Mutations of

, which encodes polycystin-2, cause autosomal dominant polycystic kidney disease (ADPKD). The prevailing view is that defects in polycystin-2-mediated calcium ion influx in the primary cilia play a central role in the pathogenesis of cyst growth. However, polycystin-2 is predominantly expressed in the endoplasmic reticulum (ER) and more permeable to potassium ions than to calcium ions.

The trimeric intracellular cation (TRIC) channel TRIC-B is an ER-resident potassium channel that mediates potassium-calcium counterion exchange for inositol trisphosphate-mediated calcium ion release. Using TRIC-B as a tool, we examined the function of ER-localized polycystin-2 and its role in ADPKD pathogenesis in cultured cells, zebrafish, and mouse models.

Agonist-induced ER calcium ion release was defective in cells lacking polycystin-2 and reversed by exogenous expression of TRIC-B.

, exogenous polycystin-2 reversed an ER calcium-release defect in cells lacking TRIC-B. In a zebrafish model, expressions as a potassium ion channel to facilitate potassium-calcium counterion exchange for inositol trisphosphate-mediated calcium release. The results advance the understanding of ADPKD pathogenesis and provides proof of principle for pharmacotherapy by TRIC-B activators.Spinal cord injury (SCI) leads to severe loss of motor and sensory functions, and the rehabilitation of SCI is a worldwide problem. Tissue-engineered scaffolds offer new hope for SCI patients, while the newly developed materials encountered a challenge in modeling the microenvironment around the lesion site. We constructed a new composite scaffold by mixing decellularized spinal cord extracellular matrix (dECM) with gelatin methacryloyl (GelMA). The dECM, as a natural biological material, retained a large number of proteins and growth factors related to neurogenesis. GelMA was a photopolymerizable material, harbored a polymer network structure, soft texture, certain shape and plenty of water. The viability, proliferation, and differentiation of neural stem cells (NSCs) on the composite scaffold were evaluated by cell count kit-8 (CCK8), Live/Dead assay, phalloidin staining, 5-Ethynyl-2′-deoxyurdine (EdU), immunofluorescence staining and western blot. The Live/Dead assay, phalloidin staining, EdU, and CCK8 assay showed that the composite scaffold had good biocompatibility and provided better support for proliferation of NSCs. Results of immunocytochemistry and western blot showed that the composite scaffolds promoted the specific differentiation of NSCs into neuron cells. Together, this dECM/GelMA composite scaffold can be used as a cell culture coating, the isolated NSCs seeded on the surface of composite scaffold expressed neuronal markers and assumed neuronal morphology. Our work provided a new method that would be widely used in tissue engineering of SCI.Silicon (Si), a high-capacity lithium-ion battery anode material, has aroused wide attention. find more Its further practical application has been limited by its huge volume change during the cycle. To reduce this defect, the double cross-linked product of glycinamide hydrochloride modified poly(acrylic acid) (PAG) and epoxidized natural rubber (ENR) was developed as a water-based binder to obtain sufficient elasticity and a sufficiently strong adhesive force. Due to the double cross-linked structures in the system, the binder was enabled to effectively disperse and transfer the stress generated by the volume expansion of the Si particles and keep the integrity of the electrode during the cycle, thus obtaining excellent cycle performance. When the current density was 1 A g-1, PE55 (PAG ENR = 11 cross-linked polymer) electrode still achieved a specific capacity of 2322.2 mAh g-1 after 100 cycles of constant current charge and discharge, and PE55 binder exhibited excellent bonding properties (4.45 N) and mechanical properties (stress 5.51 MPa, strain 87.4%). The comparison of poly(acrylic acid) (PAA) electrodes suggests that the introduction of elastic polymer and the construction of double cross-linked structures can increase the stability of Si anodes.

Although early rejection episodes are successfully controlled, the problem of unrecognized production of de novo anti-HLA antibodies and associated chronic rejection still persists.

In addition to the standard induction and maintenance therapy, we present a couple of new drugs as induction (Alemtuzumab), CNI-free protocol (Belatacept, Sirolimus, and Everolimus), and maintenance treatment in transplant patients with various types of malignancies (T cell-targeted immunomodulators blocking the immune checkpoints CTLA-4 and PD1/PDL1) and TMA (aHUS)-eculizumab and IL6 receptor antagonists in antibody-mediated rejection (AMR).

There are a couple of issues still preventing improvement in kidney transplant long-term outcomes with current and anticipated future immunosuppression patients more susceptible to infection and CNI nephrotoxicity in kidneys obtained from elderly donors and highly sensitized patients with limited chances to get appropriate kidney and a higher risk for late AMR. A lower rate of CMV/BK vincreased risk of PTLD. Eculizumab upon recurrence of aHUS is a sole cost-effective option. A new IL-6 blocking drug (clazakizumab/tocilizumab) is a promising option for prevention/treatment of AMR. Clinical experience in tailoring immunosuppression for improving as long as possible graft and patient survival is inevitable.Microbial electrosynthesis-using renewable electricity to stimulate microbial metabolism-holds the promise of sustainable chemical production. A key limitation hindering performance is slow electron-transfer rates at biotic-abiotic interfaces. Here a new n-type conjugated polyelectrolyte is rationally designed and synthesized and its use is demonstrated as a soft conductive material to encapsulate electroactive bacteria Shewanella oneidensis MR-1. The self-assembled 3D living biocomposite amplifies current uptake from the electrode ≈674-fold over controls with the same initial number of cells, thereby enabling continuous synthesis of succinate from fumarate. Such functionality is a result of the increased number of bacterial cells having intimate electronic communication with the electrode and a higher current uptake per cell. This is underpinned by the molecular design of the polymer to have an n-dopable conjugated backbone for facile reduction by the electrode and zwitterionic side chains for compatibility with aqueous media. Moreover, direct arylation polycondensation is employed instead of the traditional Stille polymerization to avoid non-biocompatible tin by-products. By demonstrating synergy between living cells with n-type organic semiconductor materials, these results provide new strategies for improving the performance of bioelectrosynthesis technologies.In recent years, neuroimaging studies have remarkably demonstrated the presence of cognitive motor dissociation in patients with disorders of consciousness (DoC). These findings accelerated the development of brain-computer interfaces (BCIs) as clinical tools for behaviorally unresponsive patients. This article reviews the recent progress of BCIs in patients with DoC and discusses the open challenges. In view of the practical application of BCIs in patients with DoC, four aspects of the relevant literature are introduced consciousness detection, auxiliary diagnosis, prognosis, and rehabilitation. For each aspect, the paradigm design, brain signal processing methods, and experimental results of representative BCI systems are analyzed. Furthermore, this article provides guidance for BCI design for patients with DoC and discusses practical challenges for future research.

 Generative pretrained transformer (GPT) models are one of the latest large pretrained natural language processing models that enables model training with limited datasets and reduces dependency on large datasets, which are scarce and costly to establish and maintain. There is a rising interest to explore the use of GPT models in health care.

 We investigate the performance of GPT-2 and GPT-Neo models for medical text prediction using 374,787 free-text dental notes.

 We fine-tune pretrained GPT-2 and GPT-Neo models for next word prediction on a dataset of over 374,000 manually written sections of dental clinical notes. Each model was trained on 80% of the dataset, validated on 10%, and tested on the remaining 10%. We report model performance in terms of next word prediction accuracy and loss. Additionally, we analyze the performance of the models on different types of prediction tokens for categories. For comparison, we also fine-tuned a non-GPT pretrained neural network model, XLNet (large), for next wth medical notes.BACKGROUND  Transnasal endoscopy presents a technical difficulty when inserting the flexible endoscope. It is unclear whether a particular breathing method is useful for transnasal endoscopy. Therefore, we conducted a prospective randomized controlled trial to compare endoscopic operability and patient tolerance between patients assigned to nasal breathing or oral breathing groups. METHODS  198 eligible patients were randomly assigned to undergo transnasal endoscopy with nasal breathing or with oral breathing. Endoscopists and patients answered questionnaires on the endoscopic operability and patient tolerance using a 100-mm visual analog scale ranging from 0 (non-existent) to 100 (most difficult/unbearable). The visibility of the upper-middle pharynx was recorded. RESULTS  Patient characteristics did not differ significantly between the groups. Nasal breathing showed a higher rate of good visibility of the upper-middle pharynx than oral breathing (91.9 % vs. 27.6 %; P  less then  0.001). Nasal breathing showed lower mean [SD] scores than oral breathing in terms of overall technical difficulty (21.0 [11.4] vs. 35.4 [15.0]; P  less then  0.001). Regarding patient tolerance, nasal breathing showed lower scores than oral breathing for overall discomfort (22.1 [18.8] vs. 30.5 [20.9]; P = 0.004) and other symptoms, including nasal and throat pain, choking, suffocating, gagging, belching, and bloating (all P  less then  0.05). The pharyngeal bleeding rate was lower in the nasal breathing group than in the oral breathing group (0 % vs. 9.2 %; P = 0.002). CONCLUSIONS  Nasal breathing is superior to oral breathing for those performing and undergoing transnasal endoscopy. Nasal breathing led to good visibility of the upper-middle pharynx, improved endoscopic operability, and better patient tolerance, and was safer owing to decreased pharyngeal bleeding.

This study aimed to determine parents‘ perception of the behavioral and auditory performance differences of children with hearing loss and anxiety levels of children and their parents during the pandemic.

This is a cross-sectional study.

The study included 75 parents who have preschool-aged children with hearing loss. The inclusion criteria were being a family member of a child with hearing loss between the ages of one and six years. The children’s mean age was 4.09 (± 1.42).

The evaluation forms included the control list to determine how the children with hearing loss and their parents were affected during the pandemic, the Parents‘ Evaluation of Aural Performance of Children rating scale to measure children’s auditory performance, the Preschool Behavior Questionnaire to assess behavior problems, the Preschool Anxiety Scale parental form, and the State-Trait Anxiety Inventory state form to measure the stress level of children and their parents. Parents were asked to fill out all forms. The Wilcoxon test was used to compare before and during the pandemic scores of PEACH and PBQ.