The performance of homopolymer detection using dichromatic and tetrachromatic fluorogenic next-generation sequencing platforms.

OBJECTIVES: Homopolymer (HP) sequencing is error-prone in next-generation sequencing (NGS) assays, and may induce false insertion/deletions and substitutions. This study aimed to evaluate the performance of dichromatic and tetrachromatic fluorogenic NGS platforms when sequencing homopolymeric regions. RESULTS: A HP-containing plasmid was constructed and diluted to serial frequencies (3%, 10%, 30%, 60%) to determine the performance of an MGISEQ-2000, MGISEQ-200, and NextSeq 2000 in HP sequencing. An evident negative correlation was observed between the detected frequencies of four nucleotide HPs and the HP length. Significantly decreased rates (P < 0.01) were found in all 8-mer HPs in all three NGS systems at all four expected frequencies, except in the NextSeq 2000 at 3%. With the application of a unique molecular identifier (UMI) pipeline, there were no differences between the detected frequencies of any HPs and the expected frequencies, except for poly-G 8-mers using the MGI 200 platform. UMIs improved the performance of all three NGS platforms in HP sequencing. CONCLUSIONS: We first constructed an HP-containing plasmid based on an EGFR gene backbone to evaluate the performance of NGS platforms when sequencing homopolymeric regions. A highly comparable performance was observed between the MGISEQ-2000 and NextSeq 2000, and introducing UMIs is a promising approach to improve the performance of NGS platforms in sequencing homopolymeric regions.

Characterization and mitigation of artifacts derived from NGS library preparation due to structure-specific sequences in the human genome.

BACKGROUND: Hybridization capture-based targeted next generation sequencing (NGS) is gaining importance in routine cancer clinical practice. DNA library preparation is a fundamental step to produce high-quality sequencing data. Numerous unexpected, low variant allele frequency calls were observed in libraries using sonication fragmentation and enzymatic fragmentation. In this study, we investigated the characteristics of the artifact reads induced by sonication and enzymatic fragmentation. We also developed a bioinformatic algorithm to filter these sequencing errors. RESULTS: We used pairwise comparisons of somatic single nucleotide variants (SNVs) and insertions and deletions (indels) of the same tumor DNA samples prepared using both ultrasonic and enzymatic fragmentation protocols. Our analysis revealed that the number of artifact variants was significantly greater in the samples generated using enzymatic fragmentation than using sonication. Most of the artifacts derived from the sonication-treated libraries were chimeric artifact reads containing both cis- and trans-inverted repeat sequences of the genomic DNA. In contrast, chimeric artifact reads of endonuclease-treated libraries contained palindromic sequences with mismatched bases. Based on these distinctive features, we proposed a mechanistic hypothesis model, PDSM (pairing of partial single strands derived from a similar molecule), by which these sequencing errors derive from ultrasonication and enzymatic fragmentation library preparation. We developed a bioinformatic algorithm to generate a custom mutation "blacklist" in the BED region to reduce errors in downstream analyses. CONCLUSIONS: We first proposed a mechanistic hypothesis model (PDSM) of sequencing errors caused by specific structures of inverted repeat sequences and palindromic sequences in the natural genome. This new hypothesis predicts the existence of chimeric reads that could not be explained by previous models, and provides a new direction for further improving NGS analysis accuracy. A bioinformatic algorithm, ArtifactsFinder, was developed and used to reduce the sequencing errors in libraries produced using sonication and enzymatic fragmentation.

Recent Advances in Revealing the Electrocatalytic Mechanism for Hydrogen Energy Conversion System.

In light of the intensifying global energy crisis and the mounting demand for environmental protection, it is of vital importance to develop advanced hydrogen energy conversion systems. Electrolysis cells for hydrogen production and fuel cell devices for hydrogen utilization are indispensable in hydrogen energy conversion. As one of the electrolysis cells, water splitting involves two electrochemical reactions, hydrogen evolution reaction and oxygen evolution reaction. And oxygen reduction reaction coupled with hydrogen oxidation reaction, represent the core electrocatalytic reactions in fuel cell devices. However, the inherent complexity and the lack of a clear understanding of the structure-performance relationship of these electrocatalytic reactions, have posed significant challenges to the advancement of research in this field. In this work, the recent development in revealing the mechanism of electrocatalytic reactions in hydrogen energy conversion systems is reviewed, including in situ characterization and theoretical calculation. First, the working principles and applications of operando measurements in unveiling the reaction mechanism are systematically introduced. Then the application of theoretical calculations in the design of catalysts and the investigation of the reaction mechanism are discussed. Furthermore, the challenges and opportunities are also summarized and discussed for paving the development of hydrogen energy conversion systems.

Influence of left ventricular ejection fraction in patients undergoing contemporary pLVAD-supported high-risk PCI.

BACKGROUND: Left ventricular (LV) systolic dysfunction worsens outcomes in patients undergoing percutaneous coronary intervention (PCI). The objective of this study, therefore, was to evaluate outcomes of pLVAD-supported high-risk PCI (HRPCI) patients according to LV ejection fraction (LVEF). METHODS: Patients from the PROTECT III study undergoing pLVAD-supported HRPCI were stratified according to baseline LVEF: severe LV dysfunction (LVEF <30%), mild and moderate LV dysfunction (LVEF ≥30% to <50%), or preserved LV function (LVEF ≥50%). Major adverse cardiovascular and cerebrovascular events (MACCE: composite of all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeat revascularization), and PCI-related complications were assessed at 90 days and mortality was assessed at 1-year. RESULTS: From March 2017 to March 2020, 940 patients had evaluable baseline LVEF recorded in the study database. Patients with preserved LV function were older, more frequently presented with myocardial infarction, and underwent more left main PCI and atherectomy. Immediate PCI-related coronary complications were infrequent (2.7%, overall), similar between groups (P = 0.98), and not associated with LVEF. Unadjusted 90-day MACCE rates were similar among LVEF groups; however, as a continuous variable, LVEF was associated with both 90-day MACCE (adj.HR per 5% 0.89, 95% CI [0.80, 0.98], P = 0.018) and 1-year mortality (adj.HR per 5% 0.84 [0.78, 0.90], P <0.0001). CONCLUSIONS: Patients who underwent pLVAD-supported HRPCI exhibited low incidence of PCI-related complications, regardless of baseline LVEF. However, LVEF was associated with 90-day MACCE and 1-year mortality.

Synergistic Enhancement on the Sensing Performance of Mixed Potential NH3 Sensors by Fe and Mo Codoping into BiVO4.

Mixed potential ammonia (NH3) sensors with the Fe- and Mo-codoped BiVO4 sensing electrode and Ag reference electrode based on the yttria-stabilized zirconia solid electrolyte were developed. Fe- and Mo-doped BiVO4 sensing materials were prepared using solution combustion synthesis and then characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS). It was observed that Fe doping could greatly improve the response rate, while Mo doping could enhance the response signal (ΔU) and sensitivity. Based on the optimal doping ratio of Fe and Mo each, the synergistic enhancement of the performance by Fe and Mo codoping was investigated. The sensor coated by BiV0.75Fe0.2Mo0.05Oδ materials exhibited a prominent sensing performance to a low concentration of 10-50 ppm of NH3 at 525 °C with the outstanding sensitivity of -148.988 mV/decade. Fe and Mo doping also improved the selectivity of the sensor to NH3, with the relative deviations less than ±8% of other typical gases' interference including NO, NO2, CO, CO2, and CH4. Besides, the sensor showed good resistance to fluctuations in the oxygen concentration and favorable stability against changes in the water vapor concentration. In addition, the sensor also exhibited good long-term stability. The mixed potential response mechanism was further discussed and analyzed through polarization curves as well as through gas chromatography and infrared absorption spectroscopy.

Paenalcaligenes faecalis sp. nov., a novel species of the family Alcaligenaceae isolated from chicken faeces.

A Gram-negative, motile, rod-shaped aerobic and alkalogenic bacterium, designated as strain YLCF04T, was isolated from chicken faeces. Its growth was optimal at 28 °C (range, 10-40 °C), pH 8 (range, pH 6-9) and in 1 % (w/v) NaCl (range, 0-10 %). It was classified to the genus Paenalcaligenes and was most closely related to Paenalcaligenes hominis CCUG 53761AT (97.5 % similarity) based on 16S rRNA gene sequence analysis. Average nucleotide identity and digital DNA-DNA hybridization values between YLCF04T and P. hominis CCUG 53761AT were 76.3 and 18.2 %, respectively. Strain YLCF04T has a genome size of 2.7 Mb with DNA G+C content of 46.3 mol%. Based on its phylogenetic, genomic, phenotypic and biochemical characteristics, strain YLCF04T represents a novel species of the genus Paenalcaligenes, for which the name Paenalcaligenes faecalis sp. nov. is proposed. The type strain is YLCF04T (=CCTCC AB 2022359T= KCTC 92789T).

Spatiotemporal mapping of nanotopography and thickness transitions of ultrathin foam films.

Freshly formed soap films, soap bubbles, or foam films display iridescent colors due to thin film interference that changes as squeeze flow drives drainage and a progressive decrease in film thickness. Ultrathin (thickness <100 nm) freestanding films of soft matter containing micelles, particles, polyelectrolyte-surfactant complexes, or other supramolecular structures or liquid crystalline phases display drainage via stratification. A fascinating array of thickness variations and transitions, including stepwise thinning and coexistence of thick-thin flat regions, arise in micellar foam films that undergo drainage via stratification. In this tutorial, we describe the IDIOM (interferometry digital imaging optical microscopy) protocols that combine the conventional interferometry principle with digital filtration and image analysis to obtain nanometer accuracy for thickness determination while having high spatial and temporal resolution. We provide fully executable image analysis codes and algorithms for the analysis of nanotopography and summarize some of the unique insights obtained for stratified micellar foam films.

A comprehensive performance evaluation, comparison, and integration of computational methods for detecting and estimating cross-contamination of human samples in cancer next-generation sequencing analysis.

Cross-sample contamination is one of the major issues in next-generation sequencing (NGS)-based molecular assays. This type of contamination, even at very low levels, can significantly impact the results of an analysis, especially in the detection of somatic alterations in tumor samples. Several contamination identification tools have been developed and implemented as a crucial quality-control step in the routine NGS bioinformatic pipeline. However, no study has been published to comprehensively and systematically investigate, evaluate, and compare these computational methods in the cancer NGS analysis. In this study, we comprehensively investigated nine state-of-the-art computational methods for detecting cross-sample contamination. To explore their application in cancer NGS analysis, we further compared the performance of five representative tools by qualitative and quantitative analyses using in silico and simulated experimental NGS data. The results showed that Conpair achieved the best performance for identifying contamination and predicting the level of contamination in solid tumors NGS analysis. Moreover, based on Conpair, we developed a Python script, Contamination Source Predictor (ConSPr), to identify the source of contamination. We anticipate that this comprehensive survey and the proposed tool for predicting the source of contamination will assist researchers in selecting appropriate cross-contamination detection tools in cancer NGS analysis and inspire the development of computational methods for detecting sample cross-contamination and identifying its source in the future.

Response of tree growth to drought variability in arid areas: Local hydroclimate and large-scale precipitation.

The impact of drought on terrestrial ecosystems is increasing, and the spatiotemporal heterogeneity of drought changes exacerbates the difficulty of determining ecosystem responses, especially in arid regions far from oceans. Tree rings have been widely used to understand how forest ecosystems respond to drought. However, the link between local hydroclimate variations related to tree rings and large-scale climate changes is not clear in the Qilian Mountains. Here, we used the tree ring width index to analyze the trend of Picea crassifolia growth and its relationship with climate in the middle Qilian Mountains. The results showed that the radial growth trend of Picea crassifolia is synchronized in the middle Qilian Mountains by calculating the Gleichläufigkeit index (GLK). Our analyses indicated that tree radial growth is positively correlated with drought during the growing season. Tree growth responds stably to drought (scPDSI and SPEI) and precipitation but unstably to temperature during 1950-2019. We further traced the meteorological factors that cause regional drought changes associated with radial growth. An increased total precipitation and decreased evaporation contribute to drought alleviation, favoring an increased tree radial growth. The increased total precipitation is mainly due to increased large-scale precipitation, which is related to water vapor transport changes. This study attempts to explore the influence of large-scale meteorology on regional drought change and its related tree radial growth response, which helps us to better understand the changes in forest ecosystems under climate change.

Suppressing UBE2N ameliorates Alzheimer's disease pathology through the clearance of amyloid beta.

INTRODUCTION: Aging is one of the risk factors for the early onset of Alzheimer's disease (AD). We previously discovered that the age-dependent increase in Ubiquitin Conjugating Enzyme E2 N (UBE2N) plays a role in the accumulation of misfolded proteins through K63 ubiquitination, which has been linked to AD pathogenesis. However, the impact of UBE2N on amyloid pathology and clearance has remained unknown. RESULTS: We observed the elevated UBE2N during the amyloid beta (Aß) generation in the brains of 5×FAD, APP/PS1 mice, and patients with AD, in comparison to healthy individuals. UBE2N overexpression exacerbated amyloid deposition in 5×FAD mice and senescent monkeys, whereas knocking down UBE2N via CRISPR/Cas9 reduced Aß generation and cognitive deficiency. Moreover, pharmacological inhibition of UBE2N ameliorated Aß pathology and subsequent transcript defects in 5×FAD mice. DISCUSSION: We have discovered that age-dependent expression of UBE2N is a critical regulator of AD pathology. Our findings suggest that UBE2N could serve as a potential pharmacological target for the advancement of AD therapeutics. HIGHLIGHTS: Ubiquitin Conjugating Enzyme E2 N (UBE2N) level was elevated during amyloid beta (Aß) deposition in AD mouse and patients' brains. UBE2N exacerbated Aß generation in the AD mouse and senescent monkey. Drug inhibition of UBE2N ameliorated Aß pathology and cognitive deficiency.

Age-Dependent Inflammatory Microenvironment Mediates Alveolar Regeneration.

Lung aging triggers the onset of various chronic lung diseases, with alveolar repair being a key focus for alleviating pulmonary conditions. The regeneration of epithelial structures, particularly the differentiation from type II alveolar epithelial (AT2) cells to type I alveolar epithelial (AT1) cells, serves as a prominent indicator of alveolar repair. Nonetheless, the precise role of aging in impeding alveolar regeneration and its underlying mechanism remain to be fully elucidated. Our study employed histological methods to examine lung aging effects on structural integrity and pathology. Lung aging led to alveolar collapse, disrupted epithelial structures, and inflammation. Additionally, a relative quantification analysis revealed age-related decline in AT1 and AT2 cells, along with reduced proliferation and differentiation capacities of AT2 cells. To elucidate the mechanisms underlying AT2 cell functional decline, we employed transcriptomic techniques and revealed a correlation between inflammatory factors and genes regulating proliferation and differentiation. Furthermore, a D-galactose-induced senescence model in A549 cells corroborated our omics experiments and confirmed inflammation-induced cell cycle arrest and a >30% reduction in proliferation/differentiation. Physiological aging-induced chronic inflammation impairs AT2 cell functions, hindering tissue repair and promoting lung disease progression. This study offers novel insights into chronic inflammation's impact on stem cell-mediated alveolar regeneration.

[Relationship Between Tim-3 and Galectin-9 Expression Levels, Clinical Pathological Characteristics, and Prognosis in Patients After Radical Resection of Colorectal Cancer]. / ç»“ç›´è‚ ç™Œæ ¹æ²»æœ¯åŽæ‚£è€ Tim-3、galectin-9è¡¨è¾¾æ°´å¹³ä¸Žå ¶ä¸´åºŠç— ç†ç‰¹å¾åŠé¢„åŽçš„å ³ç³».

Objective: Some colorectal cancer patients still face high recurrence rates and poor prognoses even after they have undergone the surgical treatment of radical resection. Identifying potential biochemical markers and therapeutic targets for the prognostic evaluation of patients undergoing radical resection of colorectal cancer is crucial for improving their clinical outcomes. Recently, it has been reported that the T cell immunoglobulin and mucin domain protein 3 (Tim-3) and its ligand galactose lectin 9 (galectin-9) play crucial roles in immune dysfunction caused by various tumors, such as colorectal cancer. However, their expressions, biological functions, and prognostic value in colorectal cancer are still unclear. This study aims to investigate the relationship between Tim-3 and galectin-9 expression levels and the clinicopathological characteristics and prognosis of patients undergoing radical resection of colorectal cancer. Methods: A total of 171 patients who underwent radical resection of colorectal cancer at Chengdu Fifth People's Hospital between February 2018 and March 2019 were selected. Immunohistochemistry was performed to assess the expression levels of Tim-3 and galectin-9 in the cancer tissue samples and the paracancerous tissue samples of the patients. The relationship between Tim-3 and galectin-9 expression levels and the baseline clinical parameters of the patients was analyzed accordingly. Kaplan-Meier analysis was performed to assess the association between Tim-3 and galectin-9 expression levels and the relapse-free survival (RFS) and the overall survival (OS) of colorectal cancer patients. Cox regression analysis was conducted to identify factors associated with adverse prognosis in the patients. Results: The immunohistochemical results showed that the high expression levels of Tim-3 and galectin-9 were observed in 70.18% (120/171) and 32.16% (55/171), respectively, of the colorectal cancer tissues, whereas the low expression levels were 29.82% (51/171) and 67.84% (116/171), respectively. Furthermore, the expression score of Tim-3 was significantly higher in colorectal cancer tissues than that in the paracancerous tissues, while the expression score of galectin-9 was lower than that in the paracancerous tissues (P<0.05). Further analysis revealed that the expression of Tim-3 and galectin-9 was associated with the depth of tumor infiltration, vascular infiltration, and clinical staging (P<0.05). During the follow-up period of 14-63 months, 7 out of 171 patients were lost to follow-up. Among the remaining patients, 49 and 112 cases presented abnormally low expression of Tim-3 and galectin-9, respectively, whereas 115 and 52 cases presented high expression of Tim-3 and galectin-9, respectively. Kaplan-Meier survival analysis demonstrated that patients with high Tim-3 expression in colorectal cancer tissues had significantly lower RFS and OS than those with low expression did (RFS: log-rank=22.66, P<0.001; OS: log-rank=19.71, P<0.001). Conversely, patients with low galectin-9 expression had significantly lower RFS and OS than those with high expression did (RFS: log-rank=19.45, P<0.001; OS: log-rank=22.24, P<0.001). Cox multivariate analysis indicated that TNM stage Ⅲ (HR=2.26, 95% CI: 1.20-5.68), high expression of Tim-3 (HR=0.80, 95% CI: 0.33-0.91), and low expression of galectin-9 (HR=1.80, 95% CI: 1.33-4.70) were independent risk factors affecting RFS and OS in patients (P<0.05). Conclusion: Aberrant expression of Tim-3 and galectin-9 is observed in colorectal cancer tissues. High expression of Tim-3 and low expression of galectin-9 are closely associated with adverse clinico-pathological characteristics and prognosis. They are identified as independent influencing factors that may trigger adverse prognostic events in patients. These findings suggest that Tim-3 and galectin-9 have potential as new therapeutic targets and clinical indicators.

High-performance visible-near-infrared photodetector based on the N2200/Sb2Se3 nanorod arrays organic-inorganic hybrid heterostructure.

Antimony selenide (Sb2Se3) is a suitable candidate for a broadband photodetector owing to its remarkable optoelectronic properties. Achieving a high-performance self-powered photodetector through a desirable heterojunction still needs more efforts to explore. In this work, we demonstrate a broadband photodetector based on the hybrid heterostructure of Sb2Se3 nanorod arrays (NRAs) absorber and polymer acceptor (P(NDI2OD-T2), N2200). Owing to the well-matched energy levels between N2200 and Sb2Se3, the recombination of photogenerated electrons and holes in N2200/Sb2Se3 hybrid heterostructure is greatly inhibited. The photodetector can detect the wavelength from 405 to 980 nm, and exhibit high responsivity of 0.39 A/W and specific detectivity of 1.84 × 1011 Jones at 780 nm without bias voltage. Meanwhile, ultrafast response rise time (0.25 ms) and fall time (0.35 ms) are obtained. Moreover, the time-dependent photocurrent of this heterostructure-based photodetector keeps almost the same value after the storge for 40 days, indicating the excellent stability and reproducibility. These results demonstrate the potential application of a N2200/Sb2Se3 NRAs heterojunction in visible-near-infrared photodetectors.

An efficient polynomial-based verifiable computation scheme on multi-source outsourced data.

With the development of cloud computing, users are more inclined to outsource complex computing tasks to cloud servers with strong computing capacity, and the cloud returns the final calculation results. However, the cloud is not completely trustworthy, which may leak the data of user and even return incorrect calculations on purpose. Therefore, it is important to verify the results of computing tasks without revealing the privacy of the users. Among all the computing tasks, the polynomial calculation is widely used in information security, linear algebra, signal processing and other fields. Most existing polynomial-based verifiable computation schemes require that the input of the polynomial function must come from a single data source, which means that the data must be signed by a single user. However, the input of the polynomial may come from multiple users in the practical application. In order to solve this problem, the researchers have proposed some schemes for multi-source outsourced data, but these schemes have the common problem of low efficiency. To improve the efficiency, this paper proposes an efficient polynomial-based verifiable computation scheme on multi-source outsourced data. We optimize the polynomials using Horner's method to increase the speed of verification, in which the addition gate and the multiplication gate can be interleaved to represent the polynomial function. In order to adapt to this structure, we design the corresponding homomorphic verification tag, so that the input of the polynomial can come from multiple data sources. We prove the correctness and rationality of the scheme, and carry out numerical analysis and evaluation research to verify the efficiency of the scheme. The experimental indicate that data contributors can sign 1000 new data in merely 2 s, while the verification of a delegated polynomial function with a power of 100 requires only 18 ms. These results confirm that the proposed scheme is better than the existing scheme.

Osteopontin Rejuvenates Senescent Adipose-Derived Stem Cells and Restores their Bone Tissue Regenerative Function.

The regenerative function of stem cells is compromised when the proportion of senescent stem cells increases with ageing advance. Therefore, combating stem cell senescence is of great importance for stem cell-based tissue engineering in the elderly, but remains largely unexplored. Osteopontin (OPN), a glycosylated phosphoprotein, is one of the key extracellular matrix molecules in bone tissue. OPN activates various signalling pathways and modulates cellular activities, including cell senescence. However, the role of OPN in stem cell senescence remains largely unknown. This study aims to investigate if OPN modulates cell senescence and bone regenerative function in human adipose-derived mesenchymal stem cells (ASCs), and to determine the underlying mechanisms. We first developed a senescent ASC model using serial passaging until passage 10 (P10), in which senescent cells were characterised by reduced proliferation and osteogenic differentiation capacity compared to P4 ASCs. The conditioned medium from P10 ASCs exhibited a diminished trophic effect on human osteoblasts (HOBs), compared to that from P4 ASCs. P10 ASCs on OPN-coated surface showed rejuvenated phenotype and enhanced osteogenic differentiation. The conditioned medium from P10 ASCs on OPN-coating improved trophic effects on HOBs. OPN regulated the morphology of senescent ASCs, transforming them from a more rounded and flattened cell shape to an elongated shape with a smaller area. These findings demonstrated the effects of OPN in restoring senescent ASCs functions, possibly through a mechanism that involves the modulation of cell morphology, indicating that OPN might hold a great potential for rejuvenating senescent stem cells and could potentially open a new venue for regenerating bone tissue in age-related diseases.

C-C Motif Chemokine 2 Regulates Macrophage Polarization and Contributes to Myocardial Infarction Healing.

Macrophages are crucial immune cells that play essential roles in the healing of myocardial infarction (MI), undergoing continuous polarization throughout this process. C-C motif chemokine 2 (CCL2) is a chemokine that regulates inflammatory responses during MI. However, the extent to which CCL2 influences macrophage polarization and MI healing remains incompletely understood. In this study, we investigate the role of CCL2 in macrophage polarization and MI healing. Our findings reveal that CCL2 is differentially expressed in lipopolysaccharide (LPS)-induced M1 and interleukin (IL)-4-induced M2 RAW264.7 macrophages. Knockdown of CCL2 attenuates TNF-α secretion stimulated by LPS, while overexpression of CCL2 mitigates IL-10 production triggered by IL-4 in these macrophages. Moreover, CCL2 deficiency disrupts LPS-induced M1 polarization, whereas CCL2 overexpression reduces M2 polarization of RAW264.7 macrophages induced by IL-4. Further exploration indicates that the promotion of M1 polarization by CCL2 is significantly impaired by inhibition of the p38-mediated MAPK pathway and NF-κB pathway. In a MI mouse model, CCL2 knockdown remarkably reduces infarct size, collagen synthesis, and the expression of cardiac fibrosis and hypertrophy markers. The activity of the p38-mediated MAPK pathway and NF-κB pathway is downregulated by CCL2 knockdown as well. Additionally, the number of total macrophages and M1 macrophages in the infarct decreases, while the number of M2 macrophages increases upon CCL2 deficiency. In conclusion, these results suggest that CCL2 is a key regulator of macrophage polarization, controlling MI healing in vivo.

Intelligent Biosensors Promise Smarter Solutions in Food Safety 4.0.

Food safety is closely related to human health. However, the regulation and testing processes for food safety are intricate and resource-intensive. Therefore, it is necessary to address food safety risks using a combination of deep learning, the Internet of Things, smartphones, quick response codes, smart packaging, and other smart technologies. Intelligent designs that combine digital systems and advanced functionalities with biosensors hold great promise for revolutionizing current food safety practices. This review introduces the concept of Food Safety 4.0, and discusses the impact of intelligent biosensors, which offer attractive smarter solutions, including real-time monitoring, predictive analytics, enhanced traceability, and consumer empowerment, helping improve risk management and ensure the highest standards of food safety.

Stimulus-Responsive Nanodelivery and Release Systems for Cancer Gene Therapy: Efficacy Improvement Strategies.

Introduction of exogenous genes into target cells to overcome various tumor diseases caused by genetic defects or abnormalities and gene therapy, a new treatment method, provides a promising strategy for tumor treatment. Over the past decade, gene therapy has made exciting progress; however, it still faces the challenge of low nucleic acid delivery and release efficiencies. The emergence of nonviral vectors, primarily nanodelivery and release systems (NDRS), has resulted in a historic breakthrough in the application of gene therapy. NDRS, especially stimulus-responsive NDRS that can respond in a timely manner to changes in the internal and external microenvironment (eg, low pH, high concentration of glutathione/reactive oxygen species, overexpressed enzymes, temperature, light, ultrasound, and magnetic field), has shown excellent loading and release advantages in the precision and efficiency of tumor gene therapy and has been widely applied. The only disadvantage is that poor transfection efficiency limits the in-depth application of gene therapy in clinical practice, owing to the presence of biological barriers in the body. Therefore, this review first introduces the development history of gene therapy, the current obstacles faced by gene delivery, strategies to overcome these obstacles, and conventional vectors, and then focuses on the latest research progress in various stimulus-responsive NDRS for improving gene delivery efficiency. Finally, the future challenges and prospects that stimulus-responsive NDRS may face in clinical application and transformation are discussed to provide references for enhancing in-depth research on tumor gene therapy.

Effect of the structure and volume fraction of nanophase on the mechanical properties of (FeNi)86B14 amorphous nanocrystalline alloys.

The influence of precipitated nanophases on the mechanical properties of Fe-based amorphous nanocrystalline alloys is an urgent issue to be explored. Two amorphous nanocrystalline alloys, i.e., (Fe0.9Ni0.1)86B14 and (Fe0.7Ni0.3)86B14 containing nanophase of the body-centered cubic and face-centered cubic structures, respectively, were selected to investigate the effect of the structure and volume fraction of nanophase on their mechanical properties. The results of nanoindentation experiments and the calculation of the volume and size of the shear transition zone reveal that the two alloys show different mechanical properties. When the volume fraction of the nanophase in (Fe0.9Ni0.1)86B14 is larger than 50%, the elastic modulus is increased suddenly and the volume and size of the shear transition zone is decreased dramatically, while no dramatic change occurs in (Fe0.7Ni0.3)86B14. Moreover, it was found by using molecular dynamics simulations that the main reason for these abnormal mechanical properties is the change of cluster type in the system due to the incorporation of nanophases with different structures.

Iron-Based Nanovehicle Delivering Fin56 for Hyperthermia-Boosted Ferroptosis Therapy Against Osteosarcoma.

Background: Although systemic chemotherapy is a standard approach for osteosarcoma (OS) treatment, its efficacy is limited by the inherent or acquired resistance to apoptosis of tumor cells. Ferroptosis is considered as an effective strategy capable of stimulating alternative pathways of cancer cell demise. The purpose of this study is to develop a novel strategy boosting ferroptotic cascade for synergistic cancer therapy. Methods and Results: A novel nanovehicle composed of arginine-glycine-aspartate (RGD) modified mesoporous silica-coated iron oxide loading Fin56 was rationally prepared (FSR-Fin56). With the RGD-mediated targeting affinity, FSR-Fin56 could achieve selective accumulation and accurate delivery of cargos into cancer cells. Upon exposure to NIR light, the nanovehicle could generate localized hyperthermia and disintegrate to liberate the therapeutic payload. The released Fin56 triggered the degradation of GPX4, while Fe3+ depleted the intracellular GSH pool, producing Fe2+ as a Fenton agent. The local rise in temperature, in conjunction with Fe2+-mediated Fenton reaction, led to a rapid and significant accumulation of ROS, culminating in LPOs and ferroptotic death. The outstanding therapeutic efficacy and safety of the nanovehicle were validated both in vitro and in vivo. Conclusion: The Fin56-loaded FSR nanovehicle could effectively disturb the redox balance in cancer cells. Coupled with NIR laser irradiation, the cooperative CDT and PTT achieved a boosted ferroptosis-inducing therapy. Taken together, this study offers a compelling strategy for cancer treatment, particularly for ferroptosis-sensitive tumors like osteosarcoma.