Estrogen regulates the transcription of guppy isotocin receptors.

Estrogen can regulate oxytocin receptor expression, which is mediated through estrogen receptors (ESRs) in mammals, initiating parturition. To further study the reproductive physiological process of ovoviviparous teleosts, guppies (Poecilia reticulata) were employed as the research model in the present study to identify the transcriptional regulation of ESRs on isotocin receptors (itrs). Since guppy embryos develop inside the ovary, in the present study, the levels of itrs in the ovarian stroma of pregnant female guppies treated with estradiol (E2) in vitro were tested. E2 increased only itr2 mRNA levels 3 h post-treatment, with no variation in itr1 mRNA expression levels. In vivo, pregnant guppies were immersed in different concentrations of E2, significantly increasing the relative expression levels of itr1 and itr2 in the ovary. Moreover, based on dual-fluorescence in situ hybridization (ISH), both esrs and itrs mRNAs were localized in the same cells around the embryos in the ovary. To further investigate the regulation of itr transcription by estrogen, a luciferase reporter assay was performed, and the results demonstrated that E2 treatment could induce E2-dependent repression of luciferase activity in cells transfected with ESR1. However, overexpression of ESR2a or ESR2b caused a robust ligand-independent increase in itr2 promoter activity. Deletion analysis of the itr2 promoter indicated that there were novel potential ESR transcription factor-binding sites at -360 bp upstream of the 5' end of the itr2 promoter. Overall, our study provided novel results regarding the ESRs mediating the onset of parturition in ovoviviparous teleosts.

Application of advanced oxidation processes for the removal of micro/nanoplastics from water: A review.

Micro/nanoplastics (MNPs) have been increasingly found in environments, food, and organisms, arousing wide public concerns. MNPs may enter food chains through water, posing a threat to human health. Therefore, efficient and environmentally friendly technologies are needed to remove MNPs from contaminated aqueous environments. Advanced oxidation processes (AOPs) produce a vast amount of active species, such as hydroxyl radicals (·OH), known for their strong oxidation capacity. As a result, an increasing number of researchers have focused on using AOPs to decompose and remove MNPs from water. This review summarizes the progress in researches on the removal of MNPs from water by AOPs, including ultraviolet photolysis, ozone oxidation, photocatalysis, Fenton oxidation, electrocatalysis, persulfate oxidation, and plasma oxidation, etc. The removal efficiencies of these AOPs for MNPs in water and the influencing factors are comprehensively analyzed, meanwhile, the oxidation mechanisms and reaction pathways are also discussed in detail. Most AOPs can achieve the degradation of MNPs, mainly manifest as the decrease of particle size and the increase of mass loss, but the mineralization rate is low, thus requiring further optimization for improved performance. Investigating various AOPs is crucial for achieving the complete decomposition of MNPs in water. AOPs will undoubtedly play a vital role in the future for the removal of MNPs from water.

Effect modification of dietary diversity on the association of air pollution with incidence, complications, and mortality of type 2 diabetes: Results from a large prospective cohort study.

BACKGROUND: It remains unknown whether the dietary diversity score (DDS) could modify the association of long-term exposure to individual air pollutants and the mixture of various pollutants with the incidence, complications, and mortality of type 2 diabetes (T2D). METHODS: We included 162,579 participants from the UK Biobank who had ≥ one 24-h dietary assessment and were free of diabetes or diabetes complications before their last response date of the 24-h dietary assessment. Exposure to benzene, NOx, NO2, SO2, PM10, and PM2.5 was estimated at each participant's residential location using a bilinear interpolation algorithm based on air dispersion models on a 1 km × 1 km grid. The DDS was calculated based on repeated 24-h dietary assessments. The outcomes were the incidence, complications, and mortality of T2D. Associations of individual pollutants and multiple pollutants mixtures with outcomes were assessed using Cox proportional hazards regression models and the quantile g-computation approach, respectively. We further stratified these analyses by DDS. RESULTS: During a median of 10.1 years of follow-up, 2978 participants developed incident T2D, 1181 developed T2D complications, and 242 died due to T2D. Long-term single-pollutant and multi-pollutant exposure were associated with elevated risk of incidence, complications, and mortality of T2D. For example, for incident T2D, the hazard ratio and 95 % confidence interval for each quantile increase were 1.155 (1.095, 1.215) for the air pollution mixture. We observed significant interactions between air pollution (benzene, NOx, NO2, PM10, PM2.5, and the air pollution mixture) and DDS (P-interaction <0.05), with the corresponding associations being significantly weaker in adults with high DDS than in those with low DDS. CONCLUSION: Higher dietary diversity may attenuate the harmful impacts of air pollution on T2D-related outcomes. A higher diversity diet could be used to prevent the onset and progression of T2D induced by long-term exposure to various air pollutants.

Hippocampal circAnk3 Deficiency Causes Anxiety-like Behaviors and Social Deficits by Regulating the miR-7080-3p/IQGAP1 Pathway in Mice.

BACKGROUND: Circular RNAs (circRNAs) are highly enriched in the synapses of the mammalian brain and play important roles in neurological function by acting as molecular sponges of microRNAs (miRNAs). CircAnk3 is derived from the 11th intron of the Ankyrin 3 (Ank3) gene, a strong genetic risk factor for neuropsychiatric disorders; however, the function of circAnk3 remains elusive. In this study, we investigated the function of circAnk3 and its downstream regulatory network for target genes in the hippocampus of mice. METHODS: The DNA sequence from which circAnk3 is generated was modified using CRISPR/Cas9 technology, and neurobehavioral tests (anxiety and depression-like behaviours, social behaviours) were performed in circAnk3+/- mice. A series of molecular and biochemical assays were used to investigate the function of circAnk3 as a microRNA sponge and its downstream regulatory network for target genes. RESULTS: CircAnk3+/- mice exhibited both anxiety-like behaviors and social deficits. CircAnk3 was predominantly located in the cytoplasm of neuronal cells and functioned as a miR-7080-3p sponge to regulate the expression of IQ motif containing GTPase activating protein 1 (Iqgap1). Inhibition of miR-7080-3p or restoration of Iqgap1 in the hippocampus ameliorated the behavioral deficits of circAnk3+/- mice. Furthermore, circAnk3 deficiency decreased the expression of the N-methyl-D-aspartate receptor (NMDAR) subunit GluN2a and impaired the structural plasticity of dendritic synapses in the hippocampus. CONCLUSION: Our results reveal an important role of the circAnk3/miR-7080-3p/IQGAP1 axis in maintaining the structural plasticity of hippocampal synapses. CircAnk3 might offer new insights into the involvement of circRNAs in neuropsychiatric disorders.

Sarcopenia and mild kidney dysfunction and risk of all-cause and cause-specific mortality in older adults.

BACKGROUND: Sarcopenia has been identified as a risk factor for increased mortality in individuals with CKD. However, when considering individuals with mild kidney dysfunction prior to CKD, the impact of sarcopenia on adverse outcomes, particularly mortality, remains uncertain. METHODS: This study included 323 801 participants from the UK Biobank. Mild kidney dysfunction was defined as eGFR between 60 and 89.9 mL/min/1.73 m2, and sarcopenia was defined according to the criteria of the 2019 European Working Group of Sarcopenia in Older People. Cox proportional hazard models with inverse probability weighting and competing risk models were used for analysis. RESULTS: During a median follow-up of 11.8 years, 20 146 participants died from all causes. Compared with participants with normal kidney function and without sarcopenia, those with mild kidney dysfunction or sarcopenia had significantly increased risks of all-cause mortality [hazard ratio (HR): 1.16, 95% confidence interval (CI): 1.12 to 1.19; HR: 1.29, 95% CI: 1.20 to 1.37]; those with both mild kidney dysfunction and sarcopenia had an even higher risk of all-cause mortality (HR: 1.61, 95% CI: 1.52 to 1.71), with a significant overall additive interaction (relative risk due to interaction 0.17, 95% CI: 0.05 to 0.29). Further subgroup analyses revealed that the associations of probable sarcopenia with all-cause and cause-specific mortality (non-accidental cause, non-communicable diseases, and cancer) were stronger among participants with mild kidney dysfunction than those with normal kidney function. CONCLUSIONS: The study indicates that sarcopenia and mild kidney dysfunction synergistically increase the risk of all-cause and cause-specific mortality. Early recognition and improvement of mild kidney function or sarcopenia in older people may reduce mortality risk but would require more prospective confirmation.

Genetically encoded zinc-binding collagen-like protein hybrid hydrogels for wound repair.

Incorporating zinc oxide nanoparticles (ZnOnps) into collagen is a promising strategy for fabricating biomaterials with excellent antibacterial activity, but modifications are necessary due to the low zinc binding affinity of native collagen, which can cause disturbances to the functions of both ZnOnps and collagen and result in heterogeneous effects. To address this issue, we have developed a genetically encoded zinc-binding collagen-like protein, Zn-eCLP3, which was genetically modified by Scl2 collagen-like protein. Our study found that Zn-eCLP3 has a binding affinity for zinc that is 3-fold higher than that of commercialized type I collagen, as determined by isothermal titration calorimetry (ITC). Using ZnOnps-coordinated Zn-eCLP3 protein and xanthan gum, we prepared a hydrogel that showed significantly stronger antibacterial activity compared to a collagen hydrogel prepared in the same manner. In vitro cytocompatibility tests were conducted to assess the potential of the Zn-eCLP3 hydrogel for wound repair applications. In vivo experiments, which involved an S. aureus-infected mouse trauma model, showed that the application of the Zn-eCLP3 hydrogel resulted in rapid wound regeneration and increased expression of collagen-1α and cytokeratin-14. Our study highlights the potential of Zn-eCLP3 and the hybrid hydrogel for further studies and applications in wound repair.

Histone deacetylase 9 exacerbates podocyte injury in hyperhomocysteinemia through epigenetic repression of Klotho.

Although hyperhomocysteinemia (hHcys) has been recognized as an important independent risk factor in the progression of end-stage renal disease and the development of cardiovascular complications related to end-stage renal disease, the mechanisms triggering pathogenic actions of hHcys are not fully understood. The present study was mainly designed to investigate the role of HDACs in renal injury induced by hHcys. Firstly, we identified the expression patterns of HDACs and found that, among zinc-dependent HDACs, HDAC9 was preferentially upregulated in the kidney from mice with hHcys. Deficiency or pharmacological inhibition of HDAC9 ameliorated renal injury in mice with hHcys. Moreover, podocyte-specific deletion of HDAC9 significantly attenuated podocyte injury and proteinuria. In vitro, gene silencing of HDAC9 attenuated podocyte injury by inhibiting apoptosis, reducing oxidative stress and maintaining the expressions of podocyte slit diaphragm proteins. Mechanically, we proved for the first time that HDAC9 reduced the acetylation level of H3K9 in the promoter of Klotho, then inhibited gene transcription of Klotho, finally aggravating podocyte injury in hHcys. In conclusion, our results indicated that targeting of HDAC9 might be an attractive therapeutic strategy for the treatment of renal injury induced by hHcys.

NADPH oxidase 4-mediating oxidative stress contributes to endometriosis.

NADPH oxidase 4 (NOX4) plays an important role in the regulation of oxidative stress, which is associated with endometriosis. This study aims to investigate the effects of NOX4 in endometriosis and its molecular mechanisms. Clinical specimens were collected, and human endometrial stromal cells (HESCs) were isolated. The knockdown of NOX4 cell lines was established on the HESCs and induced by peritoneal fluid. The levels of NOX4 were determined by using immunohistochemistry (IHC) staining, western blotting, and qPCR, respectively. The levels of oxidative stress markers were determined by using western blotting and ELISAs, respectively. The correlation of NOX4 and oxidative stress markers was analyzed by the Pearson correlation coefficient. The levels of NOX4 were dramatically elevated in the ectopic endometrium. Besides, oxidative stress biomarkers were also dysregulated in the ectopic endometrium as compared to the normal endometrium. Pearson's correlation coefficient analysis revealed a relationship between NOX4 and oxidative stress biomarkers in the ectopic endometrium. NOX4 modulated the expressions of oxidative stress markers in endometrial stromal cells stimulated by the peritoneal fluid from endometriosis. The effects of NOX4 on endometriosis are in part by its regulatory effects against oxidative stress.

Acoustic Characterization of Transmitted and Received Acoustic Properties of Air-Coupled Ultrasonic Transducers Based on Matching Layer of Organosilicon Hollow Glass Microsphere.

An air-coupled transducer was developed in this study, utilizing hollow glass microsphere-organosilicon composites as an acoustically matching layer, which demonstrated outstanding acoustic performance. Firstly, a comparison and analysis of the properties and advantages of different substrates was carried out to determine the potential application value of organosilicon substrates. Immediately after, the effect of hollow glass microspheres with different particle sizes and mass fractions on the acoustic properties of the matching layer was analyzed. It also evaluated the mechanical properties of the matching layer before and after optimization. The findings indicate that the optimized composite material attained a characteristic acoustic impedance of 1.04 MRayl and an acoustic attenuation of 0.43 dB/mm, displaying exceptional acoustic performance. After encapsulating the ultrasonic transducer using a 3D-printed shell, we analyzed and compared its emission and reception characteristics to the commercial transducer and found that its emission acoustic pressure amplitude and reception voltage amplitude were 34% and 26% higher, respectively. Finally, the transducer was installed onto a homemade ultrasonic flow meter for practical application verification, resulting in an accuracy rate of 97.4%.

Neurodevelopmental defects in human cortical organoids with N-acetylneuraminic acid synthase mutation.

Biallelic genetic variants in N-acetylneuraminic acid synthase (NANS), a critical enzyme in endogenous sialic acid biosynthesis, are clinically associated with neurodevelopmental disorders. However, the mechanism underlying the neuropathological consequences has remained elusive. Here, we found that NANS mutation resulted in the absence of both sialic acid and protein polysialylation in the cortical organoids and notably reduced the proliferation and expansion of neural progenitors. NANS mutation dysregulated neural migration and differentiation, disturbed synapse formation, and weakened neuronal activity. Single-cell RNA sequencing revealed that NANS loss of function markedly altered transcriptional programs involved in neuronal differentiation and ribosomal biogenesis in various neuronal cell types. Similarly, Nans heterozygous mice exhibited impaired cortical neurogenesis and neurobehavioral deficits. Collectively, our findings reveal a crucial role of NANS-mediated endogenous sialic acid biosynthesis in regulating multiple features of human cortical development, thus linking NANS mutation with its clinically relevant neurodevelopmental disorders.

Remote ischemic conditioning after stroke: Research progress in clinical study.

BACKGROUND AND PURPOSE: Stroke is a leading cause of global morbidity and mortality, indicating the necessity and urgency of effective prevention and treatment. Remote ischemic conditioning (RIC) is a convenient, simple, non-intrusive, and effective method that can be easily added to the treatment regime of stroke patients. Animal experiments and clinical trials have proved the neuroprotective effects of RIC on brain injury including (examples of neuroprotective effects). This neuroprotection is achieved by raising brain tolerance to ischemia, increasing local cerebral blood perfusion, promoting collateral circulations, neural regeneration, and reducing the incidence of hematomas in brain tissue. This current paper will summarize the studies within the last 2 years for the comprehensive understanding of the use of RIC in the treatment of stroke. METHODS: This paper summarizes the clinical research progress of RIC on stroke (ischemic stroke and hemorrhagic stroke (HS)). This paper is a systematic review of research published on registered clinical trials using RIC in stroke from inception through November 2022. Four major databases (PUBMED, WEB OF SCIENCE, EMBASE, and ClinicalTrials.gov) were searched. RESULTS: Forty-eight studies were identified meeting our criteria. Of these studies, 14 were in patients with acute ischemic stroke with onset times ranging from 6 h to 14 days, seven were in patients with intravenous thrombolysis or endovascular thrombectomy, 10 were in patients with intracranial atherosclerotic stenosis, six on patients with vascular cognitive impairment, three on patients with moyamoya disease, and eight on patients with HS. Of the 48 studies, 42 were completed and six are ongoing. CONCLUSIONS: RIC is safe, feasible, and effective in the treatment of stroke. Large-scale research is still required to explore the optimal treatment options and mechanisms of RIC in the future to develop a breakthrough in stroke prevention and treatment.

Regulation Mechanism of Phenolic Hydroxyl Number on Self-Assembly and Interaction between Edible Dock Protein and Hydrophobic Flavonoids.

In this study, galangin (Gal), kaempferol (Kae), quercetin (Que), and myricetin (Myr) were chosen as the representative flavonoids with different phenolic hydroxyl numbers in the B-ring. The edible dock protein (EDP) was chosen as the new plant protein. Based on this, the regulation mechanism of the phenolic hydroxyl number on the self-assembly behavior and molecular interaction between EDP and flavonoid components were investigated. Results indicated that the loading capacity order of flavonoids within the EDP nanomicelles was Myr (10.92%) > Que (9.56%) > Kae (6.63%) > Gal (5.55%). Moreover, this order was consistent with the order of the hydroxyl number in the flavonoid's B ring: Myr (3) > Que (2) > Kae (1) > Gal (0). The micro morphology exhibited that four flavonoid-EDP nanomicelles had a core-shell structure. In the meantime, the EDP encapsulation remarkably improved the flavonoids' water solubility, storage stability, and sustained release characteristics. During the interaction of EDP and flavonoids, the noncovalent interactions including van der Waals forces, hydrophobic interaction, and hydrogen bonding were the main binding forces. All of the results demonstrated that the hydroxyl number of bioactive compounds is a critical factor for developing a delivery system with high loading ability and stability.

CCDC92 deficiency ameliorates podocyte lipotoxicity in diabetic kidney disease.

BACKGROUND AND AIMS: Podocyte injury is considered as the most important early event contributing to diabetic kidney disease (DKD). Recent findings provide new insights into the roles of lipids and lipid-modulating proteins as key determinants of podocyte function in health and kidney disease. CCDC92, a novel member of coiled-coil domain-containing protein family, was indicated relevant to lipid metabolism, coronary heart disease and type 2 diabetes. However, the expression pattern and role of CCDC92 in the kidney is not clear. This study was designed to elucidate the contribution of CCDC92 in the pathogenesis of DKD. METHODS: Sections with a pathological diagnosis of different classes of DKD, including subjects with mild DKD (class II, n = 6), subjects with moderate DKD (class III, n = 6) or subjects with severe DKD (class IV, n = 6), and control samples (n = 12) were detected for the expression level of CCDC92 and lipid accumulation. Two types of diabetic mice model (db/db and HFD/STZ) in podocyte-specific Ccdc92 knockout background were generated to clarify the role of CCDC92 in podocyte lipotoxicity. RESULTS: The level of CCDC92 was increased in renal biopsies sections from patients with DKD, which was correlated with eGFR and lipid accumulation in glomeruli. In animal studies, CCDC92 were also induced in the kidney from two independent diabetic models, especially in podocytes. Podocyte-specific deletion of Ccdc92 ameliorated podocyte injury and ectopic lipid deposition under diabetic condition. Mechanically, CCDC92 promoted podocyte lipotoxicity, at least in part through ABCA1 signaling-mediated lipid homeostasis. CONCLUSION: Our studies demonstrates that CCDC92 acts as a novel regulator of lipid homeostasis to promote podocyte injury in DKD, suggesting that CCDC92 might be a potential biomarker of podocyte injury in DKD, and targeting CCDC92 may be an effective innovative therapeutic strategy for patients with DKD.

PGE 2 functions in ovoviviparous teleost black rockfish (Sebastes schlegelii): evolutionary status between parturition and ovulation.

Fish have evolved various reproductive strategies including oviparity, viviparity and ovoviviparity, which undoubtedly affect the survival of the whole species continuity. As the final step in reproduction, parturition in viviparous vertebrate and ovulation in oviparous teleost seems share the similar mechanism, when prostaglandins (PGs) act as the trigger to launch the whole process. In the present study, ovoviviparous teleost black rockfish (Sebastes schlegelii) is employed as the research object. I.P. injection showed PGE2 (500 µg/kg) could activate the delivery reactions in perinatal black rockfish. RNA-seq data of ovary in perinatal period revealed transcriptional change in cell junction, inflammation, and apoptosis, which is related to mammal parturition and teleost ovulation. Further results proved the positive correlation between ptger EP2 and previous mentioned pathways. Subsequent experiment proved that PGE2 was able to induce the ovulation and spawning in unfertilized individuals, which had a bilayer follicular structure compared to monolayer follicular in perinatal period black rockfish. Both unfertilized and perinatal ovary matrix could response to PGE2 stimulation. In conclusion, the function of PGE2 in activating both parturition and ovulation in a relatively different pathways conserved with viviparity or oviparity provided novel evidence of the evolutionary status of ovoviviparous vertebrates.

An injectable PC10ARGD/Cu2+/DOX hydrogel for combined chemodynamic and chemotherapy of tumors.

Nowadays, chemotherapy is a common clinical treatment for cancer, but it still faces many limitations and challenges. Therefore, the combination of chemotherapy and other treatments often enhances the effectiveness of treatments. Herein, an injectable hydrogel of PC10ARGD/Cu2+/DOX based on Cu2+, hydrophilic doxorubicin (DOX), and genetically engineered polypeptide PC10ARGD was prepared. First, Cu2+ was attached to the histidines in the PC10ARGD polypeptide by the coordination reaction to form PC10ARGD/Cu2+ hydrogel, then the PC10ARGD/Cu2+/DOX hydrogel was prepared by encapsulating the DOX into the PC10ARGD/Cu2+ hydrogel. The results of scanning electron microscopy showed that the PC10ARGD/Cu2+/DOX hydrogel displayed loose porous morphology. In vitro, reactive oxygen species production results showed that the PC10ARGD/Cu2+/DOX hydrogel could continuously produce ·OH in the presence of H2O2. In vitro MTT results showed that the PC10ARGD/Cu2+/DOX hydrogel had a good inhibitory effect on cell activity. Flow cytometry further confirmed the antitumor effect of the PC10ARGD/Cu2+/DOX hydrogel. In vivo experiment results showed that the tumor volume of mice treated with the PC10ARGD/Cu2+/DOX hydrogel was significantly inhibited compared with control groups, which was due to the combination of chemodynamic and chemotherapy. The results of body weight and blood analysis of mice showed that the PC10ARGD/Cu2+/DOX hydrogel possessed good biocompatibility.

Development and validation of a novel radiomics nomogram for prediction of early recurrence in colorectal cancer.

BACKGROUND: Early recurrence (ER) is a significant concern following curative resection of advanced colorectal cancer (CRC) and is linked to poor long-term survival. Reliable prediction of ER is challenging, necessitating the development of a novel radiomics-based nomogram for CRC patients. METHODS: We enrolled 405 patients, with 298 in the training set and 107 in the external test set. Radiomic features were extracted from preoperative venous-phase computed tomography (CT) images. A radiomics signature was created using univariate logistic regression analyses and the least absolute shrinkage and selection operator algorithm. Clinical factors were integrated into the analyses to develop a comprehensive predictive tool in a multivariate logistic regression model, resulting in a radiomics nomogram. Subsequently, the calibration, discrimination, and clinical usefulness of the nomogram were evaluated. RESULTS: The radiomics signature, consisting of four selected CT features, was significantly associated with ER in both the training and test datasets (P < 0.05). Independent predictors of ER included TNM stage, carcinoembryonic antigen level and differentiation grade were identified. The radiomics nomogram, incorporating all these predictors, exhibited good predictive ability in both the training set with an area under the curve (AUC) of 0.82 (95 % confidence interval (CI), 0.74-0.90) and the test set with an AUC of 0.85 (95 % CI, 0.72-0.99), surpassing the performance of any single candidate factor alone. Furthermore, additional analysis demonstrated that the nomogram was clinically useful. CONCLUSIONS: We have developed a radiomics-based nomogram that effectively predicts early recurrence in CRC patients, enhancing the potential for timely intervention and improved outcomes.

Humanized mouse models for inherited thrombocytopenia studies.

Inherited thrombocytopenia (IT) is a group of hereditary disorders characterized by a reduced platelet count as the main clinical manifestation, and often with abnormal platelet function, which can subsequently lead to impaired hemostasis. In the past decades, humanized mouse models (HMMs), that are mice engrafted with human cells or genes, have been widely used in different research areas including immunology, oncology, and virology. With advances of the development of immunodeficient mice, the engraftment, and reconstitution of functional human platelets in HMM permit studies of occurrence and development of platelet disorders including IT and treatment strategies. This article mainly reviews the development of humanized mice models, the construction methods, research status, and problems of using humanized mice for the in vivo study of human thrombopoiesis.

Humanized mouse models (HMMs) refer to immunodeficient mice that have been used for the investigation of human hematopoiesis and immunity for years. With engrafted human hematopoietic stem cells (HSCs), the differentiation process of HSCs and re-construction of platelets can be monitored in the mice. Until now, several strains of HMMs have been used in the studies of inherited thrombocytopenia (IT), a genetic disorder associated with low platelet count in the blood. In this study, we reviewed the development of these HMMs in IT studies, compared the different sources of HSCs transplanted into HMMs and summarize the strategies of HSC transplantation in HMMs. The Kit^−/− immunodeficient mice showed effectively long-term and stable implantation of human HSC without irradiation and higher implantation levels, and they also support multilinear differentiation of human HSC, such as platelets and red blood cells. The source and count of HSCs and the transplantation strategy may also impact the result. This study provides a basis information for HMMs used in IT and will help other investigators in this field choosing the right research plan.

A Pro-Metastatic Derivatives Eliminator for In Vivo Dual-Removal of Circulating Tumor Cells and Tumor-Derived Exosomes Impedes their Biodistribution into Distant Organs.

Circulating tumor cells (CTCs) and tumor-derived exosomes (TDEs) play an irreplaceable role in the metastatic cascade and preventing them from reaching distant organs via blood circulation helps to reduce the probability of cancer recurrence and metastasis. However, technologies that can simultaneously prevent CTCs and TDEs from reaching distant organs have not been thoroughly developed until now. Here, inspired by hemoperfusion, a pro-metastatic derivative eliminator (PMDE) is developed for the removal of both CTCs and TDEs from the peripheral blood, which also inhibits their biodistribution in distant organs. This device is designed with a dual antibody-modified immunosorbent filled into a capture column that draws peripheral blood out of the body to flow through the column to specifically capture CTCs and TDEs, followed by retransfusing the purified blood into the body. The PMDE can efficiently remove CTCs and TDEs from the peripheral blood and has excellent biocompatibility. Interestingly, the PMDE device can significantly inhibit the biodistribution of CTCs and TDEs in the lung and liver by scavenging them. This work provides a new perspective on anti-metastatic therapy and has broad prospects in clinical applications to prevent metastasis and recurrence.

Association between overtime and depressive symptoms among Chinese employees.

Objectives: This study examines the correlation between overtime and depressive symptoms, and analyzed the moderating effect of age, education level, and income level on their correlation by using a nationally representative sample from the Chinese Family Panel Studies (CFPS) in 2018. Methods: Participants are divided into three groups: 30-44 h/week, 44.1-61.9 h/week (defined as overtime group), and ≥ 62 h/week (heavy overtime group). The multiple ordered logistic regression models are conducted to estimate the association between overtime and depressive symptoms. The interaction term of overtime and moderators including age, education level, and income level are introduced into the models to test the moderating effect. Results: The overtime group have an increased probability of depressive symptoms (OR = 1.11, 95% CI 1.04-1.20) compared with those who reported working hours 30-44 h/week, after controlling for important confounders. What's more, the worsening of depressive symptoms is more pronounced in the heavy overtime group (OR = 1.32, 95% CI 1.22-1.44). The moderating effect results show that younger employees, employees with high education levels, and those with high income level are more likely to be affected by the negative effects of overtime. Conclusion: Working overtime increased the likelihood of depressive symptoms. Younger employees, high-educated employees and employees with high income level are more vulnerable to the negative effects of overtime on mental health.