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Temporomandibular disorders are typically accompanied by a number of clinical manifestations that involve pain and dysfunction of the masticatory muscles and temporomandibular joint. The most important subgroup of articular abnormalities in patients with temporomandibular disorders includes patients with different forms of articular disc displacement and deformation. Here, we propose a fully automated articular disc detection and segmentation system to support the diagnosis of temporomandibular disorder on magnetic resonance imaging. This system uses deep learning-based semantic segmentation approaches. The study included a total of 217 magnetic resonance images from 10 patients with anterior displacement of the articular disc and 10 healthy control subjects with normal articular discs. These images were used to evaluate three deep learning-based semantic segmentation approaches: our proposed convolutional neural network encoder-decoder named 3DiscNet (Detection for Displaced articular DISC using convolutional neural NETwork), U-Net, and SegNet-Basic. Of the three algorithms, 3DiscNet and SegNet-Basic showed comparably good metrics (Dice coefficient, sensitivity, and positive predictive value). This study provides a proof-of-concept for a fully automated deep learning-based segmentation methodology for articular discs on magnetic resonance images, and obtained promising initial results, indicating that the method could potentially be used in clinical practice for the assessment of temporomandibular disorders.

Light-driven outward H + pumps are widely distributed in nature, converting sunlight energy into proton motive force. Here we report the characterization of an oppositely directed H + pump with a similar architecture to outward pumps. A deep-ocean marine bacterium, Parvularcula oceani , contains three rhodopsins, one of which functions as a light-driven inward H + pump when expressed in Escherichia coli and mouse neural cells. Detailed mechanistic analyses of the purified proteins reveal that small differences in the interactions established at the active centre determine the direction of primary H + transfer. Outward H + pumps establish strong electrostatic interactions between the primary H + donor and the extracellular acceptor. In the inward H + pump these electrostatic interactions are weaker, inducing a more relaxed chromophore structure that leads to the long-distance transfer of H + to the cytoplasmic side. These results demonstrate an elaborate molecular design to control the direction of H + transfers in proteins. Proton pumps that are driven by light to pump protons out of the cell are involved in the conversion of sunlight into proton motive force; pumps to drive protons in the other direction have been engineered. Here, the authors report the identification and characterisation of a naturally occurring inward-driven protein pump.

Many organisms capture or sense sunlight using rhodopsin pigments 1 , 2 , which are integral membrane proteins that bind retinal chromophores. Rhodopsins comprise two distinct protein families 1 , type-1 (microbial rhodopsins) and type-2 (animal rhodopsins). The two families share similar topologies and contain seven transmembrane helices that form a pocket in which retinal is linked covalently as a protonated Schiff base to a lysine at the seventh transmembrane helix 2 , 3 . Type-1 and type-2 rhodopsins show little or no sequence similarity to each other, as a consequence of extensive divergence from a common ancestor or convergent evolution of similar structures 1 . Here we report a previously unknown and diverse family of rhodopsins—which we term the heliorhodopsins—that we identified using functional metagenomics and that are distantly related to type-1 rhodopsins. Heliorhodopsins are embedded in the membrane with their N termini facing the cell cytoplasm, an orientation that is opposite to that of type-1 or type-2 rhodopsins. Heliorhodopsins show photocycles that are longer than one second, which is suggestive of light-sensory activity. Heliorhodopsin photocycles accompany retinal isomerization and proton transfer, as in type-1 and type-2 rhodopsins, but protons are never released from the protein, even transiently. Heliorhodopsins are abundant and distributed globally; we detected them in Archaea, Bacteria, Eukarya and their viruses. Our findings reveal a previously unknown family of light-sensing rhodopsins that are widespread in the microbial world. An analysis based on functional metagenomics reveals a previously unknown group of microbial light-sensory rhodopsins that are widespread among a diverse range of microorganisms.

Traditionally, fuel cells operate by using small fuel molecules such as hydrogen and methanol to produce energy, water, and carbon dioxide. Enzyme biofuel cells use enzymes rather than precious metals as electrode catalysts. In recent years, enzyme-immobilized electrodes have been developed by combining enzyme biofuel cells with microfluidic technology to improve the efficiency and performance of fuel cells. In this review, we will provide an overview and describe the current status of recent enzyme biofuel cells, microfluidic technology, and their applications to microfluidic fuel cells.

MIR125B, particularly its 5p strand, is apparently involved in multiple cellular processes, including osteoblastogenesis and osteoclastogenesis. Given that MIR125B is transcribed from the loci Mir125b1 and Mir125b2 , three mature transcripts (MIR125B-5p, MIR125B1-3p, and MIR125B2-3p) are generated (MIR125B-5p is common to both); however, their expression profiles and roles in the bones remain poorly understood. Both primary and mature MIR125B transcripts were differentially expressed in various organs, tissues, and cells, and their expression patterns did not necessarily correlate in wild-type (WT) mice. We generated Mir125b2 knockout (KO) mice to examine the contribution of Mir125b2 to MIR125B expression profiles and bone phenotypes. Mir125b2 KO mice were born and grew normally without any changes in bone parameters. Interestingly, in WT and Mir125b2 KO, MIR125B-5p was abundant in the calvaria and bone marrow stromal cells. These results indicate that the genetic ablation of Mir125b2 does not impinge on the bones of mice, attracting greater attention to MIR125B-5p derived from Mir125b1 . Future studies should investigate the conditional deletion of Mir125b1 and both Mir125b1 and Mir125b2 in mice.

The naturally occurring channelrhodopsin variant anion channelrhodopsin-1 (ACR1), discovered in the cryptophyte algae Guillardia theta , exhibits large light-gated anion conductance and high anion selectivity when expressed in heterologous settings, properties that support its use as an optogenetic tool to inhibit neuronal firing with light. However, molecular insight into ACR1 is lacking owing to the absence of structural information underlying light-gated anion conductance. Here we present the crystal structure of G. theta ACR1 at 2.9 Å resolution. The structure reveals unusual architectural features that span the extracellular domain, retinal-binding pocket, Schiff-base region, and anion-conduction pathway. Together with electrophysiological and spectroscopic analyses, these findings reveal the fundamental molecular basis of naturally occurring light-gated anion conductance, and provide a framework for designing the next generation of optogenetic tools. The crystal structure of anion channelrhodopsin-1 (ACR1) from the algae Guillardia theta provides insights into the basis of anion conductance.

Background Guillain-Barré syndrome (GBS) is a clinically heterogenous disease and encompasses several distinct clinical variants. Overlap between these variants can pose a diagnostic challenge. We report a case of finger drop variant and acute bulbar palsy overlap as an unusual manifestation of GBS. Case presentation An 81-year-old man presented with dysarthria, dysphagia, and upper limb weakness. Neurological examination revealed impaired tongue protrusion, the finger drop sign, and diminished brachioradial and triceps muscle reflexes. Nerve conduction studies showed reduced amplitudes and decreased velocities in the median and ulnar nerves. Cerebrospinal fluid analysis revealed albuminocytological dissociation and an anti-ganglioside antibody study revealed positivity for GM1, asialo-GM1, GT1a, GD1b, and GQ1b. As GBS was suspected, we initiated intravenous immunoglobulin treatment, resulting in gradual improvement within the next 3 weeks. Conclusion To the best of our knowledge, this is the first reported case of an overlap between the finger drop variant and acute bulbar palsy in GBS, highlighting the importance of considering GBS when patients present with a combination of atypical symptoms. Anti-ganglioside antibodies can be helpful and add diagnostic value in these complex cases.

Transfer learning (TL) is an alternative approach to the full training of deep learning (DL) models from scratch and can transfer knowledge gained from large-scale data to solve different problems. ImageNet, which is a publicly available large-scale dataset, is a commonly used dataset for TL-based image analysis; many studies have applied pre-trained models from ImageNet to clinical prediction tasks and have reported promising results. However, some have questioned the effectiveness of using ImageNet, which consists solely of natural images, for medical image analysis. The aim of this study was to evaluate whether pre-trained models using RadImageNet, which is a large-scale medical image dataset, could achieve superior performance in classification tasks in dental imaging modalities compared with ImageNet pre-trained models. To evaluate the classification performance of RadImageNet and ImageNet pre-trained models for TL, two dental imaging datasets were used. The tasks were (1) classifying the presence or absence of supernumerary teeth from a dataset of panoramic radiographs and (2) classifying sex from a dataset of lateral cephalometric radiographs. Performance was evaluated by comparing the area under the curve (AUC). On the panoramic radiograph dataset, the RadImageNet models gave average AUCs of 0.68 ± 0.15 (p < 0.01), and the ImageNet models had values of 0.74 ± 0.19. In contrast, on the lateral cephalometric dataset, the RadImageNet models demonstrated average AUCs of 0.76 ± 0.09, and the ImageNet models achieved values of 0.75 ± 0.17. The difference in performance between RadImageNet and ImageNet models in TL depends on the dental image dataset used.

Both designed and natural anion-conducting channelrhodopsins (dACRs and nACRs, respectively) have been widely applied in optogenetics (enabling selective inhibition of target-cell activity during animal behaviour studies), but each class exhibits performance limitations, underscoring trade-offs in channel structure-function relationships. Therefore, molecular and structural insights into dACRs and nACRs will be critical not only for understanding the fundamental mechanisms of these light-gated anion channels, but also to create next-generation optogenetic tools. Here we report crystal structures of the dACR iC++, along with spectroscopic, electrophysiological and computational analyses that provide unexpected insights into pH dependence, substrate recognition, channel gating and ion selectivity of both dACRs and nACRs. These results enabled us to create an anion-conducting channelrhodopsin integrating the key features of large photocurrent and fast kinetics alongside exclusive anion selectivity. Crystal structures and molecular simulations of the designed anion-conducting channelrhodopsin iC++ provide molecular insights that enable structure-based design of channelrhodopsins with desirable properties for use as optogenetic tools.

Angiopoietin-like proteins (ANGPTLs) are circulating proteins that are expressed in various cells and tissues and are thought to be involved in the repair and remodeling of damaged tissues; however, ANGPTL2 hyperfunction has been shown to cause chronic inflammation, leading to the progression of various diseases. ANGPTL2 is known to exert cellular effects via receptors such as integrin α5β1 and leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2); however, their roles in ANGPTL2-induced inflammation remain unclear. In this study, we investigated the mechanisms underlying ANGPTL2-induced inflammation involving LILRB2 and various signaling pathways in human fibroblast-like synoviocytes (HFLS). The effects of ANGPTL2 and an anti-LILRB2 antibody on the gene expression of various inflammation-related factors were examined using real-time RT-PCR, while their effects on MAPK, NF-κB, and Akt phosphorylation were analyzed by western blotting. We found that the addition of ANGPTL2 enhanced the gene expression of inflammatory factors, whereas pretreatment with the anti-LILRB2 antibody for 12 h decreased the expression of these factors. Similarly, ANGPTL2 addition activated the phosphorylation of ERK, p38, JNK, NF-κB, and Akt in HFLS; however, this effect was significantly inhibited by pretreatment with the anti-LILRB2 antibody. Together, the findings of this study demonstrate that ANGPTL2 induces the expression of inflammatory factors via LILRB2 in synovial cells. Therefore, LILRB2 could be a potential therapeutic agent for treating matrix degradation in osteoarthritis.