Spatial proteomic profiling elucidates immune determinants of neoadjuvant chemo-immunotherapy in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) presents significant clinical and therapeutic challenges due to its aggressive nature and generally poor prognosis. We initiated a Phase II clinical trial (ChiCTR1900027160) to assess the efficacy of a pioneering neoadjuvant chemo-immunotherapy regimen comprising programmed death-1 (PD-1) blockade (Toripalimab), nanoparticle albumin-bound paclitaxel (nab-paclitaxel), and the oral fluoropyrimidine derivative S-1, in patients with locally advanced ESCC. This study uniquely integrates clinical outcomes with advanced spatial proteomic profiling using Imaging Mass Cytometry (IMC) to elucidate the dynamics within the tumor microenvironment (TME), focusing on the mechanistic interplay of resistance and response. Sixty patients participated, receiving the combination therapy prior to surgical resection. Our findings demonstrated a major pathological response (MPR) in 62% of patients and a pathological complete response (pCR) in 29%. The IMC analysis provided a detailed regional assessment, revealing that the spatial arrangement of immune cells, particularly CD8+ T cells and B cells within tertiary lymphoid structures (TLS), and S100A9+ inflammatory macrophages in fibrotic regions are predictive of therapeutic outcomes. Employing machine learning approaches, such as support vector machine (SVM) and random forest (RF) analysis, we identified critical spatial features linked to drug resistance and developed predictive models for drug response, achieving an area under the curve (AUC) of 97%. These insights underscore the vital role of integrating spatial proteomics into clinical trials to dissect TME dynamics thoroughly, paving the way for personalized and precise cancer treatment strategies in ESCC. This holistic approach not only enhances our understanding of the mechanistic basis behind drug resistance but also sets a robust foundation for optimizing therapeutic interventions in ESCC.

Spatio-temporal learning and explaining for dynamic functional connectivity analysis: Application to depression.

Background Functional connectivity has been shown to fluctuate over time. The present study aimed to identifying major depressive disorders (MDD) with dynamic functional connectivity (dFC) from resting-state fMRI data, which would be helpful to produce tools of early depression diagnosis and enhance our understanding of depressive etiology. Methods The resting-state fMRI data of 178 subjects were collected, including 89 MDD and 89 healthy controls. We propose a spatio-temporal learning and explaining framework for dFC analysis. A yet effective spatio-temporal model is developed to classifying MDD from healthy controls with dFCs. The model is a stacking neural network model, which learns network structure information by a multi-layer perceptron based spatial encoder, and learns time-varying patterns by a Transformer based temporal encoder. We propose to explain the spatio-temporal model with a two-stage explanation method of importance feature extracting and disorder-relevant pattern exploring. The layer-wise relevance propagation (LRP) method is introduced to extract the most relevant input features in the model, and the attention mechanism with LRP is applied to extract the important time steps of dFCs. The disorder-relevant functional connections, brain regions, and brain states in the model are further explored and identified. Results We achieved the best classification performance in identifying MDD from healthy controls with dFC data. The top important functional connectivity, brain regions, and dynamic states closely related to MDD have been identified. Limitations The data preprocessing may affect the classification performance of the model, and this study needs further validation in a larger patient population. Conclusions The experimental results demonstrate that the proposed spatio-temporal model could effectively classify MDD, and uncover structural and temporal patterns of dFCs in depression.

BrainNPT: Pre-Training Transformer Networks for Brain Network Classification.

Deep learning methods have advanced quickly in brain imaging analysis over the past few years, but they are usually restricted by the limited labeled data. Pre-trained model on unlabeled data has presented promising improvement in feature learning in many domains, such as natural language processing. However, this technique is under-explored in brain network analysis. In this paper, we focused on pre-training methods with Transformer networks to leverage existing unlabeled data for brain functional network classification. First, we proposed a Transformer-based neural network, named as BrainNPT, for brain functional network classification. The proposed method leveraged token as a classification embedding vector for the Transformer model to effectively capture the representation of brain networks. Second, we proposed a pre-training framework for BrainNPT model to leverage unlabeled brain network data to learn the structure information of brain functional networks. The results of classification experiments demonstrated the BrainNPT model without pre-training achieved the best performance with the state-of-the-art models, and the BrainNPT model with pre-training strongly outperformed the state-of-the-art models. The pre-training BrainNPT model improved 8.75% of accuracy compared with the model without pre-training. We further compared the pre-training strategies and the data augmentation methods, analyzed the influence of the parameters of the model, and explained the trained model.

Association between Deltoid Muscle Density and Proximal Humeral Fracture in Elderly Patients.

Background: The potential role of deltoid muscle density in the occurrence of proximal humeral fractures remains uncertain. Therefore, the primary objective of this study was to examine the correlation between deltoid muscle density, as measured by CT attenuation value in Hounsfield units (HU), and the incidence of proximal humeral fractures in elderly patients. By investigating this association, we aim to shed light on the possible influence of deltoid muscle density on fracture risk in this specific population. Methods: A total of 68 patients with computed tomography (CT) images were retrospectively reviewed. Among them, 34 patients presented with fractures following low-energy injuries, while the remaining 34 patients served as controls and underwent CT scans after low-energy injuries without any fractures. The muscle density of the deltoid muscles was assessed at the approximate tubercle of humerus. We compared these parameters between the two groups and conducted analyses considering factors such as age, sex, laterality, and deltoid muscle density of the shoulders. Results: The demographic factors related to the shoulder did not exhibit any significant association with proximal humeral fracture. However, we observed a noteworthy difference in deltoid muscle density between patients with fractures (40.85 ± 1.35) and the control group (47.08 ± 1.61) (p = 0.0042), indicating a lower muscle density in the fracture group. Conclusion: Based on the findings of this study, we can conclude that there exists a negative correlation between deltoid muscle density and the incidence of proximal humeral fractures. These results suggest that lower deltoid muscle density may be associated with an increased risk of proximal humeral fractures in the elderly population under investigation.

Lipidomic analysis of grain quality variation in high quality aromatic japonica rice.

To maintain the purity of the seeds and rice quality of the high-quality rice varieties, five lines with similar field and yield traits were selected from the Nanjing46 population in Liyang and used as study materials, and the original progeny were used as the control material for comparing rice quality and lipid metabolites in this study. The rice quality of the five lines still differed compared to CKN1. The Badh2-E2 gene was detected in all five lines, but its 2-AP content differed. The C11:0 content in CKN1 and VN1 was significantly greater than that in the other four lines. Most of the differentially abundant metabolites were phospholipids, including PA(16:0/18:2), PC(15:0/16:0) and PG(16:0/16:0). These metabolites can be used as potential metabolic markers for identifying quality variation. This study presents a novel methodology and theoretical framework for investigating varietal degradation and ensuring seed purity authentication.

In Situ Fabrication of Electrospun Magnetic Film Under Laparoscopic Guidance for Preventing Postoperative Recurrence of Hepatocellular Carcinoma.

Despite laparoscopic-guided minimally invasive hepatectomy emerging as the primary approach for resecting hepatocellular carcinoma (HCC), there's still a significant gap in suitable biomaterials that seamlessly integrate with these techniques to achieve effective hemostasis and suppress residual tumors at the surgical margin. Electrospun films are increasingly used for wound closure, yet the employment of prefabricated electrospun films for hemostasis during minimally invasive HCC resection is hindered by prolonged operation times, complexity in implementation, limited visibility during surgery, and inadequate postoperative prevention of HCC recurrence. In this study, we integrated montmorillonite-iron oxide sheets into the PVP polymer framework, enhancing the resulting electrospun polyvinylpyrrolidone (PVP) /montmorillonite-iron oxide (MI) film (abbreviated as PMI) with robustness, hemostatic capability, and magnetocaloric properties. In contrast to the in vitro prefabricated electrospun films, the electrospun PMI film is designed to be formed in situ on liver wounds under laparoscopic guidance during hepatectomy. This design affords superior wound adaptability, facilitating meticulous wound closure and expeditious hemostasis, thereby simplifying the operative process and ultimately alleviating the workload of healthcare professionals. Moreover, when exposed to an alternating magnetic field, the film can efficiently ablate residual tumors, significantly augmenting the treatment efficacy of HCC. This article is protected by copyright. All rights reserved.

Oxygen vacancy formation strengthened microwave catalysis of Zn-Zr solid solution for antibiotic-free therapy strategies of bacteria-infected osteomyelitis.

Osteomyelitis, a grave deep tissue infection primarily caused by Staphylococcus aureus, results in serious complications such as abscesses and sepsis. With the incidence from open fractures exceeding 30 % and prevalent antibiotic resistance due to extensive treatment regimens, there's an urgent need for innovative, antibiotic-free strategies. Photothermal therapy (PTT) and photodynamic therapy (PDT) renowned for generating localized reactive oxygen species (ROS), face limitations in penetration depth. To overcome this, our method combines the deep penetration attributes of medical microwaves (MW) with the synergistic effects of the ZnO/ZrO2 solid solution. Comprehensive in vitro and in vivo evaluations showcased the solid-solution's potent antibacterial efficacy and biocompatibility. The ZnO/ZrO2 solid solution, especially in a 7:3 M ratio, manifests superior microstructural characteristics, optimizing MW-assisted therapy. Our findings highlight the potential of this integrated strategy as a promising avenue in osteomyelitis management.

Organic acids released by submerged macrophytes with damaged leaves alter the denitrification microbial community in rhizosphere.

Submerged macrophytes have important impacts on the denitrification and anaerobic ammonia-oxidizing (anammox) processes. Leaf damage in these plants probably changes the rhizosphere environment, affecting organic acid release and denitrifying bacteria. However, there is a lack of comprehensive understanding of the specific changes. This study investigated these changes in the rhizosphere of Potamogeton crispus with four degrees of leaf excision. When 0 %, 30 %, 50 % and 70 % of leaves were excised, the concentrations of total organic acid were 31.45, 32.67, 38.26, and 35.16 mg/L, respectively. The abundances of nirS-type denitrifying bacteria were 2.10 × 1010, 1.59 × 1010, 2.54 × 1010, and 4.67 × 1010 copies/g dry sediment, respectively. The abundances of anammox bacteria were 7.58 × 109, 4.59 × 109, 3.81 × 109, and 3.90 × 109 copies/g dry sediment, respectively. The concentration of total organic acids and the abundance of two denitrification microorganisms in the rhizosphere zone were higher than those in the root zone and non-rhizosphere zone. With increasing leaf damage, the number of OTUs in the Pseudomonas genus of nirS-type denitrifying bacteria first increased and then decreased, while that of the Thauera genus was relatively stable. The overall increase in the OTU number of anammox bacteria indicated that leaf damage promotes root exudates release, thereby leading to an increase in their diversity. The co-occurrence network revealed that the two denitrification microorganisms had about 60.52 % positive connections in rhizosphere while 64.73 % negative connections in non-rhizosphere. The abundance and community composition of both denitrification microorganisms were positively correlated with the concentrations of various substances such as oxalic acid, succinic acid, total organic acids and NO2--N. These findings demonstrate that submerged plant damage has significantly impacts on the structure of denitrification microbial community in the rhizosphere, which may alter the nitrogen cycling process in the deposit sediment. SYNOPSIS: This study reveals leaf damage of macrophyte changed the rhizosphere denitrification microbial community, which is helpful to further understand the process of nitrogen cycle in water.

Advantages of unilateral percutaneous kyphoplasty for osteoporotic vertebral compression fractures-a systematic review and meta-analysis.

Data from English randomized controlled trials comparing unilateral versus bilateral PKP for the treatment of OVCFs were retrieved and analyzed, and the results showed that unilateral PKP is a better choice for the treatment of patients with OVCFs, which will provide a reliable clinical rationale for the treatment of OVCFs. PURPOSE: To investigate the advantages of unilateral percutaneous kyphoplasty (PKP) for the treatment of osteoporotic vertebral compression fractures(OVCFs). METHODS: The systematic evaluation program met all program requirements (CRD 42023422383) by successfully passing the PROSPERO International Prospective Systematic Evaluation Registry. Researchers searched the references of English-language randomized controlled trials comparing unilateral and bilateral PKP for the treatment of osteoporotic vertebral compression fractures published between 2010 and 2023 and manually searched for known primary and review articles. The study statistically analyzed data from all the included literature, which primarily included time to surgery, visual pain score(VAS) and Oswestry disability index(ODI) at postoperative follow-up time points, polymethylmethacrylate (PMMA, bone cement) injection dose, cement leakage, radiation dose, and improvement in kyphotic angle. RESULTS: This meta-analysis searched 416 articles published from 2010 to 2023 based on keywords, and 18 articles were finally included in this study. The results of the forest plot showed that unilateral PKP operative time, amount of bone cement used, and radiation dose to the patient were significantly reduced (p < 0.01, p < 0.01, and p < 0.01, respectively), and unilateral and bilateral PKP had comparable cement leakage (p = 0.49, 95% CI = 0.58-1.30), and there was no significant difference in the kyphotic angle between unilateral and bilateral PKP (p = 0.42, 95% CI = - 2.29-0.96). During follow-up, there was no significant difference in pain relief between unilateral and bilateral PKP (p = 0.70, 95% CI = - 0.09-0.06), nor was there a significant difference in ODI (p = 0.27, 95% CI = - 0.35-1.24). CONCLUSIONS: There is no difference in clinical efficacy between unilateral PKP and bilateral PKP, but unilateral PKP has a shorter operative time, a lower incidence of cement leakage, a lower amount of cement, and a lower radiation dose to the patient and operator. Unilateral PKP is a better option for patients with OVCFs.

Efficacy and Safety of Neoadjuvant Subcutaneous Envafolimab in dMMR/MSI-H Locally Advanced Colon Cancer.

BACKGROUND: Neoadjuvant immunotherapy with programmed death-ligand 1 blockade for colon cancer, especially for mismatch repair-deficient (dMMR)/high microsatellite instability (MSI-H) colon cancer, has gained considerable attention recently. OBJECTIVE: This study aimed to assess the safety and efficacy of neoadjuvant subcutaneous envafolimab in patients with dMMR/MSI-H locally advanced colon cancer. METHODS: Patients with dMMR/MSI-H locally advanced colon cancer treated with envafolimab at Sun Yat-sen University Cancer Center and Yunnan Cancer Hospital from October 2021 to July 2023 were retrospectively reviewed and analyzed. The primary endpoint was the pathological complete response (CR) rate, and secondary endpoints were treatment-related adverse events and complete clinical response rate. RESULTS: Overall, 15 patients were analyzed. After neoadjuvant immunotherapy with envafolimab, six patients achieved a CR, with five partial responses, and four stable disease. Three patients achieving a complete clinical response chose to accept a "watch and wait" strategy, and surgery was performed in 12 patients. Postoperative pathology results revealed seven patients achieved pathological CRs, and five patients achieved tumor regression grade 2, with 66.7% of the total CR rate. The most common treatment-related adverse events were pruritus and rash (40%), with no severe cases. No recurrences occurred over a 7.9-month follow-up. CONCLUSIONS: Envafolimab yielded promising surgical outcomes and safety in dMMR/MSI-H locally advanced colon cancer, representing a promising treatment modality for this population.

Preparation of NIR-II Polymer Nanoprobe Through Twisted Intramolecular Charge Transfer and Förster Resonance Energy Transfer of NIR-I Dye.

Near-infrared-II (NIR-II) fluorescence imaging is pivotal in biomedical research. Organic probes exhibit high potential in clinical translation, due to advantages such as precise structure design, low toxicity, and post-modifications convenience. In related preparation, enhancement of NIR-II tail emission from NIR-I dyes is an efficient method. In particular, the promotion of twisted intramolecular charge transfer (TICT) of relevant NIR-I dyes is a convenient protocol. However, present TICT-type probes still show disadvantages in relatively low emission, large particle sizes, or limited choice of NIR-I dyes, etc. Herein, the synthesis of stable small-sized polymer NIR-II fluoroprobes (e.g., 7.2 nm), integrating TICT and Förster resonance energy transfer process to synergistically enhance the NIR-II emission is reported. Strong enhanced emissions can be obtained from various NIR-I dyes and lanthanide elements (e.g., twelvefold at 1250 nm from Nd-DTPA/IR-808 sample). The fluorophore provides high-resolution angiography, with high-contrast imaging on middle cerebral artery occlusion model mice for distinguishing occlusion. The fluorophore can be rapidly excreted from the kidney (urine ≈65% within 4 h) in normal mice and exhibits long-term renal retention on acute kidney injury mice, showing potential applications in the prognosis of kidney diseases. This development provides an effective strategy to design and synthesize effective NIR-II fluoroprobes.

Suture Bridge Technique with 5-Ethibond: A Promising Approach for Infrapatellar Pole Fracture Treatment.

Purpose: Infrapatellar pole fractures are challenging injuries that require appropriate treatment to ensure optimal functional outcomes. This study aimed to introduce the application of the Suture Bridge technique using the 5-Ethibond for the treatment of infrapatellar patella fracture. Methods: Five cases of infrapatellar pole fracture that were treated at our institution between February 2020 and September 2021. The patients included one male and four females, with an average age of 66 years (range: 60-77 years). All patients were treated with the Suture Bridge technique using the 5-Ethibond to preserve the infrapatellar pole. Results: The average operative time was 64 min (range: 50-80 min). The average blood loss during surgery was 51 mL (range: 40-60 mL). All cases demonstrated fracture healing at an average of 10 weeks (range 8-12) after surgery. The patients were followed up for an average period of 14.8 months (8-22). No wound infection or second displacement of fracture fragment was found. Full range of motion was restored in all patients within 12-14 weeks after surgery. None of the patients complained of anterior knee pain. Conclusions: Based on the findings of the study, it appears that the Suture Bridge technique using 5-Ethibond is a promising and viable option for the treatment of infrapatellar pole fractures.

Minimally Invasive Delivery of Percutaneous Ablation Agent via Magnetic Colloidal Hydrogel Injection for Treatment of Hepatocellular Carcinoma.

Percutaneous thermotherapy, a minimally invasive operational procedure, is employed in the ablation of deep tumor lesions by means of target-delivering heat. Conventional thermal ablation methods, such as radiofrequency or microwave ablation, to a certain extent, are subjected to extended ablation time as well as biosafety risks of unwanted overheating. Given its effectiveness and safety, percutaneous thermotherapy gains a fresh perspective, thanks to magnetic hyperthermia. In this respect, an injectable- and magnetic-hydrogel-construct-based thermal ablation agent is likely to be a candidate for the aforementioned clinical translation. Adopting a simple and environment-friendly strategy, a magnetic colloidal hydrogel injection is introduced by a binary system comprising super-paramagnetic Fe3O4 nanoparticles and gelatin nanoparticles. The colloidal hydrogel constructs, unlike conventional bulk hydrogel, can be easily extruded through a percutaneous needle and then self-heal in a reversible manner owing to the unique electrostatic cross-linking. The introduction of magnetic building blocks is exhibited with a rapid magnetothermal response to an alternating magnetic field. Such hydrogel injection is capable of generating heat without limitation of deep penetration. The materials achieve outstanding therapeutic results in mouse and rabbit models. These findings constitute a new class of locoregional interventional thermal therapies with minimal collateral damages.

Methylation changes of liver DNA during the formation of gallstones.

Aim: To explore the overall methylation changes in liver tissues during the formation of gallstones, as well as the key pathways and genes involved in the process. Methods: Reduced-representation bisulfite sequencing and RNA sequencing were conducted on the liver tissues of mice with gallstones and control normal mice. Results: A total of 8705 differentially methylated regions in CpG and 1410 differentially expressed genes were identified. The joint analysis indicated that aberrant DNA methylation may be associated with dysregulated gene expression in key pathways such as cholesterol metabolism and bile secretion. Conclusion: We propose for the first time that methylation changes in some key pathway genes in liver tissue may be involved in the formation of gallstones.

Rigid-flexible coupling network solid polymer electrolytes for all-solid-state lithium metal batteries.

Poor mechanical strength at working temperature and low ionic conductivity seriously hinder the application of poly(ethylene oxide) (PEO)-based solid polymer electrolytes (SPEs) in high performance all-solid-state lithium metal batteries (LMBs). Here, we design and prepare a series of rigid-flexible coupling network SPEs (RFN-SPEs) with soft poly(ethylene glycol) (PEG) chains and rigid crosslinkers containing the benzene structure. Compared with soft crosslinkers, rigid crosslinkers provide the same amount of active crosslinking points with smaller molecular weight, and meanwhile enhance the mechanical strength of the network. Therefore, based on the rigid crosslinkers, RFN-SPEs exhibit synchronously improved ionic conductivity and mechanical strength. With these RFN-SPEs, symmetrical cells can be cycled for over 2100 h at 0.5 mA cm-2. Meanwhile, stable cycling and high-rate capability could be achieved for LMBs, revealing that SPEs with the rigid-flexible coupling network are promising electrolyte systems for all-solid-state LMBs.