Cross-sections of doubly curved sheets as confined elastica.

Although thin films are typically manufactured in planar sheets or rolls, they are often forced into three-dimensional (3D) shapes, producing a plethora of structures across multiple length scales. To understand this complex response, previous studies have either focused on the overall gross shape or the small-scale buckling that decorates it. A geometric model, which considers the sheet as inextensible yet free to compress, has been shown to capture the gross shape of the sheet. However, the precise meaning of such predictions, and how the gross shape constrains the fine features, remains unclear. Here, we study a thin-membraned balloon as a prototypical system that involves a doubly curved gross shape with large amplitude undulations. By probing its side profiles and horizontal cross-sections, we discover that the mean behavior of the film is the physical observable that is predicted by the geometric model, even when the buckled structures atop it are large. We then propose a minimal model for the horizontal cross-sections of the balloon, as independent elastic filaments subjected to an effective pinning potential around the mean shape. Despite the simplicity of our model, it reproduces a broad range of phenomena seen in the experiments, from how the morphology changes with pressure to the detailed shape of the wrinkles and folds. Our results establish a route to combine global and local features consistently over an enclosed surface, which could aid the design of inflatable structures, or provide insight into biological patterns.

GSK3ß: A ray of hope for the treatment of diabetic kidney disease.

Diabetic kidney disease (DKD), a major microvascular complication of diabetes, is characterized by its complex pathogenesis, high risk of chronic renal failure, and lack of effective diagnosis and treatment methods. GSK3ß (glycogen synthase kinase 3ß), a highly conserved threonine/serine kinase, was found to activate glycogen synthase. As a key molecule of the glucose metabolism pathway, GSK3ß participates in a variety of cellular activities and plays a pivotal role in multiple diseases. However, these effects are not only mediated by affecting glucose metabolism. This review elaborates on the role of GSK3ß in DKD and its damage mechanism in different intrinsic renal cells. GSK3ß is also a biomarker indicating the progression of DKD. Finally, the protective effects of GSK3ß inhibitors on DKD are also discussed.

c-Cbl induced podocin ubiquitination contributes to the podocytes injury in diabetic nephropathy.

The ubiquitination function in diabetic nephropathy (DN) has attracted much attention, but there is a lack of information on its ubiquitylome profile. To examine the differences in protein content and ubiquitination in the kidney between db/db mice and db/m mice, we deployed liquid chromatography-mass spectrometry (LC-MS/MS) to conduct analysis. We determined 145 sites in 86 upregulated modified proteins and 66 sites in 49 downregulated modified proteins at the ubiquitinated level. Moreover, 347 sites among the 319 modified proteins were present only in the db/db mouse kidneys, while 213 sites among the 199 modified proteins were present only in the db/m mouse kidneys. The subcellular localization study indicated that the cytoplasm had the highest proportion of ubiquitinated proteins (31.87%), followed by the nucleus (30.24%) and the plasma membrane (20.33%). The enrichment analysis revealed that the ubiquitinated proteins are mostly linked to tight junctions, oxidative phosphorylation, and thermogenesis. Podocin, as a typical protein of slit diaphragm, whose loss is a crucial cause of proteinuria in DN. Consistent with the results of ubiquitination omics, the K261R mutant of podocin induced the weakest ubiquitination compared with the K301R and K370R mutants. As an E3 ligase, c-Cbl binds to podocin, and the regulation of c-Cbl can impact the ubiquitination of podocin. In conclusion, in DN, podocin ubiquitination contributes to podocyte injury, and K261R is the most significant site. c-Cbl participates in podocin ubiquitination and may be a direct target for preserving the integrity of the slit diaphragm structure, hence reducing proteinuria in DN.

Twisting a Cylindrical Sheet Makes It a Tunable Locking Material.

A buckled sheet offers a reservoir of material that can be unfurled at a later time. For sufficiently thin yet stiff materials, this geometric process has a striking mechanical feature: when the slack runs out, the material locks to further extension. Here, we establish a simple route to a tunable locking material: a system with an interval where it is freely deformable under a given deformation mode, and where the endpoints of this interval can be changed continuously over a wide range. We demonstrate this type of mechanical response in a thin sheet formed into a cylindrical shell and subjected to axial twist and compression, and we rationalize our results with a simple geometric model.

Sculpting Liquids with Ultrathin Shells.

Thin elastic films can spontaneously attach to liquid interfaces, offering a platform for tailoring their physical, chemical, and optical properties. Current understanding of the elastocapillarity of thin films is based primarily on studies of planar sheets. We show that curved shells can be used to manipulate interfaces in qualitatively different ways. We elucidate a regime where an ultrathin shell with vanishing bending rigidity imposes its own rest shape on a liquid surface, using experiment and theory. Conceptually, the pressure across the interface "inflates" the shell into its original shape. The setup is amenable to optical applications as the shell is transparent, free of wrinkles, and may be manufactured over a range of curvatures.

Determining the refractive index, absolute thickness and local slope of a thin transparent film using multi-wavelength and multi-incident-angle interference.

We describe a high-speed interferometric method, using multiple angles of incidence and multiple wavelengths, to measure the absolute thickness, tilt, the local angle between the surfaces, and the refractive index of a fluctuating transparent wedge. The method is well suited for biological, fluid and industrial applications.

Characteristic Interfacial Structure behind a Rapidly Moving Contact Line.

In forced wetting, a rapidly moving surface drags with it a thin layer of trailing fluid as it is plunged into a second fluid bath. Using high-speed interferometry, we find characteristic structure in the thickness of this layer with multiple thin flat triangular structures separated by much thicker regions. These features, depending on liquid viscosity and penetration velocity, are robust and occur in both wetting and dewetting geometries. Their presence clearly shows the importance of motion in the transverse direction. We present a model using the assumption that the velocity profile is robust to thickness fluctuations that gives a good estimate of the gap thickness in the thin regions.

Transcutaneous auricular vagus nerve stimulation with task-oriented training improves upper extremity function in patients with subacute stroke: a randomized clinical trial.

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a promising brain stimulation modality in poststroke upper extremity rehabilitation. Although several studies have examined the safety and reliability of taVNS, the mechanisms underlying motor recovery in stroke patients remain unclear. Objectives: This study aimed to investigate the effects of taVNS paired with task-oriented training (TOT) on upper extremity function in patients with subacute stroke and explore the potential underlying mechanisms. Methods: In this double-blinded, randomized, controlled pilot trial, 40 patients with subacute stroke were randomly assigned to two groups: the VNS group (VG), receiving taVNS during TOT, and the Sham group (SG), receiving sham taVNS during TOT. The intervention was delivered 5 days per week for 4 weeks. Upper extremity function was measured using the Fugl-Meyer Assessment-Upper Extremity (FMA-UE), the Action Research Arm Test (ARAT). Activities of daily living were measured by the modified Barthel Index (MBI). Motor-evoked potentials (MEPs) were measured to evaluate cortical excitability. Assessments were administered at baseline and post-intervention. Additionally, the immediate effect of taVNS was detected using functional near-infrared spectroscopy (fNIRS) and heart rate variability (HRV) before intervention. Results: The VG showed significant improvements in upper extremity function (FMA-UE, ARAT) and activities of daily living (MBI) compared to the SG at post-intervention. Furthermore, the VG demonstrated a higher rate of elicited ipsilesional MEPs and a shorter latency of MEPs in the contralesional M1. In the VG, improvements in FMA-UE were significantly associated with reduced latency of contralesional MEPs. Additionally, fNIRS revealed increased activation in the contralesional prefrontal cortex and ipsilesional sensorimotor cortex in the VG in contrast to the SG. However, no significant between-group differences were found in HRV. Conclusion: The combination of taVNS with TOT effectively improves upper extremity function in patients with subacute stroke, potentially through modulating the bilateral cortex excitability to facilitate task-specific functional recovery.

Gate Voltage- and Bias Voltage-Tunable Staggered-Gap to Broken-Gap Transition Based on WSe2/Ta2NiSe5 Heterostructure for Multimode Optoelectronic Logic Gate.

Two-dimensional (2D) materials with superior properties exhibit tremendous potential in developing next-generation electronic and optoelectronic devices. Integrating various functions into one device is highly expected as that endows 2D materials great promise for more Moore and more-than-Moore device applications. Here, we construct a WSe2/Ta2NiSe5 heterostructure by stacking the p-type WSe2 and the n-type narrow gap Ta2NiSe5 with the aim to achieve a multifunction optoelectronic device. Owing to the large interface potential barrier, the heterostructure device reveals a prominent diode feature with a large rectify ratio (7.6 × 104) and a low dark current (10-12 A). Especially, gate voltage- and bias voltage-tunable staggered-gap to broken-gap transition is achieved on the heterostructure device, which enables gate voltage-tunable forward and reverse rectifying features. As results, the heterostructure device exhibits superior self-powered photodetection properties, including a high detectivity of 1.08 × 1010 Jones and a fast response time of 91 µs. Additionally, the intrinsic structural anisotropy of Ta2NiSe5 endows the heterostructure device with strong polarization-sensitive photodetection and high-resolution polarization imaging. Based on these characteristics, a multimode optoelectronic logic gate is realized on the heterostructure via synergistically modulating the light on/off, polarization angle, gate voltage, and bias voltage. This work shed light on the future development of constructing high-performance multifunctional optoelectronic devices.

Soybean straw biochar activating peroxydisulfate to simultaneously eliminate tetracycline and tetracycline resistance bacteria: Insights on the mechanism.

Tetracycline (TC) has been frequently detected in various environments, thus promoting the occurrence of resistance in bacterial populations. In this study, a suite of soybean straw biochars (SSBs) were fabricated under different pyrolysis temperatures (600-1000 °C), which were utilized as peroxydisulfate (PS) activators for TC degradation and TC resistant Escherichia coli (E. coli) disinfection. The purification effect of SSBs/PS systems manifested obvious positive dependence on pyrolysis temperature of SSBs with SSB1000/PS system obtained the superior TC degradation, E. coli disinfection and coexisting TC and E. coli elimination capacity. The leakage of intracellular DNA and the degradation of total DNA and extracellular DNA was revealed no matter in alone E. coli or combined pollution which can also be supported by the gradual ruptured bacterial morphology and attenuated internal components. It can be found that TC adsorption in SSBs played a significant role on TC degradation, while the electrostatic repulsion always existed between E. coli and SSB1000. Furthermore, a battery of solid evidences collectively demonstrated the significant different purification mechanism of TC and E. coli. The TC degradation was achieved dominantly by surface-bound radicals, while bactericidal activity should be attributed to free SO4·- in bulk solutions. In contrast to other SSBs, the largest mesopore volumes, highest C=O content, lowest interfacial charge transfer resistance and strongest electron donating capacity explained the outperformed catalytic performance of SSB1000.

Insights on the electron transfer pathway of phenolic pollutant degradation by endogenous N-doped carbonaceous materials and peroxymonosulfate system.

In this study, chitosan, a low-price and easily obtainable natural polymerized sugar containing abundant nitrogen element, was employed as a precursor for preparing hierarchically porous carbon (PC) to activate peroxymonosulfate (PMS). The PC fabricated at 800 °C obtained the optimum catalytic performance with complete removal of p-hydroxybenzoic acid (HBA) in 30 min. The selective degradation toward phenolic pollutants with different substituent groups and the resistance over the interference of typical anions and natural organic matter implied a non-radical pathway contributed most for HBA degradation. The investigation of structure-activity relationship suggested a positive linear correlation between graphitic N content and HBA removal. The chemical quenching experiment and electron paramagnetic resonance (EPR) excluded the crucial role of radicals and 1O2. Solid evidence based on electrochemical techniques demonstrated the essential contribution of electron transfer pathway achieved by three successive processes including the first close adsorption of PMS by PC800 to form metastable intermediates, then an internal electron transfer from active graphitic N to PMS within metastable intermediates and finally external electron transfer from HBA to metastable intermediates. This study provided insightful mechanism understanding of a promising organics elimination strategy by PMS activation through N-doped carbonaceous materials utilizing chitosan as a simultaneous carbon and nitrogen precursor.

MiR-107 overexpression attenuates neurotoxicity induced by 6-hydroxydopamine both in vitro and in vivo.

Alzheimer's disease (AD), the most common form of dementia, is a neurodegenerative disease characterized by neuronal atrophy in various brain regions. The expression of miR-107 is down-regulated in AD patients and target genes of miR-107 have been shown to directly involved in AD. In this study, we aimed to investigate the potential neuroprotective effects of miR-107. We first assessed brain activity in health controls and patients with AD. Then we examined miR-107 expression in SH-SY5Y and PC12 cells treated with 6-hydroxydopamine (6-OHDA), and investigated its function in cytotoxicity induced by 6-OHDA. We predicted a potential miR-107 target and assessed its role in miR-107 mediated effects and explored the intracellular signaling pathways downstream of miR-107. Finally, we assessed the function of miR-107 in the mouse model insulted by 6-OHDA. We found that 6-OHDA suppressed miR-107 expression and miR-107 played neuroprotective effects against 6-OHDA mediated cytotoxicity. We showed that miR-107 targeted programmed cell death 10 (PDCD10). MiR-107 suppressed PDCD10 expression and exogenous expression of PDCD10 inhibited miR-107 mediated neuroprotection. Additionally, we found that Notch signal pathway was downstream of miR-107/PDCD10. Finally, we found that 6-OHDA treatment suppressed miR-107 in mice and restoration of miR-107 alleviated motor disorder in the mouse model. Our study shows that miR-107 plays important neuroprotective roles against neurotoxicity both in vitro and in vivo by inhibiting PDCD10. Our findings confirm that miR-107 may be involved in AD pathogenesis and may be a therapeutic target for the treatment of AD-related impairments.

Association between plasma exosome neurogranin and brain structure in patients with Alzheimer's disease: a protocol study.

INTRODUCTION: Neurogranin is known to be significantly elevated in patients with Alzheimer's disease (AD) and may be an effective clinical predictor of cognitive decline and neurodegeneration. Amnestic mild cognitive impairment (aMCI) is an intermediate disease state between normal cognitive ageing and dementia, the latter of which can easily revert to AD. There remains significant uncertainty regarding the conversion of aMCI to AD, and therefore, elucidating such progression is paramount to the field of cognitive neuroscience. In this protocol study, we therefore aim to investigate the changes in plasma neurogranin in the early stage of AD and the mechanism thereof regarding the cognitive progression towards AD. METHODS AND ANALYSIS: In this study, patients with aMCI and AD patients (n=70 each) will be recruited at the memory clinic of the Department of Neurology of Hongqi Hospital affiliated with the Mudanjiang Medical University of China. Healthy older controls (n=70) will also be recruited from the community. All subjects will undergo neuroimaging and neuropsychological evaluations in addition to blood collection at the first year and the third year. We hope to identify a new biomarker of cognitive decline associated with AD and characterise its behaviour throughout the progression of aMCI to AD. This work will reveal novel targets for the therapeutic prevention, diagnosis and treatment of AD. The primary outcome measures will be (1) neuropsychological evaluation, including Mini-Mental State Examination, Montreal Cognitive Assessment, Clinical Dementia Rating scale, Shape Trail Test-A&B, Auditory Verbal Learning Test-HuaShan version; (2) microstructural alterations and hippocampal features from MRI scans; and (3) neurogranin levels in the neuronal-derived exosomes from peripheral blood samples. ETHICS AND DISSEMINATION: The ethics committee of the Hongqi Hospital affiliated with the Mudanjiang Medical University of China has approved this study protocol. The results will be published in peer-reviewed journals and presented at national or international scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR2000029055.

Trajectories of the Hippocampal Subfields Atrophy in the Alzheimer's Disease: A Structural Imaging Study.

BACKGROUND: The hippocampus and hippocampal subfields have been found to be diversely affected in Alzheimer's Disease (AD) and early stages of Alzheimer's disease by neuroimaging studies. However, our knowledge is still lacking about the trajectories of the hippocampus and hippocampal subfields atrophy with the progression of Alzheimer's disease. OBJECTIVE: To identify which subfields of the hippocampus differ in the trajectories of Alzheimer's disease by magnetic resonance imaging (MRI) and to determine whether individual differences on memory could be explained by structural volumes of hippocampal subfields. METHODS: Four groups of participants including 41 AD patients, 43 amnestic mild cognitive impairment (aMCI) patients, 35 subjective cognitive decline (SCD) patients and 42 normal controls (NC) received their structural MRI brain scans. Structural MR images were processed by the FreeSurfer 6.0 image analysis suite to extract the hippocampus and its subfields. Furthermore, we investigated relationships between hippocampal subfield volumes and memory test variables (AVLT-immediate recall, AVLT-delayed recall, AVLT-recognition) and the regression model analyses were controlled for age, gender, education and eTIV. RESULTS: CA1, subiculum, presubiculum, molecular layer and fimbria showed the trend toward significant volume reduction among four groups with the progression of Alzheimer's disease. Volume of left subiculum was most strongly and actively correlated with performance across AVLT measures. CONCLUSION: The trend changes in the hippocampus subfields and further illustrates that SCD is the preclinical stage of AD earlier than aMCI. Future studies should aim to associate the atrophy of the hippocampal subfields in SCD with possible conversion to aMCI or AD with longitudinal design.