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The susceptibility of different individuals to anesthetics varies widely, and sevoflurane is no exception. We hypothesized that polymorphisms in genes involved in pharmacokinetics and pharmacodynamics may explain this variation. A total of 151 individuals undergoing otorhinolaryngology surgery were included. The influence of genetic polymorphisms on sevoflurane sensitivity were investigated through SNaPshot technology. Individuals carrying KCNK2 rs6686529 G > C, MTRR rs3733784 TT, rs2307116 GG, or rs1801394 AA polymorphisms had a higher sensitivity to the sedative effect of sevoflurane than those without those polymorphisms. The univariate linear regression analysis indicated that MTRR rs3733784 TT, rs2307116 GG, and rs1801394 AA were potentially significant predictors of higher sensitivity to the sedative effect of sevoflurane. Moreover, CYP2E1 rs3813867 G > C and rs2031920 C > T, GABRG1 rs279858 T > C, KCNK3 rs1275988 CC, GRIN2B rs1806201 GG, MTRR rs2307116 G > A, and rs1801394 A > G were associated with a higher sensitivity to the cardiovascular effect of sevoflurane. Our results suggested that 9 single nucleotide polymorphisms in genes involved in metabolizing enzymes, transport proteins, target proteins of sevoflurane and folate metabolism may help to explain individual differences in the susceptibility to the sedative or cardiovascular effect of sevoflurane. [ABSTRACT FROM AUTHOR]

Significant effects of the bolt arrangement on the contact characteristics of bolted joints have been demonstrated, which are strongly associated with the dynamic performance of mechanical structures. However, the complexity of interfacial pressure distribution and the randomness of surface microtopography bring challenges to the accurate characterization of the multi-scale contact mechanics. Herein, a hybrid method combining fractal theory with the finite element method (FT-FEM) is proposed, which formulates the interfacial contact evolution in the elastic, elastic-plastic, and fully plastic stages. The complementarity of these two methods makes it possible to reveal the contact mechanism at both micro and macro scales and overcomes difficulties in reflecting the detailed joint contact characteristics in the overall dynamic model. To explore broader implications, FT-FEM is applied to the optimal design of bolt arrangement in an ultra-precision machine tool. Good agreements in calculation results and experimental data validate the accuracy of the proposed FT-FEM and the dynamic simulation. Replacing 15-M10 bolts with 19-M8 bolts results in a 2.9% enhancement in the contact stiffness and a 2.283% attenuation in the vibration response of the workpiece. The results also show that adjusting the bolt arrangement according to the working condition can strengthen the bolted joint effectively. FT-FEM contributes to solving contact problems in various mechanical structures, and the findings have wide practical applications in bolt arrangement optimization. [Display omitted] • A hybrid method for bolted joint modeling considering multi-scale contact mechanics. • New method combines improved fractal theory and finite element method. • Bolt arrangement optimization is carried out applying the method in dynamic analysis. • Experimental validation is done with bolted structures and machine tool. [ABSTRACT FROM AUTHOR]

Background: Clinical and animal studies demonstrated that neuroinflammation from anesthesia (sevoflurane) is the main contributor to cause perioperative neurocognitive disorders (PND). Recently, it was reported that microglia respond to hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which was the target of sevoflurane. Whether HCN channels are involved in the induction of neuroinflammation after sevoflurane exposure is still unclear. Results: Sevoflurane exposure had increased cognitive dysfunction and anxiety-like behaviors in rats. Rats inhaled with sevoflurane had activated microglia and increased neuroinflammation (IL-1β, IL-6, and TNF-α) in the hippocampus. RNA sequencing identified 132 DEGs (86 up-regulated and 46 down-regulated DEGs [differentially expressed genes]) in the hippocampus of PND rats. RNA-sequencing also uncovered that sevoflurane exposure down-regulates HCN2 expression. Pathway and process enrichment analysis suggests DEGs are mainly enriched in regulation of system process, positive regulation of glutamate secretion, secretion, regulation of synaptic transmission, regulation of nervous system process, behavior, negative regulation of sodium ion transport, and learning or memory. We validated that sevoflurane exposure can down-regulate the levels of PEX5R/Trip8b (an interaction partner and auxiliary subunit of HCN channels) and HCN1-4 channels in the hippocampus of PND rats. We used immunofluorescence staining to identify that HCN2 co-labels with neurons (Neun), astrocytes (GFAP), and microglia (iba1). We observed that the co-labeling of HCN2 with neurons or microglia decreased in the hippocampus and cortex after sevoflurane exposure. Blocking HCN2 by ZD7288 treatment further activated microglia and aggravated sevoflurane exposure-induced anxiety-like behavior, cognitive impairment, and neuroinflammation. Conclusions: We concluded that sevoflurane exposure can induce an increased level of neuroinflammation, microglial activation, cognitive dysfunction, and anxiety-like behaviors in rats. HCN2 channel, as the target of sevoflurane action, mediates this process. HCN2 might be a target for the treatment and prevention of sevoflurane-induced PND. [ABSTRACT FROM AUTHOR]

Various Cu catalysts were prepared by the calcination and reduction of Cu-containing layered double hydroxides (LDHs) including Cu–Al LDHs, Cu–Mg–Al LDHs, Cu–Zn–Al LDHs, and Cu–Zn–Cr LDHs. The catalysts were characterized by using ICP, N 2 physisorption, TG, SEM, XRD, H 2 -TPR, and N 2 O chemisorption, and tested for the water-gas shift (WGS) reaction at 453–623 K. The characterization results reveal the formation of LDHs on the as-synthesized precursors. Upon calcination and reduction, highly dispersed Cu nanoparticles, particularly for Cu/MgO/Al 2 O 3 , were formed. The Cu 0 surface area and Cu dispersion was found to be Cu/MgO/Al 2 O 3 > Cu/Al 2 O 3 > Cu/ZnO/Al 2 O 3 > Cu/ZnO/Cr 2 O 3 . The activity of the LDHs-derived Cu catalysts for WGS decreased in the order of Cu/MgO/Al 2 O 3 ∼ Cu/ZnO/Al 2 O 3 > Cu/ZnO/Cr 2 O 3 > Cu/Al 2 O 3 . The high activity of Cu/MgO/Al 2 O 3 was attributed to its high Cu 0 surface area and Cu dispersion, while the interaction between metallic Cu and ZnO on Cu/ZnO/Al 2 O 3 might be responsible for the WGS activity. Interestingly, the highly dispersed Cu metal particles on the Cu/MgO/Al 2 O 3 catalyst seemed stable during the WGS reaction. [ABSTRACT FROM AUTHOR]

Background: Humane treatment requires the provision of appropriate sedation and analgesia during medical diagnosis and treatment. However, limited information is available about the status of procedural analgesic interventions in Chinese hospitals. Therefore, a nationwide survey was established to identify challenges and propose potential improvement strategies. Methods: Forty-three members of the Pain Group of Chinese Society of Anesthesiology established and reviewed the questionnaire, which included (1) general information on the hospitals, (2) the sedation/analgesia rate in gastrointestinal endoscopy, labor, flexible bronchoscopy, hysteroscopy in China, (3) staff assignments, (4) drug use for procedural analgesic interventions, and (5) difficulties in procedural analgesic interventions. The data were obtained using an online questionnaire sent to the chief anesthesiologists of Chinese hospitals above Grade II or members of the Pain Group of Chinese Society of Anesthesiology. Results: Valid and complete questionnaires were received from 2198 (44.0%) hospitals, of which 64.5% were Grade III. The overall sedation/analgesia rates were as follows: gastroscopy (50.6%), colonoscopy (53.7%), ERCP (65.9%), induced abortion (67.5%), labor (42.3%), hysteroscopy (67.0%) and fiber bronchoscopy (52.6%). Compared with Grade II hospitals, Grade III hospitals had a higher proportion of procedural analgesic interventions services except for induced abortion. On average (median [IQR]), each anesthesiologist performed 5.7 [2.3—11.4] cases per day, with 7.3 [3.2—13.6] performed in Grade III hospitals and 3.4 [1.8—6.8] performed in Grade II hospitals (z = -7.065, p < 0.001). Conclusions: Chinese anesthesiologists have made great efforts to achieve procedural analgesic interventions, as evidenced by the increased rate. The uneven health care provided by hospitals at different levels and in different regions and the lack of anesthesiologists are the main barriers to optimal procedural analgesic interventions. [ABSTRACT FROM AUTHOR]

Here, a novel double‐crosslinked hydrogel dressing with enhanced antibacterial and anti‐inflammatory activities is reported. Carboxymethyl chitosan is crosslinked with silane and Ca2+ to form a double‐crosslinked hydrogel, and silver nanoparticles are loaded to introduce antibacterial properties to the hydrogel. The covalent crosslinking preserves the integrity of the hydrogel matrix, while the ionic crosslinking dissipates the energy under deformation. It combines high stretchability, toughness, tissue adhesion, and antimicrobial function. This hydrogel exhibits excellent cytocompatibility and hemocompatibility. Moreover, in vitro and in vivo investigations demonstrate its efficacy in accelerating bacterial‐infected wound healing. Given its excellent cytocompatibility and mechanical properties, this hydrogel is anticipated to be widely used in bacteria‐associated wound management. [ABSTRACT FROM AUTHOR]

Heart failure (HF), as the leading cause of death, is continuing to increase along with the aging of the general population all over the world. Identification of diagnostic biomarkers for early detection of HF is considered as the most effective way to reduce the risk and mortality. Herein, we collected plasma samples from HF patients (n = 40) before and after medical therapy to determine the change of circulating miRNAs through a quantitative real-time PCR (QRT-PCR)-based miRNA screening analysis. miR-30a-5p and miR-654-5p were identified as the most significantly changed miRNAs in the plasma of patients upon treatment. In consistence, miR-30a-5p showed upregulation and miR-654-5p showed downregulation in the circulation of 30 HF patients, compared to 15 normal controls in the training phase, from which a two-circulating miRNA model was developed for HF diagnosis. Next, we performed the model validation using an independent cohort including 50 HF patients and 30 controls. As high as 98.75% of sensitivity and 95.00% of specificity were achieved. A comparison between the miRNA model and NT-pro BNP in diagnostic accuracy of HF indicated an upward trend of the miRNA model. Moreover, change of the two miRNAs was further verified in association with the therapeutic effect of HF patients, in which miR-30a-5p showed decrease while miR-654-5p showed increase in the plasma of patients after LVAD implantation. In conclusion, the current study not only identified circulating miR-654-5p for the first time as a novel biomarker of HF, but also developed a novel 2-circulating miRNA model with promising potentials for diagnosis and prognosis of HF patients, and in association with therapeutic effects as well. [ABSTRACT FROM AUTHOR]

The contamination of Campylobacter in shellfish poses a health risk for its pathogenicity associated with campylobacteriosis. However, an efficient method to detect this risk is unavailable. Herein, we introduce a portable colorimetric biosensing platform that comprises three modules: an enrichment module 1, a binding and transduction module 2, and a smartphone-based module 3. Module 1 is an aptamer-modified 96-well plate for the specific capture of Campylobacter in a simple and high-throughput manner. Module 2 features a bifunctional biopolymer of L-glutamic acid γ-hydroxamate–alginate–Fe3+ coordinating fusarinine C, which can bind the captured Campylobacter cells and transduce them into amplified color signals upon reaction with Fe3+–violurate complexes. Module 1 achieves a capture efficiency of 97.24 %, and the subsequent addition of module 2 renders colorimetric indication of Campylobacter ranging from 101 to 106 CFU/mL, achieving an actual limit of detection of 8 CFU/mL validated by Campylobacter single-cells. Moreover, the generated colors can be recognized and converted into cell densities by module 3 with ultrasensitivity. Notably, this biosensor–smartphone platform accomplishe reliable high-throughput colorimetric detection of Campylobacter in real samples with an accuracy of 80 %. This work showcases a proof of principle for efficient on-site detection of Campylobacter contamination regarding shellfish farming. [Display omitted] • A chromogenic reaction between Fe3+-violurate and hydroxamate is specified. • A colorimetric biosensor for detecting C. jejuni in shellfish is developed upon. • This biosensor achieves high-throughput and ultrasensitive detection. • The biosensor coupling a smartphone facilitates a portable platform. • It enables colorimetric on-site sensing of C. jejuni in shellfish and environments. [ABSTRACT FROM AUTHOR]

Low yield and unremarkable electrochemical performance of MCMB prepared from conventional thermal polymerization are inevitable, which limits its large-scale application as anode material for lithium-ion batteries. Hence, in this work, MCMBs were prepared by co‑carbonization of low-valued FCC decant oil and conductive carbon black (CCB). CCB can enhance the nucleation, inhibit the growth of the mesophase spheres and adhere on the surface of spheres, thereby increasing the yields (38.9 wt%), influencing the microstructure and subsequent electrochemical performance of MCMB. The MCMBs prepared by doping with 3 wt% CCB exhibited a small particle size (15.0 μm) and moderate structural disorder degree with wide interlayer spacing (A D3 /A all = 18.15%, d 002 = 3.5342 Å), which shortened the transport pathway of Li+ inside the microbeads. Besides, chain-like conductive carbon black connected to the surface of the MCMBs, forming a continuous and developed conductive network, which was benefit for increasing of electron conduction and enhancing the Li+ transport rate outside the microbead. Such MCMB delivered the superior long-term cyclability with specific capacity of 394.5 mAh g−1 at 0.5 A g−1 (over 400 cycles) and presented a high-rate capability with reversible capacity of 276.0 mAh g−1 at an ultra-high current density of 3 A g−1. [Display omitted] • MCMB was prepared from low-cost FCC decant oil by adding conductive carbon black. • Conductive carbon black can increase yield and control particle size of MCMB. • As-prepared MCMB exhibits moderate disorder degree with wide interlayer spacing. • Conductive carbon black coated on the surface of MCMB formed conducting network. • LIBs with as-prepared MCMBs as anode show superior cyclability and rate performance. [ABSTRACT FROM AUTHOR]

Conventional diagnostic approaches for Helicobacter pylori lack sufficient sensitivity, accuracy, and flexibility, especially for low-density H. pylori infection. To overcome this limitation, we developed a highly reliable fluorometric/colorimetric dual-mode biosensing technique to detect minute quantities of H. pylori in human stool samples. Inspired by natural porphyrins, we discovered that the water-soluble fungal siderophore fusarinine C (FsC) emitted intense green fluorescence owing to intramolecular through-bond and intermolecular through-space conjugation, and turned reddish upon coordination with Fe3+. With FsC as an intrinsic fluorometric/colorimetric probe, a dual-mode biosensor was developed. It included an enrichment module of truncated H. pylori -specific-aptamer-modified superparamagnetic nanoparticles to capture H. pylori from samples, and a transduction module of alginate conjugated with FsC[Fe3+] and an optimized amount of FsC without Fe3+ to amplify the captured H. pylori to fluorescent and/or color signals. Remarkably, significantly increased sensitivity was achieved for this biosensor, with an actual limit of detection of 5 CFU/mL and single-cell-level detection resolution, as validated using laser-tweezer-sorted single H. pylori cells. Moreover, highly reliable dual-mode detection of low-density H. pylori (between 5 and 10 CFU/mL) was demonstrated. Using the colorimetric mode, a smartphone-biosensor platform for sensitive point-of-care testing of fecal H. pylori within 20 min was demonstrated, outperforming the clinical fecal antigen test strips; meanwhile, the fluorometric mode of the biosensor, owing to its greater sensitivity, can verify the colorimetric detection of minute H. pylori. This study first showcased a FsC-powered dual-mode biosensor for ultra-sensitive and accurate point-of-care detection of H. pylori with high reliability. • Fusarinine C (FsC) is validated as a natural fluorogenic/chromogenic probe. • FsC enables a fluorometric/colorimetric dual-mode biosensor for H. pylori. • This biosensor has ultra-sensitivity for low-density H. pylori in both modes. • The biosensor-smartphone platform facilitates a portable colorimetric detection. • The fluorometric mode-aided platform achieves reliable POCT of fecal H. pylori. [ABSTRACT FROM AUTHOR]

Ovarian cancer stands as a formidable clinical challenge, with limited therapeutic options. This investigation delves into the intricate molecular mechanisms governing ovarian cancer progression and uncovers Centromere Protein K (CENPK) as a central figure in disease pathogenesis. Elevated CENPK levels within ovarian cancer tissues conspicuously align with adverse clinical outcomes, positioning CENPK as a promising prognostic biomarker. Deeper exploration reveals a direct transcriptional connection between CENPK and the E2F1 transcription factor and clearly establishes E2F1's role as the master regulator of CENPK expression in ovarian cancer. Our inquiry revealing a suppression of tumor-promoting signaling pathways, most notably the mTOR pathway, upon CENPK silencing. Intriguingly, CENPK renders ovarian cancer cells more responsive to the mTOR inhibitor rapamycin, introducing a promising avenue for therapeutic intervention. In summation, our study unravels the multifaceted role of CENPK in ovarian cancer progression. It emerges as a prognostic indicator, a pivotal mediator of cell proliferation and tumorigenicity, and a regulator of the mTOR pathway, shedding light on potential therapeutic avenues for this formidable disease. • Elevated CENPK levels in ovarian cancer are associated with poor prognosis. • Direct transcriptional regulation between CENPK and E2F1. • CENPK regulates the mTOR signalling pathway. • Overexpression of CENPK makes ovarian cancer cells more sensitive to rapamycin. [ABSTRACT FROM AUTHOR]

CXXC5 , a zinc-finger protein, is known for its role in epigenetic regulation via binding to unmethylated CpG islands in gene promoters. As a transcription factor and epigenetic regulator, CXXC5 modulates various signaling processes and acts as a key coordinator. Altered expression or activity of CXXC5 has been linked to various pathological conditions, including tumorigenesis. Despite its known role in cancer, CXXC5 's function and mechanism in ovarian cancer are unclear. We analyzed multiple public databases and found that CXXC5 is highly expressed in ovarian cancer, with high expression correlating with poor patient prognosis. We show that CXXC5 expression is regulated by oxygen concentration and is a direct target of HIF1A. CXXC5 is critical for maintaining the proliferative potential of ovarian cancer cells, with knockdown decreasing and overexpression increasing cell proliferation. Loss of CXXC5 led to inactivation of multiple inflammatory signaling pathways, while overexpression activated these pathways. Through in vitro and in vivo experiments, we confirmed ZNF143 and EGR1 as downstream transcription factors of CXXC5 , mediating its proliferative potential in ovarian cancer. Our findings suggest that the CXXC5 - ZNF143 / EGR1 axis forms a network driving ovarian cell proliferation and tumorigenesis, and highlight CXXC5 as a potential therapeutic target for ovarian cancer treatment. • CXXC5 is highly expressed in ovarian cancer and is associated with poor prognosis. • Deletion of CXXC5 inhibits ovarian cancer cell proliferation and affects inflammatory signaling pathways • The expression of CXXC5 is regulated by oxygen concentration and is the direct target of HIF1A. • ZNF143 and EGR1 are downstream transcription factors of CXXC5 , which affect cell proliferation in ovarian cancer. • CXXC5 drove inflammation and ovarian cancer proliferation via transcriptional activation of ZNF143 and EGR1 [ABSTRACT FROM AUTHOR]

Versatile nanoplatform equipped with chemo-photodynamic therapeutic attributes play an important role in improving the effectiveness of tumor treatments. Herein, we developed multifunctional nanoparticles based on chondroitin sulfate A (CSA) for the targeted delivery of chlorin e6 (Ce6) and doxorubicin (DOX), in a combined chemo-photodynamic therapy against triple-negative breast cancer. CSA was chosen for its hydrophilic properties and its affinity to CD44 receptor-overexpressed tumor cells. The CSA-ss-Ce6 (CSSC) conjugate was synthesized utilizing a disulfide linker. Subsequently, DOX-loaded CSSC (CSSC-D) nanoparticles were fabricated, showcasing a nearly spherical shape with an average particle size of 267 nm. In the CSSC-D nanoparticles, the chemically attached Ce6 constituted 1.53 %, while the physically encapsulated DOX accounted for 8.11 %. Both CSSC-D and CSSC nanoparticles demonstrated a reduction-sensitive release of DOX or Ce6 in vitro. Under near-infrared (NIR) laser irradiation, CSSC-D showed the enhanced generation of reactive oxygen species (ROS), improving cytotoxic effects against triple-negative breast cancer 4T1 and MDA-MB-231 cells. Remarkably, the CSSC-D with NIR exhibited the most potent tumor growth inhibition in comparison to other groups in the 4T1-bearing Balb/c mice model. Overall, this CSSC-D nanoplatform shows significant promise as a powerful tool for a synergetic approach in chemo-photodynamic therapy in triple-negative breast cancer. [Display omitted] [ABSTRACT FROM AUTHOR]

• Honeycomb sandwich structures with continuous density gradients are designed. • Flexural behavior is sensitive to horizontal but insensitive to vertical gradients. • Achieved favorable flexural resistance with horizontal arched density distribution. • Detrimental effects from thin cover plates and honeycomb layers are indicated. Sandwich structures with graded cellular cores exhibit promising flexural performances, but their reliance on gradient continuity and distribution warrants further exploration. In this study, seven honeycomb sandwich structures with diverse continuous density gradients, encompassing horizontal, uniform and vertical variations, were designed based on the Voronoi technique and fabricated via 3D printing. Quasi-static three-point bending tests and numerical simulations were conducted to comprehensively analyze the flexural response of density-graded honeycomb sandwich structures. The results reveal a significant influence of the honeycomb core's density distribution on flexural performance, with pronounced sensitivity to horizontal distribution (perpendicular to the loading direction) and less sensitivity to vertical distribution. A favorable flexural resistance is achieved by strategically assigning higher relative density cells to the mid-span of a honeycomb core layer, gradually diminishing towards the ends, which was further optimized into an arched density distribution along the horizontal direction. The influences of cover plate and honeycomb thicknesses on the deformation mechanisms and energy absorption were also investigated, and indicate that thin cover plates and honeycomb layer have a detrimental effect on the bending load-bearing and energy absorption of the sandwich structure. [ABSTRACT FROM AUTHOR]

The precise involvement and mechanistic role of the signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) in ovarian cancer (OV) remain poorly understood. Here, leveraging comprehensive data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we unveil the selective overexpression of SCUBE3 in ovarian cancer tissues and cells. Intriguingly, elevated SCUBE3 expression levels correlate with an unfavorable prognosis in patients. Through meticulous manipulation of SCUBE3 expression, we elucidate its consequential impact on in vitro proliferation and invasion of ovarian cancer cells, as well as in vivo tumor growth in mice. Our multifaceted investigations, encompassing luciferase reporter assays, chromatin immunoprecipitation (ChIP) experiments, and mining of public databases, successfully identify SCUBE3 as a direct downstream target gene of TCF4 —a pivotal positive regulator within the β-catenin/TCF4 complex. Furthermore, utilizing a recessive mutant mouse line (kta41) harboring a functionally impaired point mutation at position 882 in the SCUBE3 gene, we uncover SCUBE3 's involvement in the intricate regulation of angiogenesis and epithelial-mesenchymal transition (EMT). Strikingly, Spearman correlation coefficient analysis unveils a close association between SCUBE3 and HIF1A in OV, with SCUBE3 exerting tight control over HIF1A mRNA expression. Moreover, functional inhibition of HIF1A significantly impedes the pro-proliferative and invasive capabilities of SCUBE3 -overexpressing ovarian cancer cells. Collectively, our findings underscore the pivotal role of SCUBE3 in driving ovarian cancer progression, shedding light on its intricate molecular mechanisms and establishing it as a potential therapeutic target for this devastating disease. • Selective overexpression of SCUBE3 in ovarian cancer tissues and cells is associated with poor prognosis. • SCUBE3 as a direct downstream target gene of TCF4 —a pivotal positive regulator within the β-catenin/TCF4 complex. • SCUBE3 is involved in complex regulation of angiogenesis and epithelial-mesenchymal transition (EMT). • SCUBE3 promotes OV development via HIF-1 signaling pathway. [ABSTRACT FROM AUTHOR]

Honeycomb structure, which presents potential ability in energy absorption and impact resistance, has advantages of simplicity, lightweight, easy manufacturing and designability. In this study, honeycomb structure panel is expanded to cylindrical shell by adopting the rolled-up algorithm and the crushing behaviors of the randomly honeycomb cylindrical shell (RHCS) structures are investigated under axial loading. The influence of geometrical and topological parameters, i.e. the thickness-to-diameter ratio, cell irregularity, relative density on the deformation evolution and energy absorption performance is systematically performed. It is found that the deformation modes of RHCS structures are significantly affected by thickness-to-diameter ratio and cell irregularity. Moreover, the rate-independent, rigid–plastic hardening (R–PH) idealisation with two parameters is adopted to characterize the crushing responses of RHCS structures and the parameters are quantified as power-law relations with respect to relative density. Further, the crushing behaviors of density-graded RHCS structures with continuously varying in density are carried out under different impact velocities. Results indicated that the introduction of density gradients can strongly affect the deformation mode, crushing force and energy absorption performance of density-graded RHCS structures. Combining with analysis of crushing front propagation, the theoretical determination of crushing responses of the density-graded RHCS under different loading rates is presented based on R–PH model. The results of predicted crushing force-time histories of density-graded RHCS structures show versatile agreement with that of finite element values at both impact and support ends. Additionally, the energy absorption capacity that is related to deformation mechanisms of density-graded RHCS structures is investigated. • 3D randomly honeycomb cylindrical shell (RHCS) structures are constructed. • Parametric study of the effect of topological parameters on deformation and energy absorption capacity is performed. • Propagation of crushing front through RHCS structures with continuously varying in density is quantitatively investigated. • The crushing response of density-graded RHCS structures is predicted theoretically under different loading rates. • Energy absorption mechanism of density-graded RHCS structures is revealed. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the inhibitory effects of Kaempferol, a natural flavonol active compound, on pseudo‐allergic reactions (in vivo and in vitro), particularly on the mechanism underlying its effect in human mast cells. Methods: Compound 48/80 (C48/80)‐induced immunoglobulin E (IgE)‐independent passive cutaneous anaphylaxis (PCA) model and systemic anaphylaxis were applied to investigate the anti‐allergic activity of Kaempferol. The degranulation assay, calcium imaging and the secretion of cytokines and chemokines were used to evaluate the inhibitory effect on mast cell activation. Western blot analysis was performed to investigate intracellular calcium fluctuation‐related signalling pathways. Key findings: Kaempferol dose‐dependently attenuated C48/80‐induced mice hind paw swelling, dye extravasation and skin mast cell degranulation, and rehabilitated the hypothermia, as well as reduced the serum concentrations of histamine, tryptase, tumour necrosis factor‐alpha (TNF‐α), interleukin‐8 (IL‐8) and monocyte chemo‐attractant protein‐1 (MCP‐1). Furthermore, Kaempferol suppressed C48/80‐triggered human MC degranulation and calcium fluctuations by inhibiting phospholipase Cγ (PLCγ) phosphorylation and subsequent cytokines synthesis pathways. Conclusions: The inhibition of the process of PLCγ phosphorylation to Ca2+ mobilization represents a major strategy in Kaempferol‐suppressed pseudo‐allergic reactions. Thus, Kaempferol could be considered as a therapeutic drug candidate for non‐IgE‐mediated allergic reactions or inflammations. [ABSTRACT FROM AUTHOR]

The rhodophyte marine algal genus Grateloupia (Halymeniaceae, Halymeniales) is distributed worldwide, including in offshore southeastern China. Here, we investigated morphology, carpospore development, ecological habits, and molecular analyses of a rarely studied species, Grateloupia qingdaoensis. The carpogonial branch ampullae and auxiliary cell ampullae were the typical Grateloupia type (6cpb-5auxb type) and the type of spore development was "mediate discal type". The life history included homotypic gametophytes (haploid), carposporophytes (diploid), and tetrasporophytes (diploid) and showed a typical isomorphic alternation of generations. By using single-factor and orthogonal experiments, we explored the effects of temperature, irradiance and seawater salinity on the early development of G. qingdaoensis. Each ecological factor showed distinct effect on the early development of G. qingdaoensis. Additionally, we found a significant interactive effect between temperature and irradiance on discord crust growth. The optimum conditions for the early growth of discoid crust and upright thalli were 20 °C, 80 μmol photons m−2 s−1 irradiance and 30‰ seawater salinity. To clarify its taxonomical status, we constructed the phylogenetic tree of rbcL gene sequences. Results showed that there was no pairwise divergence between G. qingdaoensis and G. asiatica from China. Our findings indicate that previous records without precise and comprehensive comparison and molecular analyses need to be re-examined to clarify the global distribution of this species. [ABSTRACT FROM AUTHOR]

• A novel plate-rod hybrid lattices (PRHL) is designed and additively manufactured. • PRHL exhibits higher stiffness and superior specific energy absorption. • Fabrication-angle-dependent material properties are incorporated in simulations. • PRHL's improved performance is due to the mutual interaction of plates and rods. Hybrid lattice structures, integrating diverse structural components from fundamental lattice topologies, have attracted significant attention for their exceptional mechanical properties encompassing elastic modulus, yield stress, and energy absorption. To amalgamate the lightweight characteristics of rod structures with the robust mechanical properties of plate structures, a novel plate-rod hybrid lattice (PRHL) with controllable geometrical parameters and higher energy absorption was proposed and fabricated via the Selective Laser Sintering technique. In the PRHL design, the hybrid rod structure, interlinked with the center of each surface of the semi-open Octet plate lattice (SOPL), mutually provides support and deformation constraints. To identify the mechanical properties of PRHL, quasi-static uniaxial compression tests of PRHL samples sintered by Polylactic Acid powder were carried out. In comparison to SOPL, the newly proposed PRHL demonstrates an approximate 13.4 % improvement in initial crush stress and an 18.5 % increase in specific energy absorption capacity. Furthermore, numerical simulations incorporating the effect of printing orientation were performed to analyze the deformation mechanism of the PRHL structures. The present study also underscores the capacity to fine-tune the mechanical properties of PRHLs by regulating the plate thickness, rod diameter and excavated hole diameter. [ABSTRACT FROM AUTHOR]

Novel honeycombs with buckling-induced features and tailorable properties have been designed and fabricated using the fused deposition modeling (FDM) method. Quasi-static out-of-plane compression tests were carried out to investigate the topological dependence of the crushing behavior of the buckling-induced honeycombs (BIHs). The results demonstrated that the crushing performance of BIHs can be artificially controlled by altering their shape parameters. In particular, the initial peak force (IPF) and the undulation of the mechanical response of BIH can be effectively reduced by increasing the layer number or arranging the asymmetric layers. A finite element model validated against experimental results was also utilized to reveal the underlying deformation mechanism and study the corresponding displacement-crushing force responses for BIHs with different topological parameters. It was uncovered that the buckling-induced mechanism is beneficial for tuning the stiffness and mitigating local buckling resistance through the pre-determined collapse behavior of cell walls. Further, a multi-objective optimization process of BIH was performed to seek the optimal design solution for energy-absorbing structures in specific scenarios. The findings of this study provide a theoretical basis for the development of new ideas and optimization solutions for the design of lightweight and performance-tailored energy-absorbing structures. [ABSTRACT FROM AUTHOR]

Radiofrequency (RF) treatment is an invasive and promising procedure in the treatment of osteoarthritis (OA). A meta-analysis based on 12 RCT studies was to investigate whether invasive RF treatment is more effective in relieving knee pain and improving knee function. Relevant studies were searched on database of Pubmed, Embase, EBSCO, Cochrane library, Wanfang digital database, VIP database, and CNKI up to January 2018. A total of 841 participants from 12 publications were included. The weighted mean difference (WMD) and the corresponding 95% CIs were used to evaluate the difference in pain scores and OKS/WOMAC scores between RF treatment and control groups. The statistical analysis was performed by Stata 12.0. The pain scores (VAS) in the RF group were lower than those in the conservative treatment group after 1 week (WMD -1.77, 95% CI -2.93 to -0.61, P<0.01), 1 month (WMD -1.40, 95% CI -1.98 to -0.82, P<0.01), and 3 months (WMD -1.32, 95% CI -2.27 to -0.37, P<0.01) of treatment, while there was no significant improvement in knee function. In subgroup analyses by site of radiofrequency, RF mode showed some discrepancies in the WMD of VAS between the treatment and control groups. In addition, subgroup analysis and meta-regression showed that the efficacy of RF treatment for reducing pain is reversely related to female ratio, and we did not find any surgery-related adverse reactions. RF treatment significantly reduces the knee pain, but rarely improves the knee joint function. Radiofrequency ablation has better efficacy than pulsed radiofrequency ablation in reducing pain. Furthermore, subgroup analysis and meta-regression suggested that women are more sensitive to RF treatment than men. [ABSTRACT FROM AUTHOR]

Highlights • Closed-cell PLA foams are fabricated by an FDM technique of rapid prototyping. • Mechanical properties of foams with different meso‑structures are evaluated. • Failure strength of foams is found to be dependent on layer deposition strategy. • A statistical constitutive model involving the relative density is proposed. • This model well captures the features of initial stress drop and three-stage deformation. Abstract The deformation characteristics and mechanical behavior of closed-cell polylactide (PLA) foams under quasi-static uniaxial compression are investigated. The PLA foam specimens are constructed numerically with 3D Voronoi technique and prepared with fused deposition modeling (FDM). The effects of meso‑structure, layer deposition strategy and relative density on the crushing and densification behaviors of PLA foams are analyzed. The experimental results indicate that PLA foams with regular meso‑structures are more likely to induce local collapse during compression, and those with random meso‑structures show good performances, such as high specific energy absorption, low stress fluctuation and stable deformation process. The experimental results further reveal that random PLA foams with the deposition layers perpendicular to the loading direction have higher strength and smaller lateral expansion than those with other orientations. The quasi-static compression stress-strain curves of random PLA foams exhibit three typical stages, namely linear elastic stage, plastic collapse stage and densification stage. A stress drop after reaching the initial peak stress is observed. To characterize these features, we propose a statistical constitutive model which takes into account the meso‑structural characteristics and deformation mechanism at the cell scale. This constitutive model contains six parameters and fits the experimental results very well. In particular, it can capture the peak stress at the onset of plastic collapse and the subsequent stress drop of cellular materials. Finally, the dependence of the six parameters in the constitutive model on the relative density is analyzed and the corresponding quantitative statistical relationships are determined. [ABSTRACT FROM AUTHOR]

Background Pseudo-allergic reactions occur when patients receive muscle relaxants during perioperative anesthesia. These reactions may result in a serious threat to the patient's life, particularly to a child's life. Cisatracurium, a relatively new NMBA, has resulted in bronchospasms and cardiovascular collapse. However, the mechanisms underlying the anaphylactoid reactions caused by cisatracurium have not been fully elucidated. Methods In the present study, the MRGPRX2-related pseudo-allergic reactions induced by cisatracurium were investigated using hindpaw swelling and extravasation assays in vivo and mast cell degranulation assays. Results Cisatracurium caused anaphylactoid reactions in wild-type mice. However, cisatracurium did not induce a similar phenomenon in KitW-sh/W-sh mice. Furthermore, mast cell-related G protein-coupled receptor B2-knockout mice did not display an inflammatory response upon treatment with cisatracurium. Cisatracurium induced LAD2 cell degranulation, leading to the dose-dependent release of β-hexosaminidase, histamine and TNF-α. However, cisatracurium only induced the release of low levels of these mediator LAD2 cells transfected with MRGPRX2 siRNA. Cisatracurium also stimulated intracellular Ca 2+ influx in MRGPRX2-HEK293 cells compared with that in NC-HKE293 cells. Interestingly, cytokine release was not observed in LAD2 cells even with high dose of cisatracurium. Conclusions Cisatracurium activated MRGPRX2 and triggered mast cell degranulation, leading to anaphylactoid reactions. Therefore, strategies targeting MRGPRX2 might potentially block cisatracurium-induced pseudo-allergic reactions. [ABSTRACT FROM AUTHOR]

Thee corrosion behavior of Alloy C-276 in high-temperature and high-pressure water at 500°C and 25 MPa, respectively, was investigated by means of mass gain, scanning electron microscopic observation, and X-ray diffraction. The results indicated that the mass gain rate of Alloy C-276 in supercritical water obeys the parabolic law. The oxide scale was formed on Alloy C-276 with a dual-layer structure, mainly consisting of an outer Ni-rich layer and an inner Cr2O3/NiCr2O4 mixed layer. Tiny microcracks can also be found in the oxide scale if exposed for longer time. Meanwhile, higher temperature promotes oxide rate and results in thermal stress in the oxide film. [ABSTRACT FROM AUTHOR]

RNF31, an atypical E3 ubiquitin ligase of the RING-between-RING protein family, is one of the important components of the linear ubiquitin chain complex LUBAC. It plays a carcinogenic role in a variety of cancers by promoting cell proliferation, invasion and inhibiting apoptosis. However, the specific molecular mechanism by which RNF31 exerts its cancer-promoting effects is still unclear. By analyzing the expression profile of RNF31-depleted cancer cells, we found that loss of RNF31 significantly resulted in the inactivation of the c-Myc pathway. We further showed that RNF31 played an important role in the maintenance of c-Myc protein levels in cancer cells by extending the half-life of c-Myc protein and reducing its ubiquitination. c-Myc protein levels are tightly regulated by the ubiquitin proteasome, in which the E3 ligase FBXO32 is required to mediate its ubiquitin-dependent degradation. We found that RNF31 inhibited the transcription of FBXO32 through EZH2-mediated trimethylation of histone H3K27 in the FBXO32 promoter region, leading to the stabilization and activation of c-Myc protein. Under this circumstance, the expression of FBXO32 was significantly increased in RNF31-deficient cells, promoting the degradation of c-Myc protein, inhibiting cell proliferation and invasion, increasing cell apoptosis, and ultimately blocking the progression of tumors. Consistent with these results, the reduced malignancy phenotype caused by RNF31 deficiency could be partially reversed by overexpression of c-Myc or further knockdown of FBXO32. Together, our results reveal a key association between RNF31 and epigenetic inactivation of FBXO32 in cancer cells, and suggest that RNF31 may be a promising target for cancer therapy. • Knockdown of RNF31 suppressed the c-Myc oncogenic signaling pathway in cancer cells. • RNF31 stabilizes c-Myc by epigenetic inactivation of FBXO32 through EZH2. • RNF31 maintains malignancy phenotype at least by epigenetic inactivation of FBXO32. [ABSTRACT FROM AUTHOR]

[Display omitted] Fusion with host cell membrane is the main mechanism of infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we propose that a new strategy to screen small-molecule antagonists blocking SARS-CoV-2 membrane fusion. Using cell membrane chromatography (CMC), we found that harringtonine (HT) simultaneously targeted SARS-CoV-2 S protein and host cell surface TMPRSS2 expressed by the host cell, and subsequently confirmed that HT can inhibit membrane fusion. HT effectively blocked SARS-CoV-2 original strain entry with the IC 50 of 0.217 μM, while the IC 50 in delta variant decreased to 0.101 μM, the IC 50 in Omicron BA.1 variant was 0.042 μM. Due to high transmissibility and immune escape, Omicron subvariant BA.5 has become the dominant strain of the SARS-CoV-2 virus and led to escalating COVID-19 cases, however, against BA.5, HT showed a surprising effectiveness. The IC 50 in Omicron BA.5 was even lower than 0.0019 μM. The above results revealed the effect of HT on Omicron is very significant. In summary, we characterize HT as a small-molecule antagonist by direct targeting on the Spike protein and TMPRSS2. [ABSTRACT FROM AUTHOR]

In addition to maintaining the power balance, the major tasks of multi-area automatic generation control (AGC) involve regulating the power exchange among subareas. This study presents a new power flow model allowing for multi-area AGC that achieves cooperation among the participating generators, which are deployed separately in the interconnected subarea networks. The formulations of the power exchange among the subareas are derived from the active power flow equations of the tie-lines. The node parameters representing the level and allocation of the unbalanced power are introduced. Then, the proposed power flow model is established by integrating the formulations of the node power injection and power exchange. Meanwhile, the unknown variables in the integrated model can be synchronously adjusted by the Newton iteration method, which depends on the integrated Jacobian matrix. Furthermore, being improved based on the integrated formulations, some related algorithms, including but not limited to sensitivity analysis, are expected to produce more precise solutions. The case studies of the IEEE 5 bus test system, the IEEE RTS-1996 test system, and the IEEE 300 bus test system illustrate the convergence and efficiency of the proposed power flow method. Moreover, the case studies also demonstrate that the integrated formulations based sensitivity analysis can generate more reliable results. [ABSTRACT FROM PUBLISHER]

Multifunctional polymeric micelles self-assembled from a DOX-conjugated methoxypolyethylene glycols- b -poly (6- O -methacryloyl- d -galactopyranose)-disulfide bond-DOX (mPEG- b -PMAGP-SS-DOX) copolymer were prepared as an antitumor carrier for doxorubicin delivery, of which the chemical modification with disulfide bonds and hydrazone bonds allowed micelles to release doxorubicin (DOX) selectively at acidic pH and high redox conditions. The resulting micelles exhibited coordinated pH/redox dual-sensitive and hepatoma-targeted multifunction with sustaining stability in aqueous media. The multifunctional micelles showed spherical shapes with a mean diameter of 93 ± 2.08 nm, a low polydispersity index (PDI) of 0.21, a low CMC value of 0.095 mg/mL, a high drug grafting degree of 56.9% and a drug content of 39.0%. Remarkably, in vitro drug release studies clearly exhibited a pH and redox dual-sensitive drug release profile with significantly accelerated drug release treated with pH 5.0 and 10 mM GSH (88.4% in 72 h) without drug burst release. The tumor proliferation assays indicated that DOX-grafted micelles, along with low cytotoxicity and well biocompatibility to normal cells up to a concentration of 10 μg/mL, inhibited the proliferation of HepG2 cells in a formulation-, time- and concentration-dependent manner in comparison with MCF-7 cells which was similar to free DOX. Anticancer activity releaved that the disulfide-modified micelles possessed much higher anti-hepatoma activity with a low IC 50 value of 1.1 μg/mL following a 72 h incubation. Furthermore, the intracellular uptake tested by CLSM and FCM demonstrated that multifunctional polymeric micelles could be more efficiently taken up by HepG2 cells compared with MCF-7 cells, agreed well with MTT assays, suggesting these well-defined micelles provide a potential drug delivery system for dual-responsive controlled drug release and enhanced anti-hepatoma therapy. [ABSTRACT FROM AUTHOR]

• Superhydrophobic fluorinated microspheres are fabricated by SPP. • The fluorinated microspheres can be used as stationary phase for HPLC. • The fluorinated column displays much lower back pressure in aqueous solutions. • The fluorinated column can separate fluorous compounds by fluorous affinity. Fluorous affinity chromatography has received growing attention in separation and purification of fluoro compounds, but the wettability of the fluorinated stationary phases is seldom noticed. Here, we construct a series of micro-sized fluorine-containing microspheres by solvothermal precipitation polymerization. The fluorinated microspheres could be obtained with narrow size distribution at even high monomer loading of 15 wt%. Through alternating fluoro monomer, both the particle size and the wettability of the microsphere array could be tuned. Among them, the poly(divinylbenzene -dodecafluoroheptyl methacrylate), P(DVB-DFHMA), microsphere (6.1 μm) arrays displays superhydrophobicity with 153.2° water contact angle. The P(DVB-DFHMA) fluorinated microspheres (7.58% fluorine content) can be packed into steel-less columns as stationary phase for high-performance liquid chromatography. The retention mechanism of the fluorinated column is proven to be the specific fluorine-fluorine interaction. Compared to the commercial C18 silica column, the fluorinated column can completely separate fluorine-containing compounds under high water content mobile phase, including small fluoro molecules and fluoro macromolecules, at much lower back pressure by fluorous affinity. [ABSTRACT FROM AUTHOR]

Fluorine-containing epoxy (FO) compounds were synthesized through a one-step process from 2,2,3,3-tetrafluoro-1-propanol (TFP) and epichlorohydrin (ECH). Cationic polymerization was adopted to prepare fluorinated polyglycol with controllable molecular weight. The structure of FO and FPO were studied by FTIR, NMR and GPC and a two-component fluorinated polyurethane coating was synthesized using FPO and methyl diphenylenediisocyanate (MDI) with a room temperature curing method. We characterized the contact angle of the surface of the coating. The water resistance and resistance to salt spray as well as SEM imaging of the film surface indicates that hydrophobicity, water resistance, and corrosion resistance are improved due to surface migration of the fluorine element. [ABSTRACT FROM AUTHOR]

• In-plane crushing of FCFH and the separate members were tested and simulated. • Deformation modes of FCFHs with varying honeycomb architectures were identified. • Interaction between foamed concrete and honeycomb skeleton was analyzed. • Crushing performance was improved with small honeycomb cell size or high cell irregularity. • Validated FE model provides a basis for further design optimization of hybrid structures. Proper design of cellular structure-based composite could well improve the mechanical properties of the constituent members acting separately. In this study, the novel foamed concrete-filled honeycombs (FCFHs) with tailored geometrical architectures of additively manufactured polymeric honeycombs were developed. The in-plane crushing performance of FCFHs subjected to quasi-static and impact loadings was investigated experimentally and numerically. It was demonstrated that the existence of foamed concrete within honeycomb cells greatly strengthens the collapse resistance of cell walls, and the premature failure of foamed concretes in FCFH is effectively prevented. The shear-dominated failure mode of FCFHs with honeycombs of relatively large cell size or regular configuration or low relative density gradually transforms to a global compression deformation by decreasing cell size or increasing cell irregularity or relative density of honeycomb. Benefiting from the interaction-induced reinforcement between the involved components, the mechanical properties of FCFHs are highly dependent on the mesostructures of honeycomb skeleton. Specially, a decrease of cell size from 5 mm to 3.5 mm yields an increase in the mean crushing strength and the specific energy absorption of FCFHs up to 49.6% and 69.0%, respectively. Further, a numerical model, which was validated against experimental tests, was adopted to study the dynamic behavior of FCFHs. It transpires that the contribution of each component to the energy absorption, relating to the mesoscale deformation mechanism, largely depends on impact velocity. This study aims to provide a promising route to design and optimize lightweight composite structures with high performance. [ABSTRACT FROM AUTHOR]

The contact stiffness of the joint interface significantly affects the dynamic characteristics of a machine tool structure. Herein, an improved theoretical model is proposed to calculate the joint interfacial contact stiffness. This model is established based on fractal theory. To mitigate the plastic and elastic contact problems, the Stronge contact model is adopted to express the contact force in the plastic regime innovatively, whereas the elastic contact force is interpreted using Hertz theory; the domain extension factor is compensated to revise the microcontact size distribution. Furthermore, the rotational contact stiffness is first derived, which renders the contact model more comprehensive. A representative test structure is designed, and the contact model is validated by comparing the simulated contact stiffness with experimental results. The transfer matrix method for multibody systems is incorporated with fractal contact model to establish a dynamic model of an ultra-precision machine tool; this ensures that the dynamic characteristics of the machine tool can be predicted more precisely. Experiments involving a vibration response test and a modal test demonstrate the feasibility of the fractal contact and dynamic models. Based on these two models, the effect of the interfacial contact stiffness on the structural dynamics is investigated. As the preloads at two joints loosen by 15%, the maximum vibration displacements increase by 1.74% and 2.90%, respectively, indicating that the joint interface between the column and lathe bed is more sensitive. The procedure presented herein will facilitate the design and optimization of the complex structures. Image 1 • Stronge contact model and domain extension factor are adopted to improve the joint interfacial contact stiffness model. • The rotational contact stiffness is first derived and validated by a representative test structure. • Transfer matrix method for multibody systems and fractal contact model are used jointly to establish the dynamic model. • One method to ensure the structural stability is proposed by discovering the sensitive joints and restraining bolt loosening. [ABSTRACT FROM AUTHOR]

To improve our understanding about the responses of microbial functional diversity to different mulching practices, this study used a metagenomic approach to reveal soil microbial functional specificity under four tillage regimes: conventional tillage (CT), organic mulch practices with ryegrass (Lolium perenne L.) intercropping cover (RE) and cornstalk mulch (CS), and inorganic mulching with black ground fabric (BF) in a 7-year field experiment in an apple orchard of the Loess Plateau in China. Enzyme activity and soil physicochemical properties were measured. A redundancy analysis showed that the RE and CS treatments had positive effects on soil nutrient and enzyme activity compared to that of the BF and CT treatments. The CS and RE treatments increased β-glucosidase, cellobiohydrolase, and β-xylosidase activities. In addition, the CS treatment significantly enhanced the β-N-acetylglucosaminidase and urease activities compared to that under CT treatment. However, the activity of these enzyme was reduced in the BF treatment compared with that of the CT treatment. The results also indicated that the enzymes activities were not completely consistent with the changing trends of the genes encoding these enzymes. In addition, the RE and CS treatments also increased the abundance of genes encoding carbohydrate enzymes. It is interesting that the RE and CS treatments had more pathway genes associated with the carbon cycle, nitrogen cycle, and amino acid metabolism compared with the BF treatment. Remarkably, RE and CS treatments effectively increased the abundance of carbon fixation gene cbbL compared to CT treatment. In summary, organic mulching practices increased the soil microbiological functional diversity related to the carbon and nitrogen cycle, while inorganic mulching practice reduced them. This study enhanced our understanding of how mulching practices may alter soil microbial functional diversity and benefit soil quality. • Organic mulching increased the abundance of genes encoding carbohydrate enzymes. • Organic mulching increased the abundance of carbon fixation gene cbbL. • Organic mulching stimulated the enrichment of pathway genes associated with C and N cycle. • Inorganic mulching reduced microbial functional diversity. • Availability of soil nutrients shaped the diversity of microbial function. [ABSTRACT FROM AUTHOR]

• Grass mulching types altered soil DOM components and bacterial communities were studied. • Protein components were predominant with legume mulching and humic-like components in gramineae grass mulching. • Gramineae grass mulching for soil nutrition provided superior improvements compared with legume mulching. • Changes in DOM components were strongly related with the soil bacterial community structure. This study aims to clarify the relationship between soil dissolved organic matter (DOM) components and bacterial communities in long-term grass mulching management apple orchards (Malus domestica). The key role of the transformation of DOM components and soil nutrient cycling in improving orchard grass mulching management strategies was assessed. Four treatments, including legumes, such as white clover (WC) and crown vetch (CV); Gramineae orchardgrass (OG); and conventional tillage (CT) as the control, were employed to explore DOM components, the bacterial community structure and their relationship. In all the management systems, the DOM identified included two humic-like components and one protein component. The protein component was dominant in leguminous mulching (43.04–77.13 %), whereas the humic-like component was dominant in graminaceous mulching (42.17–72.11 %). Component 2 accounted for less than 1% in CT, CV and WC. The three types of grass mulching increased the proportion of copiotrophic bacteria and reduced that of oligotrophic bacteria, especially Proteobacteria (34.27–28.83%) and Acidobacteria (20.96–28.42%) at the phylum level. Legumes were beneficial for DOM transformation, and Gramineae species improved soil nutrition and bacterial communities. In conclusion, mulching of different grasses in orchards significantly changes the soil DOM components and bacterial community structure through different types of organic inputs, and the connection of these communities is closely coordinated with significant effects on soil nutrient cycling and orchard grass mulching strategies. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is the most prevalent microvascular complication of diabetes mellitus, and it is the primary cause of blindness in the working-age population worldwide. Nevertheless, the pathogenic molecular mechanisms of DR remain elusive. Hub genes were identified through bioinformatics analysis in the GSE102485 and GSE60436 datasets. The DR mouse model was induced using streptozotocin (STZ, 150 mg/kg), and pathological changes in retinal tissue were assessed via HE staining. Apoptosis in retinal tissue cells was evaluated by the TUNEL assay. RT-qPCR and ELISA assays were employed to measure hub genes and inflammatory factor levels, respectively. The aryl hydrocarbon receptor (AHR)/interleukin (IL)-17A (AHR/IL-17A) pathway-associated proteins were detected by western blot. In the high glucose (HG)-induced ARPE-19 cells, CCK-8 and flow cytometry were used to perform cell function studies. Six hub genes associated with DR were screened. The expression levels of RHO, PRPH2, CRX, RCVRN, and NR2E3 were reduced, while the COL1A2 was elevated. NR2E3 overexpression reduced inflammatory factor (TNF-α, IL-1β, and IL-6) and cell apoptosis levels in DR. Furthermore, NR2E3 overexpression promoted HG-induced ARPE-19 cell proliferation. Mechanistically, NR2E3 overexpression facilitated the protein expression of AHR, while suppressing the IL-17 and ACT1 expressions. The introduction of Kyn-101, an AHR inhibitor, notably reversed the inhibitory effects of NR2E3 overexpression on inflammation and apoptosis, which were validated both in vivo and in vitro. NR2E3 inhibits the inflammation and apoptosis by regulating the AHR/IL-17A pathway, providing new insights into the DR treatment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

JOURNAL/nrgr/04.03/01300535-202419110-00029/figure1/v/2024-03-08T184507Z/r/image-tiff Our previous study has demonstrated that lnc&#95;000048 is upregulated in large-artery atherosclerotic stroke and promotes atherosclerosis in ApoE-/- mice. However, little is known about the role of lnc&#95;000048 in classically activated macrophage (M1) polarization. In this study, we established THP-1-derived testing state macrophages (M0), M1 macrophages, and alternately activated macrophages (M2). Real-time fluorescence quantitative PCR was used to verify the expression of marker genes and the expression of lnc&#95;000048 in macrophages. Flow cytometry was used to detect phenotypic proteins (CD11b, CD38, CD80). We generated cell lines with lentivirus-mediated upregulation or downregulation of lnc&#95;000048. Flow cytometry, western blot, and real-time fluorescence quantitative PCR results showed that down-regulation of lnc&#95;000048 reduced M1 macrophage polarization and the inflammation response, while over-expression of lnc&#95;000048 led to the opposite effect. Western blot results indicated that lnc&#95;000048 enhanced the activation of the STAT1 pathway and mediated the M1 macrophage polarization. Moreover, catRAPID prediction, RNA-pull down, and mass spectrometry were used to identify and screen the protein kinase RNA-activated (PKR), then catRAPID and RPIseq were used to predict the binding ability of lnc&#95;000048 to PKR. Immunofluorescence (IF)-RNA fluorescence in situ hybridization (FISH) double labeling was performed to verify the subcellular colocalization of lnc&#95;000048 and PKR in the cytoplasm of M1 macrophage. We speculate that lnc&#95;000048 may form stem-loop structure-specific binding and activate PKR by inducing its phosphorylation, leading to activation of STAT1 phosphorylation and thereby enhancing STAT1 pathway-mediated polarization of THP-1 macrophages to M1 and inflammatory factor expression. Taken together, these results reveal that the lnc&#95;000048/PKR/STAT1 axis plays a crucial role in the polarization of M1 macrophages and may be a novel therapeutic target for atherosclerosis alleviation in stroke., (Copyright © 2024 Copyright: © 2024 Neural Regeneration Research.)

Riparian zones are important depositional environments at the catchment scale and provide environmental services such as carbon sequestration. This zone is a highly dynamic interface for oxygen and electron exchange, which confers the basis for reactive oxygen species (ROS) production. However, the differences in soil ROS production and their impact on carbon turnover across various redox locations within the riparian zone remain to be fully elucidated. In this study, we investigated the distribution characteristics and generation mechanism of ROS in riparian soil based on soil samples collected in a three-month field monitoring experiment, with additional incubation experiments conducted to examine the effect of hydroxyl radical ( • OH) on soil organic carbon (SOC) mineralization. The obtained results demonstrated that the riverine wetland was the hotspot zone for • OH production, with the production flux of 13.05 μmol kg -1 d -1 , which was significantly higher than that in floodplain (7.29 μmol kg -1 d -1 ) and riverbank soils (8.61 μmol kg -1 d -1 ). Moreover, • OH levels displayed distinct rhythmic fluctuations, with significantly higher concentrations at low water levels compared to those at high water levels, and remained essentially flat over three cycles. The statistic analysis revealed that the ROS production was highly dependent on reduced species and microbial community structure, which function as biogeochemical batteries and electron shuttles under redox fluctuations. Furthermore, the generated • OH involved in the abiotic mineralization of SOC, contributing to 13.1‒21.8 % of total CO 2 efflux. Compared to particulate organic carbon (POC), mineral-associated organic carbon (MAOC) fractions of SOC were more susceptible to • OH attacks. The findings provide a novel insight to comprehensively assess the redox process on riparian carbon turnover., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: CMRF35-like molecule-1 (CLM-1) is a receptor of the CD300 family that inhibits MRGPRX2-mediated mast cell degranulation. Understanding the role and mechanism of CLM-1 agonist has significant implications for the treatment of allergic disease. Quercetin is a natural small molecule compound derived from plants and vegetables that has been shown to prevent histamine release by immune cells., Objective: This study aims to examine the inhibitory effects of quercetin on MRGPRX2-mediated mast cell degranulation via CLM-1., Results: We found that C48/80 stimulation resulted in significantly increased release of β-hexosaminidase, histamine and Ca 2+ in CLM-1-knockdown LAD2 cells than in NC-LAD2 cells. Surface plasmon resonance (SPR) and molecular docking analyses revealed high-affinity binding between quercetin and CLM-1 ( K D = 2.962×10 -5 mol/L) mediated by the formation of hydrogen bonds. In addition, quercetin can selectively bind to CLM-1 on mast cells, leading to SHP-1 phosphorylation and subsequent inhibition of downstream MyD88/IKK/NF-κB signaling. Furthermore, activation of CLM-1 modulated the surface expression of MRGPRX2 by inhibiting F-actin, leading to internalization of the MRGPRX2 receptor via the PI3K/AKT/ Rac1/Cdc42 pathway., Conclusion: Quercetin is a promising treatment for allergic diseases by acting as a CLM-1 agonist that inhibits MRGPRX2-mediated mast cell degranulation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Zhao et al.)

In this work, fusible microspheres loaded with radiopaque agents as an embolic agent for transcatheter arterial embolization (TAE) are developed. A poly(ethylene glycol) (PEG) and poly(ε-caprolactone) (PCL) multi-block copolymer basing polyurethane (PCEU) is synthesized and fabricated into blank microspheres (BMs). The microspheres are elastic in compression test. A clinical contrast agent lipiodol is encapsulated in the microspheres to receive fusible radiopaque microspheres (FRMs). The sizes of FRMs are uniform and range from 142.2 to 343.1 µm. The encapsulated lipiodol acts as the plasticizer to reduce the melting temperature point (T m ) of PECU microspheres, thus, leading to the fusion of microspheres to exhibit efficient embolization in vivo. The performance of FRMs is carried out on a rabbit ear embolization model. Serious ischemic necrosis is observed and the radiopacity of FRMs sustains much longer time than that of commercial contrast agent Loversol in vivo. The fusible and radiopaque microsphere is promising to be developed as an exciting embolic agent., (© 2024 Wiley‐VCH GmbH.)

Perioperative neurocognitive dysfunction (PND) occurs in elderly individuals undergoing anesthesia and surgery. To explore the potential molecular mechanisms, we performed right-sided cervical exploratory surgery under sevoflurane anesthesia in 18-month-old male Sprague-Dawley rats. Anxiety-depression-like behaviors and learning memory abilities were assessed using the Open Field Test (OFT) and Novel Object Recognition (NOR). Additionally, the hippocampus was collected one day after surgery for inflammatory factor detection, TUNEL staining, and metabolomics analysis. Mendelian randomization (MR) analyses were subsequently conducted to validate the causal relationships by using a series of GWAS datasets related to representative differential metabolites as exposures and cognitive impairment as endpoints. The results indicated that rats exposed to anesthesia and surgery exhibited poorer cognitive performance, significant elevations in hippocampal inflammatory factors such as IL-1β and TNF-α, and extensive neuronal apoptosis. LC-MS/MS-based untargeted metabolomics identified 19 up-regulated and 32 down-regulated metabolites in the test group, with 6 differential metabolites involved in metabolic pathways enriched according to the KEGG database. ROC analysis revealed a correlation between α-linolenic acid (ALA) and linoleic acid (LA) and the development of PND. Further MR analysis confirmed that ALA was significantly associated with cognitive performance and the risk of depression, while LA was significantly associated with the risk of memory loss. Taken together, our results identified ALA and LA as potentially powerful biomarkers for PND., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

It was common to see that older adults were reluctant to be vaccinated for coronavirus disease 2019 (COVID-19) in China. There is a lack of practical prediction models to guide COVID-19 vaccination program. A nationwide, self-reported, cross-sectional survey was conducted from September 2022 to November 2022, including people aged 60 years or older. Stratified random sampling was used to divide the dataset into derivation, validation, and test datasets at a ratio of 6:2:2. Least absolute shrinkage and selection operator and multivariable logistic regression were used for variable screening and model construction. Discrimination and calibration were assessed primarily by area under the receiver operating characteristic curve (AUC) and calibration curve. A total of 35057 samples (53.65% males and mean age of 69.64 ± 7.24 years) were finally selected, which constitutes 93.73% of the valid samples. From 33 potential predictors, 19 variables were screened and included in the multivariable logistic regression model. The mean AUC in the validation dataset was 0.802, with sensitivity, specificity, and accuracy of 0.732, 0.718 and 0.729 respectively, which were similar to the parameters in the test dataset of 0.755, 0.715 and 0.720, respectively, and the mean AUC in the test dataset was 0.815. There were no significant differences between the model predicted values and the actual observed values for calibration in these groups. The prediction model based on self-reported characteristics of older adults was developed that could be useful for predicting the willingness for COVID-19 vaccines, as well as providing recommendations in improving vaccine acceptance.

Designing adaptive and smart hydrogel wound dressings to meet specific needs across different stages of wound healing is crucial. Here, we present a composite hydrogel, GSC/PBE@Lut, that offers self-regulating release of cupric ions and luteolin and modulates mechanical properties to promote chronic wound healing. The double network hydrogel, GSC, is fabricated through photo-cross-linking of gelatin methacrylate, followed by Cu 2+ -alginate coordination cross-linking. On one hand, GSC allows for rapid Cu 2+ release to eliminate bacteria in the acidic pH environment during inflammation and reduces the hydrogel's mechanical strength to minimize tissue trauma during early dressing changes. On the other hand, GSC enables slow Cu 2+ release during the proliferation stage, promoting angiogenesis and biocompatibility. Furthermore, the inclusion of pH- and reactive oxygen species (ROS)-responsive luteolin nanoparticles (PBE@Lut) in the hydrogel matrix allows for controlled release of luteolin, offering antioxidant and anti-inflammatory effects and promoting anti-inflammatory macrophage polarization. In a murine model of Staphylococcus aureus infected wounds, GSC/PBE@Lut demonstrates exceptional therapeutic benefits in antibacterial, anti-inflammatory, angiogenic, and tissue regeneration. Overall, our results suggest that smart hydrogels with controlled bioactive agent release and mechanical modulation present a promising solution for treating chronic wounds.

In patients on maintenance hemodialysis (MHD), vascular calcification (VC) is an independent predictor of cardiovascular disease (CVD), which is the primary cause of death in chronic kidney disease (CKD). The main component of VC in CKD is the vascular smooth muscle cells (VSMCs). VC is an ordered, dynamic activity. Under the stresses of oxidative stress and calcium-‑phosphorus imbalance, VSMCs undergo osteogenic phenotypic transdifferentiation, which promotes the formation of VC. In addition to traditional epigenetics like RNA and DNA control, post-translational modifications have been discovered to be involved in the regulation of VC in recent years. It has been reported that the process of osteoblast differentiation is impacted by catalytic histone or non-histone arginine methylation. Its function in the osteogenic process is comparable to that of VC. Thus, we propose that arginine methylation regulates VC via many signaling pathways, including as NF-B, WNT, AKT/PI3K, TGF-/BMP/SMAD, and IL-6/STAT3. It might also regulate the VC-related calcification regulatory factors, oxidative stress, and endoplasmic reticulum stress. Consequently, we propose that arginine methylation regulates the calcification of the arteries and outline the regulatory mechanisms involved., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Approximately one-third of postoperative patients are troubled by postoperative pain. Effective treatments are still lacking. The aim of this study is to investigate the role of brain-derived neurotrophic factor (BDNF)-VGF (non-acronymic) in dorsal root ganglia (DRG) in postoperative pain. Pain behaviors were assessed through measurements of paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). Transcriptome analysis was conducted to identify potential targets associated with postoperative pain. Western blotting, immunofluorescence, and ELISA were employed to further detect macrophage activation as well as the expression of BDNF, VGF, TNF-α, IL-1β, and IL-6. Results showed that plantar incision induced both mechanical and thermal hyperalgesia. Transcriptome analysis suggested that plantar incision caused upregulation of BDNF and VGF. The expressions of BDNF and VGF were upregulated in isolectin B4-positive (IB4 + ) and calcitonin gene-related peptide-positive (CGRP + ) neurons, rather than neurofilament 200-positive (NF200 + ) neurons. The activation of BDNF-VGF pathway upregulated expression of IL-6, TNF-α, and IL-1β and promoted the activation of macrophages. In conclusion, BDNF-VGF pathway aggravates acute postoperative pain by promoting macrophage activation and pro-inflammatory cytokine production, which may provide a new target for the treatment of postoperative pain., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ovarian cancer (OV) poses a significant challenge in clinical settings due to its difficulty in early diagnosis and treatment resistance. FOXP4, belonging to the FOXP subfamily, plays a pivotal role in various biological processes including cancer, cell cycle regulation, and embryonic development. However, the specific role and importance of FOXP4 in OV have remained unclear. Our research showed that FOXP4 is highly expressed in OV tissues, with its elevated levels correlating with poor prognosis. We further explored FOXP4's function through RNA sequencing and functional analysis in FOXP4-deficient cells, revealing its critical role in activating the Wnt signaling pathway. This activation exacerbates the malignant phenotype in OV. Mechanistically, FOXP4 directly induces the expression of protein tyrosine kinase 7 (PTK7), a Wnt-binding receptor tyrosine pseudokinase, which causes abnormal activation of the Wnt signaling pathway. Disrupting the FOXP4-Wnt feedback loop by inactivating the Wnt signaling pathway or reducing FOXP4 expression resulted in the reduction of the malignant phenotype of OV cells, while restoring PTK7 expression reversed this effect. In conclusion, our findings underscore the significance of the FOXP4-induced Wnt pathway activation in OV, suggesting the therapeutic potential of targeting this pathway in OV treatment., (© 2024. The Author(s).)

Objective: Diabetic retinopathy (DR) can cause permanent blindness with unstated pathogenesis. We aim to find novel biomarkers and explore the mechanism of apoptotic protease activating factor 1 (APAF1) in DR., Methods: Differential expression genes (DEGs) were screened based on GSE60436 dataset to find hub genes involved in pyroptosis after comprehensive bioinformatics analysis. DR mice model was constructed by streptozotocin injection. The pathological structure of retina was observed using hematoxylin-eosin staining. The enzyme-linked immunosorbent assay was applied to assess inflammatory factors, vascular endothelial growth factor (VEGF), and oxidative stress. The mRNA and protein expression levels were detected using quantitative real-time polymerase-chain reaction and Western blot. Cell counting kit and flow cytometry were employed to detect proliferation and apoptosis in high glucose-induced ARPE-19 cells., Results: Total 71 pyroptosis-related DEGs were screened. BIRC2, CXCL8, APAF1, PPARG, TP53, and CYCS were identified as hub genes of DR. APAF1 was selected as a potential regulator of DR, which was up-regulated in DR mice. APAF1 silencing alleviated retinopathy and inhibited pyroptosis in DR mice with decreased levels of inflammatory factors, VEGF, and oxidative stress. Moreover, APAF1 silencing promoted proliferation while inhibiting apoptosis and caspase-3/GSDME-dependent pyroptosis with a decrease in TNF-α, IL-1β, IL-18, and lactate dehydrogenase in high glucose-induced ARPE-19 cells. Additionally, caspase-3 activator reversed the promotion effect on proliferation and inhibitory effect on apoptosis and pyroptosis after APAF1 silencing in high glucose-induced ARPE-19 cells., Conclusion: APAF1 is a novel biomarker for DR and APAF1 silencing inhibits the development of DR by suppressing caspase-3/GSDME-dependent pyroptosis., Competing Interests: The authors declare that they have no conflicts of interest to disclose in this work., (© 2024 Ding et al.)

Introduction: Mitochondrial fission process 1 ( MTFP1 ) is an inner mitochondrial membrane (IMM) protein implicated in the development and progression of various tumors, particularly lung squamous cell carcinoma (LUSC). This study aims to provide a more theoretical basis for the treatment of LUSC., Methods: Through bioinformatics analysis, MTFP1 was identified as a novel target gene of HIF1A . MTFP1 expression in LUSC was examined using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Proteomics Data Commons (PDC) databases. The Kaplan-Meier plotter (KM plotter) database was utilized to evaluate its correlation with patient survival. Western blot and chromatin immunoprecipitation (ChIP) assays were employed to confirm the regulatory relationship between MTFP1 and HIF1A . Additionally, cell proliferation, colony formation, and migration assays were conducted to investigate the mechanism by which MTFP1 enhances LUSC cell proliferation and metastasis., Results: Our findings revealed that MTFP1 overexpression correlated with poor prognosis in LUSC patients(P < 0.05). Moreover, MTFP1 was closely associated with hypoxia and glycolysis in LUSC (R = 0.203; P < 0.001, R = 0.391; P < 0.001). HIF1A was identified as a positive regulator of MTFP1 . Functional enrichment analysis demonstrated that MTFP1 played a role in controlling LUSC cell proliferation. Cell proliferation, colony formation, and migration assays indicated that MTFP1 promoted LUSC cell proliferation and metastasis by activating the glycolytic pathway (P < 0.05)., Conclusions: This study establishes MTFP1 as a novel HIF1A target gene that promotes LUSC growth by activating the glycolytic pathway. Investigating MTFP1 may contribute to the development of effective therapies for LUSC patients, particularly those lacking targeted oncogene therapies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is presently the most prevalent chronic liver disorder globally that is closely linked to obesity, dyslipidemia metabolic syndrome, and type 2 diabetes mellitus (T2DM). Its pathogenesis is strongly associated with inflammation, and diet is a major factor in reducing inflammation. However, current research has focused primarily on exploring the relationship between diet and NAFLD, with less research on its link to MAFLD., Methods: In this research, using dietary inflammatory index (DII) as a measure to assess dietary quality, we analyzed the relationship between diet and MAFLD. Data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018, including 3,633 adults with complete DII and MAFLD, were used to develop cross-sectional analyses. Logistic regression analysis was adapted for investigating the relationship between DII and MAFLD development. Additionally, subgroup analysis and threshold effect analysis were carried out., Results: A positive link between DII and MAFLD was found in the fully adjusted model (OR = 1.05; 95%CI, 1.00-1.11, p  < 0.05). Subgroup analysis indicated that there was no significant dependence for the connection between DII and MAFLD except for the subgroup stratified by age. Compared with other age groups, people with MAFLD had 20% higher DII scores than non-MAFLD participants in those aged 20-41 years old (OR = 1.20; 95%CI, 1.08-1.33, p  < 0.001). Furthermore, we found a U-shaped curve with an inflection point of 3.06 illustrating the non-linear connection between DII and MAFLD., Conclusion: As a result, our research indicates that pro-inflammatory diet may increase the chance of MAFLD development, thus improved dietary patterns as a lifestyle intervention is an important strategy to decrease the incidence of MAFLD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yan, Zhou, Ding and Tu.)