A phenothiazine-based ratiometric fluorescence probe for the detection of hydroxylamine in real water and living cells.

In this study, a phenothiazine-based ratiometric fluorescent probe PCHO was developed for highly sensitive and specific detection of hydroxylamine (HA). In the presence of HA, the aldehyde group on the PCHO molecule underwent a specific nucleophilic addition with HA to form an oxime group, accompanied by significant changes in fluorescence from green to blue. This detection mechanism was well supported by 1H NMR titration, HRMS and DFT calculations. The probe PCHO exhibited high sensitivity for HA detection (LOD was 0.19 µM) with a rapid response time (1 min), high selectivity and strong anti-interference performance. Surprisingly, the probe PCHO could selectively distinguish HA from its similar competing agents such as hydrazine and amines. Moreover, paper strips loaded with PCHO were prepared and combined with a smartphone to achieve point-of-care and visual detection of HA. The probe PCHO was further applied for the detection of HA in real water samples, achieving a recovery rate of 98.90% to 104.86% and an RSD of 0.86% to 2.44%, confirming the accuracy and reliability of the method. Additionally, the probe PCHO was used for imaging analysis of HA in living cells, providing a powerful visualization tool for exploring the physiological functions of HA in vivo.

Tislelizumab combined with sunitinib in the treatment of metastatic clear cell renal cell carcinoma with renal venous tumor thrombus: A case report and literature review.

In recent years, with the in-depth study of PD-1/PD-L1 related pathways, great progress has been made in cancer immunotherapy. However, the immunotherapy regimen for mccRCC is still controversial in clinical practice. A 50-year-old man with mccRCC complicated with renal venous tumor thrombus from 2019 to present, including surgical treatment, targeted therapy and the combined treatment regimen of "Tislelizumab combined with Sunitinib". Although he experienced a roller coaster of adverse reactions during treatment, the patient's prognosis was good. Tislelizumab combined with Sunitinib is safe and effective in the Treatment of mccRCC.

Expanding the toolset of fluorescent covalent staining of biological samples by labeling carboxylate and phosphate groups.

Recently, fluorescent covalent staining methods have been developed for visualization of anatomical structures in cells and tissues. Coupled with expansion microscopy, these stains revealed various ultrastructural details. However, the covalently stainable chemical groups have been limited to amines, carbohydrates, and thiols. Here, we developed procedures for covalently labeling tissues for carboxylate and phosphate groups, utilizing carbodiimide crosslinker chemistry. In porcine kidney tissues, the carboxylate and phosphate stain provides 1.8-4.8-fold higher signal intensity than those from the three existing stains. In cancer cells, such stain allows 2-8-fold more accurate identification of nucleoli than the amine stain. In expansion microscopy samples, such stain reveals a variety of sub-cellular structures in tissues when combined with the amine stain. Such stain also allows imaging of lipid-based structures in cultured cells. With these advantages, this new covalent staining method further expands the toolset for fluorescent visualization of histology.

Molecular genetic features and clinical manifestations in Chinese familial cerebral cavernous malformation: from a novel KRIT1/CCM1 mutation (c.1119dupT) to an overall view.

Cerebral cavernous malformations (CCMs) are common vascular anomaly diseases in the central nervous system associated with seizures, cerebral microbleeds, or asymptomatic mostly. CCMs can be classified as sporadic or familial, with familial cerebral cavernous malformations (fCCMs) being the autosomal dominant manner with incomplete penetrance. Germline mutations of KRIT1, CCM2, and PDCD10 are associated with the pathogenesis of fCCMs. Till now, little is known about the fCCMs mutation spectrum in the Han Chinese population. In this study, we enrolled a large, aggregated family, 11/26 of the family members were diagnosed with CCMs by pathological or neuroradiological examination, with a high percentage (5/9) of focal spinal cord involvement. Genomic DNA sequencing verified a novel duplication mutation (c.1119dupT, p.L374Sfs*9) in exon 9 of the Krev interaction trapped 1 (KRIT1) gene. The mutation causes a frameshift and is predicted to generate a truncated KRIT1/CCM1 protein of 381 amino acids. All our findings confirm that c.1119dupT mutation of KRIT1 is associated with fCCMs, which enriched the CCM genes' mutational spectrum in the Chinese population and will be beneficial for deep insight into the pathogenesis of Chinese fCCMs. Additionally, with a retrospective study, we analyzed the molecular genetic features of Chinese fCCMs, most of the Chinese fCCMs variants are in the KRIT1 gene, and all these variants result in the functional deletion or insufficiency of the C-terminal FERM domain of the KRIT1 protein.

Anatomical Evidence for Parasympathetic Innervation of the Renal Vasculature and Pelvis.

BACKGROUND: The kidneys critically contribute to body homeostasis under the control of the autonomic nerves, which enter the kidney along the renal vasculature. Although the renal sympathetic and sensory nerves have long been confirmed, no significant anatomic evidence exists for renal parasympathetic innervation. METHODS: We identified cholinergic nerve varicosities associated with the renal vasculature and pelvis using various anatomic research methods, including a genetically modified mouse model and immunostaining. Single-cell RNA sequencing (scRNA-Seq) was used to analyze the expression of AChRs in the renal artery and its segmental branches. To assess the origins of parasympathetic projecting nerves of the kidney, we performed retrograde tracing using recombinant adeno-associated virus (AAV) and pseudorabies virus (PRV), followed by imaging of whole brains, spinal cords, and ganglia. RESULTS: We found that cholinergic axons supply the main renal artery, segmental renal artery, and renal pelvis. On the renal artery, the newly discovered cholinergic nerve fibers are separated not only from the sympathetic nerves but also from the sensory nerves. We also found cholinergic ganglion cells within the renal nerve plexus. Moreover, the scRNA-Seq analysis suggested that acetylcholine receptors (AChRs) are expressed in the renal artery and its segmental branches. In addition, retrograde tracing suggested vagus afferents conduct the renal sensory pathway to the nucleus of the solitary tract (NTS), and vagus efferents project to the kidney. CONCLUSIONS: Cholinergic nerves supply renal vasculature and renal pelvis, and a vagal brain-kidney axis is involved in renal innervation.

Reasonable Construction of Hollow Carbon Spheres with an Adjustable Shell Surface for Supercapacitors.

Hollow carbon spheres (HCS) manifest specific merit in achieving large interior void space, high permeability, wide contactable area, and strong stacking ability with negligible aggregation and have attracted attention due to their high supercapacitor activity. As the key factor affecting supercapacitor performance, the surface chemical properties, shell thickness, roughness, and pore volumes of HCS are the focus of research in this field. Herein, the surface chemical properties and structures of HCS are simultaneously adjusted by a feasible and simple process of in situ activation during assembly of resin and potassium chloride (KCl). This strategy involves KCl participating in resin polymerization and the superior performance of potassium species on activating carbon. The surface N/O content, thickness, defects, and roughness degree of HCS can be controlled by adjusting the dosage of KCl. Electrochemical tests show that optimized HCS has suitable roughness, high surface area, and abundant surface N/O functional groups, which endow it with excellent electrochemical capacitance properties, showing its high potential in supercapacitors.

De-differentiation associated with drop metastasis of a recurrent intracranial solitary fibrous tumor: a case report and literature review.

BACKGROUND: Central nervous system is a rare occurring location of solitary fibrous tumors (SFTs). SFTs have a potential for recurrence, which is the leading cause of death in patients with these disease entities. De-differentiation phenomenon combined with cerebrospinal fluid (CSF) dissemination through drop metastasis of STFs from intracranial to intraspinal has only been reported in extremely limited cases. CASE DESCRIPTION: Herein, we present a case of SFT in a 54-year old male. MRI showed characteristic of mixed high and low signal with 6.3 cm × 6.5 cm × 5.9 cm. After radical surgical resection, the pathology indicated benign SFT. However, MRI re-examination of 22 months later detected local recurrence, concomitant with spreading of intracranial and intraspinal through CSF dissemination. And interestingly, the second pathology found de-differentiation phenomenon and malignance of SFT, in which some areas transformed to rhabdomyosarcoma. CONCLUSION: This is the first case report of recurrent intracranial SFT de-differentiating to rhabdomyosarcoma concurrent with CSF pathway drop metastasis. Benign intracranial SFTs have the potential of de-differentiation, which may play an important role in its distant metastasis. The underlying molecular biological and pathological mechanisms of benign SFT malignance transformation still warrant further exploration.

Yeasts-derived nitrogen-doped porous carbon microcapsule prepared by silica-confined activation for supercapacitor.

Biomass is a common carbon precursor, because of its low cost, easy access and wide sources. However, direct pyrolysis of biomass usually leads to some disadvantages such as morphology destruction, low surface area and poor porosity. Herein, a silica-confined activation strategy is developed to prepare nitrogen-doped (N-doped) porous carbon microcapsule using the renewable biomass carbon precursor of yeasts. The yeasts are wrapped by a dense silica shell, forming a limited space, which can effectively avoid the destruction of yeast morphology during pyrolysis. The pyrolysis gas derived from yeast cannot overflow due to the limitation of confined space, and it plays an in-situ activator to result in layer structure with thin wall, abundant pores and high specific surface area (870 m2 g-1). Moreover, the N-doped porous carbon microcapsule possesses a higher certain of N-doping than the carbon product derived from direct pyrolysis of yeasts. As electrode materials in supercapacitor, the N-doped porous carbon microcapsule exhibits high capacitance of 316 F g-1 at 1 A g-1 with obvious enhancement of electrochemical performance compared with the carbon product derived from direct pyrolysis of yeasts, indicating the promise as a new electrode material in energy storage.

N/B-co-doped ordered mesoporous carbon spheres by ionothermal strategy for enhancing supercapacitor performance.

Heteroatom doping in carbonaceous materials is an effective way to improve the performance of supercapacitors. Herein, the N/B-co-doped ordered mesoporous carbon spheres (N/B-OMC) were developed by a facile ionothermal strategy. The ordered mesoporous phenol/formaldehyde resin (PF) spheres were employed as carbon precursor, which was treated by ionothermal process using 1-butyl 3-methyl-imidazole tetrafronoroborate ([Bmim]BF4) as medium. The [Bmim]BF4 can be absorbed in the pores of PF spheres, leading to N/B-co-doping for the obtained carbon framework without damage in spherical morphology and ordered mesoporous structure. As a result, the dual-heteroatom doping, high surface area and enlarged mesopore size of N/B-OMC can enhance the electrochemical performance, exhibiting its promising as novel electrode materials.

Nuclear Factor κB/MicroRNA-155 Upregulates the Expression Pattern of Cytokines in Regulating the Relapse of Chronic Sinusitis with Nasal Polyps and the Underlying Mechanism of Glucocorticoid.

BACKGROUND The aim of this study was to explore the upregulated nuclear factor kappaB (NF-kappaB)/microRNA-155 (miR-155) in regulating inflammatory responses and relapse of chronic rhinosinusitis (CRS) with nasal polyps (NP), which underlies the molecular mechanism of glucocorticoid treatment. MATERIAL AND METHODS The study recruited 25 patients with eosinophilic (Eos) CRSwNP, 25 patients with Non-Eos CRSwNP, 25 patients with CRS without NP (CRSsNP) and 30 patients with nasal septum deviation (control group). The expression of NF-kappaB/miR-155 and inflammatory cytokines was detected in epithelial tissue specimens. Additionally, a mouse model of Eos CRSwNP was established, and the mice were treated by NF-kappaB inhibitor, miR-155 antagomir, or dexamethasone (DEX) to explore the role of NF-kB/miR-155 and the anti-inflammatory effects of glucocorticoid treatment. RESULTS Results showed that the expression level of NF-kappaB/miR-155 was significantly elevated in the Eos CRSwNP group, accompanied by the upregulation of cytokines: tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-4, IL-5 (P<0.05) compared with the control group, the CRSsNP group or the Non-Eos CRSwNP group. The upregulation of NF-kappaB/miR-155 increased inflammatory mediator cyclooxygenase2 (COX2) while decreasing anti-inflammatory mediator Src homology-2 domain-containing inositol 5-phosphatase 1 (SOCS1), which resulted in the aberrant expression pattern of cytokines in the mice model. DEX treatment inhibited the expression of cytokines and decreased the relapse rate of Eos CRSwNP via inhibiting NF-kappaB/miR-155 (P<0.05). CONCLUSIONS The upregulation of NF-kappaB/miR-155 was crucial in mediating the aberrant expression of inflammatory cytokines in Eos CRSwNP. This molecular mechanism is a concern with the high relapse rate of Eos CRSwNP. However, glucocorticoid treatment inhibited the relapse of CRSwNP via downregulation of NF-kappaB/miR-155.

Electrospun nanofiber-reinforced three-dimensional chitosan matrices: Architectural, mechanical and biological properties.

The poor intrinsic mechanical properties of chitosan hydrogels have greatly hindered their practical applications. Inspired by nature, we proposed a strategy to enhance the mechanical properties of chitosan hydrogels by construction of a nanofibrous and cellular architecture in the hydrogel without toxic chemical crosslinking. To this end, electrospun nanofibers including cellulose acetate, polyacrylonitrile, and SiO2 nanofibers were introduced into chitosan hydrogels by homogenous dispersion and lyophilization. With the addition of 30% cellulose acetate nanofibers, the cellular structure could be maintained even in water without crosslinking, and integration of 60% of the nanofibers could guarantee the free-standing structure of the chitosan hydrogel with a low solid content of 1%. Moreover, the SiO2 nanofiber-reinforced chitosan (SiO2 NF/CS) three-dimensional (3D) matrices exhibit complete shape recovery from 80% compressive strain and excellent injectability. The cellular architecture and nanofibrous structure in the SiO2 NF/CS matrices are beneficial for human mesenchymal stem cell adhesion and stretching. Furthermore, the SiO2 NF/CS matrices can also act as powerful vehicles for drug delivery. As an example, bone morphogenetic protein 2 could be immobilized on SiO2 NF/CS matrices to induce osteogenic differentiation. Together, the electrospun nanofiber-reinforced 3D chitosan matrices exhibited improved mechanical properties and enhanced biofunctionality, showing great potential in tissue engineering.

N-Doped Mesoporous Carbon Sheets/Hollow Carbon Spheres Composite for Supercapacitors.

Composite carbon materials with multiple morphologies (such as spheres/sheets and spheres/tubes) that combine the merits of both structures have a wide range of applications in electrochemistry, catalysis, energy storage, and so on. Therefore, the development of an efficient and simple method for preparing carbonaceous composite materials is a research hot spot. On the basis of the inhomogeneity of 3-aminophenol/formaldehyde (3-AF) polymerization spheres, the hollow 3-AF spheres were obtained after the dissolution of the internal 3-AF oligomer. The dispersed 3-AF oligomer was reassembled with silicate oligomers on the hard template of Mg(OH)2 sheets and hollow 3-AF spheres linked by CTAB through electrostatic force. The obtained N-MCS/HCS possessed both sheet and sphere structure, with a high specific surface area and uniform mesoporous distribution. As an electrode material, N-MCS/HCS exhibited a good specific capacity (270 F g-1 at the current density of 1 A g-1) and outstanding cycling life stability (96.3% after 5000 cycles) at a current density of 5 A g-1 and could be used as a new electrode material.

Immunogenicity of varicella zoster virus glycoprotein E DNA vaccine.

In the present study a eukaryotic expression vector of varicella zoster virus (VZV) glycoprotein E (gE) was constructed and enabled to express in COS7 cells. Furthermore, a specific immune response against the VZV gE eukaryotic expression plasmid was induced in BALB/c mice. The VZV gE gene was amplified using polymerase chain reaction (PCR) and cloned into a eukaryotic expression vector, pcDNA3.1. The recombinant vector was subsequently transfected into COS7 cells using a liposome transfection reagent. The recombinant protein was instantaneously expressed by the transfected cells, as detected by immunohistochemistry, and the recombinant pcDNA-VZV gE plasmid was subsequently used to immunize mice. Tissue expression levels were analyzed by reverse transcription-PCR. In addition, the levels of serum antibodies and spleen lymphocyte proliferation activity were investigated. The amplified target gene included the full-length gE gene (~2.7 kb), and the recombinant expression vector induced gE expression in COS7 cells. In addition, the expression plasmid induced sustained expression in vivo following immunization of mice. Furthermore, the plasmid was capable of inducing specific antibody production and effectively stimulating T cell proliferation. Effective humoral and cellular immunity was triggered in the mice immunized with the VZV gE eukaryotic expression vector. The results of the present study laid the foundation for future research into a VZV DNA vaccine.

MicroRNA-185 targets SOCS3 to inhibit beta-cell dysfunction in diabetes.

Diabetes is the most common and complex metabolic disorder, and one of the most important health threats now. MicroRNAs (miRNAs) are a group of small non-coding RNAs that have been suggested to play a vital role in a variety of physiological processes, including glucose homeostasis. In this study, we investigated the role of miR-185 in diabetes. MiR-185 was significantly downregulated in diabetic patients and mice, and the low level was correlated to blood glucose concentration. Overexpression of miR-185 enhanced insulin secretion of pancreatic ß-cells, promoted cell proliferation and protected cells from apoptosis. Further experiments using in silico prediction, luciferase reporter assay and western blot assay demonstrated that miR-185 directly targeted SOCS3 by binding to its 3'-UTR. On the contrary to miR-185's protective effects, SOCS3 significantly suppressed functions of ß-cell and inactivated Stat3 pathway. When treating cells with miR-185 mimics in combination with SOCS3 overexpression plasmid, the inhibitory effects of SOCS3 were reversed. While combined treatment of miR-185 mimics and SOCS3 siRNA induced synergistically promotive effects compared to either miR-185 mimics or SOCS3 siRNA treatment alone. Moreover, we observed that miR-185 level was inversely correlated with SOCS3 expression in diabetes patients. In conclusion, this study revealed a functional and mechanistic link between miR-185 and SOCS3 in the pathogenesis of diabetes. MiR-185 plays an important role in the regulation of insulin secretion and ß-cell growth in diabetes. Restoration of miR-185 expression may serve a potentially promising and efficient therapeutic approach for diabetes.

A co-confined carbonization approach to aligned nitrogen-doped mesoporous carbon nanofibers and its application as an adsorbent.

Nitrogen-doped carbon nanofibers (MCNFs) with an aligned mesoporous structure were synthesized by a co-confined carbonization method using anodic aluminum oxide (AAO) membrane and tetraethylorthosilicate (TEOS) as co-confined templates and ionic liquids as the precursor. The as-synthesized MCNFs with the diameter of 80-120nm possessed a bulk nitrogen content of 5.3wt% and bimodal mesoporous structure. The nitrogen atoms were mostly bound to the graphitic network in two forms, i.e. pyridinic and pyrrolic nitrogen, providing adsorption sites for acidic gases like SO2 and CO2. Cyclic experiments revealed a considerable stability of MCNFs over 20 runs of SO2 adsorption and 15 runs for CO2 adsorption. The MCNFs also have a preferable adsorption performance for Cd(2+).