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Abstract Miniaturization of medical tools promises to revolutionize surgery by reducing tissue trauma and accelerating recovery. Magnetic untethered devices, with their ability to access hard-to-reach areas without physical connections, emerge as potential candidates for such miniaturization. Despite the benefits, these miniature devices face challenges regarding force and torque outputs, restricting their ability to perform tasks requiring mechanical interactions such as tissue penetration and manipulation. To overcome magnetic actuation system-based force and torque limitations, this study proposes Variable Outer Radius Individually Addressable Coil Stacks (VORIACS), a novel magnetic actuation system optimized for high force output generation to magnetic devices within its workspace. The VORIACS marks significant improvements and breakthroughs in magnetic actuation within decimeter-scale workspace. The VORIACS is comprised of 12 coils that are optimized for 2D magnetic field generation under maximized power consumption of up to 12 kW. We implement six two-channel motor controllers, powered by six separate power supplies. Each of the twelve coils in the system is operated on its own motor-controller channel. This arrangement allows the system to exceed the magnetic forces and torques possible for single-coil versions of the same geometry. This study elaborates on optimizing, manufacturing, integrating, and demonstrating this system. Comparative analysis reveals that while a suboptimal, single-coil version of this system generates 0.31 N force (710 mT/m magnetic gradient magnitude), the VORIACS produces 1.673 N force (3834 mT/m magnetic gradient magnitude) on the same magnetic object placed 5 cm away from the coils. Moreover, the strong penetration force generated by VORIACS enables needle penetration to a mock gel that has the rigidity of liver tissue. In addition, we demonstrate the advantage of stacked coils with variable radii for magnetic field manipulability while maintaining the optimized force delivery property of the system, which improves control and could facilitate multi-tool manipulation. By enabling a fivefold increase in magnetic pulling force compared to its single-coil counterpart, VORICAS raises the potential penetration capabilities of untethered magnetic robotics in surgical procedures.

Abstract Unlocking the intricacies of protein structures and interactions within the dynamic landscape of subcellular organelles presents a significant challenge. To address this, we introduce SPACX, a method for spatially resolved protein complex profiling via biocompatible chemical cross(x)-linking with subcellular isolation, designed to monitor protein conformation, interactions, and translocation in living cells. By rapidly capturing protein complexes in their native physiological state and efficiently enriching cross-linked peptides, SPACX allows comprehensive analysis of the protein interactome within living cells. Leveraging structure refinement with cross-linking restraints, we identify subcellular-specific conformation heterogeneity of PTEN, revealing dynamic differences in its dual specificity domains between the nucleus and cytoplasm. Furthermore, by discerning conformational disparities, we identify 83 cytoplasm-exclusive and 109 nucleus-exclusive PTEN-interacting proteins, each associated with distinct biological functions. Upon induction of ubiquitin-proteasome system stress, we observe dynamic alterations in PTEN assembly and its interacting partners during translocation. These changes, including the identification of components and interaction sites, are characterized using the SPACX approach. Notably, SPACX enables identification of unique interacting proteins specific to PTEN isoforms, including PTEN and PTEN-Long, through the determination of sequence-specific cross-linking interfaces. These findings underscore the potential of SPACX to elucidate the functional diversity of proteins within distinct subcellular sociology.

Optical imaging in the second near-infrared (NIR-II; 900–1880 nm) window is currently a popular research topic in the field of biomedical imaging. This study aimed to explore the application value of NIR-II fluorescence imaging in foot and ankle surgeries. A lab-established NIR-II fluorescence surgical navigation system was developed and used to navigate foot and ankle surgeries which enabled obtaining more high-spatial-frequency information and a higher signal-to-background ratio (SBR) in NIR-II fluorescence images compared to NIR-I fluorescence images; our result demonstrates that NIR-II imaging could provide higher-contrast and larger-depth images to surgeons. Three types of clinical application scenarios (diabetic foot, calcaneal fracture, and lower extremity trauma) were included in this study. Using the NIR-II fluorescence imaging technique, we observed the ischemic region in the diabetic foot before morphological alterations, accurately determined the boundary of the ischemic region in the surgical incision, and fully assessed the blood supply condition of the flap. NIR-II fluorescence imaging can help surgeons precisely judge surgical margins, detect ischemic lesions early, and dynamically trace the perfusion process. We believe that portable and reliable NIR-II fluorescence imaging equipment and additional functional fluorescent probes can play crucial roles in precision surgery.

Abstract Background Testicular macrophages (TM) have long been recognized for their role in immune response within the testicular environment. However, their involvement in steroid hormone synthesis, particularly testosterone, has not been fully elucidated. This study aims to explore the capability of TM to synthesize and secrete testosterone de novo and to investigate the regulatory mechanisms involved. Results Transcriptomic analysis revealed significant expression of Cyp11a1, Cyp17a1, Hsd3b1, and Hsd17b3 in TM, which are key enzymes in the testosterone synthesis pathway. qPCR analysis and immunofluorescence validation confirmed the autonomous capability of TM to synthesize testosterone. Ablation of TM in mice resulted in decreased physiological testosterone levels, underscoring the significance of TM in maintaining testicular testosterone levels. Additionally, the study also demonstrated that Cebpb regulates the expression of these crucial genes, thereby modulating testosterone synthesis. Conclusions This research establishes that TM possess the autonomous capacity to synthesize and secrete testosterone, contributing significantly to testicular testosterone levels. The transcription factor Cebpb plays a crucial role in this process by regulating the expression of key genes involved in testosterone synthesis.

Abstract Smartphone addiction, emerging from excessive use of smartphones, poses a challenge to inhibitory control functions within society. This research employed transcranial direct current stimulation (tDCS) as an intervention alongside the stop signal task (SST) to explore behavioral distinctions between individuals with smartphone addiction and a non-addicted control group, focusing on the efficacy of tDCS intervention. The participant cohort comprised 80 individuals, divided into an addiction group (39 participants, with 19 receiving active tDCS and 20 receiving sham tDCS) and a control group (41 participants, with 20 receiving active tDCS and 21 receiving sham tDCS), with anodal stimulation applied over the right dorsolateral prefrontal cortex (dlPFC) and cathodal placement over the left arm. The findings indicate that university students struggling with smartphone addiction exhibit reduced inhibitory control compared to their non-addicted peers, while maintaining similar levels of general cognitive control. Remarkably, tDCS interventions were observed to enhance inhibitory control in both groups. Although the improvement in the addiction group appeared more pronounced numerically than in the control group, no significant interaction with group was noted. However, a higher percentage of participants in the smartphone addiction (SA) group exhibited enhanced response inhibition under active tDCS. This study demonstrates the inhibitory control deficits in individuals addicted to smartphones and underscores the potential of tDCS in enhancing response inhibition. It provides a valuable reference for future tDCS research targeting smartphone addiction and highlights the importance of developing healthier smartphone usage habits.

Abstract Developing high-performance Pt-based catalysts with low Pt loading is crucial but challenging for CO oxidation at temperatures below 100 °C. Herein, we report a Pt-based catalyst with only a 0.15 wt% Pt loading, which consists of Pt–Ti intermetallic single-atom alloy (ISAA) and Pt nanoparticles (NP) co-supported on a defective TiO2 support, achieving a record high turnover frequency of 11.59 s–1 at 80 °C and complete conversion of CO at 120 °C. This is because the coexistence of Pt–Ti ISAA and Pt NP significantly alleviates the competitive adsorption of CO and O2, enhancing the activation of O2. Furthermore, Pt single atom sites are stabilized by Pt–Ti ISAA, resulting in distortion of the TiO2 lattice within Pt–Ti ISAA. This distortion activates the neighboring surface lattice oxygen, allowing for the simultaneous occurrence of the Mars-van Krevelen and Langmuir–Hinshelwood reaction paths at low temperatures.

IntroductionDisulfidptosis is a recently identified form of non-apoptotic programmed cell death which distinguishes itself from classical cell death pathways. However, the prognostic implications of disulfidptosis-related long non-coding RNAs (DRLs) and their underlying mechanisms in hepatocellular carcinoma (HCC) remain largely unexplored.MethodsIn this study, we leveraged RNA-sequencing data and clinical information of HCC patients from the TCGA database. Through expression correlation and prognostic correlation analyses, we identified a set of top-performing long non-coding RNAs. Subsequently, a 5-DRLs predictive signature was established by conducting a Lasso regression analysis.ResultsThis signature effectively stratified patients into high- and low-risk groups, revealing notable differences in survival outcomes. Further validation through univariate and multivariate Cox regression analyses confirmed that the risk score derived from our signature independently predicted the prognosis of HCC patients. Moreover, we observed significant disparities in immune cell infiltration and tumor mutation burden (TMB) between the two risk groups, shedding light on the potential connection between immune-related mechanisms and disulfidptosis. Notably, the signature also exhibited predictive value in the context of chemotherapeutic drug sensitivity and immunotherapy efficacy for HCC patients. Finally, we performed experimental validation at both cellular and patient levels and successfully induced a disulfidptosis phenotype in HCC cells.DiscussionIn general, this multifaceted approach provides a comprehensive overview of DRLs profiles in HCC, culminating in the establishment of a novel risk signature that holds promise for predicting prognosis and therapy outcomes of HCC patients.

Lanthanum (La)-based nanotherapeutics are therapeutically advantageous due to cytoplasmic oxygen species (ROS) levels for mediating intrinsic and extrinsic tumor cell apoptosis. While they have not been extensively explored for their potential to suppress malignancies in vivo. Correspondingly, we have formulated a unique lanthanum nanocarrier with high specific surface area, dendritic-divergent mesopores, importantly, exposing more active lanthanum sites. After surface PEGlytion and ICG loading in mesoporous channels, this fantastic nanoplatform can efficaciously enrich in malignant glioblastoma regions. Meaningfully, it can be sensitively dissociated for La ions release under weak acid (pH = 6.5) tumor microenvironment. Upon 808 nm light irradiation, high light-heat conversion efficiency is further proved, then this satisfied thermal in the tumor site progressively enhances ROS production by La ions. Owing to the synergistic oxidative therapy and photothermal therapy of our dendritic La nanoplatform, glioblastoma is efficaciously and synergistically prevented both in vitro and in vivo. All outcomes highlight the therapeutic potency of La based nanoplatform with radial mesopores to treat malignant cancer in vivo and encourage future translational exploration.

Abstract Growing evidences have proved that tumors evade recognition and attack by the immune system through immune escape mechanisms, and PDL1/Pbrm1 genes have a strong correlation with poor response or resistance to immune checkpoint blockade (ICB) therapy. Herein, a multifunctional biomimetic nanocarrier (siRNA‐CaP@PD1‐NVs) is developed, which can not only enhance the cytotoxic activity of immune cells by blocking PD1/PDL1 axis, but also reduce tumor immune escape via Pbrm1/PDL1 gene silencing, leading to a significant improvement in tumor immunosuppressive microenvironment. Consequently, the nanocarrier promotes DC cell maturation, enhances the infiltration and activity of CD8+ T cells, and forms long‐term immune memory, which can effectively inhibit tumor growth or even eliminate tumors, and prevent tumor recurrence and metastasis. Overall, this study presents a powerful strategy for co‐delivery of siRNA drugs, immune adjuvant, and immune checkpoint inhibitors, and holds great promise for improving the effectiveness and safety of current immunotherapy regimens.

Tumor neoantigen peptide vaccines hold potential for boosting cancer immunotherapy, yet efficiently co-delivering peptides and adjuvants to antigen-presenting cells in vivo remains challenging. Virus-like particle (VLP), which is a kind of multiprotein structure organized as virus, can deliver therapeutic substances into cells and stimulate immune response. However, the weak targeted delivery of VLP in vivo and its susceptibility to neutralization by antibodies hinder their clinical applications. Here, we first designed a novel protein carrier using the mammalian-derived capsid protein PEG10, which can self-assemble into endogenous VLP (eVLP) with high protein loading and transfection efficiency. Then, an engineered tumor vaccine, named ePAC, was developed by packaging genetically encoded neoantigen into eVLP with further modification of CpG-ODN on its surface to serve as an adjuvant and targeting unit to dendritic cells (DCs). Significantly, ePAC can efficiently target and transport neoantigens to DCs, and promote DCs maturation to induce neoantigen-specific T cells. Moreover, in mouse orthotopic liver cancer and humanized mouse tumor models, ePAC combined with anti-TIM-3 exhibited remarkable antitumor efficacy. Overall, these results support that ePAC could be safely utilized as cancer vaccines for antitumor therapy, showing significant potential for clinical translation.

Abstract Background Targeting ferroptosis has been identified as a promising approach for the development of cancer therapies. Monounsaturated fatty acid (MUFA) is a type of lipid that plays a crucial role in inhibiting ferroptosis. Ficolin 3 (FCN3) is a component of the complement system, serving as a recognition molecule against pathogens in the lectin pathway. Recent studies have reported that FCN3 demonstrates inhibitory effects on the progression of certain tumors. However, whether FCN3 can modulate lipid metabolism and ferroptosis remains largely unknown. Methods Cell viability, BODIPY-C11 staining, and MDA assay were carried out to detect ferroptosis. Primary hepatocellular carcinoma (HCC) and xenograft models were utilized to investigate the effect of FCN3 on the development of HCC in vivo. A metabonomic analysis was conducted to assess alterations in intracellular and HCC intrahepatic lipid levels. Results Our study elucidates a substantial decrease in the expression of FCN3, a component of the complement system, leads to MUFA accumulation in human HCC specimens and thereby significantly promotes ferroptosis resistance. Overexpression of FCN3 efficiently sensitizes HCC cells to ferroptosis, resulting in the inhibition of the oncogenesis and progression of both primary HCC and subcutaneous HCC xenograft. Mechanistically, FCN3 directly binds to the insulin receptor β (IR-β) and its pro-form (pro-IR), inhibiting pro-IR cleavage and IR-β phosphorylation, ultimately resulting in IR-β inactivation. This inactivation of IR-β suppresses the expression of sterol regulatory element binding protein-1c (SREBP1c), which subsequently suppresses the transcription of genes related to de novo lipogenesis (DNL) and lipid desaturation, and consequently downregulates intracellular MUFA levels. Conclusions These findings uncover a novel regulatory mechanism by which FCN3 enhances the sensitivity of HCC cells to ferroptosis, indicating that targeting FCN3-induced ferroptosis is a promising strategy for HCC treatment.

Abstract Radiotherapy (RT) has been reported to induce abscopal effect in advanced hepatocellular carcinoma (HCC), but such phenomenon was only observed in sporadic cases. Here, we demonstrated that subcutaneous administration of Toll-like receptor 3 (TLR3) agonist poly(I:C) could strengthen the abscopal effect during RT through activating tumor cell ferroptosis signals in bilateral HCC subcutaneous tumor mouse models, which could be significantly abolished by TLR3 knock-out or ferroptosis inhibitor ferrostatin-1. Moreover, poly(I:C) could promote the presentation of tumor neoantigens by dendritic cells to enhance the recruitment of activated CD8+ T cells into distant tumor tissues for inducing tumor cell ferroptosis during RT treatment. Finally, the safety and feasibility of combining poly(I:C) with RT for treating advanced HCC patients were further verified in a prospective clinical trial. Thus, enhancing TLR3 signaling activation during RT could provide a novel strategy for strengthening abscopal effect to improve the clinical benefits of advanced HCC patients.

ABSTRACTDiet-induced metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder with limited effective interventions available. A novel approach to address this issue is through gut microbiota-based therapy. In our study, we utilized multi-omics analysis to identify Phocaeicola vulgatus (P. vulgatus) as a potential probiotic for the treatment of MASLD. Our findings from murine models clearly illustrate that the supplementation of P. vulgatus mitigates the development of MASLD. This beneficial effect is partly attributed to the metabolite 3-Hydroxyphenylacetic acid (3-HPAA) produced by P. vulgatus, which reduces the acetylation levels of H3K27 and downregulates the transcription of Squalene Epoxidase (SQLE), a rate-limiting enzyme in steroid biosynthesis that promotes lipid accumulation in liver cells. This study underscores the significant role of P. vulgatus in the development of MASLD and the critical importance of its metabolite 3-HPAA in regulating lipid homeostasis. These findings offer a promising avenue for early intervention therapy in the context of MASLD.

BackgroundSeveral observational studies have reported an association between gut microbiota and male erectile dysfunction (ED). However, it remains unclear whether there is a causal relationship between gut microbiota and male ED. Thus, we aimed to investigate the potential causal relationship between gut microbiota and male ED through Mendelian randomization (MR) analysis.ObjectiveTo assess the causal relationship between gut microbiota and male ED, we performed a two-sample MR analysis.MethodsWe obtained gut microbiota genome-wide association studies (GWAS) data from the MiBioGen consortium and publicly available GWAS data on male ED from the OPEN GWAS database. Subsequently, we performed a two-sample MR analysis to evaluate the causal relationship between gut microbiota and male ED. Finally, we performed sensitivity analysis, including Cochran’s Q test, MR-Egger intercept analysis, MR-PRESSO, and leave-one-out analysis, to assess the level of heterogeneity and horizontal pleiotropy in the results.ResultsOur MR analysis revealed a negative causal relationship between the genus Ruminococcaceae UCG013 and male ED (OR = 0.761, 95% CI 0.626–0.926), while the family Lachnospiraceae, genus Lachnospiraceae NC2004 group, genus Oscillibacter, and genus Tyzzerella3 may be associated with an increased risk of male ED, with the highest risk observed for family Lachnospiraceae (OR = 1.264, 95% CI 1.063–1.504). Furthermore, sensitivity analysis confirmed the reliability of our positive findings.ConclusionOur MR analysis revealed a causal relationship between gut microbiota and male ED. This may contribute to a better understanding of the potential applications of gut microbiota in the occurrence and treatment of male ED.

Abstract mRNA vaccines are regarded as a highly promising avenue for next‐generation cancer therapy. Nevertheless, the intricacy of production, inherent instability, and low expression persistence of linear mRNA significantly restrict their extensive utilization. Circular RNAs (circRNAs) offer a novel solution to these limitations due to their efficient protein expression ability, which can be rapidly generated in vitro without the need for extra modifications. Here, we present a novel neoantigen vaccine based on circRNA that induces a potent anti‐tumor immune response by expressing hepatocellular carcinoma‐specific tumor neoantigens. By cyclizing linearRNA molecules, we were able to enhance the stability of RNA vaccines and form highly stable circRNA molecules with the capacity for sustained protein expression. We confirmed that neoantigen‐encoded circRNA can promote dendritic cell (DC) activation and enhance DC‐induced T‐cell activation in vitro, thereby enhancing T‐cell killing of tumor cells. Encapsulating neoantigen‐encoded circRNA within lipid nanoparticles for in vivo expression has enabled the creation of a novel circRNA vaccine platform. This platform demonstrates superior tumor treatment and prevention in various murine tumor models, eliciting a robust T‐cell immune response. Our circRNA neoantigen vaccine offers new options and application prospects for neoantigen immunotherapy in solid tumors.

Summary: Background: The diagnosis of hepatocellular carcinoma (HCC) often experiences latency, ultimately leading to unfavorable patient outcomes due to delayed therapeutic interventions. Our study is designed to develop and validate a model that employs triple-phase computerized tomography (CT)-based deep learning radiomics and clinical variables for early warning of HCC in patients with cirrhosis. Methods: We studied 1858 patients with cirrhosis primarily from the PreCar cohort (NCT03588442) between June 2018 and January 2020 at 11 centres, and collected triple-phase CT images and laboratory results 3–12 months prior to HCC diagnosis or non-HCC final follow-up. Using radiomics and deep learning techniques, early warning model was developed in the discovery cohort (n = 924), and then validated in an internal validation cohort (n = 231), and an external validation cohort from 10 external centres (n = 703). Findings: We developed a hybrid model, named ALARM model, which integrates deep learning radiomics with clinical variables, enabling early warning of the majority of HCC cases. The ALARM model effectively predicted short-term HCC development in cirrhotic patients with area under the curve (AUC) of 0.929 (95% confidence interval 0.918–0.941) in the discovery cohort, 0.902 (0.818–0.987) in the internal validation cohort, and 0.918 (0.898–0.961) in the external validation cohort. By applying optimal thresholds of 0.21 and 0.65, the high-risk (n = 221, 11.9%) and medium-risk (n = 433, 23.3%) groups, which covered 94.4% (84/89) of the patients who developed HCC, had significantly higher rates of HCC occurrence compared to the low-risk group (n = 1204, 64.8%) (24.3% vs 6.4% vs 0.42%, P

Material-by-design has been a long-standing aspiration that has recently become a reality. Such designer materials have been repeatedly demonstrated using the top-down approach of mechanical exfoliation and stacking, leading to a variety of artificial 2D heterostructures with new properties that are otherwise unattainable. Consequently, tremendous research frontiers in physics, chemistry, engineering, and life science have been created. While thousands of layered crystals exist in nature, only a few dozen of them with manageable chemical-stability have been made into heterostructures using this method. Moreover, experimental investigations of materials that have received limited exploration in the 2D realm, such as cuprates, halides, and perovskites, along with their heterostructures, have been fundamentally hindered by their rapid chemical degradation. Another critical challenge imposed by exfoliating and stacking 2D layers in ambient environment is the absorption of itinerant gas molecules that further contaminate sensitive 2D interfaces in the heterostructures. Such contamination and compromised material properties significantly hinder surface-sensitive local probes—scanning probe microscopy (SPM)—that often require nanometer to atomic scale surface cleanliness. In this article, we aim to provide a technical review of recent development toward 2D materials and heterostructure fabrication in more controlled environments that are suitable for SPM characterizations. These include the development of more efficient mechanical exfoliation and dry-transfer techniques, as well as the incorporation of 2D material exfoliation and transfer in inert gas, low vacuum, and, eventually, ultra-high vacuum environments. Finally, we provide an outlook on the remaining challenges and opportunities in ultra-clean 2D material fabrication techniques.

IntroductioncGMP-dependent protein kinase 1 (PRKG1) has shown to be associated with some tumorigenesis, while the role of PRKG1 in bladder cancer is unclear.MethodsTo investigate the biological and clinical significance of PRKG1 in bladder cancer, we detected the expression of PRKG1 and explored the function of PRKG1 in bladder cancer cells. The PRKG1 transcripts data was downloaded from The Cancer Genome Atlas (TCGA) database, and immunohistochemistry staining was conducted on formalin-fixed paraffin-embedded (FFPE) sample tissues. Relationship between clinical characteristics of patients and expression of PRKG1 was analyzed in FFPE samples, TCGA database, and GSE19423 dataset. PRKG1 was over-expressed, and cell proliferation, migration, invasion, apoptosis, and spheroidizing ability were then detected. Chemosensitivity to cisplatin was detected with cell viability, and half-maximal drug inhibitory concentration (IC50) was calculated. In addition, the relation between PRKG1 expression and the infiltration level of tumor immune cells in tumor microenvironment were analyzed.ResultsThe results showed expression of PRKG1 was lower in bladder cancer, compared with normal tissues both at protein and transcript levels. Lower PRKG1 expression was related to higher tumor grade, T stage, and muscle invasion, also predicted worse overall survival and recurrence free survival in patients treated with Bacillus Calmette–Guerin (BCG) intravesical immunotherapy. Analysis of tumor immune cells infiltration showed lower PRKG1 was associated with non-inflamed tumor microenvironment.ConclusionThe present study firstly identified the anti-tumor role and tumor immune regulatory role of PRKG1, also found loss of PRKG1 could be used as a prognosis factor. The present study provided a potential biomarker and therapy target to bladder cancer.

Abstract Early intervention in acute myocardial infarction can minimize myocardial damage and improve patient survival. Herein, a low‐cost device‐free portable immunobiosensing platform for flexible monitoring of immediate myocardial infarction is reported. CuS‐Pt nanofragments (CuS‐Pt NFs) with high photothermal conversion efficiency (≈26.41%) are synthesized by liquid‐phase polarity‐mediated synthesis. The CuS NFs are loaded in situ with platinum (Pt) nanoreactors using a solvothermal reduction strategy, which is employed to enhance the efficiency of gas production. The resulting CuS‐Pt nanocatalysts are encapsulated within liposomes for signal cascade amplification. Specifically, cardiac troponin I (cTn I), a target biomarker in serum, is captured on pre‐modified microtiter plates and formed into a classical sandwich model. The thermo‐chemically kinetically enhanced CuS‐Pt reactor is released through a one‐step chemical treatment and transferred to a closed gas generator. Under the excitation of a near‐infrared laser emitter, the internal pressure in the gas generator device increases with time and drives the carbon quantum dot solution in the connected hose. The moving distance shows a correlation with the target concentration. This work provides a new implementation for the development of low‐cost, efficient pressure immunosensors without the requirement of a readout device.

Plasma fluctuations, the uncertainty of laser ablation, and bremsstrahlung limit the identification of online element analysis during laser processing and cause difficulty in achieving concentration results with sufficient accuracy and repeatability. A laser‐induced breakdown spectroscopy (LIBS) online monitoring system with plasma spatial filtering and spectral screening is proposed to solve this problem. In this system, the high‐frequency ablation noise component of the plasma is eliminated using a specially designed optical Fourier filtering structure, and a spectral screening system based on plasma time waveform monitoring is used to suppress the influence of plasma fluctuations. Without noise filters or algorithm optimizations and based only on the basic internal standard method, the calibration curves of all nine elements in the alloy sample exhibits a Pearson's R2 value ranged from 0.91 to 0.99, with a mean of 0.94. The relative standard deviations are all in the range of 3.5%–8.4% with a mean of 5.4%. The accuracy and repeatability are comparable to those of typical LIBS systems.

Background: Severe acute kidney injury (AKI) after total aortic arch replacement (TAAR) is related to adverse outcomes in patients with acute type A aortic dissection (ATAAD). However, the early prediction of severe AKI remains a challenge. This study aimed to develop a novel model to predict severe AKI after TAAR in ATAAD patients using machine learning algorithms. Methods: A total of 572 ATAAD patients undergoing TAAR were enrolled in this retrospective study, and randomly divided into a training set (70 %) and a validation set (30 %). Lasso regression, support vector machine-recursive feature elimination and random forest algorithms were used to screen indicators for severe AKI (defined as AKI stage III) in the training set, respectively. Then the intersection indicators were selected to construct models through artificial neural network (ANN) and logistic regression. The AUC-ROC curve was employed to ascertain the prediction efficacy of the ANN and logistic regression models. Results: The incidence of severe AKI after TAAR was 22.9 % among ATAAD patients. The intersection predictors identified by different machine learning algorithms were baseline serum creatinine and ICU admission variables, including serum cystatin C, procalcitonin, aspartate transaminase, platelet, lactic dehydrogenase, urine N-acetyl-β-d-glucosidase and Acute Physiology and Chronic Health Evaluation II score. The ANN model showed a higher AUC-ROC than logistic regression (0.938 vs 0.908, p

Along with the battery charge/discharge processes, the migration of the Li ions inevitably leads to an inhomogeneous distribution of the battery internal electrochemical and thermal characteristics, deteriorating the battery capacity and safety. In this work, the internal characteristics of a 20 Ah pouch LiFePO4 lithium-ion battery have been investigated based on a 3D electrochemical-thermal coupled model. It is found that the reduction of the particle size for either the cathode or anode would increase the battery capacity. Moreover, with the modulation of the thickness of cathode (Lpos) and convective heat transfer coefficient (h), the homogeneity of solid lithium concentration and temperature has been optimized. A relatively smaller Lpos and an h higher than the critical value should be adopted. From the aspect of thermal distribution, as the discharge rate increases, the irreversible reaction heat always dominates, while the proportion of ohmic heat among the total heat increases, and the high temperature region always locates on the inner sides of the tabs. The methodology proposed in this work could be applied to pouch batteries with more repeated cell units and larger sizes.

The impact of three different pulse durations (100 fs, 1, and 10 ps) on the formation of laser hyperdoped black silicon with respect to surface morphology, sub‐bandgap absorptance, the sulfur concentration profile, and the effective minority carrier lifetime after Al2O3 surface passivation is investigated. The current flow behavior is compared through the hyperdoped layer by I–V measurements after hyperdoping with different pulse durations. For conditions that give the same absolute sub‐bandgap absorptance, an increase in pulse duration from 100 fs to 10 ps results in a shallower sulfur concentration profile. Findings are explained by an increasing ablation threshold from 0.19 J cm−2 for a pulse duration of 100 fs to 0.21 J cm−2 for 1 ps and 0.34 J cm−2 for 10 ps. The formation of an equally absorbing layer with a shallower doping profile results in a reduction in contact and/or sheet resistance. Despite the higher local sulfur concentration, the samples show no decrease in carrier lifetime measured by quasi‐steady‐state photoconductance decay on Al2O3 surface‐passivated samples. The investigation shows that longer pulses of up to 10 ps during laser hyperdoping of silicon result in advanced layer properties that promise to be beneficial in a potential device application.

Abstract Background As a relatively new surgical technique, the learning curve of en bloc resection of bladder tumor (ERBT) in ex vivo models remains unaddressed. This study aimed to explore the learning curve of ERBT in an ex vivo porcine model. Methods In this prospective study, eight endoscopists without prior experience in ERBT were divided into two groups: junior endoscopists, with less than 100 transurethral resection of bladder tumor (TURBT) procedure experience, and senior endoscopists, with at least 100 TURBT procedure experience. Each endoscopist performed 30 ERBT procedures on artificial lesions in an ex vivo porcine bladder model. The procedure time, perforation, en bloc resection status, and absence of detrusor muscle (DM) were recorded. The inflection points were identified using cumulative sum (CUSUM) analysis. Procedure results were compared between the two phases and two groups. Results In all, 240 artificial lesions were successfully resected using ERBT. The CUSUM regression line indicated the inflection point at the 16th procedure for the junior endoscopists and at the 13th procedure for the senior endoscopists. In both groups, the procedure time, perforation, piecemeal resection, and DM absence rates were significantly lower in the consolidation phase than in the initial phase. The procedure time for the senior endoscopists was lower than for the junior endoscopists in both phases. Conclusions ERBT performance improved significantly after reaching the inflection point of the learning curve in the ex vivo model. We recommend a minimum of 16 ERBT procedures in ex vivo models for urologists with less than 100 TURBT experience and a minimum of 13 procedures for those with at least 100 TURBT experience before advancing to live animal training or supervised clinical practice.

Abstract This study aimed to investigate the potential of autophagy-related genes (ATGs) as a prognostic signature for HCC and explore their relationships with immune cells and immune checkpoint molecules. A total of 483 samples were collected from the GEO database (n = 115) and The Cancer Genome Atlas (TCGA) database (n = 368). The GEO dataset was used as the training set, while the TCGA dataset was used for validation. The list of ATGs was obtained from the human autophagy database (HADB). Using Cox regression and LASSO regression methods, a prognostic signature based on ATGs was established. The independent use of this prognostic signature was tested through subgroup analysis. Additionally, the predictive value of this signature for immune-related profiles was explored. Following selection through univariate Cox regression analysis and iterative LASSO Cox analysis, a total of 11 ATGs were used in the GEO dataset to establish a prognostic signature that stratified patients into high- and low-risk groups based on survival. The robustness of this prognostic signature was validated using an external dataset. This signature remained a prognostic factor even in subgroups with different clinical features. Analysis of immune profiles revealed that patients in the high-risk group exhibited immunosuppressive states characterized by lower immune scores and ESTIMATE scores, greater tumour purity, and increased expression of immune checkpoint molecules. Furthermore, this signature was found to be correlated with the infiltration of different immune cell subpopulations. The results suggest that the ATG-based signature can be utilized to evaluate the prognosis of HCC patients and predict the immune status within the tumour microenvironment (TME). However, it is important to note that this study represents a preliminary attempt to use ATGs as prognostic indicators for HCC, and further validation is necessary to determine the predictive power of this signature.

Abstract To investigate the intervention effect of an intelligent rehabilitation training system on patients with functional ankle instability (FAI) and to advance the research to optimise the effect of FAI rehabilitation training. Thirty-four FAI patients who participated in this trial in Guilin City from April 2023 to June 2023 were recruited as research subjects, and all subjects were randomly divided into the control group (n = 17) and the observation group (n = 17). Both groups received the conventional rehabilitation training intervention for 6 weeks, and the observation group received the additional training using the intelligent rehabilitation training system training invented by our team. Visual analogue scale (VAS), ankle active mobility, ankle muscle strength and Y-balance test (YBT) were assessed before and after treatment. Two-way repeated measures ANOVA shows that the interaction effect between time and group of VAS scores was significant (F = 35.644, P

Abstract The reaction system of hydrogen peroxide (H2O2) catalyzed by nanozyme has a broad prospect in antibacterial treatment. However, the complex catalytic activities of nanozymes lead to multiple pathways reacting in parallel, causing uncertain antibacterial results. New approach to effectively regulate the multiple catalytic activities of nanozyme is in urgent need. Herein, Cu single site is modified on nanoceria with various catalytic activities, such as peroxidase-like activity (POD) and hydroxyl radical antioxidant capacity (HORAC). Benefiting from the interaction between coordinated Cu and CeO2 substrate, POD is enhanced while HORAC is inhibited, which is further confirmed by density functional theory (DFT) calculations. Cu-CeO2 + H2O2 system shows good antibacterial properties both in vitro and in vivo. In this work, the strategy based on the interaction between coordinated metal and carrier provides a general clue for optimizing the complex activities of nanozymes.

Intramedullary nailing is frequently utilized in the treatment of femoral shaft fractures. However, an incorrect entry point will result in poor reduction of the shattered bones. Furthermore, intramedullary nails frequently encounter obstacles during insertion. The goal of this study contains two parts: 1) determining the ideal entry point and drill-hole shape for a given patient with its well-matched intramedullary nail (IMN), and 2) planning an appropriate insertion path for the IMN. Computed tomography scans from patients’ femurs and their well-matched IMNs are obtained to generate three-dimensional models and centerlines. A centerline self-growing strategy that combines four evaluating factors is employed to determine optimal centerline segments and align the IMN with the medullary cavity. For the first objective, the position of entry point under the optimal registration is computed. The drill-hole shape comprises all the intersections between the IMN and the femur near the entry point at 5 different depth positions. For the second objective, a visualized planning path including a series of the positions and postures is established through optimal registration. A local coordinate system is defined at the endpoint of the IMN. The transformation parameters between adjacent positions are computed for intra-operative guidance. The method was verified using the four experiments: entry point evaluation, path feasibility, path effectiveness, and IMN insertion guidance. During the whole insertion process, the maximum distance between the IMN centerline and the center point of the narrowest position of the medullary cavity is 0.673 mm, which meets clinical requirements. The IMN insertion guidance experiment demonstrates that the determined path is appropriate. In the path effectiveness experiment, the IMN can be successfully inserted into the medullary cavity, the upper and lower broken bones fit tightly without displacement, and the average time taken to plan an insertion path using this method is 9.37 min. The experimental results show that when the IMN is inserted according to the determined entry point and drill-hole, the shattered bone cracks fit closely. Additionally, the IMN can be successfully inserted without obstacles following the planned path which can minimize the damage to intramedullary tissues.

Estimating ecological environmental flow in tidal rivers is one of the major challenges for sustainable water resource management in estuaries and river basins. This paper presents an ecological environmental flow framework that was developed to accommodate highly dynamic medium tidal estuaries found along the Yellow Sea coast of China. The framework not only proposes a method of water quality-based ecological flow for tidal gate-controlled rivers but also proposes a method of water demand for scouring and silting to protect ports in coastal viscous sediment environments. The framework integrates the instream water requirements of water quality, sediment and basic ecological flow, and considers the temporal and spatial variation differences for the environmental flow requirements of tidal rivers. This study emphasizes the significance and necessity of continuous monitoring of ecological data in determining the environmental flow of tidal rivers. The output of this study could provide vital references for decision-making and management of the water resource allocation and ecological protection in tidal rivers. HIGHLIGHTS This study develops an ecological environmental flow framework for highly dynamic medium tidal estuaries.; This study suggests a method of water quality-based ecological flow for tidal gate-controlled rivers.; This study proposes a method of water demand for scouring and silting.;

Abstract Early diagnosis of hepatocellular carcinoma (HCC) lacks highly sensitive and specific protein biomarkers. Here, we describe a staged mass spectrometry (MS)-based discovery-verification-validation proteomics workflow to explore serum proteomic biomarkers for HCC early diagnosis in 1002 individuals. Machine learning model determined as P4 panel (HABP2, CD163, AFP and PIVKA-II) clearly distinguish HCC from liver cirrhosis (LC, AUC 0.979, sensitivity 0.925, specificity 0.915) and healthy individuals (HC, AUC 0.992, sensitivity 0.975, specificity 1.000) in an independent validation cohort, outperforming existing clinical prediction strategies. Furthermore, the P4 panel can accurately predict LC to HCC conversion (AUC 0.890, sensitivity 0.909, specificity 0.877) with predicting HCC at a median of 11.4 months prior to imaging in prospective external validation cohorts (No.: Keshen 2018_005_02 and NCT03588442). These results suggest that proteomics-driven serum biomarker discovery provides a valuable reference for the liquid biopsy, and has great potential to improve early diagnosis of HCC.

As the largest steel-producing country, China’s steel industry has experienced rapid development in terms of production level and quality. Owing to the high consumption of coal in the iron and steel industry, air pollutants and carbon dioxide (CO2) show similar emission properties in flue gas. In view of the collaborative reduction of pollution and carbon emissions, the emission standards for pollutants and carbon were first analyzed, suggesting that carbon emission standards for the iron and steel industry should be accelerated. A collaborative technology system for the reduction of pollution and carbon emissions from the iron and steel industry in China is demonstrated, consisting of ① optimization of present ultra-low emission technology, ② low-carbon innovation for present production processes, ③ steel production process reengineering, and ④ carbon capture, utilization, and storage (CCUS). Finally, the technical prospect for collaborative reduction of pollution and carbon emissions from the iron and steel industry in China is suggested to support high-quality green development in this industry.

Abstract Background Heat stress is a major restrictive factor that causes yield loss in rice. We previously reported the priming effect of abscisic acid (ABA) on rice for enhanced thermotolerance at the germination, seedling and heading stages. In the present study, we aimed to understand the priming effect and mechanism of ABA on grain filling capacity in rice under heat stress. Results Rice plants were pretreated with distilled water, 50 μM ABA and 10 μM fluridone by leaf spraying at 8 d or 15 d after initial heading (AIH) stage and then were subjected to heat stress conditions of 38 °C day/30 °C night for 7 days, respectively. Exogenous ABA pretreatment significantly super-activated the ABA signaling pathway and improved the SOD, POD, CAT and APX enzyme activity levels, as well as upregulated the ROS-scavenging genes; and decreased the heat stress-induced ROS content (O2 – and H2O2) by 15.0–25.5% in rice grain under heat stress. ABA pretreatment also increased starch synthetase activities in rice grain under heat stress. Furthermore, ABA pretreatment significantly improved yield component indices and grain yield by 14.4–16.5% under heat stress. ABA pretreatment improved the milling quality and the quality of appearance and decreased the incidence of chalky kernels and chalkiness in rice grain and improved the rice grain cooking quality by improving starch content and gel consistence and decreasing the amylose percentage under heat stress. The application of paraquat caused overaccumulation of ROS, decreased starch synthetase activities and ultimately decreased starch content and grain yield. Exogenous antioxidants decreased ROS overaccumulation and increased starch content and grain yield under heat stress. Conclusion Taken together, these results suggest that exogenous ABA has a potential priming effect for enhancing rice grain filling capacity under heat stress at grain filling stage mainly by inhibiting ROS overaccumulation and improving starch synthetase activities in rice grain.

The high-frequency and high-speed communication in the 5 G era puts forward requirements for the dielectric properties of polymers. Introducing fluorine into poly(ary ether ketone) can improve its dielectric properties. In this work, by introducing the fluorine group strategy, we successfully designed and synthesized three novel trifluoromethyl (−CF3) or trifluoromethoxy (−OCF3)-containing bisphenol monomers and their F-substitution PEK-based polymers (PEK-Ins). All these PEK-Ins exhibited good thermal, mechanical and dielectric properties. The T d5% of the three polymers is all higher than 520℃. The free volume fraction of novel polymers increased from 3.75% to 5.72%. Among the three polymers, exhibited the lowest dielectric constant of the films is 2.839, and the dielectric loss is 0.0048, ascribing to the increasing free volume. The Young’s modulus of the polymer film is as high as 2.9 GPa and the tensile strength is as high as 84 MPa. PEK-Ins reduced the dielectric constant by introducing a low fluorine content. This study provides a new way to design PEK to synthesize low dielectric constant polymers.

The Special Issue focused on the water environment changes within watersheds due to its critical role in sustaining ecosystems, supporting biodiversity, and providing essential resources for human life [...]

The existing residual film-recycling machines struggle to efficiently recover and separate film stubble in a single operation. With roller-type film-rolling device unloading difficulties and other problems, in order to improve the recovery efficiency of film stubble and the separation effect while reducing human labor and to improve work efficiency, we designed an automatic hydraulic unloading film stubble-recycling integrated residual film-recycling machine. The angle of the membrane lifting device was determined by theoretical calculations using the method of coupled simulation of EDEM and ANSYS Workbench. We analyzed the amount of resistance as well as the maximum stress and deformation during the working process of the membrane-lifting device and focused on the design of the membrane–soil separating device and membrane-rolling device. The depth of the film shovel, the forward speed of the machine, and the rotational speed of the driving wheel of the jogging chain were selected as the test factors, and the residual film recovery rate was taken as the evaluation index. A three-factor, three-level test was designed by applying the principles of the Box–Behnken experimental design. The results show that when the forward speed is 1.36 m/s, the soil depth is 147.16 mm, and the rotational speed of the driving wheel of the shaking chain is 77.89 r/min, the recovery rate of the residual film is 87.56%, and the relative error between the experimental value and the optimized value is 2.73%. The experimental results can provide a theoretical basis for the design of the residual film-recycling machine.

Plastic film mulching technology can effectively enhance crop yield and quality, and the use of mulch has been increasing in recent years; however, the problem of mulch residue is worsening due to the large amount of recycling work and slow natural degradation. In this study, a potato seedling killing and residual film recycling machine is designed to provide good working conditions for potato harvesters before harvesting in response to the problems of difficult separation of film tangles, the low net rate of recycling due to the mixing of residual film with soil, and the high soil content in residual film recycling operations in northwest China. The machine is based on the potato monoculture and double row planting mode in Gansu area. This paper puts forward the overall design scheme and carries out the theoretical analysis and parameter determination of the key components, such as the seedling killing device, the film surface cleaning device, the film unloading device, and so on. Using EDEM software to carry out the virtual simulation test and Design-Expert13 to analyze the test results, we determined the optimal working scheme for the machine, with a forward speed of 0.8 m/s, a film gap of 125 mm, and a spiral stirrer speed of 600 r/min. Based on a field test for verification, the test results show that the machine’s residual film recovery rate was 83.3%, the impurity rate was 3.8%, and the rate of injury to the potatoes was 1.4%. The machine meets the requirements of national and industry standards, and it can simultaneously realize straw crushing, film surface cleaning, residual film recycling, and hydraulic film unloading operations, with better operating results and while reaching the expected results. It can also provide a reference for the design and testing of a seeding and residual film recycling machine.

Femtosecond-laser-fabricated black silicon has been widely used in the fields of solar cells, photodetectors, semiconductor devices, optical coatings, and quantum computing. However, the responsive spectral range limits its application in the near- to mid-infrared wavelengths. To further increase the optical responsivity in longer wavelengths, in this work, silicon (Si) was co-hyperdoped with nitrogen (N) and selenium (Se) through the deposition of Se films on Si followed by femtosecond (fs)-laser irradiation in an atmosphere of NF3. The optical and crystalline properties of the Si:N/Se were found to be influenced by the precursor Se film and laser fluence. The resulting photodetector, a product of this innovative approach, exhibited an impressive responsivity of 24.8 A/W at 840 nm and 19.8 A/W at 1060 nm, surpassing photodetectors made from Si:N, Si:S, and Si:S/Se (the latter two fabricated in SF6). These findings underscore the co-hyperdoping method’s potential in significantly improving optoelectronic device performance.

Aiming at the problems of low soil cover and serious wear and tear of transmission parts in the soil lifting device of potato planters, this paper carries out innovative optimization design of its key parts based on TRIZ theory. The discrete element model of the soil model and the multi-body dynamic model of the soil lifting device are established, the upper scraping and lower scraping soil lifting devices are simulated respectively through the method of DEM-MBD coupling, and the working mechanism of the soil lifting device is further explored. The simulation results show that the lower scraping type lifting device has a large conveying capacity and a stable flow rate at the soil outlet. The results of the soil tank performance comparison test show that: the improved soil lifting device has a simple structure, large conveying capacity, stable flow rate, and fast flow speed and is not easily congested. It meets the standard requirements of dryland potato seedling strip mulching planting technology on mulching parameters and is of great significance for improving dryland food production on the Loess Plateau.

To address the issues of the poor filling and clearing efficiency of spoon–chain potato seed dischargers, an optimization design was implemented in this study. Based on the motion characteristics of potatoes during the filling and transport processes, an inclination angle was set for the seed spoon cavity, and a seed-clearing brush was installed at the top of the seed discharger. A DEM-MBD coupled simulation model of the seed discharger was constructed. The working speed of the driving sprocket, the inclination angle of the seed spoon cavity, and the seed holding height were used as experimental factors, while the single-seed qualification rate, missed seed rate, and over-seeding rate were used as evaluation indices to conduct a quadratic regression orthogonal rotation combination experiment. This determined the optimal technical parameter combination for the best working performance. Based on the results of the DEM-MBD coupled simulation experiments, a response surface optimization test was conducted. The results showed that the optimal working performance was achieved when the working speed of the driving sprocket was 43 rpm, the inclination angle of the seed spoon cavity was 15°, and the seed holding height was 0.2 m. Under these conditions, the single-seed qualification rate was 95.28%, the missed seed rate was 0.92%, and the over-seeding rate was 3.80%. Further soil bin tests confirmed that, under the optimal working parameters, the relative deviations of all test indices from the response surface optimization test results were less than 2%. The research results provide new insights for the optimization design of spoon–chain potato seed-metering devices.

Plastic film mulching is one of the key technologies for improving agricultural productivity in arid and semi-arid regions. However, residual plastic film can severely disrupt the structure of the topsoil in farmland, leading to a decrease in crop yield. The Hexi Corridor, as the largest seed maize production base in the arid regions of Northwest China, is facing an increasingly prominent issue of residual plastic film recovery. This study designed experiments based on the typical maize planting model in the Hexi Corridor. A discrete element simulation model of the residual film–soil–root stubble complex was established using the Bonding-V2 model and API rapid filling technology. The reliability of the simulation model was verified through shear and puncture tests. The study revealed that the soil type in the Hexi Corridor is heavy sandy soil. The differences between the average maximum shear forces in the simulated and actual shear tests for root stubble–soil complexes at depths of 30 mm, 50 mm, and 100 mm were 4.8%, 6.4%, and 6.5%, respectively. Additionally, the differences in the average maximum vertical loading forces in the simulated and actual puncture tests for root stubble–soil complexes at depths of 50 mm and 100 mm were 6.4% and 12.37%, respectively. The small discrepancies between the simulated and actual values, along with the consistency of particle movement trends with real-world conditions, confirmed the reliability and accuracy of the simulation model. This indicates that the established discrete element flexible model can effectively represent actual field conditions, providing discrete element model parameters and theoretical support for optimizing the design of key components in China’s mechanized root stubble handling and residual film recovery machinery.

Aiming at the problems of poor passability of a tracked chassis due to small plots, complicated road conditions and steep slopes during mechanized potato harvesting in hilly and mountainous areas. To design a potato combine harvester and take the tracked chassis of the harvester as the research object to study its driving performance under typical road conditions in mountainous areas. Firstly, mechanical analysis and theoretical calculation are carried out on the tracked chassis to obtain the relevant parameters of key components, and secondly, its driving performance is analyzed to obtain the driving limit values of passing performance under different working conditions; RecurDyn software was used to establish the dynamics simulation and analysis model of the whole machine, and the driving limit values of the harvester were determined under five different road conditions through simulation. The results show the following: the driving limit gradient angle is 20° in cross-gradient conditions, 25° in longitudinal up-gradient conditions, 25° in longitudinal down-gradient conditions, the limiting height of the chassis that can be overpassed in obstacle-crossing conditions is 450 mm, and the limiting width of the chassis that can be spanned in trench-crossing conditions is 1200 mm. The simulation results were verified through field tests, and the results of the field tests showed that the harvester met the requirements of stable travelling on longitudinal slopes of 24°, climbed over a 450 mm straight wall and crossed over a 1200 mm trench, which were similar to the simulation results, indicating that the simulation results were accurate and feasible, and met the design requirements for the travelling passage of the crawler potato harvester. This study provides an in-depth understanding of the tracked chassis of the potato combine harvester in hilly mountainous areas, with a view to providing reference for the design of tracked harvesters for other crops in hilly mountainous areas.

Background: Hypertension, a highly prevalent chronic disease, is known to inflict severe damage upon blood vessels. In our previous study, isoliensinine, a kind of bibenzyl isoquinoline alkaloid which isolated from a TCM named Lotus Plumule (Nelumbo nucifera Gaertn), exhibits antihypertensive and vascular smooth muscle proliferation-inhibiting effects, but its application is limited due to poor water solubility and low bioavailability. In this study, we proposed to prepare isoliensinine loaded by PEG-PLGA polymer nanoparticles to increase its efficacy Method: We synthesized and thoroughly characterized PEG-PLGA nanoparticles loaded with isoliensinine using a nanoprecipitation method, denoted as, PEG-PLGA@Isoliensinine. Additionally, we conducted comprehensive investigations into the stability of PEG-PLGA@Isoliensinine, in vitro drug release profiles, and in vivo pharmacokinetics. Furthermore, we assessed the antihypertensive efficacy of this nano-system through in vitro experiments on A7R5 cells and in vivo studies using AngII-induced mice. Result: The findings reveal that PEG-PLGA@Isoliensinine significantly improves isoliensinine absorption by A7R5 cells and enhances targeted in vivo distribution. This translates to a more effective reduction of AngII-induced hypertension and vascular smooth muscle proliferation. Conclusion: In this study, we successfully prepared PEG-PLGA@Isoliensinine by nano-precipitation, and we confirmed that PEG-PLGA@Isoliensinine surpasses free isoliensinine in its effectiveness for the treatment of hypertension, as demonstrated through both in vivo and in vitro experiments. Significance: This study lays the foundation for isoliensinine's clinical use in hypertension treatment and vascular lesion protection, offering new insights for enhancing the bioavailability of traditional Chinese medicine components. Importantly, no toxicity was observed, affirming the successful implementation of this innovative drug delivery system in vivo and offers a promising strategy for enhancing the effectiveness of Isoliensinine and propose an innovative avenue for developing novel formulations of traditional Chinese medicine monomers.

In recent years, with the in-depth study of PD-1/PD-L1 related pathways, great progress has been made in cancer immunotherapy. However, the immunotherapy regimen for mccRCC is still controversial in clinical practice.A 50-year-old man with mccRCC complicated with renal venous tumor thrombus from 2019 to present, including surgical treatment, targeted therapy and the combined treatment regimen of “Tislelizumab combined with Sunitinib”. Although he experienced a roller coaster of adverse reactions during treatment, the patient's prognosis was good.Tislelizumab combined with Sunitinib is safe and effective in the Treatment of mccRCC.

The pervasive use of smartphones, while enhancing accessibility to information and communication, has raised concerns about its potential negative effects on physical and mental health, including the impairment of decision-making abilities. This study investigates the influence of smartphone addiction on decision-making in college students. A sample of 80 individuals aged 17 to 26 was selected and divided into two groups based on their Smartphone Addiction Scale-Short Version (SAS-SV) scores. Participants underwent the Iowa Gambling Task (IGT) to evaluate their decision-making in risky and uncertain conditions, while fNIRS recorded their prefrontal cortex activity. The study found that individuals prone to smartphone addiction tend to make riskier choices in risky situations. However, when faced with decisions based on ambiguity, the smartphone addiction group showed increased brain activity in the dlPFC (specifically in channels 4, 9, and 11) compared to when making risky decisions. Despite this increased brain activation, there was no observable difference in behavior between the addiction-prone and control groups in ambiguous scenarios. Notably, the left dlPFC (e.g., channel 4) exhibited significantly higher activation in the addiction group compared to the control group. Findings suggest that smartphone addiction can detrimentally influence decision-making, behaviorally and neurologically, particularly in uncertain contexts. This study supports the classification of smartphone addiction as a genuine addiction and underscores its significance in psychiatric research. In essence, our research underscores the adverse effects of excessive smartphone use on decision-making processes, reinforcing the necessity to treat smartphone addiction as a pressing public health issue.

Abstract Traditional tumour‐dynamic therapy still inevitably faces the critical challenge of limited reactive oxygen species (ROS)‐generating efficiency due to tumour hypoxia, extreme pH condition for Fenton reaction, and unsustainable mono‐catalytic reaction. To fight against these issues, we skilfully develop a tumour‐microenvironment‐driven yolk‐shell nanoreactor to realize the high‐efficiency persistent dynamic therapy via cascade‐responsive dual cycling amplification of •SO4−/•OH radicals. The nanoreactor with an ultrahigh payload of free radical initiator is designed by encapsulating the Na2S2O8 nanocrystals into hollow tetra‐sulphide‐introduced mesoporous silica (HTSMS) and afterward enclosed by epigallocatechin gallate (EG)‐Fe(II) cross‐linking. Within the tumour microenvironment, the intracellular glutathione (GSH) can trigger the tetra‐sulphide cleavage of nanoreactors to explosively release Na+/S2O82−/Fe2+ and EG. Then a sequence of cascade reactions will be activated to efficiently generate •SO4− (Fe2+‐catalyzed S2O82− oxidation), proton (•SO4−‐catalyzed H2O decomposition), and •OH (proton‐intensified Fenton oxidation). Synchronously, the oxidation‐generated Fe3+ will be in turn recovered into Fe2+ by excessive EG to circularly amplify •SO4−/•OH radicals. The nanoreactors can also disrupt the intracellular osmolarity homeostasis by Na+ overload and weaken the ROS‐scavenging systems by GSH exhaustion to further amplify oxidative stress. Our yolk–shell nanoreactors can efficiently eradicate tumours via multiple oxidative stress amplification, which will provide a perspective to explore dynamic therapy.

Abstract mRNA therapeutics have emerged as powerful tools for cancer immunotherapy in accordance with their superiority in expressing all sequence‐known proteins in vivo. In particular, with a small dosage of delivered mRNA, antigen‐presenting cells (APCs) can synthesize mutant neo‐antigens and multi‐antigens and present epitopes to T lymphocytes to elicit antitumor effects. In addition, expressing receptors like chimeric antigen receptor (CAR), T‐cell receptor (TCR), CD134, and immune‐modulating factors including cytokines, interferons, and antibodies in specific cells can enhance immunological response against tumors. With the maturation of in vitro transcription (IVT) technology, large‐scale and pure mRNA encoding specific proteins can be synthesized quickly. However, the clinical translation of mRNA‐based anticancer strategies is restricted by delivering mRNA into target organs or cells and the inadequate endosomal escape efficiency of mRNA. Recently, there have been some advances in mRNA‐based cancer immunotherapy, which can be roughly classified as modifications of the mRNA structure and the development of delivery systems, especially the lipid nanoparticle platforms. In this review, the latest strategies for overcoming the limitations of mRNA‐based cancer immunotherapies and the recent advances in delivering mRNA into specific organs and cells are summarized. Challenges and opportunities for clinical applications of mRNA‐based cancer immunotherapy are also discussed.

Tumor vaccines are emerging as one of the most promising therapeutic strategies for cancer treatment. With the advantages of low toxicity, convenient production and stable quality control, peptide vaccines have been widely used in preclinical and clinical trials involving various malignancies. However, when used alone, they still suffer from significant challenges including poor stability and immunogenicity as well as the low delivery efficiency, leading to limited therapeutic success. Herein, the STING-activating peptide nanovaccine based on human serum albumin (HSA) and biodegradable MnO2 was constructed, which can improve the stability and immunogenicity of antigenic peptides as well as facilitate their uptake by dendritic cells (DCs). Meanwhile, Mn2+ degraded from the nanovaccine can activate the STING pathway and further promote DCs maturation. In this way, the prepared nanovaccine can efficiently mediate T-cell immune responses, thereby exerting the effects of tumor prevention and therapy. Moreover, the prepared nanovaccine possesses the advantages of low cost, convenient preparation and good biocompatibility, showing great potential for practical applications.

Hepatocellular carcinoma (HCC) is a common malignancy with poor prognosis. In recent years, immune checkpoint inhibitors (ICIs) have enabled breakthroughs in the clinical treatment of patients with HCC, but the overall response rate to ICIs in HCC patients is still low, and no validated biomarker is available to guide clinical decision making. Here, we demonstrated that the long non-coding RNA Lnc-CCNH-8 is highly expressed in HCC and correlates with poor prognosis. Functionally, elevated Lnc-CCNH-8 inactivated co-cultured T cells in vitro and compromised antitumor immunity in an immunocompetent mouse model. Mechanistically, up-regulated Lnc-CCNH-8 can sponge microRNA (miR)-217 to regulate the expression of PD-L1. In addition, Lnc-CCNH-8 can also stabilize PD-L1 through miR-3173/PKP3 axis. Furthermore, mice bearing tumors with high Lnc-CCNH-8 expression had significant therapeutic sensitivity to anti-PD-L1 monoclonal antibody treatment. More important, HCC patients with high levels of plasma exosomal Lnc-CCNH-8 had a better therapeutic response to ICIs. Taken together, our results reveal the function of Lnc-CCNH-8 in inducing immune escape from CD8+ T-cell-mediated killing by up-regulating PD-L1 in a miR-217/miR-3173-dependent manner, which also reveals a novel mechanism of PD-L1 regulation in HCC, and exosomal Lnc-CCNH-8 can serve as a predictive marker for immunotherapy response in HCC.