Clinical Comparison between HD-tDCS and tDCS for Improving Upper Limb Motor Function: A Randomized, Double-Blinded, Sham-Controlled Trial.

Background: Stroke is a common and frequently occurring disease among middle-aged and elderly people, with approximately 55%-75% of patients remaining with upper limb dysfunction. How to promote the recovery of motor function at an early stage is crucial to the life of the patient. Objectives: This study aimed to investigate whether high-definition transcranial direct current stimulation (HD-tDCS) of the primary motor cortex (M1) functional area in poststroke patients in the subacute phase is more effective in improving upper limb function than conventional tDCS. Methods: This randomized, sham-controlled clinical trial included 69 patients with subcortical stroke. They were randomly divided into the HD-tDCS, anodal tDCS (a-tDCS), and sham groups. Each group received 20 sessions of stimulation. The patients were assessed using the Action Research Arm Test, Fugl-Meyer score for upper extremities, Motor Function Assessment Scale, and modified Barthel index (MBI) pretreatment and posttreatment. Results: The intragroup comparison scores improved after 4 weeks of treatment. The HD-tDCS group showed a slightly greater, but nonsignificant improvement as compared to a-tDCS group in terms of mean change observed in function of trained items. The MBI score of the HD-tDCS group was maintained up to 8 weeks of follow-up and was higher than that in the a-tDCS group. Conclusion: Both HD-tDCS and a-tDCS can improve upper limb motor function and daily activities of poststroke patients in the subacute stage. This trial is registered with ChiCTR2000031314.

Metal-Organic Frameworks with a Bioinspired Porous Polymer Coating for Sieving Separation.

Polymer/metal-organic framework (MOF) composites have been widely studied for their favorable combination of polymer flexibility and MOF crystallinity. While traditional polymer-coated MOFs maximize the polymer properties at the surface, the dramatic loss of MOF porosity due to blockage by the nonporous polymeric coating remains a problem. Herein, we introduce intrinsically microporous synthetic allomelanin (AM) as a porous coating on the zirconium-based MOF (Zr-MOF) UiO-66 via an in situ surface-constrained oxidative polymerization of the AM precursor, 1,8-dihydroxynaphthalene (1,8-DHN). Transmission electron microscopy images verify the formation of well-defined nanoparticles with a core-shell morphology (AM@UiO-66), and nitrogen sorption isotherms indicate the porosity of the UiO-66 core remains constant and is not disturbed by the AM coating. Notably, such a strategy could be adapted to MOFs with larger pores, such as MOF-808 by generating porous AM polymer coatings from bulkier DHN oligomers, highlighting the versatility of this method. Finally, we showed that by tuning the AM coating thickness on UiO-66, the hierarchically porous structures of these AM@UiO-66 composites engender excellent hexane isomer separation selectivity and storage capacity.

Evidence of a Uranium-Paddlewheel Node in a Catecholate-Based Metal-Organic Framework.

The interactions between uranium and non-innocent organic species are an essential component of fundamental uranium redox chemistry. However, they have seldom been explored in the context of multidimensional, porous materials. Uranium-based metal-organic frameworks (MOFs) offer a new angle to study these interactions, as these self-assembled species stabilize uranium species through immobilization by organic linkers within a crystalline framework, while potentially providing a method for adjusting metal oxidation state through coordination of non-innocent linkers. We report the synthesis of the MOF NU-1700, assembled from U4+ -paddlewheel nodes and catecholate-based linkers. We propose this highly unusual structure, which contains two U4+ ions in a paddlewheel built from four linkers-a first among uranium materials-as a result of extensive characterization via powder X-ray diffraction (PXRD), sorption, transmission electron microscopy (TEM), and thermogravimetric analysis (TGA), in addition to density functional theory (DFT) calculations.

Rapid Generation of Metal-Organic Framework Phase Diagrams by High-Throughput Transmission Electron Microscopy.

Metal-organic frameworks (MOFs) constructed from Zr6 nodes and tetratopic carboxylate linkers display high structural diversity and complexity in which various crystal topologies can result from identical building units. To determine correlations between MOF topologies and experimental parameters, such as solvent choice or modulator identity and concentration, we demonstrate the rapid generation of phase diagrams for Zr6-MOFs with 1,4-dibromo-2,3,5,6-tetrakis(4-carboxyphenyl)benzene linkers under a variety of conditions. We have developed a full set of methods for high-throughput transmission electron microscopy (TEM), including automated sample preparation and data acquisition, to accelerate MOF characterization. The use of acetic acid as a modulator yields amorphous, NU-906, NU-600, and mixed-phase structures depending on the ratio of N,N-dimethylformamide to N,N-diethylformamide solvent and the quantity of the modulator. Notably, the use of formic acid as a modulator enables direct control of crystal growth along the c direction through variation of the modulator quantity, thus realizing aspect ratio control of NU-1008 crystals with different catalytic hydrolysis performance toward a nerve agent simulant.

Catalytic Degradation of Polyethylene Terephthalate Using a Phase-Transitional Zirconium-Based Metal-Organic Framework.

Polyethylene terephthalate (PET) is utilized as one of the most popular consumer plastics worldwide, but difficulties associated with recycling PET have generated a severe environmental crisis with most PET ending its lifecycle in landfills. We report that zirconium-based metal-organic framework (Zr-MOF) UiO-66 deconstructs waste PET into the building blocks terephthalic acid (TA) and mono-methyl terephthalate (MMT) within 24 hours at 260 °C (total yield of 98 % under 1 atm H2 and 81 % under 1 atm Ar). Extensive structural characterization studies reveal that during the degradation process, UiO-66 undergoes an intriguing transformation into MIL-140A, which is another Zr-MOF that shows good catalytic activity toward PET degradation under similar reaction conditions. These results illustrate the diversity of applications for Zr-MOFs and establish MOFs as a new class of polymer degradation catalysts with the potential to address long-standing challenges associated with plastic waste.

Heterometallic CeIV/ VV Oxo Clusters with Adjustable Catalytic Reactivities.

Heterometallic CeIV/M oxo clusters are underexplored yet and can benefit from synergistic properties from combining cerium and other metal cations to produce efficient redox catalysts. Herein, we designed and synthesized a series of new Ce12V6 oxo clusters with different capping ligands: Ce12V6-SO4, Ce12V6-OTs (OTs: toluenesulfonic acid), and Ce12V6-NBSA (NBSA: nitrobenzenesulfonic acid). Single crystal X-ray diffraction (SCXRD) for all three structures reveals a Ce12V6 cubane core formulated [Ce12(VO)6O24]18+ with cerium on the edges of the cube, vanadyl capping the faces, and sulfate on the corners. While infrared spectroscopy (IR), ultraviolet-visible spectroscopy (UV-vis), electrospray ionization mass spectrometry (ESI-MS), and proton nuclear magnetic resonance (1H NMR) proved the successful coordination of the organic ligands to the Ce12V6 core, liquid phase 51V NMR and small-angle X-ray scattering (SAXS) confirmed the integrity of the clusters in the organic solutions. Furthermore, functionalization of the Ce12V6 core with organic ligands both provides increased solubility in term of homogeneous application and introduces porosity to the assemblies of Ce12V6-OTs and Ce12V6-NBSA in term of heterogeneous application, thus allowing more catalytic sites to be accessible and improving reactivity as compared to the nonporous and less soluble Ce12V6-SO4. Meanwhile, the coordinated ligands also influenced the electronic environment of the catalytic sites, in turn affecting the reactivity of the cluster, which we probed by the selective oxidation of 2-chloroethyl ethyl sulfide (CEES). This work provides a strategy to make full use of the catalytic sites within a class of inorganic sulfate capped clusters via organic ligand introduction.

Transient Catenation in a Zirconium-Based Metal-Organic Framework and Its Effect on Mechanical Stability and Sorption Properties.

Interpenetration of two or more sublattices is common among many metal-organic frameworks (MOFs). Herein, we study the evolution of one zirconium cluster-based, 3,8-connected MOF from its non-interpenetrated (NU-1200) to interpenetrated (STA-26) isomer. We observe this transient catenation process indirectly using ensemble methods, such as nitrogen porosimetry and X-ray diffraction, and directly, using high-resolution transmission electron microscopy. The approach detailed here will serve as a template for other researchers to monitor the interpenetration of their MOF samples at the bulk and single-particle limits. We investigate the mechanical stability of both lattices experimentally by pressurized in situ X-ray diffraction and nanoindentation as well as computationally with density functional theory calculations. Both lines of study reveal that STA-26 is considerably more mechanically stable than NU-1200. We conclude this study by demonstrating the potential of these MOFs and their mixed phases for the capture of gaseous n-hexane, used as a structural mimic for the chemical warfare agent sulfur mustard gas.

Anisotropic Synthetic Allomelanin Materials via Solid-State Polymerization of Self-Assembled 1,8-Dihydroxynaphthalene Dimers.

Melanosomes in nature have diverse morphologies, including spheres, rods, and platelets. By contrast, shapes of synthetic melanins have been almost entirely limited to spherical nanoparticles with few exceptions produced by complex templated synthetic methods. Here, we report a non-templated method to access synthetic melanins with a variety of architectures including spheres, sheets, and platelets. Three 1,8-dihydroxynaphthalene dimers (4-4', 2-4' and 2-2') were used as self-assembling synthons. These dimers pack to form well-defined structures of varying morphologies depending on the isomer. Specifically, distinctive ellipsoidal platelets can be obtained using 4-4' dimers. Solid-state polymerization of the preorganized dimers generates polymeric synthetic melanins while maintaining the initial particle morphologies. This work provides a new route to anisotropic synthetic melanins, where the building blocks are preorganized into specific shapes, followed by solid-state polymerization.

STAT3 controls osteoclast differentiation and bone homeostasis by regulating NFATc1 transcription.

The transcription factor signal transducer and activator of transcription 3 (STAT3) plays a central role in cell survival and function. STAT3 has been demonstrated to participate in the maintenance of bone homeostasis in osteoblasts, but its role in osteoclasts in vivo remains poorly defined. Here, we generated a conditional knockout mouse model in which Stat3 was deleted in osteoclasts using a cathepsin K-Cre (Ctsk-Cre) driver. We observed that osteoclast-specific Stat3 deficiency caused increased bone mass in mice, which we attributed to impaired bone catabolism by osteoclasts. Stat3-deficient bone marrow macrophages (BMMs) showed decreased expression of nuclear factor of activated T cells, cytoplasm 1 (NFATc1), and reduced osteoclast differentiation determined by decreases in osteoclast number, tartrate-resistant acid phosphatase activity, and expression of osteoclast marker genes. Enforced expression of NFATc1 in Stat3-deficient BMMs rescued the impaired osteoclast differentiation. Mechanistically, we revealed that STAT3 could drive the transcription of NFATc1 by binding to its promoter. Furthermore, preventing STAT3 activation by using an inhibitor of upstream phosphorylases, AG490, also impaired osteoclast differentiation and formation in a similar way as gene deletion of Stat3 In summary, our data provide the first evidence that STAT3 is significant in osteoclast differentiation and bone homeostasis in vivo, and it may be identified as a potential pharmacological target for the treatment of bone metabolic diseases through regulation of osteoclast activity.

Insights into the Structure and Dynamics of Metal-Organic Frameworks via Transmission Electron Microscopy.

Metal-organic frameworks (MOFs) are hybrid materials composed of metal ions and organic linkers featuring high porosity, crystallinity, and chemical tunability at multiple length scales. A recent advancement in transmission electron microscopy (TEM) and its direct application to MOF structure-property relationships have changed how we consider rational MOF design and development. Herein, we provide a perspective on TEM studies of MOFs and highlight the utilization of state-of-the-art TEM technologies to explore dynamic MOF processes and host-guest interactions. Additionally, we provide thoughts on what the future holds for TEM in the study of MOFs.

Phase Transitions in Metal-Organic Frameworks Directly Monitored through In Situ Variable Temperature Liquid-Cell Transmission Electron Microscopy and In Situ X-ray Diffraction.

Zr6-based metal-organic frameworks (MOFs) with tetratopic organic linkers have been extensively investigated owing to their versatile structural tunability. While diverse topologies and polymorphism in the resulting MOFs are often encountered with tetratopic linkers and Zr6 nodes, reports on phase transitions within these systems are rare. Thus, we have a limited understanding of polymorph transformations, hindering the rational development of pure phase materials. In this study, a phase transition from a microporous MOF, scu-NU-906, to a mesoporous MOF, csq-NU-1008, was discovered and monitored through in situ variable temperature liquid-cell transmission electron microscopy (VT-LCTEM), high-resolution transmission electron microscopy (HRTEM), and in situ variable temperature powder X-ray diffraction (VT-PXRD). It was found that the microporous- to-mesoporous transformation in the presence of formic acid occurs via a concomitant dissolution-reprecipitation process.

Insights into the Enhanced Catalytic Activity of Cytochrome c When Encapsulated in a Metal-Organic Framework.

The encapsulation of enzymes within porous materials has shown great promise, not only in protecting the enzymes from denaturation under nonbiological environments, but also, in some cases, in facilitating their enzymatic reaction rates at favorable reaction conditions. While a number of hypotheses have been developed to explain this phenomenon, the detailed structural changes of the enzymes upon encapsulation within the porous material, which are closely related to their activity, remain largely elusive. Herein, the structural change of cytochrome c (Cyt c) upon encapsulation within a hierarchical metal-organic framework, NU-1000, is investigated through a combination of experimental and computational methods, such as electron paramagnetic resonance, solid-state ultraviolet-visible spectroscopy, and all-atom explicit solvent molecular dynamics simulations. The enhanced catalytic performance of Cyt c after being encapsulated within NU-1000 is supported by the physical and in silico observations of a change around the heme ferric active center.

Interrogating Kinetic versus Thermodynamic Topologies of Metal-Organic Frameworks via Combined Transmission Electron Microscopy and X-ray Diffraction Analysis.

Synthetic protocols that preferentially result in metal-organic framework (MOF) crystallization of one topology over another remain an elusive, empirical process. This is primarily because of a lack of fundamental insights into MOF crystal growth and the effect of various experimental parameters on the resulting topologies. In this Communication, we demonstrate the temperature-topology relationship of MOFs constructed from hexanuclear oxozirconium cluster nodes and tetrakis(4-carboxylphenyl)porphyrin linkers via a combined transmission electron microscopy and powder X-ray diffraction study. Synthesis at room temperature led to a mixed phase consisting of 12-connected (assuming no defects) MOF-525 and 6-connected PCN-224, possessing ftw and she topologies, respectively. When the temperature was raised to 145 °C, 8-connected PCN-222 (csq topology) was found, with a possible concurrence of another 8-connected NU-902 (scu topology) and 12-connected PCN-223 (shp topology), in addition to MOF-525 and PCN-224. With an increase in reaction time at 145 °C, a change in product distribution was observed where PCN-222 remained the major crystal phase after 7 days, while the contribution from MOF-525 and PCN-224 decreased. These data suggest that MOF-525 and PCN-224 are the kinetic products while PCN-222 is the thermodynamic product.

Sex differences in navigation strategy and efficiency.

Research on human navigation has indicated that males and females differ in self-reported navigation strategy as well as objective measures of navigation efficiency. In two experiments, we investigated sex differences in navigation strategy and efficiency using an objective measure of strategy, the dual-solution paradigm (DSP; Marchette, Bakker, & Shelton, 2011). Although navigation by shortcuts and learned routes were the primary strategies used in both experiments, as in previous research on the DSP, individuals also utilized route reversals and sometimes found the goal location as a result of wandering. Importantly, sex differences were found in measures of both route selection and navigation efficiency. In particular, males were more likely to take shortcuts and reached their goal location faster than females, while females were more likely to follow learned routes and wander. Self-report measures of strategy were only weakly correlated with objective measures of strategy, casting doubt on their usefulness. This research indicates that the sex difference in navigation efficiency is large, and only partially related to an individual's navigation strategy as measured by the dual-solution paradigm.

The Specific Morphological Features of Alveolar Bone.

OBJECTIVE: The aim of the study was to study the specific morphological features of alveolar bone and compare it to femoral bone in rats. METHODS: Twelve 3-month-old nonpregnant female Sprague-Dawley rats were used in the present study. The left maxillae and femurs of 6 rats were used for micro-computed tomography (micro-CT) scanning. The trabecular bone of the distal femur and the interradicular alveolar bone of the maxillary first molar were reconstructed and analyzed. Another 6 rats were used for histological analysis of trabecular bone and alveolar bone. RESULTS: Micro-CT analysis suggested that the femoral trabecular bone was porous with rod-like trabeculae with a scattered distribution in bone marrow, whereas alveolar bone showed a compact structure with plate-like trabeculae and limited bone marrow. Tissue mineral density, bone mineral density, bone volume fraction, and trabecular thickness were dramatically higher in the alveolar bone compared with that in the trabecular bone. Alveolar bone displayed lower trabecular number and trabecular separation. Histomorphometric analysis showed that alveolar bone was formed of compact bone with wide trabeculae, whereas femurs were composed of loose bone with finer trabeculae. CONCLUSIONS: In comparison to the spongiosa of the distal femur, alveolar bone displays specific morphological features with compact, wide, and highly mineralized trabeculae.

The Effects of Telerehabilitation in Patients with Voice Disorders: A Systematic Review and Meta-Analysis.

OBJECTIVES: To compare the effects of telerehabilitation (TR) and face-to-face rehabilitation (FTF) methods on the outcomes of adults with voice disorders and to analyze the effectiveness of TR. METHODS: Following Boolean Logic, a search strategy was devised, combining subject terms and keywords based on the interventions and populations outlined in the inclusion criteria. We searched PubMed, Cochrane Library, Embase, Web of Science, Scopus, CNKI, Wanfang, CQVIP databases, and manually screened academic conference papers, journal articles, and gray literature to identify eligible randomized controlled trials (RCTs) on remote voice therapy. Two researchers assessed the risk of bias in the included studies using the risk of bias assessment tool for RCTs outlined in the Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0. RESULTS: Five trials with a total of 233 patients with voice disorders were included in the study after screening. The results revealed a significant difference in Jitter change values (mean difference [MD]=-0.12, 95%CI [-0.23,-0.01], P = 0.04) between TR and FTF, maximum phonation time (MD=0.76, 95%CI [-0.60,2.13], P = 0.27), Shimmer (MD=-0.04, 95%CI [-0.11,0.03], P = 0.27), voice handicap index (MD=0.87, 95%CI [-1.77,3.50], P = 0.52), and GRBAS(G) (MD=-0.00, 95%CI [-0.01,0.01], P = 0.99) had no significant difference. CONCLUSION: TR demonstrates comparable efficacy to FTF in voice treatment and is associated with higher levels of patient satisfaction, making it a viable and effective therapeutic modality. However, given the limited sample size analyzed in this study, further validation of this conclusion necessitates additional RCTs with larger sample sizes. Furthermore, researchers should remain cognizant of the constraints associated with TR and consistently refine treatment protocols to enhance the efficacy of voice therapy.

The role of the Piezo1 channel in osteoblasts under cyclic stretching: A study on osteogenic and osteoclast factors.

OBJECTIVES: Orthodontic tooth movement is a mechanobiological reaction induced by appropriate forces, including bone remodeling. The mechanosensitive Piezo channels have been shown to contribute to bone remodeling. However, information about the pathways through which Piezo channels affects osteoblasts remains limited. Thus, we aimed to investigate the influence of Piezo1 on the osteogenic and osteoclast factors in osteoblasts under mechanical load. MATERIALS AND METHODS: Cyclic stretch (CS) experiments on MC3T3-E1 were conducted using a BioDynamic mechanical stretching device. The Piezo1 channel blocker GsMTx4 and the Piezo1 channel agonist Yoda1 were used 12 h before the application of CS. MC3T3-E1 cells were then subjected to 15% CS, and the expression of Piezo1, Piezo2, BMP-2, OCN, Runx2, RANKL, p-p65/p65, and ALP was measured using quantitative real-time polymerase chain reaction, western blot, alkaline phosphatase staining, and immunofluorescence staining. RESULTS: CS of 15% induced the highest expression of Piezo channel and osteoblast factors. Yoda1 significantly increased the CS-upregulated expression of Piezo1 and ALP activity but not Piezo2 and RANKL. GsMTx4 downregulated the CS-upregulated expression of Piezo1, Piezo2, Runx2, OCN, p-65/65, and ALP activity but could not completely reduce CS-upregulated BMP-2. CONCLUSIONS: The appropriate force is more suitable for promoting osteogenic differentiation in MC3T3-E1. The Piezo1 channel participates in osteogenic differentiation of osteoblasts through its influence on the expression of osteogenic factors like BMP-2, Runx2, and OCN and is involved in regulating osteoclasts by influencing phosphorylated p65. These results provide a foundation for further exploration of osteoblast function in orthodontic tooth movement.

Genomic characterization and resistance features of Streptococcus agalactiae isolated from non-pregnant adults in Shandong, China.

BACKGROUND: Streptococcus agalactiae is a recognized pathogen that primarily affects infants and pregnant women. However, its increasingly important role in causing invasive infections among non-pregnant adults has become a significant health concern due to the severity and variety of its clinical impacts. METHODS: Nonduplicate S. agalactiae clinical strains associated with clinical infections (n = 139) were isolated from non-pregnant adults in Shandong, China. Antibiotic susceptibility testing, whole-genome sequencing and genomic analyses were conducted to characterize the genome and identify resistance features of these strains. RESULTS: The strains exhibited universal susceptibility to penicillin, ampicillin, cefotaxime, meropenem, linezolid and vancomycin. Notably, high resistance rates were observed for erythromycin (91.4%), clindamycin (89.2%), levofloxacin (84.2%), tetracycline (54.0%) and, to a lesser extent, chloramphenicol (12.9%). Serotyping revealed seven serotypes and one non-typeable strain. Serotypes Ia, Ib, III and V predominated, representing 95.7% of the strains. Nineteen sequence types were categorized into seven clonal complexes, with CC10 being the most prevalent at 48.9%. The resistance genes mreA (100%), ermB (70.5%) and tetM (46.0%) were commonly detected. All the isolates carried at least one pilus backbone determinant and one alpha-like protein gene, with the PI-1+PI-2a and the bca gene being the most frequent at 84.2% and 54.7%, respectively. CONCLUSIONS: While S. agalactiae strains in non-pregnant adults retain sensitivity to ß-lactam antibiotics, the elevated resistance to erythromycin, clindamycin, levofloxacin and tetracycline is concerning. Given the growing elderly population worldwide, the burden of S. agalactiae infections is significant. Continuous surveillance of serotype distribution and antibiotic resistance patterns is imperative for targeted prevention and therapeutic strategies.

Fucoidan enhances the anti-tumor effect of anti-PD-1 immunotherapy by regulating gut microbiota.

Currently, the clinical efficacy of anti-PD-1/PD-L1 monotherapy strategies against breast cancer is limited, and low response rates need to be improved. Gut microbiota plays a crucial role in the sensitization process of immunotherapy. As a natural dietary supplement, fucoidan has been reported to have immunomodulatory effects, while some studies have found that oral fucoidan may act as a potential prebiotic to modulate the gut microbiota. Therefore, this study investigated whether fucoidan could enhance the effects of anti-PD-1 monoclonal antibody antitumor immunotherapy by modulating gut microbiota and its metabolites. We found that the anti-tumor effect of the combination treatment was significantly enhanced, while fucoidan significantly improved the composition of the gut microbiota by increasing the number of potentially beneficial bacteria, such as Bifidobacterium, Faecalibaculum and Lactobacillus. Interference with the gut microbiota by antibiotics revealed impaired antitumor efficacy, confirming the necessity of gut microbiota in the antitumor effects of fucoidan in vivo. Metabolomics further revealed that fucoidan may have reversed the metabolic disturbances induced by the breast cancer model through tryptophan metabolism and glycerophospholipid metabolism pathways, with the most significant increase in the content of short-chain fatty acids, especially acetic and butyric acids. These modulations improved the function of effector T cells and suppressed Treg cell production. Thus, our findings suggest that fucoidan combined with the anti-PD-1 monoclonal antibody may be a novel strategy to sensitize breast cancer patients to anti-PD-1 monoclonal antibody immunotherapy. Meanwhile, the gut microbiota might serve as a new biomarker to predict the anti-PD-1 monoclonal antibody response to breast cancer immunotherapy.