The cGAS-Ku80 complex regulates the balance between two end joining subpathways.

As the major DNA sensor that activates the STING-TBK1 signaling cascade, cGAS is mainly present in the cytosol. A number of recent reports have indicated that cGAS also plays critical roles in the nucleus. Our previous work demonstrated for the first time that cGAS is translocated to the nucleus upon the occurrence of DNA damage and inhibits homologous recombination (HR), one of the two major pathways of DNA double strand break (DSB) repair. However, whether nuclear cGAS regulates the other DSB repair pathway, nonhomologous end joining (NHEJ), which can be further divided into the less error-prone canonical NHEJ (c-NHEJ) and more mutagenic alternative NHEJ (alt-NHEJ) subpathways, has not been characterized. Here, we demonstrated that cGAS tipped the balance of the two NHEJ subpathways toward c-NHEJ. Mechanistically, the cGAS-Ku80 complex enhanced the interaction between DNA-PKcs and the deubiquitinase USP7 to improve DNA-PKcs protein stability, thereby promoting c-NHEJ. In contrast, the cGAS-Ku80 complex suppressed alt-NHEJ by directly binding to the promoter of Polθ to suppress its transcription. Together, these findings reveal a novel function of nuclear cGAS in regulating DSB repair, suggesting that the presence of cGAS in the nucleus is also important in the maintenance of genome integrity.

Undernourished Household Contacts Are at Increased Risk of Tuberculosis (TB) Disease, but not TB Infection- a Multicenter Prospective Cohort Analysis.

Undernutrition is the leading risk factor for tuberculosis (TB) globally and in India. This multicenter prospective cohort analysis from India suggests that undernutrition is associated with increased risk of TB disease but not TB infection among household contacts of persons with TB.

Lysophosphatidic acid responsive photosensitive supramolecular organic frameworks for tumor imaging, drug loading, and photodynamic therapy.

Supramolecular organic frameworks have been widely applied for biological detection and drug delivery. In this study, a supramolecular organic framework (SOF) is constructed through the self-assembly of a highly photosensitive triarylphosphine oxide guest molecule, OTPP-6-Methyl, with cucurbit [8] uril (CB [8]). The formation of the SOF gradually enhances the weak fluorescence of OTPP-6-Methyl owing to the restriction of the molecular folding motion. Although the high positive charge of OTPP-6-Methyl facilitates binding to various negatively charged substances, the SOF system only demonstrated an obvious fluorescence response to LPA, a biomarker of ovarian cancer, via the disassembly of SOF and subsequent binding of OTPP-6-Methyl with LPA. The fluorescence changes during the entire process are insufficient to allow the sensitive detection of LPA; thus, we further designed a FRET system by introducing Cy5, which can act as an energy receptor to achieve a ratiometric readout for LPA. The tumor-targeting cRGD group was introduced into the SOF system as part of another guest molecule, OTPP-5-M-1-cRGD, to improve the tumor-targeting ability of the SOF system. The SOF system further improves the photosensitivity of guest molecules, and is therefore used in the in vivo imaging of ovarian cancer subcutaneous tumors and as a DDS for loading DOX for the combined in vivo chemotherapy and photodynamic treatment of tumors.

Isotope engineering for spin defects in van der Waals materials.

Spin defects in van der Waals materials offer a promising platform for advancing quantum technologies. Here, we propose and demonstrate a powerful technique based on isotope engineering of host materials to significantly enhance the coherence properties of embedded spin defects. Focusing on the recently-discovered negatively charged boron vacancy center ([Formula: see text]) in hexagonal boron nitride (hBN), we grow isotopically purified h10B15N crystals. Compared to [Formula: see text] in hBN with the natural distribution of isotopes, we observe substantially narrower and less crowded [Formula: see text] spin transitions as well as extended coherence time T2 and relaxation time T1. For quantum sensing, [Formula: see text] centers in our h10B15N samples exhibit a factor of 4 (2) enhancement in DC (AC) magnetic field sensitivity. For additional quantum resources, the individual addressability of the [Formula: see text] hyperfine levels enables the dynamical polarization and coherent control of the three nearest-neighbor 15N nuclear spins. Our results demonstrate the power of isotope engineering for enhancing the properties of quantum spin defects in hBN, and can be readily extended to improving spin qubits in a broad family of van der Waals materials.

Environmental governance-public supervision and participation nexus under state supervision system and carbon neutrality targets in China.

China is now experiencing severe environmental issues due to its rapid socio-economic advancement. Environmental governance is crucial to preserving China's rapidly degrading natural ecology. Public supervision and participation are important factors that effectively promote environmental quality. Therefore, this analysis primarily examines the relationship between China's public participation and environmental governance. Hence, the primary focus of the analysis is to investigate the asymmetric impact of public participation on environmental governance from 1996 to 2020. We have employed the nonlinear QARDL model that estimates the short- and long-run impact across different quantiles. The study's results support that long-run estimates for positive change in environmental NGOs (ENGOs) are significantly positive for almost all quantiles, while those for negative change in ENGOs are negative and have a significant impact at higher quantiles. In the short run, the estimates of positive change in ENGOs are positive and significant; however, the negative change in ENGOs does not significantly impact environmental governance at lower quantiles. The Wald test also confirms the asymmetric impact of ENGOs on environmental governance across various quantiles in short and long run. The findings of this analysis underscore the critical role of public supervision and participation in influencing environmental governance in China.

Assessment of bidirectional relationships between multiple sclerosis and epilepsy: A two-sample Mendelian randomization study.

BACKGROUND AND OBJECTIVE: Epidemiological studies indicate that multiple sclerosis (MS) is associated with epilepsy. However, the causality and directionality of this association remain under-elucidated. This study aimed to reveal the causality between MS and epilepsy. METHODS: A two-sample Mendelian randomization (MR) analysis was performed by using summarized statistics derived from large genome-wide association studies of MS and epilepsy. We used the inverse variance weighted method as the primary approach, and then four other MR methods to bidirectionally evaluate the causality of the association between MS and epilepsy. Additional sensitivity analyses were performed to measure the robustness of the findings. RESULTS: Genetically predicted MS was positively correlated with developing all epilepsy [odds ratio (OR) = 1.027 (1.003-1.051), P  =  0.028] and generalized epilepsy [OR = 1.050 (1.008-1.094), P = 0.019]. In the reverse MR analysis, all epilepsy [OR = 1.310 (1.112-1.543), P = 0.001], generalized epilepsy [OR = 1.173 (1.010-1.363), P = 0.037], and focal epilepsy [OR = 1.264 (1.069-1.494), P  =  0.006] elevated the risk of developing MS. The result remained robust and congruous across all sensitivity analyses conducted. CONCLUSIONS: MS is potentially associated with a higher risk of developing epilepsy. Furthermore, epilepsy may be a causal determinant of MS risk. These findings may further the understanding of the interaction of the two conditions.

Analysis of the Differentially Expressed Proteins in Donkey Milk in Different Lactation Stages.

Proteins in donkey milk (DM) have special biological activities. However, the bioactive proteins and their expression regulation in donkey milk are still unclear. Thus, the differentially expressed proteins (DEPs) in DM in different lactation stages were first investigated by data-independent acquisition (DIA) proteomics. A total of 805 proteins were characterized in DM. The composition and content of milk proteins varied with the lactation stage. A total of 445 candidate DEPs related to biological processes and molecular functions were identified between mature milk and colostrum. The 219 down-regulated DEPs were mainly related to complement and coagulation cascades, staphylococcus aureus infection, systemic lupus erythematosus, prion diseases, AGE-RAGE signaling pathways in diabetic complications, and pertussis. The 226 up-regulated DEPs were mainly involved in metabolic pathways related to nutrient (fat, carbohydrate, nucleic acid, and vitamin) metabolism. Some other DEPs in milk from the lactation period of 30 to 180 days also had activities such as promoting cell proliferation, promoting antioxidant, immunoregulation, anti-inflammatory, and antibacterial effects, and enhancing skin moisture. DM can be used as a nutritional substitute for infants, as well as for cosmetic and medical purposes. Our results provide important insights for understanding the bioactive protein differences in DM in different lactation stages.

circ-hnRNPU inhibits NONO-mediated c-Myc transactivation and mRNA stabilization essential for glycosylation and cancer progression.

BACKGROUND: Recent evidence reveals the emerging functions of circular RNA (circRNA) and protein glycosylation in cancer progression. However, the roles of circRNA in regulating glycosyltransferase expression in gastric cancer remain to be determined. METHODS: Circular RNAs (circRNAs) were validated by Sanger sequencing. Co-immunoprecipitation, mass spectrometry, and RNA sequencing assays were applied to explore protein interaction and target genes. Gene expression regulation was observed by chromatin immunoprecipitation, RNA immunoprecipitation, dual-luciferase reporter, real-time quantitative RT-PCR, and western blot assays. Gain- and loss-of-function studies were performed to observe the impacts of circRNA and its partners on the glycosylation, growth, invasion, and metastasis of gastric cancer cells. RESULTS: Circ-hnRNPU, an exonic circRNA derived from heterogenous nuclear ribonuclear protein U (hnRNPU), was identified to exert tumor suppressive roles in protein glycosylation and progression of gastric cancer. Mechanistically, circ-hnRNPU physically interacted with non-POU domain containing octamer binding (NONO) protein to induce its cytoplasmic retention, resulting in down-regulation of glycosyltransferases (GALNT2, GALNT6, MGAT1) and parental gene hnRNPU via repression of nuclear NONO-mediated c-Myc transactivation or cytoplasmic NONO-facilitated mRNA stability. Rescue studies indicated that circ-hnRNPU inhibited the N- and O-glycosylation, growth, invasion, and metastasis of gastric cancer cells via interacting with NONO protein. Pre-clinically, administration of lentivirus carrying circ-hnRNPU suppressed the protein glycosylation, tumorigenesis, and aggressiveness of gastric cancer xenografts. In clinical cases, low circ-hnRNPU levels and high NONO or c-Myc expression were associated with poor survival outcome of gastric cancer patients. CONCLUSIONS: These findings indicate that circ-hnRNPU inhibits NONO-mediated c-Myc transactivation and mRNA stabilization essential for glycosylation and cancer progression.

Efficient photo-driven ion pump through slightly reduced vertical graphene oxide membranes.

Solar energy can be harvested using biological light-driven ion pumps for the sustainability of life. It remains a significant challenge to develop high-performance artificial light-driven ion pumps for solar energy harvesting in all solid-state materials. Here, we exploit the benefits of short channel lengths and efficient light absorption to demonstrate efficient photo-driven ion transport in slightly reduced vertical graphene oxide membranes (GOMs). Remarkably, this photo-driven ion pump exhibits excellent ability, countering a 10-fold electrolyte concentration gradient. We propose a plausible mechanism where light illumination enhances the electric potential of ion channels on GOMs triggered by the separation of photoexcited charge carriers between the sp2 and sp3 carbon clusters. This results in the establishment of an electric potential difference across the effective ion channels composed of sp3 carbon clusters, thus driving the directional transport of cations from the illuminated side to the non-illuminated side. The promising results of this study provide new possibilities for the application of vertical 2D nanofluidic membranes in areas such as artificial photosynthesis, light harvesting, and water treatment.

Quantifying the effect of non-ionic surfactant alkylphenol ethoxylates on the persistence of thiabendazole on fresh produce surface.

BACKGROUND: Understanding the role of adjuvants in pesticide persistence is crucial to develop effective pesticide formulations and manage pesticide residues in fresh produce. This study investigated the impact of a commercial non-ionic surfactant product containing alkylphenol ethoxylates (APEOs) on the persistence of thiabendazole on apple and spinach surfaces against the 30 kg m-3 baking soda (sodium bicarbonate, NaHCO3 ) soaking, which was used to remove the active ingredient (AI) in the cuticular wax layer of fresh produce through alkaline hydrolysis. Surface-enhanced Raman scattering (SERS) mapping method was used to quantify the residue levels on fresh produce surfaces at different experimental scenarios. Four standard curves were established to quantify surface thiabendazole in the absence and presence of APEOs, on apple and spinach leaf surfaces, respectively. RESULTS: Overall, the result showed that APEOs enhanced the persistence of thiabendazole over time. After 3 days of exposure, APEOs increased thiabendazole surface residue against NaHCO3 hydrolysis on apple and spinach surfaces by 5.39% and 10.47%, respectively. CONCLUSION: The study suggests that APEOs led to more pesticide residues on fresh produce and greater difficulty in washing them off from the surfaces using baking soda, posing food safety concerns. © 2023 Society of Chemical Industry.

A simplified prognostic score for T-cell large granular lymphocyte leukaemia.

BACKGROUND: T-cell large granular lymphocyte leukaemia (T-LGLL) generally has a favourable prognosis, but a small proportion of patients are facing a relatively short survival time. This study aimed to identify clinical factors associated with survival in patients with T-LGLL and develop a predictive model for guiding therapeutic decision-making. MATERIALS AND METHODS: We conducted a retrospective study on 120 patients with T-LGLL. Lasso regression was performed for feature selection followed by univariate and multivariate Cox regression analysis. A decision tree algorithm was employed to construct a model for predicting overall survival (OS) in T-LGLL. RESULTS: The median age of diagnosis for the entire cohort was 59 years, and 76.7% of patients reported disease-related symptoms. After a median follow-up of 75 months, the median OS was not reached. The 5-year OS rate was 82.2% and the 10-year OS rate was 63.8%. Multivariate analysis revealed that an Eastern Cooperative Oncology Group performance status over two and a platelet count below 100 × 109/L were independently associated with worse OS, leading to the development of a simplified decision tree model. The model's performance was adequate when internally validated. The median OS of the high- and intermediate-risk- risk groups was 43 and 100 months respectively, whereas the median OS of the low-risk group was not reached. Furthermore, we found that immunosuppressive agent-based conventional treatment was unsatisfactory for our high-risk patients. CONCLUSIONS: Our model is an easily applicable clinical scoring system for predicting OS in patients with T-LGLL. However, external validation is essential before implementing it widely.

Understanding Microstructural Development of Perovskite Crystallization for High Performance Solar Cells.

Solution crystallization in film devices has attracted broad interest from various fields such as perovskite solar cells. However, the detailed perovskite crystallization kinetics remain unclear due to the difficulty of in situ observation of grain cluster growth during annealing. This article presents the development of an in situ laser scanning confocal polarized microscopy with a temperature-controlled stage to observe nucleation and growth of perovskite crystal clusters. It is found that enhanced interactions by a liquid crystal with perovskite form a new intermediate complex that induces diffusion-controlled growth according to Avrami equation. The retarded cluster growth (63 nm s-1 ) originates from enlarged diffusion activation energy 40 kJ mol-1 compared with 152 nm s-1 and 37 kJ mol-1 for the Control film during annealing. Finally, the optimized perovskite films with enhanced crystallographic and optical characteristics are applied in solar cells to achieve a champion efficiency of 24.53% with open circuit voltage of 1.172 V and fill factor of 82.78%. The bare device without any protection maintains 89% of its initial efficiency after 6600 h of aging in ambient environment. This work implies that the in situ observation using fluorescence microscopy is a critical for understanding of crystallization kinetics in film devices.

Altered connectivity in the cognitive control-related prefrontal cortex in Parkinson's disease with rapid eye movement sleep behavior disorder.

Rapid eye movement sleep behavior disorder (RBD) frequently occurs in Parkinson's disease (PD), however, the exact pathophysiological mechanism is not clear. The prefrontal cortex (PFC), especially ventrolateral prefrontal cortex (VLPFC), dorsolateral prefrontal cortex (DLPFC), and inferior frontal gyrus (IFG) which may play roles by regulating cognitive control processes. The purpose of this study was to investigate whether there is abnormal functional connectivity (FC) maps and volume changes in PD with RBD(PD-RBD). We recruited 20 PD-RBD, 20 PD without RBD (PD-nRBD), and 20 normal controls (NC). We utilized resting-state functional Magnetic Resonance Imaging (rs-MRI) to explore FC changes based on regions of interest (VLPFC, DLPFC, and IFG), and used voxel-based morphology technology to analyze whole-brain volumes by 3D-T1 structural MRI. Except the REM sleep behavioral disorders questionnaire (RBDSQ), the PD-RBD showed lower visuospatial/executive and attention scores than the NC group. The RBDSQ scores were significantly positively correlated with zFC of right DLPFC to bilateral posterior cingulate cortex (PCC) (P = 0.0362, R = 0.4708, AlphaSim corrected) and also significantly positively correlated with zFC of left VLPFC to right inferior temporal (P = 0.0157, R = 0.5323, AlphaSim corrected) in PD-RBD group. Furthermore, abnormal correlations with zFC values were also found in some cognitive subdomains in PD-RBD group. The study may suggest that in PD-RBD patients, the presence of RBD may be related to the abnormal FC of VLPFC and DLPFC, meanwhile, the abnormal FC of DLPFC and IFG may be related to the mechanisms of cognitive impairment.

Therapeutic targeting of FUBP3 phase separation by GATA2-AS1 inhibits malate-aspartate shuttle and neuroblastoma progression via modulating SUZ12 activity.

Malate-aspartate shuttle (MAS) is essential for maintaining glycolysis and energy metabolism in tumors, while its regulatory mechanisms in neuroblastoma (NB), the commonest extracranial malignancy during childhood, still remain to be elucidated. Herein, by analyzing multi-omics data, GATA binding protein 2 (GATA2) and its antisense RNA 1 (GATA2-AS1) were identified to suppress MAS during NB progression. Mechanistic studies revealed that GATA2 inhibited the transcription of glutamic-oxaloacetic transaminase 2 (GOT2) and malate dehydrogenase 2 (MDH2). As a long non-coding RNA destabilized by RNA binding motif protein 15-mediated N6-methyladenosine methylation, GATA2-AS1 bound with far upstream element binding protein 3 (FUBP3) to repress its liquid-liquid phase separation and interaction with suppressor of zest 12 (SUZ12), resulting in decrease of SUZ12 activity and epigenetic up-regulation of GATA2 and other tumor suppressors. Rescue experiments revealed that GATA2-AS1 inhibited MAS and NB progression via repressing interaction between FUBP3 and SUZ12. Pre-clinically, administration of lentivirus carrying GATA2-AS1 suppressed MAS, aerobic glycolysis, and aggressive behaviors of NB xenografts. Notably, low GATA2-AS1 or GATA2 expression and high FUBP3, SUZ12, GOT2 or MDH2 levels were linked with unfavorable outcome of NB patients. These findings suggest that GATA2-AS1 inhibits FUBP3 phase separation to repress MAS and NB progression via modulating SUZ12 activity.

Antihypertensive drugs may not delay the symptom progression of Parkinson's disease: A 2-year follow-up study.

Background: Parkinson's disease (PD) is one of the most common neurodegenerative disease, and half of PD patients have hypertension as well. The effect of antihypertensive drugs on the progression of PD has been less studied. The focus of this study was on the changes in dopamine transporter (DAT) levels to assess the effect of antihypertensive drugs on the progression of PD. Methods: Data from 321 drug-naïve patients from the Parkinson's Disease Progression Marker Initiative (PPMI) were collected over a 2-year period. Patients were divided into the PD with arterial hypertension (AH) group (102 cases) with antihypertensive drugs, the PD with other cardiovascular risk factors (CVRFs) group (60 cases) with antidiabetic and/or lipid-lowering drugs, and the pure PD group (159 cases) without CVRFs. The Movement Disorder Society Sponsored Revision Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Hoehn-Yahr (H&Y) stage were used to assess progression. DAT semiquantitative values were used to evaluate damage to dopaminergic neurons in the substantia nigra, including the contralateral and ipsilateral count density ratio and asymmetry index. Results: There were no significant differences among the three groups in MDS-UPDRS score and H&Y stage. Changes in DAT levels among the three groups were without distinct differences in the first year and second year. In each group, DAT decreased more in the first year than in the second year. There was no decrease in DAT uptake in the PD with AH group compared with the other groups during the follow-up period. Conclusions: There is no evidence that antihypertensive drugs can delay PD progression within 2 years.

A comprehensive analysis of the Bencao (herbal) small RNA Atlas reveals novel RNA therapeutics for treating human diseases.

Cross-kingdom herbal miRNA was first reported in 2012. Using a modified herbal extraction protocol, we obtained 73,677,287 sequences by RNA-seq from 245 traditional Chinese Medicine (TCM), of which 20,758,257 were unique sequences. We constructed a Bencao (herbal) small RNA (sRNA) Atlas ( http://bencao.bmicc.cn ), annotated the sequences by sequence-based clustering, and created a nomenclature system for Bencao sRNAs. The profiles of 21,757 miRNAs in the Atlas were highly consistent with those of plant miRNAs in miRBase. Using software tools, our results demonstrated that all human genes might be regulated by sRNAs from the Bencao sRNA Atlas, part of the predicted human target genes were experimentally validated, suggesting that Bencao sRNAs might be one of the main bioactive components of herbal medicines. We established roadmaps for oligonucleotide drugs development and optimization of TCM prescriptions. Moreover, the decoctosome, a lipo-nano particle consisting of 0.5%-2.5% of the decoction, demonstrated potent medical effects. We propose a Bencao (herbal) Index, including small-molecule compounds (SM), protein peptides (P), nucleic acid (N), non-nucleic and non-proteinogenic large-molecule compounds (LM) and elements from Mendeleev's periodic table (E), to quantitatively measure the medical effects of botanic medicine. The Bencao sRNA Atlas is a resource for developing gene-targeting oligonucleotide drugs and optimizing botanical medicine, and may provide potential remedies for the theory and practice of one medicine.

Understanding the impact of a non-ionic surfactant alkylphenol ethoxylate on surface-enhanced Raman spectroscopic analysis of pesticides on apple surfaces.

Pesticide active ingredients (AIs) are often applied with adjuvants to facilitate the stability and functionality of AIs in agricultural practice. The objective of this study is to investigate the role of a common non-ionic surfactant, alkylphenol ethoxylate (APEO), on the surface-enhanced Raman spectroscopic (SERS) analysis of pesticides as well as its impact on pesticide persistence on apple surfaces, as a model fresh produce surface. The wetted areas of two AIs (thiabendazole and phosmet) mixed with APEO were determined respectively to correct the unit concentration applied on apple surfaces for a fair comparison. SERS with gold nanoparticle (AuNP) mirror substrates was applied to measure the signal intensity of AIs with and without APEO on apple surfaces after a short-term (45 min) and a long-term (5 days) exposure. The limit of detection (LOD) of thiabendazole and phosmet using this SERS-based method were 0.861 ppm and 2.883 ppm, respectively. The result showed that APEO decreased the SERS signal for non-systemic phosmet, while increased SERS intensity of systemic thiabendazole on apple surfaces after 45 min pesticide exposure. After 5 days, the SERS intensity of thiabendazole with APEO was higher than thiabendazole alone, and there was no significant difference between phosmet with and without APEO. Possible mechanisms were discussed. Furthermore, a 1% sodium bicarbonate (NaHCO3) washing method was applied to test the impact of APEO on the persistence of the residues on apple surfaces after short-term and long-term exposures. The results indicated that APEO significantly enhanced the persistence of thiabendazole on plant surfaces after a 5-day exposure, while there was no significant impact on phosmet. The information obtained facilitates a better understanding of the impact of the non-ionic surfactant on SERS analysis of pesticide behavior on and in plants and helps further develop the SERS method for studying complex pesticide formulations in plant systems.

White matter hyperintensities burden in the frontal regions is positively correlated to the freezing of gait in Parkinson's disease.

Objective: Previous studies have reported that white matter hyperintensities (WMHs) are associated with freezing of gait (FOG), but it is not clear whether their distribution areas have correlations with FOG in Parkinson's disease (PD) and the potential influencing factors about WMHs. Methods: Two hundred and forty-six patients with PD who underwent brain MRI were included. Participants were divided into PD with FOG (n = 111) and PD without FOG (n = 135) groups. Scheltens score was used to assess the WMHs burden in the areas of deep white matter hyperintensities (DWMHs), periventricular hyperintensities (PVHs), basal ganglia hyperintensities (BGHs), and infratentorial foci of hyperintensities (ITF). Whole brain WMHs volume was evaluated by automatic segmentation. Binary logistic regression was used to evaluate relationships between WMHs and FOG. The common cerebrovascular risk factors that may affect WMHs were evaluated by mediation analysis. Results: There were no statistical differences between PD with and without FOG groups in whole brain WMHs volume, total Scheltens score, BGHs, and ITF. Binary logistic regression showed that the total scores of DWMHs (OR = 1.094; 95% CI, 1.001, 1.195; p = 0.047), sum scores of PVHs and DWMHs (OR = 1.080; 95% CI, 1.003, 1.164; p = 0.042), especially the DWMHs in frontal (OR = 1.263; 95% CI, 1.060, 1.505 p = 0.009), and PVHs in frontal caps (OR = 2.699; 95% CI, 1.337, 5.450; p = 0.006) were associated with FOG. Age, hypertension, and serum alkaline phosphatase (ALP) are positively correlated with scores of DWMHs in frontal and PVHs in frontal caps. Conclusion: These results indicate that WMHs distribution areas especially in the frontal of DWMHs and PVHs play a role in PD patients with FOG.

Therapeutic targeting of CNBP phase separation inhibits ribosome biogenesis and neuroblastoma progression via modulating SWI/SNF complex activity.

BACKGROUND: Neuroblastoma (NB) is the most common extracranial malignancy in childhood; however, the mechanisms underlying its aggressive characteristics still remain elusive. METHODS: Integrative data analysis was performed to reveal tumour-driving transcriptional regulators. Co-immunoprecipitation and mass spectrometry assays were applied for protein interaction studies. Real-time reverse transcription-polymerase chain reaction, western blotting, sequential chromatin immunoprecipitation and dual-luciferase reporter assays were carried out to explore gene expression regulation. The biological characteristics of NB cell lines were examined via gain- and loss-of-function assays. For survival analysis, the Cox regression model and log-rank tests were used. RESULTS: Cellular nucleic acid-binding protein (CNBP) was found to be an independent factor affecting NB outcome, which exerted oncogenic roles in ribosome biogenesis, tumourigenesis and aggressiveness. Mechanistically, karyopherin subunit beta 1 (KPNB1) was responsible for nuclear transport of CNBP, whereas liquid condensates of CNBP repressed the activity of switch/sucrose-nonfermentable (SWI/SNF) core subunits (SMARCC2/SMARCC1/SMARCA4) via interaction with SMARCC2, leading to alternatively increased activity of SMARCC1/SMARCA4 binary complex in facilitating gene expression essential for 18S ribosomal RNA (rRNA) processing in tumour cells, extracellular vesicle-mediated delivery of 18S rRNA and subsequent M2 macrophage polarisation. A cell-penetrating peptide blocking phase separation and interaction of CNBP with SMARCC2 inhibited ribosome biogenesis and NB progression. High KPNB1, CNBP, SMARCC1 or SMARCA4 expression or low SMARCC2 levels were associated with poor survival of NB patients. CONCLUSIONS: These findings suggest that CNBP phase separation is a target for inhibiting ribosome biogenesis and tumour progression in NB via modulating SWI/SNF complex activity.

Titanium Doping Induced the Suppression of Irreversible Phase Transformation at High Voltage for V-based Phosphate Cathodes of Na-Ion Batteries.

Polyanionic material, specifically the NASICON-type material, is considered a promising cathode material for Na-ion batteries (SIBs) because of its stable structure and high operating voltage. Further, it improves the energy density correlated with the well utilization of all Na in the compound. For Na3 V2 (PO4 )2 F3 (NVPF), the extraction of the third Na, reported as the electrochemical inactivated, can be realized at a high voltage region while forming an irreversible tetragonal phase. In this study, we introduce Ti doping to the Na2 VTi(PO4 )2 F3 (NVTPF) material; we reveal that the Ti-doped NVTPF could effectively suppress the irreversible phase transformation, thus successfully harnessing Na in a wide voltage range. Experimental study discloses that the Ti-substituted Na2 VTi(PO4 )2 F3 could take up the Na+ from Amam phase to Cmc21 phase between 1.0 V and 4.8 V reversibly accounting for the 2 Na+ transportation that shows favorable Na+ kinetics and structural stability. Our research provides the strategy to stabilize the polyanion structure upon charging at a high voltage range and inspires the utilization of full sodium in the polyanionic materials, which could be considered as a material design for future conventional applications.