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Abstract FOXO transcription factors modulate aging-related pathways and influence longevity in multiple species, but the transcriptional targets that mediate these effects remain largely unknown. Here, we identify an evolutionarily conserved FOXO target gene, Oxidative stress-responsive serine-rich protein 1 (OSER1), whose overexpression extends lifespan in silkworms, nematodes, and flies, while its depletion correspondingly shortens lifespan. In flies, overexpression of OSER1 increases resistance to oxidative stress, starvation, and heat shock, while OSER1-depleted flies are more vulnerable to these stressors. In silkworms, hydrogen peroxide both induces and is scavenged by OSER1 in vitro and in vivo. Knockdown of OSER1 in Caenorhabditis elegans leads to increased ROS production and shorter lifespan, mitochondrial fragmentation, decreased ATP production, and altered transcription of mitochondrial genes. Human proteomic analysis suggests that OSER1 plays roles in oxidative stress response, cellular senescence, and reproduction, which is consistent with the data and suggests that OSER1 could play a role in fertility in silkworms and nematodes. Human studies demonstrate that polymorphic variants in OSER1 are associated with human longevity. In summary, OSER1 is an evolutionarily conserved FOXO-regulated protein that improves resistance to oxidative stress, maintains mitochondrial functional integrity, and increases lifespan in multiple species. Additional studies will clarify the role of OSER1 as a critical effector of healthy aging.

Abstract Purpose To analyze the situation and influencing factors of patients returning to work after spinal surgery, and to provide reference for clinical intervention measures of patients returning to work after spinal surgery. Methods A computer search was conducted in Chinese and English database on the situation and influencing factors of patients returning to work after spinal surgery from the establishment of the database to February 2023. Meta-analysis was performed using RevMan 5.3 and StataMP 17.0 software. Results A total of 10 literatures were included, involving 11,548 subjects. Meta-analysis results showed that 58% of patients returned to work after spinal surgery [95%CI (0.47–0.69)]. Gender [OR = 2.41, 95%CI (1.58–3.37)], age [OR = 1.32, 95%CI (1.03–1.51)], job nature [OR = 5.94, 95%CI (3.54–9.62)], education level [OR = 0.23, 95%CI (0.06–0.48)], fear of disease progression [OR = 0.82, 95%CI (0.84–0.95)], and social support [OR = 1.21, 95%CI (1.12–1.37)] were the influencing factors for patients returning to work after spinal surgery. Conclusion The rate of patients returning to work after spinal surgery is low, and is affected by many factors. Medical personnel should pay comprehensive attention to the above high-risk groups and give timely intervention and support.

Abstract Background Gastric cancer (GC) is a major contributor to cancer-related mortality. Glycolysis plays a pivotal role in tumor microenvironment (TME) reprogramming. In this research, the functions of glycolysis-associated genes (GRGs) were evaluated to predict the outcome and reveal the characteristics of the immune microenvironment in individuals with stomach cancer. Methods The Cancer Genome Atlas (TCGA)-stomach adenocarcinoma (STAD) cohort provided gene expression and clinical data for gastric cancer (GC) patients, which were further authenticated using datasets sourced from the Gene Expression Omnibus (GEO). By referencing the Molecular Signatures Database (MSigDB), a total of 326 GRGs were pinpointed. The various subtypes of GC were outlined through consensus clustering, derived from the expression patterns of these GRGs. Utilizing multivariate Cox regression analysis, a multigene risk score model was formulated. Both the CIBERSORT and ESTIMATE algorithms played a pivotal role in assessing the immune microenvironment. To delve into the biological functions of the key genes, wound healing, transwell invasion, and MTT assays were conducted. Results Based on the expression patterns of GRGs, patients were categorized into two distinct groups: the metabolic subtype, designated as cluster A, and the immune subtype, labeled as cluster B. Patients belonging to cluster B exhibited a poorer prognosis. A prognostic risk score model, formulated upon the expression levels of six key GRGs — ME1, PLOD2, NUP50, CXCR4, SLC35A3, and SRD35A3 — emerged as a viable tool for predicting patient outcomes. The downregulation of CXCR4 notably diminished the glycolytic capacity of gastric cancer (GC) cells, alongside their migratory, invasive, and proliferative capabilities. Intriguingly, despite the adverse prognostic implications associated with both the immune subtype (cluster B) and the high-risk cohort, these groups exhibited a favorable immune microenvironment coupled with elevated expression of immune checkpoint genes. Our investigations revealed a positive correlation between high CXCR4 expression and low ME1 expression with the infiltration of CD8+ T cells, as well as an enhanced responsiveness to treatment with an anti-PD-1 immune checkpoint inhibitor. Conclusions In this study, we discovered that the expression profiles of GRGs hold the potential to forecast the prognosis of gastric cancer (GC) patients, thereby possibly aiding in clinical treatment decision-making.

Rhodiola, belonging to the Crassulaceae family, is a perennial herbaceous plant genus. There are about 90 Rhodiola species worldwide, some of which have been reported to have medicinal properties. Rhodiola sachalinensis is a perennial medicinal herb within this genus and, in the present study, its chloroplast genome was sequenced, assembled, annotated and compared with 24 other Rhodiola species. The results obtained show that the chloroplast genome of R. sachalinensis is 151 595 bp long and has a CG content of 37.7%. The inverted repeats (IR) region of the Rhodiola chloroplast genome is the most conserved region, with the main differences being observed in the ycf1 and ndhF genes at the IRb‐small single copy boundary, and rps19 and trnH genes at the IRa‐large single copy boundary. Phylogenetic analysis showed that Rhodiola species form two major clades, and species with recorded medicinal properties, clustered together in one branch except for R. dumulosa. Within the genus, R. sachalinensis is most closely related to Rhodiola rosea, although comparative analyses showed that only R. sachalinensis and Rhodiola subopposita contained the psbZ gene, which encodes a highly conserved protein subunit of the Photosystem II core complex. Overall, the present study contributes to the understanding of the chloroplast genome of Rhodiola species, and provides a theoretical basis for the study of their genetic diversity and possible use as medicinal plants.

Highlights Site-selective superassembly was used to synthesize a nanorobot with bionic rod-shaped head/hollow tail structure, exhibiting strong photothermal effect, high drug loading capacity, precise and controlled drug release, and excellent motility. Injectable regenerated silk fibroin (RSF) nanofibril hydrogels were developed via simple sonication, offering significant production, structural, and performance advantages. Nanorobot/thrombin (Thr)/RSF nanofibril hydrogels reduced intraoperative bleeding of hepatocellular carcinoma (HCC) spinal metastasis, provided starvation embolization, and prevented post-surgery recurrence. Nanorobot/Thr/RSF nanofibril hydrogels inhibited blood supply to residual tumors and reduced neovascularization, inhibiting post-surgery HCC spinal metastasis recurrence.

Abstract Objective To investigate the effects of Lathyrol on the expression of androgen receptor (AR) and sphingosine kinase 2 (SPHK2) in renal cell carcinoma (RCC) mice and to further explore the mechanism by which Lathyrol inhibits the invasion and incidence of epithelial-mesenchymal transition (EMT). Methods An RCC xenograft mouse model was constructed, and the mice were randomly divided into a model group, an experiment group and a negative control group. The experiment group was intragastrically gavaged with Lathyrol solution (20 mg/kg), the model group was intragastrically gavaged with 0.9% NaCl (same volume as that used in the experiment group), and the negative control group was injected intraperitoneally with 2 mg/kg cisplatin aqueous solution. Changes in the body weight and tumor volume of the mice were recorded. Western blot (WB) was used to assess the protein expression levels of AR, p-AR, CYP17A1, PARP1, E-cadherin, N-cadherin, vimentin, α-SMA, β-catenin, and ZO-1. Protein expression levels of SPHK2, metal matrix protease 2 (MMP2), MMP9 and urokinase-type plasminogen activator (uPA) in tumor tissues were assessed by immunohistochemistry (IHC). AR expression in tumor tissues was assessed after immunofluorescence (IF) staining. Results After 14 days of drug administration, compared with that in the model group, the tumor volumes in the negative control and experiment groups were lower; the difference in tumor volume among the model, control and experiment groups was statistically significant (P 0.05). In the model group, the protein expression levels of AR, p-AR, CYP17A1, SPHK2, and PARP1 were relatively increased, the protein expression levels of E-cadherin and ZO-1 were relatively reduced (P

Despite the extensive application of advanced oxidation processes (AOPs) in water treatment, the efficiency of AOPs in eliminating various emerging contaminants such as halogenated antibiotics is constrained by a number of factors. Halogen moieties exhibit strong resistance to oxidative radicals, affecting the dehalogenation and detoxification efficiencies. To address these limitations of AOPs, advanced reduction processes (ARPs) have been proposed. Herein, a novel nucleophilic reductant—namely, the carbon dioxide radical anion (CO2·−)—is introduced for the simultaneous degradation, dehalogenation, and detoxification of florfenicol (FF), a typical halogenated antibiotic. The results demonstrate that FF is completely eliminated by CO2·−, with approximately 100% of Cl− and 46% of F− released after 120 min of treatment. Simultaneous detoxification is observed, which exhibits a linear response to the release of free inorganic halogen ions (R2 = 0.97, p 75%) in degrading a series of halogenated antibiotics, including chloramphenicol (CAP), thiamphenicol (THA), diclofenac (DLF), triclosan (TCS), and ciprofloxacin (CIP). The system shows high tolerance to the pH of the solution and the presence of natural water constituents, and demonstrates an excellent degradation performance in actual groundwater, indicating the strong application potential of CO2·−-based ARPs in real life. Overall, this study elucidates the feasibility of CO2·− for the simultaneous degradation, dehalogenation, and detoxification of halogenated antibiotics and provides a promising method for their regulation during water or wastewater treatment.

Abstract Diabetic corneal neuropathy (DCN) is a common diabetic ocular complication with limited treatment options. In this study, we investigated the effects of topical and oral fenofibrate, a peroxisome proliferator-activated receptor-α agonist, on the amelioration of DCN using diabetic mice (n = 120). Ocular surface assessments, corneal nerve and cell imaging analysis, tear proteomics and its associated biological pathways, immuno-histochemistry and western blot on PPARα expression, were studied before and 12 weeks after treatment. At 12 weeks, PPARα expression markedly restored after topical and oral fenofibrate. Topical fenofibrate significantly improved corneal nerve fibre density (CNFD) and tortuosity coefficient. Likewise, oral fenofibrate significantly improved CNFD. Both topical and oral forms significantly improved corneal sensitivity. Additionally, topical and oral fenofibrate significantly alleviated diabetic keratopathy, with fenofibrate eye drops demonstrating earlier therapeutic effects. Both topical and oral fenofibrate significantly increased corneal β-III tubulin expression. Topical fenofibrate reduced neuroinflammation by significantly increasing the levels of nerve growth factor and substance P. It also significantly increased β-III-tubulin and reduced CDC42 mRNA expression in trigeminal ganglions. Proteomic analysis showed that neurotrophin signalling and anti-inflammation reactions were significantly up-regulated after fenofibrate treatment, whether applied topically or orally. This study concluded that both topical and oral fenofibrate ameliorate DCN, while topical fenofibrate significantly reduces neuroinflammation.

Abstract Keratinocyte proliferation and differentiation in epidermis are well-controlled and essential for reacting to stimuli such as ultraviolet light. Imbalance between proliferation and differentiation is a characteristic feature of major human skin diseases such as psoriasis and squamous cell carcinoma. However, the effect of keratinocyte metabolism on proliferation and differentiation remains largely elusive. We show here that the gluconeogenic enzyme fructose-1,6-bisphosphatase 1 (FBP1) promotes differentiation while inhibits proliferation of keratinocyte and suppresses psoriasis development. FBP1 is identified among the most upregulated genes induced by UVB using transcriptome sequencing and is elevated especially in upper epidermis. Fbp1 heterozygous mice exhibit aberrant epidermis phenotypes with local hyperplasia and dedifferentiation. Loss of FBP1 promotes proliferation and inhibits differentiation of keratinocytes in vitro. Mechanistically, FBP1 loss facilitates glycolysis-mediated acetyl-CoA production, which increases histone H3 acetylation at lysine 9, resulting in enhanced transcription of proliferation genes. We further find that the expression of FBP1 is dramatically reduced in human psoriatic lesions and in skin of mouse imiquimod psoriasis model. Fbp1 deficiency in mice facilitates psoriasis-like skin lesions development through glycolysis and acetyl-CoA production. Collectively, our findings reveal a previously unrecognized role of FBP1 in epidermal homeostasis and provide evidence for FBP1 as a metabolic psoriasis suppressor.

ABSTRACT: Notoginseng Radix et Rhizoma (Sanqi in Chinese) is a precious traditional Chinese herbal medicine. It has the effect of dispersing blood stasis and stopping bleeding, reducing swelling and fixing pain. However, it tends to contaminate with harmful fungi during storage, which may make it much less effective. In order to understand the fungal contamination of Notoginseng Radix et Rhizoma and master its composition of the exogenous fungi. The surface fungi of Notoginseng Radix et Rhizoma samples collected from six Chinese provinces and districts were investigated by using dilution plate method. Detection of aflatoxins by UPLC-MS/MS. The results showed that Penicillium citrinum was dominantly isolated from Notoginseng Radix et Rhizoma samples from No.1 to No.4. Aspergillus flavus, which produces aflatoxin, was dominantly isolated from Notoginseng Radix et Rhizoma samples from No.5 and No.6. In addition, kinds of mycotoxin were assayed which were produced by three of those identified A. flavus. All three fungi strains produced aflatoxin B1 (AFB1) and one strain HBSQ1-5 additionally produced other three kinds of mycotoxin, AFB2, AFG1 and AFG2. It is the results implied that it will be very important to take serious cautions when using Notoginseng Radix et Rhizoma. As well as, understanding the composition of the exogenous fungi of Notoginseng Radix et Rhizoma and the strains of toxin-producing fungi, which can play an important role in guiding the storage of Notoginseng Radix et Rhizoma..

Ground hydraulic fracturing plays a crucial role in controlling the far-field hard roof, making it imperative to identify the most suitable target stratum for effective control. Physical experiments are conducted based on engineering properties to simulate the gradual collapse of the roof during longwall top coal caving (LTCC). A numerical model is established using the material point method (MPM) and the strain-softening damage constitutive model according to the structure of the physical model. Numerical simulations are conducted to analyze the LTCC process under different hard roofs for ground hydraulic fracturing. The results show that ground hydraulic fracturing releases the energy and stress of the target stratum, resulting in a substantial lag in the fracturing of the overburden before collapse occurs in the hydraulic fracturing stratum. Ground hydraulic fracturing of a low hard roof reduces the lag effect of hydraulic fractures, dissipates the energy consumed by the fracture of the hard roof, and reduces the abutment stress. Therefore, it is advisable to prioritize the selection of the lower hard roof as the target stratum.

Abstract In complex networks, contrastive learning has emerged as a crucial technique for acquiring discriminative representations from graph data. Maximizing the similarity among relevant sample pairs while minimizing that among irrelevant pairs is pivotal in contrastive learning. Therefore, careful consideration must be given to the design of sample pairs in contrastive learning. However, existing node-level self-supervised contrastive learning often treats the enhanced representation of a central node as a positive sample, while considering representations of all other nodes as negative samples. This approach can lead to conflicts in downstream tasks on some graph data, as nodes of the same class are treated as negatives during learning. Precision in sample pair design is essential for enhancing the performance of contrastive learning. To address this issue, this paper introduces a negative sample debiased sampling contrastive learning (NDSCL), specifically tailored for node classification tasks. In particular, this method integrates contrastive learning with semi-supervised learning. A trained classifier assigns pseudo-labels to unlabeled data, and debiased sampling is applied to negative samples. Unlike other methods that focus on negative sample selection, NDSCL also addresses the imbalance in pseudo-label distribution by employing debiasing techniques. Finally, in conjunction with diffusion augmentation, the model is provided with diverse views as inputs to maximize the retention of underlying semantic information. Experimental results demonstrate that the proposed model significantly outperforms baseline models in node-level classification tasks across multiple network datasets. Moreover, the model not only enhances accuracy but also improves computational speed and memory requirements for handling large-scale graph data structures.

Abstract Intramuscular fat (IMF) in pork holds significant importance for economic performance within the pig industry and dietary calcium supplementation enhances the accumulation of intramuscular fat. Additionally, calcium ions inhibit translation and reduce protein synthesis. However, the mechanism by which calcium regulates IMF deposition in muscle through translation remains largely unknown. In this study, we compared the ribosome profiles of the longissimus dorsi muscles of Duroc $$\times$$ × Landrace $$\times$$ × Large white pigs from the normal calcium (NC) group or calcium supplement (HC) group by Ribo-seq, and RNA-seq. By integrating multiple-omics analysis, we further discovered 437 genes that were transcriptionally unchanged but translationally altered and these genes were significantly enriched in the oxidative phosphorylation signaling pathway. Furthermore, experimental data showed that inhibiting the expression of COX10 and mtND4L increased triglyceride accumulation in C2C12 cells, providing new targets for intramuscular fat deposition. Finally, this work links dietary calcium, translation regulation and IMF deposition, providing a new strategy for both meat quality and economic performance within the pig industry.

Abstract Tropical Cyclones (TCs) are devastating natural disasters. Analyzing four decades of global TC data, here we find that among all global TC-active basins, the South China Sea (SCS) stands out as particularly difficult ocean for TCs to intensify, despite favorable atmosphere and ocean conditions. Over the SCS, TC intensification rate and its probability for a rapid intensification (intensification by ≥ 15.4 m s−1 day−1) are only 1/2 and 1/3, respectively, of those for the rest of the world ocean. Originating from complex interplays between astronomic tides and the SCS topography, gigantic ocean internal tides interact with TC-generated oceanic near-inertial waves and induce a strong ocean cooling effect, suppressing the TC intensification. Inclusion of this interaction between internal tides and TC in operational weather prediction systems is expected to improve forecast of TC intensity in the SCS and in other regions where strong internal tides are present.

Abstract Lakes are hotspots for the biogeochemical processing of carbon, including dissolved organic matter (DOM). A less degradable fraction of DOM, preserved for a long time, can be categorized as recalcitrant DOM (RDOM). Lake RDOM is an important but neglected carbon sink, and its characteristics and transformation processes remain largely unknown.

The dissolution mechanism of the η-Ni3(Al0.5Nb0.5) phase during hot compression in Ni-based ATI718Plus superalloy has been investigated. The results indicate that with increasing deformation, the amount of dynamic recrystallization grains in the γ matrix increases, and the dissolution of the η phase tends to be accelerated. At the precipitation temperature of the η phase of 950 °C, the η phase area fraction decreased from 9.8% to 3.0% after deformation. The deformation promotes dislocation accumulation at the boundaries of the η phase, developing into subgrains and then evolving into DRX grains due to subgrain rotation. With increased strain, the subgrain rotations and DRX grain growths result in extrusion and subsequent fracture of the η phase. Due to strain incompatibility between the η phase and γ matrix, dislocation sustains are accumulated at their interfaces, which disrupts the η/γ semi-coherent interface, leading to localized amorphization and the decomposition of the η phase. Furthermore, dislocation surrounding the η phase can act as diffusion channels for solute elements, promoting the dissolution of the η phase and resulting in the element concentration gradient distribution from the η phase to the γ matrix.

This paper investigates the distribution pattern of welding porosity defects in annular weld seams of superalloy during laser welding. The results reveal that the initial portion of the annular weld seam exhibits a higher density and larger size of porosity defects compared to the ending portion. At a laser power of P = 360 W, the numerical simulation combination showed that the A1 region's average cooling rate is 8.767 × 103 °C/s and the A2 region is 8.151 × 103 °C/s that the thermal conduction effect at the initial welding position leads to an elevation in the base metal temperature in the subsequent unwelded region, thereby reducing the solidification rate of the molten pool in the latter half of the weld seam and effectively decreasing the porosity rate at the weld seam. Furthermore, the study demonstrates that elevating the base metal temperature can effectively modify the cooling rate of the molten pool, thereby influencing the formation of porosity defects. At a laser power of P = 360 W, increasing the base metal temperature to 600 °C reduces the cooling rate of the molten pool from 8.767 × 103 °C/s at a base metal temperature of T = 20 °C to 7.451 × 103 °C/s, leading to a decrease in the porosity rate from 3.357% to 0.022%. At a laser power of P = 672 W, increasing the base metal temperature to 600 °C reduces the cooling rate of the molten pool from 6.781 × 103 °C/s at a base metal temperature of T = 20 °C to 5.056 × 103 °C/s, leading to a decrease in the porosity rate from 8.214% to 0.002%. The increase in laser power brings more heat input, so the solidification rate of the molten pool decreases, but the porosity increases significantly. However, increasing the base temperature can effectively suppress the porosity defects under different laser powers. The research further reveals the relationship between welding porosity rate and cooling conditions, providing a control strategy for achieving low porosity rate welds.

Abstract Background Vibrio parahaemolyticus is the predominant etiological agent of seafood-associated foodborne illnesses on a global scale. It is essential to elucidate the mechanisms by which this pathogen disseminates. Given the existing research predominantly concentrates on localized outbreaks, there is a pressing necessity for a comprehensive investigation to capture strains of V. parahaemolyticus cross borders. Results This study examined the frequency and genetic attributes of imported V. parahaemolyticus strains among travelers entering Shanghai Port, China, between 2017 and 2019.Through the collection of 21 strains from diverse countries and regions, Southeast Asia was pinpointed as a significant source for the emergence of V. parahaemolyticus. Phylogenetic analysis revealed clear delineation between strains originating from human and environmental sources, emphasizing that underlying genome data of foodborne pathogens is essential for environmental monitoring, food safety and early diagnosis of diseases. Furthermore, our study identified the presence of virulence genes (tdh and tlh) and approximately 120 antibiotic resistance-related genes in the majority of isolates, highlighting their crucial involvement in the pathogenesis of V. parahaemolyticus. Conclusions This research enhanced our comprehension of the worldwide transmission of V. parahaemolyticus and its antimicrobial resistance patterns. The findings have important implications for public health interventions and antimicrobial stewardship strategies, underscoring the necessity for epidemiological surveillance of pathogen at international travel hubs.

Abstract The time-varying temperature distributions on bridge structures may remarkably change structural performance, which may result in differential strain/stress responses on structural members compared with the design conditions. Therefore, it is crucial to have a comprehensive understanding of temperature distributions and its effects on bridges. In this study, taking advantage of structural health monitoring technology, 1-year field monitoring data collected from a long-span suspension bridge were used to investigate the temperature distributions and their effects on the steel box girder. Specifically, the distributions and probability statistics of temperatures on the top and bottom plates were firstly analyzed. Based on which, the transverse and vertical temperature differences on the box girder were further examined, moreover, the representative values of temperature differences for various return periods were calculated by exceedance probability method. At end, a temperature prediction method was proposed to simulated the temperature field distributions during bridge life cycle, to provide substantial temperature data for estimating future operation condition. The results of this study were beneficial to structural evaluation of in-service bridges to ensure their serviceability and integrity in the life cycle.

Abstract Propagating waves and surface waves are two distinct types of light-transporting modes, the free control of which are both highly desired in integration photonics. However, previously realized devices are bulky in sizes, inefficient, and/or can only achieve one type of light-manipulation functionality with a single device. Here, we propose a generic approach to design bi-channel meta-devices, constructed by carefully selected meta-atoms possessing reflection phases of both structural-resonance and geometric origins, which can exhibit two distinct light-manipulation functionalities in near-field (NF) and far-field (FF) channels, respectively. After characterizing the scattering properties of basic meta-atoms and briefly stating the theoretical strategy, we design/fabricate three different meta-devices and experimentally characterize their bi-channel wave-control functionalities in the telecom regime. Our experiments show that the first two devices can multiplex the generations of NF and FF optical vortices with different topological charges, while the third one exhibits anomalous surface plasmon polariton focusing in the NF and hologram formation in the FF simultaneously. Our results expand the wave-control functionalities of metasurfaces to all wave-transporting channels, which may inspire many exciting applications in integration optics.

Abstract The manipulation of excitation modes and resultant emission colors in luminescent materials holds pivotal importance for encrypting information in anti-counterfeiting applications. Despite considerable achievements in multimodal and multicolor luminescent materials, existing options generally suffer from static monocolor emission under fixed external stimulation, rendering them vulnerability to replication. Achieving dynamic multimodal luminescence within a single material presents a promising yet challenging solution. Here, we report the development of a phosphor exhibiting dynamic multicolor photoluminescence (PL) and photo-thermo-mechanically responsive multimodal emissions through the incorporation of trace Mn2+ ions into a self-activated CaGa4O7 host. The resulting phosphor offers adjustable emission-color changing rates, controllable via re-excitation intervals and photoexcitation powers. Additionally, it demonstrates temperature-induced color reversal and anti-thermal-quenched emission, alongside reproducible elastic mechanoluminescence (ML) characterized by high mechanical durability. Theoretical calculations elucidate electron transfer pathways dominated by intrinsic interstitial defects and vacancies for dynamic multicolor emission. Mn2+ dopants serve a dual role in stabilizing nearby defects and introducing additional defect levels, enabling flexible multi-responsive luminescence. This developed phosphor facilitates evolutionary color/pattern displays in both temporal and spatial dimensions using readily available tools, offering significant promise for dynamic anticounterfeiting displays and multimode sensing applications.

Abstract Background The pig (Sus Scrofa) is one of the oldest domesticated livestock species that has undergone extensive improvement through modern breeding. European breeds have advantages in lean meat development and highly-productive body type, whereas Asian breeds possess extraordinary fat deposition and reproductive performance. Consequently, Eurasian breeds have been extensively used to develop modern commercial breeds for fast-growing and high prolificacy. However, limited by the sequencing technology, the genome architecture of some nascent developed breeds and the human-mediated impact on their genomes are still unknown. Results Through whole-genome analysis of 178 individuals from an Asian locally developed pig breed, Beijing Black pig, and its two ancestors from two different continents, we found the pervasive inconsistent gene trees and species trees across the genome of Beijing Black pig, which suggests its introgressive hybrid origin. Interestingly, we discovered that this developed breed has more genetic relationships with European pigs and an unexpected introgression from Asian pigs to this breed, which indicated that human-mediated introgression could form the porcine genome architecture in a completely different type compared to native introgression. We identified 554 genomic regions occupied 63.30 Mb with signals of introgression from the Asian ancestry to Beijing Black pig, and the genes in these regions enriched in pathways associated with meat quality, fertility, and disease-resistant. Additionally, a proportion of 7.77% of genomic regions were recognized as regions that have been under selection. Moreover, combined with the results of a genome-wide association study for meat quality traits in the 1537 Beijing Black pig population, two important candidate genes related to meat quality traits were identified. DNAJC6 is related to intramuscular fat content and fat deposition, and RUFY4 is related to meat pH and tenderness. Conclusions Our research provides insight for analyzing the origins of nascent developed breeds and genome-wide selection remaining in the developed breeds mediated by humans during modern breeding.

Abstract The N6-methyladenosine (m6A) RNA modification plays essential roles in multiple biological processes, including stem cell fate determination. To explore the role of the m6A modification in pluripotent reprogramming, we used RNA-seq to map m6A effectors in human iPSCs, fibroblasts, and H9 ESCs, as well as in mouse ESCs and fibroblasts. By integrating the human and mouse RNA-seq data, we found that 19 m6A effectors were significantly upregulated in reprogramming. Notably, IGF2BPs, particularly IGF2BP1, were among the most upregulated genes in pluripotent cells, while YTHDF3 had high levels of expression in fibroblasts. Using quantitative PCR and Western blot, we validated the pluripotency-associated elevation of IGF2BPs. Knockdown of IGF2BP1 induced the downregulation of stemness genes and exit from pluripotency. Proteome analysis of cells collected at both the beginning and terminal states of the reprogramming process revealed that the IGF2BP1 protein was positively correlated with stemness markers SOX2 and OCT4. The eCLIP-seq target analysis showed that IGF2BP1 interacted with the coding sequence (CDS) and 3’UTR regions of the SOX2 transcripts, in agreement with the location of m6A modifications. This study identifies IGF2BP1 as a vital pluripotency-associated m6A effector, providing new insight into the interplay between m6A epigenetic modifications and pluripotent reprogramming.

Preventing local tumor recurrence while promoting bone tissue regeneration is an urgent need for osteosarcoma treatment. However, the therapeutic efficacy of traditional photosensitizers is limited, and they lack the ability to regenerate bone. Here, a piezo-photo nanoheterostructure is developed based on ultrasmall bismuth/strontium titanate nanocubes (denoted as Bi/SrTiO3), which achieve piezoelectric field-driven fast charge separation coupling with surface plasmon resonance to efficiently generate reactive oxygen species. These hybrid nanotherapeutics are integrated into injectable biopolymer hydrogels, which exhibit outstanding anticancer effects under the combined irradiation of NIR and ultrasound. In vivo studies using patient-derived xenograft models and tibial osteosarcoma models demonstrate that the hydrogels achieve tumor suppression with efficacy rates of 98.6 % and 67.6 % in the respective models. Furthermore, the hydrogel had good filling and retention capabilities in the bone defect region, which exerted bone repair therapeutic efficacy by polarizing and conveying electrical stimuli to the cells under mild ultrasound radiation. This study provides a comprehensive and clinically feasible strategy for the overall treatment and tissue regeneration of osteosarcoma.

Key Clinical Message Mediastinal monophasic synovial sarcoma is a rare subtype that often lacks specific imaging characteristics, posing diagnostic challenges. This case report describes a mediastinal monophasic synovial sarcoma with vertebral metastasis, emphasizing imaging findings, differential diagnosis, and pathological features, thereby providing crucial support for accurate diagnosis and treatment planning.

IntroductionCytokine release syndrome (CRS) is one of the leading causes of mortality in patients with COVID-19 caused by the SARS-CoV-2 coronavirus. However, the mechanism of CRS induced by SARS-CoV-2 is vague.MethodsUsing spike protein combined with IL-2, IFN-γ, and TNF-α to stimulate human peripheral blood mononuclear cells (PBMCs) to secrete CRS-related cytokines, the content of cytokines in the supernatant was detected, and the effects of NK, T, and monocytes were analyzed.ResultsThis study shows that dendritic cells loaded with spike protein of SARS-CoV-2 stimulate T cells to release much more interleukin-2 (IL-2,) which subsequently cooperates with spike protein to facilitate PBMCs to release IL-1β, IL-6, and IL-8. These effects are achieved via IL-2 stimulation of NK cells to release tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), as well as T cells to release IFN-γ Mechanistically, IFN-γ and TNF-α enhance the transcription of CD40, and the interaction of CD40 and its ligand stabilizes the membrane expression of toll-like receptor 4 (TLR4) that serves as a receptor of spike protein on the surface of monocytes. As a result, there is a constant interaction between spike protein and TLR4, leading to continuous activation of nuclear factor-κ-gene binding (NF-κB). Furthermore, TNF-α also activates NF-κB signaling in monocytes, which further cooperates with IFN-γ and spike protein to modulate NF-κB–dependent transcription of CRS-related inflammatory cytokines.DiscussionTargeting TNF-α/IFN-γ in combination with TLR4 may represent a promising therapeutic approach for alleviating CRS in individuals with COVID-19.

Various biological effects of ionizing radiation, especially continuous exposure to low-dose radiation (LDR), have attracted considerable attention. Impaired bone structure caused by LDR has been reported, but little is known about the mechanism involved in the disruption of bone metabolism. In this study, given that LDR was found to (at a cumulative dose of 0.10 Gy) disturb the serum Mg2+ level and Notch1 signal in the mouse femur tissues, the effects of LDR on osteogenesis and the underlying molecular mechanisms were investigated based on an in vitro culture system for bone marrow stromal cells (BMSCs). Our data showed that cumulative LDR suppressed the osteogenic potential in BMSCs as a result of upregulation of Notch1 signaling. Further analyses indicated that the upregulation of NICD1 (Notch1 intracellular domain), the key intracellular domain for Notch1 signaling, under LDR was a consequence of enhanced protein stabilization caused by SUMOylation (small ubiquitin-like modification). Specifically, the downregulation of SENP1 (sentrin/SUMO-specific protease 1) expression induced by LDR enhanced the SUMOylation of NICD1, causing the accumulation of Notch1 signaling, which eventually inhibited the osteogenic potential of BMSCs. In conclusion, this work expounded on the mechanisms underlying the impacts of LDR on bone metabolism and shed light on the research on bone regeneration under radiation.

In recent years, the utilization of solar energy for conversion of CO2 into fuels has emerged as a promising strategy for mitigating the Greenhouse effect. However, transport efficiency of photogenerated carriers plays a crucial role in determining the efficacy of CO2 photocatalytic reaction. In this paper, a 2D/2D composite material consisting of NiFe-LDH/MoS2, presenting high efficiency in separating photogenerated electron-hole pairs, has been successfully synthesized using a straightforward hydrothermal method. XRD, XPS, FTIR and other characterization results proved that the composite was successfully prepared, and its unique direct Z-scheme heterostructure improved the efficiency of CO2 photocatalytic reduction effectively. The composite material NiFe-LDH/MoS2 demonstrated enhanced rate of photo-induced electron-hole pair separation comparing with pure NiFe-LDH. Apart from this, the charge transfer resistance was reduced simultaneously, the composite material exhibited perfect photocatalytic activity. In photocatalytic reduction reaction experiment, CO yield of NiFe-LDH/MoS2 can reach 10.72 μmol/g, which is 3.93-fold and 4.17-fold that of bare NiFe-LDH and MoS2. The cyclic test also shows that the catalyst has good stability under visible light irradiation.

BackgroundIntracerebral hemorrhage (ICH) is a severe stroke subtype with high morbidity, disability, and mortality rates. Currently, no biomarkers for ICH are available for use in clinical practice. We aimed to explore the roles of RNAs in ICH pathogenesis and identify potential diagnostic biomarkers.MethodsWe collected 233 individual blood samples from two independent cohorts, including 64 patients with ICH, 59 patients with ischemic stroke (IS), 60 patients with hypertension (HTN) and 50 healthy controls (CTRL) for RNA sequencing. Differentially expressed genes (DEGs) analysis, gene set enrichment analysis (GSEA), and weighted correlation network analysis (WGCNA) were performed to identify ICH-specific modules. The immune cell composition was evaluated with ImmuneCellAI. Multiple machine learning algorithms to select potential biomarkers for ICH diagnosis, and further validated by quantitative real-time polymerase chain reaction (RT−PCR). Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were performed to evaluate the diagnostic value of the signature for ICH. Finally, we generated M1 and M2 macrophages to investigate the expression of candidate genes.ResultsIn both cohorts, 519 mRNAs and 131 lncRNAs were consistently significantly differentially expressed between ICH patients and HTN controls. Gene function analysis suggested that immune system processes may be involved in ICH pathology. ImmuneCellAI analysis revealed that the abundances of 11 immune cell types were altered after ICH in both cohorts. WGCNA and GSEA identified 18 immune-related DEGs. Multiple algorithms identified an RNA panel (CKAP4, BCL6, TLR8) with high diagnostic value for discriminating ICH patients from HTN controls, CTRLs and IS patients (AUCs: 0.93, 0.95 and 0.82; sensitivities: 81.3%, 84.4% and 75%; specificities: 100%, 96% and 79.7%, respectively). Additionally, CKAP4 and TLR8 mRNA and protein levels decreased in RAW264.7 M1 macrophages and increased in RAW264.7 M2 macrophages, while BCL6 expression increased in M1 macrophages but not in M2 macrophages, which may provide potential therapeutic targets for ICH.ConclusionsThis study demonstrated that the expression levels of lncRNAs and mRNAs are associated with ICH, and an RNA panel (CKAP4, BCL6, TLR8) was developed as a potential diagnostic tool for distinguishing ICH from IS and controls, which could provide useful insight into ICH diagnosis and pathogenesis.

Background Obesity is a major public health issue in China and around the world. While acupuncture is often used in clinical practice, there is a lack of conclusive evidence for its weight-loss effect. Thus we will conduct a parallel, randomised, sham-controlled trial to evaluate the efficacy and safety of acupuncture for treating obesity.Methods and analysis A total of 160 eligible participants with obesity will be randomly assigned to the verum acupuncture group or sham acupuncture group at a ratio of 1:1. All participants will be treated three times a week for a duration of 12 weeks, and followed up for another 16 weeks. The primary outcome is the percentage change in body weight from baseline to Week 12. The secondary outcomes include body mass index (BMI), waist circumference (WC), body fat percentage (BF%), blood pressure, fasting blood glucose, insulin, glycosylated haemoglobin A1c, blood lipids, and physical functioning score on the Short Form 36 Health Survey. Other secondary outcomes including psychological and social functions will also be evaluated using the body image scale, psychological function scale, and social function scale of the BODY-Q, Rosenberg Self-Esteem Scale, Patient Health Questionnaire-9, and Dutch Eating Behaviour Questionnaire. BMI, WC, BF% and blood pressure will be evaluated at Week 0, 4, 8, 12 and 28. Other secondary outcomes will be measured at Week 0, 12 and 28, respectively. Adverse events will be recorded in detail during the trial.Ethics and dissemination Ethical approval of this trial was granted by the Ethics Committee of Chengdu Sport University (2023–102). Written informed consent will be obtained from study participants before enrolment. The findings will be disseminated through peer-reviewed journals.Trial registration number Chinese Clinical Trial Registry (ChiCTR2200062092).

Influenza infection is associated with a risk of thrombosis. Whether factors associated with reduced thrombosis might also be associated with reduced risk in patients with severe influenza is unknown. To investigate risk factors associated with thrombosis in patients with severe influenza. We used a cohort data set to identify adults diagnosed with severe influenza. Univariable and multivariable logistic regression models explored potential risk factors for thrombosis events in patients with severe influenza. Cox regression analysis was used to examine the risk factors for mortality in patients with severe influenza. A total of 854 patients with severe influenza were included in the analysis. The incidence of VTE was 9.37% (80/854). Multivariable regression analysis showed that previous aspirin medication (OR: 0.37; 95%CI: 0.14-0.84; P = .029) could reduce the risk factor of thrombosis in patients with severe influenza. Compared with patients in the non-thrombosis group, patients in the thrombosis group required more mechanical ventilation ( P

IntroductionMultifactorial Eye disorders are a significant public health concern and have a huge impact on quality of life. The pathophysiological mechanisms underlying these eye disorders were not completely understood since functional and low-throughput biological tests were used. By identifying biomarkers linked to eye disorders, metabolomics enables early identification, tracking of the course of the disease, and personalized treatment.MethodsThe electronic databases of PubMed, Scopus, PsycINFO, and Web of Science were searched for research related to Age-Related macular degeneration (AMD), glaucoma, myopia, and diabetic retinopathy (DR). The search was conducted in August 2023. The number of cases and controls, the study’s design, the analytical methods used, and the results of the metabolomics analysis were all extracted. Using the QUADOMICS tool, the quality of the studies included was evaluated, and metabolic pathways were examined for distinct metabolic profiles. We used MetaboAnalyst 5.0 to undertake pathway analysis of differential metabolites.ResultsMetabolomics studies included in this review consisted of 36 human studies (5 Age-related macular degeneration, 10 Glaucoma, 13 Diabetic retinopathy, and 8 Myopia). The most networked metabolites in AMD include glycine and adenosine monophosphate, while methionine, lysine, alanine, glyoxylic acid, and cysteine were identified in glaucoma. Furthermore, in myopia, glycerol, glutamic acid, pyruvic acid, glycine, cysteine, and oxoglutaric acid constituted significant metabolites, while glycerol, glutamic acid, lysine, citric acid, alanine, and serotonin are highly networked metabolites in cases of diabetic retinopathy. The common top metabolic pathways significantly enriched and associated with AMD, glaucoma, DR, and myopia were arginine and proline metabolism, methionine metabolism, glycine and serine metabolism, urea cycle metabolism, and purine metabolism.ConclusionThis review recapitulates potential metabolic biomarkers, networks and pathways in AMD, glaucoma, DR, and myopia, providing new clues to elucidate disease mechanisms and therapeutic targets. The emergence of advanced metabolomics techniques has significantly enhanced the capability of metabolic profiling and provides novel perspectives on the metabolism and underlying pathogenesis of these multifactorial eye conditions. The advancement of metabolomics is anticipated to foster a deeper comprehension of disease etiology, facilitate the identification of novel therapeutic targets, and usher in an era of personalized medicine in eye research.

Abstract Solid state nanochannels provide significant practical advantages in many fields due to their interesting properties, such as controllable shape and size, robustness, ion selectivity. But their complex preparation processes severely limit their application. In this study, a simple cost‐effective method to fabricate single nanochannel by embedding a single polyethylene oxide (PEO) nanofiber is presented. Firstly, PEO nanofibers are prepared by electrospinning, and then a single PEO nanofiber are precisely transferred to the target sample using a micromanipulation platform. Then, PDMS is used for embedding, and finally, the PEO nanofiber is dissolved to obtain a single nanochannel. Unlike other methods of preparing nanochannels by embedding nanofibers, this method can prepare single nanochannel. The diameter of nanochannel can be as fine as 100 nm, and the length can reach several micrometers. The power generation between two potassium chloride solutions with various combinations of concentrations was investigated using the nanochannel. This low‐cost flexible nanochannel can also be used in various applications, including DNA sequencing and biomimetic ion channel.

Drought usually affects the normal functioning of grassland ecosystems. Due to sustained global warming, the frequency and intensity of drought have significantly increased, leading to greater impacts on many aspects of grassland ecosystem functions, such as soil moisture, vegetation physiological structure and ecosystem community structure. Ecosystem stability dimension can help us better understand the changes induced by drought occurred within ecosystems. Using the Normalized Vegetation Index (NDVI), climate and biodiversity data, we quantified resistance, resilience and temporal stability of grassland ecosystems under long term drought in northern China and calculated the ecosystem stability dimension based on the correlation between the three stability indicators. The results indicated that Qinghai Tibet Plateau and Inner Mongolian Plateau showed strong resistance to drought, while Loess Plateau region presented rapid recovery after drought. The resistance, compared to resilience and temporal stability, exhibited stronger sensitivity to drought in space. Drought promoted the transformation of grassland ecosystems into multidimensional structures. The reduction of aboveground biomass caused by frequent droughts accelerated the transformation in grassland ecosystems. Our findings provide the new insights for guiding the response mechanism of drought on grassland ecosystems.

Several research studies globally focus on the volatility of gold and oil prices, neglecting an examination of silver price volatility in relation to other market commodities. The current Covid-19 pandemic has led to various uncertainties and fluctuations in financial and stock exchange markets, yet existing literature primarily concentrates on individual product rates rather than combined rate changes. Our study aims to bridge this research gap by analyzing the relationship between oil rates, silver rates, oil rate transitions, and silver rate transitions on the security exchange in China from 1990 to 2022, using the ARDL approach and Nonlinear ARDL for a comprehensive assessment. The findings reveal a significant impact of silver and oil rates on China's security exchange in the future, with the negative effects of oil rate changes and a positive effect of silver rate transitions. In the short term, oil and silver rates play a crucial role in influencing China's security exchange, highlighting the importance of monitoring these trends for investors. It is recommended that investors respond prudently to market transitions, particularly by considering silver as a secure option during times of uncertainty, while policymakers should implement appropriate measures to manage the rapid fluctuations from oil to the security market.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide, having become a global public health problem, so the pathophysiological mechanisms and therapeutic strategies of CVDs need further study. Legumain is a powerful enzyme that is widely distributed in mammals and plays an important role in a variety of biological processes. Recent research suggests that legumain is associated with the occurrence and progression of CVDs. In this review, we provide a comprehensive overview of legumain in the pathogenesis of CVDs. The role of legumain in CVDs, such as carotid atherosclerosis, pulmonary hypertension, coronary artery disease, peripheral arterial disease, aortic aneurysms and dissection, is discussed. The potential applications of legumain as a biomarker of these diseases are also explored. By understanding the role of legumain in the pathogenesis of CVDs, we aim to support new therapeutic strategies to prevent or treat these diseases.

BackgroundIn recent years, with the continuous development of fluorescence imaging technology, research on its application in pancreatic diseases has surged. This area is currently of high research interest and holds the potential to become a non-invasive and effective tool in the diagnosis and treatment of pancreatic diseases. The objective of this study is to explore the hotspots and trends in the field of fluorescence imaging technology applications in pancreatic diseases from 2003 to 2023 through bibliometric and visual analysis.MethodsThis study utilized the Web of Science (core collection) to identify publications related to the application of fluorescence imaging technology in pancreatic diseases from 2003 to 2023. Tools such as CiteSpace (V 6.2.R6), VOSviewer (v1.6.20), and R Studio (Bibliometrix: R-tool version 4.1.4) were employed to analyze various dimensions including publication count, countries, institutions, journals, authors, co-cited references, keywords, burst words, and references.ResultsA comprehensive analysis was conducted on 913 papers published from January 1, 2003, to December 1, 2023, on the application of fluorescence imaging technology in pancreatic diseases. The number of publications in this field has rapidly increased, with the United States being the central hub. The University of California, San Diego emerged as the most active institution. “Biomaterials” was identified as the most influential journal. Authors with the most publications and the highest average citations per article are Hoffman, Robert M. and Luiken, George A., respectively. Keywords such as pancreatic cancer, cancer, expression, indocyanine green, and nanoparticles received widespread attention, with indocyanine green and nanoparticles being current active research hotspots in the field.ConclusionThis study is the first bibliometric analysis in the field of fluorescence imaging technology applications in pancreatic diseases. Our data will facilitate a better understanding of the developmental trends, identification of research hotspots, and direction in this field. The findings provide practical information for other scholars to grasp key directions and cutting-edge insights.

Abstract It is newly revealed that collagen works as a physical barrier to tumor immune infiltration, oxygen perfusion, and immune depressor in solid tumors. Meanwhile, after radiotherapy (RT), the programmed death ligand‐1 (PD‐L1) overexpression and transforming growth factor‐β (TGF‐β) excessive secretion would accelerate DNA damage repair and trigger T cell exclusion to limit RT efficacy. However, existing drugs or nanoparticles can hardly address these obstacles of highly effective RT simultaneously, effectively, and easily. In this study, it is revealed that inducing mitochondria dysfunction by using oxidative phosphorylation inhibitors like Lonidamine (LND) can serve as a highly effective multi‐immune pathway regulation strategy through PD‐L1, collagen, and TGF‐β co‐depression. Then, IR‐LND is prepared by combining the mitochondria‐targeted molecule IR‐68 with LND, which then is loaded with liposomes (Lip) to create IR‐LND@Lip nanoadjuvants. By doing this, IR‐LND@Lip more effectively sensitizes RT by generating more DNA damage and transforming cold tumors into hot ones through immune activation by PD‐L1, collagen, and TGF‐β co‐inhibition. In conclusion, the combined treatment of RT and IR‐LND@Lip ultimately almost completely suppressed the growth of bladder tumors and breast tumors.

In tunnelling and mining applications, the rock-shotcrete interface is crucial for structural stability at the initial support stage, but its complex stress distribution remains poorly understood due to the rock surface depressions. This study employs a series of simulations and model tests to investigate the influence of depression shape and depth on the interface. The results indicate that increased depression depth negatively impacts nominal tensile strength (NTS) and crack initiation energy, although these effects are lessened with rectangular-toothed depressions. The tensile stress on non-depressed surfaces is unaffected by depression depth but is influenced by its shape. Due to the concentration of tensile stress, non-concave interfaces are most prone to failure. In underground rock early support, the construction method of rectangular depression chiselling is more conducive to improving the strength of the shotcrete-rock interface.

Abstract Diffuse myocardial fibrosis is associated with adverse outcomes in heart failure with preserved ejection fraction (HFpEF). Dual-energy CT (DECT) can noninvasively assess myocardial fibrosis by quantification of extracellular volume (ECV) fraction. This study evaluated the association between ECV measured by DECT and clinical outcomes in patients with HFpEF. 125 hospitalized HFpEF patients were enrolled in this retrospective cohort study. ECV was measured using DECT with late iodine enhancement. The composite endpoint was defined as HFpEF hospitalization and all-cause mortality during the follow-up. During the median follow-up of 10.4 months, 34 patients (27.20%) experienced the composite outcomes, including 5 deaths; and 29 HFpEF hospitalizations. The higher DECT-ECV group had higher rates of composite outcomes than the low ECV group (log-rank X 2 = 6.818, P = 0.033). In multivariate Cox regression analysis, the ECV (HR 1.17, 95% CI 1.06–1.30, P = 0.001) and NT-pro BNP (HR 2.83, 95% CI 1.16–6.88, P = 0.022) were independent risk factors for the adverse outcomes. Myocardial ECV measured using DECT was an independent risk factor for adverse outcomes in patients with HFpEF.

Abstract Background The safety and efficacy of transarterial chemoembolization plus molecular targeted therapy (MTT) combined with immune checkpoint inhibitors (ICIs) in primary liver cancer have been demonstrated. However, the evidence for TACE plus MTT combined with ICIs in the treatment of recurrent hepatocellular carcinoma (RHCC) is limited. Given the excellent performance of this combination regimen in primary liver cancer, it is necessary to evaluate the efficacy of TACE plus MTT combined with ICIs in RHCC. Methods A total of 88 patients with RHCC treated with TACE plus MTT combined with camrelizumab (TACE-TC group, n = 46) or TACE plus MTT (TACE-T group, n = 42) were retrospectively collected and analyzed. In this study, we evaluated the effectiveness and safety of combination therapy for patients with RHCC by analyzing tumor response, progression-free survival (PFS), overall survival (OS), laboratory biochemical indices, and adverse events (AEs). Results TACE-TC was superior to TACE-T in PFS (14.0 vs. 8.9 months, p = 0.034) and OS (31.1 vs. 20.2 months, p = 0.009). Moreover, TACE-TC achieved more preferable benefits with respect to disease control rate (89.1% vs. 71.4%, p = 0.036) and objective response rate (47.8% vs. 26.2%, p = 0.036) compared with TACE-T in patients with RHCC. Compared with the TACE-T group, the AFP level in the TACE-TC group decreased more significantly after 3 months of treatment. Multivariate analysis showed that treatment option was a significant predictor of OS and PFS, while the portal vein tumor thrombus and interval of recurrence from initial treatment were another prognostic factor of PFS. There was no significant difference between the TACE-TC and TACE-T groups for Grade 3–4 adverse events. Conclusions A combination therapy of TACE, MTT, and camrelizumab significantly improved tumor response and prolonged survival duration, showing a better survival prognosis for RHCC patients.

Abstract Background Microdeletion of the human chromosomal region 16p11.2 (16p11.2 $${}^{+/-}$$ + / - ) is a prevalent genetic factor associated with autism spectrum disorder (ASD) and other neurodevelopmental disorders. However its pathogenic mechanism remains unclear, and effective treatments for 16p11.2 $${}^{+/-}$$ + / - syndrome are lacking. Emerging evidence suggests that the gut microbiota and its metabolites are inextricably linked to host behavior through the gut-brain axis and are therefore implicated in ASD development. Despite this, the functional roles of microbial metabolites in the context of 16p11.2 $${}^{+/-}$$ + / - are yet to be elucidated. This study aims to investigate the therapeutic potential of indole-3-propionic acid (IPA), a gut microbiota metabolite, in addressing behavioral and neural deficits associated with 16p11.2 $${}^{+/-}$$ + / - , as well as the underlying molecular mechanisms. Results Mice with the 16p11.2 $${}^{+/-}$$ + / - showed dysbiosis of the gut microbiota and a significant decrease in IPA levels in feces and blood circulation. Further, these mice exhibited significant social and cognitive memory impairments, along with hyperactivation of hippocampal dentate gyrus neurons and reduced inhibitory synaptic transmission in this region. However, oral administration of IPA effectively mitigated the histological and electrophysiological alterations, thereby ameliorating the social and cognitive deficits of the mice. Remarkably, IPA treatment significantly increased the phosphorylation level of ERK1, a protein encoded by the Mapk3 gene in the 16p11.2 region, without affecting the transcription and translation of the Mapk3 gene. Conclusions Our study reveals that 16p11.2 $${}^{+/-}$$ + / - leads to a decline in gut metabolite IPA levels; however, IPA supplementation notably reverses the behavioral and neural phenotypes of 16p11.2 $${}^{+/-}$$ + / - mice. These findings provide new insights into the critical role of gut microbial metabolites in ASD pathogenesis and present a promising treatment strategy for social and cognitive memory deficit disorders, such as 16p11.2 microdeletion syndrome. Video Abstract

Abstract In this modern era of commercialized higher education, learning and qualifications have become the essential commodities that drive nations’ economic progress. Free market principles related to consumerism appear to dictate and shape the operational framework of higher education. While a market-driven strategy may yield benefits in promoting the internationalization of higher education, it could potentially come at the expense of sustainable development of universities and proper learning. Employing a qualitative method, this study explores whether the commercialized nature and marketing of internationalized higher education contributes to or hinders its viability. It does this by comparing the practices between a Double First-Class university and a non-Double First-Class university. Findings underscore the need for more attention to be paid to creating a sustainable higher education system. Colleges and universities should strategically rebrand themselves by innovating their management and teaching systems to foster more competent international human resources, leading to sustainable universities and better prepared international students.

Abstract Soil contamination by uranium presents a burgeoning global environmental concern, exerting detrimental effects on both agricultural production and soil health. Biochar, a carbonaceous material derived from biomass pyrolysis, exhibits considerable potential for remediating uranium-contaminated soils. However, a comprehensive review of the effects of biochar on the fate and accumulation of uranium in soil–plant systems remains conspicuously absent. In this paper, uranium sources and contamination are reviewed, and the impact of biochar on uranium immobilization and detoxification in soil–plant systems is analyzed. We reviewed the status of uranium contamination in soils globally and found that mining activities are currently the main sources. Further meta-analysis revealed that biochar addition significantly reduced the soil uranium bioavailability and shoot uranium accumulation, and their effect value is 58.9% (40.8–76.8%) and 39.7% (15.7–63.8%), respectively. Additionally, biochar enhances the soil microenvironment, providing favourable conditions for promoting plant growth and reducing uranium mobility. We focused on the mechanisms governing the interaction between biochar and uranium, emphasising the considerable roles played by surface complexation, reduction, ion exchange, and physical adsorption. The modification of biochar by intensifying these mechanisms can promote uranium immobilisation in soils. Finally, biochar alleviates oxidative stress and reduces uranium accumulation in plant tissues, thereby mitigating the adverse effects of uranium on plant growth and development. Overall, our review highlights the capacity of biochar to remediate uranium contamination in soil–plant systems through diverse mechanisms, providing valuable insights for sustainable environmental remediation. Highlights Biochar reduces uranium mobility through a variety of mechanisms, including surface complexation, reduction, ion exchange, and physical adsorption. Biochar significantly reduces uranium bioavailability in soil and limits its accumulation in plants. Modified biochar has been shown to enhance its effectiveness in immobilising uranium. Biochar application to soil not only promotes uranium remediation but also improves soil quality. Graphical Abstract

Rock mass may be exposed to high temperature and cooled by water in fire, geothermal resource exploitation and deep underground engineering, which affects the safety of these engineering. In this study, cracked straight through Brazilian disc (CSTBD) specimen was used to study the fracture properties of granite treated with different water-cooling time from 25 °C to 800 °C. A camera was used to record the fracture process of the specimen, the evolution of strain at the specimen surface was obtained by using digital image correlation technology, and the morphological characteristics of fracture surface were observed by using scanning electron microscopy. The results show that water-cooling time has some effects on fracture properties of granite, but its effect is less than the temperature. With the increase of water-cooling time, the mode I fracture toughness decreases first, then increases and finally decreases at the same temperature, and the fracture toughness ranges from 0.419 MPa m1/2 to 0.567 MPa m1/2 at 400 °C. The crack tip opening displacement (CTOD), crack propagation path and fracture surface are related to the energy released during the specimen failure. When the temperature is 25 °C or 200 °C, the energy released is large and the fracture surface is relatively flat with irregular sharp edges, the main cracks are straight lines. At 600 °C, the main crack is zigzag, the CTOD and the maximum principal strain in order can reach 0.143 mm and 0.731 %. This study can help to understand the effect of water-cooling time on engineering rock mass.

Porous solid adsorbents for C2H2/CO2 separation are generally confronted with poor stability, high cost, or high regeneration energy, which largely inhibit their industrial implementation. A desired adsorbent material for practical implementation should exhibit a good balance between low cost, high stability, scale-up production feasibility, and good separation performance. An effective strategy is herein explored based on reticular chemistry through embedding methyl groups in a prototype microporous metal–organic framework (MOF) featuring low cost and high stability to effectively separate an C2H2/CO2 mixture. The anchored methyl groups on the pore surfaces could strongly boost the C2H2 packing density and specifically enhance the C2H2/CO2 separation performance, as distinctly established by single-component gas sorption isotherms. The CAU-10-CH3 material exhibits an excellent C2H2 packing density of 486 g L–1 and high adsorption differences between C2H2 and CO2 uptake (147%), outperforming the prototype benchmark material CAU-10-H (392 g L–1 and 53%). The highly selective adsorption of C2H2 over CO2 was achieved by a lower C2H2 adsorption enthalpy (25.18 kJ mol–1) compared to that with unfunctionalized CAU-10-H. In addition, dynamic column breakthrough experiments further confirm CAU-10-CH3’s efficient separation performance for the C2H2/CO2 mixture. CAU-10-CH3 accomplishes the benchmark balance between cost, stability, scale-up, and separation performance for C2H2/CO2 separation, establishing its promise for industrial implementation. This approach could further facilitate the development of advanced MOF adsorbents to address challenging separation processes. Thus, this study paves the route for the practical implementations of MOF materials in the gas adsorption and separation field.

The paper reports on the atomic investigation about β phase in Mg96Gd2Y1Ni1 alloy by using the first-principles study and the high-angle annular dark-field scanning transmission electron microscope (HAADF-STEM) corrected by atomic Cs. By using HAADF-STEM, the rectangular β phases were observed in the underage and peak aging stages in Mg96Gd2Y1Ni1 alloy. The β phase could be precipitated from the previously precipitated β phase, and the β phase grew in steps when it was precipitated. A special transition structure of three atomic layer thicknesses was first observed at the edge of the β phase and the structure of this interface is probably as the β/Mg1 interface for the analysis of thermodynamic characterization and electronic characterization. The β' phase and the βH structure were precipitated only at the edge of the length directions of the β phase. The β' phase continues to grow into a β phase directly without the formation of β1 phase, resulting in an increase in the length of the β phase, which is discovered for the first time.

Abstract The objective of this study was to analyze the antimicrobial resistance (AMR) characteristics produced by antibiotic resistance genes (ARGs), mobile genetic elements (MGEs) and gene cassettes in Escherichia coli isolated from the feces of captive black bears. Antimicrobial susceptibility testing was performed by using the disk diffusion method, and both MGEs and integron gene cassettes were detected by polymerase chain reaction. Our results showed that 43.7% (62/142) of the isolates were multidrug resistant strains and 97.9% (139/142) of the isolates were resistant to at least one antibiotic. The highest AMR phenotype was observed for tetracycline (79.6%, 113/142), followed by ampicillin (50.0%, 71/142), trimethoprim-sulfamethoxazole (43.7%, 62/142) and cefotaxime (35.9%, 51/142). However, all isolates were susceptible to tobramycin. tetA had the highest occurrence in 6 ARGs in 142 E. coli isolates (76.8%, 109/142). Ten mobile genetic elements were observed and IS26 was dominant (88.0%, 125/142). ISECP1 was positively associated with five β-lactam antibiotics. ISCR3/14, IS1133 and intI3 were not detected. Seventy-five E. coli isolates (65 intI1-positive isolates, 2 intI2-positive isolates and 8 intI1 + intI2-positive isolates) carried integrons. Five gene cassettes (dfrA1, aadA2, dfrA17-aadA5, aadA2-dfrA12 and dfrA1-aadA1) were identified in the intI1-positive isolates and 2 gene cassettes (dfrA1-catB2-sat2-aadA1 and dfrA1-catB2-sat1-aadA1) were observed in the intI2-positive isolates. Monitoring of ARGs, MGEs and gene cassettes is important to understand the prevalence of AMR, which may help to introduce measures to prevent and control of AMR in E. coli for captive black bears.

Abstract The treatment of critical-size bone defects with irregular shapes remains a major challenge in the field of orthopedics. Bone implants with adaptability to complex morphological bone defects, bone-adhesive properties, and potent osteogenic capacity are necessary. Here, a shape-adaptive, highly bone-adhesive, and ultrasound-powered injectable nanocomposite hydrogel is developed via dynamic covalent crosslinking of amine-modified piezoelectric nanoparticles and biopolymer hydrogel networks for electrically accelerated bone healing. Depending on the inorganic-organic interaction between the amino-modified piezoelectric nanoparticles and the bio-adhesive hydrogel network, the bone adhesive strength of the prepared hydrogel exhibited an approximately 3-fold increase. In response to ultrasound radiation, the nanocomposite hydrogel could generate a controllable electrical output (-41.16 to 61.82 mV) to enhance the osteogenic effect in vitro and in vivo significantly. Rat critical-size calvarial defect repair validates accelerated bone healing. In addition, bioinformatics analysis reveals that the ultrasound-responsive nanocomposite hydrogel enhanced the osteogenic differentiation of bone mesenchymal stem cells by increasing calcium ion influx and up-regulating the PI3K/AKT and MEK/ERK signaling pathways. Overall, the present work reveals a novel wireless ultrasound-powered bone-adhesive nanocomposite hydrogel that broadens the therapeutic horizons for irregular bone defects.