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In this article, a single-board integrated millimeter-wave (mm-Wave) asymmetric full-digital beamforming (AFDBF) array is developed for beyond-fifth-generation (B5G) and sixth-generation (6G) communications. The proposed integrated array effectively addresses the challenge of arranging a large number of ports in a full-digital array by designing vertical connections in a three-dimensional space and successfully integrating full-digital transmitting (Tx) and receiving (Rx) arrays independently in a single board. Unlike the traditional symmetric array, the proposed asymmetric array is composed of an 8 × 8 Tx array arranged in a square shape and an 8 + 8 Rx array arranged in an L shape. The center-to-center distance between two adjacent elements is 0.54λ0 for both the Tx and Rx arrays, where λ0 is the free-space wavelength at 27 GHz. The proposed AFDBF array possesses a more compact structure and lower system hardware cost and power consumption compared with conventional brick-type full-digital arrays. In addition, the energy efficiency of the proposed AFDBF array outperforms that of a hybrid beamforming array. The measurement results indicate that the operating frequency band of the proposed array is 24.25–29.50 GHz. An eight-element linear array within the Tx array can achieve a scanning angle ranging from −47° to +47° in both the azimuth and the elevation planes, and the measured scanning range of each eight-element Rx array is –45° to +45°. The measured maximum effective isotropic radiated power (EIRP) of the eight-element Tx array is 43.2 dBm at 28.0 GHz (considering the saturation point). Furthermore, the measured error vector magnitude (EVM) is less than 3% when 64-quadrature amplitude modulation (QAM) waveforms are used.

Abstract Background Implantable Collamer Lense (ICL) presents a viable alternative to conventional refractive surgeries, but their impact on corneal microstructure remains unclear. By employing in vivo confocal microscopy (IVCM), we examined changes in stromal and endothelial cells following the insertion of V4c ICLs, with the goal of enhancing post-surgical care and outcomes. Methods In this longitudinal investigation, we conducted detailed preoperative assessments on 103 eyes from 53 participants. Follow-up evaluations were carried out after surgery at set intervals: one day, one week, one month, three months, six months, and twelve months. We used IVCM to analyze changes in stromal and endothelial cells. To assess differences between pre- and post-surgery variables and to investigate correlations with age, axial length (AL), and spherical equivalent refraction (SER), we applied a repeated measures mixed-effects model, with statistical significance set at P

Low tumor immunogenicity, immunosuppressive tumor microenvironment, and bacterial infections have emerged as significant challenges in postsurgical immunotherapy and skin regeneration for preventing melanoma recurrence. Herein, an immunotherapeutic hydrogel booster (GelMA-CJCNPs) was developed to prevent postoperative tumor recurrence and promote wound healing by incorporating ternary carrier-free nanoparticles (CJCNPs) containing chlorine e6 (Ce6), a BRD4 inhibitor (JQ1), and a glutaminase inhibitor (C968) into methacrylic anhydride-modified gelatin (GelMA) dressings. GelMA-CJCNPs reduced glutathione production by inhibiting glutamine metabolism, thereby preventing the destruction of reactive oxygen species generated by photodynamic therapy, which could amplify oxidative stress to induce severe cell death and enhance immunogenic cell death. In addition, GelMA-CJCNPs reduced M2-type tumor-associated macrophage polarization by blocking glutamine metabolism to reverse the immunosuppressive tumor microenvironment, recruiting more tumor-infiltrating T lymphocytes. GelMA-CJCNPs also downregulated IFN-γ-induced expression of programmed cell death ligand 1 to mitigate acquired immune resistance. Benefiting from the amplified systemic antitumor immunity, GelMA-CJCNPs markedly inhibited the growth of both primary and distant tumors. Moreover, GelMA-CJCNPs demonstrated satisfactory photodynamic antibacterial effects against Staphylococcus aureus infections, thereby promoting postsurgical wound healing. Hence, this immunotherapeutic hydrogel booster, as a facile and effective postoperative adjuvant, possesses a promising potential for inhibiting tumor recurrence and accelerating skin regeneration.

Abstract The diagnosis and treatment of ovarian cancer (OC) are still a grand challenge, more than 70% of patients are diagnosed at an advanced stage with a dismal prognosis. Magnetic resonance imaging (MRI) has shown superior results to other examinations in preoperative assessment, while cisplatin‐based chemotherapy is the first‐line treatment for OC. However, few previous studies have brought together the two rapidly expanding fields. Here a technique is presented using cisplatin prodrug (Pt‐COOH), Fe3+, and natural polyphenols (Gossypol) to construct the nanoparticles (HA@PFG NPs) that have a stable structure, controllable drug release behavior, and high drug loading capacity. The acidic pH values in tumor sites facilitate the release of Fe3+, Pt‐COOH, and Gossypol from HA@PFG NPs. Pt‐COOH with GSH consumption and cisplatin‐based chemotherapy plus Gossypol with pro‐apoptotic effects displays a synergistic effect for killing tumor cells. Furthermore, the release of Fe3+ at the tumor sites promotes ferroptosis and enables MRI imaging of OC. In the patient‐derived tumor xenograft (PDX) model, HA@PFG NPs alleviate the tumor activity. RNA sequencing analysis reveals that HA@PFG NPs ameliorate OC symptoms mainly through IL‐6 signal pathways. This work combines MRI imaging with cisplatin‐based chemotherapy, which holds great promise for OC diagnosis and synergistic therapy.

Prolonged exposure to volatile anesthetics may raise the risk of developing cognitive impairment by acting on gamma-a Aminobutyric acid A receptors (GABAAR). The dentate gyrus plays an important role in the hippocampus and has a high potential for neural plasticity. However, it is unknown whether prolonged anesthesia induces a change in acute phasic or tonic inhibition in dentate gyrus granule cells (DGGCs) by acting on GABAAR. In order to verify the effects of volatile anesthetics on the current in DGGCs, a whole-cell patch was applied to record acute brain slices, and this study indicated that 4 h but not 2 h of isoflurane (ISO) exposure induced significantly larger tonic currents in DGGCs other than hippocampal CA1 pyramidal and thalamic relay neurons. Furthermore, this study demonstrated that the increased tonic current in DGGCs was dependent on the δ subunit-containing GABAARs by using transgenic δ subunit knockout mice. In conclusion, the δ subunit specific GABAAR is the key element that increased acute tonic inhibition in DGGCs of mice after prolonged ISO exposure, which may be one of the mechanisms of ISO neurotoxicity to the developing brain.

Tumor metabolic reprogramming requires high levels of adenosine triphosphate (ATP) to maintain treatment resistance, which poses major challenges to chemotherapy and photothermal therapy. Especially, high levels of ATP promote copper ion efflux for limiting the curative effect of cuproptosis. Here, an H2S-responsive mesoporous Cu2Cl(OH)3-loading chemotherapeutic cisplatin (CDDP) was synthesized, and the final nanoparticle, CDDP@Cu2Cl(OH)3-CDs (CDCuCDs), was encapsulated by electrostatic action with carbon dots (CDs). CDCuCDs reacted with overproduction H2S in colon tumor to produce photothermic copper sulfide for photothermal therapy. CDDP was released by lysis to achieve chemotherapeutic effects. Importantly, CDDP elevated H2O2 levels in cells through a cascade reaction and continuously transforms H2O2 into highly cytotoxic •OH through chemodynamic therapy between H2O2 and Cu+, which enables nanoparticles to generate •OH and improve the chemotherapeutic efficacy. Highly toxic •OH disrupts mitochondrial homeostasis, prohibiting it from performing normal energy-supplying functions. Down-regulated ATP inhibits heat shock protein expression, which promotes the therapeutic effect of mild photothermal therapy and reduces the efflux of intracellular copper ions, thus improving the therapeutic effect of cuproptosis. Our research provides a potential therapeutic strategy using overproduction H2S responses in tumors, allowing tumor microenvironment-activated •OH nanogenerators to promote tumor energy remodeling for cancer treatment.

This article designs a foreign object recognition system based on machine vision and applies it to the protection of the main transportation belt conveyor. The study uses YOLOv5s as the deep learning model to deploy the trained model to the edge computing module. Real time video is captured by an industrial intrinsic safety camera and transmitted to the edge computing module to identify the foreign matters in the coal flow. Finally, only the recognition results are transmitted externally. When a high level of foreign object danger is detected, an alarm signal will be sent to the collaborative controller, which will issue a shutdown command to the specific single controller. Simultaneously upload the processed real-time video and alarm information to the control platform for display. This design improves the intelligence, stability, and reliability of the protection of the current main conveyor belt conveyor.

Abstract The elevated level of hydrogen sulfide (H2S) in colon cancer hinders complete cure with a single therapy. However, excessive H2S also offers a treatment target. A multifunctional cascade bioreactor based on the H2S-responsive mesoporous Cu2Cl(OH)3-loaded hypoxic prodrug tirapazamine (TPZ), in which the outer layer was coated with hyaluronic acid (HA) to form TPZ@Cu2Cl(OH)3-HA (TCuH) nanoparticles (NPs), demonstrated a synergistic antitumor effect through combining the H2S-driven cuproptosis and mild photothermal therapy. The HA coating endowed the NPs with targeting delivery to enhance drug accumulation in the tumor tissue. The presence of both the high level of H2S and the near-infrared II (NIR II) irradiation achieved the in situ generation of photothermic agent copper sulfide (Cu9S8) from the TCuH, followed with the release of TPZ. The depletion of H2S stimulated consumption of oxygen, resulting in hypoxic state and mitochondrial reprogramming. The hypoxic state activated prodrug TPZ to activated TPZ (TPZ-ed) for chemotherapy in turn. Furthermore, the exacerbated hypoxia inhibited the synthesis of adenosine triphosphate, decreasing expression of heat shock proteins and subsequently improving the photothermal therapy. The enriched Cu2+ induced not only cuproptosis by promoting lipoacylated dihydrolipoamide S-acetyltransferase (DLAT) heteromerization but also performed chemodynamic therapy though catalyzing H2O2 to produce highly toxic hydroxyl radicals ·OH. Therefore, the nanoparticles TCuH offer a versatile platform to exert copper-related synergistic antitumor therapy.

The field of artificial intelligence and neural computing has been rapidly expanding due to the implementation of resistive random-access memory (RRAM) based artificial synaptic. However, the low flexibility of conventional RRAM materials hinders their ability to mimic synaptic behavior accurately. To overcome such limitation, organic-2D composites with high mechanical properties are proposed as the active layer of RRAM. Moreover, we enhance the reliability of the device by ZrO2 insertion layer, resulting in stable synaptic performance. The Ag/PVA:h-BN/ZrO2/ITO devices show stable bipolar resistive switching behavior with an ON/OFF ratio of over 5 × 102, a ∼2 400 cycles endurance and a long retention time (>6 × 103s), which are essential for the development of high-performance RRAMs. We also study the possible synaptic mechanism and dynamic plasticity of the memory device, observing the transition from short-term potentiation (STP) to long-term potentiation (LTP) under the effect of continuous voltage pulses. Moreover, the device exhibits both long-term depression (LTD) and paired-pulse facilitation (PPF) properties, which have significant implications for the design of organic-2D composite material RRAMs that aim to mimic biological synapses, representing promising avenues for the development of advanced neuromorphic computing systems.

Sorafenib is a first-line drug for liver cancer treatment, but its clinical efficacy is still limited by drawbacks such as drug tolerance, toxic effects, and low bioavailability. Therefore, it is urgent to find efficient ways to synergize sorafenib with other agents and increase its bioavailability in order to enhance its clinical efficacy. Herein, we report the successful development of a carrier-free nanoplatform of an artesunate prodrug to potentiate the efficacy of sorafenib against hepatocellular carcinoma. The artesunate prodrug was synthesized by conjugating artesunate and linoleic acid through a thioketone (TK) bond. This prodrug can self-assemble in an aqueous solution via a one-step precipitation method. Furthermore, the inclusion of sorafenib during the self-assembly process results in a carrier-free artesunate/sorafenib mixed nanomedicine (SA@NPs) with a uniform and stable particle size. In addition, SA@NPs possess ROS-responsive drug-releasing ability by breaking up thioketone bonds under high H2O2 levels in tumors. The synergistic anticancer effects of SA@NPs have been demonstrated both in vivo and in vitro. SA@NPs can achieve significantly enhanced synergetic ferroptosis of tumor cells and show potentiated sorafenib efficacy against hepatocellular carcinoma. Moreover, SA@NPs have a tumor inhibition rate of 84.2%, which is 1.63-, 4.22-, and 1.29-fold higher than that in the experimental groups treated with free sorafenib, artesunate, and the simplified combined medication of sorafenib/artesunate, respectively. Overall, this work presents a significant advancement in the clinical chemotherapy of liver cancer and may pave the way for promising developments in the compatibility and clinical combination application of traditional Chinese medicine.

BackgroundThe prevalence and incidence of Nonalcoholic fatty liver disease (NAFLD) are increasing worldwide, and NAFLD has emerged as a prominent global health concern. The link between serum alanine aminotransferase (ALT) to aspartate aminotransferase (AST) ratio and NAFLD remains unclear. This study investigated the association between the ALT/AST ratio and NAFLD prevalence, including liver steatosis and fibrosis levels in the population.MethodsWe conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 2017–2018, including 4753 participants. Subgroup analyses, stratified by age, gender, and body mass index (BMI), were performed, along with adjusted multivariable logistic regression analyses to evaluate the relationship between ALT/AST levels and the likelihood of NAFLD, liver steatosis, and hepatic fibrosis stage. A generalized additive model examined the non-linear relationship between ALT/AST and the probability of developing NAFLD.ResultsAmong 4753 participants, 1508 (31.73%) were diagnosed with NAFLD. Significant positive correlations between ALT/AST and NAFLD risk were found across all models. In addition, the subgroup analysis by gender, age, and BMI suggested that ALT/AST showed a positive correlation with NAFLD. The ALT/AST ratio was positively correlated with the degree of liver steatosis and liver fibrosis. The correlation between ALT/AST and the incidence of NAFLD showed a non-linear pattern. In women, the non-linear trend is particularly evident, showing an inverted U-shaped curve with an inflection point of 1.302. A receiver operating characteristic (ROC) analysis showed that the predictive value of ALT/AST for NAFLD was better than that of traditional liver enzyme parameters.ConclusionA higher ALT/AST ratio was independently associated with a significantly higher risk of NAFLD and liver fibrosis within American cohorts. This link is robust among females, children, and adolescents. ALT/AST ratio can be used as a simple and effective noninvasive biomarker to identify individuals with high risk of NAFLD.

The off-line discharge between the pantograph and catenary (PAC) occurs frequently in the actual operation of an electric locomotive, which affects the quality of the received current and the service life of the pantograph. The current experiments on the off-line discharge between the PAC are mainly low-power ones and the models established are static. To study the electrical behaviors during the PAC relative motion under the actual working conditions, in this paper, the voltage and current of the contact wire (CW) during its motion are measured. And the electrical behaviors during the rise, fall and reciprocating motions of the pantograph are investigated by combining a finite element method (FEM) model based on the magnetohydrodynamics with the auto transformer (AT) traction network circuit and moving mesh method. It is found that the harmonic frequencies are mainly in the range of 0-30 MHz. The voltage distortion is more obvious during the fall of the pantograph. And the negative polarity spike pulse has a larger amplitude and occurs more frequently. The novelty of this paper lies in the experimental test with the high current and high power, as well as the systematic analysis of the electrical behaviors and multi-physical field evolution during the motion of the pantograph under the working conditions. Its contribution is to present an effective method to study the dynamic behaviors of the PAC. The research results can provide an important reference for the identification of the electrical characteristics of the PAC and the protection of the PAC equipment.

With the evolution of the sixth generation (6G) mobile communication technology, the terahertz (THz) spectrum has attracted much attention in wireless communication applications due to its high bandwidth and low signal transmission delay. However, the introduction of the THz spectrum leads to higher path transmission losses and complex signal attenuation. This makes user sensing and localization in THz massive multiple-input multiple-output (MIMO) systems more challenging. In this paper, we investigate the user sensing and localization problem in THz massive MIMO systems with the assistance of reconfigurable intelligent surfaces (RIS). Firstly, the received signal is modeled as a tensor, and a parallel factor (PARAFAC) method is proposed. The minimum description length (MDL) is then utilized to detect the number of scattering paths in the channel. On this basis, the alternating least squares (ALS) algorithm is employed to estimate the factor matrices, followed by the utilization of a straightforward correlation-based approach to obtain channel parameter information. Finally, the positions of users and scattering points are estimated based on the geometric relationship between channel parameters and location coordinates. The simulation results have verified the effectiveness of the proposed scheme compared to the existing competitive algorithms, and indicate that the proposed scheme exhibits superior parameter estimation performance and can achieve localization accuracy at the decimeter level.

The convolutional neural network (CNN) has been widely applied in medical image segmentation due to its outstanding nonlinear expression ability. However, applications of CNN are often limited by the receptive field, preventing it from modeling global dependencies. The recently proposed transformer architecture, which uses a self-attention mechanism to model global context relationships, has achieved promising results. Swin-Unet is a Unet-like simple transformer semantic segmentation network that combines the dominant feature of both the transformer and Unet. Even so, Swin-Unet has some limitations, such as only learning single-scale contextual features, and it lacks inductive bias and effective multi-scale feature selection for processing local information. To solve these problems, the Residual Local induction bias-Unet (RL-Unet) algorithm is proposed in this paper. First, the algorithm introduces a local induction bias module into the RLSwin-Transformer module and changes the multi-layer perceptron (MLP) into a residual multi-layer perceptron (Res-MLP) module to model local and remote dependencies more effectively and reduce feature loss. Second, a new densely connected double up-sampling module is designed, which can further integrate multi-scale features and improve the segmentation accuracy of the target region. Third, a novel loss function is proposed that can significantly enhance the performance of multiple scales segmentation and the segmentation results for small targets. Finally, experiments were conducted using four datasets: Synapse, BraTS2021, ACDC, and BUSI. The results show that the performance of RL-Unet is better than that of Unet, Swin-Unet, R2U-Net, Attention-Unet, and other algorithms. Compared with them, RL-Unet produces significantly a lower Hausdorff Distance at 95% threshold (HD95) and comparable Dice Similarity Coefficient (DSC) results. Additionally, it exhibits higher accuracy in segmenting small targets.

Objective To investigate the HBV infection markers detection and demographic characteristics of first-time blood donors, so as to provide evidence for blood donor recruitment. Methods HBsAg was detected by ELISA, HBsAg negative samples were tested for HBV DNA, and chemiluminescence method was used to detect HBsAg, HBsAb, HBcAb, HBeAg and HBeAb in first-time blood donor HBsAg-/HBV DNA+ samples. Demographic information of HBsAg positive first-time donors was analyzed. Results From 2018 to 2022, a total of 502 739 people participated in voluntary blood donation, and first-time blood donors accounted for 33.79%. The HBsAg positive rate of first-time donors(28.37/10 000, 482/169 897)was higher than that of repeated blood donors(3.46/10 000, 115/332 842) (OR=8.23, 95%CI: 6.72~10.09), and the HBV DNA positive rate of first-time blood donors(4.83/10 000, 82/169 897)was lower than that of repeated blood donors(6.52/10 000, 217/332 842)(OR=0.74, 95%CI: 0.57~0.95). The positive rate of HBcAb in HBsAg-/HBV DNA+ samples of first-time blood donors was 73.17%. Significant differences were noticed in HBsAg-/HBV DNA+ and HBsAg positive rate among first-time blood donors among gender, age, education background and occupation (all P

Objective To analyze the basic characteristics of whole blood donors from blood stations before and after the outbreak of COVID-19. Methods After excluding invalid data, data related to the basic characteristics of whole blood donors collected from 26 blood stations in China during 2018 to 2021 were statistically analyzed, including the trend of total whole blood donors, the number of repeated blood donors, the frequency of blood donation, the average age of donors and the recruitment of first-time blood donors. Results Affected by the epidemic, 8 out of 14 indicators were with large variations, accounting for 57%. The overall growth rate of total whole blood donors during the epidemic was higher than before the epidemic (P

Over the years, electroconductive hydrogels (ECHs) have been extensively applied for stimulating nerve regeneration and restoring locomotor function after peripheral nerve injury (PNI) with diabetes, given their favorable mechanical and electrical properties identical to endogenous nerve tissue. Nevertheless, PNI causes the loss of locomotor function and inflammatory pain, especially in diabetic patients. It has been established that bone marrow stem cells-derived exosomes (BMSCs-Exos) have analgesic, anti-inflammatory and tissue regeneration properties. Herein, we designed an ECH loaded with BMSCs-Exos (ECH-Exos) electroconductive nerve dressing to treat diabetic PNI to achieve functional recovery and pain relief. Given its potent adhesive and self-healing properties, this laminar dressing is convenient for the treatment of damaged nerve fibers by automatically wrapping around them to form a size-matched tube-like structure, avoiding the cumbersome implantation process. Our in vitro studies showed that ECH-Exos could facilitate the attachment and migration of Schwann cells. Meanwhile, Exos in this system could modulate M2 macrophage polarization via the NF-κB pathway, thereby attenuating inflammatory pain in diabetic PNI. Additionally, ECH-Exos enhanced myelinated axonal regeneration via the MEK/ERK pathway in vitro and in vivo, consequently ameliorating muscle denervation atrophy and further promoting functional restoration. Our findings suggest that the ECH-Exos system has huge prospects for nerve regeneration, functional restoration and pain relief in patients with diabetic PNI.

Abstract This study aimed to investigate the awareness of high and pathological myopia among patients with high myopia. A cross‐sectional multicenter survey involving both physicians and patients was conducted between February and April 2021. The outpatient education status, doctors' expectations toward patient education, patients' awareness of high/pathological myopia, and their access to relevant knowledge were inquired, and the proportions of patients with myopia, including high and pathological myopia, were assessed. In total, the survey involved 6975 physicians and patients with myopia from 161 medical institutions in China. The prevalence of high myopia among patients was 11.3%, with 22.59% having pathological myopia. Among those with pathological myopia, 22.45% experienced high myopia complications. Approximately 48.7% of the physicians believed that patients had only a vague idea about high/pathological myopia, with certain misconceptions. Additionally, most outpatients (61.4%) had no access to specialized staff for patient education. Patients' preferences and requirements for online ophthalmology information varied based on family background, medical history, and cognition toward myopia. This study demonstrated that the awareness level among patients with myopia regarding high and pathological myopia is currently insufficient. Therefore, it is important to enhance education efforts to reduce the incidence of adverse outcomes.

Large eutectic carbides presenting in the matrix deteriorate the mechanical properties of high carbon martensitic stainless steel. In the present work, nitrogen-alloyed martensitic stainless steel with different C/N ratios were designed by partial substitution of C by N of 9Cr18Mo, and their microstructure and mechanical properties were investigated. The results show that, with increasing the content of N up to 0.15 wt% in the experimental steel, the quantity and the size of eutectic carbides decrease； and the net-work eutectic carbides are gradually eliminated. The microstructure of all the steels is composed of lath martensite, twin martensite and M23C6 carbides. With partial substitution of C by N, the morphology of martensite blocks evolves from a lath shape to a blocky one, the quantity of twin martensite increases, and the nano-scaled Cr2N nitrides precipitate in the martensite matrix. The steel containing 0.15 wt% N exhibits the hardness of 60.5 HRC, a fracture strength of 1900 MPa and an elongation rate of 1.6 % due to hot rolling and heat treatment, which is attributed to the refinement of carbides and grains, solid solution of C and N, as well as the dense dislocation.

AbstractBackground Inflammation is an important pathogenic factor of most malignant tumors. It is essential to understand mechanism underlying inflammation and cancer development, so as to formulate and develop anti-cancer treatment strategies. However, inflammatory-related gene characterization as well as risk model construction in prognosis and response chemotherapy or immunotherapy in NSCLC are still remain unclear.Methods A total of 1014 lung cancer samples with RNA-seqencing results were download from The Cancer Genome Atlas (TCGA) database. The patient cohort was randomized as a training and test cohorts, and 200 inflammatory-related genes were selected based on previously published data. Consensus clustering and Enrichment and immune function analyses base on Differential expression genes (DEGs) were performed. Prognosis Prediction Model were Constructed and Chemotherapy and immunotherapy sensitivity base on this model were performed. At last, H1299 and HCC827 cells were used to tested the mitoxantrone and oxal iplatin sensitivity after KRT6A knockdown.Results We identified the inflammatory-related genes from NSCLC datasets to build one prognosis prediction signature based on cluster inflammatory-related genes to lay a certain foundation for distinguishing high-risk NSCLC cases with dismal prognostic outcome. The nomogram provides the AUC values for 1-, 3-, and 5-year overall survival were 0.831, 0.853, and 0.86 in validation cohort. Morover, different sensitivity of immunotherapy or chemotherapy also were classified base on the different risk groups in NSCLC patients, which provided potent clinical reference. At last, targeting KRT6A sensitive to mitoxantrone and oxaliplatin in H1299 and HCC827 cells.Conclusions Inflammatory-related gene risk-score is the potential chemotherapeutic and immunotherapeutic biomarker for NSCLC, and targeting KRT6A sensitive to mitoxantrone and oxaliplatin in NSCLC.HighlightsInflammatory-related genes can lay a certain foundation for distinguishing high-risk NSCLC cases with dismal prognostic outcome.Risk-score base on inflammatory-related genes is positive correlated with CD274, TGFBR1 and TGFB1 expression.Targeting KRT6A sensitive to mitoxantrone and oxaliplatin in H1299 and HCC827 cells.

Implantable Collamer Lens (ICL) surgery has increasingly been adopted for myopia correction in recent decades. This study, employing in vivo confocal microscopy (IVCM), aimed to assess the impact of corneal incision during ICL surgery on the corneal sub-basal nerve plexus (SNP) and adjacent immune dendritiform cells (DCs). In this longitudinal study, eyes from 53 patients undergoing ICL surgery were assessed preoperatively and postoperatively over a twelve-month period. Quantification of seven SNP parameters was performed using ACCMetrics V.2 software. Ultimately, the final analysis was restricted to one eye from each of the 37 patients who completed a minimum of three months’ postoperative follow-up. Preoperative investigations revealed a positive correlation of DC density with patient age and a negative association with corneal nerve fiber density (CNFD). Additionally, both DCs and CNFD were positively linked to spherical equivalent refraction (SER) and inversely related to axial length (AL). Intriguingly, preoperative DC density demonstrated an indirect relationship with both baseline and postoperative CNFD changes. Post-surgery, an initial surge in DC density was observed, which normalized subsequently. Meanwhile, parameters like CNFD, corneal nerve fiber length (CNFL), and corneal nerve fractal dimension (CNFrD) initially showed a decline following surgery. However, at one-year follow-up, CNFL and CNFrD displayed significant recovery, while CNFD did not return to its baseline level. This study thus delineates the regeneration pattern of SNP and alterations in DC density post-ICL surgery, highlighting that CNFD in the central cornea does not completely revert to preoperative levels within a year. Given these findings, practitioners are advised to exercise caution in older patients, those with high myopia, or elevated preoperative DCs who may undergo delayed SNP regeneration.

Ovarian cancer (OC) is one of the most common and recurring malignancies in gynecology. Patients with relapsed OC always develop ''cascade drug resistance'' (CDR) under repeated chemotherapy, leading to subsequent failure of chemotherapy. To overcome this challenge, amphiphiles (P1) carrying a nitric oxide (NO) donor (Isosorbide 5-mononitrate, ISMN) and high-density disulfide are synthesized for encapsulating mitochondria-targeted tetravalent platinum prodrug (TPt) to construct a nanocomposite (INP@TPt). Mechanism studies indicated that INP@TPt significantly inhibited drug-resistant cells by increasing cellular uptake and mitochondrial accumulation of platinum, depleting glutathione, and preventing apoptosis escape through generating highly toxic peroxynitrite anion (ONOO−). To better replicate the microenvironmental and histological characteristics of the drug resistant primary tumor, an OC patient-derived tumor xenograft (PDXOC) model in BALB/c nude mice was established. INP@TPt showed the best therapeutic effects in the PDXOC model. The corresponding tumor tissues contained high ONOO− levels, which were attributed to the simultaneous release of O2•− and NO in tumor tissues. Taken together, INP@TPt-based systematic strategy showed considerable potential and satisfactory biocompatibility in overcoming platinum CDR, providing practical applications for ovarian therapy.

BackgroundColorectal cancer (CRC) is one of the most prevalent malignancies and the third most lethal cancer globally. The most reported histological subtype of CRC is colon adenocarcinoma (COAD). The zinc transport pathway is critically involved in various tumors, and its anti-tumor effect may be through improving immune function. However, the Zn transport pathway in COAD has not been reported.MethodsThe determination of Zn transport-related genes in COAD was carried out through single-cell analysis of the GSE 161277 obtained from the GEO dataset. Subsequently, a weighted co-expression network analysis of the TCGA cohort was performed. Then, the prognostic model was conducted utilizing univariate Cox regression and least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Functional enrichment, immune microenvironment, and survival analyses were also carried out. Consensus clustering analysis was utilized to verify the validity of the prognostic model and explore the immune microenvironment. Ultimately, cell experiments, including CCK-8,transwell and scratch assays, were performed to identify the function of LRRC59 in COAD.ResultsAccording to the Zn transport-related prognostic model, the individuals with COAD in TCGA and GEO databases were classified into high- and low-risk groups. The group with low risk had a comparatively more favorable prognosis. Two groups had significant variations in the immune infiltration, MHC, and the expression of genes related to the immune checkpoint. The cell experiments indicated that the proliferation, migration, and invasion of the HCT-116, DLD-1, and RKO cell lines were considerably increased after LRRC59 knockdown. It proved that LRRC59 was indeed a protective factor for COAD.ConclusionA prognostic model for COAD was developed using zinc transport-related genes. This model can efficiently assess the immune microenvironment and prognosis of individuals with COAD. Subsequently, the function of LRRC59 in COAD was validated via cell experiments, highlighting its potential as a biomarker.

Triphenyl phosphate (TPHP) has been widely used as flame retardants and been detected with increasing frequency in environment. TPHP can transform into mono-hydroxylated phosphate (OH-TPHP) and diester diphenyl phosphate (DPHP) through biotransformation. So far, information on the cytotoxicity and molecular regulatory mechanisms of TPHP metabolites are still limit. This study investigated the adverse effects of TPHP, OH-TPHP, and DPHP in HepG2 cells in terms of cell proliferation, lactate dehydrogenase release, reactive oxygen species generation, and mitochondrial membrane potential. The transcriptomic changes were measured using RNA sequencing, and bioinformatics characteristics including biological functions, signal pathways and protein-protein interaction were analyzed to explore the potential molecular mechanisms. Results displayed that the order of cytotoxicity was OH-TPHP> TPHP> DPHP. The prioritized biological functions changes induced by TPHP and OH-TPHP were correlated with lipid metabolism. Significant lipid accumulation was observed as confirmed by increased total cholesterol and triglycerides contents, and enhanced oil red O staining. Enrichment of PPARα/γ and down-stream genes suggested the participation of PPARs signal pathway in lipid metabolism disorder. In addition, TPHP and OH-TPHP induced endoplasmic reticulum stress (ERS), which was further confirmed by the ERS inhibitor experiment. In general, TPHP and OH-TPHP had obvious cytotoxic effects in HepG2 cells. PPARs signal pathway and endoplasmic reticulum stress may be involved in the lipid metabolism disorder induced by TPHP and OH-TPHP.

Abstract Abnormal expression and remodeling of cytoskeletal regulatory proteins are important mechanisms for tumor development and chemotherapy resistance. This study systematically analyzed the relationship between differential expression of cytoskeleton genes and prognosis in gastric cancer (GC). We found the Arf GTP-activating protein ASAP1 plays a key role in cytoskeletal remodeling and prognosis in GC patients. Here we analyzed the expression level of ASAP1 in tissue microarrays carrying 564 GC tissues by immunohistochemistry. The results showed that ASAP1 expression was upregulated in GC cells and can be served as a predictor of poor prognosis. Moreover, ASAP1 promoted the proliferation, migration, and invasion of GC cells both in vitro and in vivo. We also demonstrated that ASAP1 inhibited the ubiquitin-mediated degradation of IQGAP1 and thus enhanced the activity of CDC42. The activated CDC42 upregulated the EGFR-MAPK pathway, thereby promoting the resistance to chemotherapy in GC. Taken together, our results revealed a novel mechanism by which ASAP1 acts in the progression and chemotherapy resistance in GC. This may provide an additional treatment option for patients with GC.

Abstract Ovarian cancer is a highly fatal gynecologic malignancy worldwide. Chemotherapy remains the primary modality both for primary and maintenance treatments of ovarian cancer. However, the progress in developing chemotherapeutic agents for ovarian cancer has been slow in the past 20 years. Thus, new and effective chemotherapeutic drugs are urgently needed for ovarian cancer treatment. A reduction-responsive synergetic delivery strategy (PSSP@ART-ISMN) with co-delivery of artesunate and isosorbide 5-mononitrate was investigated in this research study. PSSP@ART-ISMN had various effects on tumor cells, such as (i) inducing the production of reactive oxygen species (ROS), which contributes to mitochondrial damage; (ii) providing nitric oxide and ROS for the tumor cells, which further react to generate highly toxic reactive nitrogen species (RNS) and cause DNA damage; and (iii) arresting cell cycle at the G0/G1 phase and inducing apoptosis. PSSP@ART-ISMN also demonstrated excellent antitumor activity with good biocompatibility in vivo. Taken together, the results of this work provide a potential delivery strategy for chemotherapy in ovarian cancer. Graphical Abstract

Clinical sorafenib treatment could activate C-X-C receptor type 4 (CXCR4)/stromal source factor-1α (SDF-1α) axis to aggravate intra-tumoral hypoxia of hepatocellular carcinoma (HCC), which further leads to progression, invasion, metastasis, and immunosuppression of tumors and in return causes resistance to sorafenib therapy. Therefore, a multi-functional oxygen delivery nanoplatform was rationally constructed based on an oxygen-saturated perfluorohexane (PFH)-cored liposome, with the CXCR4 antagonist LFC131 peptides modifying on the surface to simultaneously deliver sorafenib and the CSF1/CSF1R inhibitor PLX3397 (named PFH@LSLP) for sorafenib-resistant HCC treatment. The PFH@LSLP was developed to overcome sorafenib resistance by synergistic effects of the following 3 roles: 1) the O2-saturated PFH core could alleviate the tumor hypoxia by O2 supply; 2) the LFC131 peptide recognized the hypoxia-related overexpressed CXCR4 and then blocked SDF-1α/CXCR4 axis to re-sensitize the HCC cells to sorafenib; 3) PLX3397 activated the immune responses via inhibiting the CSF1/CSF1R pathway in TAMs, further enhanced CD8+ T cell infiltration to reverse immunosuppression in tumors. Antitumor performance on H22 tumor-bearing mice and HCC patient-derived tumor xenograft (PDX) model showed that PFH@LSLP could overcome sorafenib resistance by synergistic effect of hypoxia attenuation, resistance-related gene regulation, and immune-microenvironment modification.

In this study, an optical setup for generating terahertz (THz) pulses through a two-color femtosecond laser filament was carefully designed to achieve a precise overlap of two-color laser pulses in space and time. β-barium borate (BBO), α-BBO, and a dual-wavelength plate were used to compensate the phase delay of the two-color lasers. Tilting of α-BBO could further realize the precise spatial overlap of the two beams by counteracting the walk-off effect. The maximum output THz pulse energy reached 21 μJ in argon gas when using a commercial Ti:sapphire laser with a pulse energy of 6 mJ at a 1 kHz repetition rate. The corresponding conversion efficiency exceeded 0.35%.

Cisplatin is a metal platinum complex commonly used in the field of anti-tumor and one of the most commonly used drugs in combination chemotherapy. However, chemotherapy with Cisplatin induced overexpression of cyclooxygenase-2 (COX-2) protein in tumor cells, which could impair the therapeutic effect of chemotherapy on tumor progression. Here, we presented a novel method for the treatment of ovarian cancer with a self-assembly based nano-system. Cisplatin and tolfenamic acid were each linked to linoleic acid to give them the ability to self-assemble into nanoparticles in water. TPNPs had flexible drug ratio adjustability, homogeneous stability, and high drug loading capacity. Compared with Cisplatin, TPNPs could promote cellular uptake and tumor aggregation, co-induce enhanced apoptosis and tumor growth inhibition by inhibiting COX-2 in the mice xenograft model of human ovarian cancer, and reduce systemic toxicity. Therefore, TPNPs is a promising antitumor drug as a kind of self-assembly nano-prodrug with high drug load.

In recent years, electroconductive hydrogels (ECHs) have shown great potential in promoting nerve regeneration and motor function recovery following diabetic peripheral nerve injury (PNI), attributed to their similar electrical and mechanical characteristics to innate nervous tissue. It is well-established that PNI causes motor deficits and pain, especially in diabetics. Current evidence suggests that ropivacaine (ROP) encapsulated in poly lactic-co-glycolic acid (PLGA) microspheres (MSs) yield a sustained analgesic effect. In this study, an ECH electroconductive network loaded with MS/ROP (ECH-MS/ROP) was designed as a promising therapeutic approach for diabetic PNI to exert lasting analgesia and functional recovery. This dual delivery system allowed ROP's slow and sequential release, achieving sustained analgesia as demonstrated by our in vivo experiments. Meanwhile, this system was designed like a lamellar dressing, with desirable adhesive and self-curling properties, convenient for treating injured nerve tissues via automatically wrapping tube-like structures, facilitating the process of implantation. Our in vitro assays verified that ECH-MS/ROP was able to enhance the adhesion and motility of Schwann cells. Besides, both in vitro and in vivo studies substantiated that ECH-MS/ROP stimulated myelinated axon regeneration through the MEK/ERK signaling pathway, thereby improving muscular denervation atrophy and facilitating functional recovery. Therefore, this study suggests that the ECH-MS/ROP dressing provides a promising strategy for treating diabetic PNI to facilitate nerve regeneration, functional recovery and pain relief.

Abstract The fluorophores in the second near‐infrared (NIR‐II) biological window (1000 – 1700 nm) show great application prospects in the fields of biology and optical communications. However, both excellent radiative transition and nonradiative transition cannot be achieved simultaneously for the majority of traditional fluorophores. Herein, tunable nanoparticles formulated with aggregation‐induced emission (AIE) heater are developed rationally. The system can be implemented via the development of an ideal synergistic system that can not only produce photothermal from nonspecific triggers but also trigger carbon radical release. Once accumulating in tumors and subsequently being irradiated with 808 nm laser, the nanoparticles (NMB@NPs) encapsulated with NMDPA‐MT‐BBTD (NMB) are splitted due to the photothermal effect of NMB, leading to the decomposition of azo bonds in the nanoparticle matrix to generate carbon radical. Accompanied by second near‐infrared (NIR‐II) window emission from the NMB, fluorescence image‐guided thermodynamic therapy (TDT) and photothermal therapy (PTT) which significantly inhibited the growth of oral cancer and negligible systemic toxicity is achieved synergistically. Taken together, this AIE luminogens‐based synergistic photothermal‐thermodynamic strategy brings a new insight into the design of superior versatile fluorescent NPs for precise biomedical applications and holds great promise to enhance the therapeutic efficacy of cancer therapy.

Identify risk drivers is the key condition in air pollution control, and biological effect-directed analysis is the most commented method for combing chemical identify and human health. The water-soluble organic matter contained in PM2.5 plays an important role in human health, while it is also the most difficult to identify its chemical information. Exploring the structural characteristics and pollution sources of its key toxic components is the optimized strategy to meet this question. In this study, the induction of apoptosis by the water-soluble fractions (WSF) of PM2.5 samples collected in 10 major cities in China over a period of 1 year was observed in vitro in Beas-2b cells. Organic carbon structures were examined using nuclear magnetic resonance; air potential sources were identified using δ13C and 14C isotopic markers. Apoptosis induction by WSF in PM2.5 was generally stronger in northern cities than in southern cities, and in winter than in summer. Organic compounds with aromatic and double-bond carbon structures from secondary products of motor vehicle exhausts, coal-derived emissions, and emissions derived from the burning of core residues may be primarily responsible for apoptosis induction by PM2.5. Our results will contribute to understanding the toxic substances contained in WSF and provide basic data for accurate pollution control.

Abstract As a natural product with various biological activities, triptolide (TP) has been reported in anti-inflammatory, anti-tumor and anti-autoimmune studies. However, the narrow therapeutic window, poor water solubility, and fast metabolism limit its wide clinical application. To reduce its adverse effects and enhance its efficacy, research and design of targeted drug delivery systems (TDDS) based on nanomaterials is one of the most viable strategies at present. This review summarizes the reports and studies of TDDS combined with TP in recent years, including passive and active targeting of drug delivery systems, and specific delivery system strategies such as polymeric micelles, solid lipid nanoparticles, liposomes, and stimulus-responsive polymer nanoparticles. The reviewed literature presented herein indicates that TDDS is a multifunctional and efficient method for the delivery of TP. In addition, the advantages and disadvantages of TDDS are sorted out, aiming to provide reference for the combination of traditional Chinese medicine and advanced nano drug delivery systems (NDDS) in the future. Graphical Abstract

The occurrence of optical loss on the surface of solar cells is inevitable due to the difference in the refractive index between air and glass, as well as the insufficient absorption of the active layer. To address this challenge, micron-sized geometry arrays, such as hemispheres and hemisphere pits, are prepared on quartz glass through the advanced indirect patterning technology of UV-LIGA. These geometric arrays exhibit multiple mechanisms for controlling light waves, including multiple rebounds, diffraction scattering, and total internal reflection. These synergistic effects suppress optical losses at the device’s surface and prolong the photon propagation path in the active layer. After being patterned with this structure, the average transmittance and haze of the quartz glass reach 93.91% and 75%, respectively. Compared to their flat counterpart, the decorated monocrystalline silicon solar cells demonstrated an apparent improvement in photocurrent and produced a 7.2% enhancement in power conversion efficiency.

This prospective study aimed to evaluate the impact of Visian Implantable Collamer Lens (ICL) V4c implantation on retinal and choroidal morphology in patients with high myopia. A total of 97 eyes from 52 high myopic patients who underwent ICL V4c implantation were followed up for 12 months. Preoperative and postoperative evaluations included comprehensive ophthalmic assessments and enhanced depth imaging optical coherence tomography (EDI-OCT) to analyze changes in central retinal thickness (CRT), retinal volume (CRV), choroidal thickness (ChT), total choroidal area (TCA), luminal area (LA), and choroidal vascular index (CVI). Repeated measures mixed-effects models were used for comparing pre- and postoperative measurement variables and exploring relationships among age, axial length (AL), spherical equivalent refraction (SER), and postoperative retinal and choroidal changes, with statistical significance set at p < 0.05. Follow-up assessments were conducted at various time points, with participation rates ranging from 21% to 98%. Baseline characteristics showed a median age of 26.7 years, −10.14 diopters of SER, and an AL of 27.44 mm. Throughout the 12-month follow-up, CRT and 3.0 mm CRV consistently increased compared to the baseline, with statistically significant rises observed at postoperative day 1, week 1, and month 12. Most ChT measurements, including subfoveal ChT, declined over the 12 months, except at postoperative 6 months. Horizontal and vertical TCA and LA values significantly increased throughout the follow-up, except for month 6. After surgery, both horizontal and vertical CVI parameters exhibited an increase compared to the baseline, with some changes reaching statistical significance. Correlation analysis performed by repeated measures mixed-effects models showed that no relationship was found between age, AL, and SER and changes in postoperative retinal parameters and CVI parameters. However, postoperative changes in ChT and choroidal area parameters showed a negative correlation with AL and a positive correlation with SER. Our research demonstrated that ICL V4c implantation resulted in noteworthy alterations in retinal and choroidal morphology over a 1-year follow-up period. Moreover, in patients with high myopia, individuals with longer AL and higher degrees of myopia exhibited more pronounced postoperative changes in the choroid and retina. Further studies with extended follow-up durations are necessary to comprehensively understand the long-term effects of ICL implantation on retinal and choroidal morphology and function.

In vitro biological neural networks (BNNs) interconnected with robots, so-called BNN-based neurorobotic systems, can interact with the external world, so that they can present some preliminary intelligent behaviors, including learning, memory, robot control, etc. This work aims to provide a comprehensive overview of the intelligent behaviors presented by the BNN-based neurorobotic systems, with a particular focus on those related to robot intelligence. In this work, we first introduce the necessary biological background to understand the 2 characteristics of the BNNs: nonlinear computing capacity and network plasticity. Then, we describe the typical architecture of the BNN-based neurorobotic systems and outline the mainstream techniques to realize such an architecture from 2 aspects: from robots to BNNs and from BNNs to robots. Next, we separate the intelligent behaviors into 2 parts according to whether they rely solely on the computing capacity (computing capacity-dependent) or depend also on the network plasticity (network plasticity-dependent), which are then expounded respectively, with a focus on those related to the realization of robot intelligence. Finally, the development trends and challenges of the BNN-based neurorobotic systems are discussed.

Fluoroquinolone antibiotics (FQs) are of concern due to their disrupting effects on environmental bacterial communities. Evaluating FQ sorption by soil components is important to understand their interaction with soils and to address their environmental (bio)availability. However, data in soil organic components, especially humic acids, are scarce. Batch experiments following OECD guidelines are suitable for testing the sorption of pollutants in solid matrices. Here, we applied this methodology, with specific changes in the experimental setup, to derive sorption data and to identify the factors affecting sorption of four common FQs in seven humic acids with contrasting properties. The effect of shaking time, pH, calcium concentration in solution and dissolved organic carbon (DOC) content on the quantification of the solid-liquid distribution coefficient (Kd) of norfloxacin in three reference humic acids was evaluated. Sorption reversibility and sorption analogy of four FQs were additionally assessed in these three reference materials, whereas the effect of initial norfloxacin concentration was evaluated in the overall set of seven humic acids. Sorption was fast, strong, non-linear, irreversible and affected by changes in the pH and calcium levels in solution. The bell-shaped sorption trend at varying pH values confirmed the key role of FQ speciation in sorption and the high Kd values indicated a positive effect of soil organic matter components on FQ sorption in bulk soils at environmentally relevant pH values. • Relevant factors affecting sorption of pollutants in environmental matrices must be considered to derive Kd values with low variability and high representativeness. • In this article we modify the experimental conditions of standard batch tests to identify the factors that affect the sorption of FQs in humic acids. • The methodological approach followed can be extrapolated to the evaluation of other combinations of pollutant and environmental matrix.

While shale gas could complement the world's natural gas supply, its environmental tradeoffs and sustainability potential should be cautiously assessed before using it to satisfy future energy needs. Shale gas development in China is still in its infancy but has been progressing by the Central Government at a fast pace nowadays. Advanced experience from North America would greatly benefit sustainable design and decision-making for energy development in China. However, the lack of consistency concerning internal and external parameters among previous investigations does not allow an integrated impact comparison among shale gas-rich countries. Herein, we applied a meta-analysis to harmonize environmental tradeoff data through a comprehensive literature review. Greenhouse gas emission, water consumption, and energy demand were selected as environmental tradeoff indicators during shale gas production. Data harmonization suggested that environmental tradeoffs ranged from 5.6 to 37.4 g CO2-eq, 11.0–119.7 mL water, and 0.027–0.127 MJ energy to produce 1 MJ shale gas worldwide. Furthermore, sustainable development indexes (SDIs) for shale gas exploitation in China were analyzed and compared to the United States and the United Kingdom by considering environment, economy, and social demand through an analytic hierarchy process. The United States and China elicit higher SDIs than the United Kingdom, indicating higher feasibility for shale gas exploitation. Although China has relatively low scores in the environmental aspect, large reservoirs and high future market demand make Chinese shale gas favorable in the social demand aspect. Region-specific SDI characteristics identified among representative countries could improve the sustainability potential of regional development and global energy supply.

Lithium batteries incorporating LiFePO4 (LFP) as the cathode material have gained significant attention in recent research. However, the limited electronic and ionic conductivity of LFP poses challenges to its cycling performance and overall efficiency. In this study, we address these issues by synthesizing a series of LiFePO4/carbon (LFP/C) composites through low-temperature carbonization coating of LFP in the presence of Coke as the carbon source. The resulting lithium batteries utilizing LFP/C as the cathode material exhibited impressive discharge specific capacities of 148.35 mA·h/g and 126.74 mA·h/g at 0.1 C and 1 C rates, respectively. Even after 200 cycles of charging and discharging, the capacities remained remarkably high, with values of 93.74% and 97.05% retention, showcasing excellent cycling stability. Notably, the LFP/C composite displayed exceptional rate capability, and capacity retention of 99.27% after cycling at different multiplication rates. These findings underscore the efficacy of in situ low-temperature carbonization capping of LFP with Coke in significantly improving both the cycling stability and rate capability of lithium batteries.

This paper presents the development, modeling, and control of L03, an underactuated 3D bipedal robot with symmetrical hips and straight legs. This innovative design requires only five actuators, two for the legs and three for the hips. This paper is divided into three parts: (1) mechanism design and kinematic analysis; (2) trajectory planning for the center of mass and foot landing points based on the Divergent Component of Motion (DCM), enabling lateral and forward walking capabilities for the robot; and (3) gait stability analysis through prototype experiments. The primary focus of this study is to explore the application of underactuated symmetrical designs and determine the number of motors required to achieve omnidirectional movement of a bipedal robot. Our simulation and experimental results demonstrate that L03 achieves simple walking with a stable and consistent gait. Due to its lightweight construction, low leg inertia, and straight-legged design, L03 can achieve ground perception and gentle ground contact without the need for force sensors. Compared to existing bipedal robots, L03 closely adheres to the characteristics of the linear inverted pendulum model, making it an invaluable platform for future algorithm research.

Choroidal neovascularization (CNV) is a severe complication observed in individuals with pathological myopia (PM). Our hypothesis is that specific metabolic alterations occur during the development of CNV in patients with PM. To investigate this, an untargeted metabolomics analysis was conducted using gas chromatography–mass spectrometry (GC–MS) and liquid chromatography–mass spectrometry (LC–MS) on aqueous humor (AH) samples obtained from meticulously matched PM patients, including those with CNV (n = 11) and without CNV (n = 11). The analysis aimed to identify differentially expressed metabolites between the two groups. Furthermore, the discriminative ability of each metabolite was evaluated using the area under the receiver operating characteristic curve (AUC). Enriched metabolic pathways were determined using the KEGG and MetaboAnalyst databases. Our results revealed the detection of 272 metabolites using GC–MS and 1457 metabolites using LC–MS in AH samples. Among them, 97 metabolites exhibited significant differential expression between the CNV and non-CNV groups. Noteworthy candidates, including D-citramalic acid, biphenyl, and isoleucylproline, demonstrated high AUC values ranging from 0.801 to 1, indicating their potential as disease biomarkers. Additionally, all three metabolites showed a strong association with retinal cystoid edema in CNV patients. Furthermore, the study identified 12 altered metabolic pathways, with five of them related to carbohydrate metabolism, suggesting their involvement in the occurrence of myopic CNV. These findings provide possible disease-specific biomarkers of CNV in PM and suggest the role of disturbed carbohydrate metabolism in its pathogenesis. Larger studies are needed to validate these findings.

A facile sol–gel spin coating method has been proposed for the synthesis of spin-coated ZnO nanofilms on ITO substrates. The as-prepared ZnO-nanofilm-based W/ZnO/ITO memory cell showed forming-free and tunable nonvolatile multilevel resistive switching behaviors with a high resistance ratio of about two orders of magnitude, which can be maintained for over 103 s and without evident deterioration. The tunable nonvolatile multilevel resistive switching phenomena were achieved by modulating the different set voltages of the W/ZnO/ITO memory cell. In addition, the tunable nonvolatile resistive switching behaviors of the ZnO-nanofilm-based W/ZnO/ITO memory cell can be interpreted by the partial formation and rupture of conductive nanofilaments modified by the oxygen vacancies. This work demonstrates that the ZnO-nanofilm-based W/ZnO/ITO memory cell may be a potential candidate for future high-density, nonvolatile, memory applications.

Abstract Developing novel photosensitizers for deep tissue imaging and efficient photodynamic therapy (PDT) remains a challenge because of the poor water solubility, low reactive oxygen species (ROS) generation efficiency, serve dark cytotoxicity, and weak absorption in the NIR region of conventional photosensitizers. Herein, cyclometalated iridium (III) complexes (Ir) with aggregation-induced emission (AIE) feature, high photoinduced ROS generation efficiency, two-photon excitation, and mitochondria-targeting capability were designed and further encapsulated into biocompatible nanoparticles (NPs). The Ir-NPs can be used to disturb redox homeostasis in vitro, result in mitochondrial dysfunction and cell apoptosis. Importantly, in vivo experiments demonstrated that the Ir-NPs presented obviously tumor-targeting ability, excellent antitumor effect, and low systematic dark-toxicity. Moreover, the Ir-NPs could serve as a two-photon imaging agent for deep tissue bioimaging with a penetration depth of up to 300 μm. This work presents a promising strategy for designing a clinical application of multifunctional Ir-NPs toward bioimaging and PDT.

Hepatocellular carcinoma (HCC) has been known as the second common leading cancer worldwide, as it responds poorly to both chemotherapy and medication. Triptolide (TP), a diterpenoid triepoxide, is a promising treatment agent for its effective anticancer effect on multiple cancers including HCC. However, its clinical application has been limited owing to its severe systemic toxicities, low solubility, and fast elimination in the body. Therefore, to overcome the above obstacles, photo-activatable liposomes (LP) integrated with both photosensitizer Ce6 and chemotherapeutic drug TP (TP/Ce6-LP) was designed in the pursuit of controlled drug release and synergetic photodynamic therapy in HCC therapy. The TP encapsulated in liposomes accumulated to the tumor site due to the enhanced permeability and retention (EPR) effect. Under laser irradiation, the photosensitizer Ce6 generated reactive oxygen species (ROS) and further oxidized the unsaturated phospholipids. In this way, the liposomes were destroyed to release TP. TP/Ce6-LP with NIR laser irradiation (TP/Ce6-LP+L) showed the best anti-tumor effect both in vitro and in vivo on a patient derived tumor xenograft of HCC (PDXHCC). TP/Ce6-LP significantly reduced the side effects of TP. Furthermore, TP/Ce6-LP+L induced apoptosis through a caspase-3/PARP signaling pathway. Overall, TP/Ce6-LP+L is a novel potential treatment option in halting HCC progression with attenuated toxicity.

Abstract Background During the biomass-to-bio-oil conversion process, many studies focus on studying the association between biomass and bio-products using near-infrared spectra (NIR) and chemical analysis methods. However, the characterization of biomass pyrolysis behaviors using thermogravimetric analysis (TGA) with support vector machine (SVM) algorithm has not been reported. In this study, tobacco was chosen as the object for biomass, because the cigarette smoke (including water, tar, and gases) released by tobacco pyrolysis reactions decides the sensory quality, which is similar to biomass as a renewable resource through the pyrolysis process. Results SVM algorithm has been employed to automatically classify the planting area and growing position of tobacco leaves using thermogravimetric analysis data as the information source for the first time. Eighty-eight single-grade tobacco samples belonging to four grades and eight categories were split into the training, validation, and blind testing sets. Our model showed excellent performances in both the training and validation set as well as in the blind test, with accuracy over 91.67%. Throughout the whole dataset of 88 samples, our model not only provides precise results on the planting area of tobacco leave, but also accurately distinguishes the major grades among the upper, lower, and middle positions. The error only occurs in the classification of subgrades of the middle position. Conclusions From the case study of tobacco, our results validated the feasibility of using TGA with SVM algorithm as an objective and fast method for auto-classification of tobacco planting area and growing position. In view of the high similarity between tobacco and other biomasses in the compositions and pyrolysis behaviors, this new protocol, which couples the TGA data with SVM algorithm, can potentially be extrapolated to the auto-classification of other biomass types.

Natural products generally fall into the biologically relevant chemical space and always possess novel biological activities, thus making them a rich source of lead compounds for new drug discovery. With the recent technological advances, natural product-based drug discovery is now reaching a new era. Natural products have also shown promise in epigenetic drug discovery, some of them have advanced into clinical trials or are presently being used in clinic. The histone lysine specific demethylase 1 (LSD1), an important class of histone demethylases, has fundamental roles in the development of various pathological conditions. Targeting LSD1 has been recognized as a promising therapeutic option for cancer treatment. Notably, some natural products with different chemotypes including protoberberine alkaloids, flavones, polyphenols, and cyclic peptides have shown effectiveness against LSD1. These natural products provide novel scaffolds for developing new LSD1 inhibitors. In this review, we mainly discuss the identification of natural LSD1 inhibitors, analysis of the co-crystal structures of LSD1/natural product complex, antitumor activity and their modes of action. We also briefly discuss the challenges faced in this field. We believe this review will provide a landscape of natural LSD1 inhibitors.

Parallel sentences play a crucial role in various NLP tasks, particularly for cross-lingual tasks such as machine translation. However, due to the time-consuming and laborious nature of manual construction, many low-resource languages still suffer from a lack of large-scale parallel data. The objective of pseudo-parallel sentence extraction is to automatically identify sentence pairs in different languages that convey similar meanings. Earlier methods heavily relied on parallel data, which is unsuitable for low-resource scenarios. The current mainstream research direction is to use transfer learning or unsupervised learning based on cross-lingual word embeddings and multilingual pre-trained models; however, these methods are ineffective for languages with substantial differences. To address this issue, we propose a sentence extraction method that leverages image information fusion to extract Chinese–Vietnamese pseudo-parallel sentences from collections of bilingual texts. Our method first employs an adaptive image and text feature fusion strategy to efficiently extract the bilingual parallel sentence pair, and then, a multimodal fusion method is presented to balance the information between the image and text modalities. The experiments on multiple benchmarks show that our method achieves promising results compared to a competitive baseline by infusing additional external image information.

A facile hydrothermal process has been developed to synthesize the α-Fe2O3 nanowire arrays with a preferential growth orientation along the [110] direction. The W/α-Fe2O3/FTO memory device with the nonvolatile resistive switching behavior has been achieved. The resistance ratio (RHRS/RLRS) of the W/α-Fe2O3/FTO memory device exceeds two orders of magnitude, which can be preserved for more than 103s without obvious decline. Furthermore, the carrier transport properties of the W/α-Fe2O3/FTO memory device are dominated by the Ohmic conduction mechanism in the low resistance state and trap-controlled space-charge-limited current conduction mechanism in the high resistance state, respectively. The partial formation and rupture of conducting nanofilaments modified by the intrinsic oxygen vacancies have been suggested to be responsible for the nonvolatile resistive switching behavior of the W/α-Fe2O3/FTO memory device. This work suggests that the as-prepared α-Fe2O3 nanowire-based W/α-Fe2O3/FTO memory device may be a potential candidate for applications in the next-generation nonvolatile memory devices.

Nano-titanium dioxides (nano-TiO2) surface modified with isopropyl tri(dioctylpyrophosphate) titanate (NDZ-201), a titanate coupling agent, and 3-glycidoxypropyltrimethoxysilane (KH-560), a silane coupling agent, were separately mixed with bisphenol A epoxy resin (DEGBA) prepolymer and then cured using a UV-normal temperature synergistic curing process. Then, the isothermal curing process of the system was investigated by differential scanning calorimetry (DSC). The relationship between the organization structures, mechanical properties, and heat resistance properties of the cured composites and material formulation was studied, and the DSC results showed that the addition of nano-TiO2 reduced the curing reaction rate constant k1 and increased the k2 of the prepolymer, while the activation energy of the curing reaction after UV irradiation Ea1 decreased, and the activation energy in the middle and later periods Ea2 increased. The characterization results of the composite material showed that nano-TiO2 as a scattering agent reduced the photoinitiation efficiency of UV light, and due to its obvious agglomeration tendency in the epoxy resin, the mechanical properties of the composite material were poor. The dispersibility of the coupling-agent-modified nano-TiO2 in the epoxy resin was greatly enhanced, and the mechanical and heat resistance properties of the composite material improved remarkably. The comparison results of the two coupling agents showed that NDZ-201 had better performance in increasing the impact strength by 6.8% (minimum value, the same below) and the maximum thermal decomposition rate temperature by 4.88 °C of the composite, while KH-560 improved the tensile strength by 7.3% and the glass transition temperature (Tg) by 3.34 °C of the composite.

In this paper, the effect of nitrogen annealing on the resistive switching characteristics of the rutile TiO2 nanowire-based W/TiO2/FTO memory device is analyzed. The W/TiO2/FTO memory device exhibits a nonvolatile bipolar resistive switching behavior with a high resistance ratio (RHRS/RLRS) of about two orders of magnitude. The conduction behaviors of the W/TiO2/FTO memory device are attributed to the Ohmic conduction mechanism and the Schottky emission in the low resistance state and the high resistance state, respectively. Furthermore, the RHRS/RLRS of the W/TiO2/FTO memory device is obviously increased from about two orders of magnitude to three orders of magnitude after the rapid nitrogen annealing treatment. In addition, the change in the W/TiO2 Schottky barrier depletion layer thickness and barrier height modified by the oxygen vacancies at the W/TiO2 interface is suggested to be responsible for the resistive switching characteristics of the W/TiO2/FTO memory device. This work demonstrates the potential applications of the rutile TiO2 nanowire-based W/TiO2/FTO memory device for high-density data storage in nonvolatile memory devices.