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.

miRNA-143 as a potential biomarker in the detection of bladder cancer: a meta-analysis.

Aim: This study aimed to systematically evaluate the value of miRNA-143 in the early detection of bladder cancer (BCa). Methods: CNKI, WanFang, PubMed and Wiley Online Library databases were explored according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. A random-effects model was used to obtain pooled sensitivity, specificity and other related indicates. Results: Six studies were included for analysis. The overall pooled sensitivity and specificity were 0.80 (95% CI: 0.74-0.85) and 0.85 (95% CI: 0.78-0.91), and the area under the curve was 0.88 (95% CI: 0.85-0.91). Coupled with miR-100, it showed better diagnostic power (area under the curve: 0.95). Conclusion: miRNA-143 may serve as a promising noninvasive tool for the early detection of BCa.

Bladder cancer (BCa) is a common and deadly malignant tumor worldwide; however, noninvasive diagnosis can significantly improve the prognosis of patients. Recently, miRNAs have emerged as potential diagnostic biomarkers for BCa. Among them, miRNA-143 has shown promising results in several studies. This meta-analysis aimed to evaluate the overall diagnostic accuracy of miRNA-143 for BCa through a systematic review and meta-analysis of six published articles. Excitingly, the results of this meta-analysis suggest that miRNA-143 has potential diagnostic value in BCa. Particularly, miRNA-143 combined with miRNA-100 maintained better competence. Besides, miRNA-143 in plasma exhibited better diagnostic strength than that in urine. The authors believe that their study provides valuable insights into the use of miRNA-143 as a diagnostic biomarker for BCa.

Fine particulate matter exposure and systemic inflammation: A potential mediating role of bioactive lipids.

Inflammation is a key mechanism underlying the adverse health effects of exposure to fine particulate matter (PM2.5). Bioactive lipids in the arachidonic acid (ARA) pathway are important in the regulation of inflammation and are reportedly altered by PM2.5 exposure. Ceramide-1-phosphate (C1P), a class of sphingolipids, is required to initiate ARA metabolism. We examined the role of C1P in the alteration of ARA metabolism after PM2.5 exposure and explored whether changes in the ARA pathway promoted systemic inflammation based on a panel study involving 112 older adults in Beijing, China. Ambient PM2.5 levels were continuously monitored at a fixed station from 2013 to 2015. Serum cytokine levels were measured to assess systemic inflammation. Multiple bioactive lipids in the ARA pathway and three subtypes of C1P were quantified in blood samples. Mediation analyses were performed to test the hypotheses. We observed that PM2.5 exposure was positively associated with inflammatory cytokines and the three subtypes of C1P. Mediation analyses showed that C1P significantly mediated the associations of ARA and 5, 6-dihydroxyeicosatrienoic acid (5, 6-DHET), an ARA metabolite, with PM2.5 exposure. ARA, 5, 6-DHET, and leukotriene B4 mediated systemic inflammatory response to PM2.5 exposure. For example, C1P C16:0 (a subtype of C1P) mediated a 12.9 % (95 % confidence interval: 3.7 %, 32.5 %) increase in ARA associated with 3-day moving average PM2.5 exposure, and ARA mediated a 27.1 % (7.8 %, 61.2 %) change in interleukin-8 associated with 7-day moving average PM2.5 exposure. Our study indicates that bioactive lipids in the ARA and sphingolipid metabolic pathways may mediate systemic inflammation after PM2.5 exposure.

A study on vertebral refracture and scoliosis after percutaneous kyphoplasty in patients with osteoporotic vertebral compression fractures.

PURPOSE: To analyze the association between scoliosis and vertebral refracture after percutaneous kyphoplasty (PKP) in patients with osteoporotic vertebral compression fractures (OVCFs). METHODS: A retrospective study was conducted on 269 patients meeting the criteria from January 2014 to October 2022. All patients underwent PKP with complete data and were followed-up for > 12 months. First, it was verified that scoliosis was a risk factor in 269 patients. Second, patients with scoliosis were grouped based on the Cobb angle to evaluate the impact of the post-operative angle. The cox proportional hazards regression analysis and survival analysis were used to calculate the hazard ratio and recurrence time. RESULTS: A total of 56 patients had scoliosis, 18 of whom experienced refractures after PKP. The risk factors for vertebral refractures included a T-score < - 3.0 and presence of scoliosis (both p < 0.001). The results indicated that the vertebral fractured arc (T10 - L4) was highly influential in scoliosis and vertebral fractures. When scoliotic and initially fractured vertebrae were situated within T10 - L4, the risk factors for vertebral refracture included a postoperative Cobb angle of ≥ 20° (p = 0.002) and an increased angle (p = 0.001). The mean recurrence times were 17.2 (10.7 - 23.7) months and 17.6 (7.9 - 27.3) months, respectively. CONCLUSION: Osteoporosis combined with scoliosis significantly increases the risk of vertebral refractures after PKP in patients with OVCFs. A postoperative Cobb angle of ≥ 20° and an increased angle are significant risk factors for vertebral refractures when scoliotic and initially fractured vertebrae are situated within T10 - L4.

CircMEF2C(2, 3) modulates proliferation and adipogenesis of porcine intramuscular preadipocytes by miR-383/671-3p/MEF2C axis.

Circular RNA is a special category of non-coding RNA that has emerged as epigenetic regulator of adipose tissue development. However, the mechanism governing intramuscular adipogenesis of circRNA remains largely uncharted. In this study, circMEF2C(2, 3), looped by MEF2C exons 2 and 3, was identified from the pig MEF2C gene. Expression of circMEF2C(2, 3) is upregulated in early stage of intramuscular adipogenesis and muscular tissue of lean pigs (DLY pig). Subsequently, overexpression or knockdown of circMEF2C(2, 3) reflected that it participates in promoting proliferation and inhibiting adipogenic differentiation in porcine intramuscular preadipocytes and murine C3H10T1/2 cells. Mechanically, circMEF2C(2, 3) competitively combined with miR-383 and miR-671-3p to the 3'-UTR of MEF2C, which maintains MEF2C expression in regulating proliferation and adipogenesis. In summary, circMEF2C(2, 3) is a key regulator in the proliferation and adipogenic differentiation of intramuscular adipogenesis, suggesting its potential as a multi-target strategy for adipose development and associated diseases.

Leveraging Janus Substrates as a Confined "Interfacial Reactor" to Synthesize Ultrapermeable Polyamide Nanofilms.

Porous substrates act as open "interfacial reactors" during the synthesis of polyamide composite membranes via interfacial polymerization. However, achieving a thin and dense polyamide nanofilm with high permeance and selectivity is challenging when using a conventional substrate with uniform wettability. To overcome this limitation, we propose the use of Janus porous substrates as confined interfacial reactors to decouple the local monomer concentration from the total monomer amount during interfacial polymerization. By manipulating the location of the hydrophilic/hydrophobic interface in a Janus porous substrate, we can precisely control the monomer solution confined within the hydrophilic layer without compromising its concentration. The hydrophilic surface ensures the uniform distribution of monomers, preventing the formation of defects. By employing Janus substrates fabricated through single-sided deposition of polydopamine/polyethyleneimine, we significantly reduce the thickness of the polyamide nanofilms from 88.4 to 3.8 nm by decreasing the thickness of the hydrophilic layer. This reduction leads to a remarkable enhancement in water permeance from 7.2 to 52.0 l/m2·h·bar while still maintaining ~96% Na2SO4 rejection. The overall performance of this membrane surpasses that of most reported membranes, including state-of-the-art commercial products. The presented strategy is both simple and effective, bringing ultrapermeable polyamide nanofilms one step closer to practical separation applications.

Combining metabolomics and transcriptomics to reveal the potential medicinal value of rare species Glycyrrhiza squamulose.

Licorice is a well-known Chinese medicinal plant that is widely used to treat multiple diseases and process food; however, wild licorice is now facing depletion. Therefore, there is an urgent need to identify and protect licorice germplasm diversity. In this study, metabolomic and transcriptomic analyses were conducted to investigate the biodiversity and potential medicinal value of the rare wild Glycyrrhiza squamulose. A total of 182 differentially accumulated metabolites and 395 differentially expressed genes were identified by comparing Glycyrrhiza uralensis and Glycyrrhiza squamulose. The molecular weights of the chemical component of G. squamulose were comparable with those of G. uralensis, suggesting that G. squamulose may have medicinal value. Differentially accumulated metabolites (DAMs), mainly flavonoids such as kaempferol-3-O-galactoside, kaempferol-3-O-(6"malonyl) glucoside, and hispidulin-7-O-glucoside, showed potential vitality in G. squamulose. Comparative transcriptomics with G. uralensis showed that among the 395 differentially expressed genes (DEGs), 69 were enriched in the isoflavonoid biosynthesis pathway. Multiomics analysis showed that the distinction in flavonoid biosynthesis between G. squamulose and G. uralensis was strongly associated with the expression levels of IF7GT and CYP93C. In addition to identifying similarities and differences between G. squamulose and G. uralensis, this study provides a theoretical basis to protect and investigate rare species such as G. squamulose.

HMGB2 is a biomarker associated with poor prognosis promoting radioresistance in glioma by targeting base excision repair pathway.

BACKGROUND: High mobility group box 2 (HMGB2) is considered as a biomarker of poor prognosis in various cancers.This study aims to investigate the effect and mechanism of HMGB2 in gliomas. METHODS: With the glioma related on-line and our local hospital databases, the expression differences of HMGB2,Kaplan-Meier survival analysis and COX regression analysis were performed.The correlation analysis between the clinicopathological features and imaging parameters with the HMGB2 expression had been done. Then GSEA and PPI networks were carried out to find out the most significant pathway. The pathway inhibitor was applied to verify HMGB2's participation. CCK8,EDU assays,γ-H2AX immunofluorescence staining and colony formation assay were conducted to observe effects on glioma cells. RESULTS: Available datasets showed that HMGB2 was highly expressed in glioma and patients with high expression of HMGB2 had poorer prognosis and molecular characteristics. Protein level evidence of western blot and immunohistochemistry from our center supported the conclusions above. Analysis on imaging features suggested that HMGB2 expression level had an inverse association with ADCmean but positively with the thickness of enhancing margin. Results from GSEA and PPI network analysis exhibited that HMGB2 was involved in base excision repair (BER) signaling pathway. Experimental evidence demonstrated that the overexpression of HMGB2 promoted the proliferation of glioma cells and enhanced the radio-resistance. CONCLUSIONS: HMGB2 could promote glioma development and enhance the radioresistance of glioma cells, potentially related to the BER pathway, suggesting it may serve as an underlying biomarker for patients with glioma.

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.

Comparative Physio-Biochemical and Transcriptome Analyses Reveal Contrasting Responses to Magnesium Imbalances in Leaves of Mulberry (Morus alba L.) Plants.

Magnesium (Mg) deficiency is a major factor limiting the growth and development of plants. Mulberry (Morus alba L.) is an important fruit tree crop that requires Mg for optimal growth and yield, especially in acid soils. However, the molecular mechanism of Mg stress tolerance in mulberry plants remains unknown. In this study, we used next-generation sequencing technology and biochemical analysis to profile the transcriptome and physiological changes of mulberry leaves under different Mg treatments (deficiency: 0 mM, low: 1 mM, moderate low: 2 mM, sufficiency: 3 mM, toxicity: 6 mM, higher toxicity: 9 mM) as T1, T2, T3, CK, T4, T5 treatments, respectively, for 20 days. The results showed that Mg imbalance altered the antioxidant enzymatic activities, such as catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD), and non-enzymatic, including soluble protein, soluble sugar, malondialdehyde (MDA), and proline (PRO), contents of the plant. The Mg imbalances disrupted the ultrastructures of the vital components of chloroplast and mitochondria relative to the control. The transcriptome data reveal that 11,030 genes were differentially expressed (DEGs). Genes related to the photosynthetic processes (CAB40, CAB7, CAB6A, CAB-151, CAP10A) and chlorophyll degradation (PAO, CHLASE1, SGR) were altered. Antioxidant genes such as PER42, PER21, and PER47 were downregulated, but DFR was upregulated. The carbohydrate metabolism pathway was significantly altered, while those involved in energy metabolism processes were perturbed under high Mg treatment compared with control. We also identified several candidate genes associated with magnesium homeostasis via RT-qPCR validation analysis, which provided valuable information for further functional characterization studies such as promoter activity assay or gene overexpression experiments using transient expression systems.

ZnO/g-C3N4 photocatalyst activated by low-pressure ultraviolet for restoring the SWASV signals: A fast pretreatment method for electrochemically detecting Cd2+ and Pb2+ in soil extracts.

Soil organic matter (SOM) significantly impacts the detection accuracy of Cd2+ and Pb2+ using square wave anodic stripping voltammetry (SWASV) due to the complexation of SOM to heavy metal ions (HMIs), thereby attenuating SWASV signals. This study explored an effective pretreatment method that combined low-pressure ultraviolet (LPUV) photolysis with the ZnO/g-C3N4 photocatalyst, activating the photocatalyst to generate highly oxidative •OH radicals and O2•- radicals, which effectively disrupted this complexation, consequently restoring the electroactivity of HMIs and achieving high-fidelity SWASV signals. The parameters of the LPUV-ZnO/g-C3N4 photocatalytic system were meticulously optimized, including the pH of photolysis, duration of photolysis, g-C3N4 mass fraction, and concentration of the photocatalyst. Furthermore, the ZnO/g-C3N4 photocatalyst was thoroughly characterized, with an in-depth investigation on the synergistic interaction between ZnO and g-C3N4 and the mechanisms contributing to the restoration of SWASV signals. This synergistic interaction effectively separated charge carriers and reduced charge transfer resistance, enabling photogenerated electrons (e-) from the conduction band of g-C3N4 to be quickly transferred to the conduction band of ZnO, preventing the recombination of e- and hole (h+) and generating more radicals to disrupt complexation and restore the SWASV signals. Finally, the analysis of HMIs in real soil extracts using the proposed pretreatment method demonstrated high detection accuracy of 94.9% for Cd2+ and 99.8% for Pb2+, which validated the feasibility and effectiveness of the proposed method in environmental applications.

Association of lipid levels with motor and cognitive function and decline in Parkinson's disease.

BACKGROUND: Most studies have focused on comparing blood lipid biomarkers between Parkinson's disease (PD) and normal controls (NC). However, further research is necessary to explore the impact of blood lipid levels on motor and cognitive function, as well as the progression of motor dysfunction and cognitive decline over time. Thus, the aim of this study is to investigate the relationship between blood lipid biomarkers and these indicators in individuals with PD. METHODS: The cohort study enrolled 157 PD patients and 146 NC from the Tianjin Huanhu Hospital from September 2017 to September 2019. Serum lipid fractions were detected in fasting serum samples. PD patients were followed up at 2 ± 0.6 years for clinical assessment. RESULTS: PD patients exhibited lower serum triglyceride (TG) levels as compared to NC (P = 0.008). PD male patients exhibited lower serum lipoprotein cholesterol(LDL-C) and total cholesterol (TC) levels than female patients (LDL-C: P = 0.034; TC: P = 0.019). Serum TG levels correlated significantly with Unified PD Rating Scale III, Hoehn and Yahr stage and Montreal Cognitive Assessment scores in PD patients. Additionally, serum TG levels were associated with follow-up motor function decline and cognitive decline in adjusted regression models in PD patients. CONCLUSIONS: To summarise, the study findings suggest that decreased serum TG levels are significantly associated with greater motor dysfunction, cognitive dysfunction and the greater deterioration of the two indicators.

Autonomous Underwater Self-Healable Adhesive Elastomers Enabled by Dynamical Hydrophobic Phase-Separated Microdomains.

High-efficient underwater self-healing materials with reliable mechanical attributes hold great promise for applications in ocean explorations and diverse underwater operations. Nevertheless, achieving these functions in aquatic environments is challenging because the recombination of dynamic interactions will suffer from resistance to interfacial water molecules. Herein, an ultra-robust and all-environment stable self-healable polyurethane-amide supramolecular elastomer is developed through rational engineering of hydrophobic domains and multistrength hydrogen bonding interactions to provide mechanical and healing compatibility as well as efficient suppression of water ingress. The coupling of hydrophobic chains and hierarchical hydrogen bonds within a multiphase matrix self-assemble to generate dynamical hydrophobic hard-phase microdomains, which synergistically realize high stretchability (1601%), extreme toughness (87.1 MJ m-3), and outstanding capability to autonomous self-healing in various harsh aqueous conditions with an efficiency of 58% and healed strength of 12.7 MPa underwater. Furthermore, the self-aggregation of hydrophobic clusters with sufficient dynamic interactions endows the resultant elastomer with effective instantaneous adhesion (6.2 MPa, 941.9 N m-1) in extremely harsh aqueous conditions. It is revealed that the dynamical hydrophobic hard-phase microdomain composed of hydrophobic barriers and cooperative reversible interactions allows for regulating its mechanical enhancement and underwater self-healing efficiency, enabling the elastomers as intelligent sealing devices in marine applications.

Synthesis of sinomenine derivatives with potential anti-leukemia activity.

In recent years, with sinomenine hydrochloride as the main ingredient, Qingfengteng had been formulated as various dosage forms for clinical treatment. Subsequent findings confirmed a variety of biological roles for sinomenine. Here, 15 H2S-donating sinomenine derivatives were synthesized. Target hybrids a11 displayed substantial cytotoxic effects on cancer cell lines, particularly against K562 cells, with an IC50 value of 1.36 µM. In-depth studies demonstrated that a11 arrested cell cycle at G1 phase, induced apoptosis via both morphological changes in nucleus and membrane potential collapse in mitochondria. These results indicated a11 exerted an antiproliferative effect through apoptosis induction via mitochondrial pathway.

Supergravity-Steered Generic Manufacturing of Nanosheets-Embedded Nanocomposite Hydrogel with Highly Oriented, Heterogeneous Architecture.

Designing nanocomposite hydrogels with oriented nanosheets has emerged as a promising toolkit to achieve preferential performances that go beyond their disordered counterparts. Although current fabrication strategies via electric/magnetic force fields have made remarkable achievements, they necessitate special properties of nanosheets and suffer from an inferior orientation degree of nanosheets. Herein, a facile and universal approach is discovered to elaborate MXene-based nanocomposite hydrogels with highly oriented, heterogeneous architecture by virtue of supergravity to replace conventional force fields. The key to such architecture is to leverage bidirectional, force-tunable attributes of supergravity containing coupled orthogonal shear and centrifugal force field for steering high-efficient movement, pre-orientation, and stacking of MXene nanosheets in the bottom. Such a synergetic effect allows for yielding heterogeneous nanocomposite hydrogels with a high-orientation MXene-rich layer (orientation degree, f = 0.83) and a polymer-rich layer. The authors demonstrate that MXene-based nanocomposite hydrogels leverage their high-orientation, heterogeneous architecture to deliver an extraordinary electromagnetic interference shielding effectiveness of 55.2 dB at 12.4 GHz yet using a super-low MXene of 0.3 wt%, surpassing most hydrogels-based electromagnetic shielding materials. This versatile supergravity-steered strategy can be further extended to arbitrary nanosheets including MoS2, GO, and C3N4, offering a paradigm in the development of oriented nanocomposites.

Socioeconomic status, personality, and major mental disorders: a bidirectional Mendelian randomization study.

Previous research has suggested a correlation between socioeconomic status (SES) and mental diseases, while personality traits may be associated with SES and the risk of mental disorders. However, the causal nature of these associations remains largely uncertain. Our Mendelian randomization (MR) study aims to explore the bidirectional causality between SES and mental disorders, as well as to evaluate the potential mediating role of personality in these associations. Using bidirectional MR approach, we assessed the causality between SES indicators and mental disorders. We then used a two-step MR method to further investigate whether and to what extent personality mediates the causal associations in Caucasians. The forward MR analyses identified that years of education, household income, age at first birth and the Townsend deprivation index had a causal association with at least one mental disorder. The reverse MR analyses identified causal effects of genetically predicted schizophrenia, bipolar disorder, and attention deficit/hyperactivity disorder on five SES indicators. Importantly, mediation analysis showed that neuroticism partly mediated the causality of household income and years of education on major depressive disorder, respectively. In brief, our study confirmed the bidirectional relationship between SES and mental disorders. We also revealed the role of neuroticism in mediating the association between SES and major depressive disorder, highlighting the importance of considering both socioeconomic and personality factors in mental health research and interventions.

T-2 toxin-induced damage to articular cartilage in rats coincided with impaired autophagy linked to the HIF-1α/AMPK signaling axis.

T-2 toxin is one of the most toxic mycotoxins. People are primarily exposed to T-2 toxin through the consumption of spoiled food, typically over extended periods and at low doses. T-2 toxin can cause damage to articular cartilage. However, the exact mechanism is not fully understood. In this experiment, 36 male rats were divided into a control group, a solvent control group, and a T-2 toxin group. The rats in the T-2 toxin group were orally administered the toxin at a dosage of 100 ng/g BW/Day. The damage to articular cartilage and key proteins associated with the autophagy process and the HIF-1α/AMPK signaling axis was assessed at 4, 8, 12, and 16 weeks. Our findings indicate that T-2 toxin-induced damage to articular cartilage in rats coincided with impaired autophagy linked to the HIF-1α/AMPK signaling pathway. This study offers novel insights into the precise mechanism underlying T-2 toxin-induced damage to articular cartilage.

Factors influencing delayed high-dose methotrexate excretion and its correlation with adverse reactions after treatment in children with malignant hematological tumors.

Background: High-dose methotrexate (HDMTX) is crucial in treating pediatric malignant hematological tumors. However, its use is often complicated by delayed excretion and associated adverse reactions, which can significantly affect treatment outcomes and patient safety. Identifying risk factors is essential for safer, more effective therapy. This study aimed to investigate the influencing factors for delayed excretion and their correlation with adverse reactions in children with malignant hematological tumors after receiving HDMTX chemotherapy. Methods: From April to October 2021, the clinical information of children who had undergone HDMTX chemotherapy and had their blood tested for drug concentration was gathered by the Department of Hematology and Oncology at Shanghai Children's Medical Center. Via univariate and multivariate logistic regression, the factors affecting the delayed excretion of HDMTX were examined, and the relationship between delayed excretion and unfavorable effects in children was determined. Results: This study included 99 patients comprising 199 courses of HDMTX. The occurrence rate of HDMTX delayed excretion was 20.1%. Age ≥9 years and a 24-hour methotrexate (MTX) concentration of 64 µmol/L were independent risk factors for delayed MTX excretion according to multivariate logistic regression analysis (P<0.05). Negative side effects, such as fever, infection, mucositis, gastrointestinal response, and decreased platelet count in children with delayed excretion were statistically significant when compared to those of children with normal excretion. White blood cell reduction, hemoglobin levels below 65 g/L, MTX excretion delay, and concomitant etoposide treatment were all independent risk factors for infection in children. Conclusions: To estimate the risk of delayed MTX excretion during HDMTX therapy, patient laboratory data should be scrutinized, especially for patients ≥9 years or those with a 24-hour MTX concentration of greater than 64 µmol/L.

Primary cilia promote the differentiation of human neurons through the WNT signaling pathway.

BACKGROUND: Primary cilia emanate from most human cell types, including neurons. Cilia are important for communicating with the cell's immediate environment: signal reception and transduction to/from the ciliated cell. Deregulation of ciliary signaling can lead to ciliopathies and certain neurodevelopmental disorders. In the developing brain cilia play well-documented roles for the expansion of the neural progenitor cell pool, while information about the roles of cilia during post-mitotic neuron differentiation and maturation is scarce. RESULTS: We employed ciliated Lund Human Mesencephalic (LUHMES) cells in time course experiments to assess the impact of ciliary signaling on neuron differentiation. By comparing ciliated and non-ciliated neuronal precursor cells and neurons in wild type and in RFX2 -/- mutant neurons with altered cilia, we discovered an early-differentiation "ciliary time window" during which transient cilia promote axon outgrowth, branching and arborization. Experiments in neurons with IFT88 and IFT172 ciliary gene knockdowns, leading to shorter cilia, confirm these results. Cilia promote neuron differentiation by tipping WNT signaling toward the non-canonical pathway, in turn activating WNT pathway output genes implicated in cyto-architectural changes. CONCLUSIONS: We provide a mechanistic entry point into when and how ciliary signaling coordinates, promotes and translates into anatomical changes. We hypothesize that ciliary alterations causing neuron differentiation defects may result in "mild" impairments of brain development, possibly underpinning certain aspects of neurodevelopmental disorders.

Self-Flipping Solar Seesaw Evaporators Leverage Scaling to De-Scale.

Salt scaling poses a significant obstacle to the practical implementation of solar-driven evaporation for desalination. Attempts to mitigate scaling by enhancing mass transfer often lead to a compromise in evaporation efficiency due to associated heat loss. In the present work, a novel seesaw evaporator with a Janus structure to harness scaling for periodic self-descaling is reported. The seesaw evaporators are facilely fabricated by delignifying balsa wood and subsequently single-sided spray-coating it with soot and polydimethylsiloxane (PDMS). This unique Janus structure enables the evaporator to float on the brine while ensuring an ample supply of solution for evaporation. During evaporation, salt ions are transported directionally toward the cocked end of the evaporator to form scaling, triggering the seesaw evaporator to flip once a threshold is reached. The accumulated salts re-dissolve back into the solution. By adjusting the tilt angle, the evaporator can achieve an impressive evaporation rate of up to 2.65 kg m-2  h-1 when evaporating an 8 wt.% NaCl solution. Remarkably, these evaporators maintain a stable evaporation rate during prolonged 120 h operation and produce ≈3.93-6.35 L m⁻2 ·day⁻¹ of freshwater from simulated brines when assembled into an evaporation device.