PGC-1α drives small cell neuroendocrine cancer progression towards an ASCL1-expressing subtype with increased mitochondrial capacity.

Adenocarcinomas from multiple tissues can converge to treatment-resistant small cell neuroendocrine (SCN) cancers comprised of ASCL1, POU2F3, NEUROD1, and YAP1 subtypes. We investigated how mitochondrial metabolism influences SCN cancer (SCNC) progression. Extensive bioinformatics analyses encompassing thousands of patient tumors and human cancer cell lines uncovered enhanced expression of PGC-1α, a potent regulator of mitochondrial oxidative phosphorylation (OXPHOS), across several SCNC types. PGC-1α correlated tightly with increased expression of the lineage marker ASCL1 through a positive feedback mechanism. Analyses using a human prostate tissue-based SCN transformation system showed that the ASCL1 subtype has heightened PGC-1α expression and OXPHOS activity. PGC-1α inhibition diminished OXPHOS, reduced SCNC cell proliferation, and blocked SCN prostate tumor formation. PGC-1α overexpression enhanced OXPHOS, tripled the SCN prostate tumor formation rate, and promoted commitment to the ASCL1 lineage. These findings reveal the metabolic heterogeneity among SCNC subtypes and identify PGC-1α-induced OXPHOS as a regulator of SCNC lineage plasticity.

The Impact of Nanomaterials on Photosynthesis and Antioxidant Mechanisms in Gramineae Plants: Research Progress and Future Prospects.

As global food security faces challenges, enhancing crop yield and stress resistance becomes imperative. This study comprehensively explores the impact of nanomaterials (NMs) on Gramineae plants, with a focus on the effects of various types of nanoparticles, such as iron-based, titanium-containing, zinc, and copper nanoparticles, on plant photosynthesis, chlorophyll content, and antioxidant enzyme activity. We found that the effects of nanoparticles largely depend on their chemical properties, particle size, concentration, and the species and developmental stage of the plant. Under appropriate conditions, specific NMs can promote the root development of Gramineae plants, enhance photosynthesis, and increase chlorophyll content. Notably, iron-based and titanium-containing nanoparticles show significant effects in promoting chlorophyll synthesis and plant growth. However, the impact of nanoparticles on oxidative stress is complex. Under certain conditions, nanoparticles can enhance plants' antioxidant enzyme activity, improving their ability to withstand environmental stresses; excessive or inappropriate NMs may cause oxidative stress, affecting plant growth and development. Copper nanoparticles, in particular, exhibit this dual nature, being beneficial at low concentrations but potentially harmful at high concentrations. This study provides a theoretical basis for the future development of nanofertilizers aimed at precisely targeting Gramineae plants to enhance their antioxidant stress capacity and improve photosynthesis efficiency. We emphasize the importance of balancing the agricultural advantages of nanotechnology with environmental safety in practical applications. Future research should focus on a deeper understanding of the interaction mechanisms between more NMs and plants and explore strategies to reduce potential environmental impacts to ensure the health and sustainability of the ecosystem while enhancing the yield and quality of Gramineae crops.

The LANCET robotic system can improve surgical efficiency in total hip arthroplasty: A prospective randomized, multicenter, parallel-controlled clinical trial.

Objective: To evaluate the accuracy and safety of the LANCET robotic system, a robot arm assisted operation system for total hip arthroplasty via a multicenter clinical randomized controlled trial. Methods: A total of 116 patients were randomized into two groups: LANCET robotic arm assisted THA group (N = 58) and the conventional THA group (N = 58). General information about the patients was collected preoperatively. Operational time and bleeding were recorded during the surgery. The position of the acetabular prosthesis was evaluated by radiographs one week after surgery and compared with preoperative planning. Harris score, hip mobility, prosthesis position and angle and complications were compared between the two groups at three months postoperatively. Results: None of the 111 patients who ultimately completed the 3-month follow-up experienced adverse events such as hip dislocation and infection during follow-up. In the RAA group, 52 (92.9 %) patients were located in the Lewinnek safe zone and 49 (87.5 %) patients were located in the Callanan safe zone. In the control group were 47 (85.5 %) and 44 (80.0 %) patients, respectively. In the RAA group, 53 (94.6 %) patients had a postoperative acetabular inclination angle and 51 (91.1 %) patients had an acetabular version angle within a deviation of 5° from the preoperative plan. These numbers were significantly higher than those of the control group, which consisted of 42 (76.4 %) and 34 (61.8 %) patients respectively. There were no significant differences between the two groups of subjects in terms of general condition, intraoperative bleeding, hip mobility, and adverse complications. Conclusion: The results of this prospective randomized, multicenter, parallel-controlled clinical study demonstrated that the LANCET robotic system leads conventional THA surgery in accuracy of acetabular cup placement and does not differ from conventional THA surgery in terms of postoperative hip functional recovery and complications. The translational potential of this article: In the past, the success rate of total hip arthroplasty (THA) relied heavily on the surgeon's experience. As a result, junior doctors needed extensive training to become proficient in this technique. However, the introduction of surgical robots has significantly improved this situation. By utilizing robotic assistance, both junior and senior doctors can perform THA quickly and efficiently. This advancement is crucial for the widespread adoption of THA, as patients can now receive surgical treatment in local facilities instead of overwhelming larger hospitals and straining medical resources. Moreover, the development of surgical robots with fully independent intellectual property rights holds immense value in overcoming the limitations of high-end medical equipment. This aligns with the objectives outlined in the 14th Five Year Plan for National Science and Technology Strategy.

Structural and mechanistic investigations on CC bond forming α-oxoamine synthase allowing L-glutamate as substrate.

Carbon­carbon bonds serve as the fundamental structural backbone of organic molecules. As a critical CC bond forming enzyme, α-oxoamine synthase is responsible for the synthesis of α-amino ketones by performing the condensation reaction between amino acids and acyl-CoAs. We previously identified an α-oxoamine synthase, named as Alb29, involved in albogrisin biosynthesis in Streptomyces albogriseolus MGR072. This enzyme belongs to the α-oxoamine synthase (AOS) family, a subfamily under the pyridoxal 5'-phosphate (PLP) dependent enzyme superfamily. In this study, we report the crystal structures of Alb29 bound to the substrates PLP and L-Glu, which provide the atomic-level structural insights into the substrate recognition by Alb29. We discover that Alb29 can catalyze the amino transformation from L-Gln to L-Glu, besides the condensation of L-Glu with ß-methylcrotonyl coenzyme A. Subsequent structural analysis has revealed that one flexible loop in Alb29 plays an important role in both amino transformation and condensation. Based on the crystal structure of the S87G mutant in the loop region, we capture two distinct conformations of the flexible loop in the active site, compared with the wild-type Alb29. Our study offers valuable insights into the catalytic mechanism underlying substrate recognition of Alb29.

Redox homeostasis in cardiac fibrosis: Focus on metal ion metabolism.

Cardiac fibrosis is a major public health problem worldwide, with high morbidity and mortality, affecting almost all patients with heart disease worldwide. It is characterized by fibroblast activation, abnormal proliferation, excessive deposition, and abnormal distribution of extracellular matrix (ECM) proteins. The maladaptive process of cardiac fibrosis is complex and often involves multiple mechanisms. With the increasing research on cardiac fibrosis, redox has been recognized as an important part of cardiac remodeling, and an imbalance in redox homeostasis can adversely affect the function and structure of the heart. The metabolism of metal ions is essential for life, and abnormal metabolism of metal ions in cells can impair a variety of biochemical processes, especially redox. However, current research on metal ion metabolism is still very limited. This review comprehensively examines the effects of metal ion (iron, copper, calcium, and zinc) metabolism-mediated redox homeostasis on cardiac fibrosis, outlines possible therapeutic interventions, and addresses ongoing challenges in this rapidly evolving field.

A multifunctional biomimetic nanoplatform for image-guideded photothermal-ferroptotic synergistic osteosarcoma therapy.

Much effort has been devoted to improving treatment efficiency for osteosarcoma (OS). However, most current approaches result in poor therapeutic responses, thus indicating the need for the development of other therapeutic options. This study developed a multifunctional nanoparticle, PDA-MOF-E-M, an aggregation of OS targeting, programmed death targeting, and near-infrared (NIR)-aided targeting. At the same time, a multifunctional nanoparticle that utilises Fe-MOFs to create a cellular iron-rich environment and erastin as a ferroptosis inducer while ensuring targeted delivery to OS cells through cell membrane encapsulation is presented. The combination of PDA-MOF-E-M and PTT increased intracellular ROS and LPO levels and induced ferroptosis-related protein expression. A PDA-based PTT combined with erastin showed significant synergistic therapeutic improvement in the anti-tumour efficiency of the nanoparticle in vitro and vivo. The multifunctional nanoparticle efficiently prevents the osteoclasia progression of OS xenograft bone tumors in vivo. Finally, this study provides guidance and a point of reference for clinical approaches to treating OS.

Comprehensive Utilization Technology of Aronia melanocarpa.

Aronia melanocarpa fruit contains a variety of active ingredients, such as phenolic acids, anthocyanins, proanthocyanidins, etc. Relevant in vivo and in vitro studies have concluded that it has beneficial effects in terms of treating dyslipidemia, hypertension, glucose metabolism disorders, etc. This article discusses the nutritional value and food processing of Aronia melanocarpa and reviews the chemical components of Aronia melanocarpa and the pharmacological activities of related substances in order to summarize the chemical characteristics of the fruit and its development prospects. The process optimization of juice production, the impact of antioxidant capacity, and the comprehensive utilization of pomace in feed are discussed. This article provides a reference for future comprehensive application research and product development of Aronia melanocarpa.

Intensive Treatment of Organic Wastewater by Three-Dimensional Electrode System within Mn-Loaded Steel Slag as Catalytic Particle Electrodes.

Developing a green, low-carbon, and circular economic system is the key to achieving carbon neutrality. This study investigated the organics removal efficiency in a three-dimensional electrode reactor (3DER) constructed from repurposed industrial solid waste, i.e., Mn-loaded steel slag, as the catalytic particle electrodes (CPE). The CPE, a micron-grade material consisting primarily of transition metals, including Fe and Mn, exhibited excellent electric conductivity, catalytic ability, and recyclability. High rhodamine B (RhB) removal efficiency in the 3DER was observed through a physical modelling experiment. The optimal operating condition was determined through a single-factor experiment in which 5.0 g·L-1 CPE and 3 mM peroxymonosulfate (PMS) were added to a 200 mL solution of 10 mM RhB under a current intensity of 0.5 A and a 1.5 to 2.0 cm distance between the 2D electrodes. When the initial pH value of the simulated solution was 3 to 9, the RhB removal rate exceeded 96% after 20 min reaction. In addition, the main reactive oxidation species in the 3DER were determined. The results illustrated that HO• and SO4•- both existed, but that the contribution of SO4•- to RhB removal was much lower than that of HO• in the 3DER. In summary, this research provides information on the potential of the 3DER for removing refractory organics from water.

Miniaturized and untethered McKibben muscles based on photothermal-induced gas-liquid transformation.

Pneumatic artificial muscles can move continuously under the power support of air pumps, and their flexibility also provides the possibility for applications in complex environments. However, in order to achieve operation in confined spaces, the miniaturization of artificial muscles becomes crucial. Since external attachment devices greatly hinder the miniaturization and use of artificial muscles, we propose a light-driven approach to get rid of these limitations. In this study, we report a miniaturized fiber-reinforced artificial muscle based on mold editing, capable of bending and axial elongation using gas-liquid conversion in visible light. The minimum volume of the artificial muscle prepared using this method was 15.7 mm3 (d = 2 mm, l = 5 mm), which was smaller than those of other fiber-reinforced pneumatic actuators. This research can promote the development of non-tethered pneumatic actuators for rescue and exploration, and create the possibility of miniaturization of actuators.

Secondary Organic Aerosol Formation Potential from Vehicular Non-tailpipe Emissions under Real-World Driving Conditions.

Traffic emissions are a dominant source of secondary organic aerosol (SOA) in urban environments. Though tailpipe exhaust has drawn extensive attention, the impact of non-tailpipe emissions on atmospheric SOA has not been well studied. Here, a closure study was performed combining urban tunnel experiments and dynamometer tests using an oxidation flow reactor in situ photo-oxidation. Results show a significant gap between field and laboratory research; the average SOA formation potential from real-world fleet is 639 ± 156 mg kg fuel-1, higher than the reconstructed result (188 mg kg fuel-1) based on dynamometer tests coupled with fleet composition inside the tunnel. Considering the minimal variation of SOA/CO in emission standards, we also reconstruct CO and find the critical role of high-emitting events in the real-world SOA burden. Different profiles of organic gases are detected inside the tunnel than tailpipe exhaust, such as more abundant C6-C9 aromatics, C11-C16 species, and benzothiazoles, denoting contributions from non-tailpipe emissions to SOA formation. Using these surrogate chemical compounds, we roughly estimate that high-emitting, evaporative emission, and asphalt-related and tire sublimation share 14, 20, and 10% of the SOA budget, respectively, partially explaining the gap between field and laboratory research. These experimental results highlight the importance of non-tailpipe emissions to atmospheric SOA.

In-situ registration subtraction image segmentation algorithm for spatiotemporal visualization of copper adsorption onto corn stalk-derived pellet biochar by micro-computed tomography.

The non-homogeneous structure and high-density ash composition of biochar matrix pose significant challenges in characterizing the dynamic changes of heavy metal adsorption onto biochar with micro-computed tomography (Micro-CT). A novel in-situ registration subtraction image segmentation method (IRS) was developed to enhance micro-CT characterization accuracy. The kinetics of Cu(II) adsorption onto pellet biochar derived from corn stalks were tested. Respectively, the IRS and traditional K-means algorithms were used for image segmentation to the in-situ three-dimensional (3D) visual characterization of the Cu(II) adsorption onto biochar. The results indicated that the IRS algorithm reduced interference from high-density biochar composition, and thus achieved more precise results (R2 = 0.95) than that of K-means (R2 = 0.72). The visualized dynamic migration of Cu(II) from surface adsorption to intraparticle diffusion reflexed the complex mechanism of heavy metal adsorption. The developed Micro-CT method with high generalizability has great potential for studying the process and mechanism of biochar heavy metal adsorption.

Atlantoaxial rotatory subluxation following surgical treatment of a cervical teratoma in a child: a case report.

Atlantoaxial rotatory subluxation (AARS), which is characterised by an abnormal alignment of the atlantoaxial joint, is rarely reported after oral and maxillofacial surgery. A four-year-old girl developed AARS after neck surgery. The child initially had treatment for one month in a timely manner. Follow ups revealed reduced symptoms of neck pain and the previous tilt disappeared after serial treatment. This case aimed to increase awareness of AARS and provide a reference for oral and maxillofacialsurgeons.

OsCSN2 orchestrates Oryza sativa L. growth and development through modulation of the GA and BR pathways.

The COP9 signalosome (CSN) is a conserved protein complex found in higher eukaryotes, consisting of eight subunits, and it plays a crucial role in regulating various processes of plant growth and development. Among these subunits, CSN2 is one of the most conserved components within the COP9 signalosome complex. Despite its prior identification in other species, its specific function in Oryza sativa L. (Rice) has remained poorly understood. In this study, we investigated the role of CSN2 in rice using gene editing CRISPR/Cas9 technology and overexpression techniques. We created two types of mutants: the oscsn2 mutant and the OsCSN2-OE mutant, both in the background of rice, and also generated point mutants of OsCSN2 (OsCSN2K64E, OsCSN2K67E, OsCSN2K71E and OsCSN2K104E) to further explore the regulatory function of OsCSN2. Phenotypic observation and gene expression analysis were conducted on plants from the generated mutants, tracking their growth from the seedling to the heading stages. The results showed that the loss and modification of OsCSN2 had limited effects on plant growth and development during the early stages of both the wild-type and mutant plants. However, as the plants grew to 60 days, significant differences emerged. The OsCSN2 point mutants exhibited increased tillering compared to the OsCSN2-OE mutant plants, which were already at the tillering stage. On the other hand, the OsCSN2 point mutant had already progressed to the heading and flowering stages, with the shorter plants. These results, along with functional predictions of the OsCSN2 protein, indicated that changes in the 64th, 67th, 71st, and 104th amino acids of OsCSN2 affected its ubiquitination site, influencing the ubiquitination function of CSN and consequently impacting the degradation of the DELLA protein SLR1. Taken together, it can be speculated that OsCSN2 plays a key role in GA and BR pathways by influencing the functional regulation of the transcription factor SLR1 in CSN, thereby affecting the growth and development of rice and the number of tillers.

Photon-level single-pixel 3D tomography with masked attention network.

Tomography plays an important role in characterizing the three-dimensional structure of samples within specialized scenarios. In the paper, a masked attention network is presented to eliminate interference from different layers of the sample, substantially enhancing the resolution for photon-level single-pixel tomographic imaging. The simulation and experimental results have demonstrated that the axial resolution and lateral resolution of the imaging system can be improved by about 3 and 2 times respectively, with a sampling rate of 3.0 %. The scheme is expected to be seamlessly integrated into various tomography systems, which is conducive to promoting the tomographic imaging for biology, medicine, and materials science.

GCclassifier: An R package for the prediction of molecular subtypes of gastric cancer.

Gastric cancer (GC) is one of the most commonly diagnosed malignancies, threatening millions of lives worldwide each year. Importantly, GC is a heterogeneous disease, posing a significant challenge to the selection of patients for more optimized therapy. Over the last decades, extensive community effort has been spent on dissecting the heterogeneity of GC, leading to the identification of distinct molecular subtypes that are clinically relevant. However, so far, no tool is publicly available for GC subtype prediction, hindering the research into GC subtype-specific biological mechanisms, the design of novel targeted agents, and potential clinical applications. To address the unmet need, we developed an R package GCclassifier for predicting GC molecular subtypes based on gene expression profiles. To facilitate the use by non-bioinformaticians, we also provide an interactive, user-friendly web server implementing the major functionalities of GCclassifier. The predictive performance of GCclassifier was demonstrated using case studies on multiple independent datasets.

Decoding silkworm spinning programmed by pH and metal ions.

Silk is one of the toughest fibrous materials known despite spun at ambient temperature and pressure with water as a solvent. It is a great challenge to reproduce high-performance artificial fibers comparable to natural silk by bionic for the incomplete understanding of silkworm spinning in vivo. Here, we found that amphipol and digitonin stabilized the structure of natural silk fibroin (NSF) by a large-scale screening in vitro, and then studied the close-to-native ultrastructure and hierarchical assembly of NSF in the silk gland lumen. Our study showed that NSF formed reversible flexible nanofibrils mainly composed of random coils with a sedimentation coefficient of 5.8 S and a diameter of about 4 nm, rather than a micellar or rod-like structure assembled by the aggregation of globular NSF molecules. Metal ions were required for NSF nanofibril formation. The successive pH decrease from posterior silk gland (PSG) to anterior silk gland (ASG) resulted in a gradual increase in NSF hydrophobicity, thus inducing the sol-gelation transition of NSF nanofibrils. NSF nanofibrils were randomly dispersed from PSG to ASG-1, and self-assembled into anisotropic herringbone patterns at ASG-2 near the spinneret ready for silkworm spinning. Our findings reveal the controlled self-assembly mechanism of the multi-scale hierarchical architecture of NSF from nanofibrils to herringbone patterns programmed by metal ions and pH gradient, which provides novel insights into the spinning mechanism of silk-secreting animals and bioinspired design of high-performance fibers.

Two-stream vision transformer based multi-label recognition for TCM prescriptions construction.

Traditional Chinese medicine (TCM) observation diagnosis images (including facial and tongue images) provide essential human body information, holding significant importance in clinical medicine for diagnosis and treatment. TCM prescriptions, known for their simplicity, non-invasiveness, and low side effects, have been widely applied worldwide. Exploring automated herbal prescription construction based on visual diagnosis holds vital value in delving into the correlation between external features and herbal prescriptions and offering medical services in mobile healthcare systems. To effectively integrate multi-perspective visual diagnosis images and automate prescription construction, this study proposes a multi-herb recommendation framework based on Visual Transformer and multi-label classification. The framework comprises three key components: image encoder, label embedding module, and cross-modal fusion classification module. The image encoder employs a dual-stream Visual Transformer to learn dependencies between different regions of input images, capturing both local and global features. The label embedding module utilizes Graph Convolutional Networks to capture associations between diverse herbal labels. Finally, two Multi-Modal Factorized Bilinear modules are introduced as effective components to fuse cross-modal vectors, creating an end-to-end multi-label image-herb recommendation model. Through experimentation with real facial and tongue images and generating prescription data closely resembling real samples. The precision is 50.06 %, the recall rate is 48.33 %, and the F1-score is 49.18 %. This study validates the feasibility of automated herbal prescription construction from the perspective of visual diagnosis. Simultaneously, it provides valuable insights for constructing herbal prescriptions automatically from more physical information.

The neutrophil percentage-to-albumin ratio is an independent risk factor for poor prognosis in peritoneal dialysis patients.

AIM: This study aimed to investigate the predictive ability of the neutrophil percentage-to-albumin Ratio (NPAR) concerning all-cause mortality and cardio-cerebrovascular mortality in patients undergoing peritoneal dialysis (PD). METHODS: We included a total of 807 PD patients from the Peritoneal Dialysis Center of the Second Affiliated Hospital of Soochow University between January 2009 and December 2019 in this study. Patients were categorized into three groups based on their baseline NPAR. The Kaplan-Meier method, multivariate Cox proportional hazard model, and Fine-Gray competing risk model were employed to examine the relationship between NPAR level and all-cause mortality and cardio-cerebrovascular mortality among PD patients. Furthermore, the ROC curve and calibration plots were utilized to compare the performance between NPAR and other conventional indicators. RESULTS: The mean follow-up period was 38.2 months. A total of 243 (30.1%) patients passed away, with 128 (52.7%) succumbing to cardio-cerebrovascular diseases. The mortality rates of the Middle and High NPAR groups were significantly greater than that of the Low NPAR group (p < 0.001), and NPAR was independently associated with all-cause mortality and cardio-cerebrovascular mortality. Receiver Operating Characteristic (ROC) analysis indicated that the Area Under the Curve (AUC) of NPAR (0.714) was significantly superior to those of C-reactive protein (CRP) (0.597), neutrophil to lymphocyte ratio (NLR) (0.589), C-reactive protein to albumin ratio (CAR) (0.698) and platelet to lymphocyte ratio (PLR) (0.533). CONCLUSION: NPAR served as an independent predictive marker for all-cause mortality and cardio-cerebrovascular mortality in PD patients. Moreover, NPAR demonstrated superior predictive potential compared to CRP, CAR, NLR, and PLR.

Personalized differential expression analysis in triple-negative breast cancer.

Identification of individual-level differentially expressed genes (DEGs) is a pre-step for the analysis of disease-specific biological mechanisms and precision medicine. Previous algorithms cannot balance accuracy and sufficient statistical power. Herein, RankCompV2, designed for identifying population-level DEGs based on relative expression orderings, was adjusted to identify individual-level DEGs. Furthermore, an optimized version of individual-level RankCompV2, named as RankCompV2.1, was designed based on the assumption that the rank positions of genes and relative rank differences of gene pairs would influence the identification of individual-level DEGs. In comparison to other individualized analysis algorithms, RankCompV2.1 performed better on statistical power, computational efficiency, and acquired coequal accuracy in both simulation and real paired cancer-normal data from ten cancer types. Besides, single sample GSEA and Gene Set Variation Analysis analysis showed that pathways enriched with up-regulated and down-regulated genes presented higher and lower enrichment scores, respectively. Furthermore, we identified 16 genes that were universally deregulated in 966 triple-negative breast cancer (TNBC) samples and interacted with Food and Drug Administration (FDA)-approved drugs or antineoplastic agents, indicating notable therapeutic targets for TNBC. In addition, we also identified genes with highly variable deregulation status and used these genes to cluster TNBC samples into three subgroups with different prognoses. The subgroup with the poorest outcome was characterized by down-regulated immune-regulated pathways, signal transduction pathways, and apoptosis-related pathways. Protein-protein interaction network analysis revealed that OAS family genes may be promising drug targets to activate tumor immunity in this subgroup. In conclusion, RankCompV2.1 is capable of identifying individual-level DEGs with high accuracy and statistical power, analyzing mechanisms of carcinogenesis and exploring therapeutic strategy.