Mitochondrial 'Birth-Death' coordinator: An intelligent hydrogen nanogenerator to enhance intervertebral disc regeneration.

Currently, mitochondrial dysfunction caused by oxidative stress is a growing concern in degenerative diseases, notably intervertebral disc degeneration (IVDD). Dysregulation of the balance of mitochondrial quality control (MQC) has been considered the key contributor, while it's still challenging to effectively harmonize different MQC components in a simple and biologically safe way. Hydrogen gas (H2) is a promising mitochondrial therapeutic molecule due to its bio-reductivity and diffusibility across cellular membranes, yet its relationship with MQC regulation remains unknown. Herein, we propose a mitochondrial 'Birth-Death' coordinator achieved by an intelligent hydrogen nanogenerator (Fe@HP-OD), which can sustainably release H2 in response to the unique microenvironment in degenerated IVDs. Both in vitro and in vivo results prove alleviation of cellular oxidative stress and restoration of nucleus pulposus cells function, thereby facilitating successful IVD regeneration. Significantly, this study for the first time proposes the mitochondrial 'Birth-Death' coordination mechanism: 1) attenuation of overactivated mitochondrial 'Death' process (UPRmt and unselective mitophagy); and 2) activation of Adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling pathway for mitochondrial 'Birth-Death' balance (mitochondrial biogenesis and controlled mitophagy). These pioneering findings can fill in the gaps in molecular mechanisms for H2 regulation on MQC homeostasis, and pave the way for future strategies towards restoring equilibrium of MQC system against degenerative diseases.

A simple and rapid spectrophotometric method for the determination of trans-chalcone in raw-materialand topical formulation / Método espectrofotométrico simples e rápido paradeterminação de trans-chalcona em matéria-primae em formulação tópica

Trans-chalcone (TC) is a flavonoid precursor characterized by a wide spectrum of action, with anti-inflammatory and antioxidant effects. However, no validated methods are available in official compendia for the analysis of this substance. Thus, the aim of this work was to develop and validate a simple, fast, and reproducible spectrophotometric method for the analysis of TC in raw material, and in topical pharmaceutical formulation containing TC. The established conditions were: methanol as extracting solvent, and detection wavelength of 309 nm by UV spectrophotometer. All tests followed the rules of Resolution RDC 166, 2017. The proposed method was selective. Linearity was demonstrated in the concentration range of 1 to 8 µg/mL (r = 0.999). Repeatability and intermediate precision were confirmed by low relative standard deviation values of 1.53% and 2.70% for TC, and of 1.73% and 2.91% for formulation containing TC. Accuracy, evaluated through recovery test, was adequate, with minimum of 98.24% and maximum of 100.23% of recovery. It was observed that the small deliberate modifications done did not interfere with the results, demonstrating the method is robust. The results showed that the method was considered suitable for the intended purpose, inexpensive, easy to apply, selective, linear, precise, accurate, and robust for the determination TC, and pharmaceutical formulation containing TC. Thus, the method developed satisfies the need for an analytical method for the determination of TC, and topical formulation containing TC, being effective, innovative and able to aid in the development of the pharmaceutical field.

Trans-chalcona (TC) é um precursor de flavonoides caracterizado por um amplo espectro de ação, como efeitos anti-inflamatórios e antioxidantes. No entanto, não há método validado disponível em compêndio oficial para análise deste composto. Então, o objetivo deste trabalho foi desenvolver e validar um método espectrofotométrico, simples, rápido e reprodutível para análise de TC em matéria-prima, e em formulação farmacêutica tópica contendo TC. As condições estabelecidas foram: metanol como o solvente de extração, e detecção no comprimento de onda de 309 nm por espectrofotometria no UV. Todos os testes seguiram as normas da RDC 166, 2017. O método proposto foi seletivo. A linearidade foi demonstrada na faixa de concentração de 1 a 8 µg/mL (r = 0.999). A repetibilidade e a precisão intermediária foram confirmadas pelos valores baixos de desvio padrão relativo de 1,53% e 2,70% para a TC, e de 1,73% e 2,91% para a formulação contendo TC. A exatidão, avaliada por meio de testes de recuperação, foi adequada, com mínimo de 98,24% e máximo de 100,04% de recuperação. Observou-se que pequenas modificações no método não interferiram nos resultados, demonstrando que o método é robusto. Os resultados demonstraram que o método foi adequado para a finalidade pretendida, barato, de fácil aplicação, seletivo, linear, preciso, exato e robusto para determinação de TC, e de formulação contendo TC. Então o método desenvolvido satisfaz as necessidades de um método analítico para determinação de TC, e de formulação tópica contendo TC, e é eficaz, inovador e pode contribuir para o desenvolvimento da área farmacêutica.

Automated quality control analysis for American College of Radiology (ACR) digital mammography (DM) phantom images.

PURPOSE: To develop and validate an automated software analysis method for mammography image quality assessment of the American College of Radiology (ACR) digital mammography (DM) phantom images. METHODS: Twenty-seven DICOM images were acquired using Fuji mammography systems. All images were evaluated by three expert medical physicists using the Royal Australian and New Zealand College of Radiologists (RANZCR) mammography quality control guideline. To enhance the robustness and sensitivity assessment of our algorithm, an additional set of 12 images from a Hologic mammography system was included to test various phantom positional adjustments. The software automatically chose multiple regions of interest (ROIs) for analysis. A template matching method was primarily used for image analysis, followed by an additional method that locates and scores each target object (speck groups, fibers, and masses). RESULTS: The software performance shows a good to excellent agreement with the average scoring of observers (intraclass correlation coefficient [ICC] of 0.75, 0.79, 0.82 for speck groups, fibers, and masses, respectively). No significant differences were found in the scoring of target objects between human observers and the software. Both methods achieved scores meeting the pass criteria for speck groups and masses. Expert observers allocated lower scores to fiber objects, with diameters less than 0.61 mm, when compared to the software. The software was able to accurately score objects when the phantom position changed by up to 25 mm laterally, up to 5 degrees rotation, and overhanging the chest wall edge by up to 15 mm. CONCLUSIONS: Automated software analysis is a feasible method that may help improve the consistency and reproducibility of mammography image quality assessment with reduced reliance on human interaction and processing time.

Traditional uses, phytochemical constituents, pharmacological properties, and quality control of Pseudostellaria heterophylla (Miq.) Pax.

ETHNOPHARMACOLOGIC RELEVANCE: Pseudostellaria heterophylla (Miq.) Pax belongs to the Caryophyllaceae family, which is widely used in traditional Chinese medicine in Asia. P. heterophylla was first documented in the classical text Bencao Congxin, also known as "Haier Shen". As a renowned folk medicine with a long history of medicinal application in China, this plant is frequently employed to address spleen deficiency and fatigue, loss of appetite, and weakness after illness. In recent years, P. heterophylla has gained significant global attention as an important medicinal plant, attributable to its pharmacological activities on the immune and endocrine systems, as well as its diverse applications. AIM OF THE WORK: This review aims to deliver a comprehensive and analytical overview of the ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics, toxicology, and quality control of P. heterophylla, while also offering novel insights and opportunities for future research. MATERIALS AND METHODS: Relevant information regarding P. heterophylla was gathered from various databases, including Web of Science, PubMed, ACS Publications, Google Scholar, Baidu Scholar, and CNKI, in addition to The Catalogue of Life, the Flora of China database, and The World Flora Online. All published articles in multiple languages have been included and properly cited. The chemical structure of the compound was illustrated utilizing ChemDraw 19.0 software. RESULTS: P. heterophylla has been traditionally employed to address a range of ailments, including cancer, cardiovascular diseases, diabetes, and respiratory disorders. More than 289 active constituents have been identified in P. heterophylla, comprising cyclic peptides, polysaccharides, saponins, alkaloids, flavonoids, nucleosides, and amino acids. Pharmacological investigations have demonstrated that P. heterophylla and its active constituents exhibit a broad spectrum of biological activities, including anti-cancer, immunomodulatory, antioxidant, hypoglycemic, anti-inflammatory effects, modulation of intestinal flora, enhancement of cognitive function, and inhibition of tyrosine kinase activity. Furthermore, it is extensively utilized in the functional food and cosmetics industries. CONCLUSION: As a dual-purpose resource for both food and medicine, P. heterophylla possesses significant health care functions and considerable edible and medicinal value, with promising prospects for future development and utilization. However, numerous investigations into the biological activities of P. heterophylla are primarily focused on its extracts and bioactive constituents, and the mechanisms underlying the actions of these extracts and components remain unclear, with a dearth of studies on clinical efficacy and safety. Consequently, further detailed in vitro and in vivo studies investigating the mechanisms of action of pure active compounds of P. heterophylla are warranted, along with additional clinical investigations to ascertain the safety and efficacy of the plant for human use.

Mitochondrial Extracellular Vesicles (mitoEVs): Emerging mediators of cell-to-cell communication in health, aging and age-related diseases.

Mitochondria are metabolic and signalling hubs that integrate a plethora of interconnected processes to maintain cell homeostasis. They are also dormant mediators of inflammation and cell death, and with aging damages affecting mitochondria gradually accumulate, resulting in the manifestation of age-associated disorders. In addition to coordinate multiple intracellular functions, mitochondria mediate intercellular and inter-organ cross talk in different physiological and stress conditions. To fulfil this task, mitochondrial signalling has evolved distinct and complex conventional and unconventional routes of horizontal/vertical mitochondrial transfer. In this regard, great interest has been focused on the ability of extracellular vesicles (EVs), such as exosomes and microvesicles, to carry selected mitochondrial cargoes to target cells, in response to internal and external cues. Over the past years, the field of mitochondrial EVs (mitoEVs) has grown exponentially, revealing unexpected heterogeneity of these structures associated with an ever-expanding mitochondrial function, though the full extent of the underlying mechanisms is far from being elucidated. Therefore, emerging subsets of EVs encompass exophers, migrasomes, mitophers, mitovesicles, and mitolysosomes that can act locally or over long-distances to restore mitochondrial homeostasis and cell functionality, or to amplify disease. This review provides a comprehensive overview of our current understanding of the biology and trafficking of MitoEVs in different physiological and pathological conditions. Additionally, a specific focus on the role of mitoEVs in aging and the onset and progression of different age-related diseases is discussed.

Ethnobotanical usages, phytochemistry, pharmacology, and quality control of Chuanxiong Rhizoma: A review.

ETHNOPHARMACOLOGIC RELEVANCE: Chuanxiong Rhizoma (CX) is the dried root rhizomes of the plant Ligusticum chuanxiong Hort. of the family Umbelliferae. CX is listed as a superior herb in the book "Shennong Bencao Jing". It has a pungent and warm nature and belongs to the liver, gallbladder, and pericardium meridians. CX is documented in the Chinese Pharmacopoeia from 1963 to 2020 editions. CX as a well-known traditional Chinese medicine for promoting blood circulation, regulating qi, dispelling wind, and relieving pain, has been proven to contain a variety of bioactive compounds with diverse pharmacological activities and medicinal value. AIM OF THE STUDY: The current review aims to provide a comprehensive analysis of the botany, traditional uses, phytochemistry, pharmacology, toxicity, quality control and pharmacokinetics of CX. MATERIALS AND METHODS: The relevant information of CX was obtained from several databases including Web of Science, PubMed, ACS Publications, Google Scholar, Baidu Scholar, CNKI, Ph.D, MSc dissertations, as well as The Catalogue of Life, Flora of China database, and The Global Biodiversity Information Facility. RESULTS: CX is widely used in traditional medicine for treating various diseases related to the cardiovascular system, liver and kidney system, nervous system, respiratory system, and more. Over 400 compounds have been identified in CX, including phthalides, alkaloids, organic acids and its esters, polyphenols, terpenes and their derivatives, polysaccharides, hydrocarbons and their derivatives, coumarins, lignans and others. The plant extracts, compounds and Chinese patent medicines possess various pharmacological activities, including cardiovascular system protection, nervous system protection, cerebrovascular system protection, anti-inflammatory, liver and lung protection, anti-diabetes, anti-osteoporosis, anti-bacterial, anti-aging, anti-oxidant, immune regulation, prevention of DNA damage, prevention of postoperative peritoneal adhesion. CONCLUSION: Considering its traditional and modern applications, phytochemical composition, and pharmacological properties, CX can be regarded as a traditional Chinese medicine resource for treating various diseases related to the cardiovascular, hepatorenal, nervous, and respiratory systems. Current research mainly focuses on cell and animal experiments, where some active ingredients exhibit diverse pharmacological activities. However, further studies are needed to fully understand its specific mechanisms of action. In addition, there are multiple active ingredients in CX, but current research mainly focuses on the pharmacological effects of individual components, with little research on the interactions and synergistic effects between different components. It is recommended to strengthen the research on the interactions of CX compounds and their components to reveal the overall pharmacological mechanisms. This will contribute to quality control, new drug development, commercialization, and promote its continuous development in the field of medicine.

SIRT1 Regulates Mitochondrial Damage in N2a Cells Treated with the Prion Protein Fragment 106-126 via PGC-1α-TFAM-Mediated Mitochondrial Biogenesis.

Mitochondrial damage is an early and key marker of neuronal damage in prion diseases. As a process involved in mitochondrial quality control, mitochondrial biogenesis regulates mitochondrial homeostasis in neurons and promotes neuron health by increasing the number of effective mitochondria in the cytoplasm. Sirtuin 1 (SIRT1) is a NAD+-dependent deacetylase that regulates neuronal mitochondrial biogenesis and quality control in neurodegenerative diseases via deacetylation of a variety of substrates. In a cellular model of prion diseases, we found that both SIRT1 protein levels and deacetylase activity decreased, and SIRT1 overexpression and activation significantly ameliorated mitochondrial morphological damage and dysfunction caused by the neurotoxic peptide PrP106-126. Moreover, we found that mitochondrial biogenesis was impaired, and SIRT1 overexpression and activation alleviated PrP106-126-induced impairment of mitochondrial biogenesis in N2a cells. Further studies in PrP106-126-treated N2a cells revealed that SIRT1 regulates mitochondrial biogenesis through the PGC-1α-TFAM pathway. Finally, we showed that resveratrol resolved PrP106-126-induced mitochondrial dysfunction and cell apoptosis by promoting mitochondrial biogenesis through activation of the SIRT1-dependent PGC-1α/TFAM signaling pathway in N2a cells. Taken together, our findings further describe SIRT1 regulation of mitochondrial biogenesis and improve our understanding of mitochondria-related pathogenesis in prion diseases. Our findings support further investigation of SIRT1 as a potential target for therapeutic intervention of prion diseases.

Lonicerae Japonicae Flos with the homology of medicine and food: a review of active ingredients, anticancer mechanisms, pharmacokinetics, quality control, toxicity and applications.

Lonicerae Japonicae Flos (LJF, called Jinyinhua in China), comes from the dried flower buds or flowers to be opened of Lonicera japonica Thunb. in the Lonicera family. It has a long history of medicinal use and has a wide range of application prospects. As modern research advances, an increasing number of scientific experiments have demonstrated the anticancer potential of LJF. However, there is a notable absence of systematic reports detailing the anti-tumor effects of LJF. This review integrates the principles of Traditional Chinese Medicine (TCM) with contemporary pharmacological techniques, drawing upon literature from authoritative databases such as PubMed, CNKI, and WanFang to conduct a comprehensive study of LJF. Notably, a total of 507 compounds have been isolated and characterized from the plant to date, which include volatile oils, organic acids, flavonoids, iridoids, triterpenes and triterpenoid saponins. Pharmacological studies have demonstrated that LJF extract, along with components such as chlorogenic acid, luteolin, rutin, luteoloside, hyperoside and isochlorogenic acid, exhibits potential anticancer activities. Consequently, we have conducted a comprehensive review and summary of the mechanisms of action and clinical applications of these components. Furthermore, we have detailed the pharmacokinetics, quality control, and toxicity of LJF, while also discussing its prospective applications in the fields of biomedicine and preventive healthcare. It is hoped that these studies will provide valuable reference for the clinical research, development, and application of LJF.

Translation stalling induced mitochondrial entrapment of ribosomal quality control related proteins offers cancer cell vulnerability.

Ribosome-associated quality control (RQC) monitors ribosomes for aberrant translation. While the role of RQC in neurodegenerative disease is beginning to be appreciated, its involvement in cancer is understudied. Here, we show a positive correlation between RQC proteins ABCE1 and ZNF598 and high-grade muscle-invasive bladder cancer. Translational stalling by the inhibitor emetine (EME) leads to increased mitochondrial localization of RQC factors including ABCE1, ZNF598, and NEMF, which are continuously imported into mitochondria facilitated by increased mitochondrial membrane potential caused by EME. This reduces the availability of these factors in the cytosol, compromising the effectiveness of RQC in handling stalled ribosomes in the cytosol and those associated with the mitochondrial outer membrane (MOM). Imported RQC factors form aggregates inside the mitochondria in a process we term stalling-induced mitochondrial stress (SIMS). ABCE1 plays a crucial role in maintaining mitochondrial health during SIMS. Notably, cancer stem cells (CSCs) exhibit increased expression of ABCE1 and consequently are more resistant to EME-induced mitochondrial dysfunction. This points to a potential mechanism of drug resistance by CSCs. Our study highlights the significance of mitochondrial entrapment of RQC factors such as ABCE1 in determining the fate of cancer cells versus CSCs. Targeting ABCE1 or other RQC factors in translational inhibition cancer therapy may help overcome drug resistance.

A Framework for Quality Control in Quantitative Proteomics.

A thorough evaluation of the quality, reproducibility, and variability of bottom-up proteomics data is necessary at every stage of a workflow, from planning to analysis. We share vignettes applying adaptable quality control (QC) measures to assess sample preparation, system function, and quantitative analysis. System suitability samples are repeatedly measured longitudinally with targeted methods, and we share examples where they are used on three instrument platforms to identify severe system failures and track function over months to years. Internal QCs incorporated at the protein and peptide levels allow our team to assess sample preparation issues and to differentiate system failures from sample-specific issues. External QC samples prepared alongside our experimental samples are used to verify the consistency and quantitative potential of our results during batch correction and normalization before assessing biological phenotypes. We combine these controls with rapid analysis (Skyline), longitudinal QC metrics (AutoQC), and server-based data deposition (PanoramaWeb). We propose that this integrated approach to QC is a useful starting point for groups to facilitate rapid quality control assessment to ensure that valuable instrument time is used to collect the best quality data possible. Data are available on Panorama Public and ProteomeXchange under the identifier PXD051318.

Proteome and Glycoproteome Analyses Reveal Regulation of Protein Glycosylation Site-Specific Occupancy and Lysosomal Hydrolase Maturation by N-Glycan-Dependent ER-Quality Control.

N-Glycan-dependent endoplasmic reticulum quality control (ERQC) primarily mediates protein folding, which determines the fate of the polypeptide. Monoglucose residues on N-glycans determine whether the nascent N-glycosylated proteins enter into and escape from the calnexin (CANX)/calreticulin (CALR) cycle, which is a central system of the ERQC. To reveal the impact of ERQC on glycosylation and protein fate, we performed comprehensive quantitative proteomic and glycoproteomic analyses using cells defective in N-glycan-dependent ERQC. Deficiency of MOGS encoding the ER α-glucosidase I, CANX, or/and CALR broadly affected protein expression and glycosylation. Among the altered glycoproteins, the occupancy of oligomannosidic N-glycans was significantly affected. Besides the expected ER stress, proteins and glycoproteins involved in pathways for lysosome and viral infection are differentially changed in those deficient cells. We demonstrated that lysosomal hydrolases were not correctly modified with mannose-6-phosphates on the N-glycans and were directly secreted to the culture medium in N-glycan-dependent ERQC mutant cells. Overall, the CANX/CALR cycle promotes the correct folding of glycosylated peptides and influences the transport of lysosomal hydrolases.

Efficacy of a real-time intelligent quality-control system for the detection of early upper gastrointestinal neoplasms: a multicentre, single-blinded, randomised controlled trial.

Background: Oesophagogastroduodenoscopy (OGD) quality and identification of the early upper gastrointestinal (UGI) neoplasm play an important role in detecting the UGI neoplasm. However, the optimal method for quality control in daily OGD procedures is currently lacking. We aimed to evaluate the efficacy of a real-time intelligent quality-control system (IQCS), which combines OGD quality control with lesion detection of early UGI neoplasms. Methods: We performed a multicentre, single-blinded, randomised controlled trial at 6 hospitals in China. Patients aged 40-80 years old who underwent painless OGD were screened for enrolment in this study. Patients with a history of advanced UGI cancer, stenosis, or obstruction in UGI tract were excluded. Eligible subjects were randomly assigned (1:1) to either the routine or IQCS group to undergo standard OGD examination and OGD examination aided by IQCS, respectively. Patients were masked to the randomisation status. The primary outcome was the detection of early UGI neoplasms. All analyses were done on a per-protocol basis. This trial is registered with ClinicalTrials.gov, NCT04720924. Findings: Between January 16, 2021 and December 23, 2022, 1840 patients were randomised (IQCS group: 919, routine group: 921). The full analysis set consisted of 914 in the IQCS group and 915 in the routine group. The early UGI neoplasms detection rate in the IQCS group (6.1%, 56/914) was significantly higher than in the routine group (2.3%, 21/915; P = 0.0001). The IQCS group had fewer blind spots (2.3 vs. 6.2, P < 0.0001). The IQCS group had higher stomach cleanliness on cardia or fundus (99.5% vs. 87.9%, P < 0.0001), body (98.9% vs. 88.0%, P < 0.0001), angulus (99.8% vs. 88.4%, P < 0.0001) and antrum or pylorus (100.0% vs. 87.4%, P < 0.0001). The inspection time (576.2 vs. 574.5s, P = 0.91) and biopsy rate (57.2% vs. 56.6%, P = 0.83) were not different between the groups. The early UGI neoplasms detection rate in the IQCS group increased in both non-academic centres (RR = 3.319, 95% CI 1.277-9.176; P = 0.0094) and academic centres (RR = 2.416, 95% CI 1.301-4.568; P = 0.0034). The same improvements were observed for both less-experienced endoscopists (RR = 2.650, 95% CI 1.330-5.410; P = 0.0034) and experienced endoscopists (RR = 2.710, 95% CI 1.226-6.205; P = 0.010). No adverse events or serious adverse events were reported in the two groups. Interpretation: The IQCS improved the OGD quality and increased early UGI neoplasm detection in different hospital types and endoscopist experiences. IQCS could play an important role in primary basic hospitals and non-expert endoscopists to improve the diagnostic accuracy of early UGI neoplasms. The effectiveness of IQCS in real-world clinical settings needs a larger population validation. Funding: Key R&D Program of Shandong Province, China (Major Scientific and Technological Innovation Project), National Natural Science Foundation of China, the Taishan Scholars Program of Shandong Province, the National Key Research and Development Program of China, and the Shandong Provincial Natural Science Foundation.

Botany, Traditional Use, Phytochemistry, Pharmacology and Quality Control of Taraxaci herba: Comprehensive Review.

Taraxaci herba, as a traditional Chinese medicine, is the name of the Taraxacum genus in the Asteraceae family. Documented in the Tang Herbal Medicine (Tang Dynasty, AD 657-659), its medicinal properties cover a wide range of applications such as acute mastitis, lung abscess, conjunctival congestion, sore throat, damp-heat jaundice, and vision improvement. In the Chinese Pharmacopoeia (Edition 2020), more than 40 kinds of China-patented drugs containing Taraxaci herba were recorded. This review explores the evolving scientific understanding of Taraxaci herba, covering facets of ethnopharmacology, botany, phytochemistry, pharmacology, artificial cultivation, and quality control. In particular, the chemical constituents and pharmacological research are reviewed. Taraxaci herba has been certified as a traditional medicine plant, and its flavonoids, phenolic acids, and terpenoids have been identified and separated, which include Chicoric acid, taraxasterol, Taraxasteryl acetate, Chlorogenic acid, isorhamnetin, and luteolin; they are responsible for anti-inflammatory, antioxidant, antibacterial, anti-tumor, and anti-cancer activities. These findings validate the traditional uses of Taraxaci herba and lay the groundwork for further scientific exploration. The sources used in this study include Web of Science, Pubmed, the CNKI site, classic monographs, the Chinese Pharmacopoeia, the Chinese Medicine Dictionary, and doctoral and master's theses.

Latent Diffusion Models to Enhance the Performance of Visual Defect Segmentation Networks in Steel Surface Inspection.

This paper explores the use of state-of-the-art latent diffusion models, specifically stable diffusion, to generate synthetic images for improving the robustness of visual defect segmentation in manufacturing components. Given the scarcity and imbalance of real-world defect data, synthetic data generation offers a promising solution for training deep learning models. We fine-tuned stable diffusion using the LoRA technique on the NEU-seg dataset and evaluated the impact of different ratios of synthetic to real images on the training set of DeepLabV3+ and FPN segmentation models. Our results demonstrated a significant improvement in mean Intersection over Union (mIoU) when the training dataset was augmented with synthetic images. This study highlights the potential of diffusion models for enhancing the quality and diversity of training data in industrial defect detection, leading to more accurate and reliable segmentation results. The proposed approach achieved improvements of 5.95% and 6.85% in mIoU of defect segmentation on each model over the original dataset.

Two-Dimensional Mammography Imaging Techniques for Screening Women with Silicone Breast Implants: A Pilot Phantom Study.

This study aimed to evaluate the impact of three two-dimensional (2D) mammographic acquisition techniques on image quality and radiation dose in the presence of silicone breast implants (BIs). Then, we propose and validate a new International Atomic Energy Agency (IAEA) phantom to reproduce these techniques. Images were acquired on a single Hologic Selenia Dimensions® unit. The mammography of the left breast of a single clinical case was included. Three methods of image acquisition were identified. They were based on misused, recommended, and reference settings. In the clinical case, image criteria scoring and the signal-to-noise ratio on breast tissue (SNRBT) were determined for two 2D projections and compared between the three techniques. The phantom study first compared the reference and misused settings by varying the AEC sensor position and, second, the recommended settings with a reduced current-time product (mAs) setting that was 13% lower. The signal-difference-to-noise ratio (SDNR) and detectability indexes at 0.1 mm (d' 0.1 mm) and 0.25 mm (d' 0.25 mm) were automatically quantified using ATIA software. Average glandular dose (AGD) values were collected for each acquisition. A statistical analysis was performed using Kruskal-Wallis and corrected Dunn tests (p < 0.05). The SNRBT was 2.6 times lower and the AGD was -18% lower with the reference settings compared to the recommended settings. The SNRBT values increased by +98% with the misused compared to the recommended settings. The AGD increased by +79% with the misused settings versus the recommended settings. The median values of the reference settings were 5.8 (IQR 5.7-5.9), 1.2 (IQR 0.0), 7.0 (IQR 6.8-7.2) and 1.2 (IQR 0.0) mGy and were significantly lower than those of the misused settings (p < 0.03): 7.9 (IQR 6.1-9.7), 1.6 (IQR 1.3-1.9), 9.2 (IQR 7.5-10.9) and 2.2 (IQR 1.4-3.0) mGy for the SDNR, d' 0.1 mm, d' 0.25 mm and the AGD, respectively. A comparison of the recommended and reduced settings showed a reduction of -6.1 ± 0.6% (p = 0.83), -7.7 ± 0.0% (p = 0.18), -6.4 ± 0.6% (p = 0.19) and -13.3 ± 1.1% (p = 0.53) for the SDNR, d' 0.1 mm, d' 0.25 mm and the AGD, respectively. This study showed that the IAEA phantom could be used to reproduce the three techniques for acquiring 2D mammography images in the presence of breast implants for raising awareness and for educational purposes. It could also be used to evaluate and optimize the manufacturer's recommended settings.

Characterization of residual microRNAs in AAV vector batches produced in HEK293 mammalian cells and Sf9 insect cells.

With more than 130 clinical trials and 8 approved gene therapy products, adeno-associated virus (AAV) stands as one of the most popular vehicles to deliver therapeutic DNA in vivo. One critical quality attribute analyzed in AAV batches is the presence of residual DNA, as it could pose genotoxic risks or induce immune responses. Surprisingly, the presence of small cell-derived RNAs, such as microRNAs (miRNAs), has not been investigated previously. In this study, we examined the presence of miRNAs in purified AAV batches produced in mammalian or in insect cells. Our findings revealed that miRNAs were present in all batches, regardless of the production cell line or capsid serotype (2 and 8). Quantitative assays indicated that miRNAs were co-purified with the recombinant AAV particles in a proportion correlated with their abundance in the production cells. The level of residual miRNAs was reduced via an immunoaffinity chromatography purification process including a tangential flow filtration step or by RNase treatment, suggesting that most miRNA contaminants are likely non-encapsidated. In summary, we demonstrate, for the first time, that miRNAs are co-purified with AAV particles. Further investigations are required to determine whether these miRNAs could interfere with the safety or efficacy of AAV-mediated gene therapy.

MIBLood-EV: An Online Reporting Tool to Facilitate the Standardized Reporting of Preanalytical Variables and Quality Control of Plasma and Serum to Enhance Rigor and Reproducibility in Liquid Biopsy Research.

Pre-analytical variability significantly impacts the reproducibility of liquid biopsy research, which is critical for precision medicine and biomedical research. This report highlights the challenges and variability in the pre-analytical processes of liquid biopsies, especially regarding extracellular vesicles (EVs), which are crucial for diagnostics in oncology. The MIBlood-EV initiative aims to standardize the reporting of pre-analytical variables and the quality control of plasma and serum samples to enhance reproducibility in EV research. By providing a comprehensive and flexible reporting framework, MIBlood-EV seeks to improve the reliability of EV studies and facilitate the development of evidence-based protocols, ultimately advancing the field of liquid biopsy research.

Recent advances in Scutellariae radix: A comprehensive review on ethnobotanical uses, processing, phytochemistry, pharmacological effects, quality control and influence factors of biosynthesis.

Background: Scutellariae radix (SR) is the dried root of Scutellaria baicalensis Georgi. It has a long history of ethnic medicinal use, traditionally recognized for its efficacy in clearing heat， drying dampness, eliminating fire， removing toxins , stopping bleeding and tranquilizing fetus to prevent miscarriage. Clinically, it is used to treat cold, fever, migraine, hand-foot-and-mouth diseases, liver cancer and inflammatory diseases. Purpose: The review aims to provide a comprehensive reference on the ethnobotanical uses, processing, phytochemistry, pharmacological effect, quality control and influence factors of biosynthesis for a deeper understanding of SR. Results and conclusion: A total of 210 isolated components have been reported in the literature, including flavonoids and their glycosides, phenylpropanoids, phenylethanoid glycosides, phenolic acids, volatile components, polysaccharides and others. The extract of SR and its main flavonoids such as baicalin, baicalein, wogonin, wogonoside, and scutellarin showed antioxidant, anti-inflammatory, anti-tumor, antiviral, hepatoprotective, and neuroprotective effects. However, further studies are required to elucidate its mechanisms of action and clinical applications. The pharmacodynamic evaluation based on traditional efficacy should be conducted. Although various analytical methods have been established for the quality control of SR, there are gaps in the research regarding efficacy-related quality markers and the development of quality control standards for its processed products. The regulatory mechanisms of flavonoids biosynthesis remain to be explored while the influence of environmental and transcription factors on the biosynthesis have been studied. In conclusion, SR is a promising herbal medicine with significant potential for future development.

N-acetylcysteine, a small molecule scavenger of reactive oxygen species, alleviates cardiomyocyte damage by regulating OPA1-mediated mitochondrial quality control and apoptosis in response to oxidative stress.

Background: Oxidative stress-induced mitochondrial damage is the major cause of cardiomyocyte dysfunction. Therefore, the maintenance of mitochondrial function, which is regulated by mitochondrial quality control (MQC), is necessary for cardiomyocyte homeostasis. This study aimed to explore the underlying mechanisms of N-acetylcysteine (NAC) function and its relationship with MQC. Methods: A hydrogen peroxide-induced oxidative stress model was established using H9c2 cardiomyocytes treated with or without NAC prior to oxidative stress stimulation. Autophagy with light chain 3 (LC3)-green fluorescent protein (GFP) assay, reactive oxygen species (ROS) with the 2',7'-dichlorodi hydrofluorescein diacetate (DCFH-DA) fluorescent, lactate dehydrogenase (LDH) release assay, adenosine triphosphate (ATP) content assay, and a mitochondrial membrane potential detection were used to evaluate mitochondrial dynamics in H2O2-treated H9c2 cardiomyocytes, with a focus on the involvement of MQC regulated by NAC. Cell apoptosis was analyzed using caspase-3 activity assay and Annexin V-fluorescein isothiocyanate (V-FITC)/propidium iodide (PI) double staining. Results: We observed that NAC improved cell viability, reduced ROS levels, and partially restored optic atrophy 1 (OPA1) protein expression under oxidative stress. Following transfection with a specific OPA1-small interfering RNA, the mitophagy, mitochondrial dynamics, mitochondrial functions, and cardiomyocyte apoptosis were evaluated to further explore the mechanisms of NAC. Our results demonstrated that NAC attenuated cardiomyocyte apoptosis via the ROS/OPA1 axis and protected against oxidative stress-induced mitochondrial damage via the regulation of OPA1-mediated MQC. Conclusions: NAC ameliorated the injury to H9c2 cardiomyocytes caused by H2O2 by promoting the expression of OPA1, consequently improving mitochondrial function and decreasing apoptosis.

Addressing Global Gaps in Mammography Screening for Improved Breast Cancer Detection: A Review of the Literature.

Breast cancer is the second most common cancer globally, with 2.3 million new cases annually, constituting 11.6% of all cancer cases. It is also the fourth leading cause of cancer deaths, claiming 670,000 lives a year. This high incidence of breast cancer morbidity worldwide has increased the urgent need for standardized and adequate screening methods, including clinical breast examination, self-breast examination, and mammography screening tests for non-symptomatic individuals. Mammography is considered the gold standard for breast cancer screening, with early randomized control trials showing significant reductions in mortality rates in women aged 50 and over (International Agency for Research on Cancer and American College of Radiology). Despite this, discrepancies in mammography practices across different healthcare settings regarding adherence to international standards raise concerns. A comprehensive review of the vast literature looking at the practices and norms of mammography screening worldwide highlighted several domains that present limitations to screening. These include epidemiological data deficits, lack of educational training offered to radiographers and varied image quality indices, exposure technique, method of breast compression, dose calculation, reference levels, screening frequency intervals, and diverse distribution of resources, particularly in developing countries. These factors shed light on the substantial discrepancies in the implementation and efficacy of screening programs, underscoring the necessity for future research endeavors to collaborate in creating coherent, standardized, evidence-based guidelines. Addressing these issues can enhance the feasibility, sensitivity, and accessibility of screening programs, resulting in favorable impacts on the early diagnosis and survival of breast cancer on a global scale.