Dynamic regulation of stem cell adhesion and differentiation on degradable piezoelectric poly (L-lactic acid) (PLLA) nanofibers.

Degradable piezoelectric materials possess significant potential for application in the realm of bone tissue regeneration. However, the correlation between cell regulation mechanisms and the dynamic variation caused by material degradation has not been explained, hindering the optimization of material design and its in vivo application. Herein, piezoelectric poly (L-lactic acid) (PLLA) nanofibers with different molecular weights (MW) were fabricated, and the effects of their piezoelectric properties, structural morphology, and material products during degradation on the adhesion and osteogenic differentiation of mesenchymal stem cells (MSCs) were investigated. Our results demonstrated that cell adhesion-mediated piezoelectric stimulation could significantly enhance cell spreading, cell orientation, and upregulate the expression of calmodulin, which further triggers downstream signaling cascade to regulate osteogenic differentiation markers of type I collagen and runt-related transcription factor 2. Additionally, during the degradation of the nanofibers, the piezoelectric properties of PLLA weakened, the fibrous structure gradually diminished, and pH levels in the vicinity decreased, which resulting in reduced osteogenic differentiation capability of MSCs. However, nanofibers with higher MW (280 kDa) have the ability to maintain the fibrous morphology and piezoelectricity for a longer time, which can regulate the osteogenic differentiation of stem cells for more than 4 weeks. These findings have provide a new insight to correlate cell behavior with MW and the biodegradability of piezopolymers, which revealed an active method for cell regulation through material optimization for bone tissue engineering in near future.

Effects of marine eutrophication environment on microbial corrosion: A review.

Metal materials undergo severe corrosion in eutrophic environments. The effect of DO decay stimulated by high concentrations of nitrogen and phosphorus pollutants on microorganisms leads to the coupling of electrochemical and microbial corrosion processes. However, there are few studies on microbial corrosion mechanisms in eutrophic environments. This article discusses the corrosive factors of marine eutrophication, summarizes the impact of marine eutrophication on microbial corrosion and the potential mechanisms, including aerobic biofilm corrosion, aerobic & anaerobic mixed biofilm corrosion, and anaerobic microbial electron transfer corrosion, and expounds on the research methods for microbial corrosion of materials serving in estuarine areas prone to pollution. Microbial prevention and control, such as nutrient restriction and microbial interspecies competition, are of research value in the field of green protection. Microbial corrosion mechanisms studies in marine eutrophication environments are significant for environment monitor development, water intake and algae control technologies, and corrosion protection in polluted environments.

Relative validity of an intelligent ordering system to estimate dietary intake among university students from a medical school in Shanghai, China.

BACKGROUND: Dietary assessment methods have limitations in capturing real-time eating behaviour accurately. Equipped with automated dietary-data-collection capabilities, the "intelligent ordering system" (IOS) has potential applicability in obtaining long-term consecutive, relatively detailed on-campus dietary records among university students with little resource consumption. We investigated (1) the relative validity of IOS-derived nutrient/food intakes compared to those from the 7-day food diary (7DFD); (2) whether including a supplemental food frequency questionnaire (SFFQ) improves IOS accuracy; and (3) sex differences in IOS dietary intake estimation. METHODS: Medical students (n = 221; age = 22.2 ± 2.4 years; 38.5% male and 61.5% female) completed the 7DFD and SFFQ. During the consecutive 7-day survey period, students weighed and photographed each meal before and after consumption. Then, students reviewed their 3-month diet and completed the SFFQ, which includes eight underprovided school-canteen food items (e.g., dairy, fruits, nuts). Meanwhile, 9385 IOS dietary data entries were collected. We used Spearman coefficients and linear regression models to estimate the associations among the different dietary intake assessment methods. Individual- and group-level agreement was assessed using the Wilcoxon signed-rank test, cross-classification, and Bland‒Altman analysis. RESULTS: IOS mean daily energy, protein, fat, and carbohydrate intake estimations were significantly lower (-15-20%) than those of the 7DFD. The correlation coefficients varied from 0.52 (for added sugar) to 0.88 (for soybeans and nuts), with fruits (0.37) and dairy products (0.29) showing weaker correlations. Sixty-two (milk and dairy products) to 97% (soybeans and nuts) of participants were classified into the same or adjacent dietary intake distribution quartile using both methods. The energy and macronutrient intake differences between the IOS + SFFQ and 7DFD groups decreased substantially. The separate fruit intake measurements from each assessment method did not significantly differ from each other (p > 0.05). IOS and IOS + SFFQ regression models generally yielded higher R2 values for males than for females. CONCLUSION: Despite estimation differences, the IOS can be reliable for medical student dietary habit assessment. The SFFQ is useful for measuring consumption of foods that are typically unavailable in school cafeterias, improving the overall dietary evaluation accuracy. The IOS assessment was more accurate for males than for females.

An in-depth analysis of postoperative insomnia in elderly patients and its implications on rehabilitation.

OBJECTIVES: (1) Assess the prevalence of postoperative insomnia; (2) identify the risk factors for postoperative insomnia before exposure to surgery; (3) explore the impact of postoperative insomnia on rehabilitation. METHODS: A study was conducted with 132 participants aged ≥ 65 undergoing spine interbody fusion. We collected the basic demographic data, Numeric Rating Scales (NRS), Pittsburgh Sleep Quality Index (PSQI), Geriatric Depression Scale (GDS), and Beck Anxiety Inventory (BAI). We measured Quality of Recovery 40 (QoR-40), GDS, BAI, NRS, and PSQI on the first and third nights post-surgery, followed by QoR-40 and NRS assessments two weeks after surgery. RESULTS: The cases of postoperative insomnia on the first and third nights and after two weeks were 81 (61.36%), 72 (54.55%), and 64 (48.48%), respectively, and the type of insomnia was not significantly different (P = 0.138). Sleep efficiency on the first night was 49.96% ± 23.51. On the first night of postoperative insomnia, 54 (66.67%) cases were depression or anxiety, and the PSQI was higher in this group than in the group without anxiety or depression (P < 0.001). PSQI, GDS, and the time of surgery were related factors for postoperative insomnia (PPSQI < 0.001, PGDS = 0.008, and PTime = 0.040). Postoperative rehabilitation showed differences between the insomnia and non-insomnia groups (P < 0.001). CONCLUSIONS: The prevalence of postoperative insomnia in the elderly was high, and postoperative insomnia had a significant correlation with postoperative rehabilitation. Interventions that target risk factors may reduce the prevalence of postoperative insomnia and warrant further research. CLINICAL TRIAL REGISTRATION: Multivariate analysis of postoperative insomnia in elderly patients with spinal surgery and its correlation with postoperative rehabilitation ( https://www.chictr.org.cn/bin/project/edit?pid=170201 ; #ChiCTR2200059827).

Hydroa vacciniforme lymphoproliferative disorder: a retrospective study of 42 paediatric cases.

Hydroa vacciniforme lymphoproliferative disorder (HVLPD) is a rare disease related to Epstein-Barr virus (EBV), mainly in children, and is an EBV-associated cutaneous T and natural killer (NK) cell lymphoproliferative disorder. The disorder in some patients may progress to EBV-associated systemic T or NK-cell lymphoma. To summarize the characteristics of HVLPD in Chinese paediatric patients and to examine the risk factors indicating poor prognosis. We performed a retrospective analysis of patients with HVLPD from the Department of Dermatology, Beijing Children's Hospital. Based on diagnosis, medical history, examination results, and immunophenotype, we analysed HVLPD in 42 paediatric cases in order to examine the clinical features, prognoses, and risk factors. Forty-two paediatric patients were enrolled, with a median onset age of five years. All patients presented with papulovesicular lesions, and 32 systemic HVLPD (sHVLPD) patients had systemic symptoms, including fever, lymphadenopathy, hepatomegaly, splenomegaly, and liver dysfunction. Of the sHVLPD cases, 13 also had severe mosquito bite allergy (SMBA). Twenty-five cases were T-type, and nine were CD56+-dominant type. Follow-up data showed that 12 patients had complete remission, and three patients died. SMBA is a risk factor for disease progression in patients with HVLPD, and the pathological CD56+-dominant phenotype is associated with poor prognosis.

ANCA negative pulmonary vasculitis: a challenging diagnosis.

A man in his 40s with end-stage kidney disease due to IgA nephropathy and receiving peritoneal dialysis presented with a 1-week history of breathlessness, cough and nosebleeds. CT scan of the chest revealed ground glass changes while blood tests indicated elevated inflammatory markers and a negative vasculitis screen. This included negative ANCA and anti-GBM antibodies. Initial treatment for suspected atypical pneumonia with antibiotics yielded no clinical improvement.Over the course of the admission, his symptoms progressively worsened, leading to oxygen dependency with a FiO2 of 40% and episodes of haemoptysis. Suspicions of pulmonary vasculitis arose due to clinical deterioration, prompting consultation with a tertiary vasculitis centre. It was subsequently concluded that the clinical and radiological findings correlated with ANCA-negative pulmonary vasculitis or a rare case of IgA-associated pulmonary capillaritis. Treatment with methylprednisolone and rituximab led to significant improvement, allowing rapid oxygen withdrawal. The patient was discharged with a tapering prednisolone regimen.

One-step electrodeposition synthesis of NiFePS on carbon cloth as self-supported electrodes for electrochemical overall water splitting.

Electrocatalytic water splitting (EWS) for hydrogen production is considered an ideal strategy for utilizing renewable energy, reducing fossil fuel consumption, and addressing environmental pollution issues. Traditional noble metal electrocatalysts have excellent performance, but their cost is high. Developing efficient, stable, and relatively inexpensive dual functional electrocatalysts is crucial for promoting large-scale EWS hydrogen production processes. Herein, a simple one-step electrodeposition method was used to grow nickel-iron phosphorus-sulfides (NiFePS) on the surface of hydrophilic treated carbon cloth (CC). The resultant NiFePS/CC with a phosphorus to sulfur ratio of 1:4 exhibited the best electrocatalytic performance, requiring only -91 mV and 216 mV overpotentials to generate the current densities of 10 mA·cm-2 in hydrogen evolution reaction (HER) and oxygen evolution reaction (OER), respectively. When it was used as a bifunctional electrocatalyst to overall water splitting (OWS), a voltage of 1.536 V can generate a current density of 10 mA·cm-2. The excellent electrocatalytic performance can be ascribed to two factors: 1) the CC with excellent conductivity serves as a growth substrate, reducing the impedance of charge transfer from the electrode to the electrolyte and accelerating the electron transfer rate; 2) The large number of ultra-thin nanosheets formed on the surface of the catalyst increase the electrochemical specific surface area, expose more reaction sites, and thus improve the electrocatalytic reaction performance. This work provides a new approach for designing efficient non-noble metal electrocatalysts for water splitting.

Freeze-Thaw Cycle Durability and Mechanism Analysis of Zeolite Powder-Modified Recycled Concrete.

The inferior mechanical performance and freeze-thaw (FT) resistance of recycled concrete are mostly due to the significant water absorption and porosity of recycled coarse particles. In this study, different dosages of zeolite powder were used in recycled concrete. A series of macroscopic tests were used to evaluate the workability and FT durability of zeolite powder-modified recycled concrete (ZPRC). X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to reveal the micro-mechanisms of FT resistance in ZPRC. The results show that the increase in zeolite powder content leads to a decrease in the slump and water absorption of ZPRC. Additionally, ZPRC with 10% zeolite powder has superior mechanical characteristics and tolerance to FT conditions. The higher strength and FT resistance of the ZPRC can be attributed to the particle-filling effect, water storage function, and pozzolanic reaction of zeolite powder, which results in a denser microstructure. The particle-filling effect of zeolite powder promotes the reduction of surface pores in recycled coarse aggregates (RCAs). The water storage function of zeolite powder can provide water for the secondary hydration of cement particles while reducing the free water content in ZPRC. The pozzolanic reaction of zeolite powder can also promote the generation of hydrated calcium silicate and anorthite, thereby making the microstructure of ZPRC more compact. These results provide theoretical guidance for the engineering application of recycled concrete in cold regions.

A Novel Peptidomimetic Insecticide: Dippu-AstR-Based Rational Design and Biological Activity of Allatostatin Analogs.

Insect neuropeptides play an essential role in regulating growth, development, reproduction, nerve conduction, metabolism, and behavior in insects; therefore, G protein-coupled receptors of neuropeptides are considered important targets for designing green insecticides. Cockroach-type allatostatins (ASTs) (FGLamides allatostatins) are important insect neuropeptides in Diploptera punctata that inhibit juvenile hormone (JH) synthesis in the corpora allata and affect growth, development, and reproduction of insects. Therefore, the pursuit of novel insecticides targeting the allatostatin receptor (AstR) holds significant importance. Previously, we identified an AST analogue, H17, as a promising candidate for pest control. Herein, we first modeled the 3D structure of AstR in D. punctata (Dippu-AstR) and predicted the binding mode of H17 with Dippu-AstR to study the critical interactions and residues favorable to its bioactivity. Based on this binding mode, we designed and synthesized a series of H17 derivatives and assessed their insecticidal activity against D. punctata. Among them, compound Q6 showed higher insecticidal activity than H17 against D. punctata by inhibiting JH biosynthesis, indicating that Q6 is a potential candidate for a novel insect growth regulator (IGR)-based insecticide. Moreover, Q6 exhibited insecticidal activity against Plutella xylostella, indicating that these AST analogs may have a wider insecticidal spectrum. The underlying mechanisms and molecular conformations mediating the interactions of Q6 with Dippu-AstR were explored to understand its effects on the bioactivity. The present work clarifies how a target-based strategy facilitates the discovery of new peptide mimics with better bioactivity, enabling improved IGR-based insecticide potency in sustainable agriculture.

Rational Design of Triazinone Derivatives with Low Bee Toxicity Based on the Binding Mechanism of Neonicotinoids to Apis mellifera.

Bees, one of the most vital pollinators in the ecosystem and agriculture, are currently threatened by neonicotinoids. To explore the molecular mechanisms of neonicotinoid toxicity to bees, the different binding modes of imidacloprid, thiacloprid, and flupyradifurone with nicotinic acetylcholine receptor (nAChR) α1ß1 and cytochrome P450 9Q3 (CYP9Q3) were studied using homology modeling and molecular dynamics simulations. These mechanisms provided a basis for the design of compounds with a potential low bee toxicity. Consequently, we designed and synthesized a series of triazinone derivatives and assessed their bioassays. Among them, compound 5a not only displayed substantially insecticidal activities against Aphis glycines (LC50 = 4.40 mg/L) and Myzus persicae (LC50 = 6.44 mg/L) but also had low toxicity to Apis mellifera. Two-electrode voltage clamp recordings further confirmed that compound 5a interacted with the M. persicae nAChR α1 subunit but not with the A. mellifera nAChR α1 subunit. This work provides a paradigm for applying molecular toxic mechanisms to the design of compounds with low bee toxicity, thereby aiding the future rational design of eco-friendly nicotinic insecticides.

A bioactive nanocomposite integrated specific TAMs target and synergistic TAMs repolarization for effective cancer immunotherapy.

Reactive oxygen species (ROS) generated from photosensitizers exhibit great potential for repolarizing immunosuppressive tumor-associated macrophages (TAMs) toward the anti-tumor M1 phenotype, representing a promising cancer immunotherapy strategy. Nevertheless, their effectiveness in eliminating solid tumors is generally limited by the instability and inadequate TAMs-specific targeting of photosensitizers. Here, a novel core-shell integrated nano platform is proposed to achieve a coordinated strategy of repolarizing TAMs for potentiating cancer immunotherapy. Colloidal mesoporous silica nanoparticles (CMSN) are fabricated to encapsulate photosensitizer-Indocyanine Green (ICG) to improve their stability. Then ginseng-derived exosome (GsE) was coated on the surface of ICG/CMSN for targeting TAMs, as well as repolarizing TAMs concurrently, named ICG/CMSN@GsE. As expected, with the synergism of ICG and GsE, ICG/CMSN@GsE exhibited better stability, mild generation of ROS, favorable specificity toward M2-like macrophages, enhancing drug retention in tumors and superior TAMs repolarization potency, then exerted a potent antitumor effect. In vivo, experiment results also confirm the synergistic suppression of tumor growth accompanied by the increased presence of anti-tumor M1-like macrophages and maximal tumor damage. Taken together, by integrating the superiorities of TAMs targeting specificity and synergistic TAMs repolarization effect into a single nanoplatform, ICG/CMSN@GsE can readily serve as a safe and high-performance nanoplatform for enhanced cancer immunotherapy.

Distribution and spatial variation of volatile methylsiloxanes in surface water and wastewater from the Yangtze River Basin, China.

Volatile methylsiloxanes (VMSs) earned serious concerns due to their detection and toxicities after their release to the environments. They were also detected in rivers around the globe, but their distribution remained to be explored in larger rivers with longer length, higher water volume and wider watershed. In the present study, 8 cyclic VMSs (cVMSs) and 7 linear ones (lVMSs) were investigated in 42 water samples (27 surface water (including 7 drinking source water) and 15 wastewater) from the Yangtze River Basin, China. Results showed that VMSs were detected in all sampling sites. In surface water, the concentrations of total cVMSs ranged from 17.3 to 4.57 × 103 ng/L, while those of lVMSs ranged from 1.72 to 81.6 ng/L. In wastewater, the total concentrations of cVMSs and lVMSs showed ranges of 17.6-1.66 × 103 ng/L and 2.59-252 ng/L, respectively. Apparently, cVMSs showed significantly higher concentrations than lVMSs. The concentrations of cVMSs followed an order of lower > upper > middle reaches, while those of lVMSs did not show clear distribution patterns. Among cVMSs, those with less Si numbers were dominant, while those with more Si numbers were dominant in lVMSs. Notably, the VMSs were also detected in 7 surface waters that served as drinking source waters, which earned them further concerns. In addition, the VMSs in surface water showed positive correlation with those in wastewater, which led to necessity in management on industrial emissions in the future.

Small-molecule α-lipoic acid targets ELK1 to balance human neutrophil and erythrocyte differentiation.

BACKGROUND: Erythroid and myeloid differentiation disorders are commonly occurred in leukemia. Given that the relationship between erythroid and myeloid lineages is still unclear. To find the co-regulators in erythroid and myeloid differentiation might help to find new target for therapy of myeloid leukemia. In hematopoiesis, ALA (alpha lipoic acid) is reported to inhibit neutrophil lineage determination by targeting transcription factor ELK1 in granulocyte-monocyte progenitors via splicing factor SF3B1. However, further exploration is needed to determine whether ELK1 is a common regulatory factor for erythroid and myeloid differentiation. METHODS: In vitro culture of isolated CD34+, CMPs (common myeloid progenitors) and CD34+ CD371- HSPCs (hematopoietic stem progenitor cells) were performed to assay the differentiation potential of monocytes, neutrophils, and erythrocytes. Overexpression lentivirus of long isoform (L-ELK1) or the short isoform (S-ELK1) of ELK1 transduced CD34+ HSPCs were transplanted into NSG mice to assay the human lymphocyte and myeloid differentiation differences 3 months after transplantation. Knocking down of SRSF11, which was high expressed in CD371+GMPs (granulocyte-monocyte progenitors), upregulated by ALA and binding to ELK1-RNA splicing site, was performed to analyze the function in erythroid differentiation derived from CD34+ CD123mid CD38+ CD371- HPCs (hematopoietic progenitor cells). RNA sequencing of L-ELK1 and S-ELK1 overexpressed CD34+ CD123mid CD38+ CD371- HPCs were performed to assay the signals changed by ELK1. RESULTS: Here, we presented new evidence that ALA promoted erythroid differentiation by targeting the transcription factor ELK1 in CD34+ CD371- hematopoietic stem progenitor cells (HSPCs). Overexpression of either the long isoform (L-ELK1) or the short isoform (S-ELK1) of ELK1 inhibited erythroid-cell differentiation, but knockdown of ELK1 did not affect erythroid-cell differentiation. RNAseq analysis of CD34+ CD123mid CD38+ CD371- HPCs showed that L-ELK1 upregulated the expression of genes related to neutrophil activity, phosphorylation, and hypoxia signals, while S-ELK1 mainly regulated hypoxia-related signals. However, most of the genes that were upregulated by L-ELK1 were only moderately upregulated by S-ELK1, which might be due to a lack of serum response factor interaction and regulation domains in S-ELK1 compared to L-ELK1. In summary, the differentiation of neutrophils and erythrocytes might need to rely on the dose of L-ELK1 and S-ELK1 to achieve precise regulation via RNA splicing signals at early lineage commitment. CONCLUSIONS: ALA and ELK1 are found to regulate both human granulopoiesis and erythropoiesis via RNA spliceosome, and ALA-ELK1 signal might be the target of human leukemia therapy.

The value of the dermal rim sign on nonenhanced magnetic resonance imaging for predicting dermal backflow in patients with primary lower extremity lymphedema.

PURPOSE: The dermal rim sign (DRS) on nonenhanced magnetic resonance imaging has been shown to predict dermal backflow (DBF) in patients with secondary upper limb lymphedema. However, whether the DRS has the same effects on primary lower extremity lymphedema (PLEL) has not been clearly reported. Therefore, this study aimed to explore whether the DRS can be used to diagnose DBF on lymphoscintigraphy in patients with PLEL. METHODS: A total of 94 patients who were diagnosed with PLEL were recruited for this retrospective study from January 2022 to December 2023. All the patients were divided into two groups according to the lymphoscintigraphy findings: no DBF and DBF. The magnetic resonance imaging data of the two groups were recorded and statistically compared for the following indicators: range of lymphedema involvement (left, right, whole lower limbs, only thigh, only calf and ankle), signs of lymphedema (notable thickening of skin, parallel line sign, grid sign, honeycomb sign, band sign, lymph lake sign, crescent sign, DRS), and lymphedema measurement (skin thickness, band width). The DRS is characterized by notable thickening of the skin plus the grid sign and/or honeycomb sign, plus the band sign. RESULTS: The following statistically significant differences in the following indicators were found between the two groups (P < .05): notable skin thickening, parallel line sign, grid sign, honeycomb sign, band sign, DRS, skin thickness, and band width. The sensitivity, specificity, and accuracy for predicting for DBF with the DRS was 82%, 64%, and 77%, respectively. CONCLUSIONS: This study confirmed good consistency between the DRS and DBF from the perspective of imaging. This tool is suitable for children, adolescents, and patients with contraindications to lymphoscintigraphy. The DRS has important value in assessing the severity of PLEL. The DRS is suggested for the clinical use of combined surgical treatment of PLEL.

Genome-wide identification, characterization and expression of C2H2 zinc finger gene family in Opisthopappus species under salt stress.

BACKGROUND: The C2H2 zinc finger protein family plays important roles in plants. However, precisely how C2H2s function in Opisthopappus (Opisthopappus taihangensis and Opisthopappus longilobus) remains unclear. RESULTS: In this study, a total of 69 OpC2H2 zinc finger protein genes were identified and clustered into five Groups. Seven tandem and ten fragment repeats were found in OpC2H2s, which underwent robust purifying selection. Of the identified motifs, motif 1 was present in all OpC2H2s and conserved at important binding sites. Most OpC2H2s possessed few introns and exons that could rapidly activate and react when faced with stress. The OpC2H2 promoter sequences mainly contained diverse regulatory elements, such as ARE, ABRE, and LTR. Under salt stress, two up-regulated OpC2H2s (OpC2H2-1 and OpC2H2-14) genes and one down-regulated OpC2H2 gene (OpC2H2-7) might serve as key transcription factors through the ABA and JA signaling pathways to regulate the growth and development of Opisthopappus species. CONCLUSION: The above results not only help to understand the function of C2H2 gene family but also drive progress in genetic improvement for the salt tolerance of Opisthopappus species.

Mesenchymal stem/stromal cells from human pluripotent stem cell-derived brain organoid enhance the ex vivo expansion and maintenance of hematopoietic stem/progenitor cells.

BACKGROUND: Mesenchymal stem/stromal cells (MSCs) are of great therapeutic value due to their role in maintaining the function of hematopoietic stem/progenitor cells (HSPCs). MSCs derived from human pluripotent stem cells represent an ideal alternative because of their unlimited supply. However, the role of MSCs with neural crest origin derived from HPSCs on the maintenance of HSPCs has not been reported. METHODS: Flow cytometric analysis, RNA sequencing and differentiation ability were applied to detect the characteristics of stromal cells from 3D human brain organoids. Human umbilical cord blood CD34+ (UCB-CD34+) cells were cultured in different coculture conditions composed of stromal cells and umbilical cord MSCs (UC-MSCs) with or without a cytokine cocktail. The hematopoietic stroma capacity of stromal cells was tested in vitro with the LTC-IC assay and in vivo by cotransplantation of cord blood nucleated cells and stroma cells into immunodeficient mice. RNA and proteomic sequencing were used to detect the role of MSCs on HSPCs. RESULTS: The stromal cells, derived from both H1-hESCs and human induced pluripotent stem cells forebrain organoids, were capable of differentiating into the classical mesenchymal-derived cells (osteoblasts, chondrocytes, and adipocytes). These cells expressed MSC markers, thus named pluripotent stem cell-derived MSCs (pMSCs). The pMSCs showed neural crest origin with CD271 expression in the early stage. When human UCB-CD34+ HSPCs were cocultured on UC-MSCs or pMSCs, the latter resulted in robust expansion of UCB-CD34+ HSPCs in long-term culture and efficient maintenance of their transplantability. Comparison by RNA sequencing indicated that coculture of human UCB-CD34+ HSPCs with pMSCs provided an improved microenvironment for HSC maintenance. The pMSCs highly expressed the Wnt signaling inhibitors SFRP1 and SFRP2, indicating that they may help to modulate the cell cycle to promote the maintenance of UCB-CD34+ HSPCs by antagonizing Wnt activation. CONCLUSIONS: A novel method for harvesting MSCs with neural crest origin from 3D human brain organoids under serum-free culture conditions was reported. We demonstrate that the pMSCs support human UCB-HSPC expansion in vitro in a long-term culture and the maintenance of their transplantable ability. RNA and proteomic sequencing indicated that pMSCs provided an improved microenvironment for HSC maintenance via mechanisms involving cell-cell contact and secreted factors and suppression of Wnt signaling. This represents a novel method for large-scale production of MSCs of neural crest origin and provides a potential approach for development of human hematopoietic stromal cell therapy for treatment of dyshematopoiesis.

Blockade of aryl hydrocarbon receptor restricts omeprazole-induced chronic kidney disease.

Chronic kidney disease (CKD) is the 16th leading cause of mortality worldwide. Clinical studies have raised that long-term use of omeprazole (OME) is associated with the morbidity of CKD. OME is commonly used in clinical practice to treat peptic ulcers and gastroesophageal reflux disease. However, the mechanism underlying renal failure following OME treatment remains mostly unknown and the rodent model of OME-induced CKD is yet to be established. We described the process of renal injury after exposure to OME in mice; the early renal injury markers were increased in renal tubular epithelial cells (RTECs). And after long-term OME treatment, the OME-induced CKD mice model was established. Herein, aryl hydrocarbon receptor (AHR) translocation appeared after exposure to OME in HK-2 cells. Then for both in vivo and in vitro, we found that Ahr-knockout (KO) and AHR small interfering RNA (siRNA) substantially alleviated the OME-induced renal function impairment and tubular cell damage. Furthermore, our data demonstrate that antagonists of AHR and CYP1A1 could attenuate OME-induced tubular cell impairment in HK-2 cells. Taken together, these data indicate that OME induces CKD through the activation of the AHR-CYP axis in RTECs. Our findings suggest that blocking the AHR-CYP1A1 pathway acts as a potential strategy for the treatment of CKD caused by OME. KEY MESSAGES: We provide an omeprazole-induced chronic kidney disease (CKD) mice model. AHR activation and translocation process was involved in renal tubular damage and promoted the occurrence of CKD. The process of omeprazole nephrotoxicity can be ameliorated by blockade of the AHR-CYP1A1 axis.

Potential Response Patterns of Endogenous Hormones in Cliff Species Opisthopappus taihangensis and Opisthopappus longilobus under Salt Stress.

When plants are exposed to salt stress, endogenous hormones are essential for their responses through biosynthesis and signal transduction pathways. However, the roles of endogenous hormones in two cliff species (Opisthopappus taihangensis and Opisthopappus longilobus (Opisthopappus genus)) in the Taihang Mountains under salt stress have not been investigated to date. Following different time treatments under 500 mM salt concentrations, 239 differentially expressed gene (DEG)-related endogenous hormones were identified that exhibited four change trends, which in Profile 47 were upregulated in both species. The C-DEG genes of AUX, GA, JA, BR, ETH, and ABA endogenous hormones were significantly enriched in Opisthopappus taihangensis (O. taihangensis) and Opisthopappus longilobus (O. longilobus). During the responsive process, mainly AUX, GA, and JA biosynthesis and signal transduction were triggered in the two species. Subsequently, crosstalk further influenced BR, EHT, ABA, and MAPK signal transduction pathways to improve the salt resistance of the two species. Within the protein-protein interactions (PPI), seven proteins exhibited the highest interactions, which primarily involved two downregulated genes (SAUR and GA3ox) and eight upregulated genes (ACX, MFP2, JAZ, BRI1, BAK1, ETR, EIN2, and SNRK2) of the above pathways. The more upregulated expression of ZEP (in the ABA biosynthesis pathway), DELLA (in the GA signaling pathway), ABF (in the ABA signaling pathway), and ERF1 (in the ETH signaling pathway) in O. taihangensis revealed that it had a relatively higher salt resistance than O. longilobus. This revealed that the responsive patterns to salt stress between the two species had both similarities and differences. The results of this investigation shed light on the potential adaptive mechanisms of O. taihangensis and O. longilobus under cliff environments, while laying a foundation for the study of other cliff species in the Taihang Mountains.

The Use of Eye-Tracking Technology in Dento-Maxillofacial Esthetics: A Systematic Review.

The use of eye-tracking technology in dental esthetics has gained popularity over the past decade because of its ability to assess observers' visual preferences in an objective manner. The goal of this study was to provide a comprehensive review of eye-tracking studies in dentistry, which could provide a reference for the rational and effective application of eye-tracking technology by dentists in the future. A comprehensive search of articles on eye tracking, published from January 1946 to June 2023, was conducted across several databases using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The major criterion for inclusion was that the study evaluated the use of eye-tracking technology in the field of dentistry. Two independent reviewers screened the eligible studies. A total of 67 articles were identified, 41 of which met our inclusion criteria. The most common application of eye tracking was the assessment of perceptions of changes in specific dental conditions among different classes of observers. Overall differences between groups (different classes of observers, different types of conditions) among different areas or regions of interest were analyzed. This systematic review demonstrated the utility of eye-tracking technology as a quantifiable objective assessment and emerging research tool for evaluating outcomes in several domains of dentistry.