Extended Endoscopic Endonasal Approach for Giant Pediatric Craniopharyngiomas: Technical Note and Case Series.

BACKGROUND AND OBJECTIVES: Giant pediatric craniopharyngiomas are rare tumors whose clinical and surgical management is extremely challenging. A variety of open transcranial approaches has been used to resect these lesions. Although there has been an increasing acceptance of the endoscopic endonasal approach (EEA) for the resection of pediatric craniopharyngiomas in recent years, many surgeons continue to recommend against the use of the EEA for giant pediatric craniopharyngiomas. This study aimed to evaluate the feasibility of extended EEA for giant craniopharyngiomas in the pediatric population. METHODS: All consecutive pediatric patients with giant craniopharyngiomas (diameter >4 cm) who underwent endoscopic endonasal surgery at our institution were retrospectively reviewed. Data on demographic information, preoperative assessment, imaging features, surgical results, complications, and recurrences were recorded and analyzed. RESULTS: A total of 16 pediatric patients with an average age of 12 years were identified. The mean maximum diameter and volume of the tumors were 4.35 cm and 24.1 cm3, respectively. Gross total resection was achieved in 13 patients (81.3%) and subtotal resection in 3 patients (18.7%). Postoperatively, partial or complete anterior pituitary insufficiency occurred in 100% of patients, and 62.5% developed new-onset diabetes insipidus. Visual function improved in 9 patients (56.3%) and remained stable in 7 patients (43.7%). Postoperative cerebrospinal fluid leakage occurred in 2 patients and was successfully repaired through the EEA. During a mean follow-up of 44.3 months, 18.8% of patients had a >9% increase in body mass index, and 93.8% of patients successfully returned to school or work. Two patients (12.5%) suffered a recurrence. Disease control was achieved in 16 patients (100%) at final follow-up. CONCLUSION: The extended EEA allows adequate access to this challenging tumor and enables complete resection and visual improvement with a reasonable approach-related complication rate.

Concentration effects on the local structures and electronic properties of ErxBaY2-xF8: a first-principles study.

Er3+doped barium yttrium fluoride (BaY2F8) crystal has gained long-term attention due to its great potential in laser and medical device applications. However, the local structures of Er3+doped BaY2F8system (Er:BYF) remain uncertain, and the effect of doping concentration on structures and properties is unknown. Therefore, in this study, the first-principles study of the structural evolution of ErxBaY2-xF8(x= 0.125, 0.25) crystals was carried out. By means of density functional theory and particle swarm optimization algorithm, the stable structures of Er:BYF crystals with two different concentrations are shown as standard monoclinic structures withP2 symmetry for the first time. The impurity Er3+ions successfully enter the main lattice, replacing the Y3+ions, and forming a [ErF8]5-polyhedron withC2point group symmetry. By calculating the electronic properties, the band gap values of the two structures are significantly reduced compared with that of pure BaY2F8crystal. However, the conduction band does not break through the Fermi level, and the crystals still maintain the insulation characteristic. According to the calculation of the electron local density function, we conclude that Er-F and Y-F in Er:BYF are connected by ionic bonds. These results fill a theoretical gap in the study of Er:BYF crystals and provide inspiration for structural evolution and material design at different doping concentrations.

Cu-Tremella fuciformis polysaccharide-based tumor microenvironment-responsive injectable gels for cuproptosis-based synergistic osteosarcoma therapy.

Cuproptosis affects osteosarcoma locally, and the exploitation of cuproptosis-related biomaterials for osteosarcoma treatment is still in its infancy. We designed and synthesized a novel injectable gel of Cu ion-coordinated Tremella fuciformis polysaccharide (TFP-Cu) for antiosteosarcoma therapy. This material has antitumor effects, the ability to stimulate immunity and promote bone formation, and a controlled Cu2+ release profile in smart response to tumor microenvironment stimulation. TFP-Cu can selectively inhibit the proliferation of K7M2 tumor cells by arresting the cell cycle and promoting cell apoptosis and cuproptosis. TFP-Cu also promoted the M1 polarization of RAW264.7 cells and regulated the immune microenvironment. These effects increased osteogenic gene and protein expression in MC3T3-E1 cells. TFP-Cu could significantly limit tumor growth in tumor-bearing mice by inducing tumor cell apoptosis and improving the activation of anti-CD8 T cell-mediated immune responses. Therefore, TFP-Cu could be a potential candidate for treating osteosarcoma and bioactive drug carrier for further cancer-related applications.

Combined treatment of All-trans retinoic acid with Tamoxifen suppresses ovarian cancer.

BACKGROUND: Ovarian cancer is a malignant tumor of the female reproductive system, and its mortality rate is as high as 70%. Estrogen receptor α (ERα)-positive ovarian cancer accounted for most of all ovarian cancer patients. ERα can promote the growth and proliferation of tumors. METHODS: The combined effect of All-trans retinoic acid (ATRA) and tamoxifen was obtained by the combination screening of tamoxifen and compound library by MTS. In addition, colony formation assay, flow cytometry analysis, immunofluorescence staining, quantitative real-time polymerase chain reaction (PCR), western blot, and tumor xenotransplantation models were used to further evaluate the efficacy of tamoxifen and ATRA in vitro and in vivo for ER-α-positive ovarian cancer. RESULTS: In our study, we found that All-trans retinoic acid (ATRA) can cooperate with tamoxifen to cause cell cycle arrest and apoptosis and inhibit ERα-positive ovarian cancer in vivo and in vitro. Further exploration of the mechanism found that ATRA can Inhibit genes related to the ERα signaling pathway, enhance the sensitivity of ERα-positive ovarian cancer cells to tamoxifen, and ascertain the effectiveness of tamoxifen and ATRA as treatments for ovarian cancer with an ERα-positive status. CONCLUSION: Combination of ATRA and tamoxifen is a new way for the treatment of ERα-positive ovarian cancer.

The impact of family residence structure on adolescents' non-cognitive abilities: evidence from China.

Purpose: The family residence structure serves as a crucial pathway through which the family environment influences adolescents' development. Methods: Drawing on nationally representative data, this study employs multiple linear regression models and propensity score matching to examine the impact of various family residence structures on adolescents' non-cognitive abilities. Causal identification is achieved through propensity score matching, while robustness is assessed using methods such as augmented inverse probability weighting and placebo tests. Heterogeneity analysis is conducted based on gender and household registration, aiming to explore the mechanisms by which family residence structure affects adolescents' non-cognitive abilities. Results: The findings indicate that compared to two-parent co-residence households, three-generation co-residence families have significantly positive effects on emotional stability, conscientiousness, and agreeableness among adolescents. In contrast, skip-generation coresidence families exhibit significant negative effects on emotional stability and agreeableness in adolescents. Further investigation into the underlying mechanisms reveals that parental involvement and family socioeconomic status within three-generation co-residence families positively influence adolescents' non-cognitive abilities. Conclusion: This study highlights the importance of considering grandparents' role in adolescent growth and advocates for policy recommendations focusing on enhancing non-cognitive abilities in adolescents from skip-generation co-residence families.

The competition of heavy metals between hyporheic sediments and microplastics of driving factors in the Beiluo River Basin.

Both sediments and microplastics (MPs) are medias of heavy metals (HMs) in river ecosystems. This study investigated HMs (Mn, Cr, V, As, Cu, Co, Cd, Pb, and Ni) concentration and driving factors for competitive enrichment between hyporheic sediments versus MPs. The medias basic characteristics indicated that the sediments were mostly sand and rich in Fe2O3; three polymer types were identified, with blue, fragment, less than 500 µm being the main types of MPs. The results have shown that the average content of extracted HMs in MPs was much higher than that of the same metals accumulated in sediments. HMs in sediments and MPs reached heavily polluted at some points, among which As and Cd were ecological risks. Electrostatic adsorption and surface complexation, and biofilm-mediated and organic matter complexation were the interaction mechanism of HMs with sediments and MPs. Further, the driving factors affecting the distribution of HMs in the two carriers were analyzed by multivariate statistical analysis. The results demonstrated that carrier characteristics, hydrochemical factors, and the inherent metal load of MPs were the main causes of the high HMs content. These findings improved our understanding of HMs fate and environmental risks across multiple medias.

Mechanism of acacetin regulating hepatic stellate cell apoptosis based on network pharmacology and experimental verification.

Background: Hepatic fibrosis is caused by various liver diseases and eventually develops into liver cancer. There is no specific drug approved for the treatment of hepatic fibrosis in the world. Acacetin (AC), a natural flavonoid, is widely present in nature in various plants, such as black locust, Damiana, Silver birch. It has been reported that acacetin can inhibit the proliferation of cancer cells and induce apoptosis. Purpose: In this study, we investigated the effect of acacetin on hepatic stellate cell apoptosis, thereby improving hepatic fibrosis, and combined experimental validation and molecular docking to reveal the underlying mechanism. Result: First, we discovered that acacetin inhibited hepatic stellate cell proliferation as well as the expression of fibrosis-related proteins α-smooth muscle actin (α-SMA) and collagen type I 1 gene (COL1A1) in LX2 cells. Acacetin was then found to promote apoptosis of hepatic stellate cells through the caspase cascade pathway. Network pharmacology screening showed that TP53, CASP3, CASP8, BCL2, PARP1, and BAX were the most important targets related to apoptosis in the PPI network. GO and KEGG analyses of these six important targets were performed, and the top 10 enriched biological processes and related signaling pathways were revealed. Further network pharmacology analysis proved that apoptosis was involved in the biological process of acacetin's action against hepatic stellate cells. Finally, molecular docking revealed that acacetin binds to the active sites of six apoptotic targets. In vitro experiments further confirmed that acacetin could promote the apoptosis of LX2 cells by inducing the activation of P53, thereby improving hepatic fibrosis. Conclusion: acacetin induces P53 activation and promotes apoptosis of hepatic stellate cells thereby ameliorating hepatic fibrosis.

Strategically constructed AlGaN doping barriers for efficient deep ultraviolet light-emitting diodes.

Here, we propose a sandwich-like Si-doping scheme (undoped/Si-doped/undoped) in Al0.6Ga0.4N quantum barriers (QBs) to simultaneously promote the optoelectronic performances and reliability of deep ultraviolet light-emitting diodes (DUV-LEDs). Through experimental and numerical analyses, in the case of DUV-LEDs with conventional uniform Si-doping QB structure, severe operation-induced reliability degradation, including the increase of reverse leakage current (IR) and reduction of light output power (LOP), will offset the enhancement of optoelectronic performances as the Si-doping levels increase to an extent, which hinders further development of DUV-LEDs. According to a transmission electron microscope characterization and a numerical simulation, an improved interfacial quality in multiple quantum wells (MQWs) and more uniform carrier distribution within MQWs are demonstrated for our proposed Si-doping structure in comparison to the uniform Si-doping structure. Consequently, the proposed DUV-LED shows superior wall-plug efficiency (4%), IR at -6 V reduced by almost one order of magnitude, and slower LOP degradation after 168-h 100 mA-current-stress operation. This feasible doping scheme provides a promising strategy for the high-efficiency and cost-competitive DUV-LEDs.

Murine skeletal muscle satellite cells isolation and preliminary study on regulation in immune microenvironment during nurse cells formation of Trichinella spiralis infection.

As an intracellular parasitic nematode, Trichinella spiralis (T. spiralis) can induce the formation of nurse cells (NC) in host muscles and keep it to survive within the NC for an extended period. The formation of NC is similar to muscle cell injury and repair which lead to the arrest of satellite cells in the G2/M phase and build a suitable parasitic environment for the muscle larvae of T. spiralis. However, the molecular mechanisms involved in skeletal muscle repair through skeletal muscle satellite cells (SMSC) and the host immune response during T. spiralis infection have not been fully elucidated. In this study, histopathological examination revealed that the severity of damage increased as the infection progressed in the soleus muscle. SMSCs were isolated from BALB/c mice infected with T. spiralis at 4, 21 and 35 days post-infection (dpi). The immunological characteristics of these cells were analyzed by real-time PCR and flow cytometry (FCM). FCM analysis revealed a notable increase in the expression of B7 homolog 1 (B7-H1) in SMSCs following T. spiralis infection, while conversely, the expression of inducible costimulatory ligand (ICOSL) significantly decreased. Furthermore, real-time PCR results showed that toll like receptor 3 (TLR3) expression in SMSCs of the infected mice was upregulated at 21 dpi. The expression levels of three subtypes (PPARα, PPARß and PPARγ) of peroxisome proliferator-activated receptors (PPARs) also increased in the cells. This study highlights the immunological regulation significance of SMSCs host during T. spiralis infection and suggests that SMSCs actively participant in the local immune response to T. spiralis by regulating the interaction between the parasite and the host.

Impact of Three Thiazolidinone Compounds with Piperine Skeletons on Trehalase Activity and Development of Spodoptera frugiperda Larvae.

Trehalases (TREs) are pivotal enzymes involved in insect development and reproduction, making them prime targets for pest control. We investigated the inhibitory effect of three thiazolidinones with piperine skeletons (6a, 7b, and 7e) on TRE activity and assessed their impact on the growth and development of the fall armyworm (FAW), Spodoptera frugiperda. The compounds were injected into FAW larvae, while the control group was treated with 2% DMSO solvent. All three compounds effectively inhibited TRE activity, resulting in a significant extension of the pupal development stage. Moreover, the treated larvae exhibited significantly decreased survival rates and a higher incidence of abnormal phenotypes related to growth and development compared to the control group. These results suggest that these TRE inhibitors affect the molting of larvae by regulating the chitin metabolism pathway, ultimately reducing their survival rates. Consequently, these compounds hold potential as environmentally friendly insecticides.

Residues of chlorpyrifos in the environment induce resistance in Aedes albopictus by affecting its olfactory system and neurotoxicity.

Aedes albopictus, a virus-vector pest, is primarily controlled through the use of insecticides. In this study, we investigated the mechanisms of resistance in Ae. albopictus in terms of chlorpyrifos neurotoxicity to Ae. albopictus and its effects on the olfactory system. We assessed Ca2+-Mg2+-ATP levels, choline acetyltransferase (ChAT), Monoamine oxidase (MAO), odorant-binding proteins (OBPs), and olfactory receptor (OR7) gene expression in Ae. albopictus using various assays including Y-shaped tube experiments and DanioVision analysis to evaluate macromotor behavior. Our findings revealed that cumulative exposure to chlorpyrifos reduced the activity of neurotoxic Ca2+-Mg2+-ATPase and ChAT enzymes in Ae. albopictus to varying degrees, suppressed MAO-B enzyme expression, altered OBPs and OR7 expression patterns, as well as affected evasive response, physical mobility, and cumulative locomotor time under chlorpyrifos stress conditions for Ae. albopictus individuals. Consequently, these changes led to decreased feeding ability, reproductive capacity, and avoidance behavior towards natural enemies in Ae. albopictus populations exposed to chlorpyrifos stressors over time. To adapt to unfavorable living environments, Ae. albopictus may develop certain tolerance mechanisms against organophosphorus pesticides. This study provides valuable insights for guiding rational insecticide usage or dosage adjustments targeting the nervous system of Ae. albopictus.

Actively tunable and switchable terahertz metamaterials with multi-band perfect absorption and polarization conversion.

In this paper, we theoretically present and numerically demonstrate an actively tunable and switchable multi-functional metamaterial based on vanadium dioxide (VO2) and graphene in the terahertz region. When VO2 is in the metallic phase, the proposed metamaterial serves as a multi-band perfect absorber, which exhibits the characteristics of insensitive polarization and robust tolerance for variations of the incidence angle. When VO2 is in the insulator phase, the proposed metamaterial acts as a polarization converter, which can simultaneously achieve perfect linear-to-linear and linear-to-circular polarization conversions. The simulation results show the cross-polarization conversion rate can reach ∼100% at the frequency region from 6.09 to 6.43 THz as well as 8.15 THz. Moreover, the ellipticity of linear-to-circular polarization conversion reaches ±1 at frequencies of 5.75 and 8.34 THz, respectively, which means the linear polarization waves can be completely converted into circular polarization waves. The proposed metamaterial provides new insight for the design of optoelectronic devices with multi-functionality in the terahertz region.

Passivating Defects via Retarding the Reaction Rate of FAI and PbI2 Enables Stable Perovskite Solar Cells.

The two-step sequential deposition strategy has garnered widespread usage in the fabrication of high-performance perovskite solar cells based on FAPbI3. However, the rapid reaction between FAI and PbI2 during preparation often leads to incomplete reactions, reducing the device efficiency and stability. Herein, we introduced a multifunctional additive, 2-thiophenyl trifluoroacetone (TTA), into the FAI precursor. The incorporation of TTA has proven to be highly effective in slowing the reaction rate between FAI and PbI2, resulting in increased perovskite formation and improved efficiency and stability of the devices. TTA's CF3 groups interact with FAI via hydrogen bonding, effectively suppressing FA+ defects. The S and C═O groups share lone pair electrons with uncoordinated Pb2+, leading to a reduction in perovskite film defects and suppressing nonradiative recombination. Additionally, the CF3 groups impart hydrophobicity, protecting the perovskite film from moisture-induced erosion. As a result, the TTA-modified perovskite film achieves a Champion efficiency of 23.42% compared to the control's 21.52, with 20.58% efficiency for a 25 cm2 solar module. Remarkably, the unencapsulated Champion device retains 86% of its initial PCE after 1080 h under dark conditions (60 ± 5 °C, 35 ± 5% RH), indicating enhanced long-term stability. These findings offer a promising and cost-effective tactic for high-quality perovskite film fabrication.

Elevated Biomarkers of Inflammation and Vascular Dysfunction Are Associated with Distal Sensory Polyneuropathy in People with HIV.

Distal sensory polyneuropathy (DSP) is a disabling, chronic condition in people with HIV (PWH), even those with viral suppression of antiretroviral therapy (ART), and with a wide range of complications, such as reduced quality of life. Previous studies demonstrated that DSP is associated with inflammatory cytokines in PWH. Adhesion molecules, essential for normal vascular function, are perturbed in HIV and other conditions linked to DSP, but the link between adhesion molecules and DSP in PWH is unknown. This study aimed to determine whether DSP signs and symptoms were associated with a panel of plasma biomarkers of inflammation (d-dimer, sTNFRII, MCP-1, IL-6, IL-8, IP-10, sCD14) and vascular I integrity (ICAM-1, VCAM-1, uPAR, MMP-2, VEGF, uPAR, TIMP-1, TIMP-2) and differed between PWH and people without HIV (PWoH). A cross-sectional study was conducted among 143 participants (69 PWH and 74 PWoH) assessed by studies at the UC San Diego HIV Neurobehavioral Research Program. DSP signs and symptoms were clinically assessed for all participants. DSP was defined as two or more DSP signs: bilateral symmetrically reduced distal vibration, sharp sensation, and ankle reflexes. Participant-reported symptoms were neuropathic pain, paresthesias, and loss of sensation. Factor analyses reduced the dimensionality of the 15 biomarkers among all participants, yielding six factors. Logistic regression was used to assess the associations between biomarkers and DSP signs and symptoms, controlling for relevant demographic and clinical covariates. The 143 participants were 48.3% PWH, 47 (32.9%) women, and 47 (33.6%) Hispanics, with a mean age of 44.3 ± 12.9 years. Among PWH, the median (IQR) nadir and current CD4+ T-cells were 300 (178-448) and 643 (502-839), respectively. Participants with DSP were older but had similar distributions of gender and ethnicity to those without DSP. Multiple logistic regression showed that Factor 2 (sTNFRII and VCAM-1) and Factor 4 (MMP-2) were independently associated with DSP signs in both PWH and PWoH (OR [95% CI]: 5.45 [1.42-21.00], and 15.16 [1.07-215.22]), respectively. These findings suggest that inflammation and vascular integrity alterations may contribute to DSP pathogenesis in PWH, but not PWoH, possibly through endothelial dysfunction and axonal degeneration.

A point-of-care testing assay for clonorchiasis using a EuNPs-CsTR1 fluorescent probe-based immunoassay.

Clonorchis sinensis is one of the most important fish-borne zoonotic parasitic worms in humans, and is distributed in several countries with more than 15 million people infected globally. However, the lack of a point-of-care testing (POCT) method is still the critical barrier to effectively prevent clonorchiasis. With the application of novel fluorescent nanomaterials, the development of on-site testing methods with high signal enhancement can provide a simple, precise and inexpensive tool for disease detection. In this study, Eu-(III) nanoparticles (EuNPs) were used as indicative probes, combined with C. sinensis tandem repeat sequence 1 (CSTR1) antigen to capture specific antibodies. Afterward, the complex binds to mouse anti-human IgG immobilized on the test line (T-line) producing a fluorescent signal under UV light. The EuNPs-fluorescent immunoassay (EuNPs-FIA) was successfully constructed, allowing sample detection within 10 min. It enabled both qualitative determination with the naked eye under UV light and quantitative detection by scanning the fluorescence intensity on the test line and control line (C-line). A total of 133 clinical human sera (74 negative, 59 clonorchiasis, confirmed by conventional Kato-Katz (KK) methods and PCR via testing fecal samples corresponding to each serum sample) were used in this study. For qualitative analysis, the cut-off value of fluorescence for positive serum was 31.57 by testing 74 known negative human samples. The assay had no cross-reaction with other 9 parasite-infected sera, and could recognize the mixed infection sera of C. sinensis and other parasites. The sensitivity and specificity of EuNPs-FIA were both 100% compared with KK smear method. Taking advantage of its high precision and user-friendly procedure, the established EuNPs-FIA provides a powerful tool for the diagnosis and epidemiological survey of clonorchiasis.

Tunable High-Sensitivity Four-Frequency Refractive Index Sensor Based on Graphene Metamaterial.

As graphene-related technology advances, the benefits of graphene metamaterials become more apparent. In this study, a surface-isolated exciton-based absorber is built by running relevant simulations on graphene, which can achieve more than 98% perfect absorption at multiple frequencies in the MWIR (MediumWavelength Infra-Red (MWIR) band as compared to the typical absorber. The absorber consists of three layers: the bottom layer is gold, the middle layer is dielectric, and the top layer is patterned with graphene. Tunability was achieved by electrically altering graphene's Fermi energy, hence the position of the absorption peak. The influence of graphene's relaxation time on the sensor is discussed. Due to the symmetry of its structure, different angles of light source incidence have little effect on the absorption rate, leading to polarization insensitivity, especially for TE waves, and this absorber has polarization insensitivity at ultra-wide-angle degrees. The sensor is characterized by its tunability, polarisation insensitivity, and high sensitivity, with a sensitivity of up to 21.60 THz/refractive index unit (RIU). This paper demonstrates the feasibility of the multi-frequency sensor and provides a theoretical basis for the realization of the multi-frequency sensor. This makes it possible to apply it to high-sensitivity sensors.

Novel Zn0.079V2O5·0.53H2O/Graphene aerogel as high-rate and long-life cathode materials of aqueous zinc-ion batteries.

Aqueous zinc-ion batteries (ZIBs) have attracted more and more attention due to their advantages of low cost, high safety and environmental protection. Unfortunately, the unsatisfactory capacity at high current density and long-term cycling performance of cathode materials hinder the development of ZIBs. Here, a novel Zn0.079V2O5·0.53H2O/graphene (ZVOH@rGO) hybrid aerogel composed of ultrathin Zn0.079V2O5·0.53H2O (ZVOH) nanoribbons and 3D continuous graphene conductive network was successfully prepared and used as cathode of ZIBs. Taking advantage of the synergistic effects associated with ion doping, morphology control and unique aerogel structure, the ZVOH@rGO electrode demonstrated ultrafast charge/discharge capability and remarkable cycling stability: A high reversible capacity of 286.7 mAh g-1 was achieved at a current density as large as 30 A g-1, and an impressive capacity retention ratio of 75.6 % was realized over 9800 ultra-long cycles at 12 A g-1. This work is of great significance for the synthesis modification of vanadium oxides and the development of high performance ultrafast charge-discharge ZIBs.

Longitudinal analysis of CSF HIV RNA in untreated people with HIV: Identification of CSF controllers.

Interindividual variation of human immunodeficiency virus (HIV) RNA setpoint in cerebrospinal fluid (CSF) and its determinants are poorly understood, but relevant for HIV neuropathology, brain reservoirs, viral escape, and reseeding after antiretroviral interruptions. Longitudinal multicentric study on demographic, clinical, and laboratory correlates of CSF HIV RNA in 2000 follow-up visits from 597 people with HIV (PWH) off antiretroviral therapy (ART) and with plasma HIV RNA > the lower limit of quantification (LLQ). Factors associated with CSF control (CSFC; CSF HIV RNA < LLQ while plasma HIV RNA > LLQ) and with CSF/plasma discordance (CSF > plasma HIV RNA > LLQ) were also assessed through mixed-effects models. Posthoc and sensitivity analyses were performed for persistent CSFC and ART-naïve participants, respectively. Over a median follow-up of 2.1 years, CSF HIV RNA was associated with CD4+ and CD8+ T cells, CSF leukocytes, blood-brain barrier (BBB) integrity, biomarkers of iron and lipid metabolism, serum globulins, past exposure to lamivudine, and plasma HIV RNA (model p < 0.0001). CSFC (persistent in 7.7% over 3 years) and CSF/plasma discordance (persistent in <0.01% over 1 year) were variably associated with the same parameters (model p < 0.001). Sensitivity analyses confirmed most of the previous associations in participants never exposed to ART. Persistent CSFC was associated with higher CD4+ T-cell count nadir (p < 0.001), lower serum globulins (p = 0.003), and lower CSF leukocytes (p < 0.001). Without ART, one in 13 PWH had persistently undetectable CSF HIV RNA, while persistent CSF/plasma discordance was extremely rare over years. Immune responses, inflammation, BBB permeability, and iron and lipid metabolism were all associated with HIV replication in CSF.

The causal relationship between serum metabolites and the risk of psoriasis: a Mendelian randomization and meta-analysis study.

Objective: To explore the influence of serum metabolites on the risk of psoriasis. Methods: In the initial stage, we applied Mendelian randomization to evaluate the association between 1,400 serum metabolites and the risk of psoriasis. Causal effects were primarily assessed through the Inverse-Variance Weighted method and Wald Ratio's odds ratios, and 95% confidence intervals. False Discovery Rate was used for multiple comparison corrections. Sensitivity analyses were conducted using Cochran's Q Test, MR-PRESSO. MR-Steiger Test was employed to check for reverse causality. In the validation stage, we sought other sources of psoriasis GWAS data to verify the initial results and used meta-analysis to combine the effect sizes to obtain robust causal relationships. In addition, we also conducted metabolic pathway enrichment analysis on known metabolites that have a causal relationship with the risk of psoriasis in both stages. Results: In the initial stage, we identified 112 metabolites causally associated with psoriasis, including 32 metabolite ratios and 80 metabolites (69 known and 11 unknown). In the validation stage, 24 metabolites (16 known, 1 unknown, and 7 metabolite ratios) were confirmed to have a causal relationship with psoriasis onset. Meta-analysis results showed that the overall effect of combined metabolites was consistent with the main analysis in direction and robust in the causal relationship with psoriasis onset. Of the 16 known metabolites, most were attributed to lipid metabolism, with 5 as risk factors and 8 as protective factors for psoriasis. Peptidic metabolite Gamma-glutamylvaline levels had a negative causal relationship with psoriasis, while exogenous metabolite Catechol sulfate levels and amino acid 3-methylglutaconate levels had a positive causal relationship with the disease onset. The metabolites associated with psoriasis risk in the two stages are mainly enriched in the following metabolic pathways: Glutathione metabolism, Alpha Linolenic Acid and Linoleic Acid Metabolism, Biosynthesis of unsaturated fatty acids, Arachidonic acid metabolism, Glycerophospholipid metabolism. Conclusion: Circulating metabolites may have a potential causal relationship with psoriasis risk, and targeting specific metabolites may benefit psoriasis diagnosis, disease assessment, and treatment.

First Insight into Fetal Exposure to Legacy and Emerging Plasticizers Revealed by Infant Hair and Meconium: Occurrence, Biotransformation, and Accumulation.

Epidemiological studies have demonstrated the embryonic and developmental toxicity of plasticizers. Thus, understanding the in utero biotransformation and accumulation of plasticizers is essential to assessing their fate and potential toxicity in early life. In the present study, 311 infant hair samples and 271 paired meconium samples were collected at birth in Guangzhou, China, to characterize fetal exposure to legacy and emerging plasticizers and their metabolites. Results showed that most of the target plasticizers were detected in infant hair, with medians of 9.30, 27.6, and 0.145 ng/g for phthalate esters (PAEs), organic phosphate ester (OPEs), and alternative plasticizers (APs), and 1.44, 0.313, and 0.066 ng/g for the metabolites of PAEs, OPEs, and APs, respectively. Positive correlations between plasticizers and their corresponding primary metabolites, as well as correlations among the oxidative metabolites of bis(2-ethylhexyl) phthalate (DEHP) and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), were observed, indicating that infant hair retained the major phase-I metabolism of the target plasticizers. While no positive correlations were found in parent compounds or their primary metabolites between paired infant hair and meconium, significant positive correlations were observed among secondary oxidative metabolites of DEHP and DINCH in hair and meconium, suggesting that the primary metabolites in meconium come from hydrolysis of plasticizers in the fetus but most of the oxidative metabolites come from maternal-fetal transmission. The parent compound/metabolite ratios in infant hair showed a decreasing trend across pregnancy, suggesting in utero accumulation and deposition of plasticizers. To the best of our knowledge, this study is the first to report in utero exposure to both parent compounds and metabolites of plasticizers by using paired infant hair and meconium as noninvasive biomonitoring matrices and provides novel insights into the fetal biotransformation and accumulation of plasticizers across pregnancy.