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Abstract The effect of yttrium (Y) addition on the oxidation behavior of a Ni-based directionally solidified single-crystal superalloy is investigated in this study. Isothermal oxidation tests for samples with different levels of Y addition are conducted at 1100 °C in air. The Y content of the samples is determined by the actual pickup amount obtained from an Inductively Coupled Plasma-Atomic Emission Spectrometry test. It is discovered that the addition of Y increases the oxide resistance by the scale of an adhesive double-layer oxide, which is composed of Al2O3 and spinel Ni(Cr,Al)2O4. With 70 ppm of Y addition, the oxidation mass gain decreases from 12.6 g/m2 for the alloy without Y addition to 5.3 g/m2, and the oxidation rate decreases significantly. In addition, the internal nitride disappears after Y doping because of an increase in oxidation scale adherence and a decrease in oxidation products. In this study, the alloy with 660 ppm Y addition demonstrates the best oxidation resistance.

BackgroundSentinel lymph node biopsy (SLNB) has become standard procedure for early breast cancer patients with clinically node negative disease. The patients with SLN metastasis normally underwent axillary lymph node dissection (ALND). However, the metastatic status of non-sentinel Lymph nodes (non-SLNs) varied significantly in different reports. Here, we evaluated the prevalence of non-SLNs metastasis among breast cancer patients with sentinel lymph node metastasis and its impact on clinical decision-making.Materials and MethodsWe identified 892 female patients with operable cT1-3N0 invasive breast cancer who underwent ALND in our center due to SLN metastasis from 2017 to 2023, retrospectively. The prevalence of non-SLN metastasis among different clinicopathological traits and its correlation with the number of positive SLNs were analyzed. The optimal clinical decision-making was generalized.ResultsThe median number of SLN+, SLN, non-SLN+ and non-SLN was 2, 4, 1 and 14 among the enrolled 892 female patients, respectively. 504 (56.50%) patients with SLN + had at least one metastatic lymph node in the harvested non-SLNs. Among the enrolled 892 female patients, 435 (48.77%) patients with 1 positive SLN, of which 180 (41.38%) had at least one additional metastatic non-SLNs. 242 (27.13%) patients with 2 positive SLNs, of which 146 (60.33%) had at least one metastatic non-SLNs. For the rest 215 (24.10%) patients with at least 3 metastatic SLNs, 178 (82.79%) had at least one metastatic non-SLNs. In the univariate analysis, the non-SLNs metastatic status was correlated with the number of SLNs+, tumor size, tumor grade, lymphovascular invasion (LVI) and molecular subtypes, but not histopathologic type. In the multivariate analysis, the risk of additional non-SLNs metastasis correlated with the number of SLNs+, SLNs, non-SLNs and LVI.ConclusionOmiting ALND in patients with higher non-SLNs + rate outside the American College of Surgeons Oncology Group (ACSOG) Z0011 and the European Organization for Research and Treatment of Cancer (EORTC) 10,981–22023 AMAROS criteria should be considered with caution in clinical decision-making. To evaluate whether axillary radiotherapy and ALND provides equivalent regional control in breast cancer patients with obvious residual metastatic lymph nodes undesected in the axilla, a well-matched prospective randomized controlled trial is an urgent need.

Many inflammatory disorders, including diabetic kidney disease (DKD), are associated with pyroptosis, a type of inflammation-regulated cell death. The purpose of this work was to ascertain the effects of apabetalone, which targets BRD4, a specific inhibitor of the bromodomain (BRD) and extra-terminal (BET) proteins that target bromodomain 2, on kidney injury in DKD. This study utilized pharmacological and genetic approaches to investigate the effects of apabetalone on pyroptosis in db/db mice and human tubular epithelial cells (HK-2). BRD4 levels were elevated in HK-2 cells exposed to high glucose and in db/db mice. Modulating BRD4 levels led to changes in the generation of inflammatory cytokines and cell pyroptosis linked to NLRP3 inflammasome in HK-2 cells and db/db mice. Likewise, these cellular processes were mitigated by apabetalone through inhibition BRD4. Apabetalone or BRD4 siRNA suppressed PLK1 expression in HK-2 cells under high glucose by P300-dependent H3K27 acetylation on the PLK1 gene promoter, as demonstrated through chromatin immunoprecipitation and immunoprecipitation assays. To summarize, apabetalone relieves renal proptosis and fibrosis in DKD. BRD4 regulates the P300/H3K27ac/PLK1 axis, leading to the activation of the NLRP3 inflammasome and subsequent cell pyroptosis, inflammation, and fibrosis. These results may provide new perspectives on DKD treatment.

Abstract Although MXene has attracted great interest in diverse fields, it is susceptible to oxidation in water (H2O) with transition metal ions such as Co2+, Fe2+, and Cu2+, which is pronounced at high temperatures. This impedes the preparation of MXene‐based composites and their functional applications. Here, this study revealed that Co2+ increases the maximum and average atomic charge of H in H2O to improve the reactivity of H2O, which leads to the fact that Co2+ catalyzes the oxidation of Ti3C2Tx MXene. Furthermore, the addition of N,N‐dimethyl formamide (DMF) reduces the H2O activity and improves the oxidation stability of Ti3C2Tx in the presence of Co2+ via preferentially forming coordination bonds with Co2+. This strategy is also effective in enhancing the oxidation tolerance of Ti3C2Tx to Fe2+ in H2O. Moreover, it is feasible to enhance the oxidation stability of Ti2CTx MXene in H2O with the existence of Co2+. By virtue of these, the CoO/Ti3C2Tx composite was successfully prepared without obvious Ti3C2Tx oxidation, which is desirable to harness the advantages of Ti3C2Tx as the complementary component for lithium‐ion batteries. This work provides a straightforward paradigm to enhance the oxidation resistance of MXene in H2O in the presence of transition metal ions and at high temperatures, which opens a new vista to use MXene for target applications.

Abstract Background Colorectal cancer (CRC) is a major cause of cancer-related deaths worldwide, and chemoresistance is a major obstacle in its treatment. Despite advances in therapy, the molecular mechanism underlying chemoresistance in CRC is not fully understood. Recent studies have implicated the key roles of long noncoding RNAs (lncRNAs) in the regulation of CRC chemoresistance. Methods In this study, we investigated the role of the lncRNA LINC01852 in CRC chemoresistance. LINC01852 expression was evaluated in multiple CRC cohorts using quantitative reverse transcription PCR. We conducted in vitro and in vivo functional experiments using cell culture and mouse models. RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, and dual luciferase assays were used to investigate the molecular mechanism of LINC01852 in CRC. Results Our findings revealed that a lncRNA with tumor-inhibiting properties, LINC01852, was downregulated in CRC and inhibited cell proliferation and chemoresistance both in vitro and in vivo. Further mechanistic investigations revealed that LINC01852 increases TRIM72-mediated ubiquitination and degradation of SRSF5, inhibiting SRSF5-mediated alternative splicing of PKM and thereby decreasing the production of PKM2. Overexpression of LINC01852 induces a metabolic switch from aerobic glycolysis to oxidative phosphorylation, which attenuates the chemoresistance of CRC cells by inhibiting PKM2-mediated glycolysis. Conclusions Our results demonstrate that LINC01852 plays an important role in repressing CRC malignancy and chemoresistance by regulating SRSF5-mediated alternative splicing of PKM, and that targeting the LINC01852/TRIM72/SRSF5/PKM2 signaling axis may represent a potential therapeutic strategy for CRC.

Personal thermal management materials integrated with phase-change materials have significant potential to satisfy human thermal comfort needs and save energy through the efficient storage and utilization of thermal energy. However, conventional organic phase-change materials in a solid state suffer from rigidity, low thermal conductivity, and leakage, making their application challenging. In this work, polyethylene glycol (PEG) was chosen as the phase-change material to provide the energy storage density, polyethylene oxide (PEO) was chosen to provide the backbone structure of the three-dimensional polymer network and cross-linked with the PEG to provide flexibility, and carbon nanotubes (CNTs) were used to improve the mechanical and thermal conductivity of the material. The thermal conductivity of the composite fiber membranes was boosted by 77.1% when CNTs were added at 4 wt%. Water-resistant modification of the composite fiber membranes was successfully performed using glutaraldehyde-saturated steam. The resulting composite fiber membranes had a reasonable range of phase transition temperatures, and the CC4PCF-55 membranes had melting and freezing latent heats of 66.71 J/g and 64.74 J/g, respectively. The results of this study prove that the green CC4PCF-55 composite fiber membranes have excellent flexibility, with good thermal energy storage capacity and thermal conductivity and, therefore, high potential in the field of flexible wearable thermal management textiles.

Due to the severe harmful impacts of industrial dyeing wastewater on ecosystems and human health, proper treatment is crucial. Herein, the use of modified graphite as an adsorbent for dyeing wastewater treatment was investigated in this study. The graphite was oxidized and intercalated using a phosphoric acid–nitric acid–potassium permanganate system and then thermally treated at high temperatures to optimize its structure. By adjusting the thermal treatment temperature, the graphite adsorbent with varying porosity was obtained. The optimized graphite demonstrated significant improvement in adsorption performance for dyes and organic compounds, achieving a removal rate of over 85% for methylene blue (MB) dye. The optimal adsorption performance is achieved with a 1.6 mg modified graphite adsorbent at 60 °C under alkaline conditions for adsorbing 10 ppm MB. Adsorption kinetics and isotherm models were applied to elucidate the adsorption mechanisms. The results fit the Langmuir model, suggesting that monolayer homogeneous adsorption is favorable. Importantly, the results demonstrate that high-temperature treatment can significantly enhance the adsorption properties of coal-based graphite, supporting its application in dyeing wastewater treatment.

Abstract Background Gastric cancer patients harboring a TP53 mutation exhibit a more aggressive and chemoresistant phenotype. Unfortunately, efforts to identify the vulnerabilities to overcome these aggressive malignancies have made minimal progress in recent years. Therefore, there is an urgent need to explore the novel therapeutic strategies for this subclass. Histone methylation modulators are critical epigenetic targets for cancer therapies that help maintain the malignancies of cancers harboring TP53 mutations and senescence evasion. Triggering senescence is now considered to benefit multiple cancer therapies. Furthermore, senescence-based “one-two punch” therapy was validated in clinical trials. Therefore, we hypothesized that screening epigenetic modulators might help identify a novel vulnerability to trigger senescence in gastric cancer harboring TP53 mutations. Results We developed a novel efficient approach to identify senescence inducers by sequentially treating cells with drug candidates and senolytic agents. Based on this, we demonstrated that QC6352 (a selective KDM4C inhibitor) efficiently triggered cellular senescence in gastric cancer harboring TP53 mutations. More importantly, the “one-two punch’ therapy consisting of QC6352 and SSK1 eliminates tumor cells harboring TP53 mutations. This finding highlights a potential therapeutic strategy for the aggressive subgroup of gastric cancer. Besides, the functions of QC6352 were totally unknown. We demonstrated that QC6352 might possess far more powerful anti-tumor capacities compared to the traditional genotoxic drugs, 5-Fu and Oxaliplatin. Conclusions This initial investigation to identify a senescence inducer revealed that QC6352 triggers senescence in gastric cancer cells harboring TP53 mutations by regulating the SP1/CDK2 axis through suppressing KDM4C. QC6352 and senolytic agent-SSK1 represent a novel ‘one-two punch’ therapeutic strategy for the more malignant gastric cancer subtypes.

Abstract Background Elongin A (ELOA), our previous work revealed, serves as a novel tumor suppressor in colorectal cancer. However, the function and mechanism of ELOA in other cancer types, including gastric cancer (GC), remain to be elucidated. Methods The expression of ELOA was measured by quantitative reverse transcription‐polymerase chain reaction and western blot. The effects of ELOA on GC growth and metastasis were assessed through a series of in‐vitro and in‐vivo assays. Furthermore, the potential mechanism of ELOA was revealed by RNA sequencing, dual luciferase reporter assay, chromatin immunoprecipitation, and rescue experiments in GC. Results We uncovered increased expression of ELOA in GC tissues compared with paired normal tissues via bioinformatic analyses and our sample detection. Enhanced ELOA expression in GC tissues was obviously correlated with poor tumor differentiation, lymph node metastasis, advanced tumor stage, and a poor prognosis. A series of functional experiments showed that ELOA promoted the proliferation and metastasis of GC. Mechanistically, we revealed that the decreased levels of miR‐490‐3p caused the upregulation of ELOA in GC. Both RNA‐seq and ChIP assays revealed that ELOA transcriptionally activated retinol‐binding protein 1 (RBP1) by binding to its promotor. Furthermore, specific knockdown of RBP1 reduced the tumor‐promoting ability of ELOA in GC cells. Conclusions In summary, our findings demonstrate that ELOA exerts oncogenic properties by activating RBP1 expression, providing the basis for a promising therapeutic target in GC.

Ni-base superalloys operate in harsh service conditions where cyclic heating and cooling introduce deformation fields that need to be investigated in detail. We used the high-angular-resolution electron backscatter diffraction method to study the evolution of internal stress fields and dislocation density distributions in carbides, dendrites, and notch tips. The results indicate that the stress concentrations decay exponentially away from the notch, and this pattern of distribution was modified by the growth of cracks and the emission of dislocations from the crack tip. Crack initiation follows crystallographic traces and is weakly correlated with carbides and dendrites. Thermal cycles introduce local plasticity around carbides, the dendrite boundary, and cracks. The dislocations lead to higher local stored energy than the critical value that is often cited to induce recrystallization. No large-scale onset of recrystallization was detected, possibly due to the mild temperature (800 °C); however, numerous recrystallized grains were detected in carbides after 50 and 80 cycles. The results call for a detailed investigation of the microstructure-related, thermally assisted recrystallization phenomenon and may assist in the microstructure control and cooling channel design of turbine blades.

Abstract Objective Today, the development mode of public hospitals in China is turning from expansion to efficiency, and the management mode is turning from extensive to refined. This study aims to evaluate the efficiency of clinical departments in a Chinese class A tertiary public hospital (Hospital M) to analyze the allocation of hospital resources among these departments providing a reference for the hospital management. Methods The hospitalization data of inpatients from 32 clinical departments of Hospital M in 2021 are extracted from the hospital information system (HIS), and a dataset containing 38,147 inpatients is got using stratified sampling. Considering the non-homogeneity of clinical departments, the 38,147 patients are clustered using the K-means algorithm based on workload-related data labels including inpatient days, intensive care workload index, nursing workload index, and operation workload index, so that the medical resource consumption of inpatients from non-homogeneous clinical departments can be transformed into the homogeneous workload of medical staff. Taking the numbers of doctors, nurses, and beds as input indicators, and the numbers of inpatients assigned to certain clusters as output indicators, an input-oriented BCC model is built named the workload-based DEA model. Meanwhile, a control DEA model with the number of inpatients and medical revenue as output indicators is built, and the outputs of the two models are compared and analyzed. Results Clustering of 38,147 patients into 3 categories is of better interpretability. 14 departments reach DEA efficient in the workload-based DEA model, 10 reach DEA efficient in the control DEA model, and 8 reach DEA efficient in both models. The workload-based DEA model gives a relatively rational judge on the increase of income brought by scale expansion, and evaluates some special departments like Critical Care Medicine Dept., Geriatrics Dept. and Rehabilitation Medicine Dept. more properly, which better adapts to the functional orientation of public hospitals in China. Conclusion The design of evaluating the efficiency of non-homogeneous clinical departments with the workload as output proposed in this study is feasible, and provides a new idea to quantify professional medical human resources, which is of practical significance for public hospitals to optimize the layout of resources, to provide real-time guidance on manpower grouping strategies, and to estimate the expected output reasonably.

Abstract Colorectal cancer (CRC) is the third most common malignancy worldwide. It is well known that lipid metabolism reprogramming contributes to the tumor progression. However, the lipid metabolic alterations and potential remodeling mechanism underlying the chemoresistance of CRC remain largely unclear. In this study, we compared the gene expression profiles of chemoresistant versus control CRC cells from the GEO database and identified a key factor, Glycerol‐3‐phosphate acyltransferase 3 (GPAT3), that promotes lipid droplet (LD) production and confers chemoresistance of CRC. With applying of HPLC–MS and molecular dynamics simulation, we also demonstrated that the activity of lysophosphatidic acid synthesis by GPAT3 was dependent on its acetylation at K316 site. In particular, GPAT3‐mediated LD accumulation inhibited immunogenic cell death of tumor, and thus facilitated CD8+ T‐cell exhaustion and malignant progression in mouse xenografts and hepatic‐metastasis tumors in CRC patients. High GPAT3 expression turned CRC cells into nonimmunogenic cells after (Oxaliplatin) Oxa treatment, which was supported by a decrease in cytotoxic IFN‐γ release and CD8+ T‐cell exhaustion. In conclusion, these findings revealed the role of GPAT3‐associated LD accumulation, which conferred a malignant phenotype (chemoresistance) and regulated the tumor microenvironment of CRC. These results suggest that GPAT3 is a potential target to enhance CRC chemosensitivity and develop novel therapeutic interventions.

Background: There are limited population studies on the neurodevelopmental effects of bisphenol F (BPF), a substitute for bisphenol A. Furthermore, the role of placental estradiol as a potential mediator linking these two factors remains unclear. Objective: To examine the association between maternal prenatal BPF exposure and infant neurodevelopment in a prospective cohort study and to explore the mediating effects of placental estradiol between BPF exposure and neurodevelopment in a nested case-control study. Methods: The prospective cohort study included 1077 mother-neonate pairs from the Wuhu city cohort study in China. Maternal BPF was determined using the liquid/liquid extraction and Ultra-performance liquid chromatography tandem mass spectrometry method. Children's neurodevelopment was assessed at ages 3, 6, and 12 months using Ages and Stages Questionnaires. The nested case-control study included 150 neurodevelopmental delay cases and 150 healthy controls. Placental estradiol levels were measured using enzyme-linked immunosorbent assay kits. Generalized estimating equation models and robust Poisson regression models were used to examine the associations between BPF exposure and children's neurodevelopment. In the nested case-control study, causal mediation analysis was conducted to assess the role of placental estradiol as a mediator in multivariate models. Results: In the prospective cohort study, the pregnancy-average BPF concentration was positively associated with developmental delays in gross-motor, fine-motor, and problem-solving ( ORtotal ASQ: 1.14(1.05, 1.25), ORgross-motor: 1.22(1.10, 1.36), ORfine-motor: 1.19(1.07, 1.31), ORproblem-solving: 1.11(1.01, 1.23)). After sex-stratified analyses, pregnancy-average BPF concentration was associated with an increased risk of neurodevelopmental delays in the gross-motor (ORgross-motor:1.30(1.12, 1.51)) and fine-motor (ORfine-motor: 1.22(1.06, 1.40)) domains in boys. In the nested case-control study, placental estradiol mediated 16.6% (95%CI: 4.4%, 35.0%) of the effects of prenatal BPF exposure on developmental delay. Conclusions: Our study supports an inverse relationship between prenatal BPF exposure and child neurodevelopment in infancy, particularly in boys. Decreased placental estradiol may be an underlying biological pathway linking prenatal BPF exposure to neurodevelopmental delay in offspring.

PurposeA tertiary lymphoid structure (TLS) refers to an organized infiltration of immune cells that is linked to a positive prognosis and improved response to immunotherapy. However, methods that promote TLS formation are limited and challenging to implement in clinical settings. In this study, we aimed to promote the formation and maturation of TLSs in lung adenocarcinoma (LUAD) by combining low-dose radiotherapy (LDRT) with immunotherapy.MethodsTissue sections from 198 patients who had undergone surgery were examined. Risk factors for patient survival were assessed, and the relationship between TLSs and five-year survival was analyzed. The Kras-LSL-G12D spontaneous lung cancer mouse model was used to screen the optimal irradiation dose (0/1/2 Gy whole lung irradiation) for promoting TLS formation. LDRT combined with anti-PD-1 was used to promote the formation and maturation of TLSs.ResultsTLS+, TLSHigh, TLS+GC+ and CD8High within TLS+ were associated with a favorable prognosis. LDRT increased the formation of early TLSs in the Kras-LSL-G12D lung cancer mouse model. In addition, LDRT combined with anti-PD-1 treatment can significantly improve the maturity of TLSs in mouse LUAD, resulting in greater antitumor effects. This antitumor effect was strongly associated with the number of CD8+ T cells within the TLSs.ConclusionWe successfully applied LDRT combined with PD-1 inhibitor therapy for the first time, which increased both the quantity and maturity of TLSs in lung cancer. This approach achieved a promising antitumor effect.

Electrothermal elements are used in electronic devices, physiotherapy, and health care due to their lightweight and fast temperature response. However, the high cost and susceptibility to oxidation of traditional electrothermal materials limit their application. In this work, a low-cost, environment-friendly, controllable, and high-performance natural flake graphite-based electrothermal coating is proposed that can be used in various electrothermal applications. The results demonstrate that the morphology and electrothermal properties of the coatings can be controlled based on pressure engineering and the use of various adhesives. The uncompressed electrothermal coatings can reach a maximum temperature of 157.9 °C and a maximum electric conductivity of 27.89 S/m at 36 V, whereas the compressed coatings can reach a maximum temperature of 199 °C at only 18 V and a maximum conductivity of 433.6 S/m, which is 22 times higher than the corresponding uncompressed coatings. This work provides a low-cost, high-performance, and well-attainable industrialization path for the application of natural graphite-based electrothermal coatings in indoor heating, light electrothermal clothing, and snow and ice removal.

Abstract MicroRNAs (miRNAs) are a class of non‐coding single‐stranded RNA molecules with a length of approximately 18‐25 nt nucleotides that regulate gene expression post‐transcriptionally. MiR‐204‐5p originates from the sixth intron of the transient receptor potential cation channel subfamily M member 3 (TRPM3) gene. MiR‐204‐5p is frequently downregulated in various cancer types and is related to the clinicopathological characteristics and prognosis of cancer patients. So far, many studies have determined that miR‐204‐5p functions as a tumor suppressor for its extensive and powerful capacity to inhibit tumor proliferation, metastasis, autophagy, and chemoresistance in multiple cancer types. MiR‐204‐5p appears to be a promising prognostic biomarker and a therapeutic target for human cancers. This review summarized the latest advances on the role of miR‐204‐5p in human cancers.

Powered by IoT technologies, smart home systems effectively support aging-in-place. However, they have some limitations in comprehensive event perception and timely appropriate action. Homecare robot systems have been proven to be effective in homecare task executions but still have significant technological challenges. To address this problem, this paper proposes a smart home system architecture integrating a mobile robot with better event perception and task execution performance. To support the proposed system architecture, an ontology of the smart home is built to address the data heterogeneity issue. Then an event perception method is built upon multi-data integration. To perform complex tasks, this work implements an improved genetic algorithm for task planning. Finally, simulations and physical experiments are conducted to validate the feasibility of the proposed system architecture.

Abstract Background Long noncoding RNAs (lncRNAs) have driven research focused on their effects as oncogenes or tumor suppressors involved in carcinogenesis. However, the functions and mechanisms of most lncRNAs in colorectal cancer (CRC) remain unclear. Methods The expression of DLGAP1-AS2 was assessed by quantitative RT-PCR in multiple CRC cohorts. The impacts of DLGAP1-AS2 on CRC growth and metastasis were evaluated by a series of in vitro and in vivo assays. Furthermore, the underlying mechanism of DLGAP1-AS2 in CRC was revealed by RNA pull down, RNA immunoprecipitation, RNA sequencing, luciferase assays, chromatin immunoprecipitation, and rescue experiments. Results We discovered that DLGAP1-AS2 promoted CRC tumorigenesis and metastasis by physically interacting with Elongin A (ELOA) and inhibiting its protein stability by promoting tripartite motif containing 21 (Trim21)-mediated ubiquitination modification and degradation of ELOA. In particular, we revealed that DLGAP1-AS2 decreases phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) expression by inhibiting ELOA-mediated transcriptional activating of LHPP and thus blocking LHPP-dependent suppression of the AKT signaling pathway. In addition, we also demonstrated that DLGAP1-AS2 was bound and stabilized by cleavage and polyadenylation specificity factor (CPSF2) and cleavage stimulation factor (CSTF3). Conclusions The discovery of DLGAP1-AS2, a promising prognostic biomarker, reveals a new dimension into the molecular pathogenesis of CRC and provides a prospective treatment target for this disease.

MEMS resonant sensing devices require both HF ( f ) and low dissipation or high quality factor ( Q ) to ensure high sensitivity and high speed. In this study, we investigate the resonance properties and energy loss in the first three resonance modes, resulting in a significant increase in f‧Q product at higher orders. The third order resonance exhibits an approximately 15-fold increase in f‧Q product, while the Q factor remains nearly constant. Consequently, we achieved an ultrahigh f‧Q product exceeding 10 ^12 Hz by higher-order resonances in single-crystal diamond cantilevers.

ZSM-5 zeolite is a kind of high-value-added porous aluminosilicate zeolite. The use of the coal gasification slag utilization process by-product desilication liquid as a silicon raw material to replace the current raw materials such as water glass will help reduce production costs and achieve high-value utilization of solid waste. ZSM-5 zeolites for volatile organic compounds (VOCs) adsorption were prepared by a one-step hydrothermal method using the desilication solution prepared from coal gasification slag as the main silicon source and sodium source. The effects of crystallization reaction time, the crystallization temperature, the Na2O/SiO2 molar ratio, and the SiO2/Al2O3 molar ratio on the relative crystallinity and the specific surface area of the ZSM-5 zeolite were investigated and optimized. The optical reaction conditions were as follows: a crystallization time of 12 h, a crystallization temperature of 170 °C, a Na2O/SiO2 molar ratio of 0.2, and a SiO2/Al2O3 molar ratio of 200. The optimal ZSM-5 zeolite synthesized is hexagonal, with regular grains, a relative crystallinity of 101.48%, a specific surface area of 337.48 m2·g−1, and a pore volume of 0.190 cm3·g−1. And the optimal ZSM-5 zeolite was composed of SiO2 content of 97.52 wt%, Al2O3 content of 1.58 wt%, Na2O content of 0.33 wt%, and SiO2/Al2O3 molar ratio of 104.93. Na2O/SiO2 molar ratio is 0.0033. The results of static adsorption experiments show that the static adsorption capacities of ZSM-5 zeolite for p-xylene, benzene, toluene, and butyl acetate were 118.85, 69.98, 68.74, and 95.85 mg·g−1, respectively, which can effectively adsorb VOCs. The synthetic process of the ZSM-5 zeolite is a simple preparation process and short in synthesis time. The results of this study not only help to realize the high-value utilization of silicon components in solid waste, but also provide an economical and effective way to synthesize VOCs adsorption materials.

To improve the potassium availability of feldspar at ordinary temperatures, the mechanical grinding and addition of sodium hydroxide/salts were employed to study the effects of mechanical activation and strong alkali addition on particle characteristics, water-soluble potassium, and the available potassium of feldspar. A laser particle size analyzer was utilized for the direct determination of particle size distribution (PSD) using ground samples. The Brunauer–Emmett–Teller (BET) method was employed for specific surface areas. X-ray diffraction (XRD) was employed for structural characterization, scanning electron microscopy (SEM) for morphology exploration, and energy dispersive spectroscopy (EDS) to determine the chemical composition of potassium feldspar powder. The results revealed that the mechanical activation of potassium feldspar could reduce the particle size and produce agglomerated nanoparticles in the later period. The addition of NaOH and sodium salt did not cause agglomeration, and NaOH dissolved the nanoparticles. The water-soluble potassium content of feldspar in each treatment increased during mechanical grinding, from 21.64 mg kg−1 to 1495.81 mg·kg−1, by adding NaOH 5% weight of potassium feldspar powder and to 3044.08 mg·kg−1 by adding NaOH 10% weight with effects different from those of mechanical shaking. By comparison, only 162.93 mg·kg−1 water-soluble potassium was obtained by adding NaOH 5% weight. The dissolved potassium in the former case was significantly higher than in the latter, and the addition of NaOH and sodium salts significantly enhanced the water-soluble potassium contents due to ion exchange. Furthermore, the addition of sodium hydroxide improved the water-soluble potassium due to its mechanochemical action on potassium feldspar. The mechanical energy changed the crystal structure of potassium feldspar, explaining the increase in available potassium. The addition of sodium salts did not promote change in the feldspar’s structure, thereby did not raise the available potassium content. The reason for this was related to the mechanochemical action on sodium hydroxide and feldspar, which could promote the dissolution of fine particles, thereby incrementing the available potassium.

Abstract Background Surgical treatment is currently the only way to achieve the clinical cure for Klatskin tumor. However, whether combined vascular resection should be combined during surgeries is still controversial. The aim of this article was to analyze the effect of portal vein resection (PVR) and hepatic artery resection (HAR) on the long-term survival after surgery for Klatskin tumor. Methods Articles about Klatskin tumor with PVR and HAR, which were published from 2000 to 2020, were searched using PubMed, Embase, and EBSCO. HR with a 95% CI of overall survival, recurrence-free survival, disease-free survival, 3- and 5-year survival rate, and median survival time were reported to evaluate prognosis. Results A total of 17 articles were included. The total case number of these studies was 3150 (685 in the PVR group, 345 in the HAR group, and 2120 in the control group). Survival analyses showed that both vascular resection types were poor prognostic factors (PVR: HR = 1.50, 95% CI = 1.24–1.81, P < 0.001; HAR: HR = 1.68, 95% CI = 1.26–2.24, P < 0.001; the pooled effect size of the two groups: HR = 1.55, 95% CI = 1.32–1.82, P < 0.001). In general, the analyses of 3- and 5-year survival and median survival time showed that both vascular resection types tended to be poor prognostic factors, but most of recent researches showed that the PVR did not lead to a poor prognosis. Conclusion PVR should be used when necessary to achieve R0 resection of Klatskin tumor and improve the long-term survival of patients. Whether HAR should be performed or not is still need to be evaluated.

In recent years, regenerative thermal oxidizer (RTO) has been widely used in the petroleum industry, chemical industry, etc. The massive storage required by solid waste has become a serious problem. Due to their chemical composition, bauxite tailings as raw materials for high-temperature thermal storage ceramics show enormous potential in the fields of research and application. In this study, we propose a method for preparing ferric-rich and high specific storage capacity by adding Fe2O3 powder to bauxite tailings. Based on a 7:3 mass ratio of bauxite tailings to lepidolite, Fe2O3 powder with different mass fractions (7 wt%, 15 wt%, 20 wt%, 30 wt%, and 40 wt%) was added to the ceramic material to improve the physical properties and thermal storage capacity of thermal storage ceramics. The results showed that ferric-rich thermal storage ceramics with optimal performance were obtained by holding them at a sintering temperature of 1000 °C for 2 h. When the Fe2O3 content was 15 wt%, the bulk density of the thermal storage ceramic reached 2.53 g/cm3, the compressive strength was 120.81 MPa, and the specific heat capacity was 1.06 J/(g·K). This study has practical guidance significance in the preparation of high thermal storage ceramics at low temperatures and low costs.

The occurrence of fractures has emerged as one of the most prevalent injuries in the human body. In bone reconstruction surgery, after the implantation of porous hydroxyapatite materials, there is an initial infiltration of body fluids into the porous implant, followed by biomineralization-mediated apatite crystal formation and the subsequent ingrowth of bone cells. Despite extensive research efforts in this field, previous investigations have primarily focused on the formation of apatite crystals on exposed surfaces, with limited literature available regarding the formation of apatite crystals within the internal microstructures of bone implants. Herein, we demonstrate the occurrence of dynamic biomineralization within a three-dimensional porous hydroxyapatite/wollastonite (HA/WS) skeleton, leading to the abundant formation of nano-sized apatite crystals across diverse internal environments. Our findings reveal that these apatite nanocrystals demonstrate distinct rates of nucleation, packing densities, and crystal forms in comparison to those formed on the surface. Therefore, the objective of this study was to elucidate the temporal evolution of biomineralization processes by investigating the microstructures of nanocrystals on the internal surfaces of HA/WS three-dimensional porous materials at distinct stages of biomineralization and subsequently explore the biological activity exhibited by HA/WS when combined with cell investigation into apatite crystal biomineralization mechanisms at the nanoscale, aiming to comprehend natural bone formation processes and develop efficacious biomimetic implants for tissue engineering applications. The simultaneous examination of bone cell attachment and its interaction with ongoing internal nanocrystal formation will provide valuable insights for designing optimal scaffolds conducive to bone cell growth, which is imperative in tissue engineering endeavors.

Gout is a form of prevalent and painful inflammatory arthritis characterized by elevated serum urate (SUA) levels. The gut microbiota (GM) is believed to influence the development of gout and SUA levels. Our study aimed to explore the causal relationship between GM composition and gout, as well as SUA levels, utilizing a two-sample Mendelian Randomization (MR) approach. A total of 196 GM taxa from five levels were available for analysis. We identified five taxa associated with SUA levels and 10 taxa associated with gout. In reverse MR analysis, we discovered that gout affected the composition of five GM taxa, while SUA levels influenced the composition of 30 GM taxa. Combining existing research, our study unveiled a potential negative feedback loop between phylum Actinobacteria and SUA levels, establishing connections with gout. We also proposed two novel associations connecting GM taxa (genus Faecalibacterium and genus Prevotella9), SUA levels, and gout. These findings provide compelling evidence of causal relationships between specific GM taxa with SUA levels and gout, contributing valuable insights for the treatment of gout.

Abstract Background SLCO4A1-AS1 was found to be upregulated in several cancer types, including colorectal cancer (CRC). However, the detailed roles of SLCO4A1-AS1 in CRC remain to be elucidated. Therefore, we investigated the functions, mechanism, and clinical significance of SLCO4A1-AS1 in colorectal tumourigenesis. Methods We measured the expression of SLCO4A1-AS1 in CRC tissues using qRT-PCR and determined its correlation with patient prognosis. Promoter methylation analyses were used to assess the methylation status of SLCO4A1-AS1. Gain- and loss-of-function assays were used to evaluate the effects of SLCO4A1-AS1 on CRC growth in vitro and in vivo. RNA pull-down, RNA immunoprecipitation, RNA-seq, luciferase reporter and immunohistochemistry assays were performed to identify the molecular mechanism of SLCO4A1-AS1 in CRC. Results SLCO4A1-AS1 was frequently upregulated in CRC tissues based on multiple CRC cohorts and was associated with poor prognoses. Aberrant overexpression of SLCO4A1-AS1 in CRC is partly attributed to the DNA hypomethylation of its promoter. Ectopic SLCO4A1-AS1 expression promoted CRC cell growth, whereas SLCO4A1-AS1 knockdown repressed CRC proliferation both in vitro and in vivo. Mechanistic investigations revealed that SLCO4A1-AS1 functions as a molecular scaffold to strengthen the interaction between Hsp90 and Cdk2, promoting the protein stability of Cdk2. The SLCO4A1-AS1-induced increase in Cdk2 levels activates the c-Myc signalling pathway by promoting the phosphorylation of c-Myc at Ser62, resulting in increased tumour growth. Conclusions Our data demonstrate that SLCO4A1-AS1 acts as an oncogene in CRC by regulating the Hsp90/Cdk2/c-Myc axis, supporting SLCO4A1-AS1 as a potential therapeutic target and prognostic factor for CRC.

Background: Programmed death receptor ligand 1 (PD-L1) is expressed at different levels in tumour tissues and tumour-infiltrating monocytes (TIMCs). The interpretation of PD-L1 expression in gastric cancer (GC) is more difficult because of its heterogeneity. Methods: The PD-L1 immunohistochemistry (IHC) by E1L3N assay was performed in GC tissues. The level and distributed characteristics of PD-L1 expression were observed to illustrate its heterogeneity both in the cancer tissues and TIMCs. The relationship between PD-L1 level and necrotic features of tumor cells, the number of TIMCs, the distribution of tertiary lymphoid tissue (TLS) in the stroma, and other clinicopathological factors were analysed. A Cox regression model was used to assess the prognostic value of PD-L1 expression. Results: Of the 110 GC samples, not only more cases (51/110 cases) could be detected by combined positive score (CPS) for PD-L1 expression compared the other two, tumour positive score (TPS), and mononuclear immune-cell density score (MIDS), but also there were more cases with the high level of PD-L1 expression by CPS, even if with good consistency among them (P < 0.05). The tumour cells with high expression of PD-L1 was prone to show a diffuse distributing, whereas mottled type in the low level. It was noteworthy that the strongly colored tumor cells tended to exhibit a mossy pattern which were distributed along the border between cancer nests and stroma, and the same pattern happened to occur in the positive mesenchymal cells contacting the tumor border, essentially lymphocytes and macrophages. The substantial necrosis in the tumour and the number of TIMCs was analyzed statistically significant correlated with CPS (P < 0.05), while other clinicopathological factors such as histological type, tumour size, invasion depth, TNM stage were uncorrelated. The number and distribution of TLS in the tumour and para-tumoural stroma indirectly affected PD-L1 in GC by associating with the quantity and pattern of TIMCs. Cox regression analysis revealed that the prognosis was poor when PD-L1 was positive. Conclusion: CPS is the best indicator for PD-L1 expression in GC, which tend to be increased expression following a large number of TIMCs and substantial tumour necrosis appeared. Heterogeneity was reflected in the different distributed pattern of PD-L1 expression, especially the mossy-like pantten of the staining tumor cell in the interface between tumour nests and stroma, regardless of the amount and intensity of PD-L1 expression. TLS is valuable for observing microscopic images to influence the quantity and pattern of TIMCs. CPS can be used as an independent prognostic factor for GC.

Background Osteogenic differentiation of aortic valve interstitial cells (AVICs) plays a key role in the calcific aortic valve disease progression. Extracellular vesicles (EVs)-derived from M1-polarized macrophages (M1-EVs) orchestrated intercellular communication by delivering non-coding RNAs such as tRNA-derived small RNAs (tsRNAs) is crucial for cardiovascular disease. However, the role and mechanism of M1-EVs tsRNAs in osteogenic differentiation of AVICs remains largely unclear. Methods M1-EVs and PBS treated-RAW 264.7 cell-derived EVs (NC-EVs) were incubated with AVICs and subjected to small RNA sequencing. Candidate tsRNA in M1-EVs was silenced to explore their effects on AVIC osteogenic differentiation and mitophagy. Results DiI-labeled M1-EVs were internalized by AVICs, resulting in significantly increased calcium nodule formation and expression of osteogenesis-related genes in AVICs, including RUNX2, BMP2, osteopontin, and SPP1, compared with NC-EVs. Small RNA sequencing revealed that 17 tsRNAs were significantly up-regulated such as tsRNA-5006c, while 28 tsRNAs were significantly down-regulated in M1-EVs compared with NC-EVs. Intriguingly, tsRNA-5006c-deleted M1-EVs treatment significantly reduced calcium nodule formation and expression of osteogenesis-related genes in AVICs relative to control group. Moreover, target genes of tsRNA-5006c were mainly involved in autophagy-related signaling pathways, such as MAPK, Ras, Wnt, and Hippo signaling pathway. Hallmarks of mitophagy activation in AVICs including mitophagosome formation, TMRM fluorescence, expression of LC3-II, BINP3, and PGC1α, were significantly elevated in the M1-EVs group compared with NC-EVs group, whereas M1-EVs tsRNA-5006c inhibitor led to a significant reduction in these indicators. Conclusion M1-EVs carried tsRNA-5006c regulates AVIC osteogenic differentiation from the perspective of mitophagy, and we provide a new target for the prevention and treatment of aortic valve calcification.

Phase change material (PCM) with thermal energy storage capacity has been a hot topic due to the advantages of satisfying the demand for energy storage, saving and conversion. In this work, graphene oxide (GO) was introduced to prepare a three-dimensional (3D) continuous network of graphene aerogel (GA) via a simple hydrothermal process, and the GA was further employed to pack polyethylene glycols (PEG). Benefited from the abundant porous structure and high specific surface area, the mass fraction of PEG in the composite PCM was up to 96.0 wt%. Besides, the heat latent of the composite was 223.2 J/g, illustrating a high energy storage density. Moreover, due to the crosslinking graphene skeleton and its inherent high thermal conductivity, the heat transfer rate was enhanced to 116% of the pure PEG. This work could simultaneously solve the drawbacks of leakage and low thermal conductivity of PCM. And the composite PCM could be considered as a clean, energy-saving and recycled material in the application of building heat preservation.

Abstract Background Small nucleolar RNA host gene (SNHG) long noncoding RNAs (lncRNAs) are frequently dysregulated in human cancers and involved in tumorigenesis and progression. SNHG17 has been reported as a candidate oncogene in several cancer types, however, its regulatory role in colorectal cancer (CRC) is unclear. Methods SNHG17 expression in multiple CRC cohorts was assessed by RT-qPCR or bioinformatic analyses. Cell viability was evaluated using Cell Counting Kit-8 (CCK-8) and colony formation assays. Cell mobility and invasiveness were assessed by Transwell assays. Tumor xenograft and metastasis models were applied to confirm the effects of SNHG17 on CRC tumorigenesis and metastasis in vivo. Immunohistochemistry staining was used to measure protein expression in cancer tissues. RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, and dual luciferase assays were used to investigate the molecular mechanism of SNHG17 in CRC. Results Using multiple cohorts, we confirmed that SNHG17 is aberrantly upregulated in CRC and correlated with poor survival. In vitro and in vivo functional assays indicated that SNHG17 facilitates CRC proliferation and metastasis. SNHG17 impedes PES1 degradation by inhibiting Trim23-mediated ubiquitination of PES1. SNHG17 upregulates FOSL2 by sponging miR-339-5p, and FOSL2 transcription activates SNHG17 expression, uncovering a SNHG17-miR-339-5p-FOSL2-SNHG17 positive feedback loop. Conclusions We identified SNHG17 as an oncogenic lncRNA in CRC and identified abnormal upregulation of SNHG17 as a prognostic risk factor for CRC. Our mechanistic investigations demonstrated, for the first time, that SNHG17 promotes tumor growth and metastasis through two different regulatory mechanisms, SNHG17-Trim23-PES1 axis and SNHG17-miR-339-5p-FOSL2-SNHG17 positive feedback loop, which may be exploited for CRC therapy.

Background: Thalassemia is a common inherited hematological disease with genetic disorders characterized by imbalanced synthesis of the globin chains. Due to the improvement of treatment methods, patients with thalassemia can survive for a long time. Therefore, it is not uncommon for patients with thalassemia suffering from malignant tumors. However, there are quite few reports on thalassemia patients complicated with breast cancer. Herein, we try to investigate the prevalence and genetic disorders spectrum of thalassemia in patients with breast cancer.Methods: Blood routing tests and serum ferritin analysis were conducted in 1887 breast cancer patients treated in the department of radiation oncology during 1 April 2020 and 30 March 2022. The suspected thalassemia carriers with small mean corpuscular volume (MCV), mean corpuscular hemoglobin content (MCH) or mean corpuscular hemoglobin concentration (MCHC) but the concentration of serum ferritin within normal limits were further investigated by polymerase chain reaction (PCR) and flow through hybridization gene chip to detect common mutations of α-globin and β-globin genes using Thalassemia Geno Array Diagnostic Kit. The prevalence and genetic mutation spectrum of thalassemia among breast cancer patients were analyzed.Results: Four hundred and eighty-nine suspected thalassemia carriers were detected by complete blood cell counts and serum ferritin analysis among 1887 breast cancer patients. One hundred and seven cases (5.7%) were identified as carriers of thalassemia, of which 55 cases (51.4%) were α-thalassemia, 50 cases (46.7%) were β-thalassemia, and 2 cases (1.9%) were co-inheritance of α-thalassemia and β-thalassemia simultaneously. In α-thalassemia, the most prevalent genotype is -SEA/αα; as for β-thalassemia, βIVS−II−654/β is the most common genotype. The degree of anemia is more severe in β-thalassemia than in α-thalassemia.Conclusion: This is the first comprehensive molecular epidemiological investigation on thalassemia among breast cancer patients. Our data indicated that thalassemia was not uncommon in breast cancer patients. The physicians should have the knowledge to avoid misdiagnosis as iron deficiency anemia.

Abstract Background NF‐κB signaling is widely linked to the pathogenesis and treatment resistance in cancers. Increasing attention has been paid to its anti‐oncogenic roles, due to its key functions in cellular senescence and the senescence‐associated secretory phenotype (SASP). Therefore, thoroughly understanding the function and regulation of NF‐κB in cancers is necessary prior to the application of NF‐κB inhibitors. Methods We established glioblastoma (GBM) cell lines expressing ectopic TCF4N, an isoform of the β‐catenin interacting transcription factor TCF7L2, and evaluated its functions in GBM tumorigenesis and chemotherapy in vitro and in vivo. In p65 knock‐out or phosphorylation mimic (S536D) cell lines, the dual role and correlation of TCF4N and NF‐κB signaling in promoting tumorigenesis and chemosensitivity was investigated by in vitro and in vivo functional experiments. RNA‐seq and computational analysis, immunoprecipitation and ubiquitination assay, minigene splicing assay and luciferase reporter assay were performed to identify the underlying mechanism of positive feedback regulation loop between TCF4N and the p65 subunit of NF‐κB. A eukaryotic cell‐penetrating peptide targeting TCF4N, 4N, was used to confirm the therapeutic significance. Results Our results indicated that p65 subunit phosphorylation at Ser 536 (S536) and nuclear accumulation was a promising prognostic marker for GBM, and endowed the dual functions of NF‐κB in promoting tumorigenesis and chemosensitivity. p65 S536 phosphorylation and nuclear stability in GBM was regulated by TCF4N. TCF4N bound p65, induced p65 phosphorylation and nuclear translocation, inhibited its ubiquitination/degradation, and subsequently promoted NF‐κB activity. p65 S536 phosphorylation was essential for TCF4N‐led senescence‐independent SASP, GBM tumorigenesis, tumor stem‐like cell differentiation and chemosensitivity. Activation of p65 was closely connected to alterative splicing of TCF4N, a likely positive feedback regulation loop between TCF4N and p65 in GBM. 4N increased chemosensitivity, highlighting a novel anti‐cancer strategy. Conclusion Our study defined key roles of TCF4N as a novel regulator of NF‐κB through mutual regulation with p65 and provided a new avenue for GBM inhibition.

Accurate immune molecular typing is pivotal for screening out patients with colon adenocarcinoma (COAD) who may benefit from immunotherapy and whose tumor microenvironment (TME) was needed for reprogramming to beneficial immune-mediated responses. However, little is known about the immune characteristic of COAD. Here, by calculating the enrichment score of immune characteristics in three online COAD datasets (TCGA-COAD, GSE39582, and GSE17538), we identified 17 prognostic-related immune characteristics that overlapped in at least two datasets. We determined that COADs could be stratified into three immune subtypes (IS1–IS3), based on consensus clustering of these 17 immune characteristics. Each of the three ISs was associated with distinct clinicopathological characteristics, genetic aberrations, tumor-infiltrating immune cell composition, immunophenotyping (immune “hot” and immune “cold”), and cytokine profiles, as well as different clinical outcomes and immunotherapy/therapeutic response. Patients with the IS1 tumor had high immune infiltration but immunosuppressive phenotype, IS3 tumor is an immune “hot” phenotype, whereas those with the IS2 tumor had an immune “cold” phenotype. We further verified the distinct immune phenotype of IS1 and IS3 by an in-house COAD cohort. We propose that the immune subtyping can be utilized to identify COAD patients who will be affected by the tumor immune microenvironment. Furthermore, the ISs may provide a guide for personalized cancer immunotherapy and for tumor prognosis.

This paper proposed one new method to determine the residual ultimate loads of the fire-damaged beam-slab specimens. Based on the conventional yield line method, the stiffness and deflection of the edge beam was considered to establish the theoretical method, and the residual ultimate loads of several beam-slab specimens in the literature were analyzed, and the predicted results were compared to the experimental results. Results show that the conventional simply-supported and fixed-end yield line method tended to underestimate or overestimate the residual ultimate loads of the specimens, and the present method can reasonably predict the ultimate loads of the beam-slab specimens.

Background Pancreatic ductal adenocarcinoma (PDAC) has the worst five-year overall survival rate among all cancer types. Acquired chemoresistance is considered one of the main reasons for this dismal prognosis, and the mechanism of chemoresistance is unknown. Methods We previously identified a subpopulation of chemoresistant CD44high-expressing PDAC cells. Subsequently, we selected the candidate gene, gamma-aminobutyric acid receptor subunit Pi (GABRP), from three Gene Expression Omnibus datasets as the potential CD44 downstream target mediating the gemcitabine resistance. Loss and gain of function such as stable knockdown of CD44 by small hairpin (sh) RNA-mediated silencing technique and overexpression (O/E) of CD44s had been studied for comparing the gemcitabine resistance among CD44high-expressing cells, shCD44 cells, CD44low-expressing cells and O/E CD44s expressing cells. Functional assays including cell viability, colony formation, invasion, quantitative PCR and western blotting techniques were performed to validate the roles of CD44 and GABRP playing in mediating the gemcitabine resistance in pancreatic cancer cells. Results CD44s depletion significantly reduced gemcitabine resistance in shCD44 single clone cells compared to CD44high-expressing cells. Knockdown of CD44 cells formed less colonies, became less invasive and remarkably decreased the mRNA level of GABRP. While overexpression of CD44s had the opposite effect on gemcitabine resistance, colony formation and invasive property. Of note, long term gemcitabine resistant pancreatic cancer cells detected increased expression of CD44 and GABRP. Clinically, GABRP expression was significantly upregulated in the tissues of patients with pancreatic cancer compared to the normal samples, and the overall survival rate of patients with low GABRP expression was longer. CD44 and GABRP co-expression was positively correlated in 178 pancreatic cancer patients. Conclusion Our findings suggest that GABRP may serve as a CD44s downstream target to diminish gemcitabine resistance in pancreatic cancer, and both CD44s and GABRP molecules have the potential to become prognostic biomarkers for PDAC patients with gemcitabine resistance.

Ferroptosis is a new non-apoptotic form that regulates cell death and is mainly dependent on iron-mediated oxidative damage and subsequent cell membrane damage. Ferroptosis may be a potential therapeutic strategy for immunotherapy, chemotherapy, and radiotherapy in human cancers. Numerous studies have analyzed ferroptosis-correlated signatures or genes, but a systematic landscape of associations among tumor ferroptosis, clinical outcomes, tumor microenvironment, and therapies in human cancers is lacking. Here, we developed a relative ferroptosis level (RFL) combined with drive/suppress regulators and validated it in the Gene Expression Omnibus datasets of ferroptotic drug treatment. Based on this effective evaluation method, we classified about 7,000 tumor samples into high and low RFL groups in each cancer type and observed that high RFL cases demonstrate favorable survival outcomes in nine cancer types from The Cancer Genome Atlas. Then, several RFL-correlated candidate genes that have not been reported to be ferroptosis-related were selected and experimentally validated in five cancer cell lines using Erastin treatment. We further showed that both immunostimulatory and immunosuppressive phenotypes were observed in high RFL tumors, suggesting that the consideration of ferroptosis could be a potential strategy in cancer immunotherapy. Moreover, we found that high RFL cases/cells showed responder or sensitivity to chemotherapy and radiotherapy. Our study provides a comprehensive molecular-level understanding of ferroptosis and may have practical implications for clinical cancer therapies, including immunotherapy, chemotherapy, and radiotherapy.

Abstract Background Accumulating evidences have shown that long noncoding RNAs (lncRNAs) play key roles in many diseases, including cancer. Several studies reported that MCM3AP antisense RNA 1 (MCM3AP‐AS1) was associated with the tumorigenesis and progression. However, the specific function and mechanism of MCM3AP‐AS1 in colorectal cancer (CRC) have not been fully understood. Methods The expression of MCM3AP‐AS1 was detected by quantitative reverse transcription PCR (RT‐qPCR) in CRC tissues and matched noncancerous tissues (NCTs). CCK‐8 assay, colony formation assay, transwell assay, xenograft and lung metastasis mouse models were used to examine the tumor‐promoting function of MCM3AP‐AS1 in vitro and in vivo. The binding relationship between MCM3AP‐AS1, miR‐193a‐5p and sentrin‐specific peptidase 1 (SENP1) were screened and identified by databases, RT‐qPCR, dual luciferase reporter assay and western blot. Results In the present study, we got that the expression of MCM3AP‐AS1 was higher in CRC tissues than in paired NCTs, and increased MCM3AP‐AS1 expression was associated with adverse outcomes in CRC patients. Functional experiments in vitro revealed that silencing of MCM3AP‐AS1 could inhibit the proliferation, colony formation, migratory, and invasive abilities of CRC cells. The mouse models of xenograft and lung metastasis further confirmed that in vivo silencing MCM3AP‐AS1 could significantly inhibit the growth and metastasis of CRC. Further mechanism studies indicated that MCM3AP‐AS1 could sponge miR‐193a‐5p and inhibit the activity of it. What is more, SENP1 was proved to be a novel target of miR‐193a‐5p and could be upregulated by MCM3AP‐AS1. At last, we observed that SENP1 overexpression in CRC tissues was closely related to unfavorable prognosis. Conclusion Taken together, we identified in CRC the MCM3AP‐AS1/miR‐193a‐5p/SENP1 regulatory axis, which affords a therapeutic possibility for CRC.

Colon cancer is one of the most common malignancies causing death worldwide. It is well known that the cells of the tumor microenvironment contribute to the progression and prognosis of colon cancer. However, the gene alterations and potential remodeling mechanisms in the tumor microenvironment of colon cancer remain largely unknown. In this study, immune scores from the ESTIMATE algorithm were used to discriminate between patients with high or low immune-cell infiltration. There were 42 immune differentially expressed genes (DEGs) of prognostic value identified in this study. Among them, KCNJ5 is a key factor in promoting M2 macrophage recruitment and tumor immune infiltration in colon cancer. These findings may provide novel insights for decoding the complicated interplay between cancer cells and the tumor microenvironment as well as for developing new avenues for therapeutic intervention in colon cancer.

BackgroundCumulative evidence in colorectal cancer (CRC) suggests that patients with human epidermal growth factor receptor 2 (HER2) overexpression or amplification can benefit from anti-HER2 therapy. The purpose of our study was to evaluate HER2 status and its correlation with clinicopathological characteristics and survival according to currently utilized HER2 diagnostic criteria in a large cohort of Chinese CRC patients.MethodsHER2 protein expression was tested by immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded (FFPE) samples from 4,836 CRC patients in our institution. Breast cancer (BC) and gastroesophageal adenocarcinoma (GEA) criteria, as well as the HERACLES criteria, were used for the determination of HER2 status. Dual-color silver-enhanced in situ hybridization (DSISH) was performed in all IHC 2+~3+ cases determined by BC/GEA criteria.ResultsThe HER2 expression rate of IHC (1+~3+) was 7.01% (339/4,836) and 6.02% (291/4,836) in CRCs based on the BC/GEA criteria and the HERACLES criteria, respectively, while combined DSISH results in the HER2 amplification/overexpression ratio of 3.39% (164/4,836) in our cohort. HER2 expression detected by IHC was positively correlated with the female gender, whereas the HER2 overexpression/amplification showed no correlation with any clinicopathological parameter. In addition, no significant correlation was found between HER2 statuses and either disease-free survival or overall survival regardless of the evaluation criterion used. However, patients with HER2 1+ CRC showed a tendency of having the shortest overall survival as compared with any other group of patients according to the HERACLES criteria, and this trend has always existed in the rectal location, T3 stage, and TNM stage II, medium differentiation, and perineural invasion stratified group. Furthermore, the HER2 protein expression was significantly negatively correlated with RAS/BRAF mutations according to the HERACLES criteria.ConclusionTo our knowledge, this is the largest study of HER2 status in Asian patients with CRC. Our findings suggest that the current most commonly used HERACLES criteria might be too strict for patients with CRC. Future studies are needed to explore the most suitable criteria for screening CRC patients who could benefit from anti-HER2 therapy as much as possible.

Abstract Tumor‐associated macrophages (TAMs) are one of the most abundant cell types in colorectal cancer (CRC) tumor microenvironment (TME). Recent studies observed complicated “cross‐talks” between cancer cells and macrophages in TME. However, the underlying mechanisms are still poorly elucidated. Here, PD‐L1 levels are very low in CRC cells but highly abundant in TAMs, and a specific PD‐L1+CD206+ macrophage subpopulation are identified, which is induced by tumor cells and associated with a poor prognosis. Mechanistic investigations reveal that CRC cells can secrete small extracellular vesicles (sEVs) taken up by macrophages that induce M2 like polarization and PD‐L1 expression, resulting in increased PD‐L1+CD206+ macrophage abundance and decreased T cell activity in CRC TME. sEV‐derived miR‐21‐5p and miR‐200a are identified as key signaling molecules mediating the regulatory effects of CRC on macrophages. Further studies reveal that CRC‐derived miR‐21‐5p and miR‐200a synergistically induces macrophage M2 like polarization and PD‐L1 expression by regulating the PTEN/AKT and SCOS1/STAT1 pathways, resulting in decreased CD8+ T cell activity and increased tumor growth. This study suggests that inhibiting the secretion of specific sEV‐miRNAs from CRC and targeting PD‐L1 in TAMs may serve as novel methods for CRC treatment as well as a sensitization method for anti‐PD‐L1 therapy in CRC.

Abstract Background Nano‐sized extracellular vesicles secreted by cells play key roles in intercellular crosstalk, and appear to be an excellent biocompatible material as therapeutic cargoes in vivo. Previously, we have demonstrated that miR‐204‐5p is a key tumor suppressor that could inhibit tumor growth, metastasis and chemoresistance. Methods A HEK293T cell line stably expressing miR‐204‐5p (293T‐miR‐204) was constructed by lentivirus transduction. Fluorescence real‐time quantitative PCR (qPCR) was applied to measure the expression of miR‐204‐5p. CCK‐8 and colony formation assays were used to evaluate the in vitro anticancer effects, and the flow cytometry was used to detect apoptosis. The in vivo therapeutic effects of exosomal miR‐204‐5p were evaluated using a xenograft mouse model. Western blots were used to detect the protein levels of CD63, Flotillin‐2, RAB22A and Bcl2. The protein levels of RAB22A and Bcl2 in tumor tissues were measured by immunohistochemistry staining. Results MiR‐204‐5p was clearly upregulated in CRC cells after coculturing with 293T‐miR‐204 cell‐derived conditioned medium (CM) or exosomes. CCK‐8 and colony formation assays showed that the cell proliferation ability of CRC cells was clearly inhibited by 293T‐miR‐204 cell‐derived CM or exosomes. The inhibitory effects of exosomal miR‐204‐5p on cell proliferation were further confirmed in other types of cancers. Exosomal miR‐204‐5p could induce apoptosis and increase the sensitivity of cancer cells to the chemotherapeutic drug—5‐fluorourcil. In addition, exosomal miR‐204‐5p inhibited the tumor growth in mice. Western blot assay and IHC staining showed that the protein levels of miR‐204‐5p targets were clearly decreased in cancer cells or xenograft tissues treated with exosomal miR‐204‐5p. Conclusions In this study, we confirmed that exosomal miR‐204‐5p could efficiently inhibit cancer cell proliferation, induce apoptosis and increase chemosensitivity by specifically suppressing the target genes of miR‐204‐5p in human cancer cells.

Tissue engineering scaffolds made of conventional aliphatic polyesters are inherently non-fluorescent, which results in their in vivo degradation hard to be visualized. Photoluminescent biodegradable polyorganophosphazenes (PPOPs) are synthesized by introducing fluorophores onto the polyphosphazene backbone via nucleophilic substitution reaction. In this study, a fluorophore (termed as TPCA), derived from citric acid and 2-aminoethanethiol, was co-substituted with alanine ethyl ester onto the polyphosphazene backbone to obtain a photoluminescent biodegradable POPP (termed as PTA). The scaffolds made of PTA demonstrated non-cytotoxicity and cell affinity, particularly, capacity in promoting osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs). In vivo evaluations using the rat calvarial defect model confirmed its strong potential in enhancing osteogenesis, more importantly, the in vivo degradation of the PTA scaffold could be monitored via its fluorescence intensity alongside implantation time. Keywords: Tissue regeneration, Biodegradation, Photoluminescent, Polyorganophosphazene

Tight sandstone reservoirs are affected by various factors such as pore structure, formation water salinity, and siliceous cementation, which lead to the abnormal phenomenon of high-resistivity water layers and increase the difficulty in identifying gas and water layers by conventional logging. In this study, the pore types and pore size distribution characteristics of tight sandstone reservoirs were firstly determined by NMR and high-pressure mercury injection experiments, and then the iterative least-square method was used to automatically optimize the inversion method of pseudo-capillary pressure curve and search for the optimal conversion coefficient. Finally, the apparent free water porosity was inversed and the fluid identification standard was obtained and applied. The results showed that the reservoirs mainly developed intergranular pores, cutting solution pores, and intergranular pores. The pore throats were poorly sorted, and the displacement pressure was high. The median radius ranged from 0.01 to 0.48 μm, and the main peak range was from 0.02 to 0.06 μm. Pores were of mainly small-hole fine throat type. In the inversion results of the optimal conversion coefficient, the correlation coefficient between the aperture parameters and the results of high-pressure mercury injection experiments was greater than 0.93. According to the fluid property identification standard based on nuclear magnetic apparent free water porosity, the high-resistivity water layers were effectively identified and its coincidence rate with the final field test was 10.7% higher than that of the conventional method. This identification method can be used to identify complex fluids in tight sandstone reservoirs.

In order to fully excavate the fault feature information of rotating machinery and accurately recognize the fault category, a novel fault diagnosis method was proposed, which combines with smoothness priors approach (SPA), fluctuation dispersion entropy (FDE), and density peak clustering (DPC). Firstly, the smoothness priors approach is used to decompose the collected vibration signal of rotating machinery to obtain the trend term and detrend term. Secondly, the fault features of the trend term and detrend term were quantified by fluctuation dispersion entropy to construct eigenvector matrix. Finally, the eigenvector matrix was input into the density peak clustering algorithm for fault recognition and classification. The proposed novel algorithm was applied to the experimental data of the rotating machinery under various working conditions. The experimental results show that our method can precisely identify various fault patterns of rotating machinery. Moreover, our approach can attain higher recognition accuracy than other combination clustering model algorithms involved in this paper.

Objective. Disease prediction is crucial to treatment success. The aim of this study was to accurately and explicably predict, based on the first laboratory measurements, medications, and demographic information, the risk of death in patients with hypertensive chronic kidney disease within 1 and 3 years after admission to the Intensive Care Unit (ICU). Methods. Patients with hypertensive chronic kidney disease who had been registered in the Medical Information Mart for Intensive Care (MIMIC-III) database of critical care medicine were set as the subject of study, which was randomly divided into a training set and a validation set in a ratio of 7 : 3. Univariate Cox regression analysis and stepwise Cox regression analysis were applied in the training set to identify the predictive factors of prognosis of patients with hypertensive chronic kidney disease in ICU, and the predictive nomogram based on Cox regression model was constructed. We internally validated the model in the training set and externally validated that in the validation model. The efficacy was assessed primarily through area under the receiver operating characteristic (ROC) curve, clinical decision curves, and calibration curves. Results. A total of 1762 patients with hypertensive chronic kidney disease were finally included. During the 3-year follow-up, 667 patients (37.85%) died, with a median follow-up time of 220 days (1-1090). The data set were randomly divided into a training set (n=1231) and a validation set (n=531). It was identified in the training set that insurance, albumin, alkaline phosphatase, the mean corpuscular hemoglobin concentration, mean corpuscular volume, history of coronary angiogram, hyperlipemia, medication of digoxin, acute renal failure, and history of renal surgery were the most relevant features. Taking 1 year and 3 years as the cut-off points, the AUC of participants were 0.736 and 0.744, respectively, in the internal validation and were 0.775 and 0.769, respectively, in the external validation, suggesting that the model is of favorable predictive efficacy. Conclusion. We trained and validated a model using data from a large multicenter cohort, which has considerable predictive performance on an individual scale and could be used to improve treatment strategies.

Mobile-augmented-reality (MAR) applications extended into the metaverse could provide mixed and immersive experiences by amalgamating the virtual and physical worlds. However, the consideration of joining MAR and the metaverse requires reliable and high-quality support for foreground interactions and rich background content from these applications, which intensifies their consumption of energy, caching and computing resources. To tackle these challenges, a more flexible request assignment and resource allocation framework with more efficient processing are proposed in this paper through anchoring decomposed metaverse AR services at different edge nodes and proactively caching background metaverse region models embedded with target augmented-reality objects (AROs). Advanced terminals are also considered to further reduce service delays at an acceptable energy-consumption cost. We, then, propose and solve a joint-optimization problem which explicitly considers the balance between service delay and energy consumption under the constraints of perceived user quality in a mobility event. By also explicitly taking into account the capabilities of user terminals, the proposed optimized scheme is compared to a terminal-oblivious scheme. According to a wide set of numerical investigations, the proposed scheme has wide-ranging advantages in service latency and energy efficiency over other nominal baseline schemes which neglect the capabilities of terminals, user physical mobility, service decomposition and the inherent multimodality of the metaverse MAR service.

Mullite–cordierite ceramic saggar is a necessary consumable material used in the synthesis process of LiCoO2 that is easily eroded during application. In our study, we systematically investigated the characteristics and surface corrosion behavior of waste saggar samples. We divided the cross sections of waste saggar into the attached layer, hardened layer, permeability layer, and matrix layer. Then, we examined the high-temperature solid-state reactions between saggar powder and lithium carbonate or cobalt oxide to identify erosion reactants correlating with an increase in the number of recycled saggars. The results of time-of-flight secondary ion mass spectrometric analysis (TOF-SIMS) prove that the maximum erosion penetration of lithium can reach 2 mm. However, our morphology and elemental distribution analysis results show that the erosion penetration of cobalt was only 200 μm. When enough lithium carbonate reacted, lithium aluminate and lithium silicate were the main phases. Our X-ray computed tomography (X-ray CT) analysis results show that the change in phase volume before and after the reaction, including the generation of oxygen and carbon dioxide gas, led to the internal crack expansion of the material–saggar interface. Our results can contribute to improving saggar and upgrading waste saggar utilization technology.