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Biofilms and their associated infections have posed serious threats to the society from both an economical concern and a healthcare perspective. Graphene oxide (GO) has recently prompted the emergence of applications in the area of antibacterial materials owing to its high biocompatibility and surface functionalization. However, the weak biological interactions with microbial cells limit the antibiotic activity of GO. Herein, by combining GO with currently utilized antibacterial metal ions, copper ion‐graphene oxide composite (Cu2+@GO) with exceptional bactericidal activity is achieved in this work. Cu2+@GO composite possessed more than 95% antimicrobial efficiency of both Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) compared with the Cu2+ only group or GO only group. Additionally, the composite inhibits the formation of bacterial biofilms, making it a potential candidate for the development of alternative antimicrobials. Antibacterial mechanism study shows that Cu2+@GO has both bacteria‐binding ability and the property of producing reactive oxygen species (ROS) to cause the bacterial destruction. In vivo experiments indicate that Cu2+@GO possess an inhibition effect to P. aeruginosa‐induced keratitis. Overall, this work demonstrates that Cu2+@GO may be promising antibacterial agents for the treatment of bacterial infection, which contributes to designing more antibiotic and safe graphene‐based materials. [ABSTRACT FROM AUTHOR]

Uncontrolled hemorrhage is still the most common cause of potentially preventable death after trauma in prehospital settings. However, there rarely are hemostatic materials that can achieve safely and efficiently rapid hemostasis simultaneously. Here, new carbonized cellulose‐based aerogel hemostatic material is developed for the management of noncompressible torso hemorrhage, the most intractable issue of uncontrolled hemorrhage. The carbonized cellulose aerogel is derived from the Agaricus bisporus after a series of processing, including cutting, carbonization, purification, and freeze‐drying. In vitro, the carbonized cellulose aerogels with porous structure show improved hydrophilicity, good blood absorption, and coagulation ability, rapid shape recoverable ability under wet conditions. And in vivo, the carbonized aerogels show effective hemostatic ability in both small and big animal serious hemorrhage models. The amount of blood loss and the hemostatic time of carbonized aerogels are all better than the positive control group. Moreover, the mechanism studies reveal that the good hemostatic ability of the carbonized cellulose aerogel is associated with high hemoglobin binding efficiency, red blood cell absorption, and platelets absorption and activation. Together, the carbonized aerogel developed in this study could be promising for the management of uncontrolled hemorrhage. [ABSTRACT FROM AUTHOR]

In this study, highly efficient ECL luminophores composed of iridium complex-based nanowires (Ir–NCDs) were synthesized via covalently linking bis(2-phenylpyridine)-(4-carboxypropyl-2,2′-bipyridyl) iridium(III) hexafluorophosphate with nitrogen-doped carbon quantum dots (NCDs). The ECL intensity of the nanowires showed a five-fold increase in ECL intensity compared with the iridium complex monomer under the same experimental conditions. A label-free ECL biosensing platform based on Ir–NCDs was established for Salmonella enteritidis (SE) detection. The ECL signal was quenched linearly in the range of 102–108 CFU/mL for SE with a detection limit of 102 CFU/mL. Moreover, the relative standard deviations (RSD) of the stability within and between batches were 0.98% and 3.9%, respectively. In addition, the proposed sensor showed high sensitivity, selectivity and stability towards SE in sheep feces samples with satisfactory results. In summary, the excellent ECL efficiency of Ir–NCDs demonstrates the prospects for Ir(III) complexes in bioanalytical applications. [ABSTRACT FROM AUTHOR]

The impact of climate change on the basin is extensive and long-lasting, which will have a profound impact on the natural ecosystems, water resources, agriculture, and human production and life throughout the basin. An in-depth understanding of the impacts of climate change on watersheds and quantitative assessments will help to scientifically plan and manage water resources and protect the integrity of natural ecosystems. In this paper, temperature, precipitation and potential evapotranspiration data were used to analyze the response of Xiying River runoff to climatic factors in the Qilian Mountains by sliding correlation and wavelet analysis. M-K test and cumulative anomaly (CA) were used to analyze the climatic factors and runoff in the basin and use the pettitt method to test. Finally, the cumulative rate slope change rate comparison method was used to analyze the change of precipitation, potential evapotranspiration and snow-melt water contribution to runoff in this area. The results showed that temperature, precipitation and potential evapotranspiration had obvious mutations from 1961 to 2012 in this region. Compared with temperature and potential evapotranspiration, the precipitation showed greater impact on runoff. In addition, the contribution rate of ice and snow melt water to runoff was relatively larger in 1990 - 2002 compared to 1961-1989, followed by precipitation and evapotranspiration; the increase of the precipitation contribution rate became the main factor to runoff, followed by ice and snow melting and evapotranspiration compared to 1990-2002 in 2003-2017.

Purpose: Sepsis is an aggressive and life-threatening organ dysfunction induced by infection. Excessive inflammation and coagulation contribute to the negative outcomes for sepsis, resulting in high morbidity and mortality. In this study, we explored whether Eupatilin could alleviate lung injury, reduce inflammation and coagulation during sepsis. Methods: We constructed an in vitro sepsis model by stimulating RAW264.7 cells with 1 μg/mL lipopolysaccharide (LPS) for 6 hours. The cells were divided into control group, LPS group, LPS+ Eupatilin (Eup) group, and Eup group to detect their cell activity and inflammatory cytokines and coagulation factor levels. Cells in LPS+Eup and Eup group were pretreated with Eupatilin (10μM) for 2 hours. In vivo, mice were divided into sham operation group, cecal ligation and puncture (CLP) group and Eup group. Mice in the CLP and Eup groups were pretreated with Eupatilin (10mg/kg) for 2 hours by gavage. Lung tissue and plasma were collected and inflammatory cytokines, coagulation factors and signaling were measured. Results: In vitro, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and tissue factor (TF) expression in LPS-stimulated RAW264.7 cells was downregulated by Eupatilin (10μM). Furthermore, Eupatilin inhibited phosphorylation of the JAK2/STAT3 signaling pathway and suppressed p-STAT3 nuclear translocation. In vivo, Eupatilin increased the survival rate of the mice. In septic mice, plasma concentrations of TNF-α, IL-1β and IL-6, as well as TF, plasminogen activator inhibitor 1 (PAI-1), D-dimer, thrombin-antithrombin complex (TAT) and fibrinogen were improved by Eupatilin. Moreover, Eupatilin alleviated lung injury by improving the expression of inflammatory cytokines and TF, fibrin deposition and macrophage infiltration in lung tissue. Conclusion: Our results revealed that Eupatilin may modulate inflammation and coagulation indicators as well as improve lung injury in sepsis via the JAK2/STAT3 signaling pathway. [ABSTRACT FROM AUTHOR]

Electrochemiluminescence (ECL) has received considerable attention as a powerful analytical technique for the sensitive and accurate detection of biological analytes owing to its high sensitivity and selectivity and wide dynamic range. To satisfy the growing demand for ultrasensitive analysis techniques with high efficiency and accuracy in complex real sample matrices, considerable efforts have been dedicated to developing ECL strategies to improve the sensitivity of bioanalysis. As one of the most effective approaches, diverse signal amplification strategies have been integrated with ECL biosensors to achieve desirable analytical performance. This review summarizes the recent advances in ECL biosensing based on various signal amplification strategies, including DNA-assisted amplification strategies, efficient ECL luminophores, surface-enhanced electrochemiluminescence, and ratiometric strategies. Sensitivity-enhancing strategies and bio-related applications are discussed in detail. Moreover, the future trends and challenges of ECL biosensors are discussed. [ABSTRACT FROM AUTHOR]

Summary: To determine the effects of sperm DNA fragmentation (SDF) on embryo morphokinetic parameters, cleavage patterns and embryo quality, this retrospective study analyzed 151 intracytoplasmic sperm injection (ICSI) cycles (1152 embryos collected) between November 2016 and June 2019. SDF was assessed using sperm chromatin dispersion. The cycles were divided into two groups based on the SDF rate: SDF < 15% (n = 114) and SDF ≥ 15% (n = 37). The embryo morphokinetic parameters, cleavage patterns, and embryo quality were compared between the two groups. The morphokinetic parameters tPNf, t2, t3, t4, t5, t6, and t8 were achieved significantly earlier in the SDF < 15% group compared with in the SDF ≥ 15% group. The fertilization and 2PN rates seemed to be significantly higher in the SDF < 15% group compared with in the SDF ≥ 15% group, while the abnormal cleavage rates were similar. However, a significantly higher rate of chaotic cleavage (CC) was observed in the SDF ≥ 15% group. The D3 high-quality embryo and available embryo rates were similar between the two groups. The blastocyst formation, high-quality blastocyst, and available blastocyst rates in the SDF < 15% group were significantly higher than those in the SDF ≥ 15% group. With an increase in SDF level, the chemical pregnancy, clinical pregnancy and implantation rates tended to decrease, while the miscarriage rate increased. This study demonstrated that SDF ≥ 15% reduces the fertilization rate of ICSI cycles and affects certain morphokinetic parameters. A higher SDF level can also induce a higher rate of CC, with subsequent decreases in the blastocyst formation rate and blastocyst quality. [ABSTRACT FROM AUTHOR]

Herbal plants typically have complex compositions and diverse mechanisms. Among them, bioactive constituents with relatively high exposure in vivo are likely to exhibit therapeutic efficacy. On the other hand, their bioavailability may be influenced by the synergistic effects of different bioactive components. Cytochrome P450 3A (CYP3A) is one of the most abundant CYP enzymes, responsible for the metabolism of 50% of approved drugs. In recent years, many therapeutic herbal constituents have been identified as CYP3A substrates. It is more evident that CYP3A inhibition derived from the herbal formula plays a critical role in improving the oral bioavailability of therapeutic constituents. CYP3A inhibition may be the mechanism of the synergism of herbal formula. In this review, we explored the multiplicity of CYP3A, summarized herbal monomers with CYP3A inhibitory effects, and evaluated herb-mediated CYP3A inhibition, thereby providing new insights into the mechanisms of CYP3A inhibition-mediated oral herb bioavailability. [ABSTRACT FROM AUTHOR]

The aim of the present study was to explore the role of ataxia-telangiectasia mutated (ATM) in lipopolysaccharide (LPS)-induced in vitro model of septic acute kidney injury (AKI) and the association between ATM, tubular epithelial inflammatory response and autophagy. The renal tubular epithelial cell HK-2 cell line was cultured and passaged, with HK-2 cell injury induced by LPS. The effects of LPS on HK-2 cell morphology, viability, ATM expression and inflammation were observed. Lentiviral vectors encoding ATM shRNA were constructed to knock down ATM expression in HK-2 cells. The efficiency of ATM knockdown in HK-2 cells was detected by western blot analysis and reverse transcription-quantitative PCR (RT-qPCR). HK-2 cells transfected with the ATM shRNA lentivirus were used for subsequent experiments. Following ATM knockdown, corresponding controls were set up, and the effects of ATM on inflammation and autophagy were detected in HK-2 cells using RT-qPCR, western blotting and ELISA. After LPS stimulation, the HK-2 cells were rounded into a slender or fusiform shape with poorly defined outlines. LPS treatment reduced cell viability in a partly dose-dependent manner. LPS increased the expression of tumor necrosis factor-α, interleukin (IL)-1β and IL-6, with the levels reaching its highest value at 10 µg/ml. IL-6 and IL-1β expression increased with increasing LPS concentration. These findings suggest that LPS reduced HK-2 cell viability whilst increasing the expression of inflammatory factors. Following transfection with ATM shRNA, expression levels of key autophagy indicators microtubule associated protein 1 light chain 3α I/II ratio and beclin-1 in the two ATM shRNA groups were also significantly reduced compared with the NC shRNA group. In summary, downregulation of ATM expression in HK-2 cells reduced LPS-induced inflammation and autophagy in sepsis-induced AKI in vitro, suggesting that LPS may induce autophagy in HK-2 cells through the ATM pathway leading to the upregulation of inflammatory factors. [ABSTRACT FROM AUTHOR]

Aims: To investigate the association between body mass index (BMI) and all-cause mortality in patients with type 2 diabetes mellitus (T2DM) and to determine any sex-specific differences in this association. Methods: We retrospectively enrolled patients with T2DM and investigated the annual death data for seven years starting from 2010. All-cause mortality was calculated using Life Tables analysis. Multivariate Cox proportional hazards analysis was performed to identify the association between BMI and mortality. Results: During a mean survey period of 7.33 ± 1.42 years (X± SD), 996 of the 17259 patients enrolled died, resulting in an all-cause mortality rate of 5.77%, with no significant difference between women and men (6.04% vs. 5.56%; x2 = 1.766, P = 0.184). The top three causes of death were ischemic heart disease, cerebrovascular disease, and chronic kidney failure. A total of 87, 266, 332, and 311 patients with a BMI of <18.5, 18.5–23.99, 24.0–27.99, and ≥28.0 kg/m2, respectively, died, with the corresponding mortality rate calculated at 15.45%, 3.30%, 5.80%, and 10.70%, respectively. The BMI value associated with the highest all-cause mortality was <18.5 kg/m2, but this association was only significant in women aged <50 years (HR: 3.12; 95% CI, 1.62–4.34; P < 0.001). Conclusions: In patients with T2DM, a low BMI in women aged <50 years predicted high all-cause mortality. [ABSTRACT FROM AUTHOR]

IntroductionCoagulopathy plays an important role in sepsis. The aim of this study was to determine whether bone marrow stromal cell (BMSC) administration could attenuate coagulopathy in sepsis. Materials and methodsIn vitro: endothelial cells were cultured with/without BMSCs for 6 h following LPS stimulation and were collected for thrombomodulin (TM) and endothelial protein C receptor (EPCR) measurements.In vivo: Thirty-six mice were randomized into sham, sepsis, and sepsis + BMSC groups (n = 12 each group). Sepsis was induced through cecal ligation and puncture (CLP). BMSC infusion was started at 6 h after CLP. Lung tissues and plasma samples were collected at 24 h after CLP for enzyme-linked immunosorbent assay (ELISA), quantitative real-time RT-PCR, western blot, and immunohistochemistry analysis. ResultsIn vitro: BMSCs attenuated the decrease in TM and EPCR mRNA and protein expression levels in LPS-stimulated endothelial cells.In vivo: BMSC treatment decreased lung injury and mesenteric perfusion impairment, and ameliorated coagulopathy, as suggested by the reduction in elevated TF, vWF, and TAT circulation levels. BMSC infusion decreased TF mRNA transcription and protein expression levels in lung tissues, and increased TM and EPCR mRNA transcription and expression levels. DiscussionBMSC administration attenuated coagulopathy, and decreased lung injury and mesenteric perfusion impairment in sepsis. Key messagesBMSCs increased the expression of TM and EPCR from endothelium cells exposed to LPS in vitro.BMSC treatment attenuated lung injury and coagulopathy in the mice cecal ligation and puncture (CLP) model.BMSC administration-attenuated coagulopathy is related to the reduced expression of TF and increased expression of TM and EPCR. [ABSTRACT FROM PUBLISHER]

The rational design and construction of composite electrodes are crucial for overcoming the issues of poor working stability and slow ionic electron mobility of a single component. Nevertheless, it is a big challenge to construct core-shell heterostructures with crystalline/amorphous/crystalline heterointerfaces in straightforward and efficient methods. Here, we have successfully converted a portion of crystalline CoGa 2 O 4 into the amorphous phase by employing a facile sulfidation process (denoted as CoGa 2 O 4 -S), followed by anchoring crystalline NiCo-layered double hydroxide (denoted as NiCo-LDH) nanoarrays onto hexagonal plates and nucleation points of CoGa 2 O 4 -S, synthesizing dual-type hexagonal and flower-like 3D CoGa 2 O 4 -S@NiCo-LDH core-shell heterostructures with crystalline/amorphous/crystalline heterointerfaces on carbon cloth. Furthermore, we further adjust the Ni/Co ratio in LDH, achieving precise and controllable core-shell heterostructures. Benefiting from the abundant crystalline/amorphous/crystalline heterointerfaces and synergistic effect among various components, the CoGa 2 O 4 -S@Ni 2 Co 1 -LDH electrode exhibits a specific capacity of 247.8 mAh·g -1 at 1 A·g -1 and good rate performance. A CoGa 2 O 4 -S@Ni 2 Co 1 -LDH//AC flexible asymmetric supercapacitor provides an energy density of 58.2 Wh·kg -1 at a power density of 850 W·kg -1 and exhibits an impressive capacitance retention of 105.7% after 10,000 cycles at 10 A·g -1 . Our research provides profound insights into the design of other similar core-shell heterostructures.

Introduction: Attempts to artificially activate unfertilized oocytes at 24 h post intracytoplasmic sperm injection (ICSI) have generally resulted in poor outcomes. This study aims to explore a new strategy for early judgement and rescue activation of unfertilized oocytes at 5 h post ICSI to avoid unexpected fertilization failure (UFF) or unexpected low fertilization (ULF) in ICSI cycles., Methods: Firstly, time-lapse data from 278 ICSI cycles were retrospectively analyzed to establish an indicator for fertilization failure prediction. Secondly, 14 UFF and 20 ULF cycles were enrolled for an observational study, early rescue oocyte activation (EROA) was performed on oocytes without post-ICSI Pb2 extrusion to investigate fertilization efficiency, embryo development and clinical outcomes., Results: The average time to Pb2 extrusion post-ICSI was 3.03±1.21 h, 95.54% of oocytes had extruded Pb2 before 5 h, and the sensitivity and specificity for monitoring Pb2 extrusion at 5 h by time-lapse imaging to predict fertilization were 99.59% and 99.78%, respectively. Early rescue activation of oocytes with no Pb2 extrusion resulted in acceptable fertilization and embryo developmental outcomes, in terms of the fertilization rate (75.00, 72.99%), 2PN fertilization rate (61.36, 56.93%), good-quality embryo rate (42.59, 50.00%), blastocyst formation rate (48.28, 46.03%), good-quality blastocyst rate (34.48, 33.33%), and oocyte utilization rate (36.36, 27.74%), for both UFF and ULF cycles. The clinical pregnancy, embryo implantation, and early miscarriage rates in the rescue oocyte activation group did not significantly differ from those in the Pb2 extrusion group. Fourteen unexpected fertilization failures and 20 low fertilization ICSI cycles were rescued and resulted in clinical pregnancy rates of 40.00% (4/10) and 57.14% (8/14), respectively., Conclusions: This study demonstrates that monitoring Pb2 extrusion by time-lapse imaging can accurately predict fertilization outcomes, suggesting that early rescue oocyte activation at 5 h post ICSI is an effective strategy for avoiding unexpected fertilization failure and low fertilization in ICSI cycles., 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 Xue, Wang, Wei, Liu, Mao, Qin, Li, Zhang, Li, Huang, Chen, Shi and Liu.)

Background: Does short-interval second ejaculation improve sperm quality, embryo development and clinical outcomes for oligoasthenozoospermia males received intracytoplasmic sperm injection (ICSI) treatment?, Methods: All enrolled male patients underwent short-interval secondary ejaculation on the day of oocyte retrieval, and 786 sibling MII oocytes from 67 cycles were equally divided into two groups based on whether the injected spermatozoons originated from the first or second ejaculation. Semen parameters, embryo development efficiency, morphokinetic parameters and clinical outcomes were compared between the two groups to assess the efficiency and clinical value of short-interval second ejaculation in ICSI cycles., Results: Short-interval second ejaculation significantly improved sperm motility, normal morphological rate, and sperm DNA integrity both before and after sperm swim-up. The high-quality blastocyst rate (24.79% versus 14.67%), available blastocyst rate (57.56% versus 48.44%), and oocyte utilization rate (52.93% versus 45.29%) were significantly higher in the second ejaculation group ( P <0.05). The clinical pregnancy rate (59.09% versus 47.37%), implantation rate (42.11% versus 32.35%) and live birth rate (40.91% versus 31.58%) were higher in the second ejaculation group, but the differences were not significant ( P >0.05). Time-lapse analysis showed that morphokinetic time points after the 7-cell stage were earlier in the second ejaculation group but without a significant difference ( P >0.05), and abnormal embryo cleavage patterns between the two groups were not significantly different ( P >0.05)., Conclusions: Short-interval second ejaculation significantly improves sperm quality in oligoasthenozoospermic males, and is beneficial for blastocyst formation efficiency in ICSI cycles. This study suggested a non-invasive and simple but effective strategy for improving ICSI treatment outcomes., 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 © 2023 Li, Wang, Li, Huang, Liu, Zhang, Qin, Mao, Li, Chen, Wei, Shi and Xue.)

Low efficiency of targeting and delivery toward the thrombus site poses challenges to using thrombolytic drugs. Inspired by the biomimetic system of platelet membranes (PMs) and glucose oxidase (GOx) modification technologies, we develop a novel GOx-powered Janus nanomotor by asymmetrically attaching the GOx to polymeric nanomotors coated with the PMs. Then the PM-coated nanomotors were conjugated with urokinase plasminogen activators (uPAs) on their surfaces. The PM-camouflaged design conferred excellent biocompatibility to the nanomotors and improved their targeting ability to thrombus. The Janus distribution of GOx also allows the uneven decomposition of glucose in biofluids to produce a chemophoretic motion, increasing the drug delivery efficiency of nanomotors. In addition, these nanomotors are located at the lesion site due to the mutual adhesion and aggregation of platelet membranes. Furthermore, thrombolysis effects of nanomotors are enhanced in static and dynamic thrombus as well as in mouse models. It is believed that the novel PM-coated enzyme-powered nanomotors represent a great value for thrombolysis treatment.

Background: Dental follicle cells (DFCs) are promising candidates for tissue engineering. However, the molecular mechanisms that regulate the biological characteristics of DFCs are still unclear. Transient receptor potential melastatin 7 (TRPM7) is a Ca2+- and Mg2+-permeable cation channel. The aim of this study was to determine the impact of TRPM7 on the proliferation, migration and osteogenic differentiation of DFCs., Methods: PCR, Western blotting, Immunocytochemical staining and Patch clamp methods were used to identify the gene and protein expression of TRPM7 in DFCs. DFCs were infected with lentiviruses that expressed either TRPM7 specific shRNA or scrambled non-effective shRNA to investigate its functional role. Cell proliferation and migration were assessed using Cell Counting Kit-8 assays and transwell cell culture chambers separately. Cell osteogenic differentiation were determined by ALP assay kit and Alizarin Red staining., Results: Gene and protein expression of TRPM7 were detected in DFCs, but not of TRPM6, which is a closely related channel with similar function. In the absence of Mg2+, typical whole cell TRPM7-like currents were recorded by patch clamp. These were inhibited by low concentrations of 2-APB, but activated by high concentrations of 2-APB. Functional studies demonstrated that suppression of TRPM7 expression inhibited the proliferation and migration of DFCs, and promoted their osteogenic differentiation. Furthermore, Mg2+ deficiency mimicked the effects of TRPM7 knockdown in terms of osteogenic differentiation of DFCs., Conclusions: These results demonstrate that TRPM7 is involved in regulating the proliferation, migration and osteogenic differentiation of DFCs., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

Understanding the targets and interactions of long non-coding RNAs (lncRNAs) related to the retinoic acid-inducible gene-I (RIG-I) signaling pathway is essential for developing interventions, which would enable directing the host inflammatory response regulation toward protective immunity. In the RIG-I signaling pathway, lncRNAs are involved in the important processes of ubiquitination, phosphorylation, and glycolysis, thus promoting the transport of the interferon regulatory factors 3 and 7 (IRF3 and IRF7) and the nuclear factor kappa B (NF-κB) into the nucleus, and activating recruitment of type I interferons (IFN-I) and inflammatory factors to the antiviral action site. In addition, the RIG-I signaling pathway has recently been reported to contain the targets of coronavirus disease-19 (COVID-19)-related lncRNAs. The molecules in the RIG-I signaling pathway are directly regulated by the lncRNA-microRNAs (miRNAs)-messenger RNA (mRNA) axis. Therefore, targeting this axis has become a novel strategy for the diagnosis and treatment of cancer. In this paper, the studies on the regulation of the RIG-I signaling pathway by lncRNAs during viral infections and cancer are comprehensively analyzed. The aim is to provide a solid foundation of information for conducting further detailed studies on lncRNAs and RIG-I in the future and also contribute to clinical drug development., 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 © 2022 Liu, Ji, Cheng, Chen, Geng, Huang, Zhang, He and Song.)

Biomaterial-based bone grafts are emerged as an effective strategy for the treatment of large bone defects, especially for the scaffolds with enhanced osteogenic and angiogenic bioactivities. However, most studies focused on the direct interactions between scaffolds and bone-related cells such as osteoblasts and endothelial cells, and ignored the effects of material-triggered immunomodulation and the subsequent immune-regulated bone regeneration process. In this study, we developed a silicate bioceramic (Sr 2 ZnSi 2 O 7 , SZS) scaffold with well-defined pore structures using a three-dimensional (3D) printing technique. The prepared scaffolds were biodegradable, and the released bioactive ions were beneficial for immunomodulation, which stimulated macrophages to release more pro-healing cytokines and less pro-inflammatory cytokines. The obtained scaffold/macrophage conditioned medium further promoted the proliferation and osteogenic differentiation of a murine preosteoblast cell line (MC3T3-E1), as well as the angiogenic activity of human umbilical vein endothelial cells (HUVECs). Moreover, the in vivo experiments of critical-sized calvarial defects in rats revealed that the 3D printed SZS scaffolds could facilitate more vascularized bone regeneration than the 3D printed β-tricalcium phosphate (β-TCP, a typical clinically used bioceramic) scaffolds, suggesting that the 3D-printed SZS scaffolds hold the potential as implantable biomaterials with favorable osteoimmunomodulation for bone repair., 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 © 2022 Pan, Deng, Huang, Zhang, Yu, Huang, Chen and Chang.)

Backgrounds: Globally, the high morbidity and mortality of gastric carcinoma (GC) have been one of the great challenges facing humanity. However, the early diagnosis of GC is still unknown. Matrilin-3 (MATN3) is a member of the extracellular matrix (ECM) protein family. Previous studies have reported a correlation between the expression of MATN3 and bone disease. However, the role of MATN3 in GC has not been reported in depth, which can have a possible far-reaching implication for GC., Methods: We explored the diagnostic and prognostic value and pathway enrichment of MATN3 expression in GC. Limma package conducted by R was used to analysis the difference expression data of MATN3 from The Cancer Genome Atlas (TCGA). The receiver operating characteristic (ROC) curve analysis was used to estimate the diagnostic value of MATN3 expression. univariate and multivariate analysis were used to assess the prognostic value of MATN3, and gene set enrichment analysis (GSEA) to identify the enriched signaling pathways., Results: MATN3 was found to be significantly higher in GC tissue samples. GC patients with high MATN3 expression had poor prognosis. Then, GSEA showed that the gene sets were correlated with signaling pathways including ECM receptor interaction, hypertrophic cardiomyopathy (HCM), and glycosaminoglycan biosynthesis chondroitin sulfate, among others., Conclusions: The study suggests that MATN3 can serve as a potential diagnostic and prognostic biomarker for GC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/jgo-21-267). The authors have no conflicts of interest to declare., (2021 Journal of Gastrointestinal Oncology. All rights reserved.)

Background: N6-methyladenosine (m 6 A) RNA methylation is dynamically and reversibly regulated by methyl-transferases ("writers"), binding proteins ("readers"), and demethylases ("erasers"). The m 6 A is restored to adenosine and thus to achieve demethylation modification. The abnormality of m 6 A epigenetic modification in cancer has been increasingly attended. However, we are rarely aware of its diagnostic, progressive and prognostic performance in lung adenocarcinoma (LUAD). Methods and Results: The expression of 13 widely reported m 6 A RNA regulators in LUAD and normal samples were systematically analyzed. There were 12 m 6 A RNA methylation genes displaying aberrant expressions, and an 11-gene diagnostic score model was finally built (Diagnostic score =0.033*KIAA1429+0.116*HNRNPC+0.115*RBM15-0.067* METTL3-0.048*ZC3H13-0.221*WTAP+0.213*YTHDF1-0.132*YTHDC1-0.135* FTO+0.078*YTHDF2+0.014*ALKBH5). Receiver operating characteristic (ROC) analysis was performed to demonstrate superiority of the diagnostic score model (Area under the curve (AUC) was 0.996 of training cohort, P<0.0001; AUC was 0.971 of one validation cohort-GSE75037, P<0.0001; AUC was 0.878 of another validation cohort-GSE63459, P<0.0001). In both training and validation cohorts, YTHDC2 was associated with tumor stage (P<0.01), while HNRNPC was up expressed in progressed tumor (P<0.05). Besides, WTAP, RBM15, KIAA1429, YTHDF1, and YTHDF2 were all up expressed for TP53 mutation. Furthermore, using least absolute shrinkage and selection operator (lasso) regression analysis, a ten-gene risk score model was built. Risk score=0.169*ALKBH5-0.159*FTO+0.581*HNRNPC-0.348* YTHDF2-0.265*YTHDF1-0.123*YTHDC2+0.434*RBM15+0.143*KIAA1429-0.200*WTAP-0.310*METTL3. There existed correlation between the risk score and TNM stage (P<0.01), lymph node stage (P<0.05), gender (P<0.05), living status (P<0.001). Univariate and multivariate Cox regression analyses of relevant clinicopathological characters and the risk score revealed risk score was an independent risk factor of lung adenocarcinoma (HR: 2.181, 95%CI (1.594-2.984), P<0.001). Finally, a nomogram was built to facilitate clinicians to predict outcome. Conclusions: m 6 A epigenetic modification took part in the progression, and provided auxiliary diagnosis and prognosis of LUAD., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Myosin phosphatase targeting subunit 1 (Mypt1) is the regulatory subunit of myosin phosphatase which dephosphorylates the light chain of myosin II to inhibit its contraction. Although biochemical properties of Mypt1 have been characterized in detail, its biological functions in organisms are not well understood. The zebrafish mypt1 sq181 allele was found defective in the ventral pancreatic bud and extrapancreatic duct development, resulting in dysplasia of exocrine pancreas. In mypt1 sq181 mutant, the early growth of the ventral pancreatic bud was initiated but failed to expand due to impaired cell proliferation and increased cell apoptosis. As Mypt1 is essential for cell migration, the loss-of-function of Mypt1 in the mutant disrupted the lateral plate mesoderm migration during gut looping, therefore, altering the Bmp2a expression pattern within it, and eventually leading to impaired Bmp signaling in the adjacent exocrine pancreas. Overexpression of bmp2a could rescue the development of exocrine pancreas, suggesting that the impaired Bmp2a signaling is responsible for the pancreatic development defects. Bmp2a has been reported to promote the early specification of the ventral pancreatic bud, and our study reveals that it continues to serve as a cell proliferation/survival signal to ensure pancreatic bud growth properly in zebrafish., (© 2019 Wiley Periodicals, Inc.)