Uniportal Full-endoscopic Foraminotomy for Lumbar Foraminal Stenosis: Clinical Characteristics and Functional Outcomes.

OBJECTIVE: Uniportal full-endoscopic foraminotomy offers a promising alternative to conventional surgical methods for individuals afflicted by lumbar foraminal stenosis. This study aims to evaluate the efficacy and clinical outcomes of uniportal full-endoscopic foraminotomy in patients diagnosed with lumbar foraminal stenosis. METHODS: A comprehensive retrospective analysis was conducted on individuals who underwent full-endoscopic foraminotomy in our medical center, between January 2018 and December 2019. The investigation encompassed the demographic data of patients and key clinical metrics such as the visual analogue scale of leg (VAS-L) and back pain (VAS-B), Oswestry disability index (ODI) scores, the Short Form-36 Health Survey physical component summary (SF-36 PCS) and the mental component summary (SF-36 MCS), as well as modified MacNab grades, were systematically assessed and compared. Furthermore, radiological parameters: Coronal Cobb angle (CCA), Intervertebral angle changes (IAC), Disc height index (DHI), the foraminal cross-sectional area (FCSA) and the FCSA enlargement ratio were also compared. A variety of statistical analyses including Student t-test, chi-square tests, Fisher's exact tests, Pearson's and Spearman's correlation analyses, and Interclass Correlation Coefficients (ICCs) were employed. RESULTS: 64 patients, including 34 males and 30 females were enrolled. The mean follow-up period extended to 22.66 ± 7.05 months. Distribution by affected segments revealed 26.6% at L4-5, 67.1% at L5-S1 level, and 6.25% at both L4-L5 and L5-S1 levels. At the final follow-up, VAS-L decreased from 7.26 ± 1.19 to 1.37 ± 1.25, while VAS-B decreased from 6.95 ± 0.54 to 1.62 ± 1.13 (p < 0.001). ODI score also demonstrated a substantial decrease from 74.73 ± 8.68 to 23.27 ± 8.71 (p < 0.001). Both SF-36 PCS and SF-36 MCS scores improved significantly (p < 0.001). Modified MacNab criteria revealed 58 excellent-good patients (90.7%), and 6 fair-poor patients (9.3%). No significant differences were founded in the CCA (p = 0.1065), IAC (p = 0.5544), and DHI (p = 0.1348) between pre-operation and the final follow-up. However, the FCSA significantly increased from 73.41 ± 11.75 to 173.40 ± 18.62 mm2 (p < 0.001), and the enlargement ratio was 142.9% ± 49.58%. Notably, the final follow-up FCSA and the FCSA enlargement ratio were found to be larger in the excellent and good group compared to the fair and poor group, according to the modified MacNab criteria. CONCLUSION: The utilization of uniportal full-endoscopic foraminotomy has demonstrated its safety and efficacy in addressing lumbar foraminal stenosis. The clinical success of this procedure appears to be closely associated with the radiological decompression of the intervertebral foramen area. Importantly, the application of this technology does not seem to compromise the overall stability of the lumbar region.

Decoding frontotemporal and cell-type-specific vulnerabilities to neuropsychiatric disorders and psychoactive drugs.

Frontotemporal lobe abnormalities are linked to neuropsychiatric disorders and cognition, but the role of cellular heterogeneity between temporal lobe (TL) and frontal lobe (FL) in the vulnerability to genetic risk factors remains to be elucidated. We integrated single-nucleus transcriptome analysis in 'fresh' human FL and TL with genetic susceptibility, gene dysregulation in neuropsychiatric disease and psychoactive drug response data. We show how intrinsic differences between TL and FL contribute to the vulnerability of specific cell types to both genetic risk factors and psychoactive drugs. Neuronal populations, specifically PVALB neurons, were most highly vulnerable to genetic risk factors for psychiatric disease. These psychiatric disease-associated genes were mostly upregulated in the TL, and dysregulated in the brain of patients with obsessive-compulsive disorder, bipolar disorder and schizophrenia. Among these genes, GRIN2A and SLC12A5, implicated in schizophrenia and bipolar disorder, were significantly upregulated in TL PVALB neurons and in psychiatric disease patients' brain. PVALB neurons from the TL were twofold more vulnerable to psychoactive drugs than to genetic risk factors, showing the influence and specificity of frontotemporal lobe differences on cell vulnerabilities. These studies provide a cell type resolved map of the impact of brain regional differences on cell type vulnerabilities in neuropsychiatric disorders.

Compact unidirectional waveguide grating emitter with enhanced wavelength sensitivity based on the hybrid plasmonic mode.

Waveguide grating antennas are widely adopted in beam-steering devices, typically enabling the beam steering in longitudinal direction within a two-dimensional scanning optical array by changing the input wavelength. However, traditional waveguide grating antennas suffer from limited tuning range due to low dispersion of the gratings. In this paper, a compact silicon grating waveguide antenna array is proposed with enhanced wavelength sensitivity by introducing a periodically modulated hybrid plasmonic mode. The hybrid plasmonic mode is supported by the hybrid plasmonic waveguides (HPWs) composed of silicon waveguides and periodic subwavelength silver strips. In order to convert the guided waves to the radiated waves, a series of silicon emitting segments are deposited above the HPWs. Additionally, the horizontally arranged array of HPWs also acts as a reflector of the downward radiation, resulting in an effective unidirectional emission. Through the optimization of physical parameters, the proposed antenna array achieves a wavelength-length tuning efficiency up to 0.3°/nm within the wavelength range of 1500∼1600 nm, exhibiting a significant improvement compared with traditional ones. Moreover, an average upward emissivity exceeding 80% with a maximum value of 89% within the 100 nm bandwidth is demonstrated through the numerical simulations. The proposed compact antenna array provides an alternative solution in realizing large-scale integrated high-tuning-efficiency optical beam-steering devices.

Efficacy of immunotherapy in ARID1A-mutant solid tumors: a single-center retrospective study.

BACKGROUND: Immune checkpoint inhibitors (ICIs), especially those targeting programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), have introduced a new treatment landscape for many types of tumors. However, they only achieve a limited therapeutic response. Hence, identifying patients who may benefit from ICIs is currently a challenge. METHODS: 47 tumor patients harboring ARID1A mutations were retrospectively studied. The genomic profiling data through next-generation sequencing (NGS) and relevant clinical information were collected and analyzed. Additionally, bioinformatics analysis of the expression of immune checkpoints and immune cell infiltration levels was conducted in ARID1A-mutant gastric cancer (GC). RESULTS: ARID1A mutations frequently co-occur with mutations in DNA damage repair (DDR)-associated genes. Among the 35 ARID1A-mutant patients who received immunotherapy, 27 were evaluable., with the objective response rate (ORR) was 48.15% (13/27), and the disease control rate (DCR) was 92.59% (25/27). Moreover, survival assays revealed that ARID1A-mutant patients had longer median overall survival (mOS) after immunotherapy. In ARID1A-mutated GC patients, receiving ICIs treatment indicated longer progressive-free survival (PFS). Additionally, the incidence of microsatellite instability-high (MSI-H), high tumor mutation burden (TMB-H) and Epstein‒Barr virus (EBV) infection was elevated. Bioinformatic analysis showed significant enrichment of immune response and T cell activation pathway within differentially expressed genes in ARID1A-mutant GC group. Finally, ARID1A mutations status was considered to be highly correlated with the level of tumor infiltrating lymphocytes (TILs) and high expression of immune checkpoints. CONCLUSIONS: Patients with tumors harboring ARID1A mutations may achieve better clinical outcomes from immunotherapy, especially in GC. ARID1A mutations can lead to genomic instability and reshape the tumor immune microenvironment (TIME), which can be used as a biomarker for immunotherapy.

Compact, low-loss, and high-polarized-extinction ratio terahertz TM-pass polarizer based on a hybrid plasmonic waveguide with a graphene ridge.

A compact, low-loss, and high-polarized-extinction ratio TM-pass polarizer based on a graphene hybrid plasmonic waveguide (GHPW) has been demonstrated for the terahertz band. A ridge coated by a graphene layer and the hollow HPW with a semiround arch (SRA) Si core is introduced to improve structural compactness and suppress the loss. Based on this, a TM-pass polarizer has been designed that can effectively cut off the unwanted TE mode, and the TM mode passes with negligible loss. By optimizing the angle of the ridge, the height of the ridge, air gap height, and the length of the tapered mode converter, an optimum performance with a high polarization extinction ratio of 30.28 dB and a low insert loss of 0.4 dB is achieved in the 3 THz band. This work provides a scheme for the design and optimization of polarizers in the THz band, which has potential application value in integrated terahertz systems.

Kinetics and Mechanism of the Singlet Oxygen Atom Reaction with Dimethyl Ether.

We combine in situ laser spectroscopy, quantum chemistry, and kinetic calculations to study the reaction of a singlet oxygen atom with dimethyl ether. Infrared laser absorption spectroscopy and Faraday rotation spectroscopy are used for the detection and quantification of the reaction products OH, H2O, HO2, and CH2O on submillisecond time scales. Fitting temporal profiles of products with simulations using an in-house reaction mechanism allows product branching to be quantified at 30, 60, and 150 Torr. The experimentally determined product branching agrees well with master equation calculations based on electronic structure data and transition state theory. The calculations demonstrate that the dimethyl peroxide (CH3OOCH3) generated via O-insertion into the C-O bond undergoes subsequent dissociation to CH3O + CH3O through energetically favored reactions without an intrinsic barrier. This O-insertion mechanism can be important for understanding the fate of biofuels leaking into the atmosphere and for plasma-based biofuel processing technologies.

Essential role of ABA signaling and related transcription factors in phenolic acid and lignin synthesis during muskmelon wound healing.

Abscisic acid (ABA) is a key phytohormone involved in wound healing in fruits and vegetables, while fluridone (FLD) is its synthetic inhibitor. However, it is unknown whether ABA signaling and downstream transcription factors are involved in the synthesis of phenolic acids and lignin monomers in muskmelon wounds, and the underlying mechanisms. In our study, exogenous ABA promoted endogenous ABA synthesis by increasing the levels of ß-carotenoid and zeaxanthin, activating 9-cis-epoxycarotenoid dioxygenase (NCED) and zeaxanthin epoxidase (ZEP), facilitated ABA signaling by increasing the expression levels of protein phosphatases type 2C (CmPP2C) and ABA-responsive element binding factors (CmABF), upregulated the expression levels of CmMYB1 and CmWRKY1, and ABA induced phenylpropanoid metabolism by activating phenylalanine ammonia-lyase (PAL), 4-coenzyme A ligase (4CL), and cinnamyl alcohol dehydrogenase (CAD), which further increased the synthesis of phenolic acids and lignin monomers in muskmelon wounds during healing. Taken together, exogenous ABA induced phenylpropanoid metabolism and increased the synthesis of phenolic acid and lignin monomer in muskmelon wounds during healing, and may be involved in endogenous ABA synthesis and signaling and related transcription factors.

TUFM in health and disease: exploring its multifaceted roles.

The nuclear-encoded mitochondrial protein Tu translation elongation factor, mitochondrial (TUFM) is well-known for its role in mitochondrial protein translation. Originally discovered in yeast, TUFM demonstrates significant evolutionary conservation from prokaryotes to eukaryotes. Dysregulation of TUFM has been associated with mitochondrial disorders. Although early hypothesis suggests that TUFM is localized within mitochondria, recent studies identify its presence in the cytoplasm, with this subcellular distribution being linked to distinct functions of TUFM. Significantly, in addition to its established function in mitochondrial protein quality control, recent research indicates a broader involvement of TUFM in the regulation of programmed cell death processes (e.g., autophagy, apoptosis, necroptosis, and pyroptosis) and its diverse roles in viral infection, cancer, and other disease conditions. This review seeks to offer a current summary of TUFM's biological functions and its complex regulatory mechanisms in human health and disease. Insight into these intricate pathways controlled by TUFM may lead to the potential development of targeted therapies for a range of human diseases.

A combined AIMD and DFT study of the low-energy radiation responses of GaN.

Although GaN is a promising candidate for semiconductor devices, degradation of GaN-based device performance may occur when the device is bombarded by high-energy charged particles during its application in aerospace, astronomy, and nuclear-related areas. It is thus of great significance to explore the influence of irradiation on the microstructure and electronic properties of GaN and to reveal the internal relationship between the damage mechanisms and physical characteristics. Using a combined density functional theory (DFT) and ab initio molecular dynamics (AIMD) study, we explored the low-energy recoil events in GaN and the effects of point defects on GaN. The threshold displacement energies (Eds) significantly depend on the recoil directions and the primary knock-on atoms. Moreover, the Ed values for nitrogen atoms are smaller than those for gallium atoms, indicating that the displacement of nitrogen dominates under electron irradiation and the created defects are mainly nitrogen vacancies and interstitials. The formation energy of nitrogen vacancies and interstitials is smaller than that for gallium vacancies and interstitials, which is consistent with the AIMD results. Although the created defects improve the elastic compliance of GaN, these radiation damage states deteriorate its ability to resist external compression. Meanwhile, these point defects lead the Debye temperature to decrease and thus increase the thermal expansion coefficients of GaN. As for the electronic properties of defective GaN, the point defects have various effects, i.e., VN (N vacancy), Gaint (Ga interstitial), Nint (N interstitial), and GaN (Ga occupying the N lattice site) defects induce the metallicity, and NGa (N occupying the Ga lattice site) defects decrease the band gap. The presented results provide underlying mechanisms for defect generation in GaN, and advance the fundamental understanding of the radiation resistances of semiconductor materials.

Reconstitution of peripheral blood T cell receptor ß immune repertoire in immune checkpoint inhibitors associated myocarditis.

PURPOSE: Immune checkpoint inhibitors (ICIs)-associated myocarditis was a rare yet severe complication observed in individuals undergoing immunotherapy. This study investigated the immune status and characteristics of patients diagnosed with ICIs- associated myocarditis. METHODS: A total of seven patients diagnosed with ICIs-associated myocarditis were included in the study, while five tumor patients without myocarditis were recruited as reference controls. Additionally, 30 healthy individuals were recruited as blank controls. Biochemical indices, electrocardiogram, and echocardiography measurements were obtained both prior to and following the occurrence of myocarditis. High-throughput sequencing of T cell receptor (TCR) was employed to assess the diversity and distribution characteristics of TCR CDR3 length, as well as the diversity of variable (V) and joining (J) genes of T lymphocytes in peripheral blood. RESULTS: In the seven patients with ICIs-associated myocarditis, Troponin T (TNT) levels exhibited a significant increase following myocarditis, while other parameters such as brain natriuretic peptide (BNP), QTc interval, and left ventricular ejection fraction (LVEF) did not show any significant differences. Through sequencing, it was observed that the diversity and uniformity of CDR3 in the ICIs-associated myocarditis patients were significantly diminished. Additionally, the distribution of CDR3 nucleotides deviated from normality, and variations in the utilization of V and J gene segments. CONCLUSION: The reconstitution of the TCR immune repertoire may play a pivotal role in the recognition of antigens in patients with ICIs-associated myocarditis.

Ecotoxicity of Cadmium along the Soil-Cotton Plant-Cotton Bollworm System: Biotransfer, Trophic Accumulation, Plant Growth, Induction of Insect Detoxification Enzymes, and Immunocompetence.

Cadmium (Cd) is a hazardous element that may jeopardize environmental safety and human health through biotransfer and trophic accumulation. Here, we tested Cd toxicity on cotton plants, cotton bollworms, and their responses. Results demonstrated that Cd accumulated in plant roots, aerial parts, insect larvae, pupae, and frass in a dose-dependent pattern. The ∼9.35 mg kg-1 of Cd in plant aerial parts, ∼3.68 in larvae, ∼6.43 in pupae, and high transfer coefficient (∼5.59) indicate significant mobility. The ∼19.61 mg kg-1 of Cd in larvae frass suggests an effective detoxification strategy, while BAFcotton (∼1.14) and BAFworm (∼0.54) indicated low bioaccumulation. Cadmium exposure resulted in compromised plant growth and yield as well as alterations in photosynthetic pigment contents, antioxidant enzyme activities, and certain life history traits of cotton bollworms. Furthermore, carboxylesterase activity and encapsulation rates of insect larvae decreased with increasing Cd concentrations, whereas acetylcholinesterase, phenol oxidase, glutathione S-transferase, and multifunctional oxidase exhibited hormesis responses.

Cancer parents' experiences of parenting concerns about minor children: A meta-synthesis of qualitative studies.

Background: Some cancer patients not only endure physical and mental distress due to the disease and treatment but also shoulder the responsibility of raising their children. This situation significantly impacts the patients' quality of life. While there is a growing body of qualitative research focusing on parenting concerns among cancer patients, there remains a lack of comprehensive qualitative evidence. Objective: This study aims to conduct a systematic review and synthesis of qualitative research evidence, investigating the experiences of cancer patients in raising minor children. Design: Systematic review and synthesis of qualitative studies. Settings: Through a screening process employing inclusion/exclusion criteria, qualitative studies specifically addressing cancer patients raising minor children were identified. Participants: Participants: A total of 669 participants from 40 studies were included in the review. Methods: Four English (Pubmed, Web of Science, Embase and Cochrane Library) and three Chinese (CNKI, Wanfang and Sinomed) databases were searched for qualitative studies of the real-life experiences of raising children in cancer patients from the establishment of the library to January 2024. The methodological quality of the included literature was assessed using the Critical Appraisal Skill Program (CSAP). Qualitative data were extracted, summarized, and meta-synthesized. Results: A total of 26 studies were included in this meta-synthesis, encompassing 11 different countries. 160 themes were extracted from these included literatures, which were combined into ten categories, ultimately forming four themes: the impact of parents' disease on their children, the challenges of parenting, coping strategies, and multifaceted parenting needs. Based on the Confidence in the Output of Qualitative research synthesis (ConQual) approach, the confidence level of the synthesized findings ranged from moderate to low. Conclusions: Cancer patients experience significant psychological stress while raising children, which can lead to a reduction in their quality of life and influence treatment decisions. These findings elucidate the parenting concerns experienced by cancer patients, allowing medical staff to understand their emotions and treatment preferences. Additionally, healthcare professionals should pay attention to the special needs of this group and develop targeted interventions to support and reduce patients' psychological stress and burden.

The Relationship Between Stressful Life Events and Depressive Symptoms in College Students: mediation by Parenting Style and Gender's Moderating Effect.

Aim: Stressful life events have a significant impact on the mental health of college students. Depression, as a prevalent psychological issue, has garnered attention in the field of college student mental health and is closely linked to it. Additionally, parenting style is identified as an important factor influencing the development of college students' mental health. Therefore, this study aims to explore the relationship between these three factors. Methods: A total of 8079 first-year college students from two medical universities in Shandong Province, China were surveyed. The Beck Depression Inventory was utilized to evaluate depressive symptoms among the college students, while the Adolescent Self-rating Life Events Checklist and the Egna Minnen Beträfande Uppfostran were employed to gather data. Subsequently, the SPSS macro program PROCESS was utilized to analyze both the mediating and moderating effects. All statistical analyses were conducted using SPSS 26.0. Results: The study found a detection rate of 6.3% for depressive symptoms among college students. The correlation analysis of this study showed that the stressful life events of college students were significantly positively correlated with depressive symptoms (r=0.261, p< 0.01). Each dimension of parenting style was associated with depressive symptoms in different degrees and directions. At the same time, parenting styles of all sizes play a partial mediating role between stressful life events and depressive symptoms in college students, gender plays a crucial regulatory role in this mediation. Conclusion: Stressful life events experienced by college students have a significant impact on their mental health. Early intervention through positive parenting styles from parents may prove to be beneficial in promoting the development of good mental health among college students.

The Syvn1 inhibits neuronal cell ferroptosis by activating Stat3/Gpx4 axis in rat with spinal cord injury.

Spinal cord injury (SCI) leads to secondary neuronal death, which severely impedes recovery of motor function. Therefore, prevention of neuronal cell death after SCI is an important strategy. Ferroptosis, a new form of cell death discovered in recent years, has been shown to be involved in the regulation of SCI. However, the role and potential mechanisms of ferroptosis in secondary SCI are not fully understood. In this study, we report that the E3 ubiquitin ligase Syvn1 suppresses ferroptosis and promotes functional recovery from SCI in vitro and in vivo. Mechanistically, screened with bioinformatics, immunoprecipitation, and mass spectrometry, we identified Stat3, a transcription factor that induces the expression of the ferroptosis inhibitor Gpx4, as a substrate of Syvn1. Furthermore, we identified neurons as the primary cellular source of Syvn1 signalling. Moreover, we determined the binding domains of Syvn1 and Stat3 in HEK 293 T cells using full-length proteins and a series of truncated Flag-tagged and Myc-tagged fragments. Furthermore, we created the cell and animal models with silencing or overexpression of Syvn1 and Stat3 and found that Syvn1 inhibits neuronal ferroptosis by stabilizing Stat3, which subsequently activates the ferroptosis regulator Gpx4 in SCI. In summary, the Syvn1-mediated Stat3/Gpx4 signalling axis attenuates neuronal ferroptosis, reduces neuronal death, and promotes SCI repair. Therefore, our findings provide potential new targets and intervention strategies for the treatment of SCI.

Co-photoaging inhibited the heteroaggregation between polystyrene nanoplastics and different titanium dioxide nanoparticles.

Heteroaggregation between nanoplastics (NPs) and titanium dioxide nanoparticles (TiO2NPs) determines their environmental fates and ecological risks in aquatic environments. However, the co-photoaging scenario of NPs and TiO2NPs, interaction mechanisms of TiO2NPs with (aged) NPs, as well as the dependence of their heteroaggregation on TiO2NPs facets remain elusive. We found the critical coagulation concentration (CCC) of polystyrene nanoplastics (PSNPs) with coexisting RTiO2NPs was 1.9 - 2.2 times larger than that with coexisting ATiO2NPs, suggesting a better suspension stability of PSNPs+RTiO2NPs. In addition, CCC of TiO2NPs with coexisting photoaged PSNPs (APSNPs) was larger 1.7 - 2.2 times than that with PSNPs coexisting, indicating photoaging inhibited their heteroaggregation due to increasing electrostatic repulsion derived from increased negative charges on APSNPs and the polymer-derived dissolved organic carbon. Coexisted TiO2NPs promoted oxidation of PSNPs with the action of HO· and O2·- under UV light, leading to inhibited heteroaggregation. Moreover, Van der Waals and Lewis-acid interaction dominated the formation of primary heteroaggregates of PSNPs-TiO2NPs (ESE = ‒2.20 ∼ ‒2.78 eV) and APSNPs-TiO2NPs (ESE = ‒3.29 ∼ ‒3.67 eV), respectively. The findings provide a mechanistic insight into the environmental process of NPs and TiO2NPs, and are significant for better understanding their environmental risks in aquatic environments.

[Expert consensus on the prenatal diagnosis and genetic counseling for uniparental disomy-related imprinting disorders].

Uniparental disomy (UPD)-related imprinting disorders are a group of congenital disorders which can lead to severe birth defects. Their molecular etiology is the occurrence of UPD in the genomic imprinting regions, which may cause disturbed expression of parent-of-origin imprinted genes. With the widespread applications of genetic testing techniques, the prenatal diagnosis of UPD-related imprinted diseases has gradually become clinical routines. However, due to the complicated pathogenesis of such disorders, currently there is still a lack of standards and norms for the understanding, diagnosis, management and genetic counseling. By referring to the relevant guidelines and consensus, the latest progress of research, and opinions from experts in the relevant fields, the writing group has formulated a consensus over the prenatal diagnosis and genetic counseling for UPD-related imprinting disorders, with an aim to provide a more accurate and rational evaluation in prenatal clinics.

[Expert consensus on the test development and preliminary implementation of whole genome sequencing for fetal structural abnormalities].

Fetal structural anomalies and birth defects are primarily caused by genetic variants such as chromosomal number abnormalities, copy number variations (CNV), single nucleotide variants (SNV), and small insertions and deletions (indel). Whole-genome sequencing (WGS) based on next-generation sequencing (NGS) as an emerging technology for genetic disease diagnosis can detect the aforementioned types of variants. In recent years, high-depth WGS (> 30×) for prenatal diagnosis has also become available, and proved to be practical for unraveling the genetic etiology of fetal developmental abnormalities. To facilitate clinical practice, test development and preliminary implementation of WGS for diagnosing fetal structural anomalies, we have formulated a consensus over the application of WGS in prenatal diagnosis by compiling previously published consensuses, guidelines, and research findings to provide a guidance on data analysis, reporting recommendations, and consultation of prenatal WGS results.

Preparation of Medical 228Th-224Ra Radionuclide Generator Based on SiO2@TiO2 Microspheres.

224Ra (T1/2 = 3.63 d), an α-emitting radionuclide, holds significant promise in cancer endoradiotherapy. Current 224Ra-related therapy is still scarce because of the lack of reliable radionuclide supply. The 228Th-224Ra radionuclide generator can undoubtedly introduce continuous and sustainable availability of 224Ra for advanced nuclear medicine. However, conventional metal oxides for such radionuclide generators manifest suboptimal adsorption capacities for the parent nuclide, primarily attributable to their limited surface area. In this work, core-shell SiO2@TiO2 microspheres were proposed to develop as column materials for the construction of a 228Th-224Ra generator. SiO2@TiO2 microspheres were well prepared and systematically characterized, which has also been demonstrated to have good adsorption capacity to 228Th and very weak binding affinity toward 224Ra via simulated chemical separation. Upon introducing 228Th-containing solution onto the SiO2@TiO2 functional column, a 228Th-224Ra generator with excellent retention of the parent radionuclide and ideal elution efficiency of daughter radionuclide was obtained. The prepared 228Th-224Ra generator can produce 224Ra with high purity and medical usability in good elution efficiency (98.72%) even over five cycles. To the best of our knowledge, this is the first time that the core-shell mesoporous materials have been applied in a radionuclide generator, which can offer valuable insights for materials chemistry, radiochemical separation, and biological medicine.

Comprehensive analysis of abnormal methylation modification differential expression mRNAs between low-grade and high-grade intervertebral disc degeneration and its correlation with immune cells.

BACKGROUND: Intervertebral disc degeneration (IDD) is an important cause of low back pain. The aim of this study is to identify the potential molecular mechanism of abnormal methylation-modified DNA in the progression of IDD, hoping to contribute to the diagnosis and management of IDD. METHODS: Low-grade IDD (grade I-II) and high-grade IDD (grade III-V) data were downloaded from GSE70362 and GSE129789 datasets. The abnormally methylated modified differentially expressed mRNAs (DEmRNAs) were identified by differential expression analysis (screening criteria were p < .05 and |logFC| > 1) and differential methylation analysis (screening criteria were p < .05 and |뫧| > 0.1). The classification models were constructed, and the receiver operating characteristic analysis was also carried out. In addition, functional enrichment analysis and immune correlation analysis were performed and the miRNAs targeted for the abnormally methylated DEmRNAs were predicted. Finally, expression validation was performed using real-time PCR. RESULTS: Compared with low-grade IDD, seven abnormal methylation-modified DEmRNAs (AOX1, IBSP, QDPR, ABLIM1, CRISPLD2, ACTC1 and EMILIN1) were identified in high-grade IDD, and the classification models of random forests (RF) and support vector machine (SVM) were constructed. Moreover, seven abnormal methylation-modified DEmRNAs and classification models have high diagnostic accuracy (area under the curve [AUC] > 0.8). We also found that AUC values of single abnormal methylation-modified DEmRNA were all lower than those of RF and SVM classification models. Pearson correlation analysis found that macrophages M2 and EMILIN1 had significant negative correlation, while macrophages M2 and IBSP had significant positive correlation. In addition, four targeted relationship pairs (hsa-miR-4728-5p-QDPR, hsa-miR-4533-ABLIM1, hsa-miR-4728-5p-ABLIM1 and hsa-miR-4534-CRISPLD2) and multiple signalling pathways (for example, PI3K-AKT signalling pathway, osteoclast differentiation and calcium signalling pathway) were also identified that may be involved in the progression of IDD. CONCLUSION: The identification of abnormal methylation-modified DEmRNAs and the construction of classification models in this study were helpful for the diagnosis and management of IDD progression.

Hippocampal transcriptomic analyses reveal the potential antiapoptotic mechanism of a novel anticonvulsant agent Q808 on pentylenetetrazol-induced epilepsy in rats.

Brain apoptosis is one of the main causes of epileptogenesis. The antiapoptotic effect and potential mechanism of Q808, an innovative anticonvulsant chemical, have never been reported. In this study, the seizure stage and latency to reach stage 2 of pentylenetetrazol (PTZ) seizure rat model treated with Q808 were investigated. The morphological change and neuronal apoptosis in the hippocampus were detected by hematoxylin and eosin (HE) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining, respectively. The hippocampal transcriptomic changes were observed using RNA sequencing (RNA-seq). The expression levels of hub genes were verified by quantitative reverse-transcription PCR (qRT-PCR). Results revealed that Q808 could allay the seizure score and prolong the stage 2 latency in seizure rats. The morphological changes of neurons and the number of apoptotic cells in the DG area were diminished by Q808 treatment. RNA-seq analysis revealed eight hub genes, including Map2k3, Nfs1, Chchd4, Hdac6, Siglec5, Slc35d3, Entpd1, and LOC103690108, and nine hub pathways among the control, PTZ, and Q808 groups. Hub gene Nfs1 was involved in the hub pathway sulfur relay system, and Map2k3 was involved in the eight remaining hub pathways, including Amyotrophic lateral sclerosis, Cellular senescence, Fc epsilon RI signaling pathway, GnRH signaling pathway, Influenza A, Rap1 signaling pathway, TNF signaling pathway, and Toll-like receptor signaling pathway. qRT-PCR confirmed that the mRNA levels of these hub genes were consistent with the RNA-seq results. Our findings might contribute to further studies exploring the new apoptosis mechanism and actions of Q808.