Short-Term Wind Power Interval Forecasting Based on Hybrid Modal Decomposition and Improved Optimization.

Accurate wind power prediction can effectively alleviate the pressure of the power system peak frequency regulation, and is more conducive to the economic dispatch of the power system. To enhance wind power forecasting accuracy, a hybrid approach for wind power interval prediction is proposes in this study. Firstly, an Improved Complete Ensemble Empirical Mode Decomposition with Adaptive Noise (ICEEMDAN) is applied to decompose the initial wind power sequence into multiple modes, and Variational Mode Decomposition is used to further decompose the high-frequency non-stationary components. Next, Fuzzy Entropy (FE) is utilized to assess the complexity of the post-decomposed Intrinsic Mode Functions (IMFs), and different forecasting methods are employed accordingly, the point predictions were obtained by linearly summing the component predictions.Additionally, an improved sparrow search algorithm (ISSA) is used to seek the optimal hyperparameters of the prediction algorithm. Finally, the prediction intervals are constructed using the point prediction results based on kernel density estimation (KDE). The root mean square errors (RMSE) of deterministic predictions are 2.8458 MW and 1.8605 MW, with uncertainty coverage rates of 95.83% and 97.92% at a 95% confidence level.

Stability, Inheritance, Cross-Resistance, and Fitness Cost of Resistance to λ-Cyhalothrin in Cydia pomonella.

Insecticides are commonly utilized in agriculture and forestry for pest control, but their dispersal can pose hazards to humans and environment. Understanding resistance, inheritance patterns, and fitness costs can help manage resistance. A λ-cyhalothrin-resistant population (LCR) of Cydia pomonella, a global pest of pome fruits and walnuts, was obtained through selective insecticide breeding for 15 generations, showing stable moderate resistance (23.85-fold). This population was cross-resistant to deltamethrin (4.26-fold) but not to ß-cypermethrin, chlorantraniliprole, chlorpyrifos, and avermectin. Genetic analysis revealed the resistance was autosomal, incompletely dominant, and controlled by multiple genes. Increased activity of glutathione S-transferases and cytochrome P450 monooxygenases (P450s) played a primary role in resistance, with specific genes up-regulated in LCR, and exhibited significant expression in midgut. LCR also exhibited fitness costs, including delays in development, reduced fecundity, and slower population growth. These findings contribute to understanding λ-cyhalothrin resistance in C. pomonella and can guide resistance management strategies.

New insights into the enteric methane production based on the archaeal genome atlas of ruminant gastrointestinal tract.

INTRODUCTION: As one of the important components of ruminant gastrointestinal tract (GIT) microbiome, archaea are involved in many biological processes, especially methanogenesis. In spite of being a well-recognised member of the mammalian gut microbiome, it remains poorly characterized, partly due to the lack of a unified reference genome catalog. OBJECTIVES: This study aimed to construct a unified genome atlas that captures the wider diversity in archaea and is thus more appropriate for functional and taxonomic exploration of ruminant GIT archaea. METHODS: We collected archaeal genomes from public sources and new data of this study. We performed phylogenetic and functional genomics analysis, prophage identification based on the genomes. Using collected genomes as a reference, we conducted metagenomic and metatranscriptomic analysis on rumen fluid samples from 18 dairy cows, and investigated the correlation between rumen archaeal communities and methane (CH4) production profiles. RESULTS: We constructed the ruminant GIT archaeal genomes (RGAG) by compiling 405 strain-level (160 species) non-redundant archaeal genomes from more than 10 ruminant species. Investigating the functional heterogeneity and methanogenic structure within RGAG revealed that it possessed 1,124 (99.5%) unknown microbial biosynthetic gene clusters. A survey of RGAG-borne prophages identified 63 prophages with 122 host-beneficial genes and 18 auxiliary metabolic genes. The pipeline for both metagenomics and metatranscriptomics generated in the study revealed the roles of archaeal genomes under-assessed in general multi-omics analysis. The highly expressed genus Methanosphaera was negatively correlated with CH4 production at the RNA level. CONCLUSION: A unified genome atlas of ruminant GIT archaea is constructed in the study. Our analyses revealed the advantages of metatranscriptomics over metagenomics in studying rumen archaeal communities and further demonstrated that the multifaceted functions of ruminant archaea remain undiscovered. Differences in rumen archaeal community structure among cattle with different CH4 production profiles may reflect the balance between rumen hydrogen production and methanogenesis. Our work provides a new resource for interrogating archaeal functions in the ruminant GIT and potential targets for future CH4 reduction.

Increased matrix stiffness in pituitary neuroendocrine tumors invading the cavernous sinus is activated by TAFs: focus on the mechanical signatures.

PURPOSE: Pituitary neuroendocrine tumors (PitNETs) with invasion of the cavernous sinus (CS) are particularly challenging to treat. Tumor associated fibroblasts (TAFs) are recognized for their pivotal role in reprogramming extracellular matrix (ECM). Herein, we aimed to explore the potential involvement of TAFs in ECM reprogramming and elucidate the underlying mechanism involved. METHODS: We applied dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to measure tumor vessel permeability and applied atomic force microscopy (AFM) to measure the matrix stiffness of PitNETs located in both CS and sella turcica (ST). Western blotting, immunofluorescence, immunohistochemistry, and quantitative RT-PCR were utilized to analyze the ECM components. Proteomic biochemical analysis was utilized to uncover potential mechanisms governing ECM dynamics. RESULTS: We found that PitNETs in the CS were stiffer than those in the ST. Increased ECM stiffness within the CS facilitated the acquisition of stem-like properties, enhanced proliferation, and induced epithelial-to-mesenchymal transition (EMT) of GH3 cells. Furthermore, the expression levels of lysyl oxidase (LOX), matrix metallopeptidase 2 (MMP2) and MMP9 in pituitary adenoma cells increased in the stiffer matrix. Proteomic analysis suggested TAFs were activated in the CS area and contributed enhanced matrix stiffness by secreting Col-1 and Col-3. Furthermore, mTOR pathway was activated under higher matrix stiffness and the migration and invasion of GH3 cells be repressed by mTOR inhibitor. CONCLUSION: These findings demonstrated that activated TAFs contributed to stiffer matrix and increased ECM stiffness stimulating mTOR pathway in pituitary tumor cells. Our study indicated that mTOR inhibitor was a promising treatment strategy from the standpoint of PitNET biomechanical properties.

SKAP1 Expression in Cancer Cells Enhances Colon Tumor Growth and Impairs Cytotoxic Immunity by Promoting Neutrophil Extracellular Trap Formation via the NFATc1/CXCL8 Axis.

The mechanisms underlying the development and progression of colon cancer are not fully understood. Herein, Src kinase associated phosphoprotein 1 (SKAP1), an immune cell adaptor, is identified as a novel colon cancer-related gene. SKAP1 expression is significantly increased in colon cancer cells. High SKAP1 levels are independently predictive of poor survival in patients with colon cancer. Notably, SKAP1 expression in colon cancer cells exerted a significant tumor-promoting effect in vivo rather than in vitro. Screening of tumor-infiltrating immune cells revealed the involvement of neutrophils in SKAP1-induced colon tumor promotion. Enhanced formation of neutrophil extracellular traps (NETs) is found to be a key downstream event that contributed to the pro-tumor role of SKAP1. In colon cancer cells, SKAP1 increased the expression of C-X-C motif chemokine ligand 8 (CXCL8) via nuclear factor of activated T cells c1 (NFATc1). The blockade of CXCL8 or NFATc1 largely attenuated neutrophil infiltration, NET formation, and tumor promotion induced by SKAP1. Furthermore, inhibiting SKAP1-induced NET significantly enhanced the antitumor efficiency of adoptive natural killer cell therapy in colon tumor models. In conclusion, SKAP1 significantly promotes colon cancer growth via the cancer cell/neutrophil NFATc1/CXCL8/NET axis, suggesting that SKAP1 is a potential target for colon cancer therapy.

Acoustic black hole ultrasonic scalpel.

Ultrasonic scalpels (USs), as the preferred energy instruments, are facing a growing need to exhibit enhanced performance with the diversification of modern surgical challenges. Hence, we proposed an acoustic black hole ultrasonic scalpel (ABHUS) in longitudinal-bending coupled vibration for efficient surgical cutting. By incorporating an acoustic black hole profile, the local bending wave velocity is reduced and the amplitude is amplified cumulatively, thus creating a high-energy region near the blade tip to enhance the cutting performance of the ABHUS. The precise physical analysis model is established for systematic design of the ABHUS and quick estimation of its frequency characteristics. The vibration simulation and experiments demonstrate that compared with the conventional ultrasonic scalpel (CUS), the output amplitude of the ABHUS significantly increases, particularly a 425% increase in bending vibration displacement. The in-vitro cutting experiment confirms that ABHUS exhibits superior cutting performance. Our design presents vast possibilities and potential for the development of high-performance ultrasonic surgical instruments, serving as an innovative supplement with extraordinary significance for application of acoustic black holes.

Step-by-Step Description of Percutaneous Full-Endoscopic C2 Ganglionectomy: An Anatomic Feasibility Study in Human Cadavers.

BACKGROUND AND OBJECTIVES: The percutaneous full-endoscopic C2 ganglionectomy (PEC2G), an innovative procedure developed for the surgical treatment of intractable occipital neuralgia, was firstly reported by us in 2021. However, a universally accepted and well-articulated protocol modality remains elusive. The primary objective of this anatomic investigation was to meticulously elucidate the standard procedural steps of PEC2G and assess the anatomic features supporting the safe implementation of PEC2G. METHODS: Eighteen fresh adult cadavers were incorporated into this study. From this sample, 3 cadavers were subjected to bilateral PEC2G. Each procedure was documented and assessed, leading to the formulation of standard procedure criteria for PEC2G. Subsequently, 10 sets of anatomic parameters pertinent to this procedure were identified, quantified, and analyzed in 15 cadavers after complete bilateral endoscopic exposure of the C2 ganglion. An assessment of the technical feasibility and potential constraints associated with PEC2G was conducted, providing invaluable insights into the procedure's anatomic considerations. RESULTS: All 3 cadavers successfully underwent the PEC2G without any observed complications, such as dura tears or vertebral artery injuries. The C2 inferior articular process emerged as the optimal bony target for puncture, with the C2 pedicle serving as the standard guiding landmark en route to the C2 ganglion. In the 15 cadavers subjected to the planned procedure, 10 sets of anatomic parameters were quantified, establishing a foundational understanding of the anatomy in the context of PEC2G procedure. The results demonstrated that the characteristic of anatomic data pertinent to surgical site supported the safe implementation of PEC2G. CONCLUSION: This study contributes the standard surgical steps and crucial anatomic parameters relevant to PEC2G. The characteristic of anatomic data bolsters the safety credentials of this technique, which offers a reliable approach to achieve C2 ganglionectomy. These insights undeniably establish a robust foundation for the ongoing refinement and broader adoption of PEC2G.

Percutaneous Endoscope-assisted Visualized Implantation of Puncture Cylindrical Electrodes for Spinal Cord Stimulation: A Cadaveric Feasibility Study.

BACKGROUND: Spinal cord stimulation is an established technique wherein diverse electrode types are strategically implanted within the spinal epidural space for neuromodulation. Traditional percutaneous puncture cylindrical electrodes (PEs) are predominantly implanted by interventionalists utilizing a percutaneous technique under the monitor of radiation, which is a nonvisualized procedure. OBJECTIVE: Our study aimed to assess the feasibility of percutaneous endoscope-assisted visualized implantation approach for PEs, delineating its specific merits and demerits compared to the traditional method. STUDY DESIGN: Laboratory study with Institutional Review Board Number B2023-056SETTING: Clinical Anatomy Research Center, Fudan University. METHODS: Eight freshly procured adult cadavers (4 women and 4 men) were operated on in this study. They were divided into either Group A or Group B, each encompassing 4 cadavers. Group A was subjected to endoscope-assisted PEs implantation, whereas Group B followed the conventional PEs implantation route.In both groups the operative time of introducer needles placement (OTNP), total operative time (TOT), fluoroscopy time of introducer needles placement (FTNP), and total fluoroscopy time (TFT) were documented and analyzed. Furthermore, the precise positioning of the PEs and any ensuing complications were systematically examined. RESULTS: Both Group A and Group B successfully executed all predetermined surgical steps. A total of 16 PEs were implanted (dual electrodes in each cadaver): 8 using the percutaneous endoscope-assisted visualized approach (Group A) and 8 via the traditional methodology (Group B). Group A's mean ± SD durations for OTNP, TOT, FTNP, and TFT were 10.25 ± 1.03 minutes, 31.63 ± 5.87 minutes, 4.58 ± 1.35 seconds, and 43.73 ± 14.46 seconds, respectively. In contrast, Group B exhibited mean ± SD times of 11.55 ± 2.81 minutes, 44.75 ± 7.85 minutes, 23.53 ± 4.16 seconds, and 66.30 ± 6.35 seconds for the same metrics. No discernible statistical difference in OTNP and TOT emerged between the groups. However, Group A demonstrated reduced durations for both FTNP and TFT compared to Group B. The optimal position of the PEs was verified via fluoroscopy, with no recorded instances of dura rupture. These outcomes suggest that this endoscope-assisted technique neither increases surgical time nor compromises efficacy. Instead, it leads to a marked reduction in fluoroscopic duration relative to the traditional methodology. LIMITATIONS: Anatomical study on a human cadaver, the quantity of cadavers, and the procedure's steep learning curve. CONCLUSION: With the assistance of percutaneous spinal endoscopy, introducer needles can be punctured through the ligamentum flavum at the anticipated interlaminar window locus under direct visualization, improving the convenience of the puncture and reducing fluoroscopic exposure. It is a viable alternative for surgeons from diverse training backgrounds to implant PEs, particularly benefiting those well-versed in endoscopic spine surgery techniques.

Physics-Informed Online Learning for Temperature Prediction in Metal AM.

In metal additive manufacturing (AM), precise temperature field prediction is crucial for process monitoring, automation, control, and optimization. Traditional methods, primarily offline and data-driven, struggle with adapting to real-time changes and new process scenarios, which limits their applicability for effective AM process control. To address these challenges, this paper introduces the first physics-informed (PI) online learning framework specifically designed for temperature prediction in metal AM. Utilizing a physics-informed neural network (PINN), this framework integrates a neural network architecture with physics-informed inputs and loss functions. Pretrained on a known process to establish a baseline, the PINN transitions to an online learning phase, dynamically updating its weights in response to new, unseen data. This adaptation allows the model to continuously refine its predictions in real-time. By integrating physics-informed components, the PINN leverages prior knowledge about the manufacturing processes, enabling rapid adjustments to process parameters, geometries, deposition patterns, and materials. Empirical results confirm the robust performance of this PI online learning framework in accurately predicting temperature fields for unseen processes across various conditions. It notably surpasses traditional data-driven models, especially in critical areas like the Heat Affected Zone (HAZ) and melt pool. The PINN's use of physical laws and prior knowledge not only provides a significant advantage over conventional models but also ensures more accurate predictions under diverse conditions. Furthermore, our analysis of key hyperparameters-the learning rate and batch size of the online learning phase-highlights their roles in optimizing the learning process and enhancing the framework's overall effectiveness. This approach demonstrates significant potential to improve the online control and optimization of metal AM processes.

Batch-to-Batch Variation in Laser-Inscribed Graphene (LIG) Electrodes for Electrochemical Sensing.

Laser-inscribed graphene (LIG) is an emerging material for micro-electronic applications and is being used to develop supercapacitors, soft actuators, triboelectric generators, and sensors. The fabrication technique is simple, yet the batch-to-batch variation of LIG quality is not well documented in the literature. In this study, we conduct experiments to characterize batch-to-batch variation in the manufacturing of LIG electrodes for applications in electrochemical sensing. Numerous batches of 36 LIG electrodes were synthesized using a CO2 laser system on polyimide film. The LIG material was characterized using goniometry, stereomicroscopy, open circuit potentiometry, and cyclic voltammetry. Hydrophobicity and electrochemical screening (cyclic voltammetry) indicate that LIG electrode batch-to-batch variation is less than 5% when using a commercial reference and counter electrode. Metallization of LIG led to a significant increase in peak current and specific capacitance (area between anodic/cathodic curve). However, batch-to-batch variation increased to approximately 30%. Two different platinum electrodeposition techniques were studied, including galvanostatic and frequency-modulated electrodeposition. The study shows that formation of metallized LIG electrodes with high specific capacitance and peak current may come at the expense of high batch variability. This design tradeoff has not been discussed in the literature and is an important consideration if scaling sensor designs for mass use is desired. This study provides important insight into the variation of LIG material properties for scalable development of LIG sensors. Additional studies are needed to understand the underlying mechanism(s) of this variability so that strategies to improve the repeatability may be developed for improving quality control. The dataset from this study is available via an open access repository.

Design and modeling of order of addition experiment with component effects.

An order of addition experiment is an experiment to study how the order of addition of components affect the results, with the objective of predicting and determining the optimal order of addition of components. Order of addition experiment are also commonly used in the drug combination therapy, where experimenting with all drugs combinations is unaffordable. To solve this problem, we constructed a new design table, two-level component factorial design table (TLCF), which combine the component orthogonal array design table and the two-level partial factorial design table by matrix product. TLCF can explore the order and dosage effect of components on the results and can greatly reduce the number of experiments. We also prove that the relative D-efficiency of the TLCF can reach 100% and solve an explicit expression for the D-efficiency of the full design. In the simulation experiment, we compare the D-efficiency of the TLCF with the random design table to prove the superiority of TLCF. Finally, we give a treatment plan for the combination of three drugs for glioblastoma based on the TLCF, which provides a new perspective for the precision treatment of patients.

Simultaneously Improving Energy Storage and Oxygen Evolution Reaction by Causing Regional Defects in MOF-on-MOF Derived Hollow Se-Doped CoP-Fe2P Heterojunctions.

Doping heteroatoms into metal phosphides to modify their electronic structure is an effective method, but the incomplete exposure of active sites is its inherent drawback. In this experiment, both Se doping and P vacancies are simultaneously introduced into CoP-Fe2P (named CoFe-P-Se) to enhance the internal reactivity. Benefiting from the unique hollow porous structure derived from the MOF-on-MOF template, as well as the enhanced intrinsic activity achieved by P defects and Se doping, CoFe-P-Se exhibits a high specific capacitance of 8.41 F cm-2 at a current density of 2 mA cm-2 when used as a supercapacitor electrode. When assembled into a hybrid supercapacitor with activated carbon, the energy density reaches 0.488 mWh cm-2 at a power density of 1.534 mW cm-2, and the capacity retention after 5000 charge-discharge cycles is as high as 90.65%. As an oxygen evolution reaction (OER) electrode, the CoFe-P-Se electrode shows a low overpotential of only 230 mV at a current density of 10 mA cm-2 and 278 mV at 100 mA cm-2. Additionally, it exhibits excellent stability for over 50 h at a current density of 100 mA cm-2. The designed element doping and vacancy engineering in this work will provide an insight for constructing high-performance electrodes.

Multiple algorithms highlight key brain genes driven by multiple anesthetics.

Anesthesia serves as a pivotal tool in modern medicine, creating a transient state of sensory deprivation to ensure a pain-free surgical or medical intervention. While proficient in alleviating pain, anesthesia significantly modulates brain dynamics, metabolic processes, and neural signaling, thereby impairing typical cognitive functions. Furthermore, anesthesia can induce notable impacts such as memory impairment, decreased cognitive function, and diminished intelligence, emphasizing the imperative need to explore the concealed repercussions of anesthesia on individuals. In this investigation, we aggregated gene expression profiles (GSE64617, GSE141242, GSE161322, GSE175894, and GSE178995) from public repositories following second-generation sequencing analysis of various anesthetics. Through scrutinizing post-anesthesia brain tissue gene expression utilizing Gene Set Enrichment Analysis (GSEA), Robust Rank Aggregation (RRA), and Weighted Gene Co-expression Network Analysis (WGCNA), this research aims to pinpoint pivotal genes, pathways, and regulatory networks linked to anesthesia. This undertaking not only enhances comprehension of the physiological changes brought about by anesthesia but also lays the groundwork for future investigations, cultivating new insights and innovative perspectives in medical practice.

Differentially Expressed Proteins in the Serum of Elderly Patients Who Experienced Perioperative Neurocognitive Disorders Following Transurethral Resection of the Prostate.

OBJECTIVE: Perioperative neurocognitive disorders (PND) are a group of prevalent neurological complications that often occur in elderly individuals following major or emergency surgical procedures. The etiologies are not fully understood. This study endeavored to investigate novel targets and prediction methods for the occurrence of PND. METHODS: A total of 229 elderly patients diagnosed with prostatic hyperplasia who underwent transurethral resection of the prostate (TURP) combined with spinal cord and epidural analgesia were included in this study. The patients were divided into two groups, the PND group and non-PND group, based on the Z-score method. According to the principle of maintaining consistency between preoperative and intraoperative conditions, three patients from each group were randomly chosen for serum sample collection. isobaric tags for relative and absolute quantification (iTRAQ) proteomics technology was employed to analyze and identify the proteins that exhibited differential expression in the serum samples from the two groups. Bioinformatics analysis was performed on the proteins that exhibited differential expression. RESULTS: Among the 1101 serum proteins analyzed in the PND and non-PND groups, eight differentially expressed proteins were identified in PND patients. Of these, six proteins showed up-regulation, while two proteins showed down-regulation. Further bioinformatics analysis of the proteins that exhibited differential expression revealed their predominant involvement in cellular biological processes, cellular component formation, as well as endocytosis and phagocytosis Additionally, these proteins were found to possess the RING domain of E3 ubiquitin ligase. CONCLUSION: The iTRAQ proteomics technique was employed to analyze the variation in protein expression in serum samples from patients with PND and those without PND. This study successfully identified eight proteins that exhibited differential expression levels between the two groups. Bioinformatics analysis indicates that proteins exhibiting differential expression are primarily implicated in the biological processes associated with microtubules. Investigating the microtubule formation process as it relates to neuroplasticity and synaptic formation may offer valuable insights for enhancing our comprehension and potential prevention of PND. CLINICAL TRIAL REGISTRATION: Registered (ChiCTR2000028836). Date (20190306).

Schistosoma japonicum cystatin alleviates paraquat poisoning caused acute lung injury in mice through activating regulatory macrophages.

BACKGROUND: Paraquat (PQ) is a widely used herbicide that poisons human by accident or intentional ingestion. PQ poisoning causes systemic inflammatory response syndrome (SIRS) resulting in acute lung injury (ALI) with an extremely high mortality rate. Blood trematode Schistosoma japonicum-produced cystatin (Sj-Cys) is a strong immunomodulatory protein that has been experimentally used to treat inflammation related diseases. In this study, Sj-Cys recombinant protein (rSj-Cys) was used to treat PQ-induced lung injury and the immunological mechanism underlying the therapeutic effect was investigated. METHODS: PQ-induced acute lung injury mouse model was established by intraperitoneally injection of 20 mg/kg of paraquat. The poisoned mice were treated with rSj-Cys and the survival rate was observed up to 7 days compared with the group without treatment. The pathological changes of PQ-induced lung injury were observed by examining the histochemical sections of affected lung tissue and the wet to dry ratio of lung as a parameter for inflammation and edema. The levels of the inflammation related cytokines IL-6 and TNF-α and regulatory cytokines IL-10 and TGF-ß were measured in sera and in affected lung tissue using ELISA and their mRNA levels in lung tissue using RT-PCR. The macrophages expressing iNOS were determined as M1 and those expressing Arg-1 as M2 macrophages. The effect of rSj-Cys on the transformation of inflammatory M1 to regulatory M2 macrophages was measured in affected lung tissue in vivo (EKISA and RT-PCR) and in MH-S cell line in vitro (flow cytometry). The expression levels of TLR2 and MyD88 in affected lung tissue were also measured to determine their role in the therapy of rSj-Cys on PQ-induced lung injury. RESULT: We identified that treatment with rSj-Cys significantly improved the survival rate of mice with PQ-induced lung injury from 30 % (untreated) to 80 %, reduced the pathological damage of poisoning lung tissue, associated with significantly reduced levels of proinflammatory cytokines (IL-6 from 1490 to 590 pg/ml, TNF-α from 260 to 150 pg/ml) and increased regulatory cytokines (IL-10 from360 to 550 pg/ml, and TGF-ß from 220 to 410 pg/ml) in both sera (proteins) and affected lung tissue (proteins and mRNAs). The polarization of macrophages from M1to M2 type was found to be involved in the therapeutic effect of rSj-Cys on the PQ-induced acute lung injury, possibly through inhibiting TLR2/MyD88 signaling pathway. CONCLUSIONS: Our study demonstrated the therapeutic effect of rSj-Cys on PQ poisoning caused acute lung injury by inducing M2 macrophage polarization through inhibiting TLR2/MyD88 signaling pathway. The finding in this study provides an alternative approach for the treatment of PQ poisoning and other inflammatory diseases.

Integrated analysis of tertiary lymphoid structures and immune infiltration in ccRCC microenvironment revealed their clinical significances: a multicenter cohort study.

BACKGROUND: Tertiary lymphoid structures (TLSs) serve as organized lymphoid aggregates that influence immune responses within the tumor microenvironment. This study aims to investigate the characteristics and clinical significance of TLSs and tumor-infiltrating lymphocytes (TILs) in clear cell renal cell carcinoma (ccRCC). METHODS: TLSs and TILs were analyzed comprehensively in 754 ccRCC patients from 6 academic centers and 532 patients from The Cancer Genome Atlas. Integrated analysis was performed based on single-cell RNA-sequencing datasets from 21 ccRCC patients to investigate TLS heterogeneity in ccRCC. Immunohistochemistry and multiplex immunofluorescence were applied. Cox regression and Kaplan-Meier analyses were used to reveal the prognostic significance. RESULTS: The study demonstrated the existence of TLSs and TILs heterogeneities in the ccRCC microenvironment. TLSs were identified in 16% of the tumor tissues in 113 patients. High density (>0.6/mm2) and maturation of TLSs predicted good overall survival (OS) (p<0.01) in ccRCC patients. However, high infiltration (>151) of scattered TILs was an independent risk factor of poor ccRCC prognosis (HR=14.818, p<0.001). The presence of TLSs was correlated with improved progression-free survival (p=0.002) and responsiveness to therapy (p<0.001). Interestingly, the combination of age and TLSs abundance had an impact on OS (p<0.001). Higher senescence scores were detected in individuals with immature TLSs (p=0.003). CONCLUSIONS: The study revealed the contradictory features of intratumoral TLSs and TILs in the ccRCC microenvironment and their impact on clinical prognosis, suggesting that abundant and mature intratumoral TLSs were associated with decreased risks of postoperative ccRCC relapse and death as well as favorable therapeutic response. Distinct spatial distributions of immune infiltration could reflect effective antitumor or protumor immunity in ccRCC.

Single-cell transcriptomics across 2,534 microbial species reveals functional heterogeneity in the rumen microbiome.

Deciphering the activity of individual microbes within complex communities and environments remains a challenge. Here we describe the development of microbiome single-cell transcriptomics using droplet-based single-cell RNA sequencing and pangenome-based computational analysis to characterize the functional heterogeneity of the rumen microbiome. We generated a microbial genome database (the Bovine Gastro Microbial Genome Map) as a functional reference map for the construction of a single-cell transcriptomic atlas of the rumen microbiome. The atlas includes 174,531 microbial cells and 2,534 species, of which 172 are core active species grouped into 12 functional clusters. We detected single-cell-level functional roles, including a key role for Basfia succiniciproducens in the carbohydrate metabolic niche of the rumen microbiome. Furthermore, we explored functional heterogeneity and reveal metabolic niche trajectories driven by biofilm formation pathway genes within B. succiniciproducens. Our results provide a resource for studying the rumen microbiome and illustrate the diverse functions of individual microbial cells that drive their ecological niche stability or adaptation within the ecosystem.

Integrin αVß3 antagonist-c(RGDyk) peptide attenuates the progression of ossification of the posterior longitudinal ligament by inhibiting osteogenesis and angiogenesis.

BACKGROUND: Ossification of the posterior longitudinal ligament (OPLL), an emerging heterotopic ossification disease, causes spinal cord compression, resulting in motor and sensory dysfunction. The etiology of OPLL remains unclear but may involve integrin αVß3 regulating the process of osteogenesis and angiogenesis. In this study, we focused on the role of integrin αVß3 in OPLL and explored the underlying mechanism by which the c(RGDyk) peptide acts as a potent and selective integrin αVß3 inhibitor to inhibit osteogenesis and angiogenesis in OPLL. METHODS: OPLL or control ligament samples were collected in surgery. For OPLL samples, RNA-sequencing results revealed activation of the integrin family, particularly integrin αVß3. Integrin αVß3 expression was detected by qPCR, Western blotting, and immunohistochemical analysis. Fluorescence microscopy was used to observe the targeted inhibition of integrin αVß3 by the c(RGDyk) peptide on ligaments fibroblasts (LFs) derived from patients with OPLL and endothelial cells (ECs). The effect of c(RGDyk) peptide on the ossification of pathogenic LFs was detected using qPCR, Western blotting. Alkaline phosphatase staining or alizarin red staining were used to test the osteogenic capability. The effect of the c(RGDyk) peptide on angiogenesis was determined by EC migration and tube formation assays. The effects of the c(RGDyk) peptide on heterotopic bone formation were evaluated by micro-CT, histological, immunohistochemical, and immunofluorescence analysis in vivo. RESULTS: The results indicated that after being treated with c(RGDyk), the osteogenic differentiation of LFs was significantly decreased. Moreover, the c(RGDyk) peptide inhibited the migration of ECs and thus prevented the nutritional support required for osteogenesis. Furthermore, the c(RGDyk) peptide inhibited ectopic bone formation in mice. Mechanistic analysis revealed that c(RGDyk) peptide could inhibit osteogenesis and angiogenesis in OPLL by targeting integrin αVß3 and regulating the FAK/ERK pathway. CONCLUSIONS: Therefore, the integrin αVß3 appears to be an emerging therapeutic target for OPLL, and the c(RGDyk) peptide has dual inhibitory effects that may be valuable for the new therapeutic strategy of OPLL.

Tetracycline degradation by dual-frequency ultrasound combined with peroxymonosulfate.

Tetracycline has received a great deal of interest for the harmful effects of substance abuse on ecosystems and humanity. The effects of different processes on the degradation of tetracycline were compared, with dual-frequency ultrasound (DFUS) in combination with peroxymonosulfate (PMS) being the most effective for the tetracycline degradation. Free radical scavenging experiments showed that O2∙-,SO4∙- and •OH were the main reactive radicals in the degradation of tetracycline. According to the major intermediates of tetracycline degradation identified, three possible degradation pathways were proposed, which are of significance for translational studies of tetracycline degradation. Notably, these intermediates were found to be significantly less toxicity. The number of active bubbles in the degradation vessel was calculated using a semi-empirical formula, and a higher value of 1.44 × 108 L-1s-1 of bubbles was obtained when using dual-frequency ultrasound at 20 kHz (210 W/L) and 80 kHz (85.4 W/L). Therefore, compared to 20 kHz, although the yield of strong oxidizing substances from individual active bubbles decreased slightly, a significant increment of the number of active bubbles still resulted in a higher synergistic effect, and the combination of DFUS and PMS should be effective in promoting the generation of reactive free radicals and mass transfer processes within the degradation vessel, which provides a method for efficient removal of tetracycline from wastewater.

The C2 isthmus screw provided sufficient biomechanical stability in the setting of atlantoaxial dislocation-a finite element study.

BACKGROUND: The emerging of the C2 isthmus screw fixation technique is gaining popularity in the setting of atlantoaxial dislocation or other conditions requiring fixation of C2. However, the biomechanical stability of this fixation is poorly understood. PURPOSE: To compare and elucidate the biomechanical stability of C2 pedicle screw (C2PS), C2 isthmus screw (C2IS) and C2 short isthmus screw (C2SIS) fixation techniques in atlantoaxial dislocation (AAD). METHOD: A three-dimensional finite element model (FEM) from occiput to C3 was established and validated from a healthy male volunteer. Three FEMs, C1 pedicle screw (PS)-C2PS, C1PS-C2IS, C1PS-C2SIS were also constructed. The range of motion (ROM) and the maximum von Mises stress under flexion, extension, lateral bending and axial rotation loading were analyzed and compared. The pullout strength of the three fixations for C2 was also evaluated. RESULT: C1PS-C2IS model showed the greatest decrease in ROM with flexion, extension, lateral bending and axial rotation. C1PS-C2PS model showed the least ROM reduction under all loading conditions than both C2IS and C2SIS. The C1PS-C2PS model had the largest von Mises stress on the screw under all directions followed by C1PS-C2SIS, and lastly the C1PS-C2IS. Under axial rotation and lateral bending loading, the three models showed the maximum and minimum von Mises stress on the screw respectively. The stress of the three models was mainly located in the connection of the screw and rod. Overall, the maximum screw pullout strength for C2PS, C2IS and C2SIS were 729.41N, 816.62N, 640.54N respectively. CONCLUSION: In patients with atlantoaxial dislocations, the C2IS fixation provided comparable stability, with no significant stress concentration. Furthermore, the C2IS had sufficient pullout strength when compared with C2PS and C2SIS. C2 isthmus screw fixation may be a biomechanically favourable option in cases with AAD. However, future clinical trials are necessary for the evaluation of the clinical outcomes of this technique.