Exploration of the causal associations between circulating inflammatory proteins, immune cells, and neuromyelitis optica spectrum disorder: a bidirectional Mendelian randomization study and mediation analysis.

Background: An increasing body of research has demonstrated a robust correlation between circulating inflammatory proteins and neuromyelitis optica spectrum disorders (NMOSD). However, whether this association is causal or whether immune cells act as mediators currently remains unclear. Methods: We employed bidirectional two-sample Mendelian randomization (TSMR) analysis to examine the potential causal association between circulating inflammatory proteins, immune cells, and NMOSD using data from genome-wide association studies (GWAS). Five different methods for Mendelian randomization analyses were applied, with the inverse variance-weighted (IVW) method being the primary approach. Sensitivity analyses were further performed to assess the presence of horizontal pleiotropy and heterogeneity in the results. Finally, a two-step Mendelian randomization (MR) design was employed to examine the potential mediating effects of immune cells. Results: A notable causal relationship was observed between three circulating inflammatory proteins (CSF-1, IL-24, and TNFRSF9) and genetically predicted NMOSD. Furthermore, two immune cell phenotypes, genetically predicted CD8 on naive CD8+ T cells, and Hematopoietic Stem Cell Absolute Count were negatively and positively associated with genetically predicted NMOSD, respectively, although they did not appear to function as mediators. Conclusion: Circulating inflammatory proteins and immune cells are causally associated with NMOSD. Immune cells do not appear to mediate the pathway linking circulating inflammatory proteins to NMOSD.

Design, Synthesis, Antifungal Activity, and Action Mechanism of Pyrazole-4-carboxamide Derivatives Containing Oxime Ether Active Fragment As Succinate Dehydrogenase Inhibitors.

The dearomatization at the hydrophobic tail of the boscalid was carried out to construct a series of novel pyrazole-4-carboxamide derivatives containing an oxime ether fragment. By using fungicide-likeness analyses and virtual screening, 24 target compounds with theoretical strong inhibitory effects against fungal succinate dehydrogenase (SDH) were designed and synthesized. Antifungal bioassays showed that the target compound E1 could selectively inhibit the in vitro growth of R. solani, with the EC50 value of 1.1 µg/mL that was superior to that of the agricultural fungicide boscalid (2.2 µg/mL). The observations by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) demonstrated that E1 could reduce mycelial density and significantly increase the mitochondrial number in mycelia cytoplasm, which was similar to the phenomenon treated with boscalid. Enzyme activity assay showed that the E1 had the significant inhibitory effect against the SDH from R. solani, with the IC50 value of 3.3 µM that was superior to that of boscalid (7.9 µM). The mode of action of the target compound E1 with SDH was further analyzed by molecular docking and molecular dynamics simulation studies. Among them, the number of hydrogen bonds was significantly more in the SDH-E1 complex than that in the SDH-boscalid complex. This research on the dearomatization strategy of the benzene ring for constructing pyrazole-4-carboxamides containing an oxime ether fragment provides a unique thought to design new antifungal drugs targeting SDH.

Design, synthesis and herbicidal activity of novel cyclohexanedione derivations containing pyrazole and pyridine groups as potential HPPD inhibitors.

4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27; HPPD) is one of the important target enzymes in the development of herbicides. To discover novel HPPD inhibitors with unique molecular, 39 cyclohexanedione derivations containing pyrazole and pyridine groups were designed and synthesized. The preliminary herbicidal activity test results showed that some compounds had obvious inhibitory effects on monocotyledon and dicotyledonous weeds. The herbicidal spectrums of the highly active compounds were further determined, and the compound G31 exhibited the best inhibitory rate over 90% against Plantago depressa Willd and Capsella bursa-pastoris at the dosages of 75.0 and 37.5 g ai/ha, which is comparable to the control herbicide mesotrione. Moreover, compound G31 showed excellent crop safety, with less than or equal to 10% injury rates to corn, sorghum, soybean and cotton at a dosage of 225 g ai/ha. Molecular docking and molecular dynamics simulation analysis revealed that the compound G31 could stably bind to Arabidopsis thaliana HPPD (AtHPPD). This study indicated that the compound G31 could be used as a lead molecular structure for the development of novel HPPD inhibitors, which provided an idea for the design of new herbicides with unique molecular scaffold.

Densification and Surface Carbon Transformation of Diamond Powders under High Pressure and High Temperature.

A new type of poly-diamond plate without a catalyst was produced via the high-pressure high-temperature (HPHT) compression of diamond powders. The densification of diamond powders and sp3 to sp2 carbon on the surface under HPHT compression was investigated through the characterization of the microstructure, Raman spectroscopy analysis and electrical resistance measurement. The densification and sp3-sp2 transformation on the surface are mainly affected by the pressure, temperature and particle size. The quantitative analysis of the diamond sp3 and sp2 carbon amount was performed through the peak fitting of Raman spectra. It was found that finer diamond particles under a higher temperature and a lower pressure tend to produce more sp2 carbon; otherwise, they produce less. In addition, it is interesting to note that the local residual stresses measured using Raman spectra increase with the diamond particle size. The suspected reason is that the increased particle size reduces the number of contact points, resulting in a higher localized pressure at each contact point. The hypothesis was supported by finite element calculation. This study provides detailed and quantitative data about the densification of diamond powders and sp3 to sp2 transformation on the surface under HPHT treatment, which is valuable for the sintering of polycrystalline diamonds (PCDs) and the HPHT treatment of diamonds.

Assessing tobacco-related ischemic stroke in Pakistan (1990-2019): Insights from the Global Burden of Disease Study.

INTRODUCTION: This study analyzes the impact of active smoking and secondhand smoke on the ischemic stroke burden of Pakistan, 1990-2019. METHODS: We used data from the Global Burden of Disease (GBD) database to conduct a comprehensive evaluation of ischemic stroke-related indicators in Pakistan, including the number of deaths, mortality rates, disability-adjusted life years (DALYs), DALY rates, and the estimated annual percentage change (EAPC). Joinpoint analysis was applied to assess sex-specific temporal trends in the burden of active smoking and secondhand smoke in Pakistan and regions of Pakistan. These assessments incorporated the Socio-Demographic Index (SDI) and we have made comparative analyses of epidemiological differences between active smoking and secondhand smoke exposure. RESULTS: The burden of ischemic stroke related to tobacco use is presented in terms of the age-standardized mortality rate (ASMR) and the age-standardized disability-adjusted life year rate (ASDR) per 100000 population. The results (ASMR/ASDR) for Pakistan were 6.04/130.81, in the middle SDI region 7.69/176.54, and low-middle SDI region 5.64/124.22. Pakistan's ASMR is higher than the global average of 5.85, while ASDR is lower than the global average of 140.23. From 1990 to 2019, a downward trend in both ASMR and ASDR was observed, indicating progress in controlling tobacco-related stroke burdens. Individuals aged ≥70 years experienced the highest rates of stroke (ASMR: 66.31; ASDR: 1091.20). Gender disparities were evident: men were more affected by active smoking (ASMR: 3.08; ASDR: 78.47) than women (ASMR: 0.79; ASDR: 20.76), while women faced a higher burden from secondhand smoke (ASMR: 0.66; ASDR: 16.33) compared to men (ASMR: 0.79; ASDR: 9.93). Regional differences within Pakistan show fluctuating death and DALY rates. Notably, an increasing trend in female ASDR due to secondhand smoke in the Khyber Pakhtunkhwa Region (annual percentage change, APC=0.17 from 2010 to 2019) calls for focused health interventions. CONCLUSIONS: The study finds ASMR for tobacco-related ischemic stroke in Pakistan exceeds global averages, with significant gender and age disparities in exposure to smoke, highlighting the need for targeted health interventions.

Genetic insights into the relationship between immune cell characteristics and ischemic stroke: A bidirectional Mendelian randomization study.

BACKGROUND AND PURPOSE: Ischemic stroke, a major contributor to global disability and mortality, is underpinned by intricate pathophysiological mechanisms, notably neuroinflammation and immune cell dynamics. Prior research has identified a nuanced and often paradoxical link between immune cell phenotypes and ischemic stroke susceptibility. The aim of this study was to elucidate the potential causal links between the median fluorescence intensity (MFI) and morphological parameters (MP) of 731 immune cell types and ischemic stroke risk. METHODS: By analyzing extensive genetic datasets, we conducted comprehensive Mendelian randomization (MR) analyses to discern the genetic correlations between diverse immune cell attributes (MFI and MP) and ischemic stroke risk. RESULTS: Our study identified key immune cell signatures linked to ischemic stroke risk. Both B cells and T cells, among other immune cell types, have a bidirectional influence on stroke risk. Notably, the regulatory T-cell phenotype demonstrates significant neuroprotective properties, with all odds ratio (OR) values and confidence intervals (CIs) being less than 1. Furthermore, CD39 phenotype immune cells, particularly CD39+ CD8+ T cells (inverse variance weighting [IVW] OR 0.92, 95% CI 0.87-0.97; p = 0.002) and CD39+ activated CD4 regulatory T cells (IVW OR 0.93, 95% CI 0.90-0.97; p < 0.001), show notable neuroprotection against ischemic stroke. CONCLUSION: This investigation provides new genetic insights into the interplay between various immune cells and ischemic stroke, underscoring the complex role of immune processes in stroke pathogenesis. These findings lay a foundation for future research, which may confirm and expand upon these links, potentially leading to innovative immune-targeted therapies for stroke prevention and management.

Influence of the brain­gut axis on neuroinflammation in cerebral ischemia­reperfusion injury (Review).

Stroke, a debilitating cerebrovascular ailment, poses significant threats to human life and health. The intricate interplay between the gut­brain­microbiota axis (GBMA) and cerebral ischemia­reperfusion has increasingly become a focal point of scientific exploration, emerging as a pivotal research avenue in stroke pathophysiology. In the present review, the authors delved into the nexus between the GBMA and neuroinflammation observed post­stroke. The analysis underscored the pivotal roles of histone deacetylase 3 and neutrophil extracellular traps subsequent to stroke incidents. The influence of gut microbial compositions and their metabolites, notably short­chain fatty acids and trimethylamine N­oxide, on neuroinflammatory processes, was further elucidated. The involvement of immune cells, especially regulatory T­cells, and the intricate signaling cascades including cyclic GMP­AMP synthase/stimulator of interferon genes/Toll­like receptor, further emphasized the complex regulatory mechanisms of GBMA in cerebral ischemia/reperfusion injury (CI/RI). Collectively, the present review offered a comprehensive perspective on the metabolic, immune and inflammatory modulations orchestrated by GBMA, augmenting the understanding of its role in neuroinflammation following CI/RI.

Exploring causal correlations between systemic inflammatory cytokines and epilepsy: A bidirectional Mendelian randomization study.

BACKGROUND: Inflammation plays a role in the development and advancement of epilepsy, but the relationship between inflammatory cytokines and epilepsy is still not well understood. Herein, we use two-sample Mendelian randomization (MR) to examine the causal association between systemic inflammatory cytokines and epilepsy. METHODS: We conducted a bidirectional two-sample MR analysis based on genome-wide association study data of 41 serum cytokines from 8293 Finnish individuals with various epilepsy subtypes from the International League against Epilepsy Consortium. RESULTS: Our study showed that three inflammatory cytokines were associated with epilepsy, five were associated with generalized epilepsy, four were associated with focal epilepsy, one was associated with focal epilepsy-documented lesion negative, three were associated with juvenile absence epilepsy, one was associated with childhood absence epilepsy, two were associated with focal epilepsy-documented lesion other than hippocampal sclerosis, and two were associated with juvenile myoclonic epilepsy. Furthermore, the expression of systemic inflammatory cytokines was unaffected by genetically predicted epilepsy. CONCLUSION: This study suggested that several inflammatory cytokines are probably the factors correlated with epilepsy. Additional research is required to ascertain if these biomarkers have therapeutic potential to prevent or manage epilepsy.

A Bio-Inspired Free-Standing Film with Versatility: From Heterogeneous CTCs Programed Isolating to Breast Cancer Molecular Typing.

Developing a robust strategy for profiling heterogeneous circular tumor cells specifically, distinguishing the phenotypes of which in blood sample of cancer patient precisely, and releasing them sequentially, is significant for cancer management by liquid biopsy. Herein, a bio-inspired free-standing and flexible film composed of TiO2 nanotube and silk fibroin, fabricated with multiply dynamic bioactive surface (TSF/MDBS) by a simple and eco-friendly way including using polydopamine chemistry and dual dynamic covalent chemistry, is reported. The as-prepared TSF/MDBS binds specific peptides toward cells with epithelial biomarker and human epithelial growth factor receptor 2 (HER2) biomarker, and antifouling agents bovine serum albumin for obviating platelets and proteins adhering of blood, can capture heterogeneous CTCs with enhanced capability due to the cytocompatible soft film and exquisite surface design, and further release the captured cells as program, by specifically breaking down the covalent bonds in sequence via the action of adding biocompatible molecules fructose and glutathione. By applying the TSF/MDBS, it can be tailored into desired pieces for identifying CTCs with different phenotypes (HER2-high and HER2-low) from the unprocessed blood samples of breast cancer patients, and finally profiling these heterogeneous CTCs, to discriminate HER2 positive or negative of breast cancer patients in clinical applications.

Inflammatory cytokines and stroke and its subtypes: a genetic correlation and two-sample Mendelian randomization study.

Introduction: The causal relationship between inflammatory factors and stroke subtypes remains unclear. This study aimed to analyze the causal relationship between 41 inflammatory factors and these two factors using Mendelian randomization (MR). Methods: We performed a two-sample MR analysis to assess the causal effects of 41 inflammatory cytokines on stroke and its subtypes and conducted a genome-wide association study (GWAS) data. The inverse-variance weighted (IVW) method was adopted as the main MR method, and we performed a series of two-sample Mendelian randomizations and related sensitivity analyses. Results: The study indicated some suggestive evidences: using the IVW approach, we found that lower possible levels of IL-4 were positively associated with the occurrence of stroke (odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.88-0.99, p = 0.014), higher interleukin (IL)-1ß, IL-12p70 levels may be positively correlated with the occurrence of stroke (OR = 1.09, 95% CI: 1.01-1.18, p = 0.027; OR = 1.08, 95% CI: 1.02-1.15, p = 0.015). For IS, results showed that lower levels of IL-4, tumor necrosis factor-related apoptosis-inducing ligand were positively associated with the occurrence of possible ischemic stroke (IS) (OR = 0.92, 95% CI: 0.87-0.98, p = 0.006; OR = 0.95, 95% CI: 0.91-1.00, p = 0.031), higher levels of IL-1ß, IL-12p70 and vascular endothelial growth factor (VEGF) may be positively correlated with the occurrence of IS (OR = 1.09, 95% CI: 1.00-1.19, p = 0.042; OR = 1.07, 95% CI: 1.01-1.15, p = 0.035; OR = 1.06, 95% CI: 1.00-1.12, p = 0.034). Our findings suggest that decreased IL-17 levels could potentially be linked to a higher likelihood of intracerebral hemorrhage (ICH) (OR = 0.51, 95% CI: 0.28-0.93, p = 0.028). For subtypes of stroke, IS and ICH, higher levels of growth regulated oncogene-α, beta nerve growth factor, IL-18, macrophage colony-stimulating factor, and induced protein 10 upregulated the risk factors while lower levels of IL-2ra and IL-17 upregulated the risk factors. Conclusion: In summary, our research validated that inflammatory markers have a pivotal impact on the development of stroke and could potentially offer a fresh approach to treating this condition.

A Chinese patient with POLR3A-related leukodystrophy: a case report and literature review.

Background: Leukodystrophies are hereditary white matter diseases characterized by genetic polymorphisms and considerable phenotypic variability. They can be classified into myelin and non-myelin malformations. These diseases are rare, affecting 1 out of 250,000-500,000 individuals and can manifest at any age. A subtype of leukodystrophy, associated with missense mutations in the RNA polymerase subunit III (POLR3A) gene, is inherited in an autosomal recessive manner. Case report: We report and analyse a case of a 34-year-old female who presented with ataxia. Magnetic Resonance Imaging (MRI) of the brain revealed demyelinating lesions in the white matter. Genetic testing identified the c.4044C > G and c.1186-2A > G variants in the POLR3A gene. The patient was diagnosed with hypomyelinating leukodystrophy type 7 and received neurotrophic and symptomatic supportive therapy. However, after 1 month of follow-up, there was no improvement in her symptoms. Conclusion: POLR3A-induced leukodystrophy is relatively rare and not well understood, making it challenging to diagnose and easy to overlook. The prognosis for this disease is generally poor, significantly impacting the quality of life of affected individuals. Currently, no cure is available for this condition, and treatment is limited to managing symptoms. Further research into new treatment methods for POLR3A-induced leukodystrophy is imperative to improve the quality of life and potentially extend the life expectancy of patients.

[The value of non-invasive prenatal testing for the identification of numerical and structural chromosomal abnormalities and copy number variations in the fetuses].

OBJECTIVE: To assess the value of non-invasive prenatal testing (NIPT) for the identification of numerical and structural chromosomal abnormalities and copy number variations (CNVs) in fetuses. METHODS: 46 197 pregnant women undergoing NIPT at the Prenatal Diagnosis Center of Chenzhou First People's Hospital from January 2018 to December 2021 were selected as the study subjects. Positive cases were subjected to chromosomal karyotyping and copy number variation sequencing (CNV-seq) following amniocentesis. RESULTS: Nearly 50% of common chromosomal aneuploidies were found in the elder pregnant women. Among these, sex chromosome aneuploidies were mainly found in pregnant women with advanced age as well as borderline risks by serological screening. Rare autosomal aneuploidies and CNVs were mainly found in those with borderline or high risks by serological screening. The positive predictive values (PPV) for fetal chromosomal abnormalities indicated by NIPT were as follows: T21 (92.37%, 109/118), T18 (53.85%, 14/26), sex chromosome aneuploidies (45.04%, 59/131), T13 (34.62%, 9/26), CNVs (29.17%, 14/48), and rare autosomal aneuploidies (2.60%, 2/77). CONCLUSION: NIPT has a high detection rate for T21, T18, T13 and sex chromosome aneuploidies. It can also detect rare autosomal aneuploidies and CNVs, including some rare structural abnormalities, though verification is required by analyzing amniotic fluid samples.

High-intensity focused ultrasound versus transarterial chemoembolization for hepatocellular carcinoma: a meta-analysis.

PURPOSE: The application of high-intensity focused ultrasound (HIFU) in hepatocellular carcinoma (HCC) was promising. However, whether the effect of HIFU is comparable with that of transarterial chemoembolization (TACE) has not been determined. MATERIALS AND METHODS: PubMed, Embase, Cochrane Library, Web of Science, WanFang Data, CqVip, CNKI, and CBM databases were searched for randomized controlled trials (RCTs), cohort studies, and case-control studies. The methodological quality of each study was evaluated. When there is no statistical heterogeneity, the fixed effect model would be used to merge data. Otherwise, the random effect model would be utilized. Sensitivity analyses were conducted by excluding one study each time. Subgroup analyses were conducted based on age, sex, tumor number, relative number of the patients with Child-Pugh C grade in each group, the percentage of patients with Child-Pugh C grade in the whole study, and tumor load. Publication bias was evaluated by Egger's test and Begg's test. RESULTS: Six cohort studies including 188 patients from HIFU group and 224 patients from TACE group were obtained for further analysis. The meta-analysis suggested HIFU and TACE showed no differences in postoperative 1-year overall survival (OS) rate, tumor response (including complete response, partial response, stable disease, and progressive disease), and postoperative complications. Moreover, compared with TACE, HIFU showed higher postoperative 6-month and 2-year OS rates. Subgroup analyses, meta regression analysis and sensitivity analyses indicated the findings above were reliable. Additionally, no potential publication bias was detected. CONCLUSION: For HCC, when compared with TACE, HIFU might show comparable safety but better effect. Considering the limitations of current studies, more well-designed studies are needed to validate our conclusion.

Activatable Mn2+-Armed nanoagonist augments antitumor immunity in colorectal cancer: A NIR-II Photonic neoadjuvant paradigm.

Postoperative recurrence frequently occurs in patients with colorectal cancer (CRC) due to residual microtumors and host cellular immune dysfunction, leading to major setbacks in clinical outcomes and CRC staging. As an increasingly prevalent therapeutic option for CRC patients, neoadjuvant chemoradiotherapy bears unmet challenges of limited tumor targeting and common side effects of gastrointestinal reaction and radiodermatitis. It is highly desirable to develop neoadjuvant treatment paradigms that impart both tumor-targeting accuracy and protection against recurrence of resectable CRC. Here we report a versatile photo-regulated nanoagonist of plasmonic gold blackbody (AuPB) with a polydopamine (PDA) coating carrying manganese ion (Mn2+) payloads (AuPB@PDA/Mn). When armed with second near-infrared (NIR-II) light, AuPB@PDA/Mn with broad-band localized surface plasmon resonance generates local hyperthermia and discharges Mn2+ ions, which evidently amplify the effects of immunogenic cell death in tumor cells and activate the cyclic GMP-AMP synthase/stimulator of interferon genes pathway in dendritic cells (DCs), hence potentiating the maturation of DC and the secretion of type I interferon in a synergistic way. Matured DCs undertake the task of tumor antigen presentation as the crosstalk to adaptive immunity. As such, the administration of AuPB@PDA/Mn coupled with NIR-II laser irradiation has eminently augmented the infiltration of CD8+ T cells as well as the development of memory CD8+ T cells in colorectal tumor models, substantiating enhanced immunomodulatory efficacy against primary and recurrent CRC. Our strategy highlights the potency of an integrated NIR-II photothermal and immunoregulatory modality by photo-activate delivery of Mn2+ ions, as a neoadjuvant paradigm for presurgical tumor debulking and against postoperative tumor recurrence.

Silk fibroin-based piezoelectric nanofibrous scaffolds for rapid wound healing.

Piezoelectric polymer nanofibers are attracting increasing attention in the stimulation of cell growth and proliferation in tissue engineering and wound healing applications. However, their intrinsic non-biodegradability in vivo hinders widespread applications in the biological fields. Herein, we designed, synthesized and characterized composite materials of silk fibroin (SF)/LiNbO3 (LN) nanoparticles/MWCNTs by electrospinning technology, which displayed good biocompatibility and comparable piezoelectric properties with an output current of up to 15 nA and output voltage of up to 0.6 V under pressure stimulation, remaining stable after 200 cycles of pressure release without significant decay. Meanwhile, the mechanical properties of the LN/CNTs/SF-nanofiber scaffolds (SF-NFSs) are also enhanced, with a tensile strength reaching 12.84 MPa and an elongation at break reaching 80.07%. Importantly, in vitro cell proliferation experiments showed that the LN/CNTs/SF-NFSs promoted cell proliferation at a rate of 43%. Accordingly, the mouse wound healing experiments further indicated that they could accelerate the healing of skin wounds in mice that were continuously moving. Therefore, SF-based piezoelectric nanofibrous scaffolds exhibit potential for use in rapid wound healing and this sheds light on smart treatment for tissue engineering in biomedicine.

MS2-MBP-Based Affinity Purification of Nucleus- or Cytoplasm-Localized lncRNA-Protein Complexes Formed In Vivo.

With recent emergence of huge number of long noncoding RNAs (lncRNAs), purification of lncRNA-protein (lncRNP) complexes is fundamental to understand the role of lncRNA and its biological function. However, lncRNP purification is still a daunting challenge. Here we describe a protocol to purify lncRNP formed in vivo with MS2-MBP-based affinity purification. Inducible lncRNA tagged with MS2 RNA hairpins is introduced into cells of interest, and RNP on tagged lncRNA is formed in vivo. MS2-MBP fusion protein is expressed in Escherichia coli and purified with amylose resin and HiTrap heparin column. The MS2 part of MS2-MBP fusion protein binds to the hairpins, and MBP part binds to amylose resin. We also describe a protocol to separate the nucleus and the cytoplasm so that lncRNP localized in the nucleus or cytoplasm can be individually purified. The amount of lncRNP purified is well sufficient for mass spectrometry analysis.

Festuca coelestis Increases Drought Tolerance and Nitrogen Use via Nutrient Supply-Demand Relationship on the Qinghai-Tibet Plateau.

Drought and nutrient deficiency pose great challenges to the successful establishment of native plants on the Qinghai-Tibet Plateau. The dominant factors and strategies that affect the adaptation of alpine herbs to dry and nutrient-deficient environments remain unclear. Three water gradients were established using two-factor controlled experiments: low water (WL), medium water (WM), and high water (WH). The field water-holding capacities were 35%, 55%, and 75%, respectively. Nitrogen fertilizer (N) was applied at four levels: control (CK), low (FL), medium (FM), and high (FH) at 0, 110, 330, and 540 mg/kg, respectively. The results revealed that N was the main limiting factor, rather than phosphorous (P), in Festuca coelestis under drought stress. Under water shortage conditions, F. coelestis accumulated more proline and non-structural carbohydrates, especially in the aboveground parts of the leaves and stems; however, the root diameter and aboveground nitrogen use efficiency were reduced. Appropriate N addition could mitigate the adverse effects by increasing the release of N, P, and enzyme activity in the bulk soil and rhizosphere to balance their ratio, and was mainly transferred to the aboveground parts, which optimized the supply uptake relationship. The effects of water and fertilizer on the physiological adaptability and nutrient utilization of F. coelestis were verified using structural equation modeling. Based on their different sensitivities to water and nitrogen, the WHFM treatment was more suitable for F. coelestis establishment. Our results demonstrated that the disproportionate nutrient supply ability and preferential supply aboveground compared to below ground were the main factors influencing F. coelestis seedling establishment under drought conditions. This study provides evidence for a better understanding of herbaceous plants living in high mountain regions and offers important information for reducing the risk of ecological restoration failure in similar alpine regions.

Genome-wide association analysis of Fusarium crown rot resistance in Chinese wheat landraces.

KEY MESSAGE: A novel locus for Fusarium crown rot (FCR) resistance was identified on chromosome 1B at 641.36-645.13 Mb using GWAS and could averagely increase 39.66% of FCR resistance in a biparental population. Fusarium crown rot can cause considerable yield losses. Developing and growing resistance cultivars is one of the most effective approaches for controlling this disease. In this study, 361 Chinese wheat landraces were evaluated for FCR resistance, and 27 with the disease index lower than 30.00 showed potential in wheat breeding programs. Using a genome-wide association study approach, putative quantitative trait loci (QTL) for FCR resistance was identified. A total of 21 putative loci on chromosomes 1A, 1B, 2B, 2D, 3B, 3D, 4B, 5A, 5B, 7A, and 7B were significantly associated with FCR resistance. Among these, a major locus Qfcr.sicau.1B-4 was consistently identified among all the trials on chromosome 1B with the physical regions from 641.36 to 645.13 Mb. A polymorphism kompetitive allele-specific polymerase (KASP) marker was developed and used to validate its effect in an F2:3 population consisting of 136 lines. The results showed the presence of this resistance allele could explain up to 39.66% of phenotypic variance compared to its counterparts. In addition, quantitative real-time polymerase chain reaction showed that two candidate genes of Qfcr.sicau.1B-4 were differently expressed after inoculation. Our study provided useful information for improving FCR resistance in wheat.

The Intrinsic Relation between the Hydrogel Structure and In Vivo Performance of Hyaluronic Acid Dermal Fillers: A Comparative Study of Four Typical Dermal Fillers.

BACKGROUND: Hyaluronic acid dermal fillers are composed of cross-linked viscoelastic particles with high biocompatibility. The performance of the fillers is determined by the viscoelastic properties of particles and the connecting force between particles. However, the relationships among the properties of fillers, the interaction of the gels and the surrounding tissue are not clear enough. METHOD: Four kinds of typical dermal filler were selected in this research to reveal the interaction between the gels and cells. A series of analytical tools was applied to characterize the structure and physicochemical properties of the gel, as well as observing their interaction with the surrounding tissues in vivo and discussing their internal mechanism. RESULT: The large particles internal the gel and the high rheological properties endow the Restylane2 with excellent support. However, these large-size particles have a significant impact on the metabolism of the local tissue surrounding the gel. Juvéderm3 present gel integrity with the high cohesiveness and superior support. The rational matching of large and small particles provides the Juvéderm3 with supporting capacity and excellent biological performance. Ifresh is characterized by small-size particles, moderate cohesiveness, good integrity, lower viscoelasticity and the superior cellular activity located the surrounding tissues. Cryohyaluron has high cohesion and medium particle size and it is prominent in cell behaviors involving localized tissues. Specific macroporous structure in the gel may facilitate the nutrients delivering and removing the waste. CONCLUSION: It's necessary to make the filler both sufficient support and biocompatibility through the rational matching of particle sizes and rheological properties. Gels with macroporous structured particle showed an advantage in this area by providing a space inside the particle.

A hydrogel dressing with tunable critical temperature and photothermal modulating melittin release for multiply antibacterial treatment.

It is imperative to develop an antibiotic-free and long-term effective strategy for treating chronic wound infections due to the long-term utilization of antibiotics easily causing drug resistance. Herein, we fabricated a novel poly-N-isopropylacrylamide (PNIPAM)/polyacrylamide (PAM) coupling thermosensitive hydrogel integrating 1D lysozyme nanofiber doped with CuS nanoparticles (CuS/PP) and loading antibacterial peptide melittin (M) (CuS/PP-M) for combating chronic wound infection via photothermal modulating the release of melittin. For the CuS/PP-M hydrogel, the copolymerization of PNIPAM and PAM allows the lower critical solution temperature (LCST) higher than the body temperature, effectively hindering the spontaneous release of melittin when contacts the infected wound, while the integration of LNF/CuS nanofibers provides a stable photothermal treatment for triggering the release of melittin. As a result, the CuS/PP-M hydrogel exhibits synergistically enhanced effect on killing both Gram-positive and Gram-negative bacteria, which maintains more than 99 % bactericidal efficiency, even displays a long-term and multiply antibacterial performance by photothermal modulating melittin release. Moreover, the CuS/PP-M hydrogel presents both high antibacterial activity and excellent wound healing performance in the mouse wound model, thereby benefiting the chronic wound healing.