Nynrin preserves hematopoietic stem cell function by inhibiting the mitochondrial permeability transition pore opening.

Mitochondria are key regulators of hematopoietic stem cell (HSC) homeostasis. Our research identifies the transcription factor Nynrin as a crucial regulator of HSC maintenance by modulating mitochondrial function. Nynrin is highly expressed in HSCs under both steady-state and stress conditions. The knockout Nynrin diminishes HSC frequency, dormancy, and self-renewal, with increased mitochondrial dysfunction indicated by abnormal mPTP opening, mitochondrial swelling, and elevated ROS levels. These changes reduce HSC radiation tolerance and promote necrosis-like phenotypes. By contrast, Nynrin overexpression in HSCs diminishes irradiation (IR)-induced lethality. The deletion of Nynrin activates Ppif, leading to overexpression of cyclophilin D (CypD) and further mitochondrial dysfunction. Strategies such as Ppif haploinsufficiency or pharmacological inhibition of CypD significantly mitigate these effects, restoring HSC function in Nynrin-deficient mice. This study identifies Nynrin as a critical regulator of mitochondrial function in HSCs, highlighting potential therapeutic targets for preserving stem cell viability during cancer treatment.

Label-free and ultrasensitive detection of environmental lead ions based on spatially localized DNA nanomachines driven by hyperbranched hybridization chain reaction.

A label-free fluorescent sensing strategy for the rapid and highly sensitive detection of Pb2+ was developed by integrating Pb2+ DNAzyme-specific cleavage activity and a tetrahedral DNA nanostructure (TDN)-enhanced hyperbranched hybridization chain reaction (hHCR). This strategy provides accelerated reaction rates because of the highly effective collision probability and enriched local concentrations from the spatial confinement of the TDN, thus showing a higher detection sensitivity and a more rapid detection process. Moreover, a hairpin probe based on a G-triplex instead of a G-quadruplex or chemical modification makes hybridization chain reaction more controlled and flexible, greatly improving signal amplification capacities and eliminating labeled DNA probes. The enhanced reaction rates and improved signal amplification efficiency endowed the biosensors with high sensitivity and a rapid response. The label-free detection of Pb2+ based on G-triplex combined with thioflavin T can be achieved with a detection limit as low as 1.8 pM in 25 min. The proposed Pb2+-sensing platform was also demonstrated to be applicable for Pb2+ detection in tap water, river water, shrimp, rice, and soil samples, thus showing great potential for food safety and environmental monitoring.

Insights into ionizing radiation-induced bone marrow hematopoietic stem cell injury.

With the widespread application of nuclear technology across various fields, ionizing radiation-induced injuries are becoming increasingly common. The bone marrow (BM) hematopoietic tissue is a primary target organ of radiation injury. Recent researches have confirmed that ionizing radiation-induced hematopoietic dysfunction mainly results from BM hematopoietic stem cells (HSCs) injury. Additionally, disrupting and reshaping BM microenvironment is a critical factor impacting both the injury and regeneration of HSCs post radiation. However, the regulatory mechanisms of ionizing radiation injury to BM HSCs and their microenvironment remain poorly understood, and prevention and treatment of radiation injury remain the focus and difficulty in radiation medicine research. In this review, we aim to summarize the effects and mechanisms of ionizing radiation-induced injury to BM HSCs and microenvironment, thereby enhancing our understanding of ionizing radiation-induced hematopoietic injury and providing insights for its prevention and treatment in the future.

Polygenic Score for Conscientiousness Is a Protective Factor for Reversion from Mild Cognitive Impairment to Normal Cognition.

Spontaneous reversion from mild cognitive impairment (MCI) to normal cognition (NC) is little known. Based on the data of the Genetics of Personality Consortium and MCI participants from Alzheimer's Disease Neuroimaging Initiative, the authors investigate the effect of polygenic scores (PGS) for personality traits on the reversion of MCI to NC and its underlying neurobiology. PGS analysis reveals that PGS for conscientiousness (PGS-C) is a protective factor that supports the reversion from MCI to NC. Gene ontology enrichment analysis and tissue-specific enrichment analysis indicate that the protective effect of PGS-C may be attributed to affecting the glutamatergic synapses of subcortical structures, such as hippocampus, amygdala, nucleus accumbens, and caudate nucleus. The structural covariance network (SCN) analysis suggests that the left whole hippocampus and its subfields, and the left whole amygdala and its subnuclei show significantly stronger covariance with several high-cognition relevant brain regions in the MCI reverters compared to the stable MCI participants, which may help illustrate the underlying neural mechanism of the protective effect of PGS-C.

Subcutaneous fat thickness predicts postoperative seroma following laparoscopic total extra-peritoneal hernioplasty.

PURPOSE: Seroma formation is the most common cause of morbidity associated with laparoscopic inguinal hernia repair. This study aimed to examine the relationship between the thickness of subcutaneous fat (TSF) and the risk of postoperative seroma. METHODS: We reviewed data from a prospective cohort of 229 male patients who underwent laparoscopic total extra-peritoneal (TEP) hernioplasty for indirect inguinal hernia between August 2018 and July 2021. The TSF was assessed using preoperative ultrasound images. The risk factors for postoperative seroma were determined using univariate and multivariate logistic regression models. RESULTS: Postoperative seromas occurred in 26 patients (11.4%). The factors associated with postoperative seroma included longer hernia duration, larger hernia defects, extension into the scrotum, and greater TSF (P < 0.05). In multivariate analysis, a greater TSF was independently associated with a greater risk of postoperative seroma (per 1 mm: odd ratio [OR] 1.105, 95% confidence interval [CI] 1.048-1.165, P < 0.001; TSF ≥ 26.0 mm: OR 7.033, 95% CI 2.485-19.901, P < 0.001). Similar results were obtained in the subgroup analysis. The area under the curve of TSF for predicting seroma formation was 0.703 (95% CI 0.601-0.806). CONCLUSION: Ultrasound-derived TSF may be a promising prognostic factor for postoperative seroma in patients undergoing laparoscopic TEP repair. Further validation is required and then this parameter can be used to improve decision-making process.

Efficacy and safety of anlotinib in combination with immune checkpoint inhibitors or not as advanced non-small cell lung cancer treatment: a systematic review and network meta-analysis.

Background: Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality. Combined anlotinib and immune checkpoint inhibitors (ICIs) therapy may have synergistic antitumor effects in NSCLC. This study aimed to comparing the efficacy and safety of anlotinib and ICIs treatment, monotherapy and combination in NSCLC. Methods: We performed a systematic review and network meta-analysis of 14 studies involving 4,308 NSCLC patients across four regimens: anlotinib, ICIs, anlotinib plus ICIs, and placebo. Efficacy outcomes were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Safety outcomes included treatment-related adverse events (TRAEs), TRAE grade three or higher (TRAE ≥3). Analyses were performed in RevMan 5.3 and R 3.5.1 (gemtc package). P<0.05 or effect estimate with 95% confidence interval (CI) that did not include 1 indicated statistical significance. Results: Fourteen publications involving 4,308 patients across four treatment regimens (anlotinib, ICIs, anlotinib plus ICIs, placebo) were included. For PFS, network meta-analysis showed all three interventions significantly improved PFS versus placebo. Anlotinib plus ICIs demonstrated the greatest PFS improvement [hazard ratio (HR) =0.24; 95% CI: 0.14, 0.36], followed by anlotinib (HR =0.37; 95% CI: 0.23, 0.58), and ICIs (HR =0.43; 95% CI: 0.27, 0.67). For OS, compared to placebo, anlotinib plus ICIs showed the greatest OS improvement (HR =0.52; 95% CI: 0.33, 0.74), followed by anlotinib (HR =0.66; 95% CI: 0.47, 0.95), and ICIs (HR =0.72; 95% CI: 0.54, 0.97). For ORR, anlotinib plus ICIs demonstrated the greatest improvement versus placebo [odds ratio (OR) =5.29; 95% CI: 3.32, 8.58], followed by anlotinib (OR =4.38; 95% CI: 2.42, 8.19), and ICIs (OR =2.17; 95% CI: 1.65, 2.89). For DCR, anlotinib plus ICIs showed the greatest improvement versus placebo (OR =13.32; 95% CI: 4.99, 45.09), followed by anlotinib (OR =5.56; 95% CI: 2.17, 14.38), and ICIs (OR =3.46; 95% CI: 1.29, 10.85). Compared to placebo, anlotinib was associated with the highest risk of TRAEs (OR =3.67, 95% CI: 1.12, 15.77), followed by ICIs (OR =1.83; 95% CI: 1.26, 2.69). Due to lack of data on anlotinib plus ICIs, no comparison was conducted. For grade ≥3 TRAEs, compared to placebo, anlotinib increased the risk (OR =3.67; 95% CI: 1.12, 15.77), while anlotinib plus ICIs (OR =2.45; 95% CI: 0.51, 11.6) and ICIs (OR =1.29; 95% CI: 0.33, 4.38) did not increase the risk. Conclusions: Anlotinib combined with ICIs demonstrates improved efficacy over monotherapy for NSCLC treatment, without increased adverse events.

Epigenetic regulation of megakaryopoiesis and platelet formation.

Platelets, produced by megakaryocytes, play unique roles in physiological processes, such as hemostasis, coagulation, and immune regulation, while also contributing to various clinical diseases. During megakaryocyte differentiation, the morphology and function of cells undergo significant changes due to the programmed expression of a series of genes. Epigenetic changes modify gene expression without altering the DNA base sequence, effectively impacting the inner workings of the cell at different stages of growth, proliferation, differentiation, and apoptosis. These modifications also play an important role in megakaryocyte development and platelet biogenesis. However, the specific mechanisms underlying epigenetic processes or the vast epigenetic regulatory network formed by their interactions remain unclear. In this review, we systematically summarize the key roles played by epigenetics in megakaryocyte development and platelet formation, including DNA methylation, histone modification, and non-coding RNA regulation. We expect our review to provide a deeper understanding of the biological processes underlying megakaryocyte development and platelet formation and to inform the development of new clinical interventions aimed at addressing platelet-related diseases and improving patient prognoses.

P-selectin Facilitates SARS-CoV-2 Spike 1 Subunit Attachment to Vesicular Endothelium and Platelets.

SARS-CoV-2 infection starts from the association of its spike 1 (S1) subunit with sensitive cells. Vesicular endothelial cells and platelets are among the cell types that bind SARS-CoV-2, but the effectors that mediate viral attachment on the cell membrane have not been fully elucidated. Herein, we show that P-selectin (SELP), a biomarker for endothelial dysfunction and platelet activation, can facilitate the attachment of SARS-CoV-2 S1. Since we observe colocalization of SELP with S1 in the lung tissues of COVID-19 patients, we perform molecular biology experiments on human umbilical vein endothelial cells (HUVECs) to confirm the intermolecular interaction between SELP and S1. SELP overexpression increases S1 recruitment to HUVECs and enhances SARS-CoV-2 spike pseudovirion infection. The opposite results are determined after SELP downregulation. As S1 causes endothelial inflammatory responses in a dose-dependent manner, by activating the interleukin (IL)-17 signaling pathway, SELP-induced S1 recruitment may contribute to the development of a "cytokine storm" after viral infection. Furthermore, SELP also promotes the attachment of S1 to the platelet membrane. Employment of PSI-697, a small inhibitor of SELP, markedly decreases S1 adhesion to both HUVECs and platelets. In addition to the role of membrane SELP in facilitating S1 attachment, we also discover that soluble SELP is a prognostic factor for severe COVID-19 through a meta-analysis. In this study, we identify SELP as an adhesive site for the SARS-CoV-2 S1, thus providing a potential drug target for COVID-19 treatment.

Optimization of process conditions for ionic liquid-based ultrasound-enzyme-assisted extraction of resveratrol from Polygonum Cuspidatum.

This work offered a productive technique for resveratrol extraction from Polygonum Cuspidatum (P. Cuspidatum) using ionic liquids in synergy with ultrasound-enzyme-assisted extraction (UEAE). Firstly, ionic liquids with different carbon chains and anions were evaluated. Subsequently, a comprehensive investigation was carried out to evaluate the effect of seven crucial parameters on the resveratrol yield: pH value, enzyme concentration, extraction temperature, extraction time, ultrasonic power, concentration of ionic liquid (IL concentration) and the liquid-solid ratio. Employing the Plackett-Burman Design (PBD), the critical factors were effectively identified. Building upon this foundation, the process was further optimized through the application of Response Surface Methodology (RSM) and an Artificial Neural Network-Genetic Algorithm (ANN-GA). The following criteria were determined to be the ideal extraction conditions: an enzyme concentration of 2.18%, extraction temperature of 58 °C, a liquid-solid ratio of 29 mL/g, pH value of 5.5, extraction time of 30 min, ultrasonic power of 250 W, and extraction solvent of 0.5 mol/L 1-butyl-3-methylimidazolium bromide. Under these conditions, the resveratrol yield was determined to be 2.90 ± 0.15 mg/g. Comparative analysis revealed that the ANN-GA model provided a better fit to the experimental data of resveratrol yield than the RSM model, suggesting superior predictive capabilities of the ANN-GA approach. The introduction of a novel green solvent system in this experiment not only simplifies the extraction process but also enhances safety and feasibility. This research paves the way for innovative approaches to extracting resveratrol from botanical sources, showcasing its significant potential for a wide range of applications.

[Genetic analysis of a child with Generalized arterial calcification of infancy due to variant of ABCC6 gene].

OBJECTIVE: To explore the clinical manifestations and genetic basis for a rare case of Generalized arterial calcification of infancy (GACI). METHODS: A 44-day-old female infant who was treated at Baoding Hospital of Beijing Children's Hospital Affiliated to Capital Medical University on August 26, 2022 was selected as the study subject. Clinical data of the child was collected, and Trio-whole exome sequencing (Trio-WES), whole genome copy number variation sequencing (CNV-seq) and minigene splicing assay were carried out to analyze the pathogenicity of the variants. RESULTS: The child had presented with fever and high inflammatory indicators, for which treatment with various antibiotics was ineffective. Ultrasound had revealed extensive arterial calcification and arterial wall thickening. The child was suspected for GACI with arteritis related to the primary disease. Her fever was relieved by treatment with glucocorticoid and biological agents. Trio-WES revealed that she has harbored compound heterozygous variants of the ABCC6 gene, namely c.4404-1G>A and c.4041+5G>T, for which the latter was unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics, the variants were classified as likely pathogenic (PVS1+PM2_Supporting) and variant of unknown significance (PM2_Supporting+PM3+PP3), respectively. The result of CNV-seq was negative. And the minigene splicing assay has further verified that both variants can result in alternative splicing. CONCLUSION: For pyrexia with unknown causes and refractory to conventional treatment, it is necessary to recommend early genetic testing to avoid missed diagnosis of GACI.

Effects of cooking with solid fuel on hearing loss in Chinese adults-Based on two cohort studies.

The association between cooking fuel and hearing loss still needs more research to clarify, and two longitudinal cohort studies were explored to find if solid fuel use for cooking affected hearing in Chinese adults. The data from Chinese Health and Retirement Longitudinal Survey (CHARLS) and Chinese Longitudinal Healthy Longevity Survey (CLHLS) were analyzed. Participants (older than 18) without hearing loss at baseline and follow-up visits were included, which were divided into clean fuel and solid fuel groups. Hearing loss rate was from follow-up visits (both in year 2011) until the recent one (year 2018 in CHARLS and 2019 in CLHLS). Cox regressions were applied to examine the associations with adjustment for potential confounders. Fixed-effect meta-analysis was used to pool the results. A total of 9049 participants (average age 8.34 ± 9.12 [mean ± SD] years; 4247 [46.93%] males) were included in CHARLS cohort study and 2265 participants (average age, 78.75 ± 9.23 [mean ± SD] years; 1148 [49.32%] males) in CLHLS cohort study. There were 1518 (16.78%) participants in CHARLS cohort and 451 (19.91%) participants in CLHLS cohort who developed hearing loss. The group of using solid fuel for cooking had a higher risk of hearing loss (CHARLS: HR, 1.16; 95% CI 1.03-1.30; CLHLS: HR, 1.43; 95% CI 1.11-1.84) compared with the one of using clean fuel. Pooled hazard ratio showed the incidence of hearing loss in the solid fuel users was 1.17 (1.03, 1.29) times higher than that of clean fuel users. Hearing loss was associated with solid fuel use and older people were at higher risk. It is advised to replace solid fuel by clean fuel that may promote health equity.

Megakaryocytic IGF1 coordinates activation and ferroptosis to safeguard hematopoietic stem cell regeneration after radiation injury.

BACKGROUND: Hematopoietic stem cell (HSC) regeneration underlies hematopoietic recovery from myelosuppression, which is a life-threatening side effect of cytotoxicity. HSC niche is profoundly disrupted after myelosuppressive injury, while if and how the niche is reshaped and regulates HSC regeneration are poorly understood. METHODS: A mouse model of radiation injury-induced myelosuppression was built by exposing mice to a sublethal dose of ionizing radiation. The dynamic changes in the number, distribution and functionality of HSCs and megakaryocytes were determined by flow cytometry, immunofluorescence, colony assay and bone marrow transplantation, in combination with transcriptomic analysis. The communication between HSCs and megakaryocytes was determined using a coculture system and adoptive transfer. The signaling mechanism was investigated both in vivo and in vitro, and was consolidated using megakaryocyte-specific knockout mice and transgenic mice. RESULTS: Megakaryocytes become a predominant component of HSC niche and localize closer to HSCs after radiation injury. Meanwhile, transient insulin-like growth factor 1 (IGF1) hypersecretion is predominantly provoked in megakaryocytes after radiation injury, whereas HSCs regenerate paralleling megakaryocytic IGF1 hypersecretion. Mechanistically, HSCs are particularly susceptible to megakaryocytic IGF1 hypersecretion, and mTOR downstream of IGF1 signaling not only promotes activation including proliferation and mitochondrial oxidative metabolism of HSCs, but also inhibits ferritinophagy to restrict HSC ferroptosis. Consequently, the delicate coordination between proliferation, mitochondrial oxidative metabolism and ferroptosis ensures functional HSC expansion after radiation injury. Importantly, punctual IGF1 administration simultaneously promotes HSC regeneration and hematopoietic recovery after radiation injury, representing a superior therapeutic approach for myelosuppression. CONCLUSIONS: Our study identifies megakaryocytes as a last line of defense against myelosuppressive injury and megakaryocytic IGF1 as a novel niche signal safeguarding HSC regeneration.

Self-powered biosensing sutures for real-time wound monitoring.

Effective wound management has the potential to reduce both the duration and cost of wound healing. However, traditional methods often rely on direct observation or complex and expensive biological testing to monitor and evaluate the invasive damage caused by wound healing, which can be time-consuming. Biosensors offer the advantage of precise and real-time monitoring, but existing devices are not suitable for integration with sensitive wound tissue due to their external dimensions. Here, we have designed a self-powered biosensing suture (SPBS) based on biofuel cells to accurately monitor glucose concentration at the wound site and promote wound healing. The anode of the SPBS consists of carbon nanotubes-modified carbon fibers, tetrathiafulvalene (TTF), and glucose oxidase (GOx), while the cathode is composed of Ag2O and carbon nanotubes modified nanotubes modified carbon fibers. It was observed that SPBS exhibited excellent physical and chemical stability in vitro. Regardless of different bending degrees or pH values, the maximum power density of SPBS remained above 92%, which is conducive to long-term dynamic evaluation. Furthermore, the voltage generated by SPBS reflects blood glucose concentration, and measurements at wound sites are consistent with those obtained using a commercially available blood glucose meter. SPBS achieves the healing effect of traditional medical sutures after complete healing within 14 days. It offers valuable insights for intelligent devices dedicated to real-time wound monitoring.

Bidirectional two-sample Mendelian randomization analyses support causal relationships between structural and diffusion imaging-derived phenotypes and the risk of major neurodegenerative diseases.

Previous observational investigations suggest that structural and diffusion imaging-derived phenotypes (IDPs) are associated with major neurodegenerative diseases; however, whether these associations are causal remains largely uncertain. Herein we conducted bidirectional two-sample Mendelian randomization analyses to infer the causal relationships between structural and diffusion IDPs and major neurodegenerative diseases using common genetic variants-single nucleotide polymorphism (SNPs) as instrumental variables. Summary statistics of genome-wide association study (GWAS) for structural and diffusion IDPs were obtained from 33,224 individuals in the UK Biobank cohort. Summary statistics of GWAS for seven major neurodegenerative diseases were obtained from the largest GWAS for each disease to date. The forward MR analyses identified significant or suggestively statistical causal effects of genetically predicted three structural IDPs on Alzheimer's disease (AD), frontotemporal dementia (FTD), and multiple sclerosis. For example, the reduction in the surface area of the left superior temporal gyrus was associated with a higher risk of AD. The reverse MR analyses identified significantly or suggestively statistical causal effects of genetically predicted AD, Lewy body dementia (LBD), and FTD on nine structural and diffusion IDPs. For example, LBD was associated with increased mean diffusivity in the right superior longitudinal fasciculus and AD was associated with decreased gray matter volume in the right ventral striatum. Our findings might contribute to shedding light on the prediction and therapeutic intervention for the major neurodegenerative diseases at the neuroimaging level.

Application of ionic liquid ultrasound-assisted extraction (IL-UAE) of lycopene from guava (Psidium guajava L.) by response surface methodology and artificial neural network-genetic algorithm.

Lycopene-rich guava (Psidium guajava L.) exhibits significant economic potential as a functional food ingredient, making it highly valuable for the pharmaceutical and agro-food industries. However, there is a need to enhance the extraction methods of lycopene to fully exploit its beneficial uses. In this study, we evaluated various ionic liquids to identify the most effective one for extracting lycopene from guava. Among thirteen ionic liquids with varying carbon chains or anions, 1-butyl-3-methylimidazolium chloride demonstrated the highest productivity. Subsequently, a single-factor experiment was employed to test the impact of several parameters on the efficiency of lycopene extraction using this selected ionic liquid. These parameters included extraction time, ultrasonic power, liquid-solid ratio, concentration of the ionic liquid, as well as material particle size. Moreover, models of artificial neural networks using genetic algorithms (ANN-GA) and response surface methodology (RSM) were employed to comprehensively assess the first four key parameters. The optimized conditions for ionic liquid ultrasound-assisted extraction (IL-UAE) were determined as follows: 33 min of extraction time, 225 W of ultrasonic power, 22 mL/g of liquid-solid ratio, 3.0 mol/L of IL concentration, and extraction cycles of three. Under these conditions, lycopene production reached an impressive yield of 9.35 ± 0.36 mg/g while offering advantages such as high efficiency, time savings, preservation benefits, and most importantly environmental friendliness.

Establishment and validation of a CT-based prediction model for the good dissolution of mild chronic subdural hematoma with atorvastatin treatment.

PURPOSE: To develop and validate a prediction model based on imaging data for the prognosis of mild chronic subdural hematoma undergoing atorvastatin treatment. METHODS: We developed the prediction model utilizing data from patients diagnosed with CSDH between February 2019 and November 2021. Demographic characteristics, medical history, and hematoma characteristics in non-contrast computed tomography (NCCT) were extracted upon admission to the hospital. To reduce data dimensionality, a backward stepwise regression model was implemented to build a prognostic prediction model. We calculated the area under the receiver operating characteristic curve (AUC) of the prognostic prediction model by a tenfold cross-validation procedure. RESULTS: Maximum thickness, volume, mean density, morphology, and kurtosis of the hematoma were identified as the most significant predictors of good hematoma dissolution in mild CSDH patients undergoing atorvastatin treatment. The prediction model exhibited good discrimination, with an area under the curve (AUC) of 0.82 (95% confidence interval [CI], 0.74-0.90) and good calibration (p = 0.613). The validation analysis showed the AUC of the final prognostic prediction model is 0.80 (95% CI 0.71-0.86) and it has good prediction performance. CONCLUSION: The imaging data-based prediction model has demonstrated great prediction accuracy for good hematoma dissolution in mild CSDH patients undergoing atorvastatin treatment. The study results emphasize the importance of imaging data evaluation in the management of CSDH patients.

3D skin bioprinting as promising therapeutic strategy for radiation-associated skin injuries.

Both cutaneous radiation injury and radiation combined injury (RCI) could have serious skin traumas, which are collectively referred to as radiation-associated skin injuries in this paper. These two types of skin injuries require special managements of wounds, and the therapeutic effects still need to be further improved. Cutaneous radiation injuries are common in both radiotherapy patients and victims of radioactive source accidents, which could lead to skin necrosis and ulcers in serious conditions. At present, there are still many challenges in management of cutaneous radiation injuries including early diagnosis, lesion assessment, and treatment prognosis. Radiation combined injuries are special and important issues in severe nuclear accidents, which often accompanied by serious skin traumas. Mass victims of RCI would be the focus of public health concern. Three-dimensional (3D) bioprinting, as a versatile and favourable technique, offers effective approaches to fabricate biomimetic architectures with bioactivity, which provides potentials for resolve the challenges in treating radiation-associated skin injuries. Combining with the cutting-edge advances in 3D skin bioprinting, the authors analyse the damage characteristics of skin wounds in both cutaneous radiation injury and RCI and look forward to the potential value of 3D skin bioprinting for the treatments of radiation-associated skin injuries.

A Review of the Role of Caveolin-1 in Acetaminophen-Induced Liver Injury.

BACKGROUND: Acetaminophen (APAP) is commonly used as an antipyretic and analgesic agent. Excessive APAP can induce liver toxicity, known as APAP-induced liver injury (ALI). The metabolism and pathogenesis of APAP have been extensively studied in recent years, and many cellular processes such as autophagy, mitochondrial oxidative stress, mitochondrial dysfunction, and liver regeneration have been identified to be involved in the pathogenesis of ALI. Caveolin-1 (CAV-1) as a scaffold protein has also been shown to be involved in the development of various diseases, especially liver disease and tumorigenesis. The role of CAV-1 in the development of liver disease and the association between them remains a challenging and uncharted territory. SUMMARY: In this review, we briefly explore the potential therapeutic effects of CAV-1 on ALI through autophagy, oxidative stress, and lipid metabolism. Further research to better understand the mechanisms by which CAV-1 regulates liver injury will not only enhance our understanding of this important cellular process, but also help develop new therapies for human disease by targeting CAV-1 targets. KEY MESSAGES: This review briefly summarizes the potential protective mechanisms of CAV-1 against liver injury caused by APAP.

Hematopoietic Stem Cells as an Integrative Hub Linking Lifestyle to Cardiovascular Health.

Despite breakthroughs in modern medical care, the incidence of cardiovascular disease (CVD) is even more prevalent globally. Increasing epidemiologic evidence indicates that emerging cardiovascular risk factors arising from the modern lifestyle, including psychosocial stress, sleep problems, unhealthy diet patterns, physical inactivity/sedentary behavior, alcohol consumption, and tobacco smoking, contribute significantly to this worldwide epidemic, while its underpinning mechanisms are enigmatic. Hematological and immune systems were recently demonstrated to play integrative roles in linking lifestyle to cardiovascular health. In particular, alterations in hematopoietic stem cell (HSC) homeostasis, which is usually characterized by proliferation, expansion, mobilization, megakaryocyte/myeloid-biased differentiation, and/or the pro-inflammatory priming of HSCs, have been shown to be involved in the persistent overproduction of pro-inflammatory myeloid leukocytes and platelets, the cellular protagonists of cardiovascular inflammation and thrombosis, respectively. Furthermore, certain lifestyle factors, such as a healthy diet pattern and physical exercise, have been documented to exert cardiovascular protective effects through promoting quiescence, bone marrow retention, balanced differentiation, and/or the anti-inflammatory priming of HSCs. Here, we review the current understanding of and progression in research on the mechanistic interrelationships among lifestyle, HSC homeostasis, and cardiovascular health. Given that adhering to a healthy lifestyle has become a mainstream primary preventative approach to lowering the cardiovascular burden, unmasking the causal links between lifestyle and cardiovascular health from the perspective of hematopoiesis would open new opportunities to prevent and treat CVD in the present age.