Cytosolic Hmgb1 accumulation in mesangial cells aggravates diabetic kidney disease progression via NFκB signaling pathway.

Diabetic kidney disease (DKD) is the predominant type of end-stage renal disease. Increasing evidence suggests thatglomerular mesangial cell (MC) inflammation is pivotal for cell proliferation and DKD progression. However, the exactmechanism of MC inflammation remains largely unknown. This study aims to elucidate the role of inflammatoryfactor high-mobility group box 1 (Hmgb1) in DKD. Inflammatory factors related to DKD progression are screened viaRNA sequencing (RNA-seq). In vivo and in vitro experiments, including db/db diabetic mice model, CCK-8 assay, EdUassay, flow cytometric analysis, Co-IP, FISH, qRT-PCR, western blot, single cell nuclear RNA sequencing (snRNA-seq),are performed to investigate the effects of Hmgb1 on the inflammatory behavior of MCs in DKD. Here, wedemonstrate that Hmgb1 is significantly upregulated in renal tissues of DKD mice and mesangial cells cultured withhigh glucose, and Hmgb1 cytopasmic accumulation promotes MC inflammation and proliferation. Mechanistically,Hmgb1 cytopasmic accumulation is two-way regulated by MC-specific cyto-lncRNA E130307A14Rik interaction andlactate-mediated acetylated and lactylated Hmgb1 nucleocytoplasmic translocation, and accelerates NFκB signalingpathway activation via directly binding to IκBα. Together, this work reveals the promoting role of Hmgb1 on MCinflammation and proliferation in DKD and helps expound the regulation of Hmgb1 cytopasmic accumulation in twoways. In particular, Hmgb1 may be a promising therapeutic target for DKD.

Secondary-Bond-Driven Construction of a Polar Material Exhibiting Strong Broad-Spectrum Second-Harmonic Generation and Large Birefringence.

Considerable effort has been invested in the development of non-centrosymmetric (NCS) inorganic solids for ferroelectricity-, piezoelectricity- and, particularly, optical nonlinearity-related applications. While great progress has been made, a persistent problem is the difficulty in constructing NCS materials, which probably stems from non-directionality and unsaturation of the ionic bonds between metal counter-cations and covalent anionic modules. We report herein a secondary-bond-driven approach that circumvents the cancellation of dipole moments between adjacent anionic modules that has plagued second-harmonic generation (SHG) material design, and which thereby affords a polar structure with strong SHG properties. The resultant first NCS counter-cation-free iodate, VO2 (H2 O)(IO3 ) (VIO), a new class of iodate, crystallizes in a polar lattice with ∞ 1 [ ${{}_{{\rm { \infty }}}{}^{{\rm { 1}}}{\rm { [}}}$ VO2 (H2 O)(IO3 )] zigzag chains connected by weak hydrogen bonds and intermolecular forces. VIO exhibits very large SHG responses (18 × KH2 PO4 @ 1200 nm, 1.5 × KTiOPO4 @ 2100 nm) and sufficient birefringence (0.184 @ 546 nm). Calculations and crystal structure analysis attribute the large SHG responses to consistent polarization orientations of the ∞ 1 [ ${{}_{{\rm { \infty }}}{}^{{\rm { 1}}}{\rm { [}}}$ VO2 (H2 O)(IO3 )] chains controlled by secondary bonds. This study highlights the advantages of manipulating the secondary bonds in inorganic solids to control NCS structure and optical nonlinearity, affording a new perspective in the development of high-performance NLO materials.

Ultrawide Bandgap and Outstanding Second-Harmonic Generation Response by a Fluorine-Enrichment Strategy at a Transition-Metal Oxyfluoride Nonlinear Optical Material.

The development of nonlinear optical (NLO) materials has been hindered by competing microstructure requirements: the need to simultaneously engineer a large hyperpolarizability (a large second-harmonic generation (SHG)) and a wide HOMO-LUMO gap (a wide band gap). Herein, a non-centrosymmetric transition-metal (TM) oxyfluoride K5 (NbOF4 )(NbF7 )2 (KNOF) with an extremely high F/O ratio is constructed in high yield. KNOF exhibits an extremely wide band gap (5.88 eV) and a strong powder SHG response (4.0×KH2 PO4 )-both being the largest values for TM-centered oxyfluorides-as well as a birefringence sufficient for applications. The dominant roles of the partially fluorinated [NbO2 F4 ] and totally fluorinated [NbF7 ] groups in achieving the enlarged band gap in KNOF have been clarified by first-principles calculations. Our results suggest that maximizing the fluorine content of oxyfluorides may unlock the promise of short-wavelength-transparent materials with exceptional NLO performance.

A Lanthanum Ammonium Sulfate Double Salt with a Strong SHG Response and Wide Deep-UV Transparency.

The targeted synthesis of deep-ultraviolet (deep-UV) nonlinear optical (NLO) materials, especially those with non-π-conjugated sulfates, has experienced considerable difficulties due to the need to reconcile the oft-competing requirements for deep-UV transparency and strong second-harmonic generation (SHG). We report herein the designed synthesis of the first rare-earth metal-based deep-UV sulfate La(NH4 )(SO4 )2 by a double-salt strategy involving introduction of complementary cations, together with optical studies that reveal a short-wavelength deep-UV absorption edge (below 190 nm) and the strongest SHG response among deep-UV NLO sulfates (2.4×KDP). Theoretical calculations and crystal structure analysis suggest that the excellent balance between SHG response and deep-UV transparency can be attributed to a synergistic interaction of the hetero-cations La3+ and [NH4 ]+ , which optimize alignment of the [SO4 ] tetrahedra and highly polarizable [LaO8 ] polyhedra.

Large Second-Harmonic Response and Giant Birefringence of CeF2(SO4) Induced by Highly Polarizable Polyhedra.

Second-harmonic generation (SHG) response and birefringence are two critically important properties of nonlinear optical (NLO) materials. However, the simultaneous optimization of these two key properties remains a major challenge because of their contrasting microstructure requirements. Herein, we report the first tetravalent rare-earth metal fluorinated sulfate, CeF2(SO4). Its structure features novel net-like layers constructed by highly distorted [CeO4F4] polyhedra, which are further interconnected by [SO4] tetrahedra to form a three-dimensional structure. CeF2(SO4) exhibits the strongest SHG effect (8 times that of KH2PO4) and the largest birefringence for sulfate-based NLO materials, the latter exceeding the birefringent limit for oxides. Theoretical calculations and crystal structure analysis reveal that the unusually large SHG response and giant birefringence can be attributed to the introduction of the highly polarizable fluorinated [CeO4F4] polyhedra as well as the favorable alignment of [CeO4F4] polyhedra and [SO4] tetrahedra. This research affords a new paradigm for the designed synthesis of high-performance NLO materials.

A Congruent-Melting Mid-Infrared Nonlinear Optical Vanadate Exhibiting Strong Second-Harmonic Generation.

Study of mid-infrared (mid-IR) nonlinear optical (NLO) materials is hindered by the competing requirements of optimized second-harmonic generation (SHG) coefficient dij and laser-induced damage threshold (LIDT) as well as the harsh synthetic conditions. Herein, we report facile hydrothermal synthesis of a polar NLO vanadate Cs4 V8 O22 (CVO) featuring a quasi-rigid honeycomb-layered structure with [VO4 ] and [VO5 ] polyhedra aligned parallel. CVO possesses a wide IR-transparent window, high LIDT, and congruent-melting behavior. It has very strong phase-matchable SHG intensities in metal vanadate family (12.0 × KDP @ 1064 nm and 2.2 × AGS @ 2100 nm). First-principles calculations suggest that the exceptional SHG responses of CVO largely originate from virtual electronic transitions within [V4 O11 ]∞ layer; the excellent optical transmittance of CVO arises from the special characteristics of vibrational phonons resulting from the layered structure.

Porous FeO x /carbon nanocomposites with different iron oxidation degree for building high-performance lithium ion batteries.

Transition metal oxides have attracted lots of interest for lithium ion battery (LIB) due to the high theoretical capacity, however, the large specific volume change, low electrical conductivity and slow intrinsic lithiation/delithiation still limit the practical applications. In order to overcome the challenge, a novel type of high temperature annealing treatment for the synthesis of 3D porous FeO x nanocrystals embedded in a partially carbon matrix as an example for high-performance LIB is reported. The FeO x /carbon nanocomposites with coral-like architecture achieved at 700 °C (F700) exhibit good long term cyclability with a reversible capacity 1012 mAh g-1 remain after 500 cycles at 1.0 A g-1 and the high rate capacity with a reversible capacity of 233 mAh g-1 even at extremely high current density of 20 A g-1. These excellent electrochemical performances could be attributed to the 3D porous structure and carbon coating, which could not only provide excellent electronic conductivity and enough elastic buffer space to accommodate volume changes upon lithium insertion/extraction, but also effectively avoid agglomeration of the Fe3O4 nanocrystals and maintain the structural integrity of the electrode during the charge/discharge process.

Germacrone attenuates cerebral ischemia/reperfusion injury in rats via antioxidative and antiapoptotic mechanisms.

Germacrone (GM) is an anti-inflammatory compound extracted from Rhizoma curcuma. Here, we strived to investigate the neuroprotective effects of GM in rat models of transient middle cerebral artery occlusion/reperfusion injury. Rats immediately after cerebral ischemia were intraperitoneally injected with GM at doses of 5, 10, and 20 mg/kg. After 1 day of reperfusion, the water content in the brain, infarct volume, and neurological deficits were assessed. Hippocampus neurons were histopathologically examined by hematoxylin and eosin and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Activities of glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-PX) in brain tissue were detected. Real-time PCR and Western blotting were utilized to quantify the expression of apoptosis markers, such as caspase-3, Bax, and Bcl-2. The content of phospho-Akt (p-Akt) was also measured using Western blotting. GM treatment markedly decreased the brain water content, infarct volume and the neurological deficits, which was corroborated by attenuated histopathologic change. MDA levels were reduced and activities of GSH, SOD, and GSH-PX were elevated after GM treatment. Caspase-3 and Bax were decreased, and Bcl-2 was increased at both messenger RNA and protein levels by GM treatment. The p-Akt expression was increased by GM. Our data indicated that the neuroprotective effects of GM may attenuate the injuries from cerebral ischemia/reperfusion in rats through antioxidative and antiapoptotic mechanisms.

[Value of galactose-deficient IgA1 in the early diagnosis of Henoch-Schönlein purpura nephritis in children].

OBJECTIVE: To explore the value of galactose-deficient IgA1 (Gd-IgA1) in the early diagnosis of Henoch-Schönlein purpura nephritis (HSPN) in children. METHODS: A total of 67 hospitalized children who were definitely diagnosed with HSPN between January and April 2018 and 58 hospitalized children with Henoch-Schönlein purpura (HSP) were enrolled in the study. Twenty children undergoing routine physical examinations served as controls. The levels of serum and urine Gd-IgA1 were determined using ELISA. The receiver operating characteristic curve was used to analyze the value of serum Gd-IgA1 and urine Gd-IgA1/urine creatinine ratio in the diagnosis of HSPN. RESULTS: The level of serum Gd-IgA1 and urine Gd-IgA1/urine creatinine ratio in children with HSP or HSPN were significantly higher than those in healthy control group (P<0.01), with a significantly greater increase observed in children with HSPN (P<0.01). Serum Gd-IgA1 ≥1 485.57 U/mL and/or urine Gd-IgA1/urine creatinine ratio ≥105.74 were of favorable value in the diagnosis of HSPN. During the six-month follow-up of the 49 children with HSP, the incidence of HSPN was 47% (23/49), which included a 100% incidence in children with serum Gd-IgA1 ≥1 485.57 U/mL and a 73% incidence in children with urine Gd-IgA1/urine creatinine ratio ≥105.74. CONCLUSIONS: Serum and urine Gd-IgA1 is of favorable clinical value in the early diagnosis of HSPN.

Controllable synthesis of nickel bicarbonate nanocrystals with high homogeneity for a high-performance supercapacitor.

The electrochemical performance of supercapacitors might be associated with the homogeneous structure of the electrode materials. However, the relationship between the degree of uniformity for the electrode materials and the electrochemical performance of the supercapacitor is not clear. Herein, we synthesize two types of nickel bicarbonate nanocrystals with different degrees of uniformity to investigate this relationship. As the electroactive material, the nickel bicarbonate nanocrystals with a homogeneous structure could provide a larger space and offer more exposed atoms for the electrochemical reaction than the nanocrystals with a heterogeneous structure. The homogeneous nickel bicarbonate nanocrystals exhibit better electrochemical performance and show excellent specific capacitance (1596 F g-1 at 2 A g-1 and 1260 F g-1 at 30 A g-1), which is approximately twice that of the heterogeneous nickel bicarbonate nanocrystals. The cycling stability for the homogeneity (∼80%) is higher than the inhomogeneity (∼61%) at a high current density of 5 A g-1.

[Effect of a microRNA-132 antagonist on pilocarpine-induced status epilepticus in young rats].

OBJECTIVE: To study the effect of a microRNA-132 antagonist on lithium-pilocarpine-induced status epilepticus (SE) in young Sprague-Dawley (SD) rats. METHODS: Forty-five 3-week-old SD rats were randomly and equally divided into epilepticus model group, microRNA-132 antagonist group, and microRNA-132 antagonist negative control group. The young SD rat model of SE was established using lithium-pilocarpine. For the microRNA-132 antagonist group and the negative control group, pretreatment was performed 24 hours before the model establishment. Behavioral observation was performed to assess the latency of SE and success rate of induction of SE. The scale of Lado was used to evaluate the seizure severity. Electroencephalography (EEG) was used to assess the frequency and amplitude of epileptiform discharges. The mortality rate was calculated in each group. RESULTS: There was no significant difference in the success rate of induction of SE between the three groups (P>0.05). Compared with the microRNA-132 negative control group and the epilepticus model group, the microRNA-132 antagonist group had significantly prolonged SE latency after model establishment (P<0.05), a significantly lower Lado score of seizure (P<0.05), significantly lower frequency and amplitude of epileptiform discharges on EEG (P<0.05), and a slightly reduced mortality rate. CONCLUSIONS: The treatment with the microRNA-132 antagonist shows an inhibitory effect on the development and progression of lithium-pilocarpine-induced SE in young SD rats. The inhibition of microRNA-132 is likely to be a potential target or direction for drug treatment of SE.

[Comparison of therapeutic effects of prednisone combined with mycophenolate mofetil versus cyclosporin A in children with steroid-resistant nephrotic syndrome].

OBJECTIVE: To compare the therapeutic effects of prednisone combined with mycophenolate mofetil (MMF) versus cyclosporin A (CsA) in children with steroid-resistant nephrotic syndrome (SRNS). METHODS: The clinical data of 164 SRNS children who were treated with prednisone combined with MMF or CsA between January 2004 and December 2013 were collected, and the clinical effect of prednisone combined with MMF (MMF group, 112 children) or CsA (CsA group, 52 children) was analyzed retrospectively. RESULTS: At 1 month after treatment, the CsA group had a significantly higher remission rate than the MMF group (67.3% vs 42.9%; P<0.05). At 3 months after treatment, the CsA group also had a significantly higher remission rate than the MMF group (78.8% vs 63.3%; P<0.05). The 24-hour urinary protein excretion in both groups changed significantly with time (P<0.05) and differed significantly between the two groups (P<0.05). There were no serious adverse events in the two groups. CONCLUSIONS: Prednisone combined with MMF or CsA is effective and safe for the treatment of SRNS in children, and within 3 months of treatment, CsA has a better effect than MMF.

Mycophenolate mofetil therapy for steroid-resistant IgA nephropathy with the nephrotic syndrome in children.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) presents as nephrotic syndrome (NS) relatively rarely, and the current treatment experience of IgAN patients with NS is mostly with adults. The objective of our study was to investigate the efficacy of corticosteroids and mycophenolate mofetil (MMF) in treating childhood immunoglobulin A nephropathy (IgAN) with nephrotic syndrome. METHODS: A total of 58 children (39 boys and 19 girls) diagnosed with nephrotic syndrome and primary IgAN were enrolled in the study. All the patients were administered prednisone 2 mg/kg per day for 8 weeks. Steroid-resistant patients were treated with the combined use of MMF (dose of 20 ~ 30 mg/kg per day) and prednisone for 6-12 months. The prednisone dose was reduced stepwise during the combined treatment. RESULTS: Of the 58 children, 14 were steroid-sensitive (M, S, and T variants of the Oxford classification were 0 in most children), and 44 cases who presented serious pathological damage to the kidney were steroid-resistant. The estimated glomerular filtration rate (eGFR) of the steroid-resistant children (86.69 ± 26.85 ml/min/1.73 m(2)) was significantly lower (P < 0.05) than that of the steroid-sensitive children (106.89 ± 26.94 ml/min/1.73 m(2)). After 4 months of combined MMF treatment in 33 steroid-resistant children, complete remission of proteinuria was found in 21 cases, partial remission of proteinuria in 6 cases, and no response was found in 6 cases. Except for the T variant, other variants of the Oxford classification, including M, E, and S morphological variables, was not significantly different among patients complete remission, those with partial remission, and those with no response. The eGFR of children with complete remission of proteinuria (100.04 ± 18.47 ml/min/1.73 m(2)), that of those with partial remission (92.24 ± 27.63 ml/min/1.73 m(2)), and that of those with no response (72.17 ± 27.55 ml/min/1.73 m(2)) were significantly different (P < 0.05). CONCLUSION: Corticosteroid therapy showed satisfactory efficacy in IgAN children with nephrotic syndrome and slight pathological damage. The effect of MMF was good for steroid-resistant IgAN children, but poor for those with tubular atrophy/interstitial fibrosis and renal function impairment.

[Clinical characteristics of children with an initial onset of IgA nephropathy with nephrotic syndrome].

OBJECTIVE: To study the clinical characteristics of children with an initial onset of IgA nephropathy with nephrotic syndrome and compare them with children with primary nephrotic syndrome, in order to provide a theoretical basis for the differential diagnosis of the two diseases. METHODS: Fifty children diagnosed with an initial onset of IgA nephropathy with nephrotic syndrome were included in this study. Seventy-two children diagnosed with an initial onset of primary nephrotic syndrome served as the control group. The clinical and laboratory examination characteristics were compared between the two groups. RESULTS: The IgA nephropathy group had significantly higher incidence rates of gross haematuria, microscopic haematuria, hypertension, acute kidney injury, low serum high-density lipoprotein cholesterol, anemia, low serum complement C4, steroid resistance, and nephritis-type nephrotic syndrome and a significantly lower incidence of elevated serum IgE compared with the control group (P<0.05). There were significant differences in serum creatinine, serum uric acid, serum total cholesterol, serum high-density lipoprotein cholesterol, serum IgE, serum complement C4, and hemoglobin levels between the IgA nephropathy and the control groups (P<0.05). The thresholds of serum IgE (<131.2 IU/mL) and high-density lipoprotein cholesterol (<1.35 mmol/L) were reference parameters in the differential diagnosis of IgA nephropathy with nephrotic syndrome and primary nephrotic syndrome. CONCLUSIONS: Children with IgA nephropathy presenting nephrotic syndrome manifest mainly as nephritis type and steroid-resistant type in the clinical classification. Cinical manifestations accompanied by serum levels of high-density lipoprotein cholesterol and IgE are helpful for differential diagnosis of IgA nephropathy presenting nephrotic syndrome and primary nephrotic syndrome.

[Significance of trace deposition of immunoglobulin M in glomerular mesangium in children with minimal change nephrotic syndrome].

OBJECTIVE: To study the significance of trace immunoglobulin M (IgM) deposits in glomerular mesangium in children with minimal change primary nephrotic syndrome (PNS). METHODS: One hundred and six children who were clinically diagnosed with PNS and pathologically diagnosed with minimal change disease (MCD) and trace deposition of IgM in renal tissues were enrolled as subjects. Eighty-one PNS children with MCD but no deposition of immune complexes were used as the control group. The clinical characteristics and efficacies of glucocorticoids and immunosuppressants were retrospectively analyzed in the two groups. All patients were given full-dose prednisone by oral administration, and patients with glucocorticoid resistance or frequent relapses were additionally given immunosuppressants. RESULTS: The incidence of glucocorticoid resistance in the IgM deposit group was significantly higher than that in the control group (27.2% vs 12.3%; P<0.05). The incidence of frequent relapses in the IgM deposit group was also significantly higher than that in the control group (48.1% vs 10.4%; P<0.05). The complete remission rate for glucocorticoid-resistant patients treated with prednisone combined with mycophenolate mofetil (MMF) was 68% and 62% respectively in the IgM deposit and control groups (P>0.05). The relapse frequency in patients with frequent relapses was significantly reduced in both groups after treatment with prednisone and MMF in combination (P<0.05). CONCLUSIONS: Trace deposition of IgM in renal tissues may be an important factor for glucocorticoid resistance and frequent relapses in PNS children with MCD. Prednisone combined with MMF may be a better choice in the treatment of patients with glucocorticoid resistance or frequent relapses.

Clinical and pathological features of acute kidney injury in children.

OBJECTIVE: Based on the diagnostic and staging criteria of acute kidney injury (AKI), we analyze the clinical and pathological characteristics of children at different stages of AKI and explored their clinical significances. METHODS: 165 children with AKI were divided into stage 1, stage 2, and stage 3 groups. Clinical and pathologic characteristics of AKI children were analyzed. RESULTS: The three groups of patients showed significant differences in age, etiology, pathological damage, and the median recovery time of serum creatinine. Of the 165 patients, the incidence and duration of hematuria showed significant differences among the three groups, and the stage 1 group showed longer duration of proteinuria. CONCLUSION: The patients were largely in stage 1 and 3. The children with AKI in stage 1 were largely school-age children and acute glomerulonephritis (AGN) was the main etiology. The AKI children in stage 3 were mainly infants, of which the etiology was mainly drugs and septicemia. The pathological type was mainly acute tubulointerstitial nephritis, and the renal function recovery was slow.

Targeting RSK2 in Cancer Therapy: A Review of Natural Products.

P90 ribosomal S6 kinase 2 (RSK2) is an important member of the RSK family, functioning as a kinase enzyme that targets serine and threonine residues and contributes to regulating cell growth. RSK2 comprises two major functional domains: the N-terminal kinase domain (NTKD) and the C-terminal kinase domain (CTKD). RSK2 is situated at the lower end of the Mitogen-activated protein kinases (MAPK) signaling pathway and is phosphorylated by the direct regulation of Extracellular signal-regulating kinase (ERK). RSK2 has been found to play a pivotal role in regulating cell proliferation, apoptosis, metastasis, and invasion in various cancer cells, including breast cancer and melanoma. Consequently, RSK2 has emerged as a potential target for the development of anti-cancer drugs. Presently, several inhibitors are undergoing clinical trials, such as SL0101. Current inhibitors of RSK2 mainly bind to its NTK or CTK domains and inhibit their activity. Natural products serve as an important resource for drug development and screening and with the potential to identify RSK2 inhibitors. This article discusses how RSK2 influences tumor cell proliferation, prevents apoptosis, arrests the cell cycle process, and promotes cancer metastasis through its regulation of downstream pathways or interaction with other biological molecules. Additionally, the paper also covers recent research progress on RSK2 inhibitors and the mechanisms of action of natural RSK2 inhibitors on tumors. This review emphasizes the significance of RSK2 as a potential therapeutic target in cancer and offers a theoretical basis for the clinical application of RSK2 inhibitors.

Giant Optical Anisotropy in a Covalent Molybdenum Tellurite via Oxyanion Polymerization.

Large birefringence is a crucial but hard-to-achieve optical parameter that is a necessity for birefringent crystals in practical applications involving modulation of the polarization of light in modern opto-electronic areas. Herein, an oxyanion polymerization strategy that involves the combination of two different types of second-order Jahn-Teller distorted units is employed to realize giant anisotropy in a covalent molybdenum tellurite. Mo(H2O)Te2O7 (MTO) exhibits a record birefringence value for an inorganic UV-transparent oxide crystalline material of 0.528 @ 546 nm, which is also significantly larger than those of all commercial birefringent crystals. MTO has a UV absorption edge of 366 nm and displays a strong powder second-harmonic generation response of 5.4 times that of KH2PO4. The dominant roles of the condensed polytellurite oxyanions [Te8O20]8- in combination with the [MoO6]6- polyhedra in achieving the giant birefringence in MTO are clarified by structural analysis and first-principles calculations. The results suggest that polymerization of polarizability-anisotropic oxyanions may unlock the promise of birefringent crystals with exceptional birefringence.

Sfrp2 promotes renal dysfunction of diabetic kidney disease via modulating Fzd5-induced cytosolic calcium ion concentration and CaMKII/Mek/Erk pathway in mesangial cells.

OBJECTIVE: Mesangial cells (MCs) in the kidney play central role in maintaining glomerular integrity, and their abnormal proliferation leads to major glomerular diseases including diabetic kidney disease (DKD). Although high blood glucose elicits MCs impairment, the underlying molecular mechanism is poorly understood. The present study aimed to investigate the effect of secreted frizzled-related protein 2 (Sfrp2) from single-nucleus RNA profiling on MC proliferation of DKD in vitro and in vivo and explored the specific mechanisms. RESULTS: By snRNA-seq analysis of isolated renal cells from leptin receptor-deficient db/db mice and control db/m mice, we found that Sfrp2 was increased in the MCs of DKD in comparison to other intrinsic renal cells, which was further verified in vitro and in vivo. We also found that the expression of Sfrp2 was significantly upregulated in DKD patients and correlated with renal function, demonstrating that Sfrp2 might serve as an independent biomarker for DKD patients. Functionally, we showed the loss and acquisition of Sfrp2 affected cytosolic Ca2+ concentration, cell proliferation and fibrosis of MC, albuminuria and kidney injury in vitro and in vivo. Mechanistically, we identify c-Jun as a transcription factor of Sfrp2 promoting its transcription, and the Ca2+ signaling related protein frizzled receptor 5 (Fzd5) as the binding protein of Sfrp2. And we further found Sfrp2 promoted Fzd5-induced cytosolic Ca2+ concentration and the downstream CaMKII/Mek/Erk pathway activation, leading to MC proliferation and fibrosis in DKD. CONCLUSION: Our study revealed a novel involvement for Sfrp2 in the regulation of MC function and the effect of Sfrp2 on cell proliferation and fibrosis of MC via the Fzd5/Ca2+/CaMKII/Mek/Erk pathway, implying that Sfrp2 may be a possible biomarker and therapeutic target for DKD.

Organic Dye Molecule Intercalated Prussian Blue for Simultaneously Enhancing Coloration Efficiency and Energy Storage Capacity in Electrochromic Battery.

The dual-functional device combining electrochromic properties and energy storage has gained numerous attentions in the field of energy-saving smart electronics. However, achieving simultaneous optimization of coloration efficiency and energy storage capacity of materials poses a significant challenge. This study presents a novel approach by incorporating methyl orange into Prussian blue channels (PB-MO films) to adjust the internal electronic structure of Prussian blue. This modification allows the active layer to simultaneously improve the electrochromic and energy storage performance. The introduction of methyl orange not only alters the ratio of Fe3+/Fe2+ within the framework through the coordination reaction of Fe3+ with methyl orange, but also improves the reaction kinetics after intercalating organic dye molecules, including charge transfer resistance, diffusion capability of ions and capacitive contribution. The PB-MO films demonstrate remarkable properties: high optical contrast (81.4% at 670 nm), excellent coloration efficiency (265 cm2 C-1), and significant specific capacity (84 mAh m-2 at 0.05 A m-2), outperforming pure PB films. The PB-MO films are ideally suited for applications in displays and intelligent energy storage fields, boasting both high coloration efficiency and substantial energy storage capacity, thus advancing promote the development of dual-functional electrochromic devices.