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Background: Multimodal analgesia plays a key role in enhanced recovery after surgery. Herein, we describe a trial protocol investigating the effects of oxycodone-vs. sufentanil-based patient-controlled analgesia in combination with quadratus lumborum block (QLB) vs. transverse abdominis plane block (TAPB) on quality of recovery following major laparoscopic gastrointestinal surgery. Methods: and analysis: This is a prospective, randomized, controlled clinical trial with a 2 × 2 factorial design. A total of 120 adult patients undergoing laparoscopic major gastrointestinal surgery will be randomized, in a 1:1:1:1 ratio, to receive one of two patient-controlled analgesia regimens (based on oxycodone or sufentanil) and one of two regional blocks (QLB or TAPB). The primary outcome measure of this trial is the quality of recovery at 24 h after surgery, assessed using the 15-item quality of recovery (QoR-15) scale. The secondary outcomes include QoR-15 scores at 48 and 72 h after surgery; visceral and incisional pain at rest and while coughing at 1, 6, 24 and 48 h postoperatively; analgesic consumption within 0–24 h and 24–48 h postoperatively; need for rescue analgesia; postoperative flatus time; postoperative adverse events (sedation, nausea and vomiting, use of antiemetics, respiratory depression, and dizziness); and length of postoperative hospital stay. Discussion: The results of this trial will provide evidence for the optimal multimodal analgesic strategy to improve the quality of recovery for patients undergoing laparoscopic major gastrointestinal surgery. Trial registration: This trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn, identifier: ChiCTR2400080766).

PURPOSE: Oxycodone is a potent μ- and κ-opioid receptor agonist that can relieve both somatic and visceral pain. We assessed oxycodone- vs sufentanil-based multimodal analgesia on postoperative pain following major laparoscopic gastrointestinal surgery. METHODS: In this randomised double-blind controlled trial, 40 adult patients were randomised (1:1, stratified by type of surgery) to receive oxycodone- or sufentanil-based multimodal analgesia, comprising bilateral transverse abdominis plane blocks, intraoperative dexmedetomidine infusion, flurbiprofen axetil, and oxycodone- or sufentanil-based patient-controlled analgesia. The co-primary outcomes were time-weighted average (TWA) of visceral pain (defined as intra-abdominal deep and dull pain) at rest and on coughing during 0-24 h postoperatively, assessed using the numerical rating scale (0-10) with a minimal clinically important difference of 1. RESULTS: All patients completed the study (median age, 64 years; 65% male) and had adequate postoperative pain control. The mean (SD) 24-h TWA of visceral pain at rest was 1.40 (0.77) in the oxycodone group vs 2.00 (0.98) in the sufentanil group (mean difference=-0.60, 95% CI, -1.16 to -0.03; P=0.039). Patients in the oxycodone group had a significantly lower 24-h TWA of visceral pain on coughing (2.00 [0.83] vs 2.98 [1.26]; mean difference=-0.98, 95% CI, -1.66 to -0.30; P=0.006). In the subgroup analyses, the treatment effect of oxycodone vs sufentanil on the co-primary outcomes did not differ in terms of age (18-65 years or >65 years), sex (female or male), or type of surgery (colorectal or gastric). Secondary outcomes (24-h TWA of incisional and shoulder pain, postoperative analgesic usage, rescue analgesia, adverse events, and patient satisfaction) were comparable between groups. CONCLUSION: For patients undergoing major laparoscopic gastrointestinal surgery, oxycodone-based multimodal analgesia reduced postoperative visceral pain in a statistically significant but not clinically important manner. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2100052085).

Abstract Tertiary lymphoid structures are immune cell aggregates linked with cancer outcomes, but their interactions with tumour cell aggregates are unclear. Using nasopharyngeal carcinoma as a model, here we analyse single-cell transcriptomes of 343,829 cells from 77 biopsy and blood samples and spatially-resolved transcriptomes of 31,316 spots from 15 tumours to decipher their components and interactions with tumour cell aggregates. We identify essential cell populations in tertiary lymphoid structure, including CXCL13+ cancer-associated fibroblasts, stem-like CXCL13+CD8+ T cells, and B and T follicular helper cells. Our study shows that germinal centre reaction matures plasma cells. These plasma cells intersperse with tumour cell aggregates, promoting apoptosis of EBV-related malignant cells and enhancing immunotherapy response. CXCL13+ cancer-associated fibroblasts promote B cell adhesion and antibody production, activating CXCL13+CD8+ T cells that become exhausted in tumour cell aggregates. Tertiary lymphoid structure-related cell signatures correlate with prognosis and PD-1 blockade response, offering insights for therapeutic strategies in cancers.

Purpose: With a focus on undergraduate music major students in China, the study sought to examine how higher music education institutions prepare professional knowledge, professional skills and soft skills in relevance to music students' employability. Design/methodology/approach: The quantitative survey engaged 359 music students from five music institutions in Western China to report their perceptions toward music curriculum related to employability. The current study examined whether their perception varied based on their gender, location, school, educational background and professional option purpose. Findings: Perception differences in the music curriculum were observed across gender, schools, educational background and professional option purpose. School differences were the most significant among all five factors, followed by professional option purpose, educational background and gender. The location difference was insignificant among the five factors. There were insufficient opportunities for community and industrial engagement in higher music education. Originality/value: The current study provides an insight into the higher music education curriculum for employability preparation in current China. This is one of the limited empirical studies in Western China to investigate music students' perceptions of professional knowledge and skills and the soft skill line with employability. The findings can serve as a reference for prospective employees in the music industry, policymaking and curriculum design and future research.

The immersion corrosion experiment of laser-based direct energy deposited H13 steel in ADC12 aluminum alloy melt was conducted to evaluate the demands for corrosion resistance after mold repair. The effect of the anisotropic microstructure of the deposited H13 steel on corrosion behavior was elucidated by characterizing the microstructure before and after corrosion. The results show that the microstructural heterogeneity affects the initiation, development and stabilization process of corrosion. Corrosion tends to initiate near the heat-affected zone due to the heterogeneous distribution of grain size, carbides, and dislocation density. Planes with weak microstructural heterogeneity are less likely to develop cracks in the intermetallic compounds (IMCs) layer during the corrosion development stage, thus exhibiting a slower corrosion rate. The IMCs layer of plane with weak microstructural heterogeneity stabilizes more quickly during the corrosion stabilization stage. The plane perpendicular to the build direction exhibits the highest corrosion resistance due to fewer corrosion initiation locations and the weakest microstructural heterogeneity. Furthermore, the composite structure of carbide core + Si phase shell, generated during corrosion, contributes to improving localized corrosion resistance. This study provides insights into understanding the influence of the heterogeneous microstructure from additive manufacturing on the reaction-diffusion process and offers guidance on direction selection when preparing components for applications in contact with aluminum melts using additive manufacturing techniques.

Abstract Introduction and objectives In diseases characterized by fibrosis, hepatic stellate cells (HSCs) are mesenchymal cells that play an important role in liver fibrosis. circRNAs are involved in regulating hydatid exocyst formation through miRNA sponge adsorption. The mechanisms of hepatic cystic hydatid outer cyst formation, HSC, and liver fibrosis are unclear. Materials and methods Based on our sequencing data, we validated the mechanism by which circRNA-049637 regulated hepatic cystic hydatid growth and promoted outer fibrocystic wall formation. Results Our results revealed that circRNA_049637 silencing promoted the proliferation of LX-2 human HSCs, affected the cell cycle, and increased the mRNA and protein expression levels of liver fibrosis-related indicators such as α-SMA, COL1A1, COL3A1, and TGFβRII. Conclusions CircRNA_049637 may induce the formation of hepatic hydatid cysts by promoting hepatic fibrosis via HSC activation.

ObjectiveKale is an important bulk vegetable crop worldwide, its main growth characteristics are outer leaves and leaf bulbs. The traits of leaf bulb kale are crucial for adjusting water and fertilizer parameters in the field to achieve maximum yield. However, various factors such as soil quality, light exposure, leaf overlap, and shading can affect the growth of in practical field conditions. The similarity in color and texture between leaf bulbs and outer leaves complicates the segmentation process for existing recognition models. In this paper, the segmentation of kale outer leaves and leaf bulbs in complex field background was proposed, using pixel values to determine leaf bulb size for intelligent field management. A semantic segmentation algorithm, UperNet-ESA was proposed to efficiently and accurately segment nodular kale outer leaf and leaf bulb in field scenes using the morphological features of the leaf bulbs and outer leaves of nodular kale to realize the intelligent management of nodular kale in the field.MethodsThe UperNet-ESA semantic segmentation algorithm, which uses the unified perceptual parsing network (UperNet) as an efficient semantic segmentation framework, is more suitable for extracting crop features in complex environments by integrating semantic information across different scales. The backbone network was improved using ConvNeXt, which is responsible for feature extraction in the model. The similarity between kale leaf bulbs and outer leaves, along with issues of leaf overlap affecting accurate target contour localization, posed challenges for the baseline network, leading to low accuracy. ConvNeXt effectively combines the strengths of convolutional neural networks (CNN) and Transformers, using design principles from Swin Transformer and building upon ResNet50 to create a highly effective network structure. The simplicity of the ConvNeXt design not only enhances segmentation accuracy with minimal model complexity, but also positions it as a top performer among CNN architectures. In this study, the ConvNeXt-B version was chosen based on considerations of computational complexity and the background characteristics of the knotweed kale image dataset. To enhance the model's perceptual acuity, block ratios for each stage were set at 3:3:27:3, with corresponding channel numbers of 128, 256, 512 and 1 024, respectively. Given the visual similarity between kale leaf bulbs and outer leaves, a high-efficiency channel attention mechanism was integrated into the backbone network to improve feature extraction in the leaf bulb region. By incorporating attention weights into feature mapping through residual inversion, attention parameters were cyclically trained within each block, resulting in feature maps with attentional weights. This iterative process facilitated the repeated training of attentional parameters and enhanced the capture of global feature information. To address challenges arising from direct pixel addition between up-sampling and local features, potentially leading to misaligned context in feature maps and erroneous classifications at kale leaf boundaries, a feature alignment module and feature selection module were introduced into the feature pyramid network to refine target boundary information extraction and enhance model segmentation accuracy.Results and DiscussionsThe UperNet-ESA semantic segmentation model outperforms the current mainstream UNet model, PSPNet model, DeepLabV3+ model in terms of segmentation accuracy, where mIoU and mPA reached 92.45% and 94.32%, respectively, and the inference speed of up to 16.6 frames per second (fps). The mPA values were better than that of the UNet model, PSPNet model, ResNet-50 based, MobilenetV2, and DeepLabV3+ model with Xception as the backbone, showing improvements of 11.52%, 13.56%, 8.68%, 4.31%, and 6.21%, respectively. Similarly, the mIoU exhibited improvements of 12.21%, 13.04%, 10.65%, 3.26% and 7.11% compared to the mIoU of the UNet-based model, PSPNet model, and DeepLabV3+ model based on the ResNet-50, MobilenetV2, and Xception backbones, respectively. This performance enhancement can be attributed to the introduction of the ECA module and the improvement made to the feature pyramid network in this model, which strengthen the judgement of the target features at each stage to obtain effective global contextual information. In addition, although the PSPNet model had the fastest inference speed, the overall accuracy was too low to for developing kale semantic segmentation models. On the contrary, the proposed model exhibited superior inference speed compared to all other network models.ConclusionsThe experimental results showed that the UperNet-ESA semantic segmentation model proposed in this study outperforms the original network in terms of performance. The improved model achieves the best accuracy-speed balance compared to the current mainstream semantic segmentation networks. In the upcoming research, the current model will be further optimized and enhanced, while the kale dataset will be expanded to include a wider range of samples of nodulated kale leaf bulbs. This expansion is intended to provide a more robust and comprehensive theoretical foundation for intelligent kale field management.

Abstract Background Nanoplastics, are emerging pollutants, present a potential hazard to food security and human health. Titanium dioxide nanoparticles (Nano-TiO2), serving as nano-fertilizer in agriculture, may be important in alleviating polystyrene nanoplastics (PSNPs) toxicity. Results Here, we performed transcriptomic, metabolomic and physiological analyzes to identify the role of Nano-TiO2 in regulating the metabolic processes in PSNPs-stressed maize seedlings (Zea mays L.). The growth inhibition by PSNPs stress was partially relieved by Nano-TiO2. Furthermore, when considering the outcomes obtained from RNA-seq, enzyme activity, and metabolite content analyses, it becomes evident that Nano-TiO2 significantly enhance carbon and nitrogen metabolism levels in plants. In comparison to plants that were not subjected to Nano-TiO2, plants exposed to Nano-TiO2 exhibited enhanced capabilities in maintaining higher rates of photosynthesis, sucrose synthesis, nitrogen assimilation, and protein synthesis under stressful conditions. Meanwhile, Nano-TiO2 alleviated the oxidative damage by modulating the antioxidant systems. Interestingly, we also found that Nano-TiO2 significantly enhanced the endogenous melatonin levels in maize seedlings. P-chlorophenylalanine (p-CPA, a melatonin synthesis inhibitor) declined Nano-TiO2-induced PSNPs tolerance. Conclusions Taken together, our data show that melatonin is involved in Nano-TiO2-induced growth promotion in maize through the regulation of carbon and nitrogen metabolism. Graphical Abstract

Cells are the most basic structural and functional unit of living organisms. In recent years, people have paid more attention to cell heterogeneity. In order to characterize the heterogeneity of cells and prevent the life information in an individual cell from being overwhelmed by the average level of the population gained from traditional cell biology research, many new analytical techniques have been developed for single-cell analysis. However, single-cell analysis is extremely challenging due to the minimal cell volume, low content and wide variety of analytes in single cells, some of analytes change rapidly in cells and others may interfere with each other during analysis. Mass spectrometry has gradually become an ideal tool for single-cell analysis due to its high sensitivity, high resolution and high selectivity. In this review, several techniques of single-cell analysis based on mass spectrometry in the recent five years were systematically summarized and discussed including electrospray ionization mass spectrometry (ESI-MS), laser desorption ionization mass spectrometry (LDI-MS), secondary ion mass spectrometry (SIMS) and inductively coupled plasma mass spectrometry (ICP-MS). Finally, this review also looked into future developments of these mass spectrometry-based techniques. With the development of cell biology, the requirement for single-cell analysis technology is increasing as well. In the meanwhile, single-cell analysis, which focuses on studying the mechanisms of cellular and molecular behavior, has aroused more and more attention from various branches of life sciences in recent years. Although higher spatial resolution and detection sensitivity have become the development trends for single-cell mass spectrometry, none of these mass spectrometry-based techniques can be recognized flawless, which means they all have certain flaws to some extent. Consequently, single-cell analysis technology based on mass spectrometry is developing towards methodological diversification. On the one hand, it is of great importance to choose one suitable mass spectrometry-based technique according to the research purpose and actual conditions. On the other hand, it should be also emphasized that different methods can complement each other and jointly provide a more comprehensive analysis environment for single-cell mass spectrometry, thereby improving and innovating existing single-cell analysis techniques based on mass spectrometry. This review will provide insights into better understanding on and development of single-cell analysis by mass spectrometry.

BackgroundIn recent years, more severe droughts have occurred frequently in many parts of the world, drought stress is the primary abiotic stress factor restricting the growth and quality of flue-cured tobacco. Therefore, screening dryland cultivation-compatible flue-cured tobacco varieties will help reduce the negative impact of drought.MethodsTobacco varieties were selected: Qinyan 96 (Q96), Zhongyan 101 (Z101), Yunyan 87 (Y87), and Yunyan 116 (Y116). A pot experiment was conducted with four water supply gradients: sufficient, mild stress, moderate stress, and severe stress. The aim was to analyze inter-varietal differences in agronomic traits, photosynthetic traits, reactive oxygen species (ROS) metabolism, and antioxidant enzyme system under drought stress. Additionally, the drought resistance of four flue-cured tobacco varieties was evaluated using principal component analysis and membership function analysis.ResultsThe results showed that drought intensification inhibited seedling growth and development across all varieties, with Q96 showing the least decrease and Y116 the greatest. With the increasing degree of drought stress, photosynthetic rates (Pn), transpiration rate (Tr), and stomatal conduction (Gs) have shown gradually decreasing trends, while substomatal cavity CO2 concentration (Ci) showed a growing trend. Severe drought corresponded with lower chlorophyll content and decreased the maximal photochemical efficiency (Fv/Fm), photosystem II (PSII), and photochemical quenching coefficient (qP) in all varieties, while steady-state non-photochemical quenching (NPQ) increased. Increased drought stress led to significantly higher reactive oxygen species (ROS) and malondialdehyde (MDA) content accumulation in tobacco seedlings. The antioxidant enzyme activities in, Q96, Z101, and Y87 increased under mild drought stress, whereas Y116 showed decreased activity.ConclusionThe drought resistance ranking among the four varieties is as follows: Q96 > Z101 > Y87 > Y116. Therefore, Q96 is a promising drought-tolerant breeding material that can be used as a reference for dryland cultivation of flue-cured tobacco.

Background: Multimodal analgesia plays a key role in enhanced recovery after surgery. Herein, we describe a trial protocol investigating the effects of oxycodone-vs. sufentanil-based patient-controlled analgesia in combination with quadratus lumborum block (QLB) vs. transverse abdominis plane block (TAPB) on quality of recovery following major laparoscopic gastrointestinal surgery. Methods: and analysis: This is a prospective, randomized, controlled clinical trial with a 2 × 2 factorial design. A total of 120 adult patients undergoing laparoscopic major gastrointestinal surgery will be randomized, in a 1:1:1:1 ratio, to receive one of two patient-controlled analgesia regimens (based on oxycodone or sufentanil) and one of two regional blocks (QLB or TAPB). The primary outcome measure of this trial is the quality of recovery at 24 h after surgery, assessed using the 15-item quality of recovery (QoR-15) scale. The secondary outcomes include QoR-15 scores at 48 and 72 h after surgery; visceral and incisional pain at rest and while coughing at 1, 6, 24 and 48 h postoperatively; analgesic consumption within 0–24 h and 24–48 h postoperatively; need for rescue analgesia; postoperative flatus time; postoperative adverse events (sedation, nausea and vomiting, use of antiemetics, respiratory depression, and dizziness); and length of postoperative hospital stay. Discussion: The results of this trial will provide evidence for the optimal multimodal analgesic strategy to improve the quality of recovery for patients undergoing laparoscopic major gastrointestinal surgery. Trial registration: This trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn, identifier: ChiCTR2400080766).

In order to adjust and detect micro-nano periodic structure optical surface accurately and efficiently, the problem of composite scattering between micro-ellipsoidal periodic structure optical surface and pore defects is studied use the multi-resolution time domain (MRTD) approach. A calculation model is established for the intensity distribution of composite scattering, which is modulated by the micro-ellipsoidal periodic structure optical surface and microdefects. Results are in good agreement with those obtained using CST Microwave Studio software and the finite-different time-domain (FDTD) approach, which demonstrates the effectiveness of the calculation model and method. By combining the field distribution of the micro-ellipsoidal periodic structure optical surface containing microdefects with the optical response at different wavelengths, it is necessary to study the influence of various parameters of the micro-ellipsoidal structure and microdefects on the optical system of metamaterials. The effects of the parameters such as roughness, structure of micro-ellipsoidal unit, defect sizes and buried depths on the composite scattering characteristics are analyzed numerically. The results provide technical support for the fields of functional surface design, ultrasensitive detection, scattering peak orientation and frequency selection.

Abstract Photothermal therapy is favored by cancer researchers due to its advantages such as controllable initiation, direct killing and immune promotion. However, the low enrichment efficiency of photosensitizer in tumor site and the limited effect of single use limits the further development of photothermal therapy. Herein, a photo-responsive multifunctional nanosystem was designed for cancer therapy, in which myeloid-derived suppressor cell (MDSC) membrane vesicle encapsulated decitabine-loaded black phosphorous (BP) nanosheets (BP@ Decitabine @MDSCs, named BDM). The BDM demonstrated excellent biosafety and biochemical characteristics, providing a suitable microenvironment for cancer cell killing. First, the BDM achieves the ability to be highly enriched at tumor sites by inheriting the ability of MDSCs to actively target tumor microenvironment. And then, BP nanosheets achieves hyperthermia and induces mitochondrial damage by its photothermal and photodynamic properties, which enhancing anti-tumor immunity mediated by immunogenic cell death (ICD). Meanwhile, intra-tumoral release of decitabine induced G2/M cell cycle arrest, further promoting tumor cell apoptosis. In vivo, the BMD showed significant inhibition of tumor growth with down-regulation of PCNA expression and increased expression of high mobility group B1 (HMGB1), calreticulin (CRT) and caspase 3. Flow cytometry revealed significantly decreased infiltration of MDSCs and M2-macrophages along with an increased proportion of CD4+, CD8+ T cells as well as CD103+ DCs, suggesting a potentiated anti-tumor immune response. In summary, BDM realizes photothermal therapy/photodynamic therapy synergized chemotherapy for cancer.

SignificanceBig Models, or Foundation Models, have offered a new paradigm in smart agriculture. These models, built on the Transformer architecture, incorporate numerous parameters and have undergone extensive training, often showing excellent performance and adaptability, making them effective in addressing agricultural issues where data is limited. Integrating big models in agriculture promises to pave the way for a more comprehensive form of agricultural intelligence, capable of processing diverse inputs, making informed decisions, and potentially overseeing entire farming systems autonomously.ProgressThe fundamental concepts and core technologies of big models are initially elaborated from five aspects: the generation and core principles of the Transformer architecture, scaling laws of extending big models, large-scale self-supervised learning, the general capabilities and adaptions of big models, and the emerging capabilities of big models. Subsequently, the possible application scenarios of the big model in the agricultural field are analyzed in detail, the development status of big models is described based on three types of the models: Large language models (LLMs), large vision models (LVMs), and large multi-modal models (LMMs). The progress of applying big models in agriculture is discussed, and the achievements are presented.Conclusions and ProspectsThe challenges and key tasks of applying big models technology in agriculture are analyzed. Firstly, the current datasets used for agricultural big models are somewhat limited, and the process of constructing these datasets can be both expensive and potentially problematic in terms of copyright issues. There is a call for creating more extensive, more openly accessible datasets to facilitate future advancements. Secondly, the complexity of big models, due to their extensive parameter counts, poses significant challenges in terms of training and deployment. However, there is optimism that future methodological improvements will streamline these processes by optimizing memory and computational efficiency, thereby enhancing the performance of big models in agriculture. Thirdly, these advanced models demonstrate strong proficiency in analyzing image and text data, suggesting potential future applications in integrating real-time data from IoT devices and the Internet to make informed decisions, manage multi-modal data, and potentially operate machinery within autonomous agricultural systems. Finally, the dissemination and implementation of these big models in the public agricultural sphere are deemed crucial. The public availability of these models is expected to refine their capabilities through user feedback and alleviate the workload on humans by providing sophisticated and accurate agricultural advice, which could revolutionize agricultural practices.

As one of the major sources of protein in the human diet, chicken is characterized by high protein and low fat. Fresh chicken is susceptible to spoilage by microorganisms and enzymes during storage. Freezing is an effective way to extend the storage period of chicken, but ice crystals formed during the freezing process can negatively impact the chemical quality attributes of chicken, thereby affecting its eating quality. This article reviews traditional, modern, and emerging chicken freezing techniques, and elucidates the effects of freezing rate, freezing method, freezing temperature, freezing time, and freeze-thaw cycle on the quality of frozen chicken, with a focus on the changes in the eating quality (color, water-holding capacity, tenderness, and flavor) and chemical quality attributes (moisture, proteins, lipids, and pH) of chicken during freezing and frozen storage. It is our hope that this review will provide a theoretical reference for improving the key quality attributes of frozen chicken and extending its storage period.

Abstract Background Osimertinib is regarded as a promising third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for advanced non-squamous non-small cell lung cancer (NSCLC) patients who developed T790M. However the adverse effects, primarily fatigue, remain an overwhelming deficiency of Osimertinib, hindering it from achieving adequate clinical efficacy for such NSCLC. Ganoderma lucidum has been used for thousands of years in China to combat fatigue, while Ganoderma Lucidum spores powder (GLSP) is the main active ingredient. The aim of this study is to investigate whether GLSP is sufficiently effective and safe in improving fatigue and synergizing with Osimertinib in non-squamous NSCLC patients with EGFR mutant. Method/design A total of 140 participants will be randomly assigned to receive either de-walled GSLP or placebo for a duration of 56 days. The primary outcome measure is the fatigue score associated with EGFR-TKI adverse reactions at week 8, evaluated by the Chinese version of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer Patients (QLQ-C30). Secondary outcomes include evaluation of treatment effectiveness, assessment of quality of life (QoL), and exploration of immune indicators and gut microbiota relationships. Following enrollment, visits are scheduled biweekly until week 12. Trial registration China Clinical Trial Registry ChiCTR2300072786. Registrated on June 25, 2023.

Abstract Metal-organic framework (MOF) glasses are an emerging class of glasses which complement traditional inorganic, organic and metallic counterparts due to their hybrid nature. Although a few zeolitic imidazolate frameworks have been made into glasses, how to melt and quench the largest subclass of MOFs, metal carboxylate frameworks, into glasses remains challenging. Here, we develop a strategy by grafting the zwitterions on the carboxylate ligands and incorporating organic acids in the framework channels to enable the glass formation. The charge delocalization of zwitterion-acid subsystem and the densely filled channels facilitate the coordination bonding mismatch and thus reduce the melting temperature. Following melt-quenching realizes the glass formation of a family of carboxylate MOFs (UiO-67, UiO-68 and DUT-5), which are usually believed to be un-meltable. Our work opens up an avenue for melt-quenching porous molecular solids into glasses.

Abstract Background The pattern recognition receptor Dectin-1 was initially discovered to play a pivotal role in mediating pulmonary antifungal immunity and promoting neutrophil-driven inflammation. Recent studies have revealed that Dectin-1 is overexpressed in asthma, but the specific mechanism remains elusive. Additionally, Dectin-1 has been implicated in promoting pyroptosis, a hallmark of severe asthma airway inflammation. Nevertheless, the involvement of the non-classical pyroptosis signal caspase-11/4 and its upstream regulatory mechanisms in asthma has not been completely explored. Methods House dust mite (HDM)-induced mice was treated with Dectin-1 agonist Curdlan, Dectin-1 inhibitor Laminarin, and caspase-11 inhibitor wedelolactone separately. Subsequently, inflammatory cells in bronchoalveolar lavage fluid (BALF) were analyzed. Western blotting was performed to measure the protein expression of caspase-11 and gasdermin D (GSDMD). Cell pyroptosis and the expression of chemokine were detected in vitro. The correlation between Dectin-1 expression, pyroptosis factors and neutrophils in the induced sputum of asthma patients was analyzed. Results Curdlan appeared to exacerbate neutrophil airway inflammation in asthmatic mice, whereas wedelolactone effectively alleviated airway inflammation aggravated by Curdlan. Moreover, Curdlan enhanced the release of caspase-11 activation fragments and N-terminal fragments of gasdermin D (GSDMD-N) stimulated by HDM both in vivo or in vitro. In mouse alveolar macrophages (MH-S cells), Curdlan/HDM stimulation resulted in vacuolar degeneration and elevated lactate dehydrogenase (LDH) release. In addition, there was an upregulation of neutrophil chemokines CXCL1, CXCL3, CXCL5 and their receptor CXCR2, which was suppressed by wedelolactone. In asthma patients, a positive correlation was observed between the expression of Dectin-1 on macrophages and caspase-4 (the human homology of caspase-11), and the proportion of neutrophils in induced sputum. Conclusion Dectin-1 activation in asthma induced caspase-11/4 mediated macrophage pyroptosis, which subsequently stimulated the secretion of chemokines, leading to the exacerbation of airway neutrophil inflammation. Graphical Abstract

The clinical application of cancer immunotherapy is unsatisfied due to low response rates and systemic immune-related adverse events. Microwave hyperthermia can be used as a synergistic immunotherapy to amplify the antitumor effect. Herein, we designed a Gd-based metal-organic framework (Gd-MOF) nanosystem for MRI-guided thermotherapy and synergistic immunotherapy, which featured high performance in drug loading and tumor tissue penetration. The PD-1 inhibitor (aPD-1) was initially loaded in the porous Gd-MOF (Gd/M) nanosystem. Then, the phase change material (PCM) and the cancer cell membrane were further sequentially modified on the surface of Gd/MP to obtain Gd-MOF@aPD-1@CM (Gd/MPC). When entering the tumor microenvironment (TME), Gd/MPC induces immunogenic death of tumor cells through microwave thermal responsiveness, improves tumor suppressive immune microenvironment and further enhances anti-tumor ability of T cells by releasing aPD-1. Meanwhile, Gd/MPC can be used for contrast-enhanced MRI. Transcriptomics data revealed that the downregulation of MSK2 in cancer cells leads to the downregulation of c-fos and c-jun, and ultimately leads to the apoptosis of cancer cells after treatment. In general, Gd/MPC nanosystem not only solves the problem of system side effect, but also achieves the controlled drug release via PCM, providing a promising theranostic nanoplatform for development of cancer combination immunotherapy.

Abstract Photocatalytic redox reactions are important for synthesizing fine chemicals from olefins, but the limited lifetime of radical cation intermediates severely restricts semiconductor photocatalysis efficiency. Here, we report that Ag3PO4 can efficiently catalyze intramolecular and intermolecular [2 + 2] and Diels-Alder cycloadditions under visible-light irradiation. The approach is additive-free, catalyst-recyclable. Mechanistic studies indicate that visible-light irradiation on Ag3PO4 generates holes with high oxidation power, which oxidize aromatic alkene adsorbates into radical cations. In photoreduced Ag3PO4, the conduction band electron (e CB −) has low reduction power due to the delocalization among the Ag+-lattices, while the particle surfaces have a strong electrostatic interaction with the radical cations, which considerably stabilize the radical cations against recombination with e CB −. The radical cation on the particle’s surfaces has a lifetime of more than 2 ms, 75 times longer than homogeneous systems. Our findings highlight the effectiveness of inorganic semiconductors for challenging radical cation-mediated synthesis driven by sunlight.

ABSTRACT: Aging in breeder roosters is often accompanied by a decline in semen quality, negatively impacting reproductive performance. This study aimed to investigate the effect of dietary alpha-linolenic acid (ALA), an essential omega-3 polyunsaturated fatty acid, on semen quality, antioxidant capacity, and sperm survival in aging breeder roosters. Roosters were divided into 4 groups and fed diets supplemented with 0%, 0.5%, 1%, and 2% ALA for 6 wk. Results indicated significant improvements in semen volume, sperm viability, and sperm density in ALA-supplemented groups compared to the control (P < 0.05). The 1% ALA group exhibited the most notable enhancements in sperm viability and density. Additionally, ALA supplementation increased the activities of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and reduced malondialdehyde (MDA) levels, indicating enhanced antioxidant capacity (P < 0.05). Furthermore, ALA improved mitochondrial membrane potential (MMP) and reduced early and late sperm apoptosis, with the 2% ALA group showing the highest MMP and the lowest ROS-positive rate (P < 0.05). These findings suggest that dietary ALA supplementation enhances semen quality and antioxidant defenses, and mitigates oxidative stress, thus supporting the reproductive health of aging breeder roosters. This study underscores the potential of ALA as a dietary strategy to improve reproductive efficiency in poultry production.

ABSTRACTIn present paper, a universal method for multi-objective parameter optimisation of additive manufacturing processes was proposed and successfully applied to laser-based directed energy deposition (DED) experiments with mixtures of H13 and M2 steel powders that were deposited on 4Cr5Mo2SiV1 hot work die steel. The DED experiments were designed and completed based on the response surface method with 13 groups of laser parameters. The microstructure of the deposited alloy steel was observed and its mechanical properties were tested. The deposited steel alloy achieved an ultimate tensile strength (UTS) of 1821 ± 30 MPa with a reasonable elongation of approximately 4.5%, and the bond strength specimens achieved a bond toughness of ∼10.66% with a moderate UTS (1329 ± 28 MPa). A multi-objective optimisation method was proposed based on response surfaces which were established according to microstructural characteristics and mechanical properties data. It provided a basis for achieving high strength or high toughness DED-fabricated steel alloys.

Abstract Here, a photocatalytic asymmetric multicomponent cascade Minisci reaction of β‐carbolines with enamides and diazo compounds is reported, enabling an effective enantioselective radical C─H functionalization of β‐carbolines with high yields and enantioselectivity (up to 83% yield and 95% ee). This enantioselective multicomponent Minisci protocol exhibits step economy, high chemo‐/enantio‐selective control, and good functional group tolerance, allowing access to a variety of valuable chiral β‐carbolines. Notably, diazo compounds are suitable radical precursors in enantioselective cascade radical reactions. Moreover, the efficiency and practicality of this approach are demonstrated by the asymmetric synthesis of bioactive compounds and natural products.

Abstract Background Lumbar disc herniation (LDH) is the main clinical cause of low back pain. The pathogenesis of lumbar disc herniation is still uncertain, while it is often accompanied by disc rupture. In order to explore relationship between loading rate and failure mechanics that may lead to lumbar disc herniation, the failure mechanical properties of the intervertebral disc under high rates of loading were analyzed. Method Bend the lumbar motion segment of a healthy sheep by 5° and compress it to the ultimate strength point at a strain rate of 0.008/s, making a damaged sample. Within the normal strain range, the sample is subjected to quasi-static loading and high loading rate at different strain rates. Results For healthy samples, the stress–strain curve appears collapsed only at high rates of compression; for damaged samples, the stress–strain curves collapse both at quasi-static and high-rate compression. For damaged samples, the strengthening stage becomes significantly shorter as the strain rate increases, indicating that its ability to prevent the destruction is significantly reduced. For damaged intervertebral disc, when subjected to quasi-static or high rates loading until failure, the phenomenon of nucleus pulposus (NP) prolapse occurs, indicating the occurrence of herniation. When subjected to quasi-static loading, the AF moves away from the NP, and inner AF has the greatest displacement; when subjected to high rates loading, the AF moves closer to the NP, and outer AF has the greatest displacement. The Zhu–Wang–Tang (ZWT) nonlinear viscoelastic constitutive model was used to describe the mechanical behavior of the intervertebral disc, and the fitting results were in good agreement with the experimental curve. Conclusion Experimental results show that, both damage and strain rate have a significant effect on the mechanical behavior of the disc fracture. The research work in this article has important theoretical guiding significance for preventing LDH in daily life.

Abstract Background Extrachromosomal circular DNAs (eccDNAs) exist in human blood and somatic cells, and are essential for oncogene plasticity and drug resistance. However, the presence and impact of eccDNAs in type 2 diabetes mellitus (T2DM) remains inadequately understood. Methods We purified and sequenced the serum eccDNAs obtained from newly diagnosed T2DM patients and normal control (NC) subjects using Circle-sequencing. We validated the level of a novel circulating eccDNA named sorbin and SH3‐domain‐ containing‐1circle97206791–97208025 (SORBS1circle) in 106 newly diagnosed T2DM patients. The relationship between eccDNA SORBS1circle and clinical data was analyzed. Furthermore, we explored the source and expression level of eccDNA SORBS1circle in the high glucose and palmitate (HG/PA)-induced hepatocyte (HepG2 cell) insulin resistance model. Results A total of 22,543 and 19,195 eccDNAs were found in serum samples obtained from newly diagnosed T2DM patients and NC subjects, respectively. The T2DM patients had a greater distribution of eccDNA on chromosomes 1, 14, 16, 17, 18, 19, 20 and X. Additionally, 598 serum eccDNAs were found to be upregulated, while 856 eccDNAs were downregulated in T2DM patients compared with NC subjects. KEGG analysis demonstrated that the genes carried by eccDNAs were mainly associated with insulin resistance. Moreover, it was validated that the eccDNA SORBS1circle was significantly increased in serum of newly diagnosed T2DM patients (106 T2DM patients vs. 40 NC subjects). The serum eccDNA SORBS1circle content was positively correlated with the levels of glycosylated hemoglobin A1C (HbA1C) and homeostasis model assessment of insulin resistance (HOMA-IR) in T2DM patients. Intracellular eccDNA SORBS1circle expression was significantly enhanced in the high glucose and palmitate (HG/PA)-induced hepatocyte (HepG2 cell) insulin resistance model. Moreover, the upregulation of eccDNA SORBS1circle in the HG/PA-treated HepG2 cells was dependent on generation of apoptotic DNA fragmentation. Conclusions These results provide a preliminary understanding of the circulating eccDNA patterns at the early stage of T2DM and suggest that eccDNA SORBS1circle may be involved in the development of insulin resistance.