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Abstract Objective Bone incision leads to interrupted and sluggish blood flow in the process of distraction osteogenesis (DO), creating a hypoxia (0–2% oxygen tension) at the center of the bone callus. This hypoxia is critical in the coupling of osteogenesis and angiogenesis during DO. This study aimed to investigate the effect of Uniaxial Static Strain (USS) on osteogenesis in osteoblasts under hypoxic conditions, with a focus on the expression of osteogenic markers and angiogenic factors. Methods The USS was made by a multi-unit tension compression device.Osteoblasts were subjected to 10% USS made under hypoxic conditions to mimic the process of DO in vitro. The cell proliferation, alkaline phosphatase (ALP) activity, mineralized nodule formation, and expression of osteogenic and angiogenic markers were evaluated by using a CCK-8 assay, alkaline phosphatase (ALP) staining, ALP activity assay, alizarin red S staining, qRT-PCR, Western blotting and ELISA. Results Hypoxia inhibited osteoblast cell proliferation, ALP activity, mineralized nodule formation, and the expression of runt-related transcription factor 2 (Runx- 2), osteopontin(OPN), osteocalcin (OCN), collagen type I (Col1a1). Conversely, hypoxia upregulated the expression of hypoxia-inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF), which are associated with angiogenesis. However, the application of USS enhanced osteoblasts’ osteogenic capacity and upregulated angiogenic factors under hypoxic conditions. Conclusion USS can enhance osteogenesis in osteoblasts under hypoxic conditions. Moreover, it may stimulate angiogenesis by promoting the expression of VEGF, which further contributes to bone formation. This finding provides important implications for understanding the mechanisms involved in bone regeneration and may have clinical applications in optimizing the effectiveness of DO techniques.

Abstract The abounding variations in wild rice provided potential reservoirs of beneficial genes for rice breeding. Maintaining stable and high yields under environmental stresses is a long-standing goal of rice breeding but is challenging due to internal trade-off mechanisms. Here, we report wild rice GL12 W improves grain length and salt tolerance in both indica and japonica genetic backgrounds. GL12 W alters cell length by regulating grain size related genes including GS2, and positively regulates the salt tolerance related genes, such as NAC5, NCED3, under salt stresses. We find that a G/T variation in GL12 promoter determined its binding to coactivator GIF1 and transcription factor WRKY53. GIF1 promotes GL12 W expression in young panicle and WRKY53 represses GL12 W expression under salt stresses. The G/T variation also contributes to the divergence of indica and japonica subspecies. Our results provide useful resources for modern rice breeding and shed insights for understanding yield and salt tolerance trade-off mechanism.

Abstract Background Patients undergoing dialysis treatment have long been recognized as having an elevated risk of developing coronary artery disease necessitating coronary artery bypass grafting (CABG). However, the prognostic implications of CABG in dialysis-dependent patients remain underexplored. This study aimed to comprehensively assess both short- and long-term outcomes in dialysis-dependent patients undergoing CABG. Methods In this retrospective analysis, we meticulously matched 55 dialysis-dependent patients with 55 non-dialysis patients, controlling for baseline characteristics including age, sex, etiology, and date of surgery. All patients underwent CABG treatment at our institution between January 2014 and June 2022. We conducted a comparative analysis of postoperative complications and survival rates between the two groups. Results Our findings revealed that the dialysis-dependent group exhibited a significantly higher incidence of postoperative complications compared to the non-dialysis group (92.7% vs. 61.8%; p

Abstract Under subarachnoid hemorrhage (SAH) conditions, astrocytes undergo a marked intensification of glycolytic activity, resulting in the generation of substantial amounts of lactate to maintain the energy demand for neurons and other brain cells. Lactate has garnered increasing attention in recent years because of its emerging role in critical biological processes such as inflammation regulation and neuroprotection, particularly through its histone lactylation. Bromodomain-containing protein 4 (BRD4) plays a crucial role in maintaining neural development and promoting memory formation in the central nervous system. Nonetheless, the function and regulatory mechanism of BRD4 and histone lactylation in astrocytes following SAH remain elusive. Our findings indicate that BRD4, a crucial epigenetic regulator, plays a definitive role in histone lactylation. Both in vitro and in vivo, these results demonstrated that targeted silencing of BRD4 in astrocytes can significantly reduce H4K8la lactylation, thereby aggravating the A1 polarization of astrocytes and ultimately affecting the recovery of neural function and prognosis in mice after SAH. In summary, BRD4 plays a pivotal role in modulating astrocyte polarization following SAH via histone lactylation. Targeting this mechanism might offer an efficient therapeutic strategy for SAH.

The Zhundong region in Xinjiang has abundant high-Na coal resource, which can be used as high-quality fuel and chemical raw material. However, the high-Na content can lead to severe equipment pollution and ash slagging during combustion and gasification processes, thereby significantly restricting its large-scale and efficient utilization. The efficient, economical, and environmental friendly removal of Na is of great significance for the clean utilization of the Zhundong coal. This study investigates the rule and mechanism of Na removal from low-rank high-Na coal in the Zhundong region using a series of low-concentration ammonium salts. The results show that the deionized water (DI) can only remove about 52% of Na in the coal. When some low-concentration ammonium salts such as NH4Ac, NH4Cl, (NH4)2SO4, NH4NO3 and TMACl with a concentration of 0.006 mol/L are used, the total Na removal rate and organic Na removal rate can reach to 90%−97% and 80%−95%, respectively. The Na2O mass fraction in coal ash is significantly reduced from 6.21% in raw coal, 2.77% in water-treated coal and 0.27%−0.81% in coal treated with low-concentration ammonium salts. Among the various ammonium salts mentioned above, the NH4Ac shows the best Na removal effect. The size of the cation in the Na removal agent plays an important role in the removal of organic Na, and the Na removal capacity follows the order: H+ > NH4+ > TMA+, which is due to the smaller cations are more favorable for entering coal pores and interacting with organic Na through ion exchange. Ammonium salts can remove various types of Na carboxylates through conventional ion exchange mechanisms, but the removal mechanism of phenolic Na may involve ion exchange, complex decomposition of phenolic ammonium salts, and hydrolysis of NH4+. Increasing the temperature, prolonging the time, and increasing the amount of ammonium salts significantly enhance the removal of total Na, water-soluble inorganic Na, and organic Na in coal. A correlation between the amount of ammonium salt added and the removal of total Na and organic Na in coal has been established. For NH4Ac, the correlation is as follows: y(total Na) = 12479x(ammonium amount) + 2200, y(organic Na) = 12394x(ammonium amount) + 136. In order to meet the national coal combustion standard (w(Na2O) < 2.0%, mass fraction by ash) for the Zhundong coal, about 70% of the total Na needs to be removed, about 4.26 kg of NH4Ac should be added per ton of the Zhundong coal.

Abstract Background Influenza A virus infections can occur in multiple species. Eurasian avian-like swine influenza A (H1N1) viruses (EAS-H1N1) are predominant in swine and occasionally infect humans. A Eurasian avian-like swine influenza A (H1N1) virus was isolated from a boy who was suffering from fever; this strain was designated A/Shandong-binzhou/01/2021 (H1N1). The aims of this study were to investigate the characteristics of this virus and to draw attention to the need for surveillance of influenza virus infection in swine and humans. Methods Throat-swab specimens were collected and subjected to real-time fluorescent quantitative polymerase chain reaction (RT‒PCR). Positive clinical specimens were inoculated onto Madin-Darby canine kidney (MDCK) cells to isolate the virus, which was confirmed by a haemagglutination assay. Then, whole-genome sequencing was carried out using an Illumina MiSeq platform, and phylogenetic analysis was performed with MEGA X software. Results RT‒PCR revealed that the throat-swab specimens were positive for EAS-H1N1, and the virus was subsequently successfully isolated from MDCK cells; this strain was named A/Shandong-binzhou/01/2021 (H1N1). Whole-genome sequencing and phylogenetic analysis revealed that A/Shandong-binzhou/01/2021 (H1N1) is a novel triple-reassortant EAS-H1N1 lineage that contains gene segments from EAS-H1N1 (HA and NA), triple-reassortant swine influenza H1N2 virus (NS) and A(H1N1) pdm09 viruses (PB2, PB1, PA, NP and MP). Conclusions The isolation and analysis of the A/Shandong-binzhou/01/2021 (H1N1) virus provide further evidence that EAS-H1N1 poses a threat to human health, and greater attention should be given to the surveillance of influenza virus infections in swine and humans.

Gastrointestinal cancer is a common malignant tumor with a high incidence worldwide. Despite continuous improvements in diagnosis and treatment strategies, the overall prognosis of gastrointestinal tumors remains poor. Carcinoembryonic antigen (CEA) is highly expressed in various types of cancers, especially in gastrointestinal cancers, making it a potential target for therapeutic intervention. Therefore, the expression of CEA can be used as an indication of the existence of tumors, chosen as a target for molecular imaging diagnosis, and effectively utilized in the targeted therapy of gastrointestinal cancers. In this study, we report the selection and characterization of affibody molecules (ZCEA539, ZCEA546, and ZCEA919) specific to the CEA protein. Their ability to bind to recombinant and native CEA protein has been confirmed by surface plasmon resonance (SPR), immunofluorescence, and immunohistochemistry assays. Furthermore, Dylight755-labeled ZCEA affibody showed accumulation within the tumor site 1 h post injection and was continuously enhanced for 4 h. The Dylight755-labeled ZCEA affibody exhibited high tumor-targeting specificity in CEA+ xenograft-bearing mice and possesses promising characteristics for tumor-targeting imaging. Overall, our results suggest the potential use of ZCEA affibodies as fluorescent molecular imaging probes for detecting CEA expression in gastrointestinal cancer.

Abstract The abundant genetic variation harbored by wild rice (Oryza rufipogon) has provided a reservoir of useful genes for rice breeding. However, the genome of wild rice has not yet been comprehensively assessed. Here, we report the haplotype-resolved gapless genome assembly and annotation of wild rice Y476. In addition, we develop two sets of chromosome segment substitution lines (CSSLs) using Y476 as the donor parent and cultivated rice as the recurrent parents. By analyzing the gapless reference genome and CSSL population, we identify 254 QTLs associated with agronomic traits, biotic and abiotic stresses. We clone a receptor-like kinase gene associated with rice blast resistance and confirm its wild rice allele improves rice blast resistance. Collectively, our study provides a haplotype-resolved gapless reference genome and demonstrates a highly efficient platform for gene identification from wild rice.

Abstract Background There is currently a lack of functional assessment tools based on the International Classification of Functioning, Disability, and Health (ICF) theoretical framework that are specific for older adults. Objective The aim of the present study was to develop Chinese assessment standards of the ICF Geriatric Core Set for functional evaluation of older adults. Methods A two-stage study process was conducted to develop the assessment standards of the ICF Geriatric Core Set: establishment of candidate assessment standards, and a modified Delphi consensus process including a pilot survey and two-round formal expert survey. Thirty participants in the field of ICF and geriatric rehabilitation were recruited. The suitability of the assessment standards in the questionnaires was rated using a Likert 5-level scoring method. The arithmetic mean, the full mark ratio and the coefficient of variation (CV) were used as screening indicators for the assessment standards, and modification was made for several standards, in line with the Delphi results and the expert panel discussion. Results Thirty-three candidate assessment standards belonging to 17 categories were generated. A total of 26 and 24 experts in the field of ICF and geriatric rehabilitation participated in the two-round survey, respectively. Five standards belonging to four categories entered into the second-round survey directly, five standards belonged to five categories entered with minor modification, and nine standards belonging to seven categories were redesigned based on the literature and discussion of the expert panel. In the second-round survey,15 assessment standards belonging to 15 categories met the screening requirements and four assessment standards belonged to the two remaining categories that needed a criterion and which the expert panel discussed for the final decision. Conclusions Using the modified Delphi method, the assessment standards of the ICF Geriatric Core Set have been developed.Future work should focus on the reliability and validity of the the assessment standards and their application to the health management of older adults.

Abstract Functional traits are important in understanding how plants respond and adapt to their immediate environment. Parrotia subaequalis is a highly endangered arbor species found throughout eastern China, primarily inhabiting hillsides and valleys, yet, little is known about the variation in leaf traits across these environments. In the present study, we tested this by comparing leaf surface area, leaf weight, leaf length, leaf symmetry and leaf mass per unit area, as well as the relationship between leaf traits and environmental factors and the scaling relationship between leaf surface area versus leaf dry mass. We observed significant differences in leaf surface area, weight, and length among the population sites, and these variables were strongly affected by environmental factors, especially high mean annual temperatures in hillside habitats and high mean annual precipitation in valley habitats. The scaling exponents remained numerically variant among the 10 populations, with different slopes greater than 1.0, and the scaling exponents increased significantly with hillside habitats. These metrics correlated with soil thickness associated with different habitat types. The areal ratio (AR) values in all populations deviated from 1, indicating that the two lamina sides were asymmetrical. The standardized symmetry index (SI) values displayed significant variation, especially in leaves from hillside habitats with a high degree of asymmetry. Collectively, our findings demonstrated that leaf functional traits exhibit considerable variability in response to different environmental contexts and provide valuable reference data that could be useful for conserving this endangered species.

Abstract Background To report a case of retinitis with multiple intraocular viral infections after second haematopoietic stem cell transplantation. Case presentation A 39-year-old female patient developed retinitis after a second haematopoietic stem cell transplant. Right eye was tested for three viral infections– cytomegalovirus, Epstein‒Barr virus and herpes simplex virus, while left was infected with cytomegalovirus. The patient was subsequently treated with vitreous cavity ganciclovir injections, and 1 week later both eyes tested negative for aqueous humour viruses. Discussion and conclusion CMV, EBV and HSV belong to the herpes virus family. They are all commonly observed in the body and represent opportunity infectious viruses. The retinitis they cause have different characteristics. But simultaneous infection of the eye by multiple viruses is quite rare. In this case, three viruses were detected in the patient’s eye, but whether the retina was caused by all three viruses at the same time could not be determined. A satisfactory outcome was achieved after treatment with vitreous cavity ganciclovir injection.

Ascorbic acid (AA) plays an important role in many physiological and biochemical processes. Adequate quantification of AA is required for controlling the intake of AA for health management. In this study, a portable probe was fabricated based on the assembled FePO4@GO nanozyme by homogeneous precipitation. FePO4@GO exhibits excellent peroxidase (POD) activity. As an efficient free radical scavenger, ascorbic acid scavenges 1O2 free radicals produced by hydrogen peroxide catalyzed by peroxidase enzymes and then inhibits the color reaction of 3,3′,5,5′-tetramethylbenzidine (TMB). A good linear relationship between the color of the reaction system and the concentration of AA in the range of 2.5–75 μM was presented, and the detection limit is 1.25 μM. Furthermore, a visual colorimetric detection platform was constructed using a smartphone. The AA content is accurately reflected by intelligent recognition of color changes in the reaction system. It provides an alternative approach for portable and visual rapid detection of Vitamin C (VC) in medicine. Meanwhile, it also provides a reference for the assembly of an intelligent detection platform based on nanozymes.

The natural environment in the high-altitude regions of Northwest China is extremely harsh, characterized by numerous salt lakes. The high concentrations of chloride salts, sulfates, and alkali metal ions in these areas can induce alkali–silica reactions (ASRs) in concrete. These reactions generate harmful gel within the concrete, causing expansion and cracking, which significantly impacts the durability of concrete structures. This study investigates the evolution of the mechanical properties in high-performance concrete (HPC) under long-term ASR by incorporating different admixtures and varying the equivalent alkali content. A three-dimensional random aggregate mesoscopic model was used to simulate static compression tests under various operational conditions. Non-destructive testing methods were utilized to determine the expansion rate, internal, and surface damage variables of the concrete. The experimental results indicate that the 10-year expansion rate differs from the 1-year rate by approximately 1%, and under long-term ASR mitigation measures, the internal damage in the HPC is minimal, though the surface damage is more severe. As the equivalent alkali content increases, the compressive strength of the concrete cubes decreases, initially rising before falling by 5–15% over time. The HPC with only air-entraining agent added exhibited better mechanical performance than the HPC with both air-entraining and corrosion inhibitors added, with the poorest performance observed in the HPC with only a corrosion inhibitor. A relationship was established between the surface and internal damage variables, with the surface damage initially increasing rapidly before stabilizing as the internal damage rose. Numerical simulations effectively describe the damage behavior of HPC under static uniaxial compression. Comparisons with actual failure morphologies revealed that, in the cube compression tests, crack propagation directly penetrated both coarse and fine aggregates rather than circumventing them. The simulations closely matched the experimental outcomes, demonstrating their accuracy in modeling experiments. This study discusses the compressive mechanical properties of concrete under prolonged ASR through a combination of experimental and simulation approaches. It also delves into the impact of surface damage on the overall mechanical performance and failure modes of concrete. The findings provide experimental and simulation support for the concrete structures in regions with high alkali contents.

[This corrects the article DOI: 10.1371/journal.pone.0217185.].

Ethanamizuril (EZL) is a new anticoccidial drug developed by our Shanghai Veterinary Research Institute. Since EZL is almost insoluble in water, we conducted a study to improve the solubility of EZL by forming inclusion complexes with β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD). In this study, we performed molecular docking and then systematically compared the interactions of EZL with β-CD and HP-β-CD in both aqueous solution and the solid state, aiming to elucidate the solubilization effect and mechanism of cyclodextrins (CDs). The interactions were also examined in the solid state using DSC, PXRD, and FT-IR. The interactions of EZL with CDs in an aqueous solution were investigated using PSA, UV-vis spectroscopy, MS, 1H NMR, and 2D ROESY. The results of phase solubility experiments revealed that both β-CD and HP-β-CD formed inclusion complexes with EZL in a 1:1 molar ratio. Among them, HP-β-CD exhibited higher Kf (stability constant) and CE (complexation efficiency) values as well as a stronger solubilization effect. Furthermore, the two cyclodextrins were found to interact with EZL in a similar manner. The results of our FT-IR and 2D ROESY experiments are in agreement with the theoretical results derived from molecular simulations. These results indicated that intermolecular hydrogen bonds existing between the C=O group on the triazine ring of EZL and the O-H group of CDs, as well as the hydrophobic interactions between the hydrogen on the benzene ring of EZL and the hydrogen of CDs, played crucial roles in the formation of EZL/CD inclusion complexes. The results of this study can lay the foundation for the future development of high-concentration drinking water delivery formulations for EZL.

Intensive economic and human activities present challenges to the carbon storage capacity of terrestrial ecosystems, particularly in arid regions that are sensitive to climate change and ecologically fragile. Therefore, accurately estimating and simulating future changes in carbon stocks on the northern slope economic belt of Tianshan Mountains (NSEBTM) holds great significance for maintaining ecosystem stability, achieving high-quality development of the economic belt, and realizing the goal of “carbon neutrality” by 2050. This study examines the spatiotemporal evolution characteristics of the NSEBTM carbon stocks in arid regions from 1990 to 2050, utilizing a combination of multi-source data and integrating the Patch-generating Land use Simulation (PLUS) and Integrated Valuation of Ecosystem Services and Trade-offs (InVEST) models. Additionally, an attribution analysis of carbon stock changes is conducted by leveraging land use data. The findings demonstrate that (1) the NSEBTM predominantly consists of underutilized land, accounting for more than 60% of the total land area in the NSEBTM. Unused land, grassland, and water bodies exhibit a declining trend over time, while other forms of land use demonstrate an increasing trend. (2) Grassland serves as the primary reservoir for carbon storage in the NSEBTM, with grassland degradation being the leading cause of carbon loss amounting to 102.35 t over the past three decades. (3) Under the ecological conservation scenario for 2050 compared to the natural development scenario, there was a net increase in carbon storage by 12.34 t; however, under the economic development scenario compared to the natural development scenario, there was a decrease in carbon storage by 25.88 t. By quantitatively evaluating the land use change in the NSEBTM and its impact on carbon storage in the past and projected for the next 30 years, this paper provides scientific references and precise data support for the territorial and spatial decision making of the NSEBTM, thereby facilitating the achievement of “carbon neutrality” goals.

Salt stress is one of the major factors that limits rice production. Therefore, identification of salt-tolerant alleles from wild rice is important for rice breeding. In this study, we constructed a set of chromosome segment substitution lines (CSSLs) using wild rice as the donor parent and cultivated rice Nipponbare (Nip) as the recurrent parent. Salt tolerance germinability (STG) was evaluated, and its association with genotypes was determined using this CSSL population. We identified 17 QTLs related to STG. By integrating the transcriptome and genome data, four candidate genes were identified, including the previously reported AGO2 and WRKY53. Compared with Nip, wild rice AGO2 has a structure variation in its promoter region and the expression levels were upregulated under salt treatments; wild rice WRKY53 also has natural variation in its promoter region, and the expression levels were downregulated under salt treatments. Wild rice AGO2 and WRKY53 alleles have combined effects for improving salt tolerance at the germination stage. One CSSL line, CSSL118 that harbors these two alleles was selected. Compared with the background parent Nip, CSSL118 showed comprehensive salt tolerance and higher yield, with improved transcript levels of reactive oxygen species scavenging genes. Our results provided promising genes and germplasm resources for future rice salt tolerance breeding. [ABSTRACT FROM AUTHOR]

Background As aging process continues to accelerate in China, multimorbidity have become a major public problem that threatens the health of the entire population. In the current context of "Healthy China 2030", the health management of patients with multimorbidity needs to be urgently addressed. Objective To understand the preferences influencing the choice of community health services for patients with multimorbidity, explore the willingness to pay (WTP) of patients, so as to provide recommendations for improvements to the existing community health service system for chronic diseases. Methods Patients with multimorbidity were randomly selected from eight community health service centers in Chengdu during the period from May to August 2022 as survey subjects. General patient data and preferences related to discrete choice experiments were collected through on-site questionnaire surveys. Based on different types of comorbidities, patients with type 2 diabetes combined with hypertension, hypertension combined with coronary heart disease, type 2 diabetes combined with hypertension and coronary heart disease were categorized into ClassⅠ, ClassⅡ, and ClassⅢ. Regression analysis was conducted using mixed Logit model to analyze the preferences of multimorbidity patients for community health services, and to quantitatively analyze their WTP for community health services. Result A total of 360 questionnaires were distributed and 296 valid questionnaires were recovered, with a valid recovery rate of 82.7%. ClassⅠpatients (β=3.260, 95%CI=2.610 to 3.910), ClassⅡpatients (β=3.697, 95%CI=2.612 to 4.781), and ClassⅢpatients (β=3.220, 95%CI=2.271 to 4.169) expressed the strongest preference for services with high accessibility to drugs, followed by appointment referral services and traditional Chinese medicine (TCM) services. Regarding physician types and prescription service duration, both ClassⅠpatients (β=0.971, 95%CI=0.585 to 1.357) and ClassⅡpatients (β=0.686, 95%CI=0.176 to 1.197) preferred services with extended prescription services, while ClassⅢpatients (β=0.804, 95%CI=0.196 to 1.413) preferred services provided by general practitioners (β=0.804, 95%CI=0.196 to 1.413). ClassⅠpatients (β=-0.049, 95%CI=-0.057 to -0.041), ClassⅡpatients (β=-0.040, 95%CI=-0.051 to -0.029), and ClassⅢpatients (β=-0.037, 95%CI=-0.048 to -0.027) preferred services with lower out-of-pocket expenses. The results of the regression analysis of WTP for patients with different chronic comorbidity types showed that the WTP of all 3 types of patients was related to their level of preference for each attribute, with ClassⅠ, ClassⅡ, and ClassⅢpatients all had the highest WTP for a high level of drug accessibility, which were RMB 66.77/month, RMB 91.97/month, and RMB 85.95/month, respectively. Conclusion Patients with multimorbidity exhibit significant preferences for six attributes considered in this study (physician type, TCM service, prescription service duration, drug accessibility, appointment referral, and monthly out-of-pocket costs). Drug accessibility is the most important attribute influencing multimorbidity patients' health service preferences. It is recommended to target patients' specific needs accurately, improve appointment referral services, establish standards for the management of chronic diseases in the community, and accelerate the integration of TCM into the prevention and treatment of chronic diseases in the community.