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Acute kidney injury occurs frequently in COVID-19 patients infected by the coronavirus SARS-CoV-2 and infection of kidney cells by this virus has been reported. However, little is known about the direct impact of the SARS-CoV-2 infection upon the renal tubular cells. We report that SARS-CoV-2 activated Signal Transducer and Activator of Transcription 3 (STAT3) signaling and caused cellular injury in the human renal tubular cell line (HK-2). Mechanistically, the viral protein ORF3A of SARS-CoV-2 augmented both NF-κB and STAT3 signaling and increased the expression of kidney injury molecule 1(KIM-1). SARS-CoV-2 infection or expression of ORF3A alone elevated the protein level of Tripartite motif-containing protein 59 (TRIM59), a ubiquitin E3 ligase, which interacts with both ORF3A and STAT3. The excessive TRIM59 in turn dissociated the phosphatase TCPIP from binding to STAT3 and hence inhibited the dephosphorylation of STAT3, leading to persistent STAT3 activation. Consistently, ORF3A induced renal injury in zebrafish and mice. In addition, expression of TRIM59 was elevated in the kidney autopsies of COVID-19 patients with AKI. Thus, the aberrant activation of STAT3 signaling by TRIM59 plays a significant role in the renal tubular cell injury caused SARS-CoV-2, which suggest a potential targeted therapy for the renal complications of COVID-19.

Ocular allergy leads to acute and chronic inflammation that may deteriorate the conjunctiva and other ocular tissue. The conjunctiva is covered with abundant lymphatic vessels but how the conjunctival lymphatic system patriciates in the development of allergic eye disease (AED) remains to be elucidated.By using ovalbumin (OVA)+pertussis toxin (PTX) as a sensitizer followed by daily OVA challenges, we induced optimized AED manifestations in mice. We show that conjunctival lymphatics underwent significant expansion after 28 days of chronic OVA challenge, and this process can be prevented by inducible genetic ablation of lymphatic Vegfr3. Through transcriptomic profile analysis in combination with histopathological examinations, we found that pro-lymphangiogenic VEGFR3 signal promoted allergy-induced activation of T helper 2 (Th2) type immune responses, including antigen presentation, and Th2 cells, B cells and mast cell-related pathways in the conjunctiva, thereby critically contributing to the immunoglobulin E (IgE) production and AED manifestations. As a result, ocular allergy can be alleviated by genetic inhibition of lymphatic Vegfr3. Interestingly, pro-lymphangiogenic VEGFR3 signal did not appear to affect the obstruction of meibomian glands (MGs) or the activation of Th17 type and neutrophil pathways that are associated with AED.These data reveal the key role of pro-lymphangiogenic VEGFR3 signaling in the development of AED and provide experimental evidence that VEGFR3 inhibition may be useful in treating ocular allergy in patients.

Iris segmentation is one of the most important steps in iris recognition. The current iris segmentation network is based on convolutional neural network (CNN). Among these methods, there are still problems with the segmentation networks such as high complexity, insufficient accuracy, etc. To solve these problems, an improved low complexity DenseUnet is proposed to this paper based on U-net for acquiring a high-accuracy iris segmentation network. In this network, the improvements are as follows: (1) Design a dense block module that contains five convolutional layers and all convolutions are dilated convolutions aimed at enhancing feature extraction; (2) Except for the last convolutional layer, all convolutional layers output feature maps are set to the number 64, and this operation is to reduce the amounts of parameters without affecting the segmentation accuracy; (3) The solution proposed to this paper has low complexity and provides the possibility for the deployment of portable mobile devices. DenseUnet is used on the dataset of IITD, CASIA V4.0 and UBIRIS V2.0 during the experimental stage. The results of the experiments have shown that the iris segmentation network proposed in this paper has a better performance than existing algorithms.

Background: Pulmonary hypertension (PH) is associated with increased expression of VEGF-A (vascular endothelial growth factor A) and its receptor, VEGFR2 (vascular endothelial growth factor 2), but whether and how activation of VEGF-A signal participates in the pathogenesis of PH is unclear. Methods: VEGF-A/VEGFR2 signal activation and VEGFR2 Y949–dependent vascular leak were investigated in lung samples from patients with PH and mice exposed to hypoxia. To study their mechanistic roles in hypoxic PH, we examined right ventricle systolic pressure, right ventricular hypertrophy, and pulmonary vasculopathy in mutant mice carrying knock-in of phenylalanine that replaced the tyrosine at residual 949 of VEGFR2 ( Vefgr2 Y949F ) and mice with conditional endothelial deletion of Vegfr2 after chronic hypoxia exposure. Results: We show that PH leads to excessive pulmonary vascular leak in both patients and hypoxic mice, and this is because of an overactivated VEGF-A/VEGFR2 Y949 signaling axis. In the context of hypoxic PH, activation of Yes1 and c-Src and subsequent VE-cadherin phosphorylation in endothelial cells are involved in VEGFR2 Y949-induced vascular permeability. Abolishing VEGFR2 Y949 signaling by Vefgr2 Y949F point mutation was sufficient to prevent pulmonary vascular permeability and inhibit macrophage infiltration and Rac1 activation in smooth muscle cells under hypoxia exposure, thereby leading to alleviated PH manifestations, including muscularization of distal pulmonary arterioles, elevated right ventricle systolic pressure, and right ventricular hypertrophy. It is important that we found that VEGFR2 Y949 signaling in myeloid cells including macrophages was trivial and dispensable for hypoxia-induced vascular abnormalities and PH. In contrast with selective blockage of VEGFR2 Y949 signaling, disruption of the entire VEGFR2 signaling by conditional endothelial deletion of Vegfr2 promotes the development of PH. Conclusions: Our results support the notion that VEGF-A/VEGFR2 Y949–dependent vascular permeability is an important determinant in the pathogenesis of PH and might serve as an attractive therapeutic target pathway for this disease.

The strong demand on high-performance lithium ion batteries has brought up an attention upsurge in the research society and the commercial market. Carbon materials have shown the great potential as anode materials for lithium ion batteries since they are low-cost, safe, abundant, and electrochemically stable. In this work, we report a selenium-doped carbon anode through carbonizing the mixture of selenium and an organic compound of naphthalenetetracarboxylic dianhydride. Benefiting from the porous structure, enlarged BET specific area, and active defects from the doping of Se, the material shows excellent rate capability. It delivers a high specific capacity of 450 mAh g−1 after 580 cycles at the current density of 500 mA g−1 and a specific capacity of 170 mAh g−1 after 2400 cycles at the current density of 1000 mA g−1. The superb performance of this material proves its potential as anode for high-performance lithium ion batteries.

Vesical Imaging-Reporting and Data System (VI-RADS) was proposed and considered as a standardized reporting criterion for bladder magnetic resonance imaging (MRI). VI-RADS could suggest the likelihood of muscle invasion based on the multiparametric MRI (mp-MRI) findings which contain five-point scores. The current study is designed to comprehensively and systematically evaluate the diagnostic performance of VI-RADS (score 3 and 4) for predicting muscle invasion.The Cochrane Library, Embase, and PubMed were searched comprehensively from inception to October 2021.Finally, 19 studies incorporating 2900 patients were enrolled. The pooled sensitivity and specificity of VI-RADS 3 for predicting muscle invasion were 0.92 (95%CI 0.89-0.94) and 0.82 (95%CI 0.76-0.87), respectively. The pooled sensitivity and specificity of VI-RADS 4 were 0.78 (95%CI 0.72-0.83) and 0.96 (95%CI 0.93-0.97), respectively. And the area under the curve (AUCs) of VI-RADS 3 and 4 were all 0.94 (95%CI 0.92-0.96). No significant publication biases were not observed for VI-RADS 3 (P = 0.74) and 4 (P = 0.57).The VI-RADS reveals a good diagnostic performance for predicting muscle invasive in bladder cancer, which also has good clinical utilities and applicability. And VI-RADS 3 and 4 as cutoff values provide similar overall diagnostic and could be selectively applied individually. Prospective studies with a large scale are further required to validate the accuracy of the VI-RADS score.

To simplify the preparation process of a glucose-responsive microneedle patch, a cross-linking-density changeable microneedle patch was designed. The microneedle patch was made up of a hydrogel formed by phenylboronic acid-grafted polyallylamine and poly(vinyl alcohol) (PVA). The gel was cross-linked by boronate ester bonds between phenylboronic acid groups and PVA. It still had fluidity and could be filled into a mold to prepare microneedle patches. Moreover, insulin could be directly loaded into the microneedle patch by mixing with the gel. The boronate ester bond would be broken in the presence of glucose, resulting in a decrease in the cross-linking density. Therefore, the gel could achieve a greater swelling degree and insulin could be released faster. In addition, PVA chains were crystallized by repeatedly freezing and thawing to improve the mechanical strength of the microneedle patch. In terms of glucose-dependent insulin release, the gel showed good glucose-responsive insulin-release ability. Through additional ion cross-linking, the microneedle patch could also control the insulin release according to glucose concentration. In the hypoglycemic experiment of diabetic rats, the microneedle patch effectively pierced the skin and slowly released insulin.

BACKGROUND: The renal glomerulus is a tuft of capillaries in Bowman’s capsule and functions as a blood-filtration unit in the kidney. The unique glomerular capillary tuft structure is relatively conserved through vertebrate species. However, the morphogenetic mechanism governing glomerular capillary tuft formation remains elusive. METHODS: To clarify how glomerular capillaries develop, we analyzed glomerular capillary formation in the zebrafish pronephros by exploiting fluorescence-based bio-imaging technology. RESULTS: During glomerular capillary formation in the zebrafish pronephros, endothelial cells initially sprouted from the dorsal aorta and formed the capillaries surrounding the bilateral glomerular primordia in response to podocyte progenitor-derived vascular endothelial growth factor-A. After formation, blood flow immediately occurred in the glomerular primordia-associated capillaries, while in the absence of blood flow, they were transformed into sheet-like structures enveloping the glomerular primordia. Subsequently, blood flow induced formation of Bowman’s space at the lateral sides of the bilateral glomerular primordia. Concomitantly, podocyte progenitors enveloped their surrounding capillaries while moving toward and coalescing at the midline. These capillaries then underwent extensive expansion and remodeling to establish a functional glomerular capillary tuft. However, stopping blood flow inhibited the remodeling of bilateral glomerular primordia, which therefore remained unvascularized but covered by the vascular sheets. CONCLUSIONS: We delineated the morphogenetic processes governing glomerular capillary tuft formation in the zebrafish pronephros and demonstrated crucial roles of blood flow in its formation. Blood flow maintains tubular structures of the capillaries surrounding the glomerular primordia and promotes glomerular incorporation of these vessels by inducing the remodeling of glomerular primordia.

ObjectiveTo investigate the impact of different dose algorithms and calculation angle intervals (DCAI) on the in vivo dose (IVD) verification of small-field arc therapy in stereotactic body radiation therapy (SBRT).MethodsWe made an exit-dose-measuring and positioning device (EDPD) for the SRS MapCHECK (SMC) using polymethyl methacrylate (PMMA). Computed tomography data for the anthropomorphic head phantom, SMC, and EDPD combination were acquired with 1 mm slice thickness and spacing. SBRT partial arc plans were created using an SBRT cone, block, and a small square open field, with a gantry rotation angle of 60°. The dose distribution was calculated using three different dose algorithms [Pencil Beam (PB), CC Convolution (CCC), and Monte Carlo (MC)], with 1 mm isotropic resolution. We also used three different DCAIs (1°, 3°, 5°) with the PB and CCC algorithms to calculate the dose distribution of each plan three times. The uncertainty of each control point for the MC algorithm was set to 1%. The SMC was used to measure the exit dose outside the phantom for IVD verification, the detector plane was located 182.5 mm outside the scan center.ResultsWithin the phantom, the minimum passing rate of 3D gamma analysis (1%/1 mm) for the dose distributions calculated at different DCAIs was 99.1%, and the maximum relative deviation (RD) of the central point dose (CPD) was 90% for the CCC algorithm at 1° DCAI.ConclusionThe DCAI for exit-dose calculations should be ≤1° using the CCC algorithm. Furthermore, among the three algorithms verified in the current study, the MC algorithm showed the highest accuracy, followed by CCC, with the PB algorithm having the worst performance. The PB algorithm is thus not suitable for exit-dose calculation or IVD verification of SBRT.

Microfluidic electric impedance flow cytometry (IFC) devices have been applied in single cell analysis, such as cell counting, volume discrimination, cell viability, etc. A cell's shape provides specific information about cellular physiological and pathological conditions, especially in microorganisms such as yeast. In this study, the particle orientation focusing was theoretically analyzed and realized by hydrodynamics. The pulse width (passing time for the particles) of the conductance signal was used to discriminate particle shapes. Spherical and rod-shaped particles with similar volumes/lengths were differentiated by the IFC device, using the impedance pulse parameters of the events. Then, typical late-budding, early budding, and unbudded yeast cells were distinguished by the width, amplitude, and ratio of width to amplitude (R) of the impedance pulse. The pulse amplitude and the R combination gate for identifying the late-budding yeast was estimated through the statistic results. Using the gate, the late-budding rates under different conditions were calculated. Late-budding rates obtained using our method showed a high correlation (R2 = 0.83) with the manual cell counting result and represented the budding status of yeast cells under different conditions proficiently. Thus, the late-budding rate calculated using the above method can be used as a qualitative parameter to assess the reproductive performance of yeast and whether a yeast culturing environment is optimal. This IFC device and cell shape discrimination method is very simple and could be applied in the fermentation industry and other microorganisms' discrimination as a rapid analysis technique in the future.

Low-cost supercapacitors with high energy densities have attracted great research attention, since it would broaden the application of capacitors. Increasing the capacitance is one principle to obt...

The heart of the product service system is combining the product and service organically, and then achieving a certain function to meet the needs of consumers. Products and services of identification based on finger veins are important parts of the development of cloud computing and Internet of Things. At present, the products using finger vein recognition are mostly applied or used in a small scale. Because different finger veins may have same or similar 2D projections which probably lead to recognition errors. Considering the request of the user and the need of information safety construction of enterprises, this paper proposes a three-dimensional skeleton reconstruction method of finger vein based on a quadrature biplane image acquisition system. By using the topological characteristics of finger vein skeletons, the matching for feature points of two 2D finger-vein skeletons has been achieved. Finally, piecewise curve fitting based on 2D skeleton segments from two 2D projections is developed to reconstruct the complete 3D skeleton. In the industrial of the IoT, this technology can be carried in various terminal products of the PSS, which can maximize the value for consumers and expedite PSS for development.

Benefiting from abundant redox chemistry and high electrochemical properties, metal sulfides have been broadly employed as electrode materials in supercapacitor systems. However, the predominant limitation in their performance, which arises from indifferent electron and ion dynamics for transportation and a rapid slash in capacitance, is of particular concern. Herein, we portray the cobalt sulfides/carbon (CoSx/C) hierarchical hollow nanocages using ZIF-67 nanocrystals coated with carbon from resorcinol–formaldehyde (ZIF-67@RF) as a self-sacrificial template. The RF acted as a hard framework to prevent the hollow structure from breaking and was transformed to a carbon layer to enhance the charge transfer process. When used as positive electrodes in supercapacitor systems with aqueous electrolytes, the optimized CoSx/C hierarchic hollow nanocages exhibited a considerable specific capacitance (618 F g−1 at 2 A g−1), superior rate performance (83.6% capacitance retention of the initial capacity when the current density was amplified from 2 A g−1 to 50 A g−1) and an extraordinary cycle stationarity along with an undiminished specific capacitance after 10 000 cycles. In this study, the meticulously designed hierarchical hollow structure that we conceived not only provides an outstanding electrochemical performance but also provides options for other related materials, such as various MOFs.

Background Hyperandrogenemia is more common in puberty and reproductive age, but relatively rare in postmenopausal women. Postmenopausal virilization may result from androgen-producing tumors. Androgen-secreting adrenal tumors are rare in clinical practice and are diagnosed as adrenocortical carcinoma, most of which can co-secrete androgen and cortisol. Highly elevated serum testosterone level with normal adrenal androgens such as dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS) and androstenedione is usually regarded as ovary origin. Here we describe an unusual case of a postmenopausal woman with markedly elevated serum testosterone level, while DHEAS, androstenedione, 17-hydroxyprogesterone and cortisol were within the normal range. Case presentation A 67-year-old postmenopausal woman with hirsutism in the upper lip and armpit, accompanied by clitoromegaly for 5 months. Hormonal evaluation showed markedly elevated serum testosterone level (714.8 ng/ml), whereas DHEAS, androstenedione, 17-hydroxyprogesterone, and cortisol were within the normal range. Imaging examination showed a mass of 1.5 cm in diameter in the left adrenal gland and normal appearance of both ovaries. PET-CT indicated that it was a case of benign adrenal adenoma and excluded ovarian abnormalities and other ectopic tumors. Thus, a pure testosterone-secreting adrenal tumor was suspected and then adrenalectomy was performed. Histology and immunohistochemistry furtherly confirmed the benign adrenocortical adenoma with immunohistochemistry positive for inhibin α, melan A, β-captenin, SYN (focal), Ki-67(

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.

It is important to emphasize that the adjustment of an organic&ndash, 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&ndash, 253 &deg, C, tensile strengths of 31.5&ndash, 53.4 MPa, and elongations at break of 74.5&ndash, 146.0%. The membranes possessed moderate water uptake (WR) values of 90.9&ndash, 101.7% and acceptable alkali resistances (swelling degrees were 187.2&ndash, 206.5% and weight losses were 10.0&ndash, 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&minus, (UOH) were in a range of 0.013&ndash, 0.022 m/h, and separate factors (S) were in an acceptable range of 22&ndash, 33. Sulfonic groups in the interfacial regions and &ndash, OH in the PVA main chains were both deemed to play corporate roles during the transport of Na+ and OH&minus

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.

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−.

Electrical impedance flow cytometry (EIFC) based on microfluidic chip has been applied to the analysis of cells and micron particles, but the sensitivity needs further optimization for bacterial detections. In this paper, we propose an optimization of buffer conductivity to improve the sensitivity of EIFC. In this paper, polystyrene microspheres and yeast were suspended in buffers with different conductivity and detected by EIFC chip respectively. After analysing the signal-to-noise ratio (SNR) and coefficient of variation (CV) of the data, the optimum buffer conductivities for detection were obtained for Polystyrene microspheres (~1.6 S/m) and bacteria (~6.4 S/m), respectively. Then using this optimized microfluidic detection system, the O1.0 and O0.8 μm microspheres, Staphylococcus aureus and Staphylococcus albicans were analyzed, respectively. The results proved that the sensitivity of the EIFC chip can be improved by optimizing the buffer conductivity, which promotes a foundation for the detection, differentiation and analysis of submicron particles/bacteria in the future.

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.