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In this work, we report on achieving enhanced performance NiOx/beta gallium oxide ( $\beta $ -Ga2O3) heterojunction p-n diodes (HJDs) through synergistic interface engineering (SIE), which can greatly improve the electrical characteristics and interface characteristics of HJDs. It is shown that the NiOx surface undergoes morphological improvement and hole concentration enhancement after the UV/ozone treatment (UVO). Owing to the improved interfacial properties of Ni/NiOx, the forward conduction current of NiOx/ $\beta $ -Ga2O3 HJD has significantly increased. Furthermore, the HJD performance can be improved by SIE with UVO and postannealing, especially for the reverse breakdown characteristics. Finally, a high-performance HJD without any terminal structure is obtained, which exhibits a low specific on-resistance of 2.47 m $\Omega \cdot $ cm2 and a high breakdown voltage of 1355 V, yielding a high Baliga’s figure of merit (BFOM) of 0.743 GW/cm2, which is a 219.17% enhancement in performance compared to untreated device. This work offers a practical and effective strategy for developing advanced Ga2O3 devices with exceptional performance metrics, paving the way for future technological breakthroughs.

Bone nonunion poses an urgent clinical challenge that needs to be addressed. Recent studies have revealed that the metabolic microenvironment plays a vital role in fracture healing. Macrophages and bone marrow-derived mesenchymal stromal cells (BMSCs) are important targets for therapeutic interventions in bone fractures. Itaconate is a TCA cycle metabolite that has emerged as a potent macrophage immunomodulator that limits the inflammatory response. During osteogenic differentiation, BMSCs tend to undergo aerobic glycolysis and metabolize glucose to lactate. Copper ion (Cu2+) is an essential trace element that participates in glucose metabolism and may stimulate glycolysis in BMSCs and promote osteogenesis. In this study, we develop a 4-octyl itaconate (4-OI)@Cu@Gel nanocomposite hydrogel that can effectively deliver and release 4-OI and Cu2+to modulate the metabolic microenvironment and improve the functions of cells involved in the fracture healing process. The findings reveal that burst release of 4-OI reduces the inflammatory response, promotes M2 macrophage polarization, and alleviates oxidative stress, while sustained release of Cu2+stimulates BMSC glycolysis and osteogenic differentiation and enhances endothelial cell angiogenesis. Consequently, the 4-OI@Cu@Gel system achieves rapid fracture healing in mice. Thus, this study proposes a promising regenerative strategy to expedite bone fracture healing through metabolic reprogramming of macrophages and BMSCs.

In situmonitoring of bone regeneration enables timely diagnosis and intervention by acquiring vital biological parameters. However, an existing gap exists in the availability of effective methodologies for continuous and dynamic monitoring of the bone tissue regeneration process, encompassing the concurrent visualization of bone formation and implant degradation. Here, we present an integrated scaffold designed to facilitate real-time monitoring of both bone formation and implant degradation during the repair of bone defects. Laponite (Lap), CyP-loaded mesoporous silica (CyP@MSNs) and ultrasmall superparamagnetic iron oxide nanoparticles (USPIO@SiO2) were incorporated into a bioink containing bone marrow mesenchymal stem cells (BMSCs) to fabricate functional scaffolds denoted as C@M/GLU using 3D bioprinting technology. In both in vivoand in vitroexperiments, the composite scaffold has demonstrated a significant enhancement of bone regeneration through the controlled release of silicon (Si) and magnesium (Mg) ions. Employing near-infrared fluorescence (NIR-FL) imaging, the composite scaffold facilitates the monitoring of alkaline phosphate (ALP) expression, providing an accurate reflection of the scaffold's initial osteogenic activity. Meanwhile, the degradation of scaffolds was monitored by tracking the changes in the magnetic resonance (MR) signals at various time points. These findings indicate that the designed scaffold holds potential as an in situbone implant for combined visualization of osteogenesis and implant degradation throughout the bone repair process.

The rheumatoid arthritis (RA) microenvironment is often followed by a vicious circle of high inflammation, endogenous gas levels imbalance, and poor treatment. To break the circle, we develop a dual-gas-mediated injectable hydrogel for modulating the immune microenvironment of RA and simultaneously releasing therapeutic drugs. The hydrogel (DNRS gel) could be broken down on-demand by consuming excessive nitric oxide (NO) and releasing therapeutic hydrogen sulfide (H2S), resulting in endogenous gas restoration, inflammation alleviation, and macrophage polarization to M2 type. Additionally, the hydrogel could suppress osteoclastogenesis and enhance osteogenesis. Furthermore, the intra-articularly injected hydrogel with methotrexate (MTX/DNRS gel) significantly alleviated inflammation and clinical symptoms and promoted the repair of bone erosion in the collagen-induced arthritis rat model. As a result, in vivoresults demonstrated that MTX/DNRS gel restored the microenvironment and improved the therapeutic effect of MTX. This study provides a novel understanding of developing versatile smart delivery platforms for RA treatment.

In this work, a new rapid and targeted method for screening α-glucosidase inhibitors from Hypericum beaniiwas developed and verified. Ten new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperlagarol A–J (1–10), and nine known PPAPs (11–19) were obtained from H. beanii. Their structures were identified by using comprehensive analyses involving mass spectrometry, ultraviolet spectroscopy, infrared spectroscopy, nuclear magnetic resonance spectroscopy, and electron capture dissociation calculations. 1and 2are two new rare 2,3-seco-spirocyclic PPAPs, 3and 4are two novel 12,13-seco-spirocyclic PPAPs, 5and 6are two novel spirocyclic PPAPs, 7and 8are two new unusual spirocyclic PPAPs with complex bridged ring systems, and 9and 10are two novel nonspirocyclic PPAPs. α-GC inhibitory activities of all isolated compounds were tested. Most of them displayed inhibitory activities against α-glucosidase, with the IC50values ranging from 6.85 ± 0.65 to 112.5 ± 9.03 μM. Moreover, the inhibitory type and mechanism of the active compounds were further analyzed using kinetic studies and molecular docking.

Gallium oxide (Ga2O3) p–n heterojunctions play an important role in addressing the difficulties in Ga2O3p-type doping. Therefore, an efficient and economical fabrication method needs to be established to create single-crystal Ga2O3heterojunctions for device applications. In this work, we successfully achieved epitaxial growth of single-crystal nickel oxide (NiO) and β-Ga2O3heterojunctions based on the low-cost and vacuum-free mist chemical-vapor deposition. The full width at half maximum of the X-ray diffraction rocking curves of NiO (111) and β-Ga2O3(−201) reached 0.077° and 0.807°, respectively. The energy band between NiO and β-Ga2O3has a Type II heterojunction. Finally, we prepared a quasi-vertical diode based on the NiO/β-Ga2O3heterojunction, which exhibits obvious rectification characteristics of the p–n junction and provides a reverse breakdown voltage of 117 V. This work proposes a low-cost fabrication method for β-Ga2O3p–n heterojunctions.

Li et al. reported the development and application of a novel hypoxia-sensitive fullerene-based nanotherapeutic system for photodynamic therapy in cancer treatment. This system integrates a [70]fullerene scaffold with amino-modified cyclodextrin and the hypoxia-activatable anticancer prodrug tirapazamine, enhanced with tumor-targeting peptides and disulfide bond donors. The created fullerene nanomaterial exhibits selective accumulation in tumor tissues, facilitated by its enhanced water solubility and targeted specificity.

As for the deep tissue infections of chronic osteomyelitis, antibiotics are hard to deliver into the infected bone tissue, which makes it difficult to be cured completely in clinic. Microwave has strong penetration, and the medium can produce a good bactericidal effect through the microwave thermal effect (MTE). Here, a new microwave sensitizer (Fe3O4@APNs) was prepared and evaluated. Black phosphorus nanosheets modified with phytic acid dodecasodium (APNs) were fabricated by a liquid-phase exfoliation method that exhibited good water oxygen stability. A complex with Fe3O4compound and APNs (Fe3O4@APNs) was formed by an ultrasonic mixing process, which showed excellent MTE (quickly increased to 53.5 °C in 5 min at 2.45 GHz, 10 W/cm2) via dielectric versus magnetic loss (reflect loss value of −5.94 dB at 2.45 GHz). The Fe3O4@APNs microwave sensitizer developed in this study has an outstanding in vitro antibacterial effect and might show promise for the treatment of chronic osteomyelitis enabled by local tissue heating via the MTE.

Time reliability (TR) is a critical factor that affects the efficiency and service quality of the urban rail transit network (URTN). However, previous studies have not incorporated TR into the evaluation of URTN station importance, focusing instead on basic centrality measures. Therefore, this paper proposes a new metric of station-based TR for evaluating and ranking URTN station importance. The new metric in combination with traditional centrality measures was used by the weighted Technique for Order of Preference by Similarity to Ideal Solution (weighted TOPSIS) to identify the combined significance level of individual URTN station importance and rank them accordingly. To investigate the performance of this method, we exploit deliberate attacks on the top-ranked stations through different methods. A case study of Beijing’s URTN during the morning peak hour showed that the proposed method is generally a better indicator for identifying station importance in maintaining network connectivity. The case study also demonstrated the feasibility and validity of the model. This study can provide recommendations for the planning and operation of rail transit systems and can inform the effective design of station protection strategies.

In this study, thin films of Ga2O3were fabricated on sapphire substrates utilizing metal–organic chemical vapor deposition technology, with deposition conducted at a temperature of 400 °C. The investigation focused on examining the influence of oxygen on the surface morphology, phase transition, and optical characteristics of Ga2O3films synthesized at relatively low temperatures. X-ray diffraction tests indicated that all films were polycrystalline and had mixed β and ε phases. With an increase in oxygen flow rate from 1400 to 1800 sccm, β-Ga2O3became the dominant material. Atomic force microscope analysis showed that the root-mean-square roughness had decreased. Film thicknesses, as measured by scanning electron microscopy, were 285.3, 257.6, 243.2, and 254.2 nm, respectively. The high-resolution transmission electron microscope confirmed a mixed-phase structure at an oxygen rate of 2100 sccm. Moreover, the X-ray photoelectron spectroscopy results show that increasing the oxygen flow rate from 1400 to 1800 sccm is effective in reducing the oxygen vacancies and defects in the films. However, excessive oxygen flow (2100 sccm) leads to the exacerbation of prereaction and the deterioration of the film’s crystalline quality.

To cope with global warming and achieve the goal of carbon emission reduction, various carbon policies have been implemented in many countries and regions. Some studies have indicated that with the popularity of low carbon, a small proportion of consumers show a green purchasing tendency. However, for firms, it is still difficult to predict the green purchase preferences of most consumers, and firms may face greater market demand uncertainty, which will bring profit risks. We assume that a firm’s decision is subject to its behavioral considerations, that is, its risk attitude. Considering the risk preferences of decision-makers and carbon emission policies, this paper addresses decision optimization in operations management. Our purpose is to analyze the optimal production decisions of risk-averse firms under carbon cap and carbon tax policies. Adopting the CVaR (conditional value-at-risk) criterion, we construct an optimization model with the constraints of carbon policies and obtain the analytic formula of optimal solutions. Then, we compare the optimal operational decisions for risk-averse firms and risk-neutral firms and further explore the impact of risk aversion on production and the parameters of carbon policy. Finally, some numerical studies are presented to analyze the carbon policies and risk aversion on firms’ operational decisions and give some managerial insights based on the analysis results.

This study explored the influence of Cr interfacial segregation on the precipitation mechanism and mechanical properties of MC carbides in high-carbon chromium bearing steels. The precipitation of Cr-doped MC carbides at different concentrations was investigated using microscopic morphological characterization (SEM, EDS and HR-TEM) alongside first principles calculations. The results indicated that both the austenite matrix and MC carbides exhibited, FCC structures, and the following orientation relationships of crystal planes in high-carbon chromium bearing steels were as follows: MC (010)//FCC-Fe (100) and MC (111)//FCC-Fe (111). Initially, Cr atoms adsorbed on the Fe-top site of the MC carbide (010) crystal plane, maintaining a distance of 2.5 Å from the Fe atom. Notably, when the Cr atom doping amount was 0.5, the Cr–Fe metallic bond exhibited a long bond length, large bond angle and low bond strength in the MC transition state (TS), resulting in a reduced, reaction barrier (908.08 kcal/mol), thus promoting the precipitation of MC carbide in bearing steel. However, at a Cr atom doping amount level of 1, the shorter bond length, small bond angle, and higher bonding strength of the Cr–Fe metallic bond in the MC TS, elevated the reaction barrier (49709.72 kcal/mol), inhibiting the precipitation of MC carbide in bearing steel. Additionally, this study quantitatively analyzed the effect of Cr atom content on the brittle plastic properties and hardness of MC carbides. At Cr atom contents of 0.23 and 1, the MC carbide hardness reached a minimum value of 3.0 GPa and a maximum value of 17.1 GPa, respectively. This investigation not only elucidated the atomic scale effects of Cr interfacial segregation on the precipitation mechanism and mechanical properties of MC carbides but also provided new ideas for controlling carbide precipitation in high-carbon chromium bearing steels.

Low-temperature photothermal therapy (PTT) is a noninvasive method that harnesses the photothermal effect at low temperatures to selectively eliminate tumor cells, while safeguarding normal tissues, minimizing thermal damage, and enhancing treatment safety. First we evaluated the transcriptome of tumor cells at the gene level following low-temperature treatment and observed significant enrichment of genes involved in cell cycle and heat response-related signaling pathways. To address this challenge, we have developed an engineering multifunctional nanoplatform that offered an all-in-one strategy for efficient sensitization of low-temperature PTT. Specifically, we utilized MoS2nanoparticles as the photothermal core to generate low temperature (40–48 °C). The nanoplatform was coated with DPA to load CPT-11 and Fe2+and was further modified with PEG and iRGD to enhance tumor specificity (MoS2/Fe@CPT-11-PEG-iRGD). Laser- and acid-triggered release of CPT-11 can significantly increase intracellular H2O2content, cooperate with Fe2+ions to increase intracellular lipid ROS content, and activate ferroptosis. Furthermore, CPT-11 induced cell cycle arrest in the temperature-sensitive S-phase, and increased lipid ROS levels contributed to the degradation of HSPs protein expression. This synergistic approach could effectively induce tumor cell death by the sensitized low-temperature PTT and the combination of ferroptosis and chemotherapy. Our nanoplatform can also maximize tumor cell eradication and prolong the survival time of tumor-bearing mice in vivo. The multifunctional approach will provide more possibilities for clinical applications of low-temperature PTT and potential avenues for the development of multiple tumor treatments.

Owing to their appealing three-dimensional structures and tunable photophysical properties, emissive metallacages have been widely applied in recognition and sensing, adsorption and separation, catalysis, etc. Recently, the application of emissive metallacages in biomedical fields has emerged as a hot research topic, because multiple biological functionalities can be facilely integrated into metallacage-based platforms to deliver different functions. In this review, the applications of emissive metallacages in bio-imaging, delivery and cancer theranostics are systematically summarized. The dilemmas and challenges of metallacage-based biomedical materials are also raised at the end of this review. We hope this review would provide some guidance for the construction of novel emissive metallacages with biological functions, and further advance the development of emissive metallacages as biomedical materials.

Fracture nonunion remains a great challenge for orthopedic surgeons. Fracture repair comprises of three phases, the inflammatory, repair and remodeling stage. Extensive advancements have been made in the field of bone repair, including development of strategies to balance the M1/M2 macrophage populations, and to improve osteogenesis and angiogenesis. However, such developments focused on only one or the latter two phases, while ignoring the inflammatory phase during which cell recruitment occurs. In this study, we combined Stromal Cell-Derived Factor-1α (SDF-1α) and M2 macrophage derived exosomes (M2D-Exos) with a hyaluronic acid (HA)-based hydrogel precursor solution to synthesize an injectable, self-healing, adhesive HA@SDF-1α/M2D-Exos hydrogel. The HA hydrogel demonstrated good biocompatibility and hemostatic ability, with the 4% HA hydrogels displaying great antibacterial activity against gram-negative E. coliand gram-positive S. aureusand Methicillin-resistant Staphylococcus aureus(MRSA). Synchronously and sustainably released SDF-1α and M2D-Exos from the HA@SDF-1α/M2D-Exos hydrogel enhanced proliferation and migration of human bone marrow mesenchymal stem cell (HMSCs) and Human Umbilical Vein Endothelial Cells (HUVECs), promoting osteogenesis and angiogenesis both in vivo and in vitro. Overall, the developed HA@ SDF-1α/M2D-Exos hydrogel was compatible with the natural healing process of fractures and provides a new modality for accelerating bone repair by coupling osteogenesis, angiogenesis, and resisting infection at all stages.

Deep learning methods have achieved excellent results in the field of grasp detection. However, deep learning-based models for general object detection lack the proper balance of accuracy and inference speed, resulting in poor performance in real-time grasp tasks. This work proposes an efficient grasp detection network with n-channel images as inputs for robotic grasp. The proposed network is a lightweight generative structure for grasp detection in one stage. Specifically, a Gaussian kernel-based grasp representation is introduced to encode the training samples, embodying the maximum center that possesses the highest grasp confidence. A receptive field block is plugged into the bottleneck to improve the model's feature discriminability. In addition, pixel-based and channel-based attention mechanisms are used to construct a multidimensional attention fusion network to fuse valuable semantic information, achieved by suppressing noisy features and highlighting object features. The proposed method is evaluated on the Cornell, Jacquard, and extended OCID grasp datasets. The experimental results show that our method achieves excellent balancing accuracy and running speed performance. The network gets a running speed of $\text{6}\,\text{ms}$, achieving better performance on the Cornell, Jacquard, and extended OCID grasp datasets with 97.8, 95.6, and 76.4% accuracy, respectively. Subsequently, an excellent grasp success rate in a physical environment is obtained using the UR5 robot arm.

Immune homeostasis is delicately mediated by the dynamic balance between effector immune cells and regulatory immune cells. Local deviations from immune homeostasis in the microenvironment of bone fractures, caused by an increased ratio of effector to regulatory cues, can lead to excessive inflammatory conditions and hinder bone regeneration. Therefore, achieving effective and localized immunomodulation of bone fractures is crucial for successful bone regeneration. Recent research has focused on developing localized and specific immunomodulatory strategies using local hydrogel-based delivery systems. In this review, we aim to emphasize the significant role of immune homeostasis in bone regeneration, explore local hydrogel-based delivery systems, discuss emerging trends in immunomodulation for enhancing bone regeneration, and address the limitations of current delivery strategies along with the challenges of clinical translation.

Ceramic cores are widely used in investment casting, and ideal properties of cores are essential for high-quality castings. Under the circumstances requiring thick cores, solid cores are likely to encounter deformation and cracking defects due to the accumulation of shrinkage. Therefore, with the superiority of ceramic stereolithography in producing complex ceramic parts, hollow cores with lattice structures were designed and fabricated. The dimensional accuracy and properties of the green and sintered bodies were evaluated. Results show the dimensional accuracy of sintered cores is controlled within ±0.25 mm benefited from the precise green bodies. The mechanical properties are not obviously deteriorated. The bending strength reaches 11.94 MPa at room temperature and 12.87 MPa at 1,500 °C with a creep deformation of 0.345 mm. Furthermore, casting verifications prove that the hollow cores meet the requirements of investment casting. Smooth casting surfaces are obtained, at the same time, the core-removal efficiency is improved by over 3 times.

The implantation of bare metal ureteral stents may lead to bacterial colonization and scar hyperplasia. To effectively address these issues, PLGA nanoparticles co-loaded with tranilast and gallium phytate (PG-TRL-PLGA-NPs) were prepared using an emulsifying solvent volatilization technique. The PG-TRL-PLGA-NPs possess a dual function of antibacterial and proliferation inhibition, which could be used for stent functional coating. The PG-TRL-PLGA-NPs displayed a regular spherical morphology with a smooth surface, and average particle size of 163 ± 1.37 nm, Zeta potential of −16.09 mV, drug loading capacity of 9.4 ± 0.6%, and encapsulation efficiency of 97.5 ± 0.4% could be achieved. FTIR, XRD, and DSC analysis demonstrated that PG-TRL-PLGA-NPS was successfully nano-encapsulated without chemical reaction among TRL, PG, and PLGA. In vitro release profiles of TRL and gallium ions from PG-TRL-PLGA-NPs exhibited a sustained-release effect, with 89.7 ± 0.9% and 3.2 ± 0.15 mg/L released in 14 days, respectively. Furthermore, it was observed the potent antibacterial activity (against S. aureusand E. coli.) of PG-TRL-PLGA-NPs, also significantly inhibited SV-HUC-1 cell proliferation through experiments involving cell migration, cell cycle, and apoptosis studies. These results provide valuable insights into the stent coatings of PG-TRL-PGLA NPs with potential functions of antibacterial and proliferative inhibitory.

Steel tubes can significantly enhance the strength and ductility of concrete-filled steel tube (CFST) and steel tube confined concrete (STCC) columns. Existing research work have mainly focused on the former type while the later type of members not only avoid longitudinal steel bulking but also provide better ductility performance to resist seismic loads which is further investigated in this paper. Based on partial-interaction shear-friction mechanics, a passive stress-strain model for short steel tube confined concrete columns is proposed. The main benefit of the proposed model is that it is based on mechanics for rectangular and circular cross-sections which could allow for the size effect. Besides, this model also gives the ultimate strength of steel tube confined concrete columns and is further simplified as a design-oriented approach. The proposed passive stress-strain model and the simplified model for the ultimate strength of concrete columns show good correlation with experimental data. Compared with three other existing approaches, the simplified model could enhance the computing efficiency to a new level. Then a parametric study is conducted to investigate the effect of specimen size on the behaviour of steel tube confined concrete columns.

Grouted Sleeve Connections (GSC) play an important role in assembly of structural members for precast concrete structures. With many experimental work and parametric study have been done on the tension load-slip behavior of GSC, the mechanical behavior for the tension load-slip responses of GSC should also be studied and explained. The failure modes for GSC in tensile tests with different material properties are firstly analyzed here by investigations on 326 GSC specimens. To study the mechanism of the failure modes, a partial-interaction numerical model is introduced to simulate the load-slip responses of GSC with provided bond-slip characteristics. The different boundary conditions for long and short embedment lengths are described respectively. More than 400 data points in load-slip responses are collected from tensile tests of GSC. The verification between theoretical results with test results shows good agreement. Hence, with the partial-interaction numerical model, the corresponding GSC load-slip responses could be obtained by given material and dimensional properties. Furthermore, parametric study shows that load-slip responses of GSC in tensile behavior change with embedment lengths of reinforcing bars. The CT scan results also show that embedment lengths for reinforcement are suggested to be longer than the designed size by considering the original defects of the sleeves and the eccentricity of reinforcement in construction.

Hydraulic simulation is one of the critical methods to research the filling mechanism of molten metal in the casting process. However, it only performs on test pieces with relatively simple structures due to the limitation of the preparation method. In this study, the method of photocuring additive manufacturing was used to prepare the complex casting mould from transparent photosensitive resin. The pouring test was carried out under different centrifugal conditions, and the filling process of the gating system, support bars and other positions in the vertical direction was recorded and analyzed. The experimental results show that the internal liquid level and the filling process of the test piece prepared by this method can be observed clearly. The angle between the liquid surface and the horizontal plane in the test piece gradually increases as the centrifugal rotational speed increases, which means the filling process is carried out from outside to inside at high rotational speed. The velocity of the fluid entering the runner increases with the increase of rotational speed, but the filling speeds is less affected by the centrifugal speed at other positions. The liquid flow is continuous and stable during the forward filling process, without splashing or interruption of liquid droplets.

A moderate inflammatory response at the early stages of fracture healing is necessary for callus formation. Over-active and continuous inflammation, however, impairs fracture healing and leads to excessive tissue damage. Adequate fracture healing could be promoted through suppression of local over-active immune cells in the fracture site. In the present study, we achieved an enriched concentration of PD-L1 from exosomes (Exos) of a genetically engineered Human Umbilical Vein Endothelial Cell (HUVECs), and demonstrated that exosomes overexpressing PD-L1 specifically bind to PD-1 on the T cell surface, suppressing the activation of T cells. Furthermore, exosomal PD-L1 induced Mesenchymal Stem Cells (MSCs) towards osteogenic differentiation when pre-cultured with T cells. Moreover, embedding of Exos into an injectable hydrogel allowed Exos delivery to the surrounding microenvironment in a time-released manner. Additionally, exosomal PD-L1, embedded in a hydrogel, markedly promoted callus formation and fracture healing in a murine model at the early over-active inflammation phase. Importantly, our results suggested that activation of T cells in the peripheral lymphatic tissues was inhibited after local administration of PD-L1-enriched Exos to the fracture sites, while T cells in distant immune organs such as the spleen were not affected. In summary, this study provides the first example of using PD-L1-enriched Exos for bone fracture repair, and highlights the potential of Hydrogel@Exos systems for bone fracture therapy through immune inhibitory effects.

ABSTRACT This study examined the combustion characteristics of wood-based panels and gypsum particle board (GPB) made from wood particles using a cone calorimeter according to the ISO 5660-1 specifications. The [...]

Background and Aims: Despite efforts to minimize publication reporting bias in medical research, it remains unclear whether the magnitude and patterns of the bias have changed over time. We aim to assess the frequency in which the statistical information is presented in forms other than P-values and evaluate how statistical significance was reported in the abstracts of reproductive medicine studies.Method: We studied reproductive medicine studies published in 23 Q1 journals in reproductive medicine, and five top medical journals, including JAMA, Lancet, BMJ, NEJM, and PLOS Medicine. We text-mined abstracts from 1990 to 2022 to extract P-value, confidence interval (CI), and text description in statistical significance; the presence of effect size metrics and Bayes factors were searched. One thousand abstracts were randomly selected and manually checked. The extracted statistical significance information was then analysed for temporal trends and distribution.Results: We identified 24,550 reproductive medicine abstracts. The proportion of abstracts reporting isolated P-values was 13.9% in 1990 and 18.8% in 2021 (Figure 1); reporting isolated P-values was 3.0% (95% CI, 0.5%-11.3%) in meta-analyses, 20.8% (95% CI, 11.3%-34.5%) in randomized controlled trials, and 33.3% (95% CI, 23.8%-44.3%) in basic research in 2021. By contrast, the proportion of abstracts in reporting effect measures without P-value surged from 4.1% to 23.3% from 1990 to 2021. The reported P-values (n = 18,132) mainly clustered at 0.001 (20.0%) and 0.05 (16.2%). Of the 14,689 abstracts containing at least one statement describing statistical significance, 74.9% of abstracts made at least one statistically significant statement; this proportion had merely changed over time (Figure 2).Conclusion: Despite the increasing adoption of effect measures to convey statistical significance, reporting isolated P-values remains common. Publication reporting bias is pervasive and persisting in reproductive medicine abstracts; the inflated treatment could mislead all types of patient care and policy decisions.

Six unusual meroterpenoids, psidiguajadiol A–J (1–6), and three known meroterpenoids (7–9) were isolated from the leaves of Psidium guajavaL. Compounds 2–6represent the first examples of 6/8-formyl-5,7-dihydroxy-4-phenylchromane-coupled sesquiterpenoids. The structures of the undescribed compounds, including their absolute configurations, were elucidated by spectroscopic analyses, X-ray diffraction, and computational calculations. Compounds 3, 4, and 6exhibited inhibitory activities against PTP1B with IC50values of 9.83, 18.52, and 16.87 μM, respectively. In light of these findings, we performed molecular docking studies to predict their inhibition mechanisms at the atomic level.

Bone tissue scaffolds with good bulk or surface osteoconductivity are always pursued by biomaterial scientists. In this paper, we design a tough and flexible amphoteric copolymer-based (AC) hydrogel with bioactive groups for bone regeneration. In detail, our hydrogels are copolymerized with N-acyl glycinamide (NAGA), anionic acrylate alendronate (AcAln), and cationic (2-(acryloyloxy)ethyl) trimethyl ammonium chloride (DMAEA-Q) by free radical polymerization. There are three kinds of synergetic physical cross-links among our polyamphion hydrogels: (1) double hydrogen bonds between amide groups in NAGA to provide toughness, (2) hydrogen bonds between dual bisphosphite groups in AcAln, and (3) weak ionic pairs between the anionic bisphosphite groups and the cationic quaternary ammonium groups in DMAEA-Q to offer flexibility. The AC hydrogel shows osteoid-like viscoelasticity, which makes the AC hydrogel osteogenesis inductive. During the repairing process, the bioactive bisphosphite groups accelerate the calcium fixation to expedite the mineralization of the new-formed bone. At the same time, the surface charge property of AC hydrogels also prevents fibrous cyst formation, thus guaranteeing osseointegration. Our in vitro data strongly demonstrate that the AC hydrogel is an excellent matrix to induce osteogenesis of rat bone marrow mesenchymal stem cells. More importantly, the following in vivo experiments further prove that the AC hydrogel can reach satisfactory bone regeneration without encapsulation of seed cells or application of external simulating cues. These exciting results demonstrate that our AC hydrogel is a promising scaffold for bone regeneration. Our work can also inspire the constituent and structure design of biomaterial scaffolds for tissue regeneration.

Carbon isotope fractionation serves as a crucial tool for assessing gas-in-place content and the gas-adsorbed ratio of shale gas during production. However, a significant gap exists in the understanding of the mechanism and impacts of diverse composition and organic matter on carbon isotope fractionation. To address this gap, this study conducted adsorption and desorption experiments on ten shale samples from the Longmaxi Formation. Various integrated analytical techniques were employed, encompassing X-ray diffraction, bitumen reflectance measurement, total organic carbon (TOC) content analysis, stable carbon isotope analysis, low-pressure gas adsorption tests, and field emission scanning electron microscopic observations. The results reveal that methane dominates the shale gas, with the carbon isotopes exhibiting a distinctive full reversal, attributed to the redox reaction between the ethane and water or transition metals. Differential adsorption capacities of shale led to varied carbon isotope distribution during desorption experiments. Increased micropore quantity in shale is anticipated to augment its adsorption capacity, while elevated feldspar content constrains adsorption due to the absence of intraparticle pores. Consequently, a negative correlation is observed between feldspar content and shale gas fractionation. Although intraparticle pores exist in carbon minerals, their connectivity and low carbonate content limit adsorption capacity in clay-rich shale. Deep burial depletes slit pores in clay minerals, resulting in a low adsorption capacity in clay-rich shale. Notably, the over-mature stage exhibits a substantial increase in micropores within organic matter, positively correlating with carbon isotope fractionation. The positive correlation between quartz content and TOC content is attributed to the positive relationship between the quartz content and carbon isotope fractionation. Additionally, the isotopic values of desorbed gas exhibit significant variability when TOC content exceeds 2.0%, remaining stable when TOC content is less than 2.0%.

Graphical Abstract: The study developed an optimized injectable hydrogel for photothermal therapy in osteoarthritis, focusing on the modulation of the inflammatory environment.

In adult mammals, injured retinal ganglion cells (RGCs) fail to spontaneously regrow severed axons, resulting in permanent visual deficits. Robust axon growth, however, is observed after intra-ocular injection of particulate β-glucan isolated from yeast. Blood-borne myeloid cells rapidly respond to β-glucan, releasing numerous pro-regenerative factors. Unfortunately, the pro-regenerative effects are undermined by retinal damage inflicted by an overactive immune system. Here, we demonstrate that protection of the inflamed vasculature promotes immune-mediated RGC regeneration. In the absence of microglia, leakiness of the blood-retina barrier increases, pro-inflammatory neutrophils are elevated, and RGC regeneration is reduced. Functional ablation of the complement receptor 3 (CD11b/integrin-αM), but not the complement components C1q−/−or C3−/−, reduces ocular inflammation, protects the blood-retina barrier, and enhances RGC regeneration. Selective targeting of neutrophils with anti-Ly6G does not increase axogenic neutrophils but protects the blood-retina barrier and enhances RGC regeneration. Together, these findings reveal that protection of the inflamed vasculature promotes neuronal regeneration.

Stomach adenocarcinoma (STAD) is a one of most common malignancies with high mortality-to-incidence ratio. Programmed cell death (PCD) exerts vital functions in the progression of cancer. The role of PCD-related genes (PRGs) in STAD are not fully clarified. Using TCGA, GSE15459, GSE26253, GSE62254 and GSE84437 datasets, PCD-related signature (PRS) was constructed with an integrative procedure including 10 machine learning methods. The role of PRS in predicting the immunotherapy benefits was evaluated by several predicting score and 3 immunotherapy datasets (GSE91061, GSE78220, and IMvigor210). The model developed by Lasso + CoxBoost algorithm having a highest average C-index of 0.66 was considered as the optimal PRS. As an independent risk factor for STAD patients, PRS had a good performance in predicting the overall survival rate of patients, with an AUC of 1-, 3-, and 5-year ROC curve being 0.771, 0.751 and 0.827 in TCGA cohort. High PRS score demonstrated a lower gene set score of some immune-activated cells and immune-activated activities. Patient with high PRS score had a higher TIDE score, higher immune escape score, lower PD1&CTLA4 immunophenoscore, lower TMB score, lower response rate and poor prognosis, indicating a less immunotherapy response. The IC50 value of some drugs correlated with chemotherapy and targeted therapy was higher in high PRS score group. Our investigation developed an optimal PRS in STAD and it acted as an indicator for predicting the prognosis, stratifying risk and guiding treatment for STAD patients.

Bone Repair Monitoring In article 2302687by Xiaojun Zhou, Chuanglong He, and co‐workers, a multimodal imaging‐incorporated biocomposite scaffold composed of 3D printed microfilaments and hydrogel networks is fabricated. The multifunctional scaffold significantly promote osteogenesis via sustained release of simvastatin, and effectively provide non‐invasive visualization of osteogenic level and scaffold degradation by using near‐infrared fluorescence imaging and magnetic resonance imaging.

The osteoblast/osteoclast and M1/M2 macrophage ratios play critical roles in delayed fracture healing. Robust osteoblast differentiation and M2 macrophage polarization can substantiality promote fracture repair; however, the combined effect of these strategies has not been previously studied. In this study, we constructed a cocktail therapy to simultaneously regulate the osteoblast/osteoclast and M1/M2 macrophage balance. The cocktail therapy composed of a natural polymer hyaluronic-acid-based hydrogel (HA hydrogel, which has a tissue-adhesive, injectable, self-healing, anti-inflammation profile), engineered endothelial cell-derived exosomes (EC-ExosmiR-26a-5p), and APY29, an IRE-1α inhibitor. This allowed for specific delivery of EC-ExosmiR-26a-5pand APY29 for osteoblast/osteoclast and macrophage regulation, respectively. The results suggested that the cocktail therapy exerted pro-fracture repair effects with each of its components established as indispensable. The assessed cocktail therapy provides insight into synergistic strategies and is useful for developing more suitable pro-fracture repair therapy.

In this note, we present an effective solution to the stabilization of linear input delay systems subject to dissipative constraints while all the effect of input delay is compensated by a controller with novel structure. The method is inspired by the recent development in the mathematical treatment of distributed delays and predictor controllers, which are critical for the derivation of the solution. An important conceptual innovation is the use of a parameterized dynamical state feedback controller (DSFC), where the dimension of the controller equals the dimension of the control input. A sufficient condition for the existence of a dissipative DSFC is obtained via the Krasovskii functional approach, where the condition includes a bilinear matrix inequality (BMI). To solve the BMI, we apply an inner convex approximation algorithm which can be initialized based on an explicit construction of a predictor controller gain. The proposed DSFC can be considered as an extension of the classical predictor controller, thereby capable of compensating all the effects of the pointwise input delay while satisfying dissipative constraints. A numerical example is given to illustrate the effectiveness of our proposed methodology.

Graphical Abstract: Schematic illustration of nanofibers applied in immunoregulation-based therapy. A variety of diseases can be treated via regulating immune microenvironment including tendon regeneration, bone/cartilage repair, nerve regeneration, skin regeneration and cancer therapy. Therefore, multifunctional nanofibers can provide opportunities for future construction of efficient immune therapy for cancer immunotherapy, tissue regeneration

[Display omitted] • Micro-Nano Structured VNb9O25 composites with rich oxygen vacancies have been prepared via a facile method. • Several effective strategies were used to unveil the conductivity enhancement and structure stabilization mechanism. • The VNb9O25 anodes can deliver remarkably LIB performance especially with ultra-long cycling performance. The oxygen vacancies and micro-nano structure can optimize the electron/Li+ migration kinetics in anode materials for lithium batteries (LIBs). Here, porous micro-nano structured VNb 9 O 25 composites with rich oxygen vacancies were reasonably prepared via a facile solvothermal method combined with annealing treatment at 800℃ for 30 h (VNb 9 O 25 -30 h). This micro-nano structure can enhance the contact of active material/electrolyte, and shorten the Li+ diffusion distance. The introduction of oxygen vacancies can further boosts the intrinsic conductivity of VNb 9 O 25 -30 h for achieving excellent LIB performance. The as-prepared VNb 9 O 25 -30 h anode showed advanced rate capability with reversible capacity of 122.2 mA h g−1 at 4 A g−1, and delivered excellent capacity retention of ∼100 % after 2000 cycles. Meanwhile, VNb 9 O 25 -30 h provides unexpected long-cycle life (i.e., reversible capacity of 165.7 mA h g−1 at 1 A g−1 with a high capacity retention of 85.6 % even after 8000 cycles). Additionally, coupled with the LiFePO 4 cathode, the LiFePO 4 //VNb 9 O 25 -30 h full cell delivers superior LIB properties with high reversible capacities of 91.6 mA h g−1 at 5C for 1000 cycles. Thus, such reasonable construction method can assist in other high-performance niobium-based oxides in LIBs. [ABSTRACT FROM AUTHOR]

Background: Robotic distal gastrectomy (RDG) has been increasingly used for the treatment of gastric cancer in recent year. However, whether RDG could reduce the morbidity when compared to laparoscopic distal gastrectomy (LDG) remains controversial. This study aimed to compare the morbidity and short-term surgical outcomes of RDG and LDG for gastric cancer and identify the related risk factors. Methods: Between March 2010 and August 2019, consecutive patients undergoing RDG or LDG (519 and 957 patients, respectively) at our institution were included in this study. Postoperative complications were stratified according to the Clavien–Dindo (C–D) classification. We performed one-to-one propensity score matching (PSM) analysis, and evaluated postoperative morbidity and short-term surgical outcomes in PSM 1032 patients undergoing RDG or LDG. Results: After PSM, the two groups were well-balanced. The mean blood loss of the RDG group was about 27 mL less than that of the LDG group (112.1 vs 139.0 mL, P< 0.001). The RDG group had more retrieved lymph nodes than that in the LDG group (32.7 v 30.2, P< 0.001). The RDG group showed a similar overall (9.9% vs 10.7%, P= 0.682), severe (2.7% vs 3.7%, P= 0.376), local (5.6% vs 5.2%, P= 0.783), and systemic complication rates (5.4% vs 6.0%, P= 0.688). There were no significant differences in mortality between the two groups (RDG 0% vs LDG 0.2%, P= 1.000). Subgroup analyses showed no significant differences in most stratified parameters. Age > 65 years and ASA III were identified as two major risk factors for complications. Conclusion: RDG could be a safe and feasible in treating gastric cancer compared to LDG. However, we did not observe significant reduction in postoperative complications of RDG compared with LDG, although the use of robotic system is assumed to provide a technically superior operative environment.

To evaluate cranial ultrasound markers during a first‐trimester routine ultrasound examination for screening for open spina bifida (OSB). Midsagittal and axial images of the fetal head obtained from fetuses with spina bifida and unaffected control fetuses at 11 weeks to 13 weeks 6 days were analyzed retrospectively. The observed markers of the posterior brain included the 4‐ versus 3‐line view, the brain stem (BS)‐to‐brain stem‐occipital bone (BSOB) distance ratio (BS/BSOB), the position relationship between the maxillo‐occipital (MO) line and the midbrain‐BS junction, and the crash sign status. This study included 9 OSB cases, 2 closed spina bifida (CSB) cases, and 200 unaffected controls. Eight of 9 OSB cases had informative midsagittal views of the head. The 3‐line view (abnormal) and BS/BSOB greater than 1 (abnormal) were observed in 87.5% (7 of 8) and 100% (8 of 8), respectively. The midbrain‐BS junction was below or nearly on the MO line (abnormal) in 100% (8 of 8). Seven of the cases had informative axial views of the head. The crash sign (abnormal) was observed in 85.7% (6 of 7). A 3‐line view was seen in all of the cases that had a positive crash sign. Neither of the 2 cases of CSB and none of the controls had any of the 4 first‐trimester intracranial ultrasound markers of OSB. The 4 first‐trimester intracranial ultrasound markers investigated in this study appear to be very good markers of OSB, especially a BS/BSOB greater than 1 and an abnormal MO line. The crash sign and 3‐line view were observed in the same fetus. In our study, these ultrasound findings were not helpful in CSB.

AbstractObjectiveOur study aimed at exploring whether miR-124-3p and miR-506-3p collaboratively modulated sirtuin 1 (SIRT1) protein expression in liver cancer. Materials and methods:In this study, cell viability, migration and invasion were assessed using CCK8 and transwell assays, respectively. Immunohistochemical (IHC) staining and immunoblotting analysis were performed to evaluate SIRT1 protein expression levels in tissue specimens and cell lines. Moreover, the nude-mouse transplanted tumour model was used to assess liver cancer cell growth in vivo. Results:Our results showed that SIRT1 protein levels were significantly up-regulated in liver cancer tissues and cancerous cell lines. Conversely, miR-124-3p and miR-506-3p were down-regulated in liver cancer tissues and cell lines. The protein expression of SIRT1 was significantly declined in HepG2 and SMMC7721 cells after transfection with miR-124-3p or miR-506-3p mimics. miR-124-3p and miR-506-3p collaboratively caused a marked inhibition of liver cancer cell growth, migration and invasion, while the phenomena were neutralized by overexpression of SIRT1. In vivoexperimental measurements also revealed that miR-124-3p and miR-506-3p synergistically inhibited SIRT1 protein expression and tumour growth in the nude-mouse transplanted tumour model. Conclusion:It was observed that miR-124-3p and miR-506-3p could cooperatively retard liver cancer cell growth via co-inhibiting SIRT1 protein expression.

The simulation model of a depletion-mode (D-mode) β-Ga2O3metal–oxide–semiconductor field-effect transistor (MOSFET) is constructed by Silvaco ATLAS technology computer-aided design (TCAD) simulation, which employs an epitaxial drift layer grown on a sapphire substrate. On this basis, the floating field plate (F-FP) structure based on the gate-pad-connected field plate (P-FP) is proposed to improve the breakdown characteristics of the device, which is easy to be prepared. The working principle of F-FP is investigated with the help of the device with one F-FP. Based on the principle that the number of floating field plates is increased on an optimized floating field plate structure. Subsequently, the devices with two and three floating field plates are simulated in turn, and the optimal structural parameters of the three F-FPs device are finally obtained, and the breakdown voltage is 3800 V at this time. In addition, it is found that the device breakdown voltage is increased by approximately 500–600 V for each additional floating field plate.

The marine-continental transitional shale of the Upper Permian Longtan Formation serves as a crucial target for both shale gas exploration and development, as well as a significant research object of the dramatic geological events during the Middle-Late Permian period. In this study, X-ray diffraction (XRD), polished section, scanning electron microscopy (SEM), energy spectrum analysis (EDS), total organic carbon content (TOC) and elemental geochemistry were conducted to elucidate the sedimentological and geochemical characteristics of the transitional shale in the Longtan Formation and the underlying Emeishan basalt in Western Guizhou. Additionally, the paleoenvironment conditions, the environmental effect of the Emeishan large igneous province and the organic matter enrichment mechanism of the transitional shale are investigated.

Microneedles are a novel drug delivery system that offers advantages such as safety, painlessness, minimally invasive administration, simplicity of use, and controllable drug delivery. As a type of polymer microneedle with a three-dimensional network structure, hydrogel microneedles (HMNs) possess excellent biocompatibility and biodegradability and encapsulate various therapeutic drugs while maintaining drug activity, thus attracting significant attention. Recently, they have been widely employed to promote wound healing and have demonstrated favorable therapeutic effects. Although there are reviews about HMNs, few of them focus on wound management. Herein, we present a comprehensive overview of the design and preparation methods of HMNs, with a particular emphasis on their application status in wound healing, including acute wound healing, infected wound healing, diabetic wound healing, and scarless wound healing. Finally, we examine the advantages and limitations of HMNs in wound management and provide suggestions for future research directions.

Postoperative adhesion is a common complication after abdominal surgery, but current clinical products have unsatisfactory therapeutic effects. Here, we present a hydrogel patch formed in a single step through dialysis. The exchange of DMSO into water facilitates hydrophobic aggregate in situ formation and the formation of hydrogen bonds within the hydrogel. Thanks to the optimized component ratio and precise structural design. The hydrogel patch has soft-tissue-like mechanical characteristics, including high strength, high toughness, low modulus similar to the abdominal wall, good fatigue resistance, and fast self-recovery properties. The nonswellable hydrogel patch retains over 80% of its original mechanical properties after 7 days of immersion in physiological saline, with a maximum swelling ratio of 5.6%. Moreover, the hydrophobic biomultifunctionality of benzyl isothiocyanate can self-assemble onto the hydrogel patch during the sol–gel transition process, enabling it to remodel the inflammatory microenvironment through synergistic antibacterial, antioxidant, and anti-inflammatory effects. The hydrogel patch prevents postsurgical adhesion in a rat sidewall defect-cecum abrasion model and outperforms the leading commercial Interceed. It holds promising potential for clinical translation, considering that FDA-approved raw materials (PVA and gelatin) form the backbone of this effective hydrogel patch.

We describe an 82-year-old man who was taken to our emergency department after being found unconscious. His electrocardiogram (ECG) showed ST-segment elevation in leads V4-V6 and cardiac troponin I (cTnI) was abnormally elevated. In addition to ECG and cTnI changes, this patient was combined with unconsciousness, high fever, abnormal liver function, acute renal failure, and rhabdomyolysis. The initial diagnosis was heat stroke, so cooling measures were initiated immediately, but a concurrent myocardial infarction was suspected. Meanwhile, emergency coronary angiography was performed, but no severe coronary stenosis or thrombosis was found. We first evaluated quantitative flow ratio (QFR) and coronary angiography-derived index of microvascular resistance (ca-IMR) in patients with heat stroke. Ca-IMR was 260 mmHg*s/m in the left circumflex artery, indicating the presence of coronary microvascular dysfunction (CMD). After several days of treatment, the patient recovered from multiple organ damage. Therefore, ECG and troponin results should be interpreted carefully in patients with high fever and coma during high temperature seasons.

Background: The application of molecular targeting therapy and immunotherapy has notably prolonged the survival of patients with hepatocellular carcinoma (HCC). However, multidrug resistance and high molecular heterogeneity of HCC still prevent the further improvement of clinical benefits. Dysfunction of tumor-infiltrating natural killer (NK) cells was strongly related to HCC progression and survival benefits of HCC patients. Hence, an NK cell-related prognostic signature was built up to predict HCC patients’ prognosis and immunotherapeutic response. Methods: NK cell markers were selected from scRNA-Seq data obtained from GSE162616 data set. A consensus machine learning framework including a total of 77 algorithms was developed to establish the gene signature in TCGA–LIHC data set, GSE14520 data set, GSE76427 data set and ICGC–LIRI–JP data set. Moreover, the predictive efficacy on ICI response was externally validated by GSE91061 data set and PRJEB23709 data set. Results: With the highest C-index among 77 algorithms, a 11-gene signature was established by the combination of LASSO and CoxBoost algorithm, which classified patients into high- and low-risk group. The prognostic signature displayed a good predictive performance for overall survival rate, moderate to high predictive accuracy and was an independent risk factor for HCC patients’ prognosis in TCGA, GEO and ICGC cohorts. Compared with high-risk group, low-risk patients showed higher IPS–PD1 blocker, IPS–CTLA4 blocker, common immune checkpoints expression but lower TIDE score, which indicated low-risk patients might be prone to benefiting from ICI treatment. Moreover, a real-world cohort, PRJEB23709, also revealed better immunotherapeutic response in low-risk group. Conclusions: Overall, the present study developed a gene signature based on NK cell-related genes, which offered a novel platform for prognosis and immunotherapeutic response evaluation of HCC patients.

Developing novel emissive supramolecular assemblies with elegant architectures and tunable performance remains highly desirable yet challenging. Herein, we report the design and synthesis of several 9,10-bis(diphenylmethylene)-9,10-dihydroanthracene-based metal-organic assembles with aggregation-induced emission characteristics. Such assemblies feature intriguing thermochromic and mechanochromic properties, i.e., distinguishable fluorescence responses in terms of emission wavelength and intensity under variable temperatures and pressures. Moreover, these assemblies can serve as excellent fluorescent sensors for the detection of polysaccharide molecules. Due to the differentiated charge type and density, the assembles display distinct sensing mechanisms toward different polysaccharide molecules. This study provides novel perspectives for the synthesis of butterfly-like platinum(II) supramolecular coordination complexes with multistimuli-responsiveness for polysaccharide sensing, which will facilitate the development of stimuli-responsive materials

Pancreatic cancer is one of the most fatal cancers in humans. While it thrives in a state of malnutrition, the mechanism by which pancreatic cancer cells adapt to metabolic stress through metabolic reprogramming remains unclear. Here, we showed that UBR5, an E3 ubiquitin ligase, was significantly upregulated in pancreatic cancer patient samples compared to the levels in adjacent normal tissues. Levels of UBR5 were closely related to a malignant phenotype and shorter survival among pancreatic cancer patients. Multivariate analyses also revealed that UBR5 overexpression was an independent predictor of poor outcomes among patients with pancreatic cancer. Functional assays revealed that UBR5 contributes to the growth of pancreatic cancer cells by inducing aerobic glycolysis. Furthermore, we demonstrated that UBR5 knockdown increased levels of fructose-1,6-bisphosphatase (FBP1), an important negative regulator in the process of aerobic glycolysis in many cancers. We found a significant negative correlation between levels of UBR5 and FBP1, further demonstrating that UBR5-induced aerobic glycolysis is dependent on FBP1 in pancreatic cancer cells. Mechanistically, UBR5 regulates FBP1 expression by modulating C/EBPa, directly binding to C/EBPa, and promoting its ubiquitination and degradation. Together, these results identify a mechanism used by pancreatic cancer cells to survive the nutrient-poor tumour microenvironment and also provide insight regarding the role of UBR5 in pancreatic cancer cell adaptation to metabolic stresses.

The leucine-rich repeat-containing G-protein-coupled receptor 6 (LGR6) is considered to be a stem cell marker in many normal tissues and promotes tissue development, regeneration, and repair. LGR6 is also related to the initiation and progression of some malignant tumors. However, the role of LGR6 in cervical cancer has not been reported. Here, immunohistochemistry and western blotting showed that LGR6 was significantly upregulated in cervical cancer, compared with the normal cervix. By analyzing The Cancer Genome Atlas database, LGR6 was found to be correlated with a poor prognosis of cervical cancer. Then, a small population of LGR6highcells isolated by using the fluorescence-activated cell sorting exhibited enhanced properties of cancer stem cells including self-renewal, differentiation, and tumorigenicity. Moreover, RNA sequencing revealed that LGR6 was correlated with the Wnt signaling pathway and TOP/FOP, reverse transcription-PCR, and western blotting further proved that LGR6 could activate the Wnt/β-catenin signaling pathway. Interestingly, LGR6 upregulated the expression of TCF7L2 by activating the Wnt/β-catenin pathway. Then, TCF7L2 combining with β-catenin in the nucleus enhanced LGR6 transcription by binding the promoter of LGR6, which further activated the Wnt signaling to form a positive feedback loop. Thus, our study demonstrated that LGR6 activated a novel β-catenin/TCF7L2/LGR6-positive feedback loop in LGR6highcervical cancer stem cells (CSCs), which provided a new therapeutic strategy for targeting cervical CSCs to improve the prognosis of cervical cancer patients.

We present a new approach for the stability analysis of linear coupled differential-difference systems with a general distributed delay. The distributed delay term in this note can contain any ${\mathbb{L}}^{2}$ function which is approximated via a class of elementary functions including polynomial, trigonometric, exponential functions, etc. Through the application of a new proposed integral inequality, a sufficient condition for the stability of the system is derived in terms of linear matrix inequalities based on the construction of a Lyapunov Krasovskii functional. The methods proposed in this note can handle problems that cannot be dealt using existing approaches. Two numerical examples are presented to show the effectiveness of our proposed stability condition. [ABSTRACT FROM AUTHOR]