Functionalized Thienopyrazines on NiOx Film as Self-Assembled Monolayer for Efficient Tin-Perovskite Solar Cells Using a Two-Step Method.

Three functionalized thienopyrazines (TPs), TP-MN (1), TP-CA (2), and TPT-MN (3) were designed and synthesized as self-assembled monolayers (SAMs) deposited on the NiOx film for tin-perovskite solar cells (TPSCs). Thermal, optical, electrochemical, morphological, crystallinity, hole mobility, and charge recombination properties, as well as DFT-derived energy levels with electrostatic surface potential mapping of these SAMs, have been thoroughly investigated and discussed. The structure of the TP-MN (1) single crystal was successfully grown and analyzed to support the uniform SAM produced on the ITO/NiOx substrate. When we used NiOx as HTM in TPSC, the device showed poor performance. To improve the efficiency of TPSC, we utilized a combination of new organic SAMs with NiOx HTM, the TPSC device exhibited the highest PCE of 7.7% for TP-MN (1). Hence, the designed NiOx/TP-MN (1) acts as a new model system for the development of efficient SAM-based TPSC. To the best of our knowledge, the combination of organic SAMs with anchoring CN/CN or CN/COOH groups, and NiOx HTM for TPSC has never been reported elsewhere. The TPSC device based on the NiOx/TP-MN bilayer exhibits great enduring stability for performance, retaining ~80% of its original value for shelf storage over 4000 h.

Regulation of primary cilia disassembly through HUWE1-mediated TTBK2 degradation plays a crucial role in cerebellar development and medulloblastoma growth.

Development of the cerebellum requires precise regulation of granule neuron progenitor (GNP) proliferation. Although it is known that primary cilia are necessary to support GNP proliferation, the exact molecular mechanism governing primary cilia dynamics within GNPs remains elusive. Here, we establish the pivotal roles for the centrosomal kinase TTBK2 (Tau tubulin kinase-2) and the E3 ubiquitin ligase HUWE1 in GNP proliferation. We show that TTBK2 is highly expressed in proliferating GNPs under Sonic Hedgehog (SHH) signaling, coinciding with active GNP proliferation and the presence of primary cilia. TTBK2 stabilizes primary cilia by inhibiting their disassembly, thereby promoting GNP proliferation in response to SHH. Mechanistically, we identify HUWE1 as a novel centrosomal E3 ligase that facilitates primary cilia disassembly by targeting TTBK2 degradation. Disassembly of primary cilia serves as a trigger for GNP differentiation, allowing their migration from the external granule layer (EGL) of the cerebellum to the internal granule layer (IGL) for subsequent maturation. Moreover, we have established a link between TTBK2 and SHH-type medulloblastoma (SHH-MB), a tumor characterized by uncontrolled GNP proliferation. TTBK2 depletion inhibits SHH-MB proliferation, indicating that TTBK2 may be a potential therapeutic target for this cancer type. In summary, our findings reveal the mechanism governing cerebellar development and highlight a potential anti-cancer strategy for SHH-MB.

Combining magnetic resonance fingerprinting with voxel-based morphometric analysis to reduce false positives for focal cortical dysplasia detection.

OBJECTIVE: We aim to improve focal cortical dysplasia (FCD) detection by combining high-resolution, three-dimensional (3D) magnetic resonance fingerprinting (MRF) with voxel-based morphometric magnetic resonance imaging (MRI) analysis. METHODS: We included 37 patients with pharmacoresistant focal epilepsy and FCD (10 IIa, 15 IIb, 10 mild Malformation of Cortical Development [mMCD], and 2 mMCD with oligodendroglial hyperplasia and epilepsy [MOGHE]). Fifty-nine healthy controls (HCs) were also included. 3D lesion labels were manually created. Whole-brain MRF scans were obtained with 1 mm3 isotropic resolution, from which quantitative T1 and T2 maps were reconstructed. Voxel-based MRI postprocessing, implemented with the morphometric analysis program (MAP18), was performed for FCD detection using clinical T1w images, outputting clusters with voxel-wise lesion probabilities. Average MRF T1 and T2 were calculated in each cluster from MAP18 output for gray matter (GM) and white matter (WM) separately. Normalized MRF T1 and T2 were calculated by z-scores using HCs. Clusters that overlapped with the lesion labels were considered true positives (TPs); clusters with no overlap were considered false positives (FPs). Two-sample t-tests were performed to compare MRF measures between TP/FP clusters. A neural network model was trained using MRF values and cluster volume to distinguish TP/FP clusters. Ten-fold cross-validation was used to evaluate model performance at the cluster level. Leave-one-patient-out cross-validation was used to evaluate performance at the patient level. RESULTS: MRF metrics were significantly higher in TP than FP clusters, including GM T1, normalized WM T1, and normalized WM T2. The neural network model with normalized MRF measures and cluster volume as input achieved mean area under the curve (AUC) of .83, sensitivity of 82.1%, and specificity of 71.7%. This model showed superior performance over direct thresholding of MAP18 FCD probability map at both the cluster and patient levels, eliminating ≥75% FP clusters in 30% of patients and ≥50% of FP clusters in 91% of patients. SIGNIFICANCE: This pilot study suggests the efficacy of MRF for reducing FPs in FCD detection, due to its quantitative values reflecting in vivo pathological changes. © 2024 International League Against Epilepsy.

Bicyclopentadithiophene-Based Organic Semiconductor for Stable and High-Performance Perovskite Solar Cells Exceeding 22.

Well-performing organic-inorganic halide perovskites are susceptible to poor efficiency and instability due to their various defects at the interphases, grain boundaries (GBs), and surfaces. In this study, an in situ method is utilized for effectively passivating the under-coordinated Pb2+ defects of perovskite with new non-fullerene acceptors (NFAs) (INXBCDT; X = H, Cl, and Br) through their carbonyl and cyano functional groups during the antisolvent dripping process. It reveals that the bicyclopentadithiophene (BCDT) core with highly electron-withdrawing end-capping groups passivates GBs and boosts perovskite grain growth. This effective defect passivation decreases the trap density to increase the carrier recombination lifetime of the perovskite film. As a result, bromo-substituted dicyanomethylene indanone (INBr)-end-capped BCDT (INBrBCDT-b8; 3a)-passivated devices exhibit the highest power conversion efficiency (PCE) of 22.20% (vs those of 18.09% obtained for perovskite films without passivation) upon an optimized film preparation process. Note that devices treated with more soluble 2-ethylhexyl-substituted compounds (1a, 2a, and 3a) exhibit higher PCE than those treated with less soluble octyl-substituted compounds (1b, 2b, and 3b). It is also worth noting that BCDT is a cost-effective six-ring core that is easier to synthesize with a higher yield and therefore much cheaper than those with highly fused-ring cores. In addition, a long-term stability test in a glovebox for 1500 h reveals that the perovskite solar cells (PSCs) based on a perovskite absorber treated with compound 3a maintain ∼90% of their initial PCE. This is the first example of the simplest high-conjugation additive for perovskite film to achieve a PCE greater than 22% of the corresponding lead-based PSCs.

Therapeutic effects of extracorporeal shock wave therapy on patients with spastic cerebral palsy and Rett syndrome: clinical and ultrasonographic findings.

BACKGROUND: Extracorporeal shock wave therapy (ESWT) is reportedly effective for improving spasticity and motor function in children with cerebral palsy (CP). Because late-stage Rett syndrome has a similar presentation, this study aimed to investigate the effects of ESWT on these two diseases. MATERIAL AND METHODS: Patients diagnosed with spastic CP and Rett syndrome received 1500 impulses of ESWT at 4 Hz and 0.1 mJ/mm2, on their spastic legsonce weekly for a total of 12 weeks. Outcomes were assessed before and 4 and 12 weeks after ESWT. Clinical assessments included the Modified Ashworth Scale (MAS), passive range of motion (PROM), and Gross Motor Function Measure 88 (GMFM-88). Ultrasonographic assessments included muscle thickness, acoustic radiation force impulse (ARFI), and strain elastography. RESULTS: Fifteen patients with CP and six with Rett syndrome were enrolled in this study. After ESWT, patients with CP showed significant clinical improvement in the MAS (P = 0.011), ankle PROM (P = 0.002), walking/running/jumping function (P = 0.003), and total function (P < 0.001) of the GMFM-88. The patients with Rett syndrome showed improved MAS scores (P = 0.061) and significantly improved total gross motor function (P = 0.030). Under ARFI, patients with CP demonstrated decreased shear wave speed in the gastrocnemius medial head (P = 0.038). Conversely, patients with Rett syndrome show increased shear-wave speeds after ESWT. CONCLUSION: Our study provides evidence that a weekly course of low-dose ESWT for 12 weeks is beneficial for children with both CP and Rett syndrome, with the clinical effects of reducing spasticity and improving the gross motor function of the lower limbs. The ARFI sonoelastography reveals improvement of muscle stiffness in patients with CP after ESWT, but deteriorated in patients with Rett syndrome. The diverse therapeutic response to ESWT may be caused by the MECP2 mutation in Rett syndrome, having a continuous impact and driving the pathophysiology differently as compared to CP, which is secondary to a static insult. Trial registration IRB 201700462A3. Registered 22March 2017, https://cghhrpms.cgmh.org.tw/HRPMS/Default.aspx .

Directed Self-Assembly of Oxide Nanocomposites by Ion-Beam Lithography.

Vertically aligned self-assembled nanocomposite films have provided a unique platform to study magnetoelectric effects and other forms of coupling between complex oxides. However, the distribution in the locations and sizes of the phase-separated nanostructures limits their utility. In this work, we demonstrate a process to template the locations of the self-assembled structure using ion lithography, which is effective for general insulating substrates. This process was used to produce a nanocomposite consisting of fin-shaped vertical nanostructures of ferroelectric BiFeO3 and ferrimagnetic CoFe2O4 with a feature size of 100 nm on (111)-oriented SrTiO3 substrates. Cross-sectional imaging of the three-phase perovskite-spinel-substrate epitaxial interface reveals the selective nucleation of CoFe2O4 in the trenches of the patterned substrate, and the magnetic domains of CoFe2O4 were manipulated by applying an external magnetic field.

Feasibility of ketogenic diet therapy variants for refractory epilepsy in neonates to infants under 2 years old.

BACKGROUND: Ketogenic diet Therapy (KDT) has been reported as a possible beneficial management strategy for controlling seizures in infants aged <2 years, but the safety and efficacy of this therapy remain to be investigated. We investigated the achievability, tolerability, efficacy, and safety of KDT for patients under 2 years old. MATERIALS AND METHODS: Infants younger than 2 years old with pharmacoresistant epilepsy were enrolled in this prospective study. We divided cases into three age groups: I) neonates; II) infants aged 1-12 months; III) infants aged 12-24 months. KDT initiation protocol were administration through parenteral route, enteral route or oral feeding. Seizure reduction rate, physical growth, and adverse effects were assessed at monthly visit. RESULTS: Thirteen patients who completed 6 months of KDT were recruited. There was one neonate in group I, 9 infants in group II, and 3 infants in group III. Eleven of them (11/13, 84.6%) were responders to KDT. All infants with underlying genetic etiology were seizure free after treating with KDT. The starting keto ratio was 1.1 mmol/L in group I, 2.3 mmol/L in group II, and 2.8 mmol/L in group III, which gradually approached 3:1-4:1 over 5-7 days. There were no symptomatic adverse effects or growth retardation in any of the study subjects. CONCLUSIONS: KDT is a promising alternative therapy with high feasibility, safety, and efficacy for pharmacoresistant epilepsy in infants under 2 years old, especially for those with genetic etiology. The starting keto ratio should be lower, and the keto ratio titration period should be longer than for children older than 2 years.

Porous Core-membrane Microstructured Nanomaterial Composed of Deep Eutectic Solvents and MOF-808 for CO2 Capture.

A series of porous core-membrane microstructured nanomaterials, constructed of a deep eutectic solvent (DES) membrane and porous MOF-808 core via liquid surface tensions and electrostatic interactions, are introduced for carbon dioxide capture with the sorption mechanism coupling diffusion, physisorption, and chemisorption. MOF-808 as the porous core considerably improves the diffusion interactions for DES membranes, hence significantly enhancing the sorption performance of DESs. Although the DES consisted by monoethanolamine and tetrapropylammonium chloride (MEA-TPAC-7) has the highest sorption capacity among all DESs, it is only 4.39 mmol g-1 at 2.4 bar and further attenuates by fastidious diffusion interactions when increasing viscosity or dose. The sorption capacities of DES@MOF-120 are 5.18 mmol g-1 at 3.0 bar and 4.78 mmol g-1 at 2.4 bar without apparent sorption hysteresis in pressure swing sorption, which are substantially improved contrasted to MEA-TPAC-7. The sorption isotherms are reconstructed via Sips models considering surface heterogeneity with regression correlation coefficients over 0.9454 to forecast maximum sorption capacity over 6.33 mmol g-1 .

Reversible Morphology Locking via Metal Infiltration in a Block Copolymer.

Metal infiltration from an acid solution of a metal precursor into the poly(2-vinylpyridine) (P2VP) microdomains of a polystyrene-b-P2VP block copolymer is shown to reduce the uptake of solvent vapor during a subsequent solvent annealing process, locking the morphology of the self-assembled microdomains. The amount of metal, here Pt, incorporated into the P2VP increases with both metal precursor [PtCl4]2- and hydrochloric acid concentrations, reaching 0.83 Pt atom per pyridine unit. The metal is then exfiltrated using a KOH + ethylenediaminetetraacetic acid disodium salt dihydrate (Na2EDTA) complexing solution, which restores solvent uptake and unlocks the morphology. The reversibility of the metal infiltration and morphology locking is demonstrated in a multistage annealing process and is confirmed for Fe as well as Pt. Reversible locking and unlocking of block copolymer microdomain morphologies expand their utility for nanofabrication processes by allowing the morphology to be fixed during subsequent process steps.

Emergence of layered nanoscale mesh networks through intrinsic molecular confinement self-assembly.

Block copolymer self-assembly is a powerful tool for two-dimensional nanofabrication; however, the extension of this self-assembly concept to complex three-dimensional network structures is limited. Here we report a simple method to experimentally generate three-dimensional layered mesh morphologies through intrinsic molecular confinement self-assembly. We designed triblock bottlebrush polymers with two Janus domains: one perpendicular and one parallel to the polymer backbone. The former enforces a lamellar superstructure that intrinsically confines the intralayer self-assembly of the latter, giving rise to a mesh-like monoclinic (54°) M15 network substructure with excellent long-range order, as well as a tetragonal (90°) T131 mesh. Numerical simulations show that the spatial constraints exerted on the polymer backbone drive the assembly of M15 and yield T131 in the strong segregation regime. This work demonstrates that intrinsic molecular confinement is a viable path to bottom-up assembly of new geometrical phases of soft matter, extending the capabilities of block copolymer nanofabrication.

Evaluating whole-brain tissue-property changes in MRI-negative pharmacoresistant focal epilepsies using MR fingerprinting.

OBJECTIVE: We aim to quantify whole-brain tissue-property changes in patients with magnetic resonance imaging (MRI)-negative pharmacoresistant focal epilepsy by three-dimensional (3D) magnetic resonance fingerprinting (MRF). METHODS: We included 30 patients with pharmacoresistant focal epilepsy and negative MRI by official radiology report, as well as 40 age- and gender-matched healthy controls (HCs). MRF scans were obtained with 1 mm3 isotropic resolution. Quantitative T1 and T2 relaxometry maps were reconstructed from MRF and registered to the Montreal Neurological Institute (MNI) space. A two-sample t test was performed in Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library (FSL) to evaluate significant abnormalities in patients comparing to HCs, with correction by the threshold-free cluster enhancement (TFCE) method. Subgroups analyses were performed for extra-temporal epilepsy/temporal epilepsy (ETLE/TLE), and for those with/without subtle abnormalities detected by morphometric analysis program (MAP), to investigate each subgroup's pattern of MRF changes. Correlation analyses were performed between the mean MRF values in each significant cluster and seizure-related clinical variables. RESULTS: Compared to HCs, patients exhibited significant group-level T1 increase ipsilateral to the epileptic origin, in the mesial temporal gray matter (GM) and white matter (WM), temporal pole GM, orbitofrontal GM, hippocampus, and amygdala, with scattered clusters in the neocortical temporal and insular GM. No significant T2 changes were detected. The ETLE subgroup showed a T1-increase pattern similar to the overall cohort, with additional involvement of the ipsilateral anterior cingulate GM. The subgroup of MAP+ patients also showed a T1-increase pattern similar to the overall cohort, with additional cluster in the ipsilateral lateral orbitofrontal GM. Higher T1 was associated with younger seizure-onset age, longer epilepsy duration, and higher seizure frequency. SIGNIFICANCE: MRF revealed group-level T1 increase in limbic/paralimbic structures ipsilateral to the epileptic origin, in patients with pharmacoresistant focal epilepsy and no apparent lesions on MRI, suggesting that these regions may be commonly affected by seizures in the epileptic brain. The significant association between T1 increase and higher seizure burden may reflect progressive tissue damage.

Normative quantitative relaxation atlases for characterization of cortical regions using magnetic resonance fingerprinting.

Quantitative magnetic resonance (MR) has been used to study cyto- and myelo-architecture of the human brain non-invasively. However, analyzing brain cortex using high-resolution quantitative MR acquisition can be challenging to perform using 3T clinical scanners. MR fingerprinting (MRF) is a highly efficient and clinically feasible quantitative MR technique that simultaneously provides T1 and T2 relaxation maps. Using 3D MRF from 40 healthy subjects (mean age = 25.6 ± 4.3 years) scanned on 3T magnetic resonance imaging, we generated whole-brain gyral-based normative MR relaxation atlases and investigated cortical-region-based T1 and T2 variations. Gender and age dependency of T1 and T2 variations were additionally analyzed. The coefficient of variation of T1 and T2 for each cortical-region was 3.5% and 7.3%, respectively, supporting low variability of MRF measurements across subjects. Significant differences in T1 and T2 were identified among 34 brain regions (P < 0.001), lower in the precentral, postcentral, paracentral lobule, transverse temporal, lateral occipital, and cingulate areas, which contain sensorimotor, auditory, visual, and limbic functions. Significant correlations were identified between age and T1 and T2 values. This study established whole-brain MRF T1 and T2 atlases of healthy subjects using a clinical 3T scanner, which can provide a quantitative and region-specific baseline for future brain studies and pathology detection.

Graph Theory-Based Electroencephalographic Connectivity via Phase-Locking Value and Its Association with Ketogenic Diet Responsiveness in Patients with Focal Onset Seizures.

Ketogenic diets (KDs) are a promising alternative therapy for pediatric refractory epilepsy. Several predictors of KD responsiveness have been identified, including biochemical parameters, seizure types, and electroencephalography (EEG) examinations. We hypothesized that graph theory-based EEG functional connectivity could explain KD responses in patients presenting focal onset seizure (FOS). A total of 17 patients aged 0-30 years old with focal onset seizures (FOS) were recruited as a study group between January 2015 and July 2021. Twenty age-matched children presenting headache with no intracranial complications nor other medical issues were enrolled as a control group. Data were obtained at baseline and at 12 months after initiating KD therapy (KDT) using the child behavior checklist (CBCL) and brain functional connectivity parameters based on phase-locking value from 19 scalp EEG signals, including nodal strength, global efficiency, clustering coefficient, and betweenness centrality. Compared with age-matched controls, patients presenting FOS with right or bilateral EEG lateralization presented higher baseline functional connectivity, including parameters such as global efficiency, mean cluster coefficient and mean nodal strength in the delta and beta frequency bands. In patients presenting FOS with right or bilateral EEG lateralization, the global efficiency of functional connectivity parameters in the delta and theta frequency bands was significantly lower at 12 months after KDT treatment than before KDT. Those patients also presented a significantly lower mean clustering coefficient and mean nodal strength in the theta frequency band at 12 months after KDT treatment. Changes in brain functional connectivity were positively correlated with social problems, attention, and behavioral scores based on CBCL assessments completed by parents. This study provides evidence that KDT might be beneficial in the treatment of patients with FOS. Graph theoretic analysis revealed that the observed effects were related to decreased functional connectivity, particularly in terms of global efficiency. Our findings related to brain connectivity revealed lateralization to the right (non-dominant) hemisphere; however, we were unable to define the underlying mechanism. Our data revealed that in addition to altered brain connectivity, KDT improved the patient's behavior and emotional state.

Black Line Sign in Focal Cortical Dysplasia IIB: A 7T MRI and Electroclinicopathologic Study.

BACKGROUND AND OBJECTIVES: We aim to provide detailed imaging-electroclinicopathologic characterization of the black line sign, a novel MRI marker for focal cortical dysplasia (FCD) IIB. METHODS: 7T T2*-weighted gradient-echo (T2*w-GRE) images were retrospectively reviewed in a consecutive cohort of patients with medically intractable epilepsy with pathology-proven FCD II, for the occurrence of the black line sign. We examined the overlap between the black line region and the seizure-onset zone (SOZ) defined by intracranial EEG (ICEEG) and additionally assessed whether complete inclusion of the black line region in the surgical resection was associated with postoperative seizure freedom. The histopathologic specimen was aligned with the MRI to investigate the pathologic underpinning of the black line sign. Region-of-interest-based quantitative MRI (qMRI) analysis on the 7T T1 map was performed in the black line region, entire lesional gray matter (GM), and contralateral/ipsilateral normal gray and white matter (WM). RESULTS: We included 20 patients with FCD II (14 IIB and 6 IIA). The black line sign was identified in 12/14 (85.7%) of FCD IIB and 0/6 of FCD IIA on 7T T2*w-GRE. The black line region was highly concordant with the ICEEG-defined SOZ (5/7 complete and 2/7 partial overlap). Seizure freedom was seen in 8/8 patients whose black line region was completely included in the surgical resection; in the 2 patients whose resection did not completely include the black line region, both had recurring seizures. Inclusion of the black line region in the surgical resection was significantly associated with seizure freedom (p = 0.02). QMRI analyses showed that the T1 mean value of the black line region was significantly different from the WM (p < 0.001), but similar to the GM. Well-matched histopathologic slices in one case revealed accumulated dysmorphic neurons and balloon cells in the black line region. DISCUSSION: The black line sign may serve as a noninvasive marker for FCD IIB. Both MRI-pathology and qMRI analyses suggest that the black line region was an abnormal GM component within the FCD. Being highly concordant with ICEEG-defined SOZ and significantly associated with seizure freedom when included in resection, the black line sign may contribute to the planning of ICEEG/surgery of patients with medically intractable epilepsy with FCD IIB. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in individuals with intractable focal epilepsy undergoing resection who have a 7T MRI with adequate image quality, the presence of the black line sign may suggest FCD IIB, be concordant with SOZ from ICEEG, and be associated with more seizure freedom if fully included in resection.

Characterizing thalamic and basal ganglia nuclei in medically intractable focal epilepsy by MR fingerprinting.

OBJECTIVES: Magnetic resonance fingerprinting (MRF) is a novel, quantitative, and noninvasive technique to measure brain tissue properties. We aim to use MRF for characterizing normal-appearing thalamic and basal ganglia nuclei in the epileptic brain. METHODS: A three-dimensional (3D) MRF protocol (1 mm3 isotropic resolution) was acquired from 48 patients with unilateral medically intractable focal epilepsy and 39 healthy controls (HCs). Whole-brain T1 and T2 maps (containing T1 and T2 relaxation times) were reconstructed for each subject. Ten subcortical nuclei in the thalamus and basal ganglia were segmented as regions of interest (ROIs), within which the mean T1 and T2 values, as well as their coefficient of variation (CV) were compared between the patients and HCs at the group level. Subgroup and correlation analyses were performed to examine the relationship between significant MRF measures and various clinical characteristics. Using significantly abnormal MRF measures from the group-level analyses, support vector machine (SVM) and logistic regression machine learning models were built and tested with 5-fold and 10-fold cross-validations, to separate patients from HCs, and to separate patients with left-sided and right-sided epilepsy, at the individual level. RESULTS: MRF revealed increased T1 mean value in the ipsilateral thalamus and nucleus accumbens; increased T1 CV in the bilateral thalamus, bilateral pallidum, and ipsilateral caudate; and increased T2 CV in the ipsilateral thalamus in patients compared to HCs (p < .05, false discovery rate [FDR] corrected). The SVM classifier produced 78.2% average accuracy to separate individual patients from HCs, with an area under the curve (AUC) of 0.83. The logistic regression classifier produced 67.4% average accuracy to separate patients with left-sided and right-sided epilepsy, with an AUC of 0.72. SIGNIFICANCE: MRF revealed bilateral tissue-property changes in the normal-appearing thalamus and basal ganglia, with ipsilateral predominance and thalamic preference, suggesting subcortical involvement/impairment in patients with medically intractable focal epilepsy. The individual-level performance of the MRF-based machine-learning models suggests potential opportunities for predicting lateralization.

Comparison of the treatment efficacy of umbilical mesenchymal stem cell transplantation via renal subcapsular and parenchymal routes in AKI-CKD mice.

BACKGROUND: Mesenchymal stem cells (MSCs) have emerged as a promising cell-based therapy for acute kidney injury (AKI). However, the optimal route of MSC transplantation remains controversial, and there have been no comparisons of the therapeutic benefits of MSC administration through different delivery routes. METHODS: In this study, we encapsulated MSCs into a collagen matrix to help achieve local MSC retention in the kidney and assessed the survival of MSCs in vitro and in vivo. After transplanting collagen matrix-encapsulated-MSCs (Col-MSCs) under the renal capsule or into the parenchyma using the same cell dose and suspension volume in an ischemia/reperfusion injury model, we evaluated the treatment efficacy of two local transplantation routes at different stages of AKI. RESULTS: We found that Col-MSCs could be retained in the kidney for at least 14 days. Both local MSC therapies could reduce tubular injury, promote the proliferation of renal tubular epithelial cells on Day 3 and alleviate renal fibrosis on Day 14 and 28. MSC transplantation via the subcapsular route exerts better therapeutic effects for renal functional and structural recovery after AKI than MSC administration via the parenchymal route. CONCLUSIONS: Subcapsular MSC transplantation may be an ideal route of MSC delivery for AKI treatment, and collagen I can provide a superior microenvironment for cell-cell and cell-matrix interactions to stabilize the retention rate of MSCs in the kidney.

TFEB- and TFE3-dependent autophagy activation supports cancer proliferation in the absence of centrosomes.

Centrosome amplification is a phenomenon frequently observed in human cancers, so centrosome depletion has been proposed as a therapeutic strategy. However, despite being afflicted with a lack of centrosomes, many cancer cells can still proliferate, implying there are impediments to adopting centrosome depletion as a treatment strategy. Here, we show that TFEB- and TFE3-dependent autophagy activation contributes to acentrosomal cancer proliferation. Our biochemical analyses uncover that both TFEB and TFE3 are novel PLK4 (polo like kinase 4) substrates. Centrosome depletion inactivates PLK4, resulting in TFEB and TFE3 dephosphorylation and subsequent promotion of TFEB and TFE3 nuclear translocation and transcriptional activation of autophagy- and lysosome-related genes. A combination of centrosome depletion and inhibition of the TFEB-TFE3 autophagy-lysosome pathway induced strongly anti-proliferative effects in cancer cells. Thus, our findings point to a new strategy for combating cancer.Abbreviations: AdCre: adenoviral Cre recombinase; AdLuc: adenoviral luciferase; ATG5: autophagy related 5; CQ: chloroquine; DAPI: 4',6-diamidino-2-phenylindole; DKO: double knockout; GFP: green fluorescent protein; KO: knockout; LAMP1: lysosomal associated membrane protein 1; LAMP2: lysosomal associated membrane protein 2; LTR: LysoTracker Red; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MITF: melanocyte inducing transcription factor; PLK4: polo like kinase 4; RFP: red fluorescent protein; SASS6: SAS-6 centriolar assembly protein; STIL: STIL centriolar assembly protein; TFEB: transcription factor EB; TFEBΔNLS: TFEB lacking a nuclear localization signal; TFE3: transcription factor binding to IGHM enhancer 3; TP53/p53: tumor protein p53.

The experience of caregivers of chronically ill patients during the COVID-19: A Systematic Review.

OBJECTIVES: This study aimed to identify the difficulties that caregivers of chronically ill patients experienced during the COVID-19 pandemic and to provide directions for future studies. METHODS: Five electronic databases, including PubMed, Web of Science, CINAHL Plus Full Text, EMBASE, and Scopus, were systematically searched from January 2019 to February 2021. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were employed for the literature screening, inclusion, and exclusion. The Mixed Methods Appraisal Tool was adopted for qualifying appraisal. RESULTS: Six studies met the study criteria, including three quantitative studies, two qualitative studies, and one mixed-method study. Mental health, personal experience, financial problems, physical health, and improvement approaches were the major five themes that participants reported regarding the impact of COVID-19 they encountered during the pandemic. DISCUSSION: The results could heighten healthcare providers, stakeholders, and policy leaders' awareness of providing appropriate support for caregivers. Future research incorporating programs that support caregivers' needs is recommended.

Early Life Factors Associated with Preschool Wheezing in Preterm Infants.

Advanced neonatal care has increased the survival of neonates born prematurely, and prematurity is a well-known risk factor for asthma/wheezing disorders. Thus, this prospective study aimed to determine the early life factors associated with preschool wheezing in premature neonates. Preterm neonates born between 2012 and 2017 were recruited, excluding those with bacterial infection within 7 days of life, maternal sepsis, and maternal chorioamnionitis. Birth and admission history, comorbidities, and maternal history were documented. Respiratory problems were followed-up at the neonatal outpatient department. Patients were divided into wheezing and non-wheezing groups. Data were analyzed using the Mann-Whitney test and Fisher's exact test, and multivariable logistic regression was used to define the risk factors of preschool wheezing/asthma. A total of 125 preterm infants were enrolled, including 19 in the wheezing group and 106 in the non-wheezing group. Patients in the wheezing group had longer duration of intubation (p = 0.025), higher rates for exclusive breast milk feeding (p = 0.012), and higher re-hospitalization rates for respiratory tract infections (p < 0.001), especially for respiratory syncytial virus (RSV) bronchiolitis (p = 0.045). The incidence of allergic rhinitis was also higher in the wheezing group (p = 0.005). After multivariable logistic regression, allergic rhinitis and re-hospitalization for respiratory tract infections were two significant risk factors for preschool wheezing/asthma in premature neonates. Close follow-up of premature infants at high risk for asthma susceptibility is recommended.

An antisite defect mechanism for room temperature ferroelectricity in orthoferrites.

Single-phase multiferroic materials that allow the coexistence of ferroelectric and magnetic ordering above room temperature are highly desirable, motivating an ongoing search for mechanisms for unconventional ferroelectricity in magnetic oxides. Here, we report an antisite defect mechanism for room temperature ferroelectricity in epitaxial thin films of yttrium orthoferrite, YFeO3, a perovskite-structured canted antiferromagnet. A combination of piezoresponse force microscopy, atomically resolved elemental mapping with aberration corrected scanning transmission electron microscopy and density functional theory calculations reveals that the presence of YFe antisite defects facilitates a non-centrosymmetric distortion promoting ferroelectricity. This mechanism is predicted to work analogously for other rare earth orthoferrites, with a dependence of the polarization on the radius of the rare earth cation. Our work uncovers the distinctive role of antisite defects in providing a mechanism for ferroelectricity in a range of magnetic orthoferrites and further augments the functionality of this family of complex oxides for multiferroic applications.