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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 The creep characteristics and potential deformation patterns of gangue backfill material are crucial in backfill mining operations. This study utilizes crushed gangue from the Gangue Yard in Fuxin City as the research material. An in-house designed, large-scale, triaxial gangue compaction test system was used. Triaxial compaction creep tests were conducted on gangue materials with varying particle size distributions. Analysis was performed based on different particle sizes, stresses, and confinement pressures. The study investigates the creep characteristics of the gangue under different conditions and explores the underlying causes. It reveals the relationship between the creep deformation of gangue materials and the passage of time. Mathematical methods are applied to develop a triaxial compaction creep power law model for gangue backfill materials. Finally, the creep results are fitted using an empirical formula approach.

AbstractContext Liuwei Dihuang pill (LWDH) has been used to treat postmenopausal osteoporosis (PMOP).Objective To explore the effects and mechanisms of action of LWDH in PMOP.Materials and methods Forty-eight female Sprague-Dawley rats were divided into four groups: sham-operated (SHAM), ovariectomized (OVX), LWDH high dose (LWDH-H, 1.6 g/kg/d) and LWDH low dose (LWDH-L, 0.8 g/kg/d); the doses were administered after ovariectomy via gavage for eight weeks. After eight weeks, the bone microarchitecture was evaluated. The effect of LWDH on the differentiation of bone marrow mesenchymal stem cells (BMSCs) was assessed via osteogenesis- and lipogenesis-induced BMSC differentiation. The senescence-related biological indices were also detected using senescence staining, cell cycle analysis, quantitative real-time polymerase chain reaction and western blotting. Finally, the expression levels of autophagy-related proteins and Yes-associated protein (YAP) were evaluated.Results LWDH-L and LWDH-H significantly modified OVX-induced bone loss. LWDH promoted osteogenesis and inhibited adipogenesis in OVX-BMSCs. Additionally, LWDH decreased the positive ratio of senescence OVX-BMSCs and improved cell viability, cell cycle, and the mRNA and protein levels of p53 and p21. LWDH upregulated the expression of autophagy-related proteins, LC3, Beclin1 and YAP, in OVX-BMSCs and downregulated the expression of p62.Discussion and conclusions LWDH improves osteoporosis by delaying the BMSC senescence through the YAP-autophagy axis.

Abstract Zika virus (ZIKV) belongs to the Flavivirus genus of the Flaviviridae family along with the four serotypes of dengue virus (DENV1–4). The recent global outbreaks of contemporary ZIKV strains demonstrated that infection can lead to neurological sequelae in adults and severe abnormalities in newborns that were previously unreported with ancestral strains. As such, there remains an unmet need for efficacious vaccines and antiviral agents against ZIKV. The non-structural protein 1 (NS1) is secreted from the infected cell and is thought to be associated with disease severity besides its proven usefulness for differential diagnoses. However, its physiologically relevant structure and pathogenesis mechanisms remain unclear. Here, we present high-resolution cryoEM structures of ZIKV recombinant secreted NS1 (rsNS1) and its complexes with three human monoclonal antibodies (AA12, EB9, GB5), as well as evidence for ZIKV infection-derived secreted NS1 (isNS1) binding to High Density Lipoprotein (HDL). We show that ZIKV rsNS1 forms tetramers and filamentous repeats of tetramers. We also observed that antibody binding did not disrupt the ZIKV NS1 tetramers as they bound to the wing and connector subdomain of the β-ladder. Our study reveals new insights into NS1 multimerization, highlights the need to distinguish the polymorphic nature of rsNS1 and isNS1, and expands the mechanistic basis of the protection conferred by antibodies targeting NS1.

Abstract When pressure relief mining of a non‐all‐coal protective layer, to realize the accurate regulation of the pressure relief range and pressure release value of mining height, it is necessary to carry out research on the migration of overburden and the stress distribution law of stope under mining height control. Through similar material simulation experiments, four groups of similar material simulation experimental models were established. The laws of rock strata movement and stress distribution at 2, 4, and 5 m mining heights under different geological conditions, and the laws of rock strata movement and stress distribution at 5 and 8 m mining heights under the same geological conditions were obtained. The research results show that the geological conditions and mining height do not affect the evolution of the rock strata movement range. The highest position of the strata movement and deformation is linearly related to the advancing distance of the coalface. The maximum height of rock strata movement increases abruptly when encountering the key strata, but it still has a linear relationship. The highest position of each expansion of the fracture zone has an exponential relationship with the advancing distance of the coalface. When the key strata are encountered, the maximum height of the fracture zone increases abruptly. The change in mining height only affects the distribution range of the “three zones.” The mining height controls the stress distribution of stope by adjusting the “three zones” of the roof. With the increase in mining height, the caving zone and fracture zone range increase. The corresponding pressure relief range and pressure relief value show the change law of first increasing and then decreasing. There is an optimal mining height, which can make the pressure relief effect of stope best.

Triple-negative breast cancer (TNBC) is labeled as an aggressive type of breast cancer and still has limited therapeutic targets despite the advanced development of cancer therapy. Neutrophils, representing the conventional inflammatory response, significantly influence the malignant phenotype of tumors, supported by abundant evidence. As a vital function of neutrophils, NETs are the extracellular fibrous networks including the depolymerized chromatin DNA frames with several antimicrobial proteins. They are produced by activated neutrophils and are involved in host defence or immunological reactions. This review focuses more on the interactions between neutrophils and TNBC, focusing on how neutrophils modulate the immune response within the tumor milieu. Specifically, we delve into the role of NETs, which are involved in promoting tumor growth and metastasis, inhibiting anti-tumor immunity, and promoting tumor-associated thrombosis. Furthermore, we discuss recent advancements in therapeutic strategies aimed at targeting NETs to enhance the efficacy of TNBC treatment. The advances in the knowledge of the dynamics between neutrophils and TNBC may lead to the opportunity to devise new immunotherapeutic strategies targeted to fight this hostile type of breast cancer.

The pursuit of effective treatments for brain tumors has increasingly focused on the promising area of nanoparticle-enhanced radiotherapy (NERT). This review elucidates the context and significance of NERT, with a particular emphasis on its application in brain tumor therapy—a field where traditional treatments often encounter obstacles due to the blood-brain barrier (BBB) and tumor cells’ inherent resistance. The aims of this review include synthesizing recent advancements, analyzing action mechanisms, and assessing the clinical potential and challenges associated with nanoparticle (NP) use in radiotherapy enhancement. Preliminary preclinical studies have established a foundation for NERT, demonstrating that nanoparticles (NPs) can serve as radiosensitizers, thereby intensifying radiotherapy’s efficacy. Investigations into various NP types, such as metallic, magnetic, and polymeric, have each unveiled distinct interactions with ionizing radiation, leading to an augmented destruction of tumor cells. These interactions, encompassing physical dose enhancement and biological and chemical radio sensitization, are crucial to the NERT strategy. Although clinical studies are in their early phases, initial trials have shown promising results in terms of tumor response rates and survival, albeit with mindful consideration of toxicity profiles. This review examines pivotal studies affirming NERT’s efficacy and safety. NPs have the potential to revolutionize radiotherapy by overcoming challenges in targeted delivery, reducing off-target effects, and harmonizing with other modalities. Future directions include refining NP formulations, personalizing therapies, and navigating regulatory pathways. NERT holds promise to transform brain tumor treatment and provide hope for patients.

Abstract The continuous operation of coal mine underground reservoirs exposes the coal pillar dams to mining disturbances and prolonged water immersion, resulting in the deterioration of coal pillars' mechanical properties and posing a serious threat to the dam stability. To this end, coal samples from the proposed pillar dam in the 5–2 coal seam of Daliuta Mine in Shendong Mining Area were selected for conducting water absorption tests and triaxial compression tests under conditions of repeated water immersion, in order to study the deterioration of the mechanical properties and acoustic emission damage characteristic of coal samples as well as the mechanism behind the deterioration of coal samples under the water–rock interaction. The results indicated that: (1) the saturated water content of coal samples exhibited a progressive increase as the water immersion times increased, but with a diminishing rate of growth. (2) As the water immersion times increased, the compressive strength, cohesive force, and internal friction angle of coal samples gradually decreased. Notably, the deterioration effect was more pronounced in compressive strength and cohesive force, while the decline in internal friction angle was relatively minor, and the total deterioration degree and the stage deterioration degree of the above three had evident cumulativity and non-uniformity. The progressive rise in water immersion times led to a gradual attenuation of the deterioration effect. Meanwhile, the confining pressure exhibited a certain inhibitory impact on the strength deterioration of coal samples. (3) Compared to the dry coal samples, the average AE count rate of coal samples subjected to a single water immersion exhibited a significant decrease, and subsequent water immersion for two, three, and four times resulted in a very minor decrease in the average AE count rate. (4) The AE cumulative ringing counts in coal samples exhibited varying degrees of reduction as water immersion times increased. Specifically, the most significant decrease in AE cumulative ringing counts occurred after the initial water immersion, followed by a gradual decrease thereafter. The energy-releasing capacity of coal samples decreased, while their plasticity exhibited a gradual increase. (5) A damage model was developed for coal samples based on the water immersion times. The model indicated that the damage to coal samples increased as the water immersion times increased, and the damage rate gradually decreased and eventually stabilized. (6) The deterioration mechanism of coals under the water–rock interaction was explained. Through repeated water immersion, the physical, chemical, and mechanical interactions between water and coal induced alterations in the internal microstructure of coal samples, resulting in the deterioration of mechanical properties such as compressive strength, cohesive force, and internal friction angle, which was a cumulative damage process from the microscopic to the macroscopic level.

Real-time coal flow monitoring is crucial for efficient coal mine transportation. Traditional vision acquisition devices generate two-dimensional images that are not accurately identified in the complex underground coal mine environment, such as dust, water mist, and low light. In this paper, we propose a conveyor belt coal flow detection method that integrates laser scanning and binocular vision to address this problem. Our proposed method has several advantages over traditional approaches. Firstly, we calibrate the binocular camera using Zhang’s calibration method to enhance the accuracy of the system. Secondly, we extract the centerline of the laser stripe using the grayscale center of gravity method, which improves the system’s performance in complex environments. Thirdly, we calculate the cross-sectional area of the material accurately using the trapezoidal area accumulation method, and visualize it in two dimensions based on a single frame, while the point cloud data from multiple consecutive frames are visualized in a 3D model at a realistic scale. Finally, we use the continuous multi-frame cross-sectional area to calculate the current conveyor flow, and apply the BP neural network to establish an energy-saving optimization model for the belt conveyor. We also design a PLC fuzzy controller based on fuzzy control algorithms to adjust the belt’s operating speed intelligently according to the coal flow size, achieving energy-saving operation and intelligent control of the belt conveyor. Our experiments show that our method can accurately obtain coal volume and control the belt speed of the conveyor in real-time, making it an innovative and practical solution for coal flow detection and energy-saving operation in underground coal mines.

Abstract Tuning CO2 hydrogenation product distribution to obtain high-selectivity target products is of great significance. However, due to the imprecise regulation of chain propagation and hydrogenation reactions, the oriented synthesis of a single product is challenging. Herein, we report an approach to controlling multiple sites with graphene fence engineering that enables direct conversion of CO2/H2 mixtures into different types of hydrocarbons. Fe-Co active sites on the graphene fence surface present 50.1% light olefin selectivity, while the spatial Fe-Co nanoparticles separated by graphene fences achieve liquefied petroleum gas of 43.6%. With the assistance of graphene fences, iron carbides and metallic cobalt can efficiently regulate C-C coupling and olefin secondary hydrogenation reactions to achieve product-selective switching between light olefins and liquefied petroleum gas. Furthermore, it also creates a precedent for CO2 direct hydrogenation to liquefied petroleum gas via a Fischer-Tropsch pathway with the highest space-time yields compared to other reported composite catalysts.

Introduction To examine the reliability, sensitivity, and specificity of fluorescent oxidation products (FlOPs; markers of global oxidative damage) for measuring global oxidative stress. Methods To improve FlOP measurement reliability, we mixed plasma samples with the extractant at eight ratios and measured FlOPs with a fluorescent microplate reader (excitation/emission wavelengths 320/420 nm denoted FlOP_320; 360/420 nm [FlOP_360]; and 400/475 nm [FlOP_400]). In a human study, we examined the reliability of an improved FlOP measurement. In an animal study, we examined the sensitivity and specificity of FlOPs for measuring D-galactose induced global oxidative stress. Results At a 1:20 (plasma/extractant) mixture ratio, the overall inter-/intra-assay coefficients of variation (CV) for FlOP measurements among healthy and coronary heart disease participants were

The public's health is gravely at risk due to the current global outbreak of emerging viruses, specifically SARS-CoV-2 and MPXV. Recent studies have shown that SARS-CoV-2 mutants (such as Omicron) exhibit a higher capability to antagonize the host innate immunity, increasing their human adaptability and transmissibility. Furthermore, current studies on the strategies for MPXV to antagonize the host innate immunity are still in the initial stages. These multiple threats from emerging viruses make it urgent to study emerging virus-host interactions, especially the viral antagonism of host antiviral innate immunity. Given this, we selected several representative viruses that significantly threatened human public health and interpreted the multiple strategies for these viruses to antagonize the host antiviral innate immunity, hoping to provide ideas for molecular mechanism research that emerging viruses antagonize the host antiviral innate immunity and accelerate the research progress. The IAV, SARS-CoV-2, SARS-CoV, MERS-CoV, EBOV, DENV, ZIKV, and HIV are some of the typical viruses. Studies have shown that viruses could antagonize the host antiviral innate immunity by directly or indirectly blocking antiviral innate immune signaling pathways. Proviral host factors, host restriction factors, and ncRNAs (microRNAs, lncRNAs, circRNAs, and vtRNAs) are essential in indirectly blocking antiviral innate immune signaling pathways. Furthermore, via controlling apoptosis, ER stress, stress granule formation, and metabolic pathways, viruses may antagonize it. These regulatory mechanisms include transcriptional regulation, post-translational regulation, preventing complex formation, impeding nuclear translocation, cleavage, degradation, and epigenetic regulation.

Introduction: Global environmental issues have become one of the most prominent risk issues in society, and it is of great theoretical and practical importance to study the intrinsic correlation between environmental change and population migration.Methods: Based on the Web of Science core ensemble database (WOS) and National Knowledge Infrastructure database (CNKI) sources, CiteSpace visual bibliometric software was used to construct a map of research hotspots in the field of environmental migration. The specific research methods included word frequency analysis, cluster analysis, and burst word detection analysis.Results: The study found that the research hotspots of environmental migration mainly include:migration caused by environmental pollution; migration caused by the construction of environmental protection projects; migration caused by environmental protection activities; migration caused by environmental degradation; migration caused by climate change; migration caused by environmental disasters; and migration caused by environmental improvement activities.Discussion: Our new insights into the relationship between environmental factors and migration include:non-linear relationships, multi-dimensional vulnerability, livelihood diversification, local context and agency, feedback loops and feedback effects. For future research directions on environmental migration, we can start from the following aspects: (1) Multidisciplinary Approaches; (2) Longitudinal Studies; (3) Regional and Localized Studies; (4) Climate Change Projections; (5) Policy Impact Analysis; (6) Migration and Urbanization; (7) Social and Cultural Adaptation; (8) Technological and Data Advancements; (9) Ethical Considerations; (10) Community-Based Research.

BackgroundMedical staff play a crucial role in delivering healthcare services, especially during epidemics of infectious diseases such as coronavirus disease 2019 (COVID-19). However, there is a growing issue of burnout and low wellbeing among this group. While it is widely recognized that burnout has a negative impact on subjective wellbeing, the exact relationship between the two is not yet completely understood. The purpose of this study is to explore the chain mediating role of psychological capital and perceived social support between burnout and subjective wellbeing among medical staff.MethodsUsing the convenient sampling method, 604 medical staff were selected for a cross-sectional study. All participants completed a self-report questionnaire that collected demographic information, as well as data from the Maslach Burnout Inventory-Human Services Survey, General Wellbeing Schedule, Psychological Capital Questionnaire, and Perceived Social Support Scale. SPSS 27.0 and SPSS PROCESS macro were used for data analysis.ResultsThere was a significant correlation between burnout, psychological capital, perceived social support, and subjective wellbeing (p

Severe dengue infections are characterized by endothelial dysfunction shown to be associated with the secreted nonstructural protein 1 (sNS1), making it an attractive vaccine antigen and biotherapeutic target. To uncover the biologically relevant structure of sNS1, we obtained infection-derived sNS1 (isNS1) from dengue virus (DENV)-infected Vero cells through immunoaffinity purification instead of recombinant sNS1 (rsNS1) overexpressed in insect or mammalian cell lines. We found that isNS1 appeared as an approximately 250 kDa complex of NS1 and ApoA1 and further determined the cryoEM structures of isNS1 and its complex with a monoclonal antibody/Fab. Indeed, we found that the major species of isNS1 is a complex of the NS1 dimer partially embedded in a high-density lipoprotein (HDL) particle. Crosslinking mass spectrometry studies confirmed that the isNS1 interacts with the major HDL component ApoA1 through interactions that map to the NS1 wing and hydrophobic domains. Furthermore, our studies demonstrated that the sNS1 in sera from DENV-infected mice and a human patient form a similar complex as isNS1. Our results report the molecular architecture of a biological form of sNS1, which may have implications for the molecular pathogenesis of dengue.

Abstract The disposal and utilization of solid waste of coal gangue is one of the main problems in coal mining in China. Injecting coal gangue into goaf in the form of slurry can effectively solve the problems of ground stacking and environmental pollution prevention. In order to obtain the flow law of gangue slurry in the void of the accumulated rock in the goaf, a visualization simulation test device for gangue slurry permeation grouting in the goaf was independently designed. The flow and diffusion characteristics, flow and diffusion velocity changes, void pressure changes, and viscosity changes of three mass concentrations (76%, 78%, 80%) of gangue slurry in the void between caved rock blocks in goaf were studied by visual grouting simulation test. The results show that: (1) The seepage process of gangue slurry in the goaf simulation test is divided into three diffusion forms, namely radial diffusion, axial diffusion, and bidirectional diffusion. The three diffusion forms are interrelated and inseparable. (2) The initial flow velocity of the slurry with different concentrations is different under the same permeation grouting pressure, and the higher the slurry concentration, the smaller the initial flow velocity of the slurry. The velocity of the slurry has a nonlinear relationship with the diffusion distance of the slurry. (3) With the permeation and diffusion of slurry, pressure sensors at different positions are subjected to pressure from bottom to top and enter the pressure boost stage, gradually forming stress peaks. When the slurry exceeds the position of the pressure sensor, the pressure on the pressure sensor is weakened and begins to enter the pressure relief stage, and the stress decline trend gradually becomes gentle with time. (4) The water loss effect occurs during slurry flow interaction with rock mass, resulting in slurry viscosity increasing. The viscosity of the slurry affects the difference in the amount of viscosity change. The research results can provide a certain theoretical basis for the goaf gangue slurry filling project.

Abstract The occurrence of human infections caused by avian H9N2 influenza viruses has raised concerns regarding the potential for human epidemics and pandemics. The molecular basis of viral adaptation to a new host needs to be further studied. Here, the bases of nucleotides 627 and 701 of PB2 were changed according to the uncoverable purine-to-pyrimidine transversion to block the development of PB2 627K and 701N mutations during serial passaging in mice. The purpose of this experiment was to identify key adaptive mutations in polymerase and NP genes that were obscured by the widely known host range determinants PB2 627K and 701N. Mouse-adapted H9N2 variants were obtained via twelve serial lung-to-lung passages. Sequence analysis showed that the mouse-adapted viruses acquired several mutations within the seven gene segments (PB2, PB1, PA, NP, HA, NA, and NS). One variant isolate with the highest polymerase activity possessed three substitutions, PB2 S155N, PA S49Y and D347G, which contributed to the highly virulent and mouse-adaptative phenotype. Further studies demonstrated that these three mutations resulted in increased polymerase activity, viral transcription and replication in mammalian cells, severe interstitial pneumonia, excessive inflammatory cellular infiltration and increased growth rates in mice. Our results suggest that the substitution of these three amino acid mutations may be an alternative strategy for H9N2 avian influenza viruses to adapt to mammalian hosts. The continued surveillance of zoonotic H9N2 influenza viruses should also include these mammalian adaptation markers as part of our pandemic preparedness efforts.

Abstract Coloading adjuvant drugs or biomacromolecules with photosensitizers into nanoparticles to enhance the efficiency of photodynamic therapy (PDT) is a common strategy. However, it is difficult to load positively charged photosensitizers and negatively charged adjuvants into the same nanomaterial and further regulate drug release simultaneously. Herein, a single‐component dual‐functional prodrug strategy is reported for tumor treatment specifically activated by tumor microenvironment (TME)‐generated HOCl. A representative prodrug (DHU‐CBA2) is constructed using indomethacin grafted with methylene blue (MB). DHU‐CBA2 exhibited high sensitivity toward HOCl and achieved simultaneous release of dual drugs in vitro and in vivo. DHU‐CBA2 shows effective antitumor activity against lung cancer and spinal metastases via PDT and cyclooxygenase‐2 (COX‐2) inhibition. Mechanistically, PDT induces immunogenic cell death but stimulates the gene encoding COX‐2. Downstream prostaglandins E2 and Indoleamine 2,3 dioxygenase 1 (IDO1) mediate immune escape in the TME, which is rescued by the simultaneous release of indomethacin. DHU‐CBA2 promotes infiltration and function of CD8+ T cells, thus inducing a robust antitumor immune response. This work provides an autoboost strategy for a single‐component dual‐functional prodrug activated by TME‐specific HOCl, thereby achieving favorable tumor treatment via the synergistic therapy of PDT and a COX‐2 inhibitor.

ContextOsteoporotic fracture is a major public health issue globally. Human research on the association between amino acids (AAs) and fracture is still lacking.ObjectiveTo examine the association between AAs and recent osteoporotic fractures.MethodsThis age and sex matched incident case-control study identified 44 recent x-ray confirmed fracture cases in the Second Hospital of Jilin University and 88 community-based healthy controls aged 50+ years. Plasma AAs were measured by high performance liquid chromatography coupled with mass spectrometry. After adjusting for covariates (i.e., body mass index, milk intake >1 time/week, falls and physical activity), we conducted conditional logistical regression models to test the association between AAs and fracture.ResultsAmong cases there were 23 (52.3%) hip fractures and 21 (47.7%) non-hip fractures. Total, essential, and non-essential AAs were significantly lower in cases than in controls. In the multivariable conditional logistic regression models, after adjusting for covariates, each standard deviation increase in the total (odds ratio [OR]: 0.304; 95% confidence interval [CI]: 0.117–0.794), essential (OR: 0.408; 95% CI: 0.181–0.923) and non-essential AAs (OR: 0.290; 95%CI: 0.107–0.782) was negatively associated with recent fracture. These inverse associations were mainly found for hip fracture, rather than non-hip fractures. Among these AAs, lysine, alanine, arginine, glutamine, histidine and piperamide showed the significantly negative associations with fracture.ConclusionThere was a negative relationship between AAs and recent osteoporotic fracture; such relationship appeared to be more obvious for hip fracture.

IntroductionThe perceived social support individuals receive from their others plays a crucial role in shaping conformity with social norms. However, the specific mechanism underlying perceived social support and the detection of social norms remains unclear.MethodsIn this study, college students with high and low levels of perceived social support were asked to judge the appropriateness of stranger’s behaviors (e.g., singing) in different situations (e.g., library). The participants’ electroencephalography activities were analyzed aiming to uncover the neural mechanism underlying how perceived social support influences the detection of others’ normative behavior.ResultsThe ERP results indicate that, for individuals with a lower level of perceived social support, larger amplitudes of the N1 component (related to primary processing) and the N400 component (related to cognitive conflict) were observed when detecting others’ social norm violation compared to the conformity condition. However, for individuals with a higher level of perceived social support, no significant differences were found in detecting others’ conformity or violation of social norms.DiscussionThe results indicate that, when the perceived social support level of the individual is low, detecting others’ social norm violation elicits deeper primary processing and stronger cognitive conflict compared to conformity condition.

Abstract Dysregulation of histone modifications has been implicated in the pathogenesis of both inflammatory bowel disease (IBD) and colorectal cancer (CRC). These diseases are characterized by chronic inflammation, and alterations in histone modifications have been linked to their development and progression. Furthermore, the gut microbiota plays a crucial role in regulating immune responses and maintaining gut homeostasis, and it has been shown to exert effects on histone modifications and gene expression in host cells. Recent advances in our understanding of the roles of histone-modifying enzymes and their associated chromatin modifications in IBD and CRC have provided new insights into potential therapeutic interventions. In particular, inhibitors of histone-modifying enzymes have been explored in clinical trials as a possible therapeutic approach for these diseases. This review aims to explore these potential therapeutic interventions and analyze previous and ongoing clinical trials that examined the use of histone-modifying enzyme inhibitors for the treatment of IBD and CRC. This paper will contribute to the current body of knowledge by exploring the latest advances in the field and discussing the limitations of existing approaches. By providing a comprehensive analysis of the potential benefits of targeting histone-modifying enzymes for the treatment of IBD and CRC, this review will help to inform future research in this area and highlight the significance of understanding the functions of histone-modifying enzymes and their associated chromatin modifications in gastrointestinal disorders for the development of potential therapeutic interventions.

Atherosclerosis is a significant risk factor for coronary heart disease (CHD) and myocardial infarction (MI). Atherosclerosis develops during foam cell generation, which is caused by an imbalance in cholesterol uptake, esterification, and efflux. LOX-1, SR-A1, and CD36 all increased cholesterol uptake. ACAT1 and ACAT2 promote free cholesterol (FC) esterification to cholesteryl esters (CE). The hydrolysis of CE to FC was aided by nCEH. FC efflux was promoted by ABCA1, ABCG1, ADAM10, and apoA-I. SR-BI promotes not only cholesterol uptake but also FC efflux. Circular RNAs (circRNAs), which are single-stranded RNAs with a closed covalent circular structure, have emerged as promising biomarkers and therapeutic targets for atherosclerosis due to their highly tissue, cell, and disease state-specific expression profiles. Numerous studies have shown that circRNAs regulate foam cell formation, acting as miRNA sponges to influence atherosclerosis development by regulating the expression of SR-A1, CD36, ACAT2, ABCA1, ABCG1, ADAM10, apoA-I, SR-B1. Several circRNAs, including circ-Wdr91, circ 0004104, circRNA0044073, circRNA_0001805, circDENND1B, circRSF1, circ 0001445, and circRNA 102682, are potential biomarkers for atherosclerosis to better evaluate cardiovascular risk. It is difficult to deliver synthetic therapeutic circRNAs to the desired target tissues. Nanotechnology, such as GA-RM/GZ/PL, may be an important solution to this problem. In this review, we focus on the potential role and mechanism of circRNA/miRNA axis in foam cell formation in the hopes of discovering new targets for the diagnosis, prevention, and treatment of atherosclerosis.

In underground coal mines, fibre reinforced polymer (FRP) bolt is ideal for mined rib reinforcements as it can prevent gas explosions caused by shearer frictional spark. With increasing mining depth, small diameter FRP bolts used in shallow underground mining cannot fulfil the rib support requirements. Under the engineering background of deep underground shortwall mining in Wudong coal mine, this paper systematically studies Φ27 mm FRP bolt support for large deformation coal rib. Specimens with a fan-shaped cross-section were used to enable the tensile testing of the bolt rod, the measured average tensile strength of the studied FRP bolt was (486.1 ± 9.6) MPa with a maximum elongation of 5.7%±0.6%. The shear strength of the bolt was measured as approximately 258 MPa using a self-made double shear testing apparatus. Based on the equivalent radial stiffness principle, a laboratory short encapsulation pullout test (SEPT) method for rib bolting has been developed undertaken consideration of the mechanical properties of the coal seam. Results showed that the average peak anchorage forces of the Φ27 mm FRP bolt and Φ20 mm steel rebar bolt were 108.4 and 66.4 kN, respectively, which were agreed with the theoretical calculations and field measurements. Based on theoretical analysis of the loading states of the bolt under site conditions, bolting method of full-length resin grouting was adopted to offset the weaknesses of the FRP bolt. Numerical method was employed to compare the bolting effect using Φ27 mm FRP bolts and steel rebar bolts. Large diameter FRP bolting was determined as the optimum rib support scheme to increase the productivity of the coal mine and to enhance the ground control capability for +425 level mining roadways. This study provides the laboratory testing design and theoretical prediction of large diameter FRP bolts used for rib support in large deformation roadways.

This is an essay in the field of earth sciences. With the opening of a new round of mining breakthrough strategic action, the search for key mineral resources such as lithium and rare earth is the core and key to national energy resource security and is crucial to the development of the national economy, national defense and strategic emerging industries. The profile measurement and comprehensive study of the Lower Permian Liangshan Formation (P1l) clay rock system in the Panzhihua area, Sichuan Province are carried out. The key metals such as lithium, gallium and rare earth may come from the weathering products of the underlying layer (ancient weathering crust), which are widely distributed in the area from Panzhihua to Ya 'an. The aluminous clay rock of the Liangshan Formation, which is related to weathering, is a rich layer of lithium, gallium and rare earth metals, which has good prospecting prospects.

Biopolymers have become popular in geotechnical engineering as they provide a carbon-neutral alternative for soil solidification. Xanthan gum (XG) and jute fiber (JF) were selected to solidify the Yellow River dredged soil. The mechanical behavior of solidified dredged soil (SDS) was investigated using a series of uniaxial compression and splitting tension tests at different XG and JF contents and fiber lengths. The results indicate that on the 28th day, the unconfined compressive strength (UCS) values of SDS samples reached 2.83 MPa and splitting tensile strength (STS) of 0.763 MPa at an XG content of 1.5%. When the JF content was greater than 0.9%, the STS of the SDS samples decreased. This is because that the large fiber content weakened the cementation ability of XG. The addition of JF can significantly increase the strain at peak strength of SDS samples. There is a linear relationship between the UCS and STS of the dredged soils solidified by XG and JF. Microanalysis shows that the strength of SDS samples was improved mainly via the cementation of XG itself and the network structure formed by JF with soil particles. The dredged soil reinforced by XG and JF shows better mechanical performance and has great potential for application.

This study offers a comprehensive morpho-histological analysis of the gastrointestinal tract (GIT) of the Malabar red snapper. A comparison of its GIT morphology with that of the Asian seabass reveals similarities and differences between the two species. Additionally, the moisture content, crude protein, and ash in the fillets of Malabar red snapper and Asian seabass were slightly different, with Malabar red snapper exhibiting higher levels of essential fatty acids. Furthermore, higher levels of the polyunsaturated fatty acid (PUFA)/saturated fatty acid (SFA) ratio and docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) ratio, and a lower omega-6/omega-3 ratio, were observed in Malabar red snapper compared to Asian seabass. The Malabar red snapper’s esophagus featured protective mechanisms such as simple columnar epithelial cells, mucous-secreting glands, and goblet cells that were predominantly stained for acid and neutral mucosubstances. Furthermore, its stomach, with mucus cells that were weakly stained for acid mucosubstances, exhibited distinct regions with varying glandular densities, with the pyloric region featuring few glands. The pyloric caeca of the fish were composed of five finger-like structures and few goblet cells. Several goblet cells gradually increased from the anterior to the posterior region of the intestine. These findings provide useful insights for the aquaculture sector, focusing on Malabar red snapper.

(1) Background: Antibiotic resistance in bacteria is an urgent global threat to public health. Migratory birds can acquire antibiotic-resistant and pathogenic bacteria from the environment or through contact with each other and spread them over long distances. The objectives of this study were to explore the relationship between migratory birds and the transmission of drug-resistant pathogenic Escherichia coli. (2) Methods: Faeces and swab samples from migratory birds were collected for isolating E. coli on the Inner Mongolia Plateau of northern China from 2018 to 2023. The resistant phenotypes and spectra of isolates were determined using a BD Phoenix 100 System. Conjugation assays were performed on extended-spectrum β-lactamase (ESBL)-producing strains, and the genomes of multidrug-resistant (MDR) and ESBL-producing isolates were sequenced and analysed. (3) Results: Overall, 179 isolates were antibiotic-resistant, with 49.7% MDR and 14.0% ESBL. Plasmids were successfully transferred from 32% of ESBL-producing strains. Genome sequencing analysis of 91 MDR E. coli strains identified 57 acquired resistance genes of 13 classes, and extraintestinal pathogenic E. coli and avian pathogenic E. coli accounted for 26.4% and 9.9%, respectively. There were 52 serotypes and 54 sequence types (STs), including ST48 (4.4%), ST69 (4.4%), ST131 (2.2%) and ST10 (2.2%). The international high-risk clonal strains ST131 and ST10 primarily carried blaCTX-M-27 and blaTEM-176. (4) Conclusions: There is a high prevalence of multidrug-resistant virulent E. coli in migratory birds on the Inner Mongolian Plateau. This indicates a risk of intercontinental transmission from migratory birds to livestock and humans.

Gut microbes thrive by utilising host energy and, in return, provide valuable benefits, akin to a symbiotic relationship. Here, metagenomic sequencing was performed to characterise and compare the community composition, diversity and antibiotic resistance of the gut microbiota of Relict gull (Larus relictus) and Anatidae species. Alpha diversity analysis revealed that the intestinal microbial richness of L. relictus was significantly lower than that of Anatidae, with distinct differences observed in microbial composition. Notably, the intestines of L. relictus harboured more pathogenic bacteria such as clostridium, which may contribute to the decline in their population and endangered status. A total of 117 strains of Escherichia coli were isolated, with 90.60% exhibiting full susceptibility to 21 antibiotics, while 25.3% exhibited significant biofilm formation. Comprehensive Antibiotic Resistance Database data indicated that glycopeptide resistance genes were the most prevalent type carried by migratory birds, alongside quinolone, tetracycline and lincosamide resistance genes. The abundance of resistance genes carried by migratory birds decreased over time. This metagenomic analysis provides valuable insights into the intestinal microbial composition of these wild bird species, offering important guidance for their conservation efforts, particularly for L. relictus, and contributing to our understanding of pathogen spread and antibiotic-resistant bacteria.

Abstract Malignant bone tumors result in high rates of disability and death and are difficult to treat in terms of killing tumors and repairing bone defects. Compared with other hyperthermia strategies, magnetic hyperthermia has become an effective therapy for treating malignant bone tumors due to its lack of depth limitations. However, tumor cells express heat shock protein (HSP) to resist hyperthermia, which reduces its curative effect. Competitive ATP consumption can reduce HSP production; fortunately, the basic principle of starvation therapy by glucose oxidase (GOx) is consuming glucose to control ATP production, thereby restricting HSP generation. We developed a triple-functional magnetic gel (Fe3O4/GOx/MgCO3@PLGA) as a magnetic bone repair hydrogels (MBRs) with liquid‒solid phase transition capability to drive magneto-thermal effects to simultaneously trigger GOx release and inhibit ATP production, reducing HSP expression and thereby achieving synergistic therapy for osteosarcoma treatment. Moreover, magnetic hyperthermia improves the effect of starvation therapy on the hypoxic microenvironment and achieves a reciprocal strengthening therapeutic effect. We further demonstrated that in situ MBRs injection effectively suppressed tumor growth in 143B osteosarcoma tumor-bearing mice and an in-situ bone tumor model in the rabbit tibial plateau. More importantly, our study also showed that liquid MBRs could effectively match bone defects and accelerate their reconstruction via magnesium ion release and enhanced osteogenic differentiation to augment the regeneration of bone defects caused by bone tumors, which generates fresh insight into malignant bone tumor treatment and the acceleration of bone defect repair.

Abstract Background Pseudorabies virus (PRV) was thought to only infect animals. Recent studies have shown that it can also infect human. Case presentation We report a case of pseudorabies virus encephalitis and endophthalmitis, diagnosed 89 days after onset, confirmed with intraocular fluid metagenomic next generation sequencing (mNGS) after the result of two cerebrospinal fluid (CSF) mNGS tests were negative. Although treatment with intravenous acyclovir, foscarnet sodium, and methylprednisolone improved the symptoms of encephalitis, significant diagnostic delay resulted in permanent visual loss. Conclusions This case suggests that pseudorabies virus (PRV) DNA in the intraocular fluid may have a higher positivity than that in the CSF. PRV may persist in the intraocular fluid for an extended period and may thus require extended antiviral therapy. Patients with severe encephalitis and PRV should be examined with the focus on pupil reactivity and light reflex. A fundus examination should be performed in patients with a central nervous system infection, specifically, those in a comatose state, to help reduce eye disability.

Abstract With the shift of coal resources to deep mining, the occurrence of long‐distance coal seams has increased, and protective layer mining is facing new challenges. This paper attempts to explain the stress evolution law of the upper coal group in the long‐distance mining of the lower coal group in Pingdingshan No. 8 Coal Mine. A simulation model of advance mining of lower‐group coal long‐distance was established. The stress evolution law of the upper coal seam under the influence of advanced mining disturbance of the lower coal seam is studied. The following conclusions were obtained: The advance mining of the lower coal group had a positive or negative impact on the stress distribution of the upper coal seam group. With the recovery of the lower coal group of the F‐21030 working face, the overburden of the F‐21030 goaf finally formed a “Y” type pressure relief area. The pressure relief effect of the E‐21070 working face near the stopping line was obvious. The coal seam of Group E was divided into three areas affected by the advance mining of the lower coal seam. The maximum pressure relief value was 6.6% lower than the initial stress. According to the simulation results, the E‐21070 working face was divided into three regions, namely, the pressure relief region, the stress increase region, and the original stress region. According to the field drainage results of pressure relief gas, the extraction curve could be divided into three parts, namely, the stable area, pressure relief area, and stress recovery area. The maximum pure gas drainage volume could reach seven to eight times of the original area. The pressure relief extraction effect was remarkable, and the optimal extraction range was 22–210 m behind the coal face of the group.

Abstract Diabetic ulcers (DUs) are one of the most serious complications of diabetes mellitus. The application of a functional dressing is a crucial step in DU treatment and is associated with the patient's recovery and prognosis. However, traditional dressings with a simple structure and a single function cannot meet clinical requirements. Therefore, researchers have turned their attention to advanced polymer dressings and hydrogels to solve the therapeutic bottleneck of DU treatment. Hydrogels are a class of gels with a three-dimensional network structure that have good moisturizing properties and permeability and promote autolytic debridement and material exchange. Moreover, hydrogels mimic the natural environment of the extracellular matrix, providing suitable surroundings for cell proliferation. Thus, hydrogels with different mechanical strengths and biological properties have been extensively explored as DU dressing platforms. In this review, we define different types of hydrogels and elaborate the mechanisms by which they repair DUs. Moreover, we summarize the pathological process of DUs and review various additives used for their treatment. Finally, we examine the limitations and obstacles that exist in the development of the clinically relevant applications of these appealing technologies. Graphical Abstract This review defines different types of hydrogels and carefully elaborate the mechanisms by which they repair diabetic ulcers (DUs), summarizes the pathological process of DUs, and reviews various bioactivators used for their treatment.

Abstract Background Radiation-induced xerostomia and oral mucositis are serious complications of radiation therapy for head and neck cancers. Current treatment options have limited efficacy. Mesenchymal stem cell (MSC) therapy has shown promising results in supporting the restoration of glandular secretion function and the regeneration of damaged tissues. This study aim to (1) assess the quality of evidence for MSCs treatment in rodent models of radiation-induced oral complications and (2) determine whether MSCs can improve the therapeutic effect of radiation-induced oral mucositis. Methods Intervention studies using MSCs in rodent models were comprehensively retrieved in the Pubmed, Medline, Embase, Web of Science, and Cochrane library databases on June 1, 2022. The quality of all in vivo experiments was assessed using SYRCLE, and this article is written following the PRISMA guidelines. Results A total of 12 studies were included in this systematic review. The study found that in animal models of radiation-induced xerostomia, MSCs could increase salivary protein secretion, improve SFR, shorten the salivary lag time, anti-apoptosis, etc. In animal models of radiation-induced oral mucositis, MSCs improve the micromorphology and macromorphology of RIOM. Moreover, the effect of MSCs on the modification of ulcer duration and latency may be related to the time of MSCs transplantation but further studies are needed. Conclusion The results of our systematic review suggest that MSCs appeared to be effective in the treatment of radiation-induced xerostomia and oral mucositis. Graphical Abstract

Abstract Aiming at the problem of spontaneous combustion of coal relics caused by the overburden fracture network penetrating the upper and lower coal seams in the process of shallow-buried and short-distance coal seam mining, the 31114 working face of Lijiahao coal mine was used as the research background to study the characteristics of overburden transport and fracture development in shallow-buried and short-distance coal seam mining by using physical similar simulation test; the fractal dimension and image processing techniques were used to quantify the overburden fractures; the classical mechanical models of "solid support beam" and "masonry beam" were combined to analyze the causes of fracture dynamic evolution. The results show that: (1) Before the key seam fracture, the stress in the upper rock seam only changes in a small amount, and the stress in the lower rock seam evolves similarly to the single coal seam mining; when the key seam fracture is broken, the stress in the upper and lower rock seams will change by jumps. (2) The fractal dimension of the fissures rised from 1.4 to 1.5, the total area of fissures is increased from 16,638 pixels to 17,707 pixels, and the total length is increased from 2217 to 3071 pixels; after the main key layer of the overlying rock is broken, the fractal dimension of the fissures is reduced from 1.56 to 1.5, and the total area of fissures is reduced from 31,451 pixels to 29,089 pixels, the total length has increased from 5657 to 6619 pixels. (3) Before the key layer between the coal seams is broken, it will be suspended to form a "fixed beam". After the first break, the broken rock above it will settle synchronously until the rock blocks form a hinged structure and then collapse. After the fall stops, the key layer periodically breaks to form a "masonry beam" structure, and the overlying stratum settles synchronously.

The electrical microenvironment plays an important role in bone repair. However, the underlying mechanism by which electrical stimulation (ES) promotes bone regeneration remains unclear, limiting the design of bone microenvironment–specific electroactive materials. Herein, by simple co-incubation in aqueous suspensions at physiological temperatures, biocompatible regenerated silk fibroin (RSF) is found to assemble into nanofibrils with a β-sheet structure on MXene nanosheets, which has been reported to inhibit the restacking and oxidation of MXene. An electroactive hydrogel based on RSF and bioencapsulated MXene is thus prepared to promote efficient bone regeneration. This MXene/RSF hydrogel also acts as a piezoresistive pressure transducer, which can potentially be utilized to monitor the electrophysiological microenvironment. RNA sequencing is performed to explore the underlying mechanisms, which can activate Ca2+/CALM signaling in favor of the direct osteogenesis process. ES is found to facilitate indirect osteogenesis by promoting the polarization of M2 macrophages, as well as stimulating the neogenesis and migration of endotheliocytes. Consistent improvements in bone regeneration and angiogenesis are observed with MXene/RSF hydrogels under ES in vivo. Collectively, the MXene/RSF hydrogel provides a distinctive and promising strategy for promoting direct osteogenesis, regulating immune microenvironment and neovascularization under ES, leading to re-establish electrical microenvironment for bone regeneration.

Trophoblast cell surface antigen 2 (Trop2) exhibits limited expression in normal tissues but is over-expressed across various solid tumors. The effectiveness of anti-Trop2 antibody-drug conjugate (ADC) in managing breast cancer validates Trop2 as a promising therapeutic target for cancer treatment. However, excessive toxicity and a low response rate of ADCs pose ongoing challenges. Safer and more effective strategies should be developed for Trop2-positive cancers. The dynamic structural attributes and the oligomeric assembly of Trop2 present formidable obstacles to the progression of innovative targeted therapeutics. In this review, we summarize recent advancements in understanding Trop2’s structure and provide an overview of the epitope characteristics of Trop2-targeted agents. Furthermore, we discuss the correlation between anti-Trop2 agents’ epitopes and their respective functions, particularly emphasizing their efficacy and specificity in targeted therapies.

Despite the emergence of molecular targeted therapy and immune checkpoint inhibitors as standard first-line treatments for non-small cell lung cancer (NSCLC), their efficacy in some patients is limited by intrinsic and acquired resistance. Antibody-drug conjugates (ADCs), a revolutionary class of antitumor drugs, have displayed promising clinical outcomes in cancer treatment. In 2022, trastuzumab deruxtecan (Enhertu) was approved for treating HER2-mutated NSCLC, thereby underscoring the clinical value of ADCs in NSCLC treatment strategies. An increasing number of ADCs, focusing on NSCLC, are undergoing clinical trials, potentially positioning them as future treatment options. In this review, we encapsulate recent advancements in the clinical research of novel ADCs for treating NSCLC. Subsequently, we discuss the mechanisms of action, clinical efficacy, and associated limitations of these ADCs.

The use of biopolymers in combination with natural plant fibers to solidify soils has proven effective in civil engineering, as they are not only considered sustainable, but also have excellent mechanical properties. However, the specific quantitative relationships between mechanical strength and residual moisture content (RMC) in the cured system are still unclear. In this study, the solidification effects of xanthan gum (XG, weight ratio to dry soil of 1.5%) and jute fiber (JF, weight ratio to dry soil of 0.6% and length of 20 mm) on the Yellow River dredged soil (YRDS) were investigated at different degrees of compaction (90%, 94% and 98%) after reaching a preset RMC (75%, 50%, 25% and 0%). The results show that unconfined compressive strength (UCS) and splitting tensile strength (STS) increase significantly with decreasing RMC and increasing compaction. The effect of internal moisture on STS was even more dramatic, with a maximum increase of 404% especially when the RMC was reduced from 25% to 0%. The contribution rate of strength (Rcsi) of UCS reaches 49.09%–51.85%, while the Rcsi values of STS at the same RMC of 25% reach only 19.86%–23.08%. A logistic function based model can predict well the mechanical strength at different RMC (R2 ≥ 0.9789). MIP and SEM results show that increasing the degree of compaction mainly affects the large pores (20–100 μm) and improves the mechanical strength by enhancing the bonding effect between XG and JF in the soil particles. In addition, 94% compaction ratio is an optimal choice for practical engineering applications.

AbstractThe strength deterioration and fracture tendency of freeze-thaw rock determine the construction and operation safety of rock engineering. This article conducted compression-shear composite load tests on sandstones with various saturations to examine the failure law of rocks in cold climates and the contributing elements of strength degradation. It was found that with an increase in saturation and loading angle, the compressive strength and elastic modulus dropped. The concept of freeze crack threshold and saturation threshold was proposed. The peak shear stress was negatively correlated with saturation and positively correlated with loading angle. The σCI (crack initiation stress) and σCD (crack damage stress) in the saturated state were only 39.91% and 45.18% of those in the dry state. Serious damage occurred at high saturations, which is consistent with the scanning electron microscopy results. The σCI and σCD under 30°loading angle are 49.72% and 42.91% of those under uniaxial, respectively. This is mainly due to the change of the failure mode from tensile-shear failure to combined tension-shear failure, and finally to single-shear failure. A strength prediction model was established based on sandstone damage characteristics. The research results have important reference value for rock engineering design in frigid climates and complex load environments.

Cerebellar degeneration-related protein 1 antisense RNA (CDR1as), also known as ciRS-7, is a circular natural antisense transcript of CDR1. It is a widely studied and powerful representative of circular RNAs. Based on its widely reported role in cancer, CDR1as is considered one of the most promising biomarkers for diagnosing and treating tumours. However, some recent studies have extensively focused on its regulatory role in cardio-cerebrovascular diseases instead of in tumours. Studies have shown that CDR1as plays a unique role in the occurrence of cardio-cerebrovascular diseases; thus, it may be a potential target for preventing and treating cardio-cerebrovascular diseases. Furthermore, CDR1as has also been found to be related to signal transduction pathways related to inflammatory response, oxidative stress, etc., which may reveal its potential mechanism in cardio-cerebrovascular diseases. However, there is no literature to summarize the role and possible mechanism of CDR1as in cardio-cerebrovascular diseases. Therefore, in the present review, we have comprehensively summarised the latest progress in the biological characteristics, development processes, regulatory mechanisms, and roles of CDR1as in cardio-cerebrovascular diseases, aiming to provide a reference and guidance for future studies.

ObjectivesThe aim of this study was to find a new loss function to automatically segment temporal lobes on localized CT images for radiotherapy with more accuracy and a solution to dealing with the classification of class-imbalanced samples in temporal lobe segmentation.MethodsLocalized CT images for radiotherapy of 70 patients with nasopharyngeal carcinoma were selected. Radiation oncologists sketched mask maps. The dataset was randomly divided into the training set (n = 49), the validation set (n = 7), and the test set (n = 14). The training set was expanded by rotation, flipping, zooming, and shearing, and the models were evaluated using Dice similarity coefficient (DSC), Jaccard similarity coefficient (JSC), positive predictive value (PPV), sensitivity (SE), and Hausdorff distance (HD). This study presented an improved loss function, focal generalized Dice-binary cross-entropy loss (FGD-BCEL), and compared it with four other loss functions, Dice loss (DL), generalized Dice loss (GDL), Tversky loss (TL), and focal Tversky loss (FTL), using the U-Net model framework.ResultsWith the U-Net model based on FGD-BCEL, the DSC, JSC, PPV, SE, and HD were 0.87 ± 0.11, 0.78 ± 0.11, 0.90 ± 0.10, 0.87 ± 0.13, and 4.11 ± 0.75, respectively. Except for the SE, all the other evaluation metric values of the temporal lobes segmented by the FGD-BCEL-based U-Net model were improved compared to the DL, GDL, TL, and FTL loss function-based U-Net models. Moreover, the FGD-BCEL-based U-Net model was morphologically more similar to the mask maps. The over- and under-segmentation was lessened, and it effectively segmented the tiny structures in the upper and lower poles of the temporal lobe with a limited number of samples.ConclusionsFor the segmentation of the temporal lobe on localized CT images for radiotherapy, the U-Net model based on the FGD-BCEL can meet the basic clinical requirements and effectively reduce the over- and under-segmentation compared with the U-Net models based on the other four loss functions. However, there still exists some over- and under-segmentation in the results, and further improvement is needed.

Osteolytic lesions of bone tumors lead to stress-induced loss of load-bearing bones, making it difficult to treat tumors and repair bone tissue structures. Magnetic hyperthermia has become an effective minimally invasive treatment for malignant bone tumors without depth limitations. However, the effectiveness of magnetic heat therapy alone is not satisfactory, and if combined with chemotherapy, it can lead to significant systemic side effects. It is important to efficiently target chemotherapy substances to the correct area for combined therapy. We have developed a biomimetic bone magnet (BBM) that uses polymethyl methacrylate (PMMA) bone cement-loaded permanent magnet materials with good support performance to create an intrinsic tumor magnetic field. This magnetic field has magnetothermal properties and collects drug-loaded magnetic phase change nanoparticles (mCNPs) circulating in the blood for magnetothermally triggered chemotherapy. Moreover, PMMA has good mechanical properties, providing potential stress support for bone reconstruction after bone tumor treatment. Importantly, both in vivo and in vitro experimental results demonstrated the effectiveness of magnetic hyperthermia through minimally invasive injection of BBM phase transition. This new method achieves magnetic targeting by manufacturing tumor biomagnets to generate strong magnetic fields within the tumor, which opens up new avenues for treatment strategies for malignant bone tumors.

Pseudomonas aeruginosa is a leading cause of hospital-acquired infections. Treatment of P. aeruginosa infections is difficult given its multiple virulence mechanisms, intrinsic antibiotic resistance mechanisms, and biofilm-forming ability. Auranofin, an approved oral gold compound for rheumatoid arthritis treatment, was recently reported to inhibit the growth of multiple bacterial species. Here, we identify P. aeruginosa’s global virulence factor regulator Vfr as one target of auranofin. We report the mechanistic insights into the inhibitory mechanism of auranofin and gold(I) analogues to Vfr through structural, biophysical, and phenotypic inhibition studies. This work suggests that auranofin and gold(I) analogues have potential to be developed as anti-virulence drugs against P. aeruginosa.

As urbanization has accelerated, China has started to build smart cities, which have formed smart-city clusters. It is critical to coordinate development within smart-city clusters to enhance the efficiency of city-cluster construction. From the perspective of demographic economics, this study innovatively constructed an evaluation system for the coordinated development of smart-city clusters and utilized the coupled coordination degree model to conduct an in-depth study of smart-city clusters in Jiangsu Province. The results show that there are clear differences in the development between the three regions of Jiangsu Province: Southern Jiangsu, Central Jiangsu, and Northern Jiangsu. The development within Jiangsu Province is imbalanced, where the overall development trend is high in the southern region and low in the northern region. The main driving factors include geography, the Matthew effect, game thinking, and industrial structure. Accordingly, the results suggest the following recommendations for the coordinated development of smart-city clusters: strengthening cross-regional cooperation, promoting data sharing and interoperability, deepening synergistic industrial development, and expanding innovation capacity.

BackgroundIrreversible electroporation (IRE) is a novel local tumor ablation approach with the potential to stimulate an antitumor immune response. However, it is not effective in preventing distant metastasis in isolation. This study aimed to compare the potential of augmenting the antitumor immune response in patients with locally advanced pancreatic cancer (LAPC) who underwent IRE combined with chemotherapy and PD-1/PD-L1 blockade with those who underwent IRE combined with chemotherapy.MethodsA retrospective review was conducted on LAPC patients treated either with IRE in combination with chemotherapy and PD-1/PD-L1 blockade (group A) or with IRE with chemotherapy alone (group B) from July 2015 to June 2021. The primary outcomes were overall survival (OS) and progression-free survival (PFS), with immune responses and adverse events serving as secondary endpoints. Risk factors for OS and PFS were identified using univariate and multivariate analyses.ResultsA total of 103 patients were included in the final analysis, comprising 25 in group A and 78 in group B. The median duration of follow-up was 18.2 months (3.0–38.6 months). Group A patients demonstrated improved survival compared to group B (median OS: 23.6 vs. 19.4 months, p = 0.001; median PFS: 18.2 vs. 14.7 months, p = 0.022). The data suggest a robust immune response in group A, while adverse events related to the treatment were similar in both groups. The multivariate analysis identified the combination of IRE, chemotherapy, and PD-1/PD-L1 blockade as an independent prognostic factor for OS and PFS.ConclusionThe addition of PD-1/PD-L1 blockade to the regimen of IRE combined with chemotherapy enhanced antitumor immunity and extended survival in LAPC patients.

Three-dimensional (3D) microdisplacement monitoring plays a crucial role in the assembly of large aircraft. This paper presents a broadly applicable high-precision online 3D microdisplacement monitoring method and system based on proximity sensors as well as a corresponding in situ calibration method, which can be applied under various extreme working conditions encountered in the aircraft assembly process, such as compact and obstructed spaces. A 3D monitoring model is first established to achieve 3D microdisplacement monitoring based only on the one-dimensional distances measured by proximity sensors, which concerns the extrinsic sensor parameters, such as the probe base point (PBP) and the unit displacement vector (UDV). Then, a calibration method is employed to obtain these extrinsic parameters with high precision by combining spatial transformation principles and weighted optimization. Finally, calibration and monitoring experiments performed for a tailplane assembly process are reported. The calibration precision for the PBP is better than ±10 μm in the X and Y directions and ±2 μm in the Z direction, and the calibration precision for the UDV is better than 0.07°. Moreover, the accuracy of the 3D microdisplacement monitoring system can reach ±15 μm. In general, this paper provides new insights into the modeling and calibration of 3D microdisplacement monitoring based on proximity sensors and a precise, efficient, and low-cost technical means for performing related measurements in compact spaces during the aircraft assembly process.

Currently, SARS-CoV-2, especially the Omicron strain, is ravaging the world and even co-infecting human beings with IAV, which is a serious threat to human public health. As of yet, no specific antiviral drug has been discovered for SARS-CoV-2. This requires deeper understandings of the molecular mechanisms of SARS-CoV-2-host interaction, to explore antiviral drug targets and provide theoretical basis for developing anti-SARS-CoV-2 drugs. This article discussed IAV, which has been comprehensively studied and is expected to provide the most important reference value for the SARS-CoV-2 study apart from members of the Coronaviridae family. We wish to establish a theoretical system for the studies on virus-host interaction. Previous studies have shown that host PRRs recognize RNAs of IAV or SARS-CoV-2 and then activate innate immune signaling pathways to induce the expression of host restriction factors, such as ISGs, to ultimately inhibit viral replication. Meanwhile, viruses have also evolved various regulatory mechanisms to antagonize host innate immunity at transcriptional, translational, post-translational modification, and epigenetic levels. Besides, viruses can hijack supportive host factors for their replication. Notably, the race between host antiviral innate immunity and viral antagonism of host innate immunity forms virus-host interaction networks. Additionally, the viral replication cycle is co-regulated by proteins, ncRNAs, sugars, lipids, hormones, and inorganic salts. Given this, we updated the mappings of antiviral drug targets based on virus-host interaction networks and proposed an innovative idea that virus-host interaction networks as new antiviral drug targets for IAV and SARS-CoV-2 from the perspectives of viral immunology and systems biology.

In this study, a TaqMan real-time PCR method for rapid detection of wild rice in foods was established. Specific primers and probes were designed according to conserved sequence of internal transcribed space (ITS) gene of Z. latifolia, Z. aquatica, Z. palustris and Z. texana to test the target gene fragment in the samples, and then species-specific detection, sensitivity detection and practical application detection were carried out. Results showed that this real-time PCR method had strong specificity, only showed specific amplification curves for wild rice genomic DNA, and there was no amplification curve for other grains, animal and plant materials. The limit of detection was 0.001 ng/μL genomic DNA or 0.01% (W/W) wild rice powder per reaction. The feasibility of the method was further verified by detecting 100 samples of commercial imported wild rice, broken wild rice, coarse grain and rice flour. The wild rice ingredients were detected in 80 commercial imported wild rice and 5 broken wild rice samples. This method has the characteristics of strong specificity, high sensitivity, rapidity and high sufficiency, and is suitable for rapid identification of wild rice ingredients.

Abstract Background Identifying protein complexes from protein-protein interaction network is one of significant tasks in the postgenome era. Protein complexes, none of which exceeds 10 in size play an irreplaceable role in life activities and are also a hotspot of scientific research, such as PSD-95, CD44, PKM2 and BRD4. And in MIPS, CYC2008, SGD, Aloy and TAP06 datasets, the proportion of small protein complexes is over 75%. But up to now, protein complex identification methods do not perform well in the field of small protein complexes. Results In this paper, we propose a novel method, called BOPS. It is a three-step procedure. Firstly, it calculates the balanced weights to replace the original weights. Secondly, it divides the graphs larger than MAXP until the original PPIN is divided into small PPINs. Thirdly, it enumerates the connected subset of each small PPINs, identifies potential protein complexes based on cohesion and removes those that are similar. Conclusions In four yeast PPINs, experimental results have shown that BOPS has an improvement of about 5% compared with the SOTA model. In addition, we constructed a weighted Homo sapiens PPIN based on STRINGdb and BioGRID, and BOPS gets the best result in it. These results give new insights into the identification of small protein complexes, and the weighted Homo sapiens PPIN provides more data for related research.