizing constraint relaxation technique to discover the CPF in the pull stage; and (iii) revisiting the search for the UPF through knowledge transfer in the repush stage. Additionally, a novel reward-switching mechanism (RSM) is employed to transition between different stages, considering the extent of changes in the convergence and diversity of populations. Finally, the experimental results on three benchmark test sets and 30 real-world CMOPs demonstrate that TSRSM achieves competitive performance when compared with nine state-of-the-art CMOEAs. The source code is available at https://github.com/Qu-jq/TSRSM .

Abstract Selective ion transport underpins fundamental biological processes for efficient energy conversion and signal propagation. Mimicking these ‘ionics’ in synthetic nanofluidic channels has been increasingly promising for realizing self-sustained systems by harvesting clean energy from diverse environments, such as light, moisture, salinity gradient, etc. Here, we report a spatially nanoconfined ion separation strategy that enables harvesting electricity from CO2 adsorption. This breakthrough relies on the development of Nanosheet-Agarose Hydrogel (NAH) composite-based generators, wherein the oppositely charged ions are released in water-filled hydrogel channels upon adsorbing CO2. By tuning the ion size and ion-channel interactions, the released cations at the hundred-nanometer scale are spatially confined within the hydrogel network, while ångström-scale anions pass through unhindered. This leads to near-perfect anion/cation separation across the generator with a selectivity (D-/D+) of up to 1.8 × 106, allowing conversion into external electricity. With amplification by connecting multiple as-designed generators, the ion separation-induced electricity reaching 5 V is used to power electronic devices. This study introduces an effective spatial nanoconfinement strategy for widely demanded high-precision ion separation, encouraging a carbon-negative technique with simultaneous CO2 adsorption and energy generation.

Abstract To verify the novel method of achieving a true-triaxial stress path with the pseudo-triaxial apparatus, a series of drained and undrained tests were carried out for the identical scheme with pseudo-triaxial apparatus and true-triaxial apparatus respectively. The differences between the two types of tests were quantified. The results show that the novel method effectively achieved the true-triaxial stress path by controlling the loading ratio of the pseudo-triaxial apparatus. The relationships of q − ε 1 and η − ε s measured by the two apparatuses had a higher similarity which decreases slightly with the b increase. When 0 ≤ b

The reduction in compressive strength (CS) of cementitious composites incorporating waste plastic is the main concern limiting its applicability in the building sector. Using industrial wastes as cement substitutes to enhance the CS of plastic mortar is a sustainable approach. This study used fine powdered waste materials such as silica fume (SF), marble powder (MP), and glass powder (GP) in plastic-based mortar for their effectiveness in enhancing CS. Plastic mortar specimens were cast using plastic waste in 5–25 % contents as sand replacement by mass, and their 28-day CS was recorded as a reference. SF, GP, and MP were utilized in plastic mortar mixtures separately in proportions of 5–25 %, with a 5 % increment, substituting cement by mass. These waste powders were also used in combinations of two (SF+GP, SF+MP, and GP+MP) and three (SF+GP+MP) in plastic mortar mixtures. Moreover, prediction models were built using the experimental database for the CS of plastic mortar. Gradient boosting and bagging ensemble machine learning (ML) techniques were chosen for model development. The decrease in CS was limited by substituting SF, GP, and MP for cement in plastic mortar. It was determined that the most effective substitution levels for SF, GP, and MP in plastic mortar, according to the strength enhancement, were 15, 10, and 15 wt.% of cement, respectively. The ML models closely matched experimental results, and in terms of R2 and error evaluations, bagging model outputs were more accurate than gradient boosting. The gradient boosting and bagging models had R2 of 0.89 and 0.94, respectively, with average absolute errors of 0.87 and 0.65 MPa.

Objective To comprehensively assess the dose-response association between dietary glycemic index (GI) and glycemic load (GL) and gestational diabetes mellitus (GDM) risk.Methods PubMed, Embase, Cochrane Library, Web of Science, CNKI, WanFang, and VIP databases were searched up to May 29, 2024. Studies with at least three exposure categories were included. Dose-response analysis was also performed when covariates were adjusted in the included studies.Results Thirteen studies involving 39,720 pregnant women were included. A linear relationship was found between GI and the risk of GDM (χ2 = 4.77, Pnon-linearity = .0923). However, association was not significant (χ2 = 0.06, p = .8000). For every unit increase in GI (range 0–30), GDM risk increased by 0.29%. After adjusting for covariates, the linear relationship persisted (χ2 = 4.95, Pnon-linearity = .084) with no significant association (χ2 = 0.08, p = .7775). For GL, a linear relationship was also found (χ2 = 4.17, Pnon-linearity =.1245), but GL was not significantly associated with GDM risk (χ2 = 2.63, p = .1049). The risk of GDM increased by 0.63% per unit increase in GL. After covariate adjustment, a significant association was observed (χ2 = 6.28, p = .0122).Conclusion No significant association between GI and GDM risk was found. After adjusting for covariates, GL shows a significant association with GDM risk. Our findings emphasize the importance of considering dietary GL in managing the risk of GDM. Future research should continue to explore these relationships with standardized diagnostic criteria and robust adjustment for potential confounders.

To ameliorate the diminished antimicrobial efficiency and physiological stability associated with monomeric antimicrobial peptides (AMPs) molecules, future research will focus on the artificial design of self-assembling peptides to replace monomeric entities, aiming to combat the antibiotic resistance crisis caused by microbial infections. In this study, the “bola” structure was used as the foundational architecture driving molecular self-assembly, with hydrophobic amino acids at the termini to anchor and finely adjust the sequence, thereby organizing a range of novel multidomain peptides (MDPs) templates into an ABA block motif. The results indicate that FW2 (GMSI = 53.94) exhibits the highest selectivity index among all MDPs and can form spherical micelles in an aqueous medium without the addition of any exogenous additives. FW2 exhibited high stability in vitro in the presence of physiological salt ions, serum, and various pH conditions. It exhibited excellent biocompatibility and efficacy both in vivo and in vitro. Furthermore, FW2 strongly interacts with the lipid membrane and employs various synergistic mechanisms, such as reactive oxygen species (ROS) accumulation, collectively driving cellular apoptosis. This study demonstrates a straightforward strategy for designing self-assembling peptides and promotes the advancement of peptide-based biomaterials integration progress with nanotechnology.

The development of human papillomavirus (HPV) vaccines has made substantive progress, as represented by the approval of five prophylactic vaccines since 2006. Generally, the deployment of prophylactic HPV vaccines is effective in preventing newly acquired infections and incidences of HPV-related malignancies. However, there is still a long way to go regarding the prevention of all HPV infections and the eradication of established HPV infections, as well as the subsequent progression to cancer. Optimizing prophylactic HPV vaccines by incorporating L1 proteins from more HPV subtypes, exploring adjuvants that reinforce cellular immune responses to eradicate HPV-infected cells, and developing therapeutic HPV vaccines used either alone or in combination with other cancer therapeutic modalities might bring about a new era getting closer to the vision to get rid of HPV infection and related diseases. Herein, we summarize strategies for the development of HPV vaccines, both prophylactic and therapeutic, with an emphasis on the selection of antigens and adjuvants, as well as implications for vaccine efficacy based on preclinical studies and clinical trials. Additionally, we outline current cutting-edge insights on formulation strategies, dosing schedules, and age expansion among HPV vaccine recipients, which might play important roles in addressing barriers to vaccine uptake, such as vaccine hesitancy and vaccine availability.

The accountability audit of natural resources (AANR) is a major institutional arrangement for advancing the construction of an ecological civilization in China. Based on the panel data of 271 cities in China from 2005 to 2017, this paper investigates the relationship between the AANR and carbon dioxide (CO2) emissions using a multi-period difference-in-differences (DID) model. The results show that AANR significantly increases the CO2 emission reduction rate by 0.009 units at the 5% significance level. The results still hold after a series of robustness tests. Given all else being equal, this significant effect is 0.001. Further analyses show that AANR improves pilot cities’ CO2 emission reduction rates mainly by enhancing their green innovation capability. The mediating effect of cities’ green technology innovation capability accounts for 96.00%, while the AANR’s direct effect only accounts for 4.00%. The AANR has significantly positive effects of 0.017% and 0.029% for western cities and cities with high fiscal pressure at the 5% and 1% significance levels, respectively. Therefore, strengthening AANR implementation by enhancing the mediating efficiency of cities’ green technology innovations and implementing dynamically differentiated AANR policies in Chinese meso-cities will contribute to the achievement of China’s carbon peaking and carbon neutrality targets.

BackgroundEngaging in regular physical activity has been consistently linked to improved physical health and academic performance. Despite its known benefits, there is a concerning trend of decreased physical activity among children globally. The study primarily aims to investigate the level of physical activity among junior high school students in Taiyuan and analyse the main affecting factors from a socio-ecological perspective.MethodsA cross-sectional study was conducted, involving 650 junior high school students from 7 schools in Taiyuan, and 648 valid questionnaires were ultimately collected. The data on students’ physical activity levels were collected through the Children’s Leisure Activities Study Survey Questionnaire, and the data on factors affecting students’ physical activity were collected through the Student Perceived Factors Affecting Physical Activity Questionnaire.ResultsIn this study, students from the 7th, 8th, and 9th grades participated in physical activities, averaging 214.500 min per week in moderate-intensity and 25.000 min in high-intensity activities, cumulatively averaging 280.000 min weekly. Notably, a significant disparity (p = 0.012) was observed in the combined duration of moderate and high-intensity activities, with male students engaging more time compared to their female counterparts (307.500 vs. 255.000 min). This variance extended across different grades, particularly evident in 8th graders who recorded the highest weekly high-intensity activity duration (31.000 min) and overall physical activity time (320.500 min), surpassing the 7th graders(p = 0.007 for high-intensity activities). Furthermore, an exploratory factor analysis of a 32-item questionnaire, designed to identify determinants of physical activity, revealed six principal components. These components were found to positively correlate with both moderate and high-intensity physical activities.ConclusionResults emphasize that educational institutions and community programs should collaborate to offer engaging weekend physical activity programs. Schools should develop and implement tailored physical education curricula addressing gender and grade differences. Furthermore, schools and local governments should invest in high-quality sports equipment and facilities.

BackgroundEvaluating the correlation between serum potassium and Parkinson’s disease (PD) in US adults.MethodsA cross-sectional study was conducted on 20,495 adults aged 40 years or older using NHANES data from 2005 to 2020. The study utilized one-way logistic regression and multifactorial logistic regression to examine the correlation between serum potassium levels and PD. Additionally, a smoothed curve fitting approach was employed to assess the concentration-response relationship between serum potassium and PD. Stratified analyses were carried out to investigate potential interactions between serum potassium levels and PD with variables such as age, sex, race, marital status, education, BMI, smoking and medical conditions like coronary, stroke, diabetes, hypertension, and hypercholesterolemia.ResultsIn this study, a total of 20,495 participants, comprising 403 PD and 20,092 non-PD individuals, were included. After adjusted for covariates, multivariable logistic regression revealed that high serum potassium level was an independent risk factor for PD (OR:1.86, 95% CI:1.45 ~ 2.39, p 0.05).ConclusionSerum potassium levels are elevated in patients with Parkinson's disease compared to non-PD patients. Additional prospective studies are required to explore the significance of serum potassium levels in individuals with Parkinson's disease.

Abstract Background N6-methyladenosine (m6A) mRNA modification plays a critical role in various human biological processes. However, there has been no study reported to elucidate its role in hepatic ischemia-reperfusion injury (IRI). This study was aimed to explore the expression pattern together with the potential functions of m6A regulators in hepatic IRI. Methods The gene expression data (GSE23649) of m6A regulators in human liver tissue samples before cold perfusion and within 2 h after portal vein perfusion from Gene Expression Omnibus database was analyzed. The candidate m6A regulators were screened using random forest (RF) model to predict the risk of hepatic IRI. The evaluation of infiltrating abundance of 23 immune cells was performed using single sample gene set enrichment analysis. Besides, quantitative real time polymerase chain reaction (qRT-PCR) assay was carried out to validate the expression of key m6A regulators in mouse hepatic IRI model. Results The expressions of WTAP, CBLL1, RBM15, and YTHDC1 were found to be increased in liver tissues 2 h after portal vein perfusion; in contrast, the expressions of LRPPRC, FTO, METTL3, and ALKBH5 were decreased. Based on RF model, we identified eight m6A methylation regulators for the prediction of the risk of hepatic IRI. Besides, a nomogram was built to predict the probability of hepatic IRI. In addition, the levels of WTAP, ALKBH5, CBLL1, FTO, RBM15B, LRPPRC and YTHDC1 were correlated with the immune infiltration of activated CD4 T cell, activated dendritic cell (DC), immature DC, mast cell, neutrophil, plasmacytoid DC, T helper (Th) cell (type 1, 2, and 17), gamma delta T cell, T follicular helper (Tfh) cell, myeloid-derived suppressor cell (MDSC), macrophage, natural killer cell, and regulatory Th cell. Among mouse hepatic IRI model, the mRNA level of CBLL1 and YTHDC1 was increased with statistical significance; however, the mRNA level of FTO and METTL3 was decreased among post-reperfusion liver samples compared with those in pre-reperfusion samples with statistical significance. Conclusions The m6A regulators exerted a pivotal impact on hepatic IRI. The m6A patterns that found in this study might provide novel targets and strategies for the alleviation/treatment of hepatic IRI in the future.

Abstract The recent success of mRNA therapeutics against pathogenic infections has increased interest in their use for other human diseases including cancer. However, the precise delivery of the genetic cargo to cells and tissues of interest remains challenging. Here, we show an adaptive strategy that enables the docking of different targeting ligands onto the surface of mRNA-loaded small extracellular vesicles (sEVs). This is achieved by using a microfluidic electroporation approach in which a combination of nano- and milli-second pulses produces large amounts of IFN-γ mRNA-loaded sEVs with CD64 overexpressed on their surface. The CD64 molecule serves as an adaptor to dock targeting ligands, such as anti-CD71 and anti-programmed cell death-ligand 1 (PD-L1) antibodies. The resulting immunogenic sEVs (imsEV) preferentially target glioblastoma cells and generate potent antitumour activities in vivo, including against tumours intrinsically resistant to immunotherapy. Together, these results provide an adaptive approach to engineering mRNA-loaded sEVs with targeting functionality and pave the way for their adoption in cancer immunotherapy applications.

Abstract Background Dipeptidyl peptidase-4 inhibitors (DPP-4i) have become firmly established in treatment algorithms and national guidelines for improving glycemic control in type 2 diabetes mellitus (T2DM).To report the findings from a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, which was designed to assess the efficacy and safety of a novel DPP-4 inhibitor fotagliptin in treatment-naive patients with T2DM. Methods Patients with T2DM were randomized to receive fotagliptin (n = 230), alogliptin (n = 113) or placebo (n = 115) at a 2:1:1 ratio for 24 weeks of double-blind treatment period, followed by an open-label treatment period, making up a total of 52 weeks. The primary efficacy endpoint was to determine the superiority of fotagliptin over placebo in the change of HbA1c from baseline to Week 24. All serious or significant adverse events were recorded. Results After 24 weeks, mean decreases in HbA1c from baseline were -0.70% for fotagliptin, -0.72% for alogliptin and -0.26% for placebo. Estimated mean treatment differences in HbA1c were -0.44% (95% confidence interval [CI]: -0.62% to -0.27%) for fotagliptin versus placebo, and -0.46% (95% CI: -0.67% to -0.26%) for alogliptin versus placebo, and 0.02% (95%CI: -0.16% to 0.19%; upper limit of 95%CI

Sunitinib, the first-line targeted therapy for metastatic clear cell renal cell carcinoma (ccRCC), faces a significant challenge as most patients develop acquired resistance. Integrated genomic and proteomic analyses identified PYGL as a novel therapeutic target for ccRCC. PYGL knockdown inhibited cell proliferation, cloning capacity, migration, invasion, and tumorigenesis in ccRCC cell lines. PYGL expression was increased in sunitinib-resistant ccRCC cell lines, and CP-91149 targeting the PYGL could restore drug sensitivity in these cell lines. Moreover, chromatin immune-precipitation assays revealed that PYGL upregulation is induced by the transcription factor, hypoxia-inducible factor 1α. Overall, PYGL was identified as a novel diagnostic biomarker by combining genomic and proteomic approaches in ccRCC, and sunitinib resistance to ccRCC may be overcome by targeting PYGL.

Lithostratigraphic modeling holds a vital role in mineral resource exploration and geological studies. In this study, we introduce a novel approach for automating pseudo-lithostratigraphic modeling in the deep subsurface, leveraging inversed geophysical properties. We propose a three-dimensional convolutional neural network with adaptive moment estimation (3D Adam-CNN) to achieve this objective. Our model employs 3D geophysical properties as input features for training, concurrently reconstructing a 3D geological model of the shallow subsurface for lithostratigraphic labeling purposes. To enhance the accuracy of pseudo-lithostratigraphic modeling during the model training phase, we redesign the 3D CNN framework, fine-tuning its parameters using the Adam optimizer. The Adam optimizer ensures controlled parameter updates with minimal memory overhead, rendering it particularly well-suited for convolutional learning involving huge 3D datasets with multi-dimensional features. To validate our proposed 3D Adam-CNN model, we compare the performance of our approach with 1D and 2D CNN models in the Qingniandian area of Heilongjiang Province, Northeastern China. By cross-matching the model’s predictions with manually modeled shallow subsurface lithostratigraphic distributions, we substantiate its reliability and accuracy. The 3D Adam-CNN model emerges as a robust and effective solution for lithostratigraphic modeling in the deep subsurface, utilizing geophysical properties.

Abstract The balance among different CD4+ T cell subsets is crucial for repairing the injured spinal cord. Dendritic cell (DC)‐derived small extracellular vesicles (DsEVs) effectively activate T‐cell immunity. Altered peptide ligands (APLs), derived from myelin basic protein (MBP), have been shown to affect CD4+ T cell subsets and reduce neuroinflammation levels. However, the application of APLs is challenging because of their poor stability and associated side effects. Herein, it is demonstrate that DsEVs can act as carriers for APL MBP87‐99A91 (A91‐DsEVs) to induce the activation of 2 helper T (Th2) and regulatory T (Treg) cells for spinal cord injury (SCI) in mice. These stimulated CD4+ T cells can efficiently “home” to the lesion area and establish a beneficial microenvironment through inducing the activation of M2 macrophages/microglia, inhibiting the expression of inflammatory cytokines, and increasing the release of neurotrophic factors. The microenvironment mediated by A91‐DsEVs may enhance axon regrowth, protect neurons, and promote remyelination, which may support the recovery of motor function in the SCI model mice. In conclusion, using A91‐DsEVs as a therapeutic vaccine may help induce neuroprotective immunity in the treatment of SCI.

Non-motor symptoms are prevalent among individuals with Parkinson’s disease (PD) and seriously affect patient quality of life, even more so than motor symptoms. In the past decade, an increasing number of studies have investigated non-motor symptoms in PD. The present study aimed to comprehensively analyze the global literature, trends, and hotspots of research investigating non-motor symptoms in PD through bibliometric methods. Studies addressing non-motor symptoms in the Web of Science Core Collection (WoSCC), published between January 2013 and December 2022, were retrieved. Bibliometric methods, including the R package “Bibliometrix,” VOS viewer, and CiteSpace software, were used to investigate and visualize parameters, including yearly publications, country/region, institution, and authors, to collate and quantify information. Analysis of keywords and co-cited references explored trends and hotspots. There was a significant increase in the number of publications addressing the non-motor symptoms of PD, with a total of 3,521 articles retrieved. The United States was ranked first in terms of publications (n = 763) and citations (n = 11,269), maintaining its leadership position among all countries. King’s College London (United Kingdom) was the most active institution among all publications (n = 133) and K Ray Chaudhuri was the author with the most publications (n = 131). Parkinsonism & Related Disorders published the most articles, while Movement Disorders was the most cited journal. Reference explosions have shown that early diagnosis, biomarkers, novel magnetic resonance imaging techniques, and deep brain stimulation have become research “hotspots” in recent years. Keyword clustering revealed that alpha-synuclein is the largest cluster for PD. The keyword heatmap revealed that non-motor symptoms appeared most frequently (n = 1,104), followed by quality of life (n = 502), dementia (n = 403), and depression (n = 397). Results of the present study provide an objective, comprehensive, and systematic analysis of these publications, and identifies trends and “hot” developments in this field of research. This work will inform investigators worldwide to help them conduct further research and develop new therapies.

An experimental study on the axial compressive failure of a notched unidirectional (UD) glass fiber-reinforced composites has been performed to better understand the failure mechanisms in three dimensions (3D). A sequence of failure initiation and propagation has been monitored based on X-ray computed tomography (CT) images of the sample during failure. The CT images have shown that fiber kinking failure is the main failure mechanism, and there are two different types of kink bands, classified as type 1 and type 2 by final geometric form. The type 1 kink band, which has an X shape, extends outward from the notch along the width direction before finally creating a shear type 2 kink band at a distance from the notch. The novelty of this work involves observing the nucleation and propagation of fiber kink bands in three-dimensional space, as well as defining and quantifying kink band variables.

Abstract Pepper (Capsicum spp.) is one of the earliest cultivated crops and includes five domesticated species, C. annuum var. annuum, C. chinense, C. frutescens, C. baccatum var. pendulum and C. pubescens. Here, we report a pepper graph pan-genome and a genome variation map of 500 accessions from the five domesticated Capsicum species and close wild relatives. We identify highly differentiated genomic regions among the domesticated peppers that underlie their natural variations in flowering time, characteristic flavors, and unique resistances to biotic and abiotic stresses. Domestication sweeps detected in C. annuum var. annuum and C. baccatum var. pendulum are mostly different, and the common domestication traits, including fruit size, shape and pungency, are achieved mainly through the selection of distinct genomic regions between these two cultivated species. Introgressions from C. baccatum into C. chinense and C. frutescens are detected, including those providing genetic sources for various biotic and abiotic stress tolerances.

In response to the problems of large deformation, fracture closure and poor permeability of the surrounding rocks in the weak rock roadways of the 1 000 m or deeper coal mines, it is required that the grouting material has good injectability, fast solidification speed, high early strength, and strong bonding performance. A new method of synergistic preparation of inorganic grouting materials was designed using “component optimization + ultra-fine + nano-reinforcement + organic modification”. An inorganic grouting material with an optimum composition ratio of 50∶40∶10 for the ternary cementing system of calcium sulphate aluminate, gypsum and lime was developed. After ultra grinding, the compressive strength of the concretion increased by 163.0% within 4 hours, achieving initial early strength and rapid solidification. A nano-lithium-aluminium hydrotalcite reinforcement material with synergistic effects of nano-nucleation-induced crystallization and lithium ion promotion was developed, resulting in a 183.7% increase in the 2 h strength of the ultra grinding grouting material. The organic modifier with directional coupling effect at the coal-rock interface was synthesized, which formed a bridge through bonding with the grout and coal interface, significantly improving the bonding between the slurry concretion and the coal rock interface. The synergistically prodeuced inorganic-organic composite grouting reinforcement materials has small particle size (D95

In recent years, the demand for marine new energy, oil and gas, and transportation in coastal areas has increased significantly. The rigid demand for marine space resources has increased sharply, and the contradiction between supply and demand has become increasingly tense. In particular, the sea use of offshore wind power, affected by the national macro strategy, has shown a leap forward development, with the installed capacity ranking first in the world. The construction of large-scale offshore wind power has put forward higher requirements for the allocation of marine space resources. How to ensure the demand for offshore wind power and coordinate the contradiction between offshore wind power and other industries in the use of sea has become an important problem to be solved. Establishing the concept of intensive use of natural resources can solve the above problems well. The concept of intensive use is not only the internal requirement to comprehensively improve the utilization efficiency of marine space resources, the urgent need to solve the outstanding contradiction between protection and development, but also the key to coordinate the relationship between protection and development. Based on this, this paper aimed to systematically analyze the existing data of the sea area covered by offshore wind farms and the sea area for right confirmation, adopted the concept of intensive space resource development, and improved the sea area control index system for offshore wind power from the aspects of project site selection and submarine cable routing, wind farm design and technical requirements, sea use scope and area control for right confirmation, so as to improve the sea use intensive level of offshore wind power projects.

Abstract Introduction Immune factors contribute to the onset of myelodysplastic syndrome (MDS). Arginine metabolism affects tumor‐associated macrophage (TAM) polarization. This study investigated the infiltration of TAMs and effect of arginine metabolism key enzymes on MDS prognosis. Methods We used the GEO (Gene Express Omnibus database) dataset “GSE19429” to analyze and compare metabolism‐associated pathways between MDS patients with excess blasts and those without. The markers of TAMs and arginine metabolism key enzymes, including CD68, iNOS, ARG1 and ASS1 were included in this study. A cohort of 79 patients with acute myeloid leukemia or MDS extracted from GenomicScape's online data mining platform was used to analyze the prognostic significance of the mRNA levels. Fifty‐eight patients with primary MDS admitted to Sichuan University's West China Hospital from 2013 to 2017 were evaluated for protein levels. The coexpression of CD68, iNOS, and ARG1 was investigated using an Opal polychromatic immunofluorescence kit. Results The “Arginine and proline metabolism” pathways (padjusted = 0.01) were associated with excess blasts in patients with MDS. In the mRNA expression cohort, patients with low NOS2 (or iNOS) and high ARG1, ASS1, and CD68 expression levels had worse prognosis. Patients with high CD68 (p = 0.01), high iNOS (p

Abstract Red blood cells (RBCs) are the most abundant cells in the body, possessing unique biological and physical properties. RBCs have demonstrated outstanding potential as delivery vehicles due to their low immunogenicity, long-circulating cycle, and immune characteristics, exhibiting delivery abilities. There have been several developments in understanding the delivery system of RBCs and their derivatives, and they have been applied in various aspects of biomedicine. This article compared the various physiological and physical characteristics of RBCs, analyzed their potential advantages in delivery systems, and summarized their existing practices in biomedicine. Graphical Abstract

Shape-shifting polymers usually require not only reversible stimuli-responsive ability, but also strong mechanical properties. A novel shape-shifting photochromic hydrogel system was designed and fabricated by embedding hydrophobic spiropyran (SP) into double polymeric network (DN) through micellar copolymerisation. Here, sodium alginate (Alg) and poly acrylate-co-methyl acrylate-co-spiropyran (P(SA-co-MA-co-SPMA)) were employed as the first network and the second network, respectively, to realise high mechanical strength. After being soaked in the CaCl2 solution, the carboxyl groups in the system underwent metal complexation with Ca2+ to enhance the hydrogel. Moreover, after the hydrogel was exposed to UV-light, the closed isomer of spiropyran in the hydrogel network could be converted into an open zwitterionic isomer merocyanine (MC), which was considered to interact with Ca2+ ions. Interestingly, Ca2+ and UV-light responsive programmable shape of the copolymer hydrogel could recover to its original form via immersion in pure water. Given its excellent metal ion and UV light stimuli-responsive and mechanical properties, the hydrogel has potential applications in the field of soft actuators.

Shape-shifting polymers are widely used in various fields such as intelligent switches, soft robots and sensors, which require both multiple stimulus-response functions and qualified mechanical strength. In this study, a novel near-infrared-light (NIR)-responsible shape-shifting hydrogel system was designed and fabricated through embedding vinylsilane-modified carbon nanotubes (CNTs) into particle double-network (P-DN) hydrogels by micellar copolymerisation. The dispersed brittle Poly(sodium 2-acrylamido-2-methylpropane-1-sulfonate) (PNaAMPS) network of the microgels can serve as sacrificial bonds to toughen the hydrogels, and the CNTs endow it with NIR photothermal conversion ability. The results show that the CNTs embedded in the P-DN hydrogels present excellent mechanical strength, i.e., a fracture strength of 312 kPa and a fracture strain of 357%. Moreover, an asymmetric bilayer hydrogel, where the active layer contains CNTs, can achieve 0°–110° bending deformation within 10 min under NIR irradiation and can realise complex deformation movement. This study provides a theoretical and experimental basis for the design and manufacture of photoresponsive soft actuators.

Abstract Background To investigate the outcomes and safety of using minimally invasive percutaneous new transpedicular lag-screw fixation with intraoperative, full rotation, three-dimensional image (O-arm)-based navigation for the management of Hangman fracture. Methods Twenty-two patients with Hangman fracture were treated with minimally invasive percutaneous new transpedicular lag-screws using intraoperative, full rotation, and three-dimensional image (O-arm)-based navigation. The preoperative and postoperative conditions of the patients were evaluated according to the ASIA (American Spinal Injury Association) scale. The patient's VAS (visual analog scale) scores before and after surgery, operation time, cervical vertebral activity, intervertebral angle and bone healing were recorded and collected, and repeated measures analysis of variance was used for statistical analysis. Results All patients were satisfactorily repositioned after surgery, and the VAS scores for neck pain were significantly lower than those before surgery on the first day and at 1 month, 3 months and the last follow-up (P

Fhb7 is a major gene that was transferred from Thinopyrum ponticum to chromosome 7D of wheat (Triticum aestivum) and confers resistance to both Fusarium head blight (FHB) and Fusarium crown rot (FCR). However, Fhb7 is tightly linked to the PSY-E2 gene, which causes yellow flour, limiting its application in breeding. To break this linkage, marker K-PSY was developed for tagging PSY-E2 and used with Fhb7 markers to identify recombination between the two genes. Screening 21,000 BC1F2 backcross progeny (Chinese Spring ph1bph1b*2/SDAU 2028) revealed two Fhb7+ wheat-Tp7el2L lines, Shannong 2–16 and Shannong 16–1, that carry a desired truncated Fhb7+ translocation segment without PSY-E2. The two lines show levels of resistance to FHB and FCR similar to those of the original translocation line SDAU 2028, but have white flour. To facilitate Fhb7 use in wheat breeding, STS markers were developed and used to isolate Fhb7 on a truncated Tp7el2 translocation segment. Near-isogenic lines carrying the Fhb7+ segment were generated in the backgrounds of three commercial cultivars, and Fhb7+ lines showed increased FHB and FCR resistance without yield penalty. The breakage of the tight linkage between Fhb7 and PSY-E2 via homoeologous recombination provides genetic resources for improvement of wheat resistance to FHB and FCR and permit the large-scale deployment of Fhb7 in breeding using marker-assisted selection.

Abstract Background More than 2 million anterior cruciate ligament (ACL) injuries occur worldwide each year. Most surgeons suggest that athletes and active persons with significant knee functional demands, including cutting motions, require and should be offered ligament reconstruction surgery. Despite concentrated rehabilitation efforts, deficits in quadriceps size and strength can persist for years after surgery. Blood flow restriction (BFR) training can help overcome disuse muscular atrophy in the mid-term postoperative period after anterior cruciate ligament reconstruction (ACLR) surgery. The purpose of this study was to evaluate the effects of quadriceps training with different levels of blood flow restriction on quadriceps strength and thickness of participants after ACLR. Methods In this study, 30 post-ACL reconstruction participants were randomly divided into three groups (control, 40% Arterial Occlusion Pressure [AOP] and 80% AOP groups). All patients were subjected to different levels of BFR, combined with conventional quadriceps rehabilitation, for 8 weeks. Assessments included scaled maximal isokinetic knee extension strength at 60°/s and 180°/s, the sum of the thickness of the affected femoris rectus and vastus intermedius, Y-balance test performance, and International Knee Documentation Committee questionnaire responses before and after the intervention. Results In total, 23 participants completed the entire study. The 80% AOP compression group showed an increase in quadriceps femoris muscle strength and muscle thickness (p

Ovarian toxicity is most common gynecologically related malignancy, arising for most cases owing to the advanced stage of diagnosis. The aim of the current study was to explore the anticancer potential of baicalin against cyclophosphamide (CP) induced ovarian toxicity in mice and explore the possible mechanism. ovarian cancer cells (Hey, SKOv3ip and HO891PM) were treated with different doses of baicalin and examined via flow cytometry and cell proliferation assay. Subcutaneous administration of CP (200 mg/kg) was used to induce the ovary toxicity and mice were received the oral administration of baicalin. Oxidative, pro-inflammatory, inflammatory, apoptosis parameters, progesterone, estrogen hormones and histopathological were also estimated at end of the study. Baicalin increased the apoptosis and caused the cell cycle arrest at the G2/M stage in ovarian cancer cells. Baicalin significantly (P

In order to alleviate the contradiction between human and land, and expand the city living space, the sea reclamation activities have been developed rapidly in a short time. However, while the reclamation projects have brought remarkable economic benefits, they have caused a lot of negative effects on marine environment and biological resources in the coastal areas.In this paper,the threats of sea reclamation activities on marine hydrological dynamic conditions, water quality, disaster prevention and mitigation were analyzed, and the damages to biodiversity, habitat protection and ecosystem service function value were discussed. The practical countermeasures were put forward, such as improving the management system of national policies and regulations on sea reclamation, strengthening research on ecological restoration planning, and establishing a system for assessing the impact of land reclamation on the ecological environment.

Leaf color is directly related to altered photosynthesis. Hence, leaf yellowing mutants can be widely used for the researching plant physiology and functional genomes, for cultivating new varieties of popular horticultural plants, and for identifying hybrid purity (as markers). Here, we constructed a 60Co-γ F2 population from the leaf -yellowing mutant R24 via radiation mutation with the inbred line WT21 of pepper. Genetic analysis showed that the leaf-yellowing of the mutant was controlled by a single recessive gene. By applying the Bulk Segregation Analysis and Kompetitive Allele Specific PCR markers, the leaf-yellowing gene CaLY1 (Capsicum annuum Leaf yellow 1) was mapped on chromosome 9, SNP5791587–SNP6011215, with a size of 214.5 kb. One non-synonymous mutated gene Capana09g000166 was found in the interval. The gene encoded a PsbX, which is the core complex of PSII. Transcriptome analysis further showed that 2301 differentially expressed genes were identified under shading treatment for 24 h in R24. The Gene Ontology enrichment pathways were related to photosynthesis light harvesting, cell wall, activity of quercetin 3-O-glucosyltransferase and flavonoid metabolic process, which likely regulate the response of pepper leaves to different light levels. Functional enrichment analysis indicated that the most abundant pathways were photosynthesis antenna proteins and metabolic.

There is a continuing need for artificial bone substitutes for bone repair and reconstruction, Magnesium phosphate bone cement (MPC) has exceptional degradable properties and exhibits promising biocompatibility. However, its mechanical strength needs improved and its low osteo-inductive potential limits its therapeutic application in bone regeneration. We functionally modified MPC by using a polymeric carboxymethyl chitosan-sodium alginate (CMCS/SA) gel network. This had the advantages of: improved compressive strength, ease of handling, and an optimized interface for bioactive bone in-growth. The new composites with 2% CMCS/SA showed the most favorable physicochemical properties, including mechanical strength, wash-out resistance, setting time, injectable time and heat release. Biologically, the composite promoted the attachment and proliferation of osteoblast cells. It was also found to induce osteogenic differentiation in vitro, as verified by expression of osteogenic markers. In terms of molecular mechanisms, data showed that new bone cement activated the Wnt pathway through inhibition of the phosphorylation of β-catenin, which is dependent on focal adhesion kinase. Through micro-computed tomography and histological analysis, we found that the MPC-CMCS/SA scaffolds, compared with MPC alone, showed increased bone regeneration in a rat calvarial defect model. Overall, our study suggested that the novel composite had potential to help repair critical bone defects in clinical practice.

Top-down exfoliation is one of the most promising approaches for the scalable production of 2D materials, but the current techniques are limited by low yield of monolayers. Here, the authors report the exfoliation of graphene and other layered materials via viscous-polymer-assisted ball-milling, leading to a production of graphene products with monolayer percentage up to 97.9% at a yield of 78.3%.

The impact of fabric anisotropy, fractal dimension, and breakage on the strength and deformation of granular materials were diminished by uniform-size spherical glass beads. Triaxial drained and undrained tests were performed on glass beads based on a novel method to substitute true triaxial stress paths with conventional triaxial apparatus equivalents with varying intermediate principal stress coefficients (b-values). The result indicates that all specimens manifested a noticeable strain-softening phenomenon. The peak strength decreased with increasing b-value, and the specimens showed more pronounced dilatancy. This pattern is similar to the results of the true triaxial test in current research. Compared to the undrained test, the peak friction angle in the drained test displayed a greater variation with varying b-values, which indicated that the mechanical response of glass beads is sensitive to water. This difference provides experimental evidence for comprehending effective stress in granular materials with constant friction coefficients. The experiments reflect the effect of b-value changes on the p-q stress path, as well as on the peak stress ratio, the state transition stress ratio, and the critical state stress ratio. The specimens exhibited a distinct shear band at different b-values ranging from 0.2 to 0.6, which is different from observations in conventional triaxial tests for granular materials.

The goaf treatment of underground metal mines is an important link in mining, and it is particularly important to master the laws of overlying rock strata and surface movement of goaf. In this paper, Persistent Scatterer Interferometric Synthetic Aperture Radar (PS-InSAR) technology is used to monitor the surface subsidence of the Taibao lead-zinc mine, and the surface subsidence laws of goaf-closure, partial-filling, and full-filling treatments are analyzed by the time-series method. The findings indicate that the surface subsidence of the closed goaf is solely governed by the pillars, with the quality of these pillars playing a pivotal role in controlling such subsidence. Factors like stope span also influence the surface subsidence of partially filled goaf. Prior to compaction, it is primarily the pillars that control surface subsidence; however, after compaction, filling and pillars jointly regulate this phenomenon. Notably, in filled goaf, the quality of both roof and pillars significantly impacts surface subsidence. Before compaction occurs, control over surface subsidence is not evident, yet post-compaction, the filling is effective and tends to stabilize this process. The research findings are significant in enhancing goaf’s treatment efficacy, mitigating surface damage and minimizing ecological environmental impact.

Until now, how the magnetic fields in M/X-class flaring active regions (ARs) differ from C-class flaring ARs remains unclear. Here, we calculate the key magnetic field parameters within the area of high photospheric free energy density (HED region) for 323 ARs (217 C- and 106 M/X-flaring ARs), including total photospheric free magnetic energy density E _free , total unsigned magnetic flux Φ _HED , mean unsigned current helicity h _c , length of the polarity inversion lines L _PIL with a steep horizontal magnetic gradient, etc., and compare these with flare/coronal mass ejection (CME) properties. We first show the quantitative relations among the flare intensity, the eruptive character, and Φ _HED . We reveal that Φ _HED is a measure for the GOES flux upper limit of the flares in a given region. For a given Φ _HED , there exists the lower limit of F _SXR for eruptive flares. This means that only the relatively strong flares with the large fraction of energy release compared to the total free energy are likely to generate a CME. We also find that the combinations of E _free – L _PIL and E _free – h _c present a good ability to distinguish between C-class and M/X-class flaring ARs. Using determined critical values of E _free and L _PIL , one predicts correctly 93 out of 106 M/X-class flaring ARs and 159 out of 217 C-class flaring ARs. The large L _PIL or h _c for M/X-class flaring ARs probably implies the presence of a compact current with twisted magnetic fields winding about it.