Encapsulation of Pd Single-Atom Sites in Zeolite for Highly Efficient Semihydrogenation of Alkynes.

Palladium (Pd)-based single-atom catalysts (SACs) have shown outstanding selectivity for semihydrogenation of alkynes, but most Pd single sites coordinated with highly electronegative atoms (such as N, O, and S) of supports will result in a decrease in the electron density of Pd sites, thereby weakening the adsorption of reactants and reducing catalytic performance. Constructing a rich outer-shell electron environment of Pd single-atom sites by changing the coordination structure offers a novel opportunity to enhance the catalytic efficiency with excellent alkene selectivity. Therefore, in this work, we first propose the in situ preparation of isolated Pd sites encapsulated within Al/Si-rich ZSM-5 structure using the one-pot seed-assisted growth method. Pd1@ZSM-5 features Pd-O-Al/Si bonds, which can boost the domination of d-electron near the Fermi level, thereby promoting the adsorption of substrates on Pd sites and reducing the energy barrier for the semihydrogenation of alkynes. In semihydrogenation of phenylacetylene, Pd1@ZSM-5 catalyst performs the highest turnover frequency (TOF) value of 33582 molC═C/molPd/h with 96% selectivity of styrene among the reported heterogeneous catalysts and nearly 17-fold higher than that of the commercial Lindlar catalyst (1992 molC═C/molPd/h). This remarkable catalytic performance can be retained even after 6 cycles of usage. Particularly, the zeolitic confinement structure of Pd1@ZSM-5 enables precise shape-selective catalysis for alkyne reactants with a size less than 4.3 Å.

A Metal-Sulfur-Carbon Catalyst Mimicking the Two-Component Architecture of Nitrogenase.

The production of ammonia (NH3) from nitrogen sources involves competitive adsorption of different intermediates and multiple electron and proton transfers, presenting grand challenges in catalyst design. In nature nitrogenases reduce dinitrogen to NH3 using two component proteins, in which electrons and protons are delivered from Fe protein to the active site in MoFe protein for transfer to the bound N2. We draw inspiration from this structural enzymology, and design a two-component metal-sulfur-carbon (M-S-C) catalyst composed of sulfur-doped carbon-supported ruthenium (Ru) single atoms (SAs) and nanoparticles (NPs) for the electrochemical reduction of nitrate (NO3-) to NH3. The catalyst demonstrates a remarkable NH3 yield rate of ~37 mg L-1 h-1 and a Faradaic efficiency of ~97% for over 200 hours, outperforming those consisting solely of SAs or NPs, and even surpassing most reported electrocatalysts. Our experimental and theoretical investigations reveal the critical role of Ru SAs with the coordination of S in promoting the formation of the HONO intermediate and the subsequent reduction reaction over the NP-surface nearby. This study proves a better understanding of how M-S-Cs act as a synthetic nitrogenase mimic during ammonia synthesis, and contributes to the future mechanism-based catalyst design.

Progressive auto-segmentation for cone-beam computed tomography-based online adaptive radiotherapy.

Background and purpose: Accurate and automated segmentation of targets and organs-at-risk (OARs) is crucial for the successful clinical application of online adaptive radiotherapy (ART). Current methods for cone-beam computed tomography (CBCT) auto-segmentation face challenges, resulting in segmentations often failing to reach clinical acceptability. Current approaches for CBCT auto-segmentation overlook the wealth of information available from initial planning and prior adaptive fractions that could enhance segmentation precision. Materials and methods: We introduce a novel framework that incorporates data from a patient's initial plan and previous adaptive fractions, harnessing this additional temporal context to significantly refine the segmentation accuracy for the current fraction's CBCT images. We present LSTM-UNet, an innovative architecture that integrates Long Short-Term Memory (LSTM) units into the skip connections of the traditional U-Net framework to retain information from previous fractions. The models underwent initial pre-training with simulated data followed by fine-tuning on a clinical dataset. Results: Our proposed model's segmentation predictions yield an average Dice similarity coefficient of 79% from 8 Head & Neck organs and targets, compared to 52% from a baseline model without prior knowledge and 78% from a baseline model with prior knowledge but no memory. Conclusions: Our proposed model excels beyond baseline segmentation frameworks by effectively utilizing information from prior fractions, thus reducing the effort of clinicians to revise the auto-segmentation results. Moreover, it works together with registration-based methods that offer better prior knowledge. Our model holds promise for integration into the online ART workflow, offering precise segmentation capabilities on synthetic CT images.

Exploring the causal role of immune cells in vascular dementia: A bidirectional mendelian randomization study.

BACKGROUND: The aim of this study was to explore the causal association between immune cells and VaD based on a two-sample bidirectional Mendelian randomization study. METHODS: Bidirectional two-sample MR analyses based on pooled datasets from publicly available genome-wide association studies were performed using inverse variance weighted (IVW), weighted median (WE), and MR-Egger regressions to evaluate the causal relationships between immune cells and vascular dementia. Heterogeneity was assessed using Cochran's Q statistic. The reliability of the MR analysis results was verified by using the MR-PRESSO method for outlier detection, the MR-Egger method for horizontal multivariate analysis, and the leave-one-out method for sensitivity analysis. RESULTS: Specifically, 27 immunophenotypes were associated with VaD pathogenesis, including Sw mem %lymphocyte (P = 0.043), CD38 on CD20- (P = 0.039), CD11c+ monocyte AC (P = 0.024), DC AC (P = 0.002), CCR2 on CD62L+ myeloid DC (P = 0.039), Resting Treg %CD4 (P = 0.042), Activated & resting Treg %CD4+ (P = 0.038), CD28+ CD45RA- CD8br %CD8br (P = 0.047), NK %CD3- lymphocyte (P = 0.042), CD45 on B cell (P = 0.029), FSC-A on NKT (P = 0.033), CD45 on CD33br HLA DR+ CD14- (P = 0.039) were significantly correlated with increased VaD risk. Additionally, four immune phenotypes, namely, CD19 on CD20-, Resting Treg %CD4, Activated & resting Treg %CD4+, and CD11c+ monocyte AC, showed bidirectional effects on VaD. CONCLUSIONS: MR analysis revealed potential causal relationships between certain immune cells and VaD. Our preliminary exploration through immune cell infiltration analysis highlights the significant value of immune cells in VaD. Therefore, this study may provide a new perspective for the prevention and treatment of VaD.

Precise measurement of chiral spectrum in the ultraviolet band using weak measurement and a deep neural network model.

Circular dichroism (CD) spectrum and optical rotation (OR) spectrum, crucial for understanding molecular properties and configurations, present challenges due to limited testing methods and equipment accuracy in the ultraviolet (UV) region. This study proposes a weak measurement system for chiral signals in varying concentrations in the ultraviolet range, optimized using a deep neural network (DNN) model. Introducing different post-selections to detect the circular dichroism spectrum and optical rotation spectrum separately, with contrast as a probe, it achieves a detection resolution of up to 10-6 rad. Moreover, the fitted value of the training data can reach 0.9989, enhancing the prediction accuracy of chiral molecule concentrations. This method exhibits considerable promise for applications in chiral measurement and sensor technologies.

Ubiquitin-specific protease 22 controls melanoma metastasis and vulnerability to ferroptosis through targeting SIRT1/PTEN/PI3K signaling.

Metastasis is a major contributing factor that affects the prognosis of melanoma patients. Nevertheless, the underlying molecular mechanisms involved in melanoma metastasis are not yet entirely understood. Here, we identified ubiquitin-specific protease 22 (USP22) as a pro-oncogenic protein in melanoma through screening the survival profiles of 52 ubiquitin-specific proteases (USPs). USP22 demonstrates a strong association with poor clinical outcomes and is significantly overexpressed in melanoma. Ablation of USP22 expression remarkably attenuates melanoma migration, invasion, and epithelial-mesenchymal transition in vitro and suppresses melanoma metastasis in vivo. Mechanistically, USP22 controls melanoma metastasis through the SIRT1/PTEN/PI3K pathway. In addition, we conducted an United States Food and Drug Administration-approved drug library screening and identified topotecan as a clinically applicable USP22-targeting molecule by promoting proteasomal degradation of USP22. Finally, we found that both pharmacological and genetic silence of USP22 sensitize RSL3-induced ferroptosis through suppressing the PI3K/Akt/mTOR pathway and its downstream SCD, and ferroptosis inhibitor could partly rescued the decreased lung metastasis by topotecan in vivo. Overall, our findings reveal a prometastatic role of USP22 and identify topotecan as a potent USP22-targeting drug to limit melanoma metastasis.

Ubiquitin-Specific Protease 22 Plays a Key Role in Increasing Extracellular Vesicle Secretion and Regulating Cell Motility of Lung Adenocarcinoma.

Tumor-derived extracellular vesicles (EVs) are potential biomarkers for tumors, but their reliable molecular targets have not been identified. The previous study confirms that ubiquitin-specific protease 22 (USP22) promotes lung adenocarcinoma (LUAD) metastasis in vivo and in vitro. Moreover, USP22 regulates endocytosis of tumor cells and localizes to late endosomes. However, the role of USP22 in the secretion of tumor cell-derived EVs remains unknown. In this study, it demonstrates that USP22 increases the secretion of tumor cell-derived EVs and accelerates their migration and invasion, invadopodia formation, and angiogenesis via EV transfer. USP22 enhances EV secretion by upregulating myosin IB (MYO1B). This study further discovers that USP22 activated the SRC signaling pathway by upregulating the molecule KDEL endoplasmic reticulum protein retention receptor 1 (KDELR1), thereby contributing to LUAD cell progression. The study provides novel insights into the role of USP22 in EV secretion and cell motility regulation in LUAD.

Oleanane-type triterpenoids from Sabia limoniacea and their anti-inflammatory activities.

Eighteen new oleanane-type triterpenoids were isolated from the stems of Sabia limoniacea, including sabialimon A (1), a triterpenoid with an unprecedented 6/6/6/7/7 pentacyclic skeleton and seventeen undescribed triterpenoids, sabialimons B-R (2 - 18), along with six previously described analogs (19 - 24). Their structures were fully elucidated via extensive spectroscopic analysis including 1D and 2D NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), experimental electronic circular dichroism measurements and X-ray crystallographic studies. Compound 1 is the first triterpenoid that possesses a rare ring system (6/6/6/7/7) with an oxygen-bearing bridge between C-17 and C-18 and a hemiketal form at C-17, which is generated a larger ring by the degradation of C-28 and D/E-ring expansion. Biological evaluation revealed that sabialimon I (9), sabialimon K (11), sabialimon P (16) and 11,13(18)-oleanadien-28-hydroxymethyl 3-one (20) exhibited significantly inhibitory activities against nitric oxide (NO) release with IC50 values of 29.65, 23.41, 18.12 and 26.64 µM, respectively, as compared with the positive control (dexamethasone, IC50 value: 40.35 µM). Furthermore, sabialimon P markedly decreased the secretion of TNF-α, iNOS, IL-6 and NF-κB and inhibited the expression of COX-2 and NF-κB/p65 in LPS-induced RAW264.7 cells in a dose-dependent manner.

Supported IrO2 Nanocatalyst with Multilayered Structure for Proton Exchange Membrane Water Electrolysis.

The design of a low-iridium-loading anode catalyst layer with high activity and durability is a key challenge for a proton exchange membrane water electrolyzer (PEMWE). Here, the synthesis of a novel supported IrO2 nanocatalyst with a tri-layered structure, dubbed IrO2@TaOx@TaB that is composed of ultrasmall IrO2 nanoparticles anchored on amorphous TaOx overlayer of TaB nanorods is reported. The composite electrocatalyst shows great activity and stability toward the oxygen evolution reaction (OER) in acid, thanks to its dual-interface structural feature. The electronic interaction in IrO2/TaOx interface can regulate the coverage of surface hydroxyl groups, the Ir3+/ Ir4+ ratio, and the redox peak potential of IrO2 for enhancing OER activity, while the dense TaOx overlayer can prevent further oxidation of TaB substrate and stabilize the IrO2 catalytic layers for improving structural stability during OER. The IrO2@TaOx@TaB can be used to fabricate an anode catalyst layer of PEMWE with an iridium-loading as low as 0.26 mg cm-2. The low-iridium-loading PEMWE delivers high current densities at low cell voltages (e.g., 3.9 A cm-2@2.0 V), and gives excellent activity retention for more than 1500 h at 2.0 A cm-2 current density.

Vonoprazan-Amoxicillin Dual Therapy With Different Amoxicillin Administration Regimens for Helicobacter pylori Treatment: A Randomized Controlled Trial.

BACKGROUND: The effect of preprandial or postprandial administration of amoxicillin on the efficacy of vonoprazan-amoxicillin dual therapy (VA-dual therapy) for Helicobacter pylori treatment has not been studied. It is also unclear whether amoxicillin dosing four times daily is more effective than three times daily. We aimed to investigate the effect of different amoxicillin administration regimens on the efficacy of VA-dual therapy. MATERIALS AND METHODS: H. pylori-infected subjects were randomly assigned to three groups in a 1:1:1 ratio to receive a 14-day dual therapy consisting of vonoprazan 20 mg twice daily + amoxicillin 1000 mg three times daily before meals (BM-TID) or 1000 mg three times daily after meals (AM-TID) or 750 mg four times daily after meals (AM-QID). H. pylori eradication rates, adverse events rates, compliance, and antibiotic resistance were compared. RESULTS: Between May 2021 to April 2023, 327 subjects were enrolled. The eradication rates of BM-TID, AM-TID, and AM-QID dual therapy were 88.1%, 89.9%, and 93.6% in intention-to-treat (ITT) analysis, 90.6%, 94.2%, and 99.0% in modified ITT (MITT) analysis, and 90.4%, 94.1%, and 99.0% in per-protocol (PP) analysis. Although there was non-inferiority between BM-TID and AM-TID, as well as between AM-TID and AM-QID, AM-QID was significantly more effective than BM-TID. There were no significant differences in adverse event rates, compliance, and antibiotic resistance among the three groups. CONCLUSIONS: Postprandial administration and the increased frequency of administration of amoxicillin may contribute to a better efficacy of VA-dual therapy, especially for rescue therapy. All VA-dual therapy in our study could achieve good efficacy for first-line treatment. TRIAL REGISTRATION: clinicaltrials.gov: NCT05901051.

Anlotinib potentiates anti-PD1 immunotherapy via transferrin receptor-dependent CD8+ T-cell infiltration in hepatocellular carcinoma.

BACKGROUND: The therapeutic potential of immune checkpoint blockade (ICB) extends across various cancers; however, its effectiveness in treating hepatocellular carcinoma (HCC) is frequently curtailed by both inherent and developed resistance. OBJECTIVE: This research explored the effectiveness of integrating anlotinib (a broad-spectrum tyrosine kinase inhibitor) with programmed death-1 (PD-1) blockade and offers mechanistic insights into more effective strategies for treating HCC. METHODS: Using patient-derived organotypic tissue spheroids and orthotopic HCC mouse models, we assessed the effectiveness of anlotinib combined with PD-1 blockade. The impact on the tumour immune microenvironment and underlying mechanisms were assessed using time-of-flight mass cytometry, RNA sequencing, and proteomics across cell lines, mouse models, and HCC patient samples. RESULTS: The combination of anlotinib with an anti-PD-1 antibody enhanced the immune response against HCC in preclinical models. Anlotinib remarkably suppressed the expression of transferrin receptor (TFRC) via the VEGFR2/AKT/HIF-1α signaling axis. CD8+ T-cell infiltration into the tumour microenvironment correlated with low expression of TFRC. Anlotinib additionally increased the levels of the chemokine CXCL14, crucial for attracting CD8+ T cells. CXCL14 emerged as a downstream effector of TFRC, exhibiting elevated expression following the silencing of TFRC. Importantly, low TFRC expression was also associated with a better prognosis, enhanced sensitivity to combination therapy, and a favourable response to anti-PD-1 therapy in patients with HCC. CONCLUSIONS: Our findings highlight anlotinib's potential to augment the efficacy of anti-PD-1 immunotherapy in HCC by targeting TFRC and enhancing CXCL14-mediated CD8+ T-cell infiltration. This study contributes to developing novel therapeutic strategies for HCC, emphasizing the role of precision medicine in oncology. HIGHLIGHTS: Synergistic effects of anlotinib and anti-PD-1 immunotherapy demonstrated in HCC preclinical models. Anlotinib inhibits TFRC expression via the VEGFR2/AKT/HIF-1α pathway. CXCL14 upregulation via TFRC suppression boosts CD8+ T-cell recruitment. TFRC emerges as a potential biomarker for evaluating prognosis and predicting response to anti-PD-1-based therapies in advanced HCC patients.

Role of hydrogen sulfide in health and disease.

In the past, hydrogen sulfide (H2S) was recognized as a toxic and dangerous gas; in recent years, with increased research, we have discovered that H2S can act as an endogenous regulatory transmitter. In mammals, H2S-catalyzing enzymes, such as cystathionine-ß-synthase, cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase, are differentially expressed in a variety of tissues and affect a variety of biological functions, such as transcriptional and posttranslational modification of genes, activation of signaling pathways in the cell, and metabolic processes in tissues, by producing H2S. Various preclinical studies have shown that H2S affects physiological and pathological processes in the body. However, a detailed systematic summary of these roles in health and disease is lacking. Therefore, this review provides a thorough overview of the physiological roles of H2S in different systems and the diseases associated with disorders of H2S metabolism, such as ischemia-reperfusion injury, hypertension, neurodegenerative diseases, inflammatory bowel disease, and cancer. Meanwhile, this paper also introduces H2S donors and novel release modes, as well as the latest preclinical experimental results, aiming to provide researchers with new ideas to discover new diagnostic targets and therapeutic options.

Cellulose Nanofiber-Based Nanocomposite Films with Efficient Electromagnetic Interference Shielding and Fire-Resistant Performance.

Cellulose nanofiber (CNF) has been widely used as a flexible and lightweight polymer matrix for electromagnetic shielding and thermally conductive composite films because of its excellent mechanical strength, environmental performance, and low cost. However, the lack of flame retardancy seriously hinders its further application. Herein, renewable and biomass-sourced l-arginine (AR) was used to surface-modify ammonium polyphosphate (APP) and an environmentally friendly biobased flame retardant was synthesized by the coordination of zinc sulfate heptahydrate (ZnSO4·7H2O), which was named AAZ. AAZ was deposited on the surface of CNF by electrostatic adsorption and Zn2+ complexation. The biobased compatibilizer Triton X-100 was employed to assist the exfoliation of graphene nanoplatelets (GNPs) and their dispersion in the CNF matrix. Due to the formation of a dense lamellar layer resembling a shell structure, the CNF/GNPs composite films with a tensile strength of 52 MPa were obtained via vacuum-assisted filtration. Because the phosphorus-containing group produces a protective layer of PxOy compound and promotes the formation of a carbon layer by CNF and the combustion releases ammonia gas, the fire-resistant performance of the composite films was greatly improved. Compared with the pure CNF film, the composite film exhibits 33% reduction in PHRR value and 40% reduction in THR. In addition, the CNF/GNPs composite film with 20 wt % GNPs possessed high conductivity (2079.2 S/m) and electromagnetic interference (EMI) shielding effectiveness (37 dB). The ultrathin CNF/GNPs composite films have excellent potential for use as efficient flame retardant and EMI shielding materials.

Ensuring Stability of Anode Catalysts in PEMWE: From Material Design to Practical Application.

Proton Exchange Membrane Water Electrolysis (PEMWE) has emerged as a clean and effective approach for the conversion and storage of renewable electricity, particularly due to its compatibility with fluctuating photovoltaic and wind power. However, the high cost and limited performance of iridium oxide catalysts (i.e. IrO2) used as anode catalyst in industrial PEM electrolyzers remain significant obstacles to widespread application. Although numerous low-cost and efficient alternative catalysts have been developed in laboratory research, comprehensive stability studies critical for industrial use are often overlooked. This leads to the failure of performance transfer from catalysts tested in liquid half-cell systems to those employed in PEM electrolyzers. This concept presents a thorough overview for the stability issues of anode catalysts in PEMWE, and discuss their degradation mechanisms in both liquid half-cell systems and PEM electrolyzers. We summarize comprehensive protocol for the assessment and characterization, analyze the effective strategies for stability optimization, and explore the opportunities for designing viable anode catalysts for PEM electrolyzers.

A general pHLA-CD80 scaffold fusion protein to promote efficient antigen-specific T cell-based immunotherapy.

Inadequate antigen-specific T cells activation hampers immunotherapy due to complex antigen presentation. In addition, therapeutic in vivo T cell expansion is constrained by slow expansion rates and limited functionality. Herein, we introduce a model fusion protein termed antigen-presenting cell-mimic fusion protein (APC-mimic), designed to greatly mimicking the natural antigen presentation pattern of antigen-presenting cells and directly expand T cells both in vitro and in vivo. The APC-mimic comprises the cognate peptide-human leukocyte antigen (pHLA) complex and the co-stimulatory marker CD80, which are natural ligands on APCs. Following a single stimulation, APC-mimic leads to an approximately 400-fold increase in the polyclonal expansion of antigen-specific T cells compared with the untreated group in vitro without the requirement for specialized antigen-presenting cells. Through the combination of single-cell TCR sequencing (scTCR-seq) and single-cell RNA sequencing (scRNA-seq), we identify an approximately 600-fold monoclonal expansion clonotype among these polyclonal clonotypes. It also exhibits suitability for in vivo applications confirmed in the OT-1 mouse model. Furthermore, T cells expanded by APC-mimic effectively inhibits tumor growth in adoptive cell transfer (ACT) murine models. These findings pave the way for the versatile APC-mimic platform for personalized therapeutics, enabling direct expansion of polyfunctional antigen-specific T cell subsets in vitro and in vivo.

Atomic-Level Asymmetric Tuning of the Co1-N3P1 Catalyst for Highly Efficient N-Alkylation of Amines with Alcohols.

Despite the extensive development of non-noble metals for the N-alkylation of amines with alcohols, the exploitation of catalysts with high selectivity, activity, and stability still faces challenges. The controllable modification of single-atom sites through asymmetric coordination with a second heteroatom offers new opportunities for enhancing the intrinsic activity of transition metal single-atom catalysts. Here, we prepared the asymmetric N/P hybrid coordination of single-atom Co1-N3P1 by absorbing the Co-P complex on ZIF-8 using a concise impregnation-pyrolysis process. The catalyst exhibits ultrahigh activity and selectivity in the N-alkylation of aniline and benzyl alcohol, achieving a turnover number (TON) value of 3480 and a turnover frequency (TOF) value of 174-h. The TON value is 1 order of magnitude higher than the reported catalysts and even 37-fold higher than that of the homogeneous catalyst CoCl2(PPh3)2. Furthermore, the catalyst maintains its high activity and selectivity even after 6 cycles of usage. Controlling experiments and isotope labeling experiments confirm that in the asymmetric Co1-N3P1 system, the N-alkylation of aniline with benzyl alcohol proceeds via a transfer hydrogenation mechanism involving the monohydride route. Theoretical calculations prove that the superior activity of asymmetric Co1-N3P1 is attributed to the higher d-band energy level of Co sites, which leads to a more stable four-membered ring transition state and a lower reaction energy barrier compared to symmetrical Co1-N4.

Universal Copolymerization of Crosslinked Polyether Electrolytes for All-Solid-State Lithium-Metal Batteries.

Solid polymer electrolytes (SPEs) are pivotal in advancing the practical implementation of all-solid-state batteries. Poly(1,3-dioxane) (PDOL)-based electrolytes have attracted significant attention due to the pseudo-high conductivity achieved through sophisticated in situ polymerization methods; however, such PDOL-based electrolytes present challenges of crystallization over time and monomers residual during processing. In this study, integrating LiTFSI and LiDFOB as a universal copolymerization strategy for developing high-performance PDOL electrolytes with a wide range of epoxy crosslinkers is proposed. It is discovered that this approach leverages the protective effects of TFSI anions on the boron active center and catalyzes polymer chain growth via crosslinking. The homogenously crosslinked (benzene-centered) PDOL electrolyte exhibits remarkable thermo-mechanical stability (up to 100 °C), high ion migration number (tLi+ = 0.42), a wide electrochemical window (≈5.0 V vs Li+/Li), and high ionic conductivity (4.5×10-4 S cm-1). Notably, the crosslinked PDOL electrolyte is in the all-solid-state with minimal monomer/oligomer residual, exhibiting no crystallization during relaxation, delivering a robust performance in all-solid-state lithium metal batteries.

Variation of odontoid incidence according to age in asymptomatic children.

OBJECTIVE: To investigate the effect of age and sex on odontoid parameters and their relationships with cervical sagittal alignment in children. METHODS: A total of 155 Chinese children without cervical symptoms were divided into groups by age: 3-12 years (87 participants) and 13-18 years (68 participants) and sex: male (91 participants) and female (64 participants). Lateral plain radiographs of the whole spine were analyzed for (1) odontoid parameters: odontoid incidence (OI), odontoid tilt (OT), and C2 slope (C2S); and (2) cervical sagittal parameters: C0-2, C2-3, C2-4, C2-5, C2-6, and C2-7 angles (cervical lordosis; CL), T1 slope (T1S), and T1S minus CL (T1S-CL). Student's t-tests, linear regression analyses, and Pearson's correlation coefficient analyses were performed. RESULTS: OI showed a significant difference between the 3-12 and 13-18 years groups (13.35° ± 4.32° vs. 17.21° ± 4.26°, p < 0.001), and significant differences were also observed in OT (p = 0.001) and C2S (p < 0.001) between different sexes. Positive correlations were found between age and OI in the 3-12 and 13-18 years groups (adjusted R2 = 0.104 and 0.048, respectively). OI and C2S were positively correlated with the C0-2 angle in all age and sex groups. CONCLUSIONS: Age emerged as a critical determinant of OI, which increased with age among pediatric populations. Clinicians should carefully consider the disparity in OI during the assessment and restoration of cervical sagittal balance in children.

Toxicokinetics and bioavailability of indoxacarb enantiomers and their new metabolites in rats.

Indoxacarb is a chiral insecticide that consists of two enantiomers, S-(+)-indoxacarb and R-(-)-indoxacarb, of which only S-(+)-indoxacarb has insecticidal activity. Previous enantioselective toxicology studies of indoxacarb focused mostly on simple environmental model organisms. The lack of a toxicology evaluation of indoxacarb conducted in a mammalian system could mean that the extent of the potential health risk posed by the insecticide to humans is not adequately known. In this study, we reported on a new pair of enantiomers, S-IN-RM294 and R-IN-RM294, derived from the metabolic breakdown of S-(+)-indoxacarb and R-(-)-indoxacarb, respectively, in rats. The toxicokinetics of S-(+)-indoxacarb, R-(-)-indoxacarb, S-IN-RM294, and R-IN-RM294 in rats were evaluated to provide a more comprehensive risk assessment of these molecules. The bioavailability and excretion rates of both S-(+)-indoxacarb and R-(-)-indoxacarb were relatively low, which may be due to their faster metabolism and accumulation in the tissues. In addition, there were significant differences in the metabolism and distribution between the two indoxacarb enantiomers and their metabolites in vivo. S-(+)-Indoxacarb was found to be more easily metabolized in the blood compared with R-(-)-indoxacarb, as shown by the differences in pharmacokinetic parameters between oral and intravenous administration. Analysis of their tissue distribution showed that S-(+)-indoxacarb was less likely to accumulate in most tissues. The results obtained for the two metabolites were consistent with those of the two parent compounds. S-IN-RM294 was more readily cleared from the blood and less likely to accumulate in the tissues compared with R-IN-RM294. Therefore, whether from the perspective of insecticidal activity or from the perspective of mammalian and environmental friendliness, the application of optically pure S-(+)-indoxacarb in agriculture may be a more efficient and safer strategy.