The root-knot nematode effector MiEFF12 targets the host ER quality control system to suppress immune responses and allow parasitism.

Root-knot nematodes (RKNs) are microscopic parasitic worms able to infest the roots of thousands of plant species, causing massive crop yield losses worldwide. They evade the plant's immune system and manipulate plant cell physiology and metabolism to transform a few root cells into giant cells, which serve as feeding sites for the nematode. RKN parasitism is facilitated by the secretion in planta of effector molecules, mostly proteins that hijack host cellular processes. We describe here a conserved RKN-specific effector, effector 12 (EFF12), that is synthesized exclusively in the oesophageal glands of the nematode, and we demonstrate its function in parasitism. In the plant, MiEFF12 localizes to the endoplasmic reticulum (ER). A combination of RNA-sequencing analysis and immunity-suppression bioassays revealed the contribution of MiEFF12 to the modulation of host immunity. Yeast two-hybrid, split luciferase and co-immunoprecipitation approaches identified an essential component of the ER quality control system, the Solanum lycopersicum plant bap-like (PBL), and basic leucine zipper 60 (BZIP60) proteins as host targets of MiEFF12. Finally, silencing the PBL genes in Nicotiana benthamiana decreased susceptibility to Meloidogyne incognita infection. Our results suggest that EFF12 manipulates PBL function to modify plant immune responses to allow parasitism.

The German cochlear implant registry: one year experience and first results on demographic data.

PURPOSE: Clinical registries have great potential for quality control of medical procedures regarding the indications, therapeutic processes and results, including their possible complications. This is particularly true when providing patients with severe hearing loss or deafness with a cochlear implant (CI). This treatment represents a lifelong care process that requires continuous quality control over time. On the initiative of the Executive Committee of the German Society of Otorhinolaryngology (Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e.V., DGHNO-KHC), a national German CI registry (Deutsches Cochlear Implant Register, DCIR) was established in January 2022. This article focuses on the first demographic and baseline data of the DCIR. METHODS: The DCIR covers the complete therapeutic process from indication, surgery, fitting and lifelong aftercare in CI therapy. By the end of 2022, 75 hospitals in Germany had agreed to contribute to the DCIR. RESULTS: During the year 2022, 63 hospitals actively contributed data to the DCIR. Pseudonymized data from 2,292 CI implantations (2,176 primary implantations, 99 explantations with immediate re-implantations and 17 re-implantations following an earlier explantation) in 2,108 patients were documented. Cochlear implantation was accomplished in 1,807 adults (≥ 18 years) and 301 children (< 18 years). Fourty patients (1,9%) were children < 1 year of age and 55 (2,6%) were patients > 85 years. From the total of 2,292 implantations, 226 (9.9%) were performed as simultaneous bilateral implantations (CI implantation in both ears of 113 patients on the same day of surgery) and 412 implantations (19.1% of 2,162 implantations with data provided on the contralateral ear's hearing status) were in patients with single sided deafness (normal hearing in the contralateral ear). In addition, the reported complications in 2022 were also evaluated. Seven reports (0.4%) of mild to moderate severe facial nerve dysfunctions were documented. No reports of severe or total facial nerve dysfunction (House-Brackmann grade V/VI), meningitis or death related to CI therapy were documented. CONCLUSION: Although still in the start-up phase, these initial DCIR data already provide an interesting first insight into the demographic structure and baseline data of CI therapy in Germany. The successful implementation of the DCIR represents an important step towards continuous quality control of CI care.

A comprehensive strategy based on ultra-high performance liquid chromatography with diode array detector fingerprinting and multi-component ultra-performance liquid chromatography with tandem mass spectrometry technology for quality control of Jiawei Huoxiang Zhengqi Pill.

Jiawei Huoxiang Zhengqi Pill (JHZP) is a commonly used Chinese patent medicine for the clinical treatment of headache, dizziness, chest tightness as well as abdominal distension, and pain caused by wind-cold flu. In this study, a comprehensive strategy combining ultra-high performance liquid chromatography with diode array detector (UHPLC-DAD) fingerprinting and multi-component quantitative analysis was established and validated for quality evaluation of JHZP. A total of 49 characteristic common peaks were selected in a chromatographic fingerprinting study to assess the similarity of 15 batches of JHZP. Furthermore, 109 compounds were identified or preliminarily identified from JHZP by coupling with an advanced hybrid linear ion trap-Orbitrap mass spectrometer. For quantification, the optimized ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method was employed for the simultaneous determination of 13 target compounds within 12 min. The sensitivity, precision, reproducibility, and accuracy of the method were satisfactory. This validated UPLC-MS/MS method was successfully applied to analyzing 15 batches of JHZP. The proposed comprehensive strategy combining UHPLC-DAD fingerprinting and multi-component UPLC-MS/MS analysis proved to be highly efficient, accurate, and reliable for the quality evaluation of JHZP, which can be considered as a reference for the overall quality evaluation of other Chinese herbal formulations.

Considerations for the development of iPSC-derived cell therapies: a review of key challenges by the JSRM-ISCT iPSC Committee.

Since their first production in 2007, human induced pluripotent stem cells (iPSCs) have provided a novel platform for the development of various cell therapies targeting a spectrum of diseases, ranging from rare genetic eye disorders to cancer treatment. However, several challenges must be tackled for iPSC-based cell therapy to enter the market and achieve broader global adoption. This white paper, authored by the Japanese Society for Regenerative Medicine (JSRM) - International Society for Cell Therapy (ISCT) iPSC Committee delves into the hurdles encountered in the pursuit of safe and economically viable iPSC-based therapies, particularly from the standpoint of the cell therapy industry. It discusses differences in global guidelines and regulatory frameworks, outlines a series of quality control tests required to ensure the safety of the cell therapy, and provides details and important considerations around cost of goods (COGs), including the impact of automated advanced manufacturing.

Evaluating the Quality of Local Programs for Early Detection of Significant Prostate Cancer.

Quality control of programs for detection of significant prostate cancer (sPCa) could be defined by the correlation between observed and reference 95% confidence intervals (CIs) for Prostate Imaging-Reporting and Data System (PI-RADS) categories. We used the area under the receiver operating characteristic curve (AUC) for the Barcelona magnetic resonance imaging (MRI) predictive model to screen the quality of ten participant centers in the sPCa opportunistic early detection program in Catalonia. We set an AUC of <0.8 as the criterion for suboptimal quality. Quality was confirmed in terms of the correlation between actual sPCa detection rates and reference 95% CIs. For a cohort of 2624 men with prostate-specific antigen >3.0 ng/ml and/or a suspicious digital rectal examination who underwent multiparametric MRI and two- to four-core targeted biopsies of PI-RADS ≥3 lesions and/or 12-core systematic biopsy, AUC values ranged from 0.527 to 0.914 and were <0.8 in four centers (40%). There was concordance between actual sPCa detection rates and reference 95% CIs for one or two PI-RADS categories when the AUC was <0.8, and for three or four PI-RADS categories when the AUC was ≥0.8. A review of procedures used for sPCa detection should be recommended in centers with suboptimal quality. Patient summary: We tested a method for assessing quality control for centers carrying out screening for early detection of prostate cancer. We found that the method can identify centers that may need to review their procedures for detection of significant prostate cancer.

Ethnobotany, phytochemistry, pharmacology and quality control of Peucedanum decursivum (Miq.) Maxim: A critical review.

ETHNOPHARMACOLOGICAL RELEVANCE: Dried roots of Peucedanum decursivum, a traditional Chinese medicine (TCM), has historically respiratory diseases such as cough, thick phlegm, headache, fever, and gynecological diseases, rheumatoid arthritis, and nasopharyngeal carcinoma. AIM OF THE STUDY: Made an endeavor to evaluate the research trajectory of P. decursivum, comprehensively discern its developmental status, and offer a guideline for future investigations. MATERIALS AND METHODS: A meticulous search of literatures and books from 1955 to 2024 via databases like PubMed, Web of Science and CNKI was conducted, including topics and keywords of " P. decursivum" "Angelica decursivum" and "Zihua Qianhu". RESULTS: P. decursivum and its prescriptions have traditionally been used for treating phlegm-heat cough, wind-heat cough, gastrointestinal diseases, pain relief and so on. It contains 234 identified compounds, encompassing coumarins, terpenes, volatile oils, phenolic acids, fatty acids and derivatives. It exhibits diverse pharmacological activities, including anti-asthmatic, anti-inflammatory, antioxidant effects, anti-hypertensive, anti-diabetic, anti-Alzheimer, and anti-cancer properties, primarily attributed to coumarins. Microscopic identification, HPLC fingerprinting, and bioinformatics identification are the primary methods currently used for the quality control. CONCLUSION: P. decursivum demonstrates anti-asthmatic, anti-inflammatory, and antioxidant effects, aligning with its traditional use. However, experimental validation of its efficacy against phlegm and viruses is needed. Additionally, analgesic effects mentioned in historical texts lack modern pharmacological studies. Numerous isolated compounds exhibit highly valuable medicinal properties. Future research can delve into exploring these substances further. Rigorous of heavy metal contamination, particularly Cd and Pb, is necessary. Simultaneously, investigating its pharmacokinetics and toxicity in humans is crucial for the safety.

BL-918 activates PINK1/Parkin signaling pathway to ameliorate the progression of Parkinson's disease.

The pathogenesis of Parkinson's disease (PD) has been associated with mitochondrial dysfunction. Given that the PINK1/Parkin pathway governs mitochondrial quality control by inducing mitophagy to remove damaged mitochondria, therapeutic approaches to activate PINK1/Parkin-mediated mitophagy have the potential in the treatment of PD. Here, we have identified a new small molecule, BL-918, as an inducer of mitophagy via activating the PINK1/Parkin pathway. BL-918 triggers PINK1 accumulation and Parkin mitochondrial translocation to initiate PINK1/Parkin-mediated mitophagy. We found that mitochondrial membrane potential and mitochondrial permeability transition (mPT) pore were involved in BL-918-induced PINK1/Parkin pathway activation. Moreover, we showed that BL-918 mitigated PD progression in MPTP-induced PD mice in a PINK1-dependent manner. Our results unravel a new activator of the PINK1/Parkin signaling pathway and provide a potential strategy for the treatment of PD and other diseases with dysfunctional mitochondria.

Automatic quality assessment of knee radiographs using knowledge graphs and convolutional neural networks.

BACKGROUND: X-ray radiography is a widely used imaging technique worldwide, and its image quality directly affects diagnostic accuracy. Therefore, X-ray image quality control (QC) is essential. However, subjectively assessing image quality is inefficient and inconsistent, especially when large amounts of image data are being evaluated. Thus, subjective assessment cannot meet current QC needs. PURPOSE: To meet current QC needs and improve the efficiency of image quality assessment, a complete set of quality assessment criteria must be established and implemented using artificial intelligence (AI) technology. Therefore, we proposed a multi-criteria AI system for automatically assessing the image quality of knee radiographs. METHODS: A knee radiograph QC knowledge graph containing 16 "acquisition technique" labels representing 16 image quality defects and five "clarity" labels representing five grades of clarity were developed. Ten radiographic technologists conducted three rounds of QC based on this graph. The single-person QC results were denoted as QC1 and QC2, and the multi-person QC results were denoted as QC3. Each technologist labeled each image only once. The ResNet model structure was then used to simultaneously perform classification (detection of image quality defects) and regression (output of a clarity score) tasks to construct an image QC system. The QC3 results, comprising 4324 anteroposterior and lateral knee radiographs, were used for model training (70% of the images), validation (10%), and testing (20%). The 865 test set data were used to evaluate the effectiveness of the AI model, and an AI QC result, QC4, was automatically generated by the model after training. Finally, using a double-blind method, the senior QC expert reviewed the final QC results of the test set with reference to the results QC3 and QC4 and used them as a reference standard to evaluate the performance of the model. The precision and mean absolute error (MAE) were used to evaluate the quality of all the labels in relation to the reference standard. RESULTS: For the 16 "acquisition technique" features, QC4 exhibited the highest weighted average precision (98.42% ± 0.81%), followed by QC3 (91.39% ± 1.35%), QC2 (87.84% ± 1.68%), and QC1 (87.35% ± 1.71%). For the image clarity features, the MAEs between QC1, QC2, QC3, and QC4 and the reference standard were 0.508 ± 0.021, 0.475 ± 0.019, 0.237 ± 0.016, and 0.303 ± 0.018, respectively. CONCLUSIONS: The experimental results show that our automated quality assessment system performed well in classifying the acquisition technique used for knee radiographs. The image clarity quality evaluation accuracy of the model must be further improved but is generally close to that of radiographic technologists. Intelligent QC methods using knowledge graphs and convolutional neural networks have the potential for clinical applications.

Body Part Selection for Size Classification of Two Trichogramma Species.

Body size is an important morphological characteristic that covaries with the quality of parasitoids and predators. Data show that the larger the organism is, the better the biological parameters and the host location by natural enemies in the field. The standard way of evaluating the size of parasitoids of the genus Trichogramma (Hymenoptera: Trichogrammatidae) is by measuring the tibia, but using only one body part to estimate the size of organisms can lead to miscalculations. In this paper, commercial Trichogramma pretiosum Riley, 1879 (Hymenoptera: Trichogrammatidae) and Trichogramma galloi Zucchi, 1988 (Hymenoptera: Trichogrammatidae) were mounted on slides for microscopy and photographed, and the photographs were used to measure their antennae, scutellum, ovipositor, tibia, and wing. Principal component analysis (PCA) and linear discriminant analysis (LDA) were performed to select the body part that best represents their size. PCA showed that all body parts represented size in a similar way, and LDA showed that the ovipositor was the most representative. We conclude that the best body parts for representing the size of the Trichogramma species studied are the wing and ovipositor, and at least two body parts are needed to detect two size groups.

PeakQC: A Software Tool for Omics-Agnostic Automated Quality Control of Mass Spectrometry Data.

Mass spectrometry is broadly employed to study complex molecular mechanisms in various biological and environmental fields, enabling 'omics' research such as proteomics, metabolomics, and lipidomics. As study cohorts grow larger and more complex with dozens to hundreds of samples, the need for robust quality control (QC) measures through automated software tools becomes paramount to ensure the integrity, high quality, and validity of scientific conclusions from downstream analyses and minimize the waste of resources. Since existing QC tools are mostly dedicated to proteomics, automated solutions supporting metabolomics are needed. To address this need, we developed the software PeakQC, a tool for automated QC of MS data that is independent of omics molecular types (i.e., omics-agnostic). It allows automated extraction and inspection of peak metrics of precursor ions (e.g., errors in mass, retention time, arrival time) and supports various instrumentations and acquisition types, from infusion experiments or using liquid chromatography and/or ion mobility spectrometry front-end separations and with/without fragmentation spectra from data-dependent or independent acquisition analyses. Diagnostic plots for fragmentation spectra are also generated. Here, we describe and illustrate PeakQC's functionalities using different representative data sets, demonstrating its utility as a valuable tool for enhancing the quality and reliability of omics mass spectrometry analyses.

Glycation in the cardiomyocyte.

Glycation is a protein post-translational modification that can occur on lysine and arginine residues as a result of a non-enzymatic process known as the Maillard reaction. This modification is irreversible, so the only way it can be removed is by protein degradation and replacement. Small reactive carbonyl species, glyoxal and methylglyoxal, are the primary glycating agents and are elevated in several conditions associated with an increased risk of cardiovascular disease, including diabetes, rheumatoid arthritis, smoking, and aging. Thus, how protein glycation impacts the cardiomyocyte is of particular interest, to both understand how these conditions increase the risk of cardiovascular disease and how glycation might be targeted therapeutically. Glycation can affect the cardiomyocyte through extracellular mechanisms, including RAGE-based signaling, glycation of the extracellular matrix that modifies the mechanical environment, and signaling from the vasculature. Intracellular glycation of the cardiomyocyte can impact calcium handling, protein quality control and cell death pathways, as well as the cytoskeleton, resulting in a blunted contractility. While reducing protein glycation and its impact on the heart has been an active area of drug development, multiple clinical trials have had mixed results and these compounds have not been translated to the clinic-highlighting the challenges of modulating myocyte glycation. Here we will review protein glycation and its effects on the cardiomyocyte, therapeutic attempts to reverse these, and offer insight as to the future of glycation studies and patient treatment.

Addressing researcher fraud: retrospective, real-time, and preventive strategies-including legal points and data management that prevents fraud.

Researcher fraud is often easy and enticing in academic research, with little risk of detection. Cases of extensive fraud continue to occur. The amount of fraud that goes undetected is unknown and may be substantial. Three strategies for addressing researcher fraud are (a) retrospective investigations after allegations of fraud have been made, (b) sting operations that provide conclusive evidence of fraud as it occurs, and (c) data management practices that prevent the occurrence of fraud. Institutional and regulatory efforts to address researcher fraud have focused almost exclusively on the retrospective strategy. The retrospective approach is subject to controversy due to the limitations of post-hoc evidence in science, the difficulty in establishing who actually committed the fraud in some cases, the application of a legal standard of evidence that is much lower than the usual standards of evidence in science, and the lack of legal expertise by scientists investigating fraud. The retrospective strategy may be reliably effective primarily in cases of extensive, careless fraud. Sting operations can overcome these limitations and controversies, but are not feasible in many situations. Data management practices that are effective at preventing researcher fraud and unintentional errors are well-established in clinical trials regulated by government agencies, but appear to be largely unknown or unimplemented in most academic research. Established data management practices include: archiving secure copies of the raw data, audit trails, restricted access to the data and data collection processes, software validation, quality control checks, blinding, preregistration of data processing and analysis programs, and research audits that directly address fraud. Current discussions about data management in academic research focus on sharing data with little attention to practices that prevent intentional and unintentional errors. A designation or badge such as error-controlled data management could be established to indicate research that was conducted with data management practices that effectively address intentional and unintentional errors.

MAMs and Mitochondrial Quality Control: Overview and Their Role in Alzheimer's Disease.

Alzheimer's disease (AD) represents the most widespread neurodegenerative disorder, distinguished by a gradual onset and slow progression, presenting a substantial challenge to global public health. The mitochondrial-associated membrane (MAMs) functions as a crucial center for signal transduction and material transport between mitochondria and the endoplasmic reticulum, playing a pivotal role in various pathological mechanisms of AD. The dysregulation of mitochondrial quality control systems is considered a fundamental factor in the development of AD, leading to mitochondrial dysfunction and subsequent neurodegenerative events. Recent studies have emphasized the role of MAMs in regulating mitochondrial quality control. This review will delve into the molecular mechanisms underlying the imbalance in mitochondrial quality control in AD and provide a comprehensive overview of the role of MAMs in regulating mitochondrial quality control.

Cycle-Based Control of Injection Moulding Process in Presence of Material Dual Sourcing Using Mass Feedback.

The low cost and precise tolerances of plastic injection moulded products are a major reason for the popularity of the manufacturing method. The tolerances are greatly influenced by the equipment, raw material and moulding process. One challenge is the raw material variation. This paper presents a production process using cycle based feedback of cycle mass, for control of part properties in the presence of material variation from dual sourcing. The part properties considered are part mass and outer dimensions. The process uses direct cycle mass feedback without additional process measurements in the proposed controller structure. The designed controller structure is tested in a multi-cavity mould while using raw materials from multiple vendors, encompassing five different grades. The results show a total decrease in part mass variance of approximately 50% and a decrease of length and width variance of approximately 40% compared to a moulding process with fixed settings.

Joint WHO/EDQM Collaborative study for the establishment of WHO 3rd International Standard and Ph. Eur. Biological Reference Preparation for Prekallikrein activator in albumin batch 7.

An international collaborative study was jointly organised by the World Health Organization (WHO) and the European Directorate for the Quality of Medicines & HealthCare (EDQM) to establish the WHO 3rd International Standard (IS) for Prekallikrein activator (PKA) and European Pharmacopoeia (Ph. Eur.) PKA in albumin Biological Reference Preparation (BRP) batch 7. Twenty-six laboratories took part in the study to calibrate these replacement batches, as well as an additional reserve batch for the WHO IS, against the current WHO 2nd IS for PKA (02/168). Ph. Eur. PKA in albumin BRP batch 6 was also included to evaluate the continuity of the consecutive batches of BRP. The centrally calculated overall Huber's means based on the results from laboratories with at least two valid assays were 29.6 and 29.6 IU/ampoule for the candidate WHO 3rd IS (Sample A) and reserve batch (Sample B), and were 38.4 and 37.0 IU/vial for the current BRP batch 6 (Sample C) and the candidate BRP batch 7 (Sample D). The intra-laboratory variation expressed as coefficient of variation (CV) ranged between 1.4 and 16.6 %. The inter-laboratory variation expressed as CV based on Huber's means ranged between 4.4 and 5.4 %. The Huber's mean activity of Sample D against Sample C was 36.6 IU/vial with a CV of 1.7 %. These results confirm the good continuity of the consecutive batches of BRP. Based on the results of this study, it is recommended to establish Sample A as the WHO 3rd IS for PKA with an assigned potency of 30 IU/ampoule and Sample D as the Ph. Eur. PKA in albumin BRP batch 7 with an assigned potency of 37 IU/vial. Sample B is intended to be kept as a future reserve replacement WHO IS.

Advancing Green Chemistry in Antiviral Therapeutics: A Comprehensive Review.

Cytomegalovirus (CMV) is a prevalent virus across the world that belongs to the family Herpesviridae but remains dormant in the body unless the immune system is compromised. In addition, when the bacterium is compromised without any health risks, the infection spreads from one person to another person through body fluids, such as saliva, blood, etc. Ganciclovir is an anti- viral medication used in treating viral infections, especially in the treatment of CMV in people with acquired immune deficiency syndrome and immunity at risk. The quality control of ganciclovir in industries is carried out by using anti-green solvents in large volumes; these solvents are not safe in consideration of environmental factors and analysts. Also, the waste generation by these solvents causes hazardous effects on the environment. Further, using 12 green analytical chemistry principles promotes the awareness of analytical judgments among the research groups. It is a revolutionary step in the analytical field to enhance the safety of the environment, and analysts, apart from safety, help to control waste production and conserve energy-reducing occupational hazards. Many works have been carried out for the quality control of ganciclovir using different solvents, such as acetonitrile, methanol, etc. Despite this, there are no existing methods with green solvents or procedures to reduce energy and waste generation. Therefore, the purpose of this review is to understand the drug profile of ganciclovir and the methods developed.

Preclinical SPECT and PET: Joint EANM and ESMI procedure guideline for implementing an efficient quality control programme.

The aim of this guideline is to provide recommendations for the implementation of an effective and efficient quality control (QC) programme for SPECT and PET systems in a preclinical imaging lab. These recommendations aim to strengthen the translational power of preclinical imaging results obtained using preclinical SPECT and PET. As for clinical imaging, reliability, reproducibility, and repeatability are essential when groups of animals are used in a longitudinal imaging experiment. The larger the variability of the imaging endpoint, the more animals are needed to be able to observe statistically significant differences between groups. Therefore, preclinical imaging requires quality control procedures to maintain reliability, reproducibility, and repeatability of imaging procedures, and to ensure the accuracy and precision of SPECT and PET quantification. While the Physics Committee of the European Association of Nuclear Medicine (EANM) has already published excellent procedure guidelines for Routine Quality Control Recommendations for Nuclear Medicine Instrumentation that also includes procedures for small animal PET systems, and important steps have already been made concerning preclinical quality control aspects, this new guideline provides a review and update of these previous guidelines such that guidelines are also adapted to new technological developments.

Mitochondrial Quality Control Processes at the Crossroads of Cell Death and Survival: Mechanisms and Signaling Pathways.

Biological aging results from an accumulation of damage in the face of reduced resilience. One major driver of aging is cell senescence, a state in which cells remain viable but lose their proliferative capacity, undergo metabolic alterations, and become resistant to apoptosis. This is accompanied by complex cellular changes that enable the development of a senescence-associated secretory phenotype (SASP). Mitochondria, organelles involved in energy provision and activities essential for regulating cell survival and death, are negatively impacted by aging. The age-associated decline in mitochondrial function is also accompanied by the development of chronic low-grade sterile inflammation. The latter shares some features and mediators with the SASP. Indeed, the unloading of damage-associated molecular patterns (DAMPs) at the extracellular level can trigger sterile inflammatory responses and mitochondria can contribute to the generation of DAMPs with pro-inflammatory properties. The extrusion of mitochondrial DNA (mtDNA) via mitochondrial outer membrane permeabilization under an apoptotic stress triggers senescence programs. Additional pathways can contribute to sterile inflammation. For instance, pyroptosis is a caspase-dependent inducer of systemic inflammation, which is also elicited by mtDNA release and contributes to aging. Herein, we overview the molecular mechanisms that may link mitochondrial dyshomeostasis, pyroptosis, sterile inflammation, and senescence and discuss how these contribute to aging and could be exploited as molecular targets for alleviating the cell damage burden and achieving healthy longevity.

Extracellular vesicles as carriers for mitochondria: Biological functions and clinical applications.

In recent years, research has increasingly focused on the biogenesis of extracellular vesicles (EVs) and the sorting mechanisms for their contents. Mitochondria can be selectively loaded into EVs, serving as a way to maintain cellular mitochondrial homeostasis. EV-mediated mitochondrial transfer has also been shown to greatly impact the function of target cells. Based on the mechanism of EV-mediated mitochondrial transfer, therapies can be developed to treat human diseases. This review summarizes the recent advances in the biogenesis and molecular composition of EVs. It also highlights the sorting and trafficking mechanisms of mitochondrial components into EVs. Furthermore, it explores the current role of EV-mediated mitochondrial transfer in the development of human diseases, as well as its diagnostic and therapeutic applications.