Distribution characteristics and prognosis of tumor-infiltrating lymphocytes in the brain metastases of small cell lung cancer: a retrospective cohort study.

Background: The efficacy of immunotherapy for brain metastases from small cell lung cancer (SCLC) is relatively low, and the tumor microenvironment of SCLC brain metastases is still unknown. Therefore, we investigated the distribution of tumor-infiltrating lymphocytes (TILs) and the expression of programmed cell death-ligand 1 (PD-L1) in patients with brain metastases from SCLC to explore the tumor microenvironment of SCLC brain metastases. Methods: A retrospective analysis was performed on 12 surgical specimens of brain metastases from patients with SCLC treated in the Department of Neurosurgery of The First Affiliated Hospital of Anhui Medical University from June 2017 to June 2022. The inclusion criteria for this study were the following: (I) a pathologically confirmed diagnosis of SCLC brain metastases; (II) surgical resection of brain metastases; (III) age >18 years; (IV) and complete clinical data. Patient-related data were retrieved from the inpatient medical record system, telephone follow-up of patients date of death, and overall survival (OS). The immunofluorescence-based tissue microenvironment analysis panel (MAP) was utilized for the detection of TILs, including CD3, CD8, programmed cell death 1 (PD-1), and PD-L1, in formalin-fixed and paraffin-embedded archival specimens of brain metastases. The expression levels of PD-L1 in tumor cells were detected by immunohistochemistry. The correlation between the OS and the above-mentioned markers was analyzed in the 12 patients. Results: Twelve patients were included in the study. The patients' ages ranged from 51-78 years with a median of 68 years, with 1 female and 11 males. Among 12 patients with SCLC brain metastases: positive rates of CD3+ TILs in the tumor parenchyma vs. tumor stroma were 0.60%±0.94% vs. 1.76%±2.72% (P=0.01), respectively; positive rates of CD8+ TILs in the tumor parenchyma vs. tumor stroma were 0.80%±0.78% vs. 2.46%±3.72% (P=0.02), respectively. There was no co-expression of CD8+ and PD-1+ TILs in the tumor parenchyma of 11 cases, and the infiltration density of coexpressed CD3+ and PD-1+ TILs was more than 10/mm2 in only 1 case. There was no coexpression of CD3+ and PD-1+ TIL in the stroma of 10 cases, and the infiltration density of CD8+ and PD-1+ TILs was more than 10/mm2 in 2 cases. Immunohistochemistry was used to detect the expression of PD-L1 in 12 cases of SCLC metastatic lesions, and 3 cases (25%) were positive. Survival analysis showed that patients with positive intraepithelial CD3+ TILs had significantly longer OS [hazard ratio 3.383, 95% confidence interval (CI): 0.959-11.940; P=0.04]. Conclusions: Our study further demonstrated the immune microenvironment of SCLC brain metastases. The distribution of TILs in SCLC brain metastases is low and mainly distributed in the stroma, with the expression of PD-L1 in these tumor tissues being low. Further exploration of the immune microenvironment of SCLC brain metastases is of great significance for potential treatment.

Copper-based carbon dots modified hydrogel with osteoimmunomodulatory and osteogenesis for bone regeneration.

Biomaterials with dual functions of osteoimmunomodulation and bone repair are very promising in the field of orthopedic materials. For this purpose, we prepared copper-based carbon dots (CuCDs) and doped them into oxychondroitin sulfate/poly-acrylamide hydrogel (OPAM) to obtain a hybrid hydrogel (CuCDs/OPAM). We evaluated its osteoimmunomodulatory and bone repair properties in vitro and in vivo. The obtained CuCDs/OPAM exhibited good rBMSCs-cytocompatibility and anti-inflammatory properties in vitro. It also could effectively promote rBMSCs differentiation and the expression of osteogenic differentiation factors from rBMSCs under an inflammatory environment. Moreover, CuCDs/OPAM could induce macrophage phenotype switching (from M1-type macrophages to M2-type macrophages) in vivo, which is beneficial for anti-inflammatory action and presents good osteoimmunomodulation capability to induce a bone immune microenvironment to promote the differentiation of rBMSCs. In conclusion, CuCDs/OPAM hydrogel has dual functions of osteoimmunomodulatory and bone repair and is a promising bone filling and repair material.

Efficacy and safety of anti-programmed cell death protein 1 antibody combination therapy in patients with advanced experienced epidermal growth factor receptor-tyrosine kinase inhibitor-resistant lung adenocarcinoma: a retrospective cohort study.

Background: The effectiveness of combining anti-programmed cell death protein 1 (PD-1) and chemotherapy has been evaluated as superior to that of chemotherapy alone in the patients with advanced epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-resistant non-small cell lung cancer (NSCLC). In this study the efficacy and safety of anti-PD-1 combination therapy were evaluated retrospectively in patients who experienced EGFR-TKI-resistant with advanced lung adenocarcinoma (LUAD), with the goal of providing helpful guidance for clinical application. Methods: The clinical results of patients with incurable LUAD who received anti-PD-1 antibody combined with or without anti-angiogenic or chemotherapy after EGFR-TKI therapy failure were collected. The efficacy was calculated based on the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). The efficacy of the regimes was compared according to treatment groups and programmed cell death ligand 1 (PD-L1) expression. Results: The final analysis included a total of 43 patients with advanced EGFR-mutant LUAD. The overall cohort had an ORR of 23.3%, median PFS (mPFS) of 6.5 months, and median OS (mOS) of 10.6 months. No notable distinction was observed in mPFS and mOS among patients receiving three types of anti-PD-1 antibody combination therapies. Patients with positive PD-L1 expression showed a longer mPFS compared to patients with negative PD-L1 expression. No statistical difference was detected in terms of mPFS between the use of immune combination chemotherapy and immune combination anti-angiogenic therapy in the PD-L1 positive subgroup, and PFS was prolonged regardless of the PD-L1 expression status being positive or negative in the population receiving immune combination chemotherapy. Treatment-related adverse events (TRAEs) of grade 3 or higher were observed in 16.3% of patients, including chemotherapy-containing immunotherapy. No deaths resulting from immune-related adverse events (irAEs) were reported, and only 1 patient receiving immunotherapy plus chemotherapy had to discontinue treatment due to irAEs. Conclusions: Combination immunotherapy is feasible in post-TKI resistant individuals with LUAD harboring EGFR mutations. Immune combination chemotherapy and immune combination anti-angiogenic therapy have equivalent efficacy in the PD-L1 positive population. PD-L1 expression can be used as a reference for screening candidates for combination immunotherapy.

A Molecular Dynamics Study on the Dislocation-Precipitate Interaction in a Nickel Based Superalloy during the Tensile Deformation.

In the present paper, the dislocation-precipitate interaction in the Inconel 718 superalloy is studied by means of molecular dynamics simulation. The atomistic model composed of the ellipsoidal Ni3Nb precipitate (γ″ phase) and the Ni matrix is constructed, and tensile tests on the composite Ni3Nb@Ni system along different loading directions are simulated. The dislocation propagation behaviors in the precipitate interior and at the surface of the precipitate are characterized. The results indicate that the dislocation shearing and bypassing simultaneously occur during plastic deformation. The contact position of the dislocation on the surface of the precipitate could affect the penetration depth of the dislocation. The maximum obstacle size, allowing for the dislocation shearing on the slip planes, is found to be close to 20 nm. The investigation of anisotropic plastic deformation behavior shows that the composite system under the loading direction along the major axis of the precipitate experiences stronger shear strain localizations than that with the loading direction along the minor axis of the precipitate. The precipitate size effect is quantified, indicating that the larger the precipitate, the lower the elastic limit of the flow stress of the composite system. The dislocation accumulations in the precipitate are also examined with the dislocation densities given on specific slip systems. These findings provide atomistic insights into the mechanical behavior of nickel-based superalloys with nano-precipitates.

The crescent-like Golgi ribbon is shaped by the Ajuba/PRMT5/Aurora-A complex-modified HURP.

BACKGROUND: Golgi apparatus (GA) is assembled as a crescent-like ribbon in mammalian cells under immunofluorescence microscope without knowing the shaping mechanisms. It is estimated that roughly 1/5 of the genes encoding kinases or phosphatases in human genome participate in the assembly of Golgi ribbon, reflecting protein modifications play major roles in building Golgi ribbon. METHODS: To explore how Golgi ribbon is shaped as a crescent-like structure under the guidance of protein modifications, we identified a protein complex containing the scaffold proteins Ajuba, two known GA regulators including the protein kinase Aurora-A and the protein arginine methyltransferase PRMT5, and the common substrate of Aurora-A and PRMT5, HURP. Mutual modifications and activation of PRMT5 and Aurora-A in the complex leads to methylation and in turn phosphorylation of HURP, thereby producing HURP p725. The HURP p725 localizes to GA vicinity and its distribution pattern looks like GA morphology. Correlation study of the HURP p725 statuses and GA structure, site-directed mutagenesis and knockdown-rescue experiments were employed to identify the modified HURP as a key regulator assembling GA as a crescent ribbon. RESULTS: The cells containing no or extended distribution of HURP p725 have dispersed GA membranes or longer GA. Knockdown of HURP fragmentized GA and HURP wild type could, while its phosphorylation deficiency mutant 725A could not, restore crescent Golgi ribbon in HURP depleted cells, collectively indicating a crescent GA-constructing activity of HURP p725. HURP p725 is transported, by GA membrane-associated ARF1, Dynein and its cargo adaptor Golgin-160, to cell center where HURP p725 forms crescent fibers, binds and stabilizes Golgi assembly factors (GAFs) including TRIP11, GRASP65 and GM130, thereby dictating the formation of crescent Golgi ribbon at nuclear periphery. CONCLUSIONS: The Ajuba/PRMT5/Aurora-A complex integrates the signals of protein methylation and phosphorylation to HURP, and the HURP p725 organizes GA by stabilizing and recruiting GAFs to its crescent-like structure, therefore shaping GA as a crescent ribbon. Therefore, the HURP p725 fiber serves a template to construct GA according to its shape. Video Abstract.

Research on essential performance of oxidized chitosan-crosslinked acellular porcine aorta modified with bioactive SCPP/DOPA for esophageal scaffold with enhanced mechanical strength, biocompatibility and anti-inflammatory.

Acellular porcine aorta (APA) is an excellent candidate for an implanted scaffold but needs to be modified with appropriate cross-linking agent to increase its mechanical property and storage time in vitro as well as to give itself some bioactivities and eliminate its antigenicity for acting as a novel esophageal prosthesis. In this paper, a polysaccharide crosslinker (oxidized chitosan, OCS) was prepared by oxidizing chitosan using NaIO4 and further used to fix APA to prepare a novel esophageal prosthesis (scaffold). And then the surface modification with dopamine (DOPA) and strontium-doped calcium polyphosphate (SCPP) were performed one after another to prepare DOPA/OCS-APA and SCPP-DOPA/OCS-APA to improve the biocompatibility and inhibit inflammation of the scaffolds. The results showed that the OCS with a feeding ratio of 1.5:1.0 and a reaction time of 24 h had a suitable molecular weight and oxidation degree, almost no cytotoxicity and good cross-linking effect. Compared with glutaraldehyde (GA) and genipin (GP), OCS-fixed APA could provide a more suitable microenvironment for cell proliferation. The vital cross-linking characteristics and cytocompatibility of SCPP-DOPA/OCS-APA were evaluated. Results suggested that SCPP-DOPA/OCS-APA exhibited suitable mechanical properties, excellent resistance to enzymatic degradation/acid degradation, suitable hydrophilicity, and the ability to promote the proliferation of Human normal esophageal epithelial cells (HEECs) and inhibit inflammation in vitro. In vivo tests also confirmed that SCPP-DOPA/OCS-APA could diminish the immunological response to samples and had a positive impact on bioactivity and anti-inflammatory. In conclusion, SCPP-DOPA/OCS-APA could act as an effective, bioactive artificial esophageal scaffold and be expected to be used for clinical in the future.

Effects of histone methylation modification on low temperature seed germination and growth of maize.

Low temperature is a limiting factor of seed germination and plant growth. Although there is a lot information on the response of maize to low temperatures, there is still poorly description of how histone methylation affects maize germination and growth development at low temperatures. In this study, the germination rate and physiological indexes of wild-type maize inbred lines B73 (WT), SDG102 silencing lines (AS), SDG102 overexpressed lines (OE) at germination stage and seedling stage were measured under low temperature stress (4 â„ƒ), and transcriptome sequencing was applied to analyze the differences of gene expression in panicle leaves among different materials. The results showed that the germination rate of WT and OE maize seeds at 4 â„ƒ was significantly lower than 25 â„ƒ. The content of MDA, SOD and POD of 4 â„ƒ seeding leaves higher than contrast. Transcriptome sequencing results showed that there were 409 different expression genes (DEGs) between WT and AS, and the DEGs were mainly up-regulated expression in starch and sucrose metabolism and phenylpropanoid biosynthesis. There were 887 DEGs between WT and OE, which were mainly up-regulated in the pathways of plant hormone signal transduction, porphyrin and chlorophyll metabolism. This result could provide a theoretical basis for analyzing the growth and development of maize from the perspective of histone methylation modification.

Dialdehyde xanthan gum and curcumin synergistically crosslinked bioprosthetic valve leaflets with anti-thrombotic, anti-inflammatory and anti-calcification properties.

Currently commercial glutaraldehyde (GA)-crosslinked bioprosthetic valve leaflets (BVLs) suffer from thromboembolic complications, calcification, and limited durability, which are the major stumbling block to wider clinical application of BVLs. Thus, developing new-style BVLs will be an urgent need to enhance the durability of BVLs and alleviate thromboembolic complications. In this study, a quick and effective collaborative strategy of the double crosslinking agents (oxidized polysaccharide and natural active crosslinking agent) was reported to realize enhanced mechanical, and structural stability, excellent hemocompatibility and anti-calcification properties of BVLs. Dialdehyde xanthan gum (AXG) exhibiting excellent stability to heat, acid-base, salt, and enzymatic hydrolysis was first introduced to crosslink decellularized porcine pericardium (D-PP) and then curcumin with good properties of anti-inflammatory, anti-coagulation, anti-liver fibrosis, and anti-atherosclerosis was used to synergistically crosslink and multi-functionalize D-PP to obtain AXG + Cur-PP. A comprehensive evaluation of structural characterization, hemocompatibility, endothelialization potential, mechanical properties and component stability showed that AXG + Cur-PP exhibited better anti-thrombotic properties and endothelialization potential, milder immune responses, excellent anti-calcification properties and enhanced mechanical properties compared with GA-crosslinked PP. Overall, this cooperative crosslinking strategy provides a novel solution to achieve BVLs with enhanced mechanical properties and excellent anti-coagulation, anti-inflammatory, anti-calcification, and the ability to promote endothelial cell proliferation.

Cascade Regulation of the Proliferation, Recruitment, and Differentiation of Stem Cells to Prevent Aseptic Loosening by GNPs/ECPP Particles Responding to Macrophages: In Vitro and In Vivo.

Modulating both inflammation and stem cells by designing an artificial joint material to obtain the continuous prevention and control on aseptic loosening (AL) is a novel strategy. In this paper, graphene/europium-doped calcium polyphosphate (GNPs/ECPP) particles were obtained by ultrasound method and spark plasma sintering (SPS) method. The prepared particles were used to modulate the inflammatory response and further obtain cascade regulation on the proliferation, recruitment, and differentiation of stem cells. The results showed that particles obtained by SPS had a stronger effect on promoting the proliferation and differentiation of stem cells, while by ultrasound method more stem cells were recruited. Besides, the graphene and Eu3+ contained in the particles obtained by SPS method could effectively play a synergistic role on the differentiation of stem cells. In vivo experiment results demonstrated that the composite particles effectively suppress the inflammatory response, recruit stem cells, and prevent AL by inhibiting the secretion of inflammatory factors.

The protective immunity induced by intranasally inoculated serotype 63 chimpanzee adenovirus vector expressing human respiratory syncytial virus prefusion fusion glycoprotein in BALB/c mice.

Human respiratory syncytial virus (RSV) is a ubiquitous pediatric pathogen causing serious lower respiratory tract disease worldwide. No licensed vaccine is currently available. In this work, the coding gene for mDS-Dav1, the full-length and prefusion conformation RSV fusion glycoprotein (F), was designed by introducing the stabilized prefusion F (preF) mutations from DS-Cav1 into the encoding gene of wild-type RSV (wtRSV) F protein. The recombinant adenovirus encoding mDS-Cav1, rChAd63-mDS-Cav1, was constructed based on serotype 63 chimpanzee adenovirus vector and characterized in vitro. After immunizing mice via intranasal route, the rChAd63-mDS-Cav1 induced enhanced neutralizing antibody and F-specific CD8+ T cell responses as well as good immune protection against RSV challenge with the absence of enhanced RSV disease (ERD) in BALB/c mice. The results indicate that rChAd63-mDS-Cav1 is a promising mucosal vaccine candidate against RSV infection and warrants further development.

Sulfonated, oxidized pectin-based double crosslinked bioprosthetic valve leaflets for synergistically enhancing hemocompatibility and cytocompatibility and reducing calcification.

Clinically frequently-used glutaraldehyde (GA)-crosslinked bioprosthetic valve leaflets (BVLs) are still curbed by acute thrombosis, malignant immunoreaction, calcification, and poor durability. In this study, an anticoagulant heparin-like biomacromolecule, sulfonated, oxidized pectin (SAP) with a dialdehyde structure was first obtained by modifying citrus pectin with sulfonation of 3-amino-1-propane sulfonic acid and then oxidating with periodate. Notably, a novel crosslinking approach was established by doubly crosslinking BVLs with SAP and the nature-derived crosslinking agent quercetin (Que), which play a synergistic role in both crosslinking and bioactivity. The double crosslinked BVLs also presented enhanced mechanical properties and enzymatic degradation resistance owing to the double crosslinking networks formed via CN bonds and hydrogen bonds, respectively, and good HUVEC-cytocompatibility. The in vitro and ex vivo assay manifested that the double-crosslinked BVLs had excellent anticoagulant and antithrombotic properties, owing to the introduction of SAP. The subcutaneous implantation also demonstrated that the obtained BVLs showed a reduced inflammatory response and great resistance to calcification, which is attributed to quercetin with multiple physiological activities and depletion of aldehyde groups by hydroxyl aldehyde reaction. With excellent stability, hemocompatibility, anti-inflammatory, anti-calcification, and pro-endothelialization properties, the obtained double-crosslinked BVLs, SAP + Que-PP, would have great potential to substitute the current clinical GA-crosslinked BVLs.

Novel multifunctional dexamethasone carbon dots synthesized using the one-pot green method for anti-inflammatory, osteogenesis, and osteoimmunomodulatory in bone regeneration.

Bone tissue regeneration is still a major orthopedic challenge. The process of bone regeneration is often disrupted by inflammation. Elevated levels of reactive oxygen species (ROS) can lead to aggravated inflammation and even hinder tissue repairs. Therefore, inhibiting the inflammatory response during the process of bone regeneration and promoting bone tissue regeneration under inflammatory conditions are the goals that need to be achieved urgently. In this work, dexamethasone carbon dots (DCDs) were developed by a one-pot facile hydrothermal method using citric acid, ammonium fluoride, and a trace amount of dexamethasone. The obtained DCDs exhibited good biocompatibility and could promote the differentiation of rBMSCs under both normal and inflammatory conditions. Owing to the abundant-reducing groups, DCDs could also scavenge ROS (˙OH) and retain the pharmacological activity of dexamethasone, thereby reducing the inflammatory response. Moreover, DCDs presented a good osteoimmunomodulatory activity to induce a bone immune microenvironment and further promote the differentiation of BMSCs. DCDs could promote macrophage phenotype switching (from M1-type macrophages to M2-type macrophages) under inflammatory conditions, which was beneficial to the anti-inflammatory response. All in all, DCDs could reduce the inflammatory response of bone tissue and accelerate bone regeneration in combination with the regulation of the bone immune. Undoubtedly, it also provided a new idea for developing a novel carbon nanomaterial for repairing bone tissue defects.

Estimation of Soil Organic Carbon Using Vis-NIR Spectral Data and Spectral Feature Bands Selection in Southern Xinjiang, China.

Soil organic carbon (SOC) plays an important role in the global carbon cycle and soil fertility supply. Rapid and accurate estimation of SOC content could provide critical information for crop production, soil management and soil carbon pool regulation. Many researchers have confirmed the feasibility and great potential of visible and near-infrared (Vis-NIR) spectroscopy in evaluating SOC content rapidly and accurately. Here, to evaluate the feasibility of different spectral bands variable selection methods for SOC prediction, we collected a total of 330 surface soil samples from the cotton field in the Alar Reclamation area in the southern part of Xinjiang, which is located in the arid region of northwest China. Then, we estimated the SOC content using laboratory Vis-NIR spectral. The Particle Swarm optimization (PSO), Competitive adaptive reweighted sampling (CARS) and Ant colony optimization (ACO) were adopted to select SOC feature bands. The partial least squares regression (PLSR), random forest (RF) and convolutional neural network (CNN) inversion models were constructed by using full-bands (400-2400 nm) spectra (R) and feature bands, respectively. And we also analyzed the effects of spectral feature band selection methods and modeling methods on the prediction accuracy of SOC. The results indicated that: (1) There are significant differences in the feature bands selected using different methods. The feature bands selected methods substantially reduced the spectral variable dimensionality and model complexity. The models built by the feature bands selected by CARS, PSO and ACO methods showed the different potential of improvement in model accuracy compared with the full-band models. (2) The CNN model had the best performance for predicting SOC. The R2 of the optimal CNN model is 0.90 in the validation, which was improved by 0.05 and 0.04 in comparison with the PLSR and RF model, respectively. (3) The highest prediction accuracy was archived by the CNN model using the feature bands selected by CARS (validation set R2 = 0.90, RMSE = 0.97 g kg-1, RPD = 3.18, RPIQ = 3.11). This study indicated that using the CARS method to select spectral feature bands, combined with the CNN modeling method can well predict SOC content with higher accuracy.

An agar-polyvinyl alcohol hydrogel loaded with tannic acid with efficient hemostatic and antibacterial capacity for wound dressing.

Rapid hemostasis, antibacterial effect and promotion of wound healing are the most important functions that wound dressings need to have. In this work, we designed and prepared a hydrogel with antibacterial effect, hemostatic ability and wound healing promotion using agar, polyvinyl alcohol (PVA) and tannic acid (TA). We performed a series of tests to characterize the structure and properties of AGAR@PVA-TA hydrogels. The results showed that the AGAR@PVA-TA hydrogels had good mechanical properties and excellent antibacterial ability as well as good hemocompatibility. The cytotoxicity results showed that the AGAR@PVA-TA hydrogels had good cytocompatibility. And the TA loaded hydrogels also presented some good performances in animal studies. In the liver hemostasis model, the AGAR@PVA-TA hydrogel showed good hemostatic ability. Also, the AGAR@PVA-TA hydrogel was able to promote wound healing in an S. aureus-infected rat wound model. More importantly, our research results demonstrated that compared to other polyphenols (such as proanthocyanidins), TA could better improve the mechanical properties, antibacterial ability and rapid hemostasis of hydrogels, which illustrated the uniqueness of TA. Therefore, the TA loaded hydrogel (AGAR@PVA-TA hydrogel) has the potential to be applied as a wound dressing.

Well-designed two-fold crosslinked biological valve leaflets with heparin-loaded hydrogel coating for enhancing anticoagulation, endothelialization, and anticalcification.

Commercial biological valve leaflets (BVLs) crosslinked with glutaraldehyde (GA) are at risk of accelerating damage and even failure, owing to the high cell toxicity of GA, acute thrombosis, and calcification in clinical applications. In this study, a novel joint strategy of double crosslinking agents (dialdehyde pectin (AP) and carbodiimide) and heparin-loaded hydrogel coating was developed, endowing BVLs with excellent mechanical properties and multiple performances. Herein, AP played two essential roles, the crosslinking agent and the main component of the hydrogel coating. Both experimental and theoretical results indicated that the mechanical properties and stability of double-crosslinked BVLs were comparable to those of GA, and heparin loaded in hydrogel coating could improve the hemocompatibility of AP + EDC/NHS-PP. Further, cytocompatibility and in vivo tests showed that compared with GA-PP, AP + EDC/NHS + CS + Hep-PP has exhibited good endothelialization ability, mild immune response and anti-calcification performance and therefore prompts it to be an extremely valuable candidate for more durable and multifunctional BVLs.

SDG102, a H3K36-Methyltransferase-Encoding Gene, Plays Pleiotropic Roles in Growth and Development of Maize (Zea mays L.).

Although histone lysine methylation has been studied in thale cress (Arabidopsis thaliana (L.) Heynh.) and rice (Oryza sativa L.) in recent years, its function in maize (Zea mays L.) remains poorly characterized. To better understand the function of histone lysine methylation in maize, SDG102, a H3 lysine 36 (H3K36) methylase, was chosen for functional characterization using overexpressed and knockout transgenic plants. SDG102-deficiency in maize caused multiple phenotypes including yellow leaves in seedlings, late-flowering, and increased adult plant height, while the overexpression of SDG102 led to reduced adult plant height. The key flowering genes, ZCN8/ZCN7 and MADS4/MADA67, were downregulated in SDG102-deficient plants. Chromatin immunoprecipitation (ChIP) experiments showed that H3 lysine 36 trimethylation (H3K36me3) levels were reduced at these loci. Perturbation of SDG102 expression caused the misexpression of multiple genes. Interestingly, the overexpression or knockout of SDG102 also led to genome-wide decreases and increases in the H3K36me3 levels, respectively. Together, our results suggest that SDG102 is a methyltransferase that catalyzes the trimethylation of H3K36 of many genes across the maize genome, which are involved in multiple biological processes including those controlling flowering time.

The construction of a self-assembled coating with chitosan-grafted reduced graphene oxide on porous calcium polyphosphate scaffolds for bone tissue engineering.

Bone regeneration in large bone defects remains one of the major challenges in orthopedic surgery. Calcium polyphosphate (CPP) scaffolds possess excellent biocompatibility and exhibits good bone ingrowth. However, the present CPP scaffolds lack enough osteoinductive activity to facilitate bone regeneration at bone defects that exceed the critical size threshold. To endow CPP scaffolds with improved osteoinductive activity for better bone regeneration, in this study, a self-assembled coating with chitosan-grafted reduced graphene oxide (CS-rGO) sheets was successfully constructed onto the surface of CPP scaffolds through strong electrostatic interaction and hydrogen bonds. Our results showed that the obtained CPP/CS-rGO composite scaffolds exhibited highly improved biomineralization and considerable antibacterial activity. More importantly, CPP/CS-rGO composite scaffolds could drive osteogenic differentiation of BMSCs and significantly up-regulate the expression of osteogenesis-related proteinsin vitro. Meanwhile, the CS-rGO coating could inhibit aseptic loosening and improve interfacial osseointegration through stimulating bone marrow mesenchymal stem cells (BMSCs) to secrete more osteoprotegerin (OPG) and lesser receptor activator of nuclear factor-κB ligand (RANKL). Overall, the CS-rGO coating adjusts CPP scaffolds' biological environment interface and endows CPP scaffolds with more bioactivity.

Application of nanoindentation technology in testing the mechanical properties of skull materials.

Three-point bending test, compression test and tensile test can detect the mechanical properties of the whole layer of skull, but cannot detect the mechanical properties of the inner plate, the diploe and the outer plate of the skull. In this study, nanoindentation technology was applied to detect mechanical properties of micro-materials of the skull, and differences in micro-mechanical properties of the inner, diploe and outer plates of the skull and cranial suture of human carcasses at different ages were analyzed. The differences in hardness (HIT) and modulus of elasticity (E) were statistically significant among different age groups (P < 0.01). In terms of structure, the E of diploe was higher than that of other structures, while HIT had no significant statistical difference. In terms of location, both HIT and E showed that left frontal (LF) was significantly higher than coronal suture (CS). The above results were consistent with the multi-factor ANOVAs. In addition, the multi-factor ANOVAs further explained the interaction of HIT and E with age, location and structure. It was believed that the nanoindentation technique could be used to analyze laws of micromechanical properties of different structures of human cadaveric skull and cranial suture.

Fatal postoperative malignant hyperthermia following rhinoplasty in a patient with one variant of the ryanodine receptor 1 (RYR1) gene.

Malignant hyperthermia (MH) is characterized by a rapid rise in body temperature after using inhalational anesthetics and depolarizing muscle relaxants. A 19-year-old female had a rapidly developing fever up to 43.0 °C, after rhinoplasty surgery. Inhalational anesthetics and depolarizing muscle relaxants were used in general anesthesia. It was suspected that the patient died of MH. The medico-legal autopsy findings showed classical MH histopathological changes in the skeletal muscles, cardiac muscles, as well as lungs. Additionally, postmortem blood biochemical results indicated rhabdomyolysis. A combination of clinical records and autopsy revealed that MH might have caused the death. A diagnostic genetic testing was performed to confirm the existence of MH, and an MH diagnostic variant RYR1 c.7048G >A (p. A2350T) was detected. Eventually, the cause of death was determined as MH based on clinical records, autopsy, and genetic analysis. This case highlights that diagnostic genetic analysis plays a vital role in postmortem diagnosis of MH in routine medico-legal contexts.

Metabolic Profiles of Brassica juncea Roots in Response to Cadmium Stress.

Brassica juncea has great application potential in phytoremediation of cadmium (Cd)-contaminated soil because of its excellent Cd accumulating and high biomass. In this study, we compared the effects of Cd under 48 h and 7 d stress in roots of Brassica juncea using metabolite profiling. The results showed that many metabolic pathways and metabolites in Brassica juncea roots were altered significantly in response to Cd stress. We found that significant differences in levels of amino acids, organic acids, carbohydrates, lipids, flavonoids, alkaloids, and indoles were induced by Cd stress at different times, which played a pivotal role in the adaptation of Brassica juncea roots to Cd stress. Meanwhile, Brassica juncea roots could resist 48 h Cd stress by regulating the biosynthesis of amino acids, linoleic acid metabolism, aminoacyl-tRNA biosynthesis, glycerophospholipid metabolism, ABC transporters, arginine biosynthesis, valine, leucine and isoleucine biosynthesis, and alpha-linolenic acid metabolism; however, they regulated alpha-linolenic acid metabolism, glycerophospholipid metabolism, ABC transporters, and linoleic acid metabolism to resist 7 d Cd stress. A metabolomic expedition to the response of Brassica juncea to Cd stress will help to comprehend its tolerance and accumulation mechanisms of Cd.