Quantitative Study on the Anticollapse Ability of Casing in Shale Gas Wells under Complex Load Conditions.

Implementing novel technologies, including the "well factory" model and zipper fracturing techniques, has become prevalent in shale gas development. During completion operations such as lowering casing and multistage fracturing, the casing is subjected to many complex loads, reducing its strength and increasing the risk of casing deformation. By establishing a casing wear model and conducting multistage cyclic loading experiments and numerical simulations, we analyzed the change rule of casing anticollapse strength under complex loads, developed a calculation method for casing comprehensive anticollapse ability under complex loads, and applied the method to an illustrative calculation. The study shows that the wear effect during completion has a negligible impact on the strength of the casing. The casing anticollapse strength exhibits a linear decline in correlation with the number of cycles. The zipper fracturing operation resulted in a nonuniform distribution of geo-stress around the well, and the casing anticollapse strength demonstrated a nearly linear decline in correlation with the nonuniformity of geo-stress. In the presence of both internal and external effects, the casing anticollapse strength exhibited a decline exceeding 15%, thereby increasing the risk of casing deformation. This research method can provide computational guidance for preventing casing deformation in field fracturing construction.

Seed priming with graphene oxide improves salinity tolerance and increases productivity of peanut through modulating multiple physiological processes.

Graphene oxide (GO), beyond its specialized industrial applications, is rapidly gaining prominence as a nanomaterial for modern agriculture. However, its specific effects on seed priming for salinity tolerance and yield formation in crops remain elusive. Under both pot-grown and field-grown conditions, this study combined physiological indices with transcriptomics and metabolomics to investigate how GO affects seed germination, seedling salinity tolerance, and peanut pod yield. Peanut seeds were firstly treated with 400 mg L⁻¹ GO (termed GO priming). At seed germination stage, GO-primed seeds exhibited higher germination rate and percentage of seeds with radicals breaking through the testa. Meanwhile, omics analyses revealed significant enrichment in pathways associated with carbon and nitrogen metabolisms in GO-primed seeds. At seedling stage, GO priming contributed to strengthening plant growth, enhancing photosynthesis, maintaining the integrity of plasma membrane, and promoting the nutrient accumulation in peanut seedlings under 200 mM NaCl stress. Moreover, GO priming increased the activities of antioxidant enzymes, along with reduced the accumulation of reactive oxygen species (ROS) in response to salinity stress. Furthermore, the differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) of peanut seedlings under GO priming were mainly related to photosynthesis, phytohormones, antioxidant system, and carbon and nitrogen metabolisms in response to soil salinity. At maturity, GO priming showed an average increase in peanut pod yield by 12.91% compared with non-primed control. Collectively, our findings demonstrated that GO plays distinguish roles in enhancing seed germination, mitigating salinity stress, and boosting pod yield in peanut plants via modulating multiple physiological processes.

Preclinical Evaluation of Dihydropyrazole-Cored Positron Emission Tomography (PET) Ligands for Imaging of Receptor-Interacting Serine/Threonine Protein Kinase 1 (RIPK1) in the Brain.

Receptor-interacting serine/threonine protein kinase 1 (RIPK1) has emerged as an important regulator of pathologic cell death and inflammation and is implicated in the pathologies of various central nervous system diseases. In this study, we reported the development of three potent dihydropyrazole-cored RIPK1 positron emission tomography (PET) ligands [18F]WL1-3. Among these, [18F]WL1 showed specific binding to RIPK1 in mouse brain sections in vitro through autoradiography and exhibited favorable brain kinetics in mice, characterized by a high initial uptake (brain2 min = 4.89% ID/g) and rapid washout (brain60 min = 0.21% ID/g). PET studies in rat brains revealed that [18F]WL1 could readily penetrate the brain with specific binding confirmed by inhibition effects of unlabeled WL1 and GSK'547. Notably, [18F]WL1 showed significant potential in imaging the alterations of RIPK1 in a rat brain of tumor necrosis factor α-induced systemic inflammatory response syndrome model. These findings may pave the way for the future design of potent RIPK1 PET ligands.

CRISPR/Gal4BD-Cas donor adapting systems based on miniaturized Cas proteins for improved gene editing.

Targeted precise point editing and knock-in can be achieved by homology-directed repair(HDR) based gene editing strategies in mammalian cells. However, the inefficiency of HDR strategies seriously restricts their application in precision medicine and molecular design breeding. In view of the problem that exogenous donor DNA cannot be efficiently recruited autonomously at double-stranded breaks(DSBs) when using HDR strategies for gene editing, the concept of donor adapting system(DAS) was proposed and the CRISPR/Cas9-Gal4BD DAS was developed previously. Due to the large size of SpCas9 protein, its fusion with the Gal4BD adaptor is inconvenient for protein expression, virus vector packaging and in vivo delivery. In this study, two novel CRISPR/Gal4BD-SlugCas9 and CRISPR/Gal4BD-AsCas12a DASs were further developed, using two miniaturized Cas proteins, namely SlugCas9-HF derived from Staphylococcus lugdunensis and AsCas12a derived from Acidaminococcus sp. Firstly, the SSA reporter assay was used to assess the targeting activity of different Cas-Gal4BD fusions, and the results showed that the fusion of Gal4BD with SlugCas9 and AsCas12a N-terminals had minimal distraction on their activities. Secondly, the HDR efficiency reporter assay was conducted for the functional verification of the two DASs and the corresponding donor patterns were optimized simultaneously. The results demonstrated that the fusion of the Gal4BD adaptor binding sequence at the 5'-end of intent dsDNA template (BS-dsDNA) was better for the CRISPR/Gal4BD-AsCas12a DAS, while for the CRISPR/Gal4BD-SlugCas9 DAS, the dsDNA-BS donor pattern was recommended. Finally, CRISPR/Gal4BD-SlugCas9 DAS was used to achieve gene editing efficiency of 24%, 37% and 31% respectively for EMX1, NUDT5 and AAVS1 gene loci in HEK293T cells, which was significantly increased compared with the controls. In conclusion, this study provides a reference for the subsequent optimization of the donor adapting systems, and expands the gene editing technical toolbox for the researches on animal molecular design breeding.

RpoS sigma factor mediates adaptation and virulence in Vibrio mimicus.

The alternative sigma factor RpoS functions as a regulator of stress and virulence response in numerous bacterial species. Vibrio mimicus is a critical opportunistic pathogen causing huge losses to aquaculture. However, the exact role of RpoS in V. mimicus remains unclear. In this study, rpoS deletion mutant of V. mimicus was constructed through allelic exchange and the phenotypic and transcriptional changes were investigated to determine the function of RpoS. The abilities of growth, motility, biofilm production, hemolytic activity and pathogenicity were significantly impaired in ΔrpoS strain. Stationary-phase cells of ΔrpoS strain showed lower tolerance to H2O2, heat, ethanol, and starvation stress than the wild-type strain. Transcriptome analyses revealed the involvement of rpoS in various cellular processes, notably bacterial-type flagellum synthesis and assembly, membrane synthesis and assembly and response to various stimuli. Phenotypic and RNA-seq analysis revealed that RpoS is required for biofilm formation, stress resistance, and pathogenicity in V. mimicus. Furthermore, ß-galactosidase activity showed that rpoS is essential for optimal transcription of the flgK, fliA, cheA, mcpH mRNA. These results offer significant insight into the function and regulatory network of rpoS/RpoS, thereby improving our understanding and facilitating selection of molecular targets for future prevention strategies against V. mimicus.

Neutrophil PPIF exacerbates lung ischemia-reperfusion injury after lung transplantation by promoting calcium overload-induced neutrophil extracellular traps formation.

Lung ischemia-reperfusion (I/R) injury is the main risk factor for primary graft dysfunction and patient death after lung transplantation (LTx). It is widely accepted that the main pathological mechanism of lung I/R injury are calcium overload, oxygen free radical explosion and neutrophil-mediated damage, which leading to the lack of effective treatment options. The aim of this study was to further explore the mechanisms of lung I/R injury after LTx and to provide potential therapeutic strategies. Our bioinformatics analysis revealed that the neutrophil extracellular traps (NETs) formation was closely involved in lung I/R injury after LTx, which was accompanied by up-regulation of peptidylprolyl isomerase F (PPIF) and peptidyl arginine deiminase 4 (PADI4). We further established an orthotopic LTx mouse model to simulate lung I/R injury in vivo, and found that PPIF and PADI4 inhibitors effectively reduced neutrophil infiltration, NETs formation, inflammatory response, and lung I/R injury. In the neutrophil model induced by HL-60 cell line in vitro, we found that PPIF inhibitor cyclosporin A (Cys A) better alleviated calcium overload induced inflammatory response, reactive oxygen species content and NETs formation. Further study demonstrated that interfering with neutrophil PPIF protected mitochondrial function by alleviating store-operated calcium entry (SOCE) during calcium overload and played the above positive role. On this basis, we found that the reduction of calcium content in neutrophils was accompanied by the inhibition of calcineurin (CN) and nuclear factor of activated T cells (NFAT). In conclusion, our findings suggested that neutrophil PPIF could serve as a novel biomarker and potential therapeutic target of lung I/R injury after LTx, which provided new clues for its treatment by inhibiting calcium overload-induced NETs formation.

Structure-based discovery of a 4,5-Dihydropyrazole-cored PET ligand for imaging of receptor-interacting serine/threonine-protein kinase 1 (RIPK1) in the brain.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) regulates programmed cell death and inflammation, contributing to a wide range of human pathologies, including inflammatory disorders, neurodegenerative conditions, and cancer. Despite this, no RIPK1 positron emission tomography (PET) ligand with significant in vivo specificity has been reported to date. In this work, we designed and synthesized a new family of dihydropyrazole-cored ligands suitable for 18F-labeling at the late stage. Among these, WL8 showed a strong binding affinity to RIPK1 (EC50 = 19.9 nM, Kd = 25 nM) and was successfully labeled with 18F in the 6-position of pyridine ring, yielding a high radiochemistry yield of 27.9 % (decay-corrected) and a high molar activity of 18.8-31.2 GBq/µmol. In in vitro autoradiography, [18F]WL8 showed some specific binding in the brain sections of rats and lipopolysaccharide (LPS) model mice. Preliminary PET studies in rat brains revealed that [18F]WL8 could efficiently penetrate the blood-brain barrier and was rapidly washed out. As anticipated, [18F]WL8 exhibited a high initial uptake (brain2min = 4.80 % ID/g) in mouse brains, followed by a rapid washout (brain60min = 0.14 % ID/g), although no clear specific binding to RIPK1 was observed. Moderate in vivo stability was noted for [18F]WL8 in mouse brains with 35.2 % of the parent fraction remaining after 30 min post-administration. Altogether, our work broadens the landscape and offers a new chemotype for RIPK1 PET ligand development.

Polydopamine-Based Targeted Nanosystem for Chemo/Photothermal Therapy of Retinoblastoma in a Mouse Orthotopic Model.

Background: At present, the few photothermal/chemotherapy studies about retinoblastoma that have been reported are mainly restricted to ectopic models involving subcutaneous implantation. However, eyeball is unique physiological structure, the blood-retina barrier (BRB) hinders the absorption of drug molecules through the systemic route. Moreover, the abundant blood circulation in the fundus accelerates drug metabolism. To uphold the required drug concentration, patients must undergo frequent chemotherapy sessions. Purpose: To address these challenges above, we need to develop a secure and effective drug delivery system (FA-PEG-PDA-DOX) for the fundus. Methods: We offered superior therapeutic efficacy with minimal or no side effects and successfully established orthotopic mouse models. We evaluated cellular uptake performance and targeting efficiency of FA-PEG-PDA-DOX nanosystem and assessed its synergistic antitumor effects in vitro and vivo. Biodistribution assessments were performed to determine the retention time and targeting efficiency of the NPs in vivo. Additionally, safety assessments were conducted. Results: Cell endocytosis rates of the FA-PEG-PDA-DOX+Laser group became 5.23 times that of the DOX group and 2.28 times that of FA-PEG-PDA-DOX group without irradiation. The fluorescence signal of FA-PEG-PDA-DOX persisted for more than 120 hours at the tumor site. The number of tumor cells (17.2%) in the proliferative cycle decreased by 61.6% in the photothermal-chemotherapy group, in contrast to that of the saline control group (78.8%). FA-PEG-PDA-DOX nanoparticles(NPs) exhibited favorable biosafety and high biocompatibility. Conclusion: The dual functional targeted nanosystem, with the effects of DOX and mild-temperature elevation by irradiation, resulted in precise chemo/photothermal therapy in nude mice model.

Prognostic value of Naples Prognostic Score in locally advanced cervical cancer patients undergoing concurrent chemoradiotherapy.

This study aimed to investigate the prognostic value of the Naples Prognostic Score (NPS) in patients with locally advanced cervical cancer (LACC) who received curative concurrent chemoradiotherapy (CCRT). Clinicopathological data from 213 (training set) and 106 (validation set) LACC cases undergoing CCRT were retrospectively analyzed. The receiver operating characteristic curve (ROC) was used to compare the predictive ability of NPS and other indicators for survival. Cox proportional hazard regression was conducted for overall survival (OS) and progression-free survival (PFS). A prediction model using a nomogram was developed with independent prognostic factors in the training set and validated in the validation set. The 5-year OS for the NPS = 1, 2, and 3 groups was 56.8%, 45.4%, and 28.9% (P < 0.001), and the 5-year PFS for the NPS = 1, 2, and 3 groups was 44.9%, 36.7%, and 28.4% (P = 0.001), respectively. NPS showed better predictive ability for OS and PFS compared to other indicators. Multivariate regression analysis identified NPS as an independent prognostic factor for OS (P < 0.001) and PFS (P < 0.001). A predictive nomogram based on NPS was established and validated. The C-indices of the nomogram in the training set were 0.722 for OS and 0.683 for PFS, while in the validation set the C-indices were 0.731 for OS and 0.693 for PFS. This study confirmed that preoperative NPS could serve as a useful independent prognostic factor in LACC patients treated with CCRT.

1,25-D3 ameliorates ischemic brain injury by alleviating endoplasmic reticulum stress and ferroptosis: Involvement of vitamin D receptor and p53 signaling.

Endoplasmic reticulum stress (ERS) and ferroptosis are linked to cerebral ischemia reperfusion injury (CIRI). The neuroprotective properties of 1α, 25-dihydroxyvitamin D3 (VitD3 or 1,25-D3) have been well established; however, the mechanism by which VitD3 treats CIRI through ERS and ferroptosis has not been examined. Hence, we developed middle cerebral artery occlusion/reperfusion (MCAO/R) model in SD rats to ascertain if VitD3 preconditioning mediates ERS and ferroptosis involving of p53 signaling. In this study, we observed that VitD3 can reduce infarction volume and cerebral edema, which leads to the improvement of nerve function. HE, Nissl and Tunel staining showed that VitD3 treatment significantly improved the morphology of neuronal cells and reduced their death. The expression and activation of Vitamin D receptor (VDR), PKR-like ER kinase (PERK), C/EBP-homologous protein (CHOP), p53, nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4) and reactive oxygen species (ROS) in the ischemic penumbral area were detected by real-time qPCR, Western-blotting and Elisa. The results showed that after VitD3 treatment, VDR increased, ERS-related indices (PERK, CHOP) significantly decreased and ferroptosis-related indices (Nrf2, GPX4) increased. As a VDRs antagonist, pyridoxal-5-phosphate (P5P) can partially block the neuroprotective effects of VitD3. Therefore, CIRI can induce ERS and ferroptosis in the ischemic penumbra area and VitD3 may ameliorate nerve damage in CIRI rats by up-regulating VDR, alleviating p53-associated ERS and ferroptosis.

Bacterial and Archaeal Communities in Erhai Lake Sediments: Abundance and Metabolic Insight into a Plateau Lake at the Edge of Eutrophication.

The littoral zones of lakes are potential hotspots for local algal blooms and biogeochemical cycles; however, the microbial communities within the littoral sediments of eutrophic plateau lakes remain poorly understood. Here, we investigated the taxonomic composition, co-occurrence networks, and potential functional roles of both abundant and rare taxa within bacterial and archaeal communities, as well as physicochemical parameters, in littoral sediments from Erhai Lake, a mesotrophic lake transitioning towards eutrophy located in the Yunnan-Guizhou Plateau. 16S rRNA gene sequencing revealed that bacterial communities were dominated by Proteobacteria, Bacteroidetes, and Chloroflexi, while Euryarchaeota was the main archaeal phylum. Co-occurrence network analysis revealed that keystone taxa mainly belonged to rare species in the bacterial domain, but in the archaeal domain, over half of keystone taxa were abundant species, demonstrating their fundamental roles in network persistence. The rare bacterial taxa contributed substantially to the overall abundance (81.52%), whereas a smaller subset of abundant archaeal taxa accounted for up to 82.70% of the overall abundance. Functional predictions highlighted a divergence in metabolic potentials, with abundant bacterial sub-communities enriched in pathways for nitrogen cycling, sulfur cycling, and chlorate reduction, while rare bacterial sub-communities were linked to carbon cycling processes such as methanotrophy. Abundant archaeal sub-communities exhibited a high potential for methanogenesis, chemoheterotrophy, and dark hydrogen oxidation. Spearman correlation analysis showed that genera such as Candidatus competibacter, Geobacter, Syntrophobacter, Methanocella, and Methanosarcina may serve as potential indicators of eutrophication. Overall, this study provides insight into the distinct roles that rare and abundant taxa play in the littoral sediments of mesotrophic plateau lakes.

Comprehensive Analysis of Laser Peening Forming Effects on 5083 Aluminum Alloy.

In order to investigate the laws of the laser peening forming process and the effects of laser peening on the surface quality and tensile properties of 5083 aluminum alloy, experiments were conducted utilizing various laser peening paths, energies, and plate thicknesses. Subsequently, laser peening forming experiments were performed on S-shaped and different shapes of aluminum alloy substrates. The impact of different laser peening durations on surface morphology and tensile properties was then analyzed. Results indicated that the largest bending deformation perpendicular to the laser peening path reached 12.5 mm. In cases where the laser peening path was inclined relative to the horizontal direction, torsional deformations were observed in the aluminum alloy plate. For laser energy levels of 5 J, 6 J, and 7 J, deformation amounts were 3.8 mm, 4.9 mm, and 5.4 mm, respectively. Plates with thicknesses of 4 mm exhibited convex deformation, while those with 2 mm thickness showed concave deformation. Furthermore, following one and two laser peening cycles, the residual stresses in the alloy plates were -80 MPa and -107 MPa, the surface hardness increased by 16 HV and 31 HV, the roughness increased by 2.495 µm and 3.615 µm, and the tensile strength increased by 9.5 MPa and 18.5 MPa, respectively.

The prion-like protein Doppel: A soluble biomarker steering ovarian cancer's peritoneal to circulatory dissemination.

Detecting ovarian cancer (OC) early using existing biomarkers, e.g., cancer antigen 125 (CA125), is challenging due to its ubiquitous expression in many tissues. Doppel, a prion-like protein, expresses in male reproductive organ but absent in female reproductive systems and healthy tissues, but plays an important role in neoangiogenesis. Here, we have shown two platforms, soluble Doppel in sera/ascites and Doppel expressed circulating tumor cells ( Dpl+ CTC) in the whole blood, to detect subsets of epithelial OC (EOC). Increased level of Doppel in the sera of OC patients, in three different cohorts, confirm Doppel as OC specific biomarker. Serum Doppel level distinguishes EOC subtypes and early stages HGSOCs from non-cancerous conditions with high sensitivity and specificity. Stratifying the EOCs based on Doppel level, we categorized them into Doppel-high (Dpl hi ) and Doppel-low (Dpl low ) groups. Using ascites-derived organoids and single cell sequencing of whole ascites of Dpl hi and Dpl low patients, we identify that Doppel induces epithelial-mesenchymal transition (EMT) and creates an immunosuppressive microenvironment, respectively. Doppel levels in the sera/ascites correlate with the changes of Dpl+ CTC number in whole blood, highlighting the association of Doppel-induced EMT with CTC dissemination in circulation. Thus, Doppel-based detection of EOC subtypes could be a promising platform as clinical biomarker and link Doppel-axis with OC dissemination.

A GhLac1-centered transcriptional regulatory cascade mediates cotton resistance to Verticillium dahliae through the lignin biosynthesis pathway.

The lignin biosynthesis pathway plays a crucial role in the defense response against V. dahliae in cotton, and it is essential to identify the key regulators in this pathway for disease-resistant breeding. In a previous study, the cotton laccase gene GhLac1 was identified as mediating plant broad-spectrum biotic stress tolerance by manipulating phenylpropanoid metabolism. However, the upstream master regulators and regulatory mechanism of lignin are still largely unknown. This study aims to identify the upstream regulators of GhLac1 and explore the molecular mechanism underlying cotton's disease resistance response to V. dahliae. Through the study, three WRKY, three MYB, and one APETALA2/ETHYLENE RESPONSIVE FACTOR (ERF) TFs were identified as differentially responding to V. dahliae infection in cotton. Among these TFs, GhWRKY30, GhWRKY41, GhMYB42, and GhTINY2 were found to directly bind to the GhLac1 promoter and activate its expression. Transient overexpression of these four TFs in cotton led to increased expression of GhLac1 and other the laccase family members, while knockdown of these TFs resulted in reduced lignin accumulation and increased susceptibility to V. dahliae. Additionally, GhWRKY30 and GhWRKY41 were observed to interact with themselves and with each other, synergistically transactivating the GhLac1 promoter. This study reveals a GhLac1-centered transcriptional regulatory cascade of lignin synthesis that contributes to cotton's defense response by modulating lignin metabolism.

Metagenome-assembled bacterial genomes derived from various aging flue-cured tobacco samples.

We recovered 16 bacterial metagenome-assembled genomes from 11 flue-cured tobacco samples with different aging stage and various geographic origins. Their sizes range from 2.3 M to 5.4 M, with GC contents of 43.17%-74.45%, completeness of 78.80%-99.25%, and contamination of 0.47%-8.56%.

Recent Advances in Electroluminescent Metallic Nanoclusters: From Materials to Devices.

Metallic nanoclusters (MNCs) were developed rapidly in recent decades, owing to their unique electronic structures and excited state characteristics, leading to their wide applications. Luminescence as one of the most important functions for MNCs has also been used to realize biodetection, displays, and lighting, through either electrochemiluminescence (ECL) or electroluminescence (EL). Both emissive properties and electrochemical activities of MNCs were utilized to enhance ECL and EL through facilitating exciton formation and radiation, rendering the rapid emerging of the latter in the last ten years. Through ligand modification, radiative excited-state components were increased to realize state-of-the-art photo- and electroluminescence efficiencies up to ∼100% and ∼30%, as well as ultralow biodetection limits. Nonetheless, material selection space and processing technologies are still limited. Herein, we overview and discuss recent advances of MNCs-based ECL and EL, through both aspects of materials/systems and devices, which would enlighten continuous innovations in optoelectronic MNCs.

Innovative Colorimetric NQO1 Detection Strategy via Substrate Competitive and Biomimetic Cascade Reactions with a Highly Active NADH Oxidase Mimic.

NAD(P)H: quinone oxidoreductase-1 (NQO1) plays critical roles in antioxidation and abnormally overexpresses in tumors. Developing a fast and sensitive method of monitoring NQO1 will greatly promote cancer diagnosis in clinical practice. This study introduces a transformative colorimetric detection strategy for NQO1, harnessing an innovative competitive substrate mechanism between NQO1 and a new NADH oxidase (NOX) mimic, cobalt-nitrogen-doped carbon nanozyme (CoNC). This method ingeniously exploits the differential consumption of NADH in the presence of NQO1 to modulate the generation of H2O2 from CoNC catalysis, which is then quantified through a secondary, peroxidase-mimetic cascade reaction involving Prussian blue (PB) nanoparticles. This dual-stage reaction framework not only enhances the sensitivity of NQO1 detection, achieving a limit of detection as low as 0.67 µg mL-1, but also enables the differentiation between cancerous and noncancerous cells by their enzymatic activity profiles. Moreover, CoNC exhibits exceptional catalytic efficiency, with a specific activity reaching 5.2 U mg-1, significantly outperforming existing NOX mimics. Beyond mere detection, CoNC serves a dual role, acting as both a robust mimic of cytochrome c reductase (Cyt c) and a cornerstone for enzymatic regeneration, thereby broadening the scope of its biological applications. This study not only marks a significant step forward in the bioanalytical application of nanozymes but also sets the stage for their expanded use in clinical diagnostics and therapeutic monitoring.

Research progress on the protection and mechanism of active peptides in Alzheimer's disease and Parkinson's disease.

Neurodegenerative diseases are the main causes of death and morbidity among elderly people worldwide. From the pathological point of view, oxidative stress, neuroinflammation, mitochondrial damage and apoptosis are the causes of neuronal diseases, and play a harmful role in the process of neuronal cell death and neurodegeneration. The most common neurodegenerative diseases are Alzheimer's disease(AD) and Parkinson's disease(PD), and there is no effective treatment. The physiological role of active peptides in the human body is significant. Modern medical research has found that animal and plant peptides, natural peptides in human body, can act on the central nervous system, and their active components can improve learning and memory ability, and play the roles of antioxidation, anti-inflammation, anti-apoptosis and maintaining the structure and function of mitochondria. This review reviews the reports on neurodegenerative diseases such as AD and PD by active peptides from animals and plants and natural peptides from the human body, and summarizes the neuroprotective mechanism of peptides. A theoretical basis for further research and development of active peptides was provided by examining the research and application of peptides, which provided a theoretical basis for further research and development.

The association between IGF-1 levels and four types of osteoarthritis: a bidirectional and two-step mendelian randomization study.

Background: Insulin-like Growth Factor-1 (IGF-1) plays a crucial role in the growth and metabolic functions of various tissues and cells in the body. Recently, there has been increased attention to the association between IGF-1 and osteoarthritis (OA). However, there is controversy in current research regarding the correlation between IGF-1 levels and OA. Furthermore, the specific manner in which Body Mass Index (BMI), a key risk factor for OA, mediates the impact of IGF-1 levels on OA remains unclear. Object: This study aimed to investigate the bidirectional causal link between IGF-1 levels and OA in four body regions, and to explore how BMI influences the impact of IGF-1 on these types of OA. Method: Two-sample Mendelian Randomization (MR) and its combined forms were utilized to investigate the bidirectional relationship between IGF-1 levels and four types of OA, as well as the mediating role of BMI in the impact of IGF-1 levels on OA. Data from various Genome-Wide Association Studies (GWAS) and multiple analytical methods, including inverse variance weighted, MR-Egger regression, and weighted median were utilized. Sensitivity analyses, such as MR-Egger intercept, Cochran Q test, leave-one-out, and MR-PRESSO, were conducted to ensure the robustness of the results. Results: Higher IGF-1 levels are correlated with an increased risk for knee (OR, 1.07; 95% CI, 1.01-1.03; p = 1.49e-01; q = 9.86e-03), hip (OR, 1.13; 95% CI, 1.06-1.20; p = 7.61e-05; q = 7.44e-05), and hand OA (OR, 1.09; 95% CI, 1.01-1.17; p = 1.88e-02; q = 1.15e-02), but not spine OA but not spine OA (OR, 1.05; 95% CI, 0.99-1.10; p = 9.20e-02; q = 5.52e-02). Different types of OA do not affect IGF-1 levels. BMI mediates the increase in OA risk associated with higher IGF-1, including indirect spine OA risk through BMI. Conclusion: The study elucidates the bidirectional causality between IGF-1 levels and OA in various body parts, highlighting BMI's mediating role in the impact of IGF-1 levels on OA. This provides valuable insights for OA prevention, diagnosis, and treatment strategies. Future research will expand our study to include a broader spectrum of ethnicities and explore the underlying mechanisms involved.

The first-in-human preclinical evaluation of the new probe [123I]I-PSMA-7 for real-time intraoperative targeted biopsy and SPECT/CT imaging in prostate cancer.

PURPOSE: PSMA/PET has been increasingly used to detect PCa, and PSMA/PET-guided biopsy has shown promising results. However, it cannot be confirmed immediately whether the tissues are the targeted area. In this study, we aimed to develop a novel probe, [123I]I-PSMA-7. First, we hope that [123I]I-PSMA-7 can provide instant confirmation for prostate biopsy. Second, we hope it will help detect PCa. METHODS: We synthesized a high-affinity probe, [123I]I-PSMA-7, and evaluated its properties. We included ten patients with suspected PCa and divided them into two groups. The injection and biopsy were approximately 24 h apart. The activity in biopsy lesions was measured as the cpm by a γ-counter. Moreover, we enrolled 3 patients to evaluate the potential of [123I]I-PSMA-7 for detecting PCa. RESULTS: Animal experiments verified the safety, targeting and effectiveness of [123I]I-PSMA-7, and the tumor-to-muscle ratio was greatest at 24 h, which confirmed the results of this study in humans. After injection of 185MBq [123I]I-PSMA-7, 18/55 cores were positive, and the cpm was significantly greater (4345 ± 3547 vs. 714 ± 547, P < 0.001), with an AUC of 0.97 and a cutoff of 1312 (sens/spec of 94.40%/91.90%). At a lower dose, 10/55 biopsy cores were cancerous, and the cpm was 2446 ± 1622 vs. 153 ± 112 (P < 0.001). The AUC was 1, with a cutoff value of 490 (sens/spec of 100%). When the radiopharmaceuticals were added to 370 MBq, we achieved better SPECT/CT imaging. CONCLUSION: With the aid of [123I]I-PSMA-7 and via cpm-based biopsy, we can reduce the number of biopsies to a minimum operation. [123I]I-PSMA-7 PSMA SPECT/CT can also provide good imaging results. TRIAL REGISTRATION: Chinese Clinical trial registry ChiCTR2300069745, Registered 24 March 2023.