Search

Summary: Schlemm’s canal (SC) functions to maintain proper intraocular pressure (IOP) by draining aqueous humor and has emerged as a promising therapeutic target for glaucoma, the second-leading cause of irreversible blindness worldwide. However, our current understanding of the mechanisms governing SC development and functionality remains limited. Here, we show that vitronectin (VTN) produced by limbal macrophages promotes SC formation and prevents intraocular hypertension by activating integrin αvβ3 signaling. Genetic inactivation of this signaling system inhibited the phosphorylation of AKT and FOXO1 and reduced β-catenin activity and FOXC2 expression, thereby causing impaired Prox1 expression and deteriorated SC morphogenesis. This ultimately led to increased IOP and glaucomatous optic neuropathy. Intriguingly, we found that aged SC displayed downregulated integrin β3 in association with dampened Prox1 expression. Conversely, FOXO1 inhibition rejuvenated the aged SC by inducing Prox1 expression and SC regrowth, highlighting a possible strategy by targeting VTN/integrin αvβ3 signaling to improve SC functionality.

Abstract Lithium-selenium (Li-Se) batteries possess high volumetric capacity and have attracted considerable attention as a high energy storage system. However, the shuttling of polyselenides seriously worsens the electrochemical performance and retards their application advancement. Herein, we engineered a bifunctional membrane consisted of polyethylenimine derived carbon quantum dots (Cdots) to efficiently restrict the shuttling of polyselenides under a high Se loading (Se≈70 wt%) and promote Li-Se conversion kinetics, which can be accounted by the greatly accelerated transportation of charge carriers and dipole–dipole interactions between polar moieties and long-chain polyselenides (Li2Se4 and Li2Se6) as corroborated by theoretical calculations. Thus, the bifunctional membrane endows Li-Se batteries with a specific capacity of 658.60 mAh g−1 at 0.1 C and coulombic efficiency of 97.8% in average, and demonstrates the effectiveness of defect-rich Cdots on suppressing polyselenides shuttling and reinforcing Li-Se conversion kinetics in augmenting the battery’s durability and efficiency. Graphical Abstract

Quantitative susceptibility mapping (QSM) is a technique for obtaining quantitative information on tissue susceptibility and has shown promising potential for clinical applications, in which the magnetic susceptibility is calculated by solving an ill-posed inverse problem. Recently, deep learning-based methods are proposed to address this issue, but the diversity of data distribution was not well considered, and thus the model generalization is limited in clinical applications. In this paper, we propose a Latent Code based Multi-Variable modulation network for QSM reconstruction (LCMnet). Particularly, a specific modulation module is exploited to incorporate three variables, i.e., field map, magnitude image, and initial susceptibility. The latent code in the modulated convolution is learned from feature maps of the field data using the encoder-decoder framework. The susceptibility map pre-estimated from simple thresholding is the constant input of the module, thereby enhancing the network stability and accelerating training convergence. As another input, multi-level features generated by a cross-fusion block integrate the information of field and magnitude data effectively. Experimental results on in vivo human brain data, challenge data, clinical data and synthetic data demonstrate that the proposed method LCMnet can achieve outstanding performance on accurate susceptibility measurement and also excellent generalization.

Abstract The majority of kidney diseases arise from the loss of podocytes and from morphological changes of their highly complex foot process architecture, which inevitably leads to a reduced kidney filtration and total loss of kidney function. It could have been shown that microRNAs (miRs) play a pivotal role in the pathogenesis of podocyte-associated kidney diseases. Due to their fully functioning pronephric kidney, larval zebrafish have become a popular vertebrate model, to study kidney diseases in vivo. Unfortunately, there is no consensus about a proper normalization strategy of RT-qPCR-based miRNA expression data in zebrafish. In this study we analyzed 9 preselected candidates dre-miR-92a-3p, dre-miR-206-3p, dre-miR-99-1, dre-miR-92b-3p, dre-miR-363-3p, dre-let-7e, dre-miR-454a, dre-miR-30c-5p, dre-miR-126a-5p for their capability as endogenous reference genes in zebrafish experiments. Expression levels of potential candidates were measured in 3 different zebrafish strains, different developmental stages, and in different kidney disease models by RT-qPCR. Expression values were analyzed with NormFinder, BestKeeper, GeNorm, and DeltaCt and were tested for inter-group differences. All candidates show an abundant expression throughout all samples and relatively high stability. The most stable candidate without significant inter-group differences was dre-miR-92b-3p making it a suitable endogenous reference gene for RT-qPCR-based miR expression zebrafish studies.

Abstract Background Variants of chromodomain helicase DNA binding protein 7 (CHD7) gene are commonly associated with Kallmann syndrome (KS) and account for 5–6% of idiopathic hypogonadotropic hypogonadism (IHH) cases. Here we report a novel mutation of CHD7 gene in a patient with KS, which may contribute to the better understanding of KS. Case presentation A 29-year-old male patient with KS and a chief complaint of delayed puberty for 13 years (Tanner B Stage T mutation of TCD7 gene (p.G4856V) was detected, whereas none of his family members had this mutation. Human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) were injected for three times/week to treat idiopathic hypogonadotropic hypogonadism (IHH). After several months of therapy, the patient’s health condition improved. His testicles became larger, and his secondary sexual characteristics improved after treatment. Conclusion Exploration of the novel splice-site mutation of CHD7 may further our current understanding of KS.

Nephrotic syndrome (NS) is a disease characterized by proteinuria and subsequent hypoalbuminemia, hyperlipidemia and edema due to the defective renal glomerular filtration barrier (GFB). Mutations of NPHS1, encoding NEPHRIN, a podocyte protein essential for normal GFB, cause congenital nephrotic syndrome (CNS) of the Finnish type (CNF), which accounts for about 50% of CNS cases. We generated zebrafish nphs1 mutants by using CRISPR/Cas9. These mutants completely lack nephrin proteins in podocytes and develop progressive peri-orbital and whole-body edema after 5 days post fertilization. Ultra-structurally, loss of nephrin results in absence of slit-diaphragms and progressive foot process effacement in zebrafish pronephric glomeruli, similar to the pathological changes in human CNF patients. Interestingly, some nphs1 mutants are viable to adulthood despite ultra-structural defects in renal glomeruli. Using a reporter line Tg (l-fabp:VDBP-GFP) expressing GFP-tagged vitamin-D-binding protein in the blood plasma, we observed a reduction of intravascular GFP fluorescence in the nphs1 mutants, a hypoalbuminemia-like phenotype. In addition, we detected excretion of GFP by the nphs1 mutants, reminiscent of proteinuria. Therefore, we have demonstrated that the nphs1 mutant zebrafish recapitulate the human NS phenotypes and provide a novel and relevant animal model useful for screening therapeutical agents for this disease.

Managing the power transients with both high efficiency and thermal management constraints is a difficult task in the solid oxide fuel cell (SOFC) hybrid direct-current (DC) microgrids. This article proposed a SOFC-based DC microgrid, which consists of the SOFC stand-alone system, DC microgrid network, and DC/DC boost converter, along with the associated DC/DC load. The control and optimization strategy of the SOFC-based DC microgrids has been designed, including the thermal and electrical characteristics analysis. First, the voltage and current regulator based on the proportional–integral (PI) is designed, which can maintain the voltage stability of the proposed SOFC system. In addition, the optimal regulator based on the optimal operating points (OOPs) is designed, which can realize high efficiency and steady-state thermal safety of the proposed SOFC system. Finally, the main performance, including the SOFC stack electrical characteristics verification, SOFC stand-alone system electrical and thermal response, load-tracking characteristics, and system efficiency is observed and discussed in the proposed control and optimization strategy. Experimental results verify the correctness of the theoretical analysis and the effectiveness of the proposed optimization and control strategy.

An uncommon cause of primary hyperparathyroidism is a cystic parathyroid adenoma. This paper describes two patients with hypercalcemia and right knee disease. Their serum calcium concentration was high, phosphorus concentration was low, and parathyroid hormone (PTH) concentration was high. Ultrasound and computed tomography scans of the neck indicated a cystic mass near the thyroid. Parathyroid scintigraphy showed no focal uptake in one patient and low tracer concentration in the cystic mass in the other patient. Following resection of the cystic masses, both were pathologically confirmed to be a cystic parathyroid adenoma with predominantly cystic degeneration. The calcium and PTH concentrations gradually decreased to the reference range. Both patients were stable at their last follow-up. The diagnosis of a functional cystic parathyroid adenoma is highly challenging because of the different clinical manifestations and negative result on parathyroid tracer scintigraphy. For patients with high serum calcium and PTH concentrations and a cystic mass in the neck, resection of the mass and subsequent postoperative pathological diagnosis is necessary even if the clinical diagnosis of a parathyroid adenoma cannot be confirmed preoperatively. Decreases in the PTH and serum calcium concentrations indicate successful resection of a functional parathyroid adenoma.

The impermeable engineering surface layer in the cold regions blocks the water and heat exchange between the foundation soil and the atmospheric environment. Especially in cold areas with significant temperature differences, the moisture in the foundation soil accumulates at the bottom of the structure layer to form a covering effect. This will exacerbate the occurrence of engineering freeze-thaw diseases. This paper conducts a disease survey of the Guanshan oil and gas station site, which is located in a seasonally frozen soil zone. The ponding and freeze-thaw diseases under the concrete cover are analyzed. The formation process of the pot covering effect in the lower part of the concrete surface layer was reproduced through indoor tests. In addition, a water-vapor-heat coupling model of unsaturated soil was established, which quantitatively produced the formation process of silty clay covering under the concrete slab. The results show that (1) in-situ monitoring demonstrated that the water content of the roadbed soil from 0 to 50 cm below the concrete slab gathered significantly, with the water content increasing by 5 to 30%. (2) Under the action of the indoor time-varying covering effect, the moisture content of silty clay will increase with the number of freezing-thawing cycles, with a maximum migration amount of 6%. (3) Seasonal temperature changes lead to the accumulation of water in the subgrade surface, and the maximum accumulation amount is 32%. (4) During the freezing period, the liquid water and vapor water in the subgrade migrate to the surface layer of the subgrade. As a result, the moisture content of the subgrade surface layer increases, while the melting period is the opposite. The above research results can provide theoretical support and scientific countermeasures for engineering design and disease control in cold regions.

Abstract Background Langerhans cell histiocytosis (LCH) is a rare disease that mainly affects children, but this disease is significantly rarer in patients who are older than 15 years. In this disease, any organ can be involved. The skeleton, skin and lung are commonly affected, and isolated hypothalamic-pituitary (HP) involvement is relatively rare. Here we report a 17-year-old adolescent with isolated HP-LCH of enlarged pituitary stalk presented with central diabetes insipidus (CDI). Case presentation A 17-year-old male adolescent with polydipsia and polyuria accompanied with elevated serum sodium level and low urine osmolality for 3 weeks was referred to our hospital. After admission, hormonal evaluation showed that his growth hormone (GH) was slightly elevated, and serum osmolality and glucose were normal. The fluid deprivation-vasopressin test demonstrated CDI. Imaging examination showed an obvious thickening of the pituitary stalk. Lymphocytic hypophysitis, sarcoidosis and granulation tissue lesions were suspected. After oral 1-deamino-8-Darginine vasopressin (DDAVP) and prednisone were administered for 2 months, symptoms were relieved, and he discontinued taking the drugs by himself. On reexamination, imaging revealed changes in the size and shape of the pituitary stalk, with thickened nodules. Then, a diagnostic biopsy of the pituitary stalk lesion was performed. Immunohistochemistry confirmed the definitive diagnosis of LCH. The clinical symptoms subsided with oral hormone replacements. Conclusion CDI is a rare symptom in children and adolescents. Most of the causes are idiopathic, while others are caused by central nervous system (CNS) disorders. Meanwhile, lymphocytic hypophysitis, germinoma, LCH and other CNS disorders can all present as thickening of the pituitary stalk, diffuse enlargement of the pituitary gland, and weakening of high signal intensity in the neurohypophysis on magnetic resonance imaging (MRI). The differential diagnosis among these diseases depends on immunohistochemistry evidence.

In today’s information age, how to accurately identify a person’s identity and protect information security has become a hot topic of people from all walks of life. At present, a more convenient and secure solution to identity identification is undoubtedly biometric identification, but a single biometric identification cannot support increasingly complex and diversified authentication scenarios. Using multimodal biometric technology can improve the accuracy and safety of identification. This paper proposes a biometric method based on finger vein and face bimodal feature layer fusion, which uses a convolutional neural network (CNN), and the fusion occurs in the feature layer. The self-attention mechanism is used to obtain the weights of the two biometrics, and combined with the RESNET residual structure, the self-attention weight feature is cascaded with the bimodal fusion feature channel Concat. To prove the high efficiency of bimodal feature layer fusion, AlexNet and VGG-19 network models were selected in the experimental part for extracting finger vein and face image features as inputs to the feature fusion module. The extensive experiments show that the recognition accuracy of both models exceeds 98.4%, demonstrating the high efficiency of the bimodal feature fusion.

PurposeThe novel coronavirus COVID-19, has caused a worldwide pandemic, impairing several human organs and systems. Whether COVID-19 affects human thyroid function remains unknown.MethodsEighty-four hospitalized COVID-19 patients in the First Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou, China) were retrospectively enrolled in this study, among which 22 cases had complete records of thyroid hormones. In addition, 91 other patients with pneumonia and 807 healthy subjects were included as controls.ResultsWe found that levels of total triiodothyronine (TT3) and thyroid stimulating hormone (TSH) were lower in COVID-19 patients than healthy group (p < 0.001). Besides, TSH level in COVID-19 patients was obviously lower than non-COVID-19 patients (p < 0.001). Within the group of COVID-19, 61.9% (52/84) patients presented with thyroid function abnormalities and the proportion of thyroid dysfunction was higher in severe cases than mild/moderate cases (74.6 vs. 23.8%, p < 0.001). Patients with thyroid dysfunction tended to have longer viral nucleic acid cleaning time (14.1 ± 9.4 vs. 10.6 ± 8.3 days, p = 0.088). To note, thyroid dysfunction was also associated with decreased lymphocytes (p < 0.001) and increased CRP (p = 0.002). The correlation between TT3 and TSH level seemed to be positive rather than negative in the early stage, and gradually turned to be negatively related over time.ConclusionThyroid function abnormalities are common in COVID-19 patients, especially in severe cases. This might be partially explained by nonthyroidal illness syndrome.

Autoimmune polyglandular syndrome (APS) is a rare disease that is characterized by autoimmune reactions to multiple endocrine and non-endocrine organs, which can be divided into four main types. The principal manifestations of APS-3 are autoimmune thyroid disease and other autoimmune diseases, such as type 1 diabetes, atrophic gastritis, pernicious anemia, vitiligo, alopecia, and myasthenia gravis, but not Addison’s disease or hypoparathyroidism. Here we report a case demonstrating the rare coexistence of growth hormone deficiency and hyperthyroidism with sexual dysgenesis, secondary amenorrhea, cardiomegaly, splenomegaly, hypoproteinemia, pleural effusion, seroperitoneum, pericardial effusion, anasarca, osteoporosis, vitamin D deficiency, iron-deficiency anemia, poor blood coagulation, leucocytopenia, peripheral neuropathy, hyperuricemia, ichthyosis, tinea cruris, and onychomycosis.

Background Fibrocalculous pancreatic diabetes (FCPD), an uncommon form of secondary diabetes, is caused by chronic nonalcoholic calcific pancreatitis and primarily occurs in tropical countries. Objective To present our first-hand experiences in the diagnosis and management of FCPD in two patients from a non-tropical location. Case report Two male Chinese patients (29 and 32 years old) presented with poor insulin function, negative islet cell and glutamate decarboxylase antibodies, and no spontaneous ketosis or abdominal pain. A careful clinical assessment was made and the results were correlated with laboratory findings. Abdominal ultrasound and computed tomography scans further revealed pancreatic calcification, calculi, and pancreatic duct dilation. Differential diagnosis confirmed FCPD and excluded the potential misdiagnosis of type 2 diabetes mellitus. FCPD in these patients was managed with insulin and symptomatic treatment with close monitoring. At the time of submission of this report, the first patient was stable at his last follow-up, but the second had been re-hospitalized for worsening symptoms. Conclusion Early differential diagnosis of FCPD based on clinical examination and biochemical and radiological investigations, in tandem with insulin therapy, can help manage FCPD effectively.

Unraveling the genetic susceptibility of complex diseases such as chronic kidney disease remains challenging. Here, we used inbred rat models of kidney damage associated with elevated blood pressure for the comprehensive analysis of a major albuminuria susceptibility locus detected in these models. We characterized its genomic architecture by congenic substitution mapping, targeted next-generation sequencing, and compartment-specific RNA sequencing analysis in isolated glomeruli. This led to prioritization of transmembrane protein Tmem63c as a novel potential target. Tmem63c is differentially expressed in glomeruli of allele-specific rat models during onset of albuminuria. Patients with focal segmental glomerulosclerosis exhibited specific TMEM63C loss in podocytes. Functional analysis in zebrafish revealed a role for tmem63c in mediating the glomerular filtration barrier function. Our data demonstrate that integrative analysis of the genomic architecture of a complex trait locus is a powerful tool for identification of new targets such as Tmem63c for further translational investigation.

It is important to emphasize that the adjustment of an organic–inorganic interfacial chemical environment plays an important role during the separation performance of composite materials. In this paper, a series of hybrid membranes were prepared by blending polyvinyl alcohol (PVA) solution and sulfonated nano-TiO2 (SNT) suspension. The effects of different interfacial chemical surroundings on ions transfer were explored by regulating the dosage content of SNT. The as-prepared membranes exhibited high thermal and mechanical stability, with initial decomposition temperatures of 220–253 °C, tensile strengths of 31.5–53.4 MPa, and elongations at break of 74.5–146.0%. The membranes possessed moderate water uptake (WR) values of 90.9–101.7% and acceptable alkali resistances (swelling degrees were 187.2–206.5% and weight losses were 10.0–20.8%). The as-prepared membranes were used for the alkali recovery of a NaOH/Na2WO4 system via the diffusion dialysis process successfully. The results showed that the dialysis coefficients of OH− (UOH) were in a range of 0.013–0.022 m/h, and separate factors (S) were in an acceptable range of 22–33. Sulfonic groups in the interfacial regions and –OH in the PVA main chains were both deemed to play corporate roles during the transport of Na+ and OH−.

PZT matrix ferroelectric composite is an important research topic in material science because of its many practical, industrial, and scientific applications. Materials with high dielectric permittivity are used to manufacture electronic devices, particularly capacitors and dynamic random access memory (DRAM). Therefore, the development of reliable and efficient micro models to be utilized in analyzing electrical properties can be of great value in accelerating research in this field. In this paper, a 3D microstructure model for PZT matrix ferroelectric composites has been developed and adopted the finite element method (FEM) to calculate the dielectric constant. The microscopy parameters of developed microstructure model are acquired based on the real composites from X-ray (micro-) diffraction and stereological method. The dielectric constant of different volume ratios of PZT matrix ferroelectric composites can be calculated by accurately controlling the volume of Ferrite particles. At the point of validation, the proposed approach makes visual and numeric comparisons between the morphology of the real microstructure and the model generated by the proposed technique. The simulation results by our method was essentially in agreement with experimental results in other literature. Simulation Experimental results also demonstrate that the dielectric constant of PZT matrix ferroelectric composites is significantly changed while the volume ratio of high dielectric phase particles was below 20%. PZT matrix ferroelectric composites Consequently, this method can be easily extended to composites preparation.

Linking the ferrite fraction in a dual-phase (DP) steel microstructure and its electromagnetic properties is critical in the effort to develop on-line measurement techniques for phase transformation using electromagnetic (EM) sensors. This paper developed a seamlessly integrated method for generating 3D microstructures and evaluating their equivalent permeability values. Both the generation of 3D microstructures and evaluation of equivalent permeability have been achieved through custom modelling packages developed by the authors. Voronoi modelling based on the random close packing of spheres (RCPS-VM) was used to precisely control the ferrite fraction in DP steel microstructure, and an equivalent uniform field method for 3D finite element simulation was developed for efficient analysis.

The identification of recessive disease-causing genes by homozygosity mapping is often restricted by lack of suitable consanguineous families. To overcome these limitations, we apply homozygosity mapping to single affected individuals from outbred populations. In 72 individuals of 54 kindred ascertained worldwide with known homozygous mutations in 13 different recessive disease genes, we performed total genome homozygosity mapping using 250,000 SNP arrays. Likelihood ratio Z-scores (ZLR) were plotted across the genome to detect ZLR peaks that reflect segments of homozygosity by descent, which may harbor the mutated gene. In 93% of cases, the causative gene was positioned within a consistent ZLR peak of homozygosity. The number of peaks reflected the degree of inbreeding. We demonstrate that disease-causing homozygous mutations can be detected in single cases from outbred populations within a single ZLR peak of homozygosity as short as 2 Mb, containing an average of only 16 candidate genes. As many specialty clinics have access to cohorts of individuals from outbred populations, and as our approach will result in smaller genetic candidate regions, the new strategy of homozygosity mapping in single outbred individuals will strongly accelerate the discovery of novel recessive disease genes.

The pituitary gland orchestrates multiple endocrine organs by secreting tropic hormones, and therefore plays a significant role in a myriad of physiological processes, including skeletal modeling and remodeling, fat and glucose metabolism, and cognition. Expression of receptors for each pituitary hormone and the hormone itself in the skeleton, fat, immune cells, and the brain suggest that their role is much broader than the traditionally attributed functions. FSH, believed solely to regulate gonadal function is also involved in fat and bone metabolism, as well as in cognition. Our emerging understanding of nonreproductive functions of FSH, thus, opens potential therapeutic opportunities to address detrimental health consequences during and after menopause, namely, osteoporosis, obesity, and dementia. In this review, we outline current understanding of the cross-talk between the pituitary, bone, adipose tissue, and brain through FSH. Preclinical evidence from genetic and pharmacologic interventions in rodent models, and human data from population-based observations, genetic studies, and a small number of interventional studies provide compelling evidence for independent functions of FSH in bone loss, fat gain, and congnitive impairment. [ABSTRACT FROM AUTHOR]