An angel or a devil? Current view on the role of CD8+ T cells in the pathogenesis of myasthenia gravis.

BACKGROUND: Myasthenia gravis (MG) and the experimental autoimmune MG (EAMG) animal model are characterized by T-cell-induced and B-cell-dominated autoimmune diseases that affect the neuromuscular junction. Several subtypes of CD4+ T cells, including T helper (Th) 17 cells, follicular Th cells, and regulatory T cells (Tregs), contribute to the pathogenesis of MG. However, increasing evidence suggests that CD8+ T cells also play a critical role in the pathogenesis and treatment of MG. MAIN BODY: Herein, we review the literature on CD8+ T cells in MG, focusing on their potential effector and regulatory roles, as well as on relevant evidence (peripheral, in situ, cerebrospinal fluid, and under different treatments), T-cell receptor usage, cytokine and chemokine expression, cell marker expression, and Treg, Tc17, CD3+CD8+CD20+ T, and CXCR5+ CD8+ T cells. CONCLUSIONS: Further studies on CD8+ T cells in MG are necessary to determine, among others, the real pattern of the Vß gene usage of autoantigen-specific CD8+ cells in patients with MG, real images of the physiology and function of autoantigen-specific CD8+ cells from MG/EAMG, and the subset of autoantigen-specific CD8+ cells (Tc1, Tc17, and IL-17+IFN-γ+CD8+ T cells). There are many reports of CD20-expressing T (or CD20 + T) and CXCR5+ CD8 T cells on autoimmune diseases, especially on multiple sclerosis and rheumatoid arthritis. Unfortunately, up to now, there has been no report on these T cells on MG, which might be a good direction for future studies.

Superrepellency of underwater hierarchical structures on Salvinia leaf.

Biomimetic superhydrophobic surfaces display many excellent underwater functionalities, which attribute to the slippery air mattress trapped in the structures on the surface. However, the air mattress is easy to collapse due to various disturbances, leading to the fully wetted Wenzel state, while the water filling the microstructures is difficult to be repelled to completely recover the air mattress even on superhydrophobic surfaces like lotus leaves. Beyond superhydrophobicity, here we find that the floating fern, Salvinia molesta, has the superrepellent capability to efficiently replace the water in the microstructures with air and robustly recover the continuous air mattress. The hierarchical structures on the leaf surface are demonstrated to be crucial to the recovery. The interconnected wedge-shaped grooves between epidermal cells are key to the spontaneous spreading of air over the entire leaf governed by a gas wicking effect to form a thin air film, which provides a base for the later growth of the air mattress in thickness synchronously along the hairy structures. Inspired by nature, biomimetic artificial Salvinia surfaces are fabricated using 3D printing technology, which successfully achieves a complete recovery of a continuous air mattress to exactly imitate the superrepellent capability of Salvinia leaves. This finding will benefit the design principles of water-repellent materials and expand their underwater applications, especially in extreme environments.

An association study on imputed whole-genome resequencing from high-throughput sequencing data for body traits in crossbred pigs.

Body traits are important economic factors in the pig industry. Genome-wide association studies (GWASs) have been widely applied using high-density genotype data to detect QTL in pigs. The aim of the present study was to detect the genetic variants significantly associated with body traits in crossbred pigs using the Illumina Porcine SNP50 BeadChip and imputed whole-genome sequence data. A set of seven body traits - body length, body height, chest circumference, cannon bone circumference, leg buttock circumference, back fat thickness and loin muscle depth - were measured. Moderate to high heritabilities were obtained for most traits (from 0.14 to 0.46), and significant genetic and phenotypic correlations among them were observed. GWAS identified 714 significantly associated SNPs located at 39 regions on all autosomes for body traits, and a total of seven functionally related candidate genes: PIK3CD, HOXA, PCGF2, CHST11, COL2A1, BMI1 and OSR2. Functional enrichment analysis revealed that candidate genes were enriched in the estrogen signaling pathway, embryonic skeletal system morphogenesis and embryonic skeletal system development. These results aim to uncover the genetic mechanisms underlying body development and marker-assisted selection programs focusing on body traits in pigs.

Ultimate Stable Underwater Superhydrophobic State.

Underwater metastability hinders the durable application of superhydrophobic surfaces. In this work, through thermodynamic analysis, we theoretically demonstrate the existence of an ultimate stable state on underwater superhydrophobic surfaces. Such a state is achieved by the synergy of mechanical balance and chemical diffusion equilibrium across the entrapped liquid-air interfaces. By using confocal microscopy, we in situ examine the ultimate stable states on structured hydrophobic surfaces patterned with cylindrical micropores in different pressure and flow conditions. The equilibrium morphology of the meniscus is tuned by the dissolved gas saturation degree within a critical range at a given liquid pressure. Moreover, with fresh lotus leaves, we prove that the ultimate stable state can also be realized on randomly rough superhydrophobic surfaces. The finding here paves the way for applying superhydrophobic surfaces in environments with different liquid pressure and flow conditions.

Influence of fluid flow on the stability and wetting transition of submerged superhydrophobic surfaces.

Superhydrophobic surfaces have attracted great attention for drag reduction application. However, these surfaces are subject to instabilities, especially under fluid flow. In this work, we in situ examine the stability and wetting transition of underwater superhydrophobicity under laminar flow conditions by confocal microscopy. The absolute liquid pressure in the flow channel is regulated to acquire the pinned Cassie-Baxter and depinned metastable states. The subsequent dynamic evolution of the meniscus morphology in the two states under shear flow is monitored. It is revealed that fluid flow does not affect the pressure-mediated equilibrium states but accelerates the air exchange between entrapped air cavities and bulk water. A diffusion-based model with varying effective diffusion lengths is used to interpret the experimental data, which show a good agreement. The Sherwood number representing the convection-enhanced mass transfer coefficient is extracted from the data, and is found to follow a classic 1/3-power-law relation with the Reynolds number as has been discovered in channel flows with diffusive boundary conditions. The current work paves the way for designing durable superhydrophobic surfaces under flow conditions.

Receding dynamics of contact lines and size-dependent adhesion on microstructured hydrophobic surfaces.

The microstructure size on textured surfaces of a given solid fraction exhibits an important effect on their properties. To understand the size effect on surface adhesion, we study the receding dynamics of the microscopic three-phase contact lines, the adhesive properties, and the relation between them on microstructured surfaces. Two types of surfaces are used, which are micropillar and micropore, respectively. First, the receding process of the contact line is directly observed by laser scanning confocal microscopy (LSCM), which shows distinct characteristics on the two types of surfaces. The micro contact line experiences pinnning, sliding, and rupture on micropillar-patterned surfaces while no rupture occurs on micropore-patterned surfaces. The three-dimensional morphology of the micromeniscus on the micropillared surfaces and the two-dimensional scanning of the cross-sections of the micromeniscus along the diagonal direction are imaged. Based on the images, the local contact angles around the micropillar at the receding front, and the curvatures of the micro-meniscus are obtained. Then, the adhesive force on these surfaces is measured, which surprisingly shows an increasing trend with the size of the microstructure for micropillared surfaces but no obvious size dependence for micropored surfaces. Wetting hysteresis is also measured to testify the similar trend with the size for the two types of surfaces. Further investigation shows that the monotonic increase of the adhesive force with the increasing size of micropillars is due to the growing difficulty of the detachment of the contact lines. The underlying mechanism responsible for the size dependence of the adhesive force is the enhancement of the local reduced pressure exerted on the top of the micropillar with increasing size, resulting from the concave profile of the outer micromeniscus.

Liquid plasticine: controlled deformation and recovery of droplets with interfacial nanoparticle jamming.

Air-exposed droplet systems are widely applied in material preparation and experimental design. Recently, a droplet system with unusual properties featured by a liquid-like appearance and solid-like deformability was produced. However, it was then just an interesting and perplexing phenomenon in the absence of basic understandings and clear perspectives for applications. Here we reveal that stable droplet deformation is attributed to monolayer nanoparticle jamming at the water/vapor interface, and that the normal shape can be recovered by jamming relieving. The degree of jamming affects the droplet shape and transparency and can be tuned by the squeezing force and droplet volume. Using these properties and control methods, we develop the deformed droplet into "liquid plasticine" with predesigned shapes, super-high transparency, and arbitrarily large volume. We demonstrate that liquid plasticine could be used as liquid lenses, channel-like containers, and miniature reactors.

How solid-liquid adhesive property regulates liquid slippage on solid surfaces?

The influence of solid-liquid adhesive property on liquid slippage at solid surfaces has been investigated using experiment approach on well-defined model surfaces as well as theoretical analysis. Based on a classical molecular-kinetic description for molecular and hydrodynamic slip, we propose a simple theoretical model that directly relates the liquid slip length to the liquid adhesive force on solid surfaces, which yields an exponential decay function. Well-defined smooth surfaces with varied surface wettability/adhesion are fabricated by forming self-assembled monolayers on gold with different mole ratios of hydrophobic and hydrophilic thiols. The adhesive force of a water droplet and the molecular slippage on these surfaces are probed by surface force apparatus and quartz crystal microbalance measurements, respectively. The experiment results are well consistent with our theoretical prediction. Our finding benefits the understanding of the underlying mechanism of liquid slippage on solid surfaces at molecular level and the rational design of microfluidics with an aim to be frictionless or highly controllable.

Symmetric and asymmetric meniscus collapse in wetting transition on submerged structured surfaces.

The wetting transition from the Cassie-Baxter to the Wenzel state is a phenomenon critically pertinent to the functionality of microstructured superhydrophobic surfaces. This work focuses on the last stage of the transition, when the liquid-gas interface touches the bottom of the microstructure, which is also known as the "collapse" phenomenon. The process was examined in situ on a submerged surface patterned with cylindrical micropores using confocal microscopy. Both symmetric and asymmetric collapses were observed. The latter significantly shortens the progression of the metastable state prior to the collapse when compared with the former and hence may affect the lifespan of superhydrophobicity. Further experiments identified that asymmetric collapse were induced by impurities due to prior use of the structure. The problem is thus of broad relevance, since endurance through cycles is a practical requirement for these functional surfaces. Finally, the use of hierarchical structures is proposed as a remedy. The embedded self-cleaning mechanism serves to effectively remove the impurities, so as to avoid the triggering mechanism for asymmetric collapses.

Metastable states and wetting transition of submerged superhydrophobic structures.

Superhydrophobicity on structured surfaces is frequently achieved via the maintenance of liquid-air interfaces adjacent to the trapped air pockets. These interfaces, however, are subject to instabilities due to the Cassie-Baxter-to-Wenzel transition and total wetting. The current work examines in situ liquid-air interfaces on a submerged surface patterned with cylindrical micropores using confocal microscopy. Both the pinned Cassie-Baxter and depinned metastable states are directly observed and measured. The metastable state dynamically evolves, leading to a transition to the Wenzel state. This process is extensively quantified under different ambient pressure conditions, and the data are in good agreement with a diffusion-based model prediction. A similarity law along with a characteristic time scale is derived which governs the lifetime of the air pockets and which can be used to predict the longevity of underwater superhydrophobicity.

Ginkgo biloba and Its Chemical Components in the Management of Alzheimer's Disease.

The pathogenesis of Alzheimer's disease (AD), a degenerative disease of the central nervous system, remains unclear. The main manifestations of AD include cognitive and behavioral disorders, neuropsychiatric symptoms, neuroinflammation, amyloid plaques, and neurofibrillary tangles. However, current drugs for AD once the dementia stage has been reached only treat symptoms and do not delay progression, and the research and development of targeted drugs for AD have reached a bottleneck. Thus, other treatment options are needed. Bioactive ingredients derived from plants are promising therapeutic agents. Specifically, Ginkgo biloba (Gb) extracts exert anti-oxidant, anticancer, neuroplastic, neurotransmitter-modulating, blood fluidity, and anti-inflammatory effects, offering alternative options in the treatment of cardiovascular, metabolic, and neurodegenerative diseases. The main chemical components of Gb include flavonoids, terpene lactones, proanthocyanidins, organic acids, polysaccharides, and amino acids. Gb and its extracts have shown remarkable therapeutic effects on various neurodegenerative diseases, including AD, with few adverse reactions. Thus, high-quality Gb extracts are a well-established treatment option for AD. In this review, we summarize the insights derived from traditional Chinese medicine, experimental models, and emerging clinical trials on the role of Gb and its chemical components in the treatment of the main clinical manifestations of AD.

True or false? Alzheimer's disease is type 3 diabetes: Evidences from bench to bedside.

Globally, Alzheimer's disease (AD) is the most widespread chronic neurodegenerative disorder, leading to cognitive impairment, such as aphasia and agnosia, as well as mental symptoms, like behavioral abnormalities, that place a heavy psychological and financial burden on the families of the afflicted. Unfortunately, no particular medications exist to treat AD, as the current treatments only impede its progression.The link between AD and type 2 diabetes (T2D) has been increasingly revealed by research; the danger of developing both AD and T2D rises exponentially with age, with T2D being especially prone to AD. This has propelled researchers to investigate the mechanism(s) underlying this connection. A critical review of the relationship between insulin resistance, Aß, oxidative stress, mitochondrial hypothesis, abnormal phosphorylation of Tau protein, inflammatory response, high blood glucose levels, neurotransmitters and signaling pathways, vascular issues in AD and diabetes, and the similarities between the two diseases, is presented in this review. Grasping the essential mechanisms behind this detrimental interaction may offer chances to devise successful therapeutic strategies.

Bioinspired carbon nanotube-based nanofluidic ionic transistor with ultrahigh switching capabilities for logic circuits.

The voltage-gated ion channels, also known as ionic transistors, play substantial roles in biological systems and ion-ion selective separation. However, implementing the ultrafast switchable capabilities and polarity switching of ionic transistors remains a challenge. Here, we report a nanofluidic ionic transistor based on carbon nanotubes, which exhibits an on/off ratio of 104 at operational gate voltage as low as 1 V. By controlling the morphology of carbon nanotubes, both unipolar and ambipolar ionic transistors are realized, and their on/off ratio can be further improved by introducing an Al2O3 dielectric layer. Meanwhile, this ionic transistor enables the polarity switching between p-type and n-type by controlled surface properties of carbon nanotubes. The implementation of constructing ionic circuits based on ionic transistors is demonstrated, which enables the creation of NOT, NAND, and NOR logic gates. The ionic transistors are expected to have profound implications for low-energy consumption computing devices and brain-machine interfacing.

Current and future therapeutic strategies for Alzheimer's disease: an overview of drug development bottlenecks.

Alzheimer's disease (AD) is the most common chronic neurodegenerative disease worldwide. It causes cognitive dysfunction, such as aphasia and agnosia, and mental symptoms, such as behavioral abnormalities; all of which place a significant psychological and economic burden on the patients' families. No specific drugs are currently available for the treatment of AD, and the current drugs for AD only delay disease onset and progression. The pathophysiological basis of AD involves abnormal deposition of beta-amyloid protein (Aß), abnormal tau protein phosphorylation, decreased activity of acetylcholine content, glutamate toxicity, autophagy, inflammatory reactions, mitochondria-targeting, and multi-targets. The US Food and Drug Administration (FDA) has approved five drugs for clinical use: tacrine, donepezil, carbalatine, galantamine, memantine, and lecanemab. We have focused on the newer drugs that have undergone clinical trials, most of which have not been successful as a result of excessive clinical side effects or poor efficacy. Although aducanumab received rapid approval from the FDA on 7 June 2021, its long-term safety and tolerability require further monitoring and confirmation. In this literature review, we aimed to explore the possible pathophysiological mechanisms underlying the occurrence and development of AD. We focused on anti-Aß and anti-tau drugs, mitochondria-targeting and multi-targets, commercially available drugs, bottlenecks encountered in drug development, and the possible targets and therapeutic strategies for future drug development. We hope to present new concepts and methods for future drug therapies for AD.

An update on malignant tumor-related stiff person syndrome spectrum disorders: clinical mechanism, treatment, and outcomes.

Stiff person syndrome (SPS) is a rare central nervous system disorder associated with malignancies. In this review, we retrieved information from PubMed, up until August 2023, using various search terms and their combinations, including SPS, stiff person syndrome spectrum disorders (SPSSDs), paraneoplastic, cancer, and malignant tumor. Data from peer-reviewed journals printed in English were organized to explain the possible relationships between different carcinomas and SPSSD subtypes, as well as related autoantigens. From literature searching, it was revealed that breast cancer was the most prevalent carcinoma linked to SPSSDs, followed by lung cancer and lymphoma. Furthermore, classic SPS was the most common SPSSD subtype, followed by stiff limb syndrome and progressive encephalomyelitis with rigidity and myoclonus. GAD65 was the most common autoantigen in patients with cancer and SPSSDs, followed by amphiphysin and GlyR. Patients with cancer subtypes might have multiple SPSSD subtypes, and conversely, patients with SPSSD subtypes might have multiple carcinoma subtypes. The first aim of this review was to highlight the complex nature of the relationships among cancers, autoantigens, and SPSSDs as new information in this field continues to be generated globally. The adoption of an open-minded approach to updating information on new cancer subtypes, autoantigens, and SPSSDs is recommended to renew our database. The second aim of this review was to discuss SPS animal models, which will help us to understand the mechanisms underlying the pathogenesis of SPS. In future, elucidating the relationship among cancers, autoantigens, and SPSSDs is critical for the early prediction of cancer and discovery of new therapeutic modalities.

Importance of hierarchical structures in wetting stability on submersed superhydrophobic surfaces.

Submersed superhydrophobic surfaces exhibit great potential for reducing flow resistance in microchannels and drag of submersed bodies. However, the low stability of liquid-air interfaces on those surfaces limits the scope of their application, especially under high liquid pressure. In this paper, we first investigate the wetting states on submersed hydrophobic surfaces with one-level structure under hydrostatic pressure. Different equilibrium states based on free-energy minimization are formulated, and their stabilities are analyzed as well. Then, by comparison with the existing numerical and experimental studies, we confirm that a new metastable state, which happens after depinning of the three-phase contact line (TCL), exists. Finally, we show that a strategy of using hierarchical structures can strengthen the TCL pinning of the liquid-air interface in the metastable state. Therefore, the hierarchical structure on submersed surfaces is important to further improve the stability of superhydrophobicity under high liquid pressure.

A multifunctional and environmentally safe superhydrophobic membrane with superior oil/water separation, photocatalytic degradation and anti-biofouling performance.

Wastewater is typically complicated with spilled oil, water soluble toxic dyes and microorganisms, making it hard to be processed and causing a significant threat to the environmental safety and human health. In this paper, we demonstrate a simple solution immersion method to obtain a multifunctional cellulose-based membrane (CBM) that possesses both superhydrophobicity with a water contact angle of 163° and superior functionalities including self-cleaning, oil-water separation, anti-biofouling, and photocatalytic degradation capabilities. The achievement of separation efficiency (96%), comparatively high flux (141 L·m-2·h-1) and recyclable (7 times) oil/water separation performance is attributed to the robust superhydrophobicity enabled by the synergy of metal oxide (i.e., CuO) nanostructure coating and stearic acid (SA) modification. The superhydrophobic CBM also preferentially adsorbs organic dyes in aqueous solution, e.g., methylene blue (MB), promoting their efficient decomposition (about 70.3% of MB decomposed in 3 h) with high recyclability under UV irradiation. Most remarkably, the CBM exhibits superior anti-biofouling capability and persistently resists the algae adhesion in long duration (over 20 days), as a result of the self-cleaning ability as well as the antimicrobial property of CuO nanoparticles. Our finding here paves the way to use simple, cost-effective, environmentally safe, and reliable method to fabricate multifunctional materials for wastewater treatment in complex environments.

Genome-Wide Association Study Reveals Additive and Non-Additive Effects on Growth Traits in Duroc Pigs.

Growth rate plays a critical role in the pig industry and is related to quantitative traits controlled by many genes. Here, we aimed to identify causative mutations and candidate genes responsible for pig growth traits. In this study, 2360 Duroc pigs were used to detect significant additive, dominance, and epistatic effects associated with growth traits. As a result, a total number of 32 significant SNPs for additive or dominance effects were found to be associated with various factors, including adjusted age at a specified weight (AGE), average daily gain (ADG), backfat thickness (BF), and loin muscle depth (LMD). In addition, the detected additive significant SNPs explained 2.49%, 3.02%, 3.18%, and 1.96% of the deregressed estimated breeding value (DEBV) variance for AGE, ADG, BF, and LMD, respectively, while significant dominance SNPs could explain 2.24%, 13.26%, and 4.08% of AGE, BF, and LMD, respectively. Meanwhile, a total of 805 significant epistatic effects SNPs were associated with one of ADG, AGE, and LMD, from which 11 sub-networks were constructed. In total, 46 potential genes involved in muscle development, fat deposition, and regulation of cell growth were considered as candidates for growth traits, including CD55 and NRIP1 for AGE and ADG, TRIP11 and MIS2 for BF, and VRTN and ZEB2 for LMD, respectively. Generally, in this study, we detected both new and reported variants and potential candidate genes for growth traits of Duroc pigs, which might to be taken into account in future molecular breeding programs to improve the growth performance of pigs.

Atomic-scale ion transistor with ultrahigh diffusivity.

Biological ion channels rapidly and selectively gate ion transport through atomic-scale filters to maintain vital life functions. We report an atomic-scale ion transistor exhibiting ultrafast and highly selective ion transport controlled by electrical gating in graphene channels around 3 angstroms in height, made from a single flake of reduced graphene oxide. The ion diffusion coefficient reaches two orders of magnitude higher than the coefficient in bulk water. Atomic-scale ion transport shows a threshold behavior due to the critical energy barrier for hydrated ion insertion. Our in situ optical measurements suggest that ultrafast ion transport likely originates from highly dense packing of ions and their concerted movement inside the graphene channels.

Characterization and comparison of the bacterial community between complete intensive and extensive feeding patterns in pigs.

To investigate and compare the gut microbiota structures in complete intensive feeding pattern (CP) and extensive feeding pattern (EP) groups, a total of 20 pigs were divided into two groups and fed the same diet. The fecal microbial composition was profiled using 16S rRNA gene sequencing. Our results showed that seventeen predominant genera were present in each pig sample and constituted the phylogenetic core of the microbiota at the class level. The abundance of most of the core microbial flora were significantly higher in the CP group than in the EP group (P < 0.05), while the abundance of Gammaproteobacteria was significantly lower in the CP group than in the EP group (P < 0.05). The CP group had significantly greater community diversity, richness, and evenness than the EP group (P < 0.05). Functional prediction analysis indicated that intestinal microbial species potentially led to faster growth and an increased fat accumulation capacity in the CP group; however, disease resistance was weaker in the CP group than in the EP group. In conclusion, EP pigs have a wider range of activity and better animal welfare than CP pigs, which helps reduce the occurrence of diseases and neurological symptoms. To explore the effect of intestinal flora on disease resistance in pigs at the molecular level, Coprococcus, which is a key gut bacterium in the intestine, was selected for isolation and purification and cocultured with intestinal epithelial cells. qPCR was performed to determine the effect of Coprococcus on SLA-DRB gene expression in intestinal epithelial cells. The results showed that Coprococcus enhanced SLA-DRB gene expression in intestinal epithelial cells. The results provide useful reference data for further study on the relationship between intestinal flora and pig disease resistance.