Row Transmission for High Volume-Rate Ultrasound Imaging with a Matrix Array.

The widely used Vermon 1024-element matrix array for three-dimensional (3D) ultrasound imaging has three blank rows in the elevational direction, which breaks the elevation periodicity, thus degrading volumetric image quality. To bypass the blank rows in elevation while maintaining the steering capability in azimuth, we proposed a row transmission (RT) scheme to improve 3D spatial resolution. Specifically, we divided the full array into four apertures, each with multiple rows along the elevation. Each multi-row aperture (MRA) was further divided into subapertures to transmit diverging waves sequentially. Coherent diverging wave compounding (CDWC) was realized in azimuth, while the elevation was multi-element synthetic aperture (M-SA) imaging by regarding each row as an array of dashed line elements. An in-house spatiotemporal coding strategy, cascaded synthetic aperture (CaSA), was incorporated into the RT scheme as RT-CaSA to increase the signal-to-noise ratio (SNR). We compared the proposed RT with conventional bank-by-bank transmission-reception (Bank) and sparse-random-aperture compounding (SRAC) in a wire phantom and the in vivo human abdominal aorta to assess the performance of anatomical imaging and aortic wall motion estimation. Phantom results demonstrated superior lateral resolution achieved by our RT scheme (+19.52% and +16.88% versus Bank, +15.32% and +19.72% versus SRAC, in the azimuth-depth and elevation-depth planes, respectively). Our RT-CaSA showed excellent contrast ratios (+8.19dB and +8.08dB versus Bank, +6.81dB and +5.85dB versus SRAC, +0.99dB and +0.90dB versus RT) and the highest in vivo aortic wall motion estimation accuracy. The RT scheme was demonstrated to have potential for various matrix array-based 3D imaging research.

Computer-assisted discovery and evaluation of potential ribosomal protein S6 kinase beta 2 inhibitors.

S6K2 is an important protein in mTOR signaling pathway and cancer. To identify potential S6K2 inhibitors for mTOR pathway treatment, a virtual screening of 1,575,957 active molecules was performed using PLANET, AutoDock GPU, and AutoDock Vina, with their classification abilities compared. The MM/PB(GB)SA method was used to identify four compounds with the strongest binding energies. These compounds were further investigated using molecular dynamics (MD) simulations to understand the properties of the S6K2/ligand complex. Due to a lack of available 3D structures of S6K2, OmegaFold served as a reliable 3D predictive model with higher evaluation scores in SAVES v6.0 than AlphaFold, AlphaFold2, and RoseTTAFold2. The 150 ns MD simulation revealed that the S6K2 structure in aqueous solvation experienced compression during conformational relaxation and encountered potential energy traps of about 19.6 kJ mol-1. The virtual screening results indicated that Lys75 and Lys99 in S6K2 are key binding sites in the binding cavity. Additionally, MD simulations revealed that the ligands remained attached to the activation cavity of S6K2. Among the compounds, compound 1 induced restrictive dissociation of S6K2 in the presence of a flexible region, compound 8 achieved strong stability through hydrogen bonding with Lys99, compound 9 caused S6K2 tightening, and the binding of compound 16 was heavily influenced by hydrophobic interactions. This study suggests that these four potential inhibitors with different mechanisms of action could provide potential therapeutic options.

DNA methylation of IFI44L as a potential blood biomarker for childhood-onset systemic lupus erythematosus.

BACKGROUND: IFN-induced protein 44-like (IFI44L) promoter methylation has been demonstrated to serve as an effective blood diagnostic biomarker for adult-onset SLE. However, its utility as a diagnostic marker for childhood-onset SLE (cSLE) remains to be verified. METHODS: Initially, we conducted a differential analysis of gene methylation and mRNA expression patterns in cSLE whole blood samples obtained from the public GEO database to determine IFI44L gene expression and assess the methylation status at its CpG sites. Subsequently, we collected clinical whole blood samples from 49 cSLE patients and 12 healthy children, employing an HRM-qPCR-based IFI44L methylation detection technique to evaluate its diagnostic efficacy in pediatric clinical practice. RESULTS: A total of 26 hypomethylated, highly expressed genes in cSLE were identified by intersecting differentially expressed genes (DEGs) and differentially methylation genes (DMGs). GO enrichment analysis for these 26 genes indicated a robust association with type I IFN. Among the overlapping genes, IFI44L exhibited the most pronounced differential expression and methylation. In subsequent clinical validation experiments, IFI44L methylation was confirmed as an effective blood-based diagnostic biomarker for cSLE, achieving an AUC of 0.867, a sensitivity of 0.753, and a specificity of 1.000. CONCLUSIONS: IFI44L methylation is a promising blood biomarker for cSLE. IMPACT: IFI44L promoter methylation was reported to serve as a highly sensitive and specific diagnostic marker for adult-onset SLE. However, the diagnostic efficacy of IFI44L in childhood-onset SLE (cSLE) still remains to be confirmed. In this study, we utilized bioinformatics analysis and conducted clinical experiments to demonstrate that IFI44L methylation can also serve as a promising blood biomarker for cSLE. The findings of this study can facilitate the diagnosis of cSLE and broaden our understanding of its molecular mechanisms, with a particular focus on those related to type I interferons.

Sialic Acid-Functionalized Pyroptosis Nanotuner for Epigenetic Regulation and Enhanced Cancer Immunotherapy.

The efficacy of immune checkpoint blockade (ICB) in promoting an immune response against tumors still encounters challenges such as low response rates and off-target effects. Pyroptosis, an immunogenic cell death (ICD) mechanism, holds the potential to overcome the limitations of ICB by activating and recruiting immune cells. However, the expression of the pyroptosis-related protein Gasdermin-E(GSDME) in some tumors is limited due to mRNA methylation. To overcome this obstacle, sialic acid-functionalized liposomes coloaded with decitabine, a demethylation drug, and triclabendazole, a pyroptosis-inducing drug are developed. This nanosystem primarily accumulates at tumor sites via sialic acid and the Siglec receptor, elevating liposome accumulation in tumors up to 3.84-fold at 24 h and leading to the upregulation of pyroptosis-related proteins and caspase-3/GSDME-dependent pyroptosis. Consequently, it facilitates the infiltration of CD8+ T cells into the tumor microenvironment and enhances the efficacy of ICB therapy. The tumor inhibition rate of the treatment group is 89.1% at 21 days. This study highlights the potential of sialic acid-functionalized pyroptosis nanotuners as a promising approach for improving the efficacy of ICB therapy in tumors with low GSDME expression through epigenetic alteration and ICD.

Anti-VEGFR2 F(ab')2 drug conjugate promotes renal accumulation and glomerular repair in diabetic nephropathy.

Poor renal distribution of antibody-based drugs is the key factor contributing to low treatment efficiency for renal diseases and side effects. Here, we prepare F(ab')2 fragmented vascular endothelial growth factor receptor 2 antibody (anti-VEGFR2 (F(ab')2) to block VEGFR2 overactivation in diabetic nephropathy (DN). We find that the anti-VEGFR2 F(ab')2 has a higher accumulation in DN male mice kidneys than the intact VEGFR2 antibody, and simultaneously preserves the binding ability to VEGFR2. Furthermore, we develop an antibody fragment drug conjugate, anti-VEGFR2 F(ab')2-SS31, comprising the anti-VEGFR2 F(ab')2 fragment linked to the mitochondria-targeted antioxidant peptide SS31. We find that introduction of SS31 potentiates the efficacy of anti-VEGFR2 F(ab')2. These findings provide proof of concept for the premise that antibody fragment drug conjugate improves renal distribution and merits drug validation in renal disease therapy.

[Unilateral interlaminar approach 270° circular spinal canal decompression under the iLESSYS Delta for the treatment of lumbar spinal stenosis in the elderly].

OBJECTIVE: To investigate the clinical effect of unilateral interlaminar approach 270° circular spinal canal decompression under the Interlaminar Endoscopic Surgical System(iLESSYS) Delta for the treatment of lumbar spinal stenosis (LSS) in the elderly. METHODS: Total of 29 patients with LSS treated with the iLESSYS Delta from December 2018 to January 2021 were retrospectively analyzed, including 12 males and 17 females with an average age of (71.52±10.82) years old ranging from 63 to 83 years old. All patients had definite intermittent claudication, mainly neurogenic symptoms of both lower limbs. All patients had single-level spinal stenosis, including L3,4 5 cases, L4,5 21 cases, and L5S1 3 cases. Visual analogue scale (VAS), Oswestry Disability Index (ODI) and modified Macnab assessment criteria were used to evaluate pain, low back pain dysfunction index and clinical efficacy, respectively. RESULTS: All 29 cases were successfully completed. The operation time was (73.45±5.89) min, the intraoperative blood loss was (9.93±0.83) ml, the hospital stay was (4.03±0.41) days, and the follow-up was more than 12 months. The VAS scores of low back pain before surgery and 1 day, 1 month, 3 months, 1 year after surgery were 2.31±0.88, 1.45±0.62, 1.21±0.61, 1.10±0.55, 1.03±0.49;VAS of leg pain were 6.48±0.49 0.56, 1.97±0.61, 1.31±0.59, 1.17±0.59, 1.10±0.55;ODI scores were 38.41±2.74, 18.14±1.17, 5.17±0.53, 5.07±0.45, 4.90±0.48;low back and leg pain VAS score and ODI score have statistically significant differences between preoperative and postoperative follow-up time points (P<0.05). The MacNab efficacy evaluation at 1-year follow-up:excellent in 22 cases, good in 5 cases and fair in 2 cases. CONCLUSION: The clinical effect of unilateral interlaminar approach 270° circular spinal canal decompression under the iLESSYS Delta for the treatment of lumbar spinal stenosis in the elderly is satisfactory, with the advantages of less trauma and less bleeding, large microscopic operation space, sufficient decompression, and ideal post-operative recovery, and at the same time, it can minimize the damage to the stable structure of the lumbar spine, which is an ideal surgical method for the treatment of elderly lumbar spinal stenosis.

Nanodrug Delivery Strategies to Signaling Pathways in Alopecia.

Over 50% of the global population suffers from hair loss. The mixed results in the treatment of hair loss reveal the limitations of conventional commercial topical drugs. One the one hand, the definite pathogenesis of hair loss is still an enigma. On the other hand, targeted drug carriers ensure the drug therapeutic effect and low side effects. This review highlights the organization and overview of nine crucial signaling pathways associated with hair loss, as well as the development of nanobased topical delivery systems loading the clinical drugs, which will fuel emerging hair loss treatment strategies.

Risk factors for renal outcomes in children with antineutrophil cytoplasmic antibody-associated vasculitis: a nationwide retrospective study in China.

BACKGROUND: Pediatric antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a life-threatening systemic vasculitis featured by liability to renal involvement. However, there are few studies on the risk factors and predictive models for renal outcomes of AAV in children. METHODS: Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected retrospectively. The risk factors and predictive model of end-stage renal disease (ESRD) in AAV were explored. RESULTS: Renal involvement was the most typical manifestation (95.5%), and the crescent was the predominant pathological lesion (84.9%). The estimated glomerular filtration rate (eGFR) was evaluated in 114 patients, of whom 59.6% developed ESRD, and the median time to ESRD was 3.20 months. The eGFR [P = 0.006, odds ratio (OR) = 0.955, 95% confidence interval (CI) = 0.924-0.987] and the percentages of global glomerulosclerosis (pGGS; P = 0.018, OR = 1.060, 95% CI = 1.010-1.112) were independent risk factors for ESRD of renal biopsy. Based on the pGGS and eGFR at renal biopsy, we developed three risk grades of ESRD and one predictive model. The Kaplan‒Meier curve indicated that renal outcomes were significantly different in different risk grades (P < 0.001). Compared with serum creatinine at baseline, the predictive model had higher accuracy (0.86 versus 0.58, P < 0.001) and a lower coefficient of variation (0.07 versus 0.92) in external validation. CONCLUSIONS: Renal involvement is the most common manifestation of pediatric AAV in China, of which more than half deteriorates into ESRD. The predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children. Supplementary file 2 (MP4 18937 KB).

The pentraxin family in autoimmune disease.

The pentraxins represent a family of multifunctional proteins composed of long and short pentamers. The latter includes serum amyloid P component (SAP) and C-reactive protein (CRP) whereas the former includes neuronal PTX1 and PTX2 (NPTX1 and NPTX2, respectively), PTX3 and PTX4. These serve as a bridge between adaptive immunity and innate immunity and a link between inflammation and immunity. Similarities and differences between long and short pentamers are examined and their roles in autoimmune disease are discussed. Increased CRP and PTX3 could indicate the activity of rheumatoid arthritis, systemic lupus erythematosus or other autoimmune diseases. Mechanistically, CRP and PTX3 may predict target organ injury, regulate bone metabolic immunity and maintain homeostasis as well as participate in vascular endothelial remodeling. Interestingly, PTX3 is pleiotropic, being involved in inflammation and tissue repair. Given the therapeutic potential of PTX3 and CRP, targeting these factors to exert a beneficial effect is the focus of research efforts. Unfortunately, studies on NPTX1, NPTX2, PTX4 and SAP are scarce and more research is clearly needed to elaborate their potential roles in autoimmune disease.

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Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organ systems, presenting a complex and diverse clinical manifestation. The heterogeneous treatment response and prognosis of SLE pose significant challenges to its diagnosis, classification, and homogeneous treatment. The emergence of new technologies and fields, such as synthetic biology, genomics, and proteomics, has contributed to a deeper exploration of the pathogenesis and biomarkers of SLE, facilitating precision diagnosis and treatment. This review summarizes the latest research data and achievements in SLE for the years 2021-2022, providing an overview and summary of relevant studies conducted in the past two years.

Adipose-Derived Mesenchymal Stem Cell-Derived Exosomes Biopotentiated Extracellular Matrix Hydrogels Accelerate Diabetic Wound Healing and Skin Regeneration.

Wound healing is an urgent clinical challenge, particularly in the case of chronic wounds. Traditional approaches to wound healing have limited therapeutic efficacy due to lengthy healing times, risk of immune rejection, and susceptibility to infection. Recently, adipose-derived mesenchymal stem cell-derived exosomes (ADSC-exos) have emerged as a promising modality for tissue regeneration and wound repair. In this study, the development of a novel extracellular matrix hydrogel@exosomes (ECM@exo) is reported, which entails incorporation of ADSC-exos into an extracellular matrix hydrogel (ECM hydrogel). This solution forms a hydrogel at physiological temperature (≈37 °C) upon local injection into the wound site. ECM@exo enables sustained release of ADSC-exos from the ECM hydrogel, which maintains high local concentrations at the wound site. The ECM hydrogel displays good biocompatibility and biodegradability. The in vivo and in vitro results demonstrate that ECM@exo treatment effectively reduces inflammation and promotes angiogenesis, collagen deposition, cell proliferation, and migration, thereby accelerating the wound healing process. Overall, this innovative therapeutic approach offers a new avenue for wound healing via a biological hydrogel with controlled exosome release.

Analysis of 6 pediatric nephrotic syndrome cases with complications of cerebral sinovenous thrombosis and literature review.

Background: Cerebral venous sinus thrombosis (CVST) is a rare but serious complication of nephrotic syndrome (NS) in children. To investigate the clinical characteristics of CVST in children with NS in order to timely diagnose this complication and reduce poor outcome. Methods: Collect and analyze clinical data and magnetic resonance venography (MRV) results of children with NS complicated with CVST. Results: Data of 6 patients with NS complicated with CVST were collected. 4 of the patients were steroid-sensitive nephrotic syndrome (SSNS) and 2 were steroid-resistant nephrotic syndrome (SRNS). The occurrence of CVST was observed within a time frame ranging from 12 days to 3 years following the diagnosis of NS. One patient had two episodes of thrombosis in three years, while the other five patients had only one episode of thrombosis. All patients had proteinuria at the time of episode of thrombosis. All patients presented with headache, and three of them had strabismus, seizures, and transient blindness, respectively. Neurological examination was negative. All patients were diagnosed with CVST by MRV within 3-16 days of the onset of headache. Two patients had TRPC6 gene mutation. All patients had resolution of neurological symptoms after anticoagulation treatment. Conclusion: CVST may occur in the early stages of NS. There is currently a lack of specific diagnostic indicators to reliably identify the presence of CVST in patients with NS. Children with NS who have neurological symptoms should be promptly evaluated with imaging studies. Whether TRPC6 gene mutation is also a risk factor for CVST remains to be further studied.

Multifunctional Drugs-Loaded Carbomol Hydrogel Promotes Diabetic Wound Healing via Antimicrobial and Immunoregulation.

Diabetic wound healing poses a significant clinical dilemma. Bacterial infection and immune dysregulation are the predominant reasons. However, conventional wound dressings with a single treatment approach often limit therapeutic efficacy and continue working with difficulty. These limitations cause high treatment failure for diabetic wounds. In this study, we developed a multiple drug-loaded carbomer hydrogel containing Que/Van/Rif (QVR-CBMG) for the simultaneous treatment of infection and immune dysregulation. Honeycomb-like QVR-CBMG hydrogel exhibits excellent abilities to eliminate bacterial infection and biofilms in vitro. Moreover, QVR-CBMG hydrogel possesses an immunomodulatory capacity via affecting the Sirt3/SOD2 signaling pathway to promote M2 macrophages. Furthermore, QVR-CBMG hydrogel effectively promotes wound healing in diabetic rats through several mechanisms. The multidrug-loaded wound dressing not only eliminates bacterial infection and facilitated angiogenesis but also promotes collagen deposition and remodulates the local immune microenvironment in the areas of wounds. In summary, this synthetic strategy to eliminate infection and regulate immune disorders has potential translational value for the prevention and management of diabetic wounds.

Evaluation of belimumab in treatment of Chinese childhood-onset systemic lupus erythematosus: a prospective analysis from multicenter study.

OBJECTIVE: The aim of this study is to identify whether low lupus disease activity status (LLDAS) and clinical remission (CR) of belimumab plus standard of care (SoC) therapy are achievable goals in childhood-onset SLE (cSLE). METHODS: This multicentre, one arm pre-post intervention study was conducted at 15 centers in China. The primary end point was to describe the proportion of patients who achieved LLDAS and CR after 3, 6, and 12 months after treatment with belimumab plus SoC therapy. A multiple regression model was used to impute missing data. A Poisson regression model was used to calculate the effect of belimumab treatment on the reduced risk of serious diseases and the incidence of new damage. RESULT: 193 (92.2% female) with active cSLE from 15 centers were included. At 3, 6 and 12 months, the proportion of LLDAS (CR) was 12.4% (1.0%), 25.6% (4.5%) and 70.3% (29.7%), respectively. The mean SELENA-SLEDAI score decreased from 11.0 at baseline to 3.7, 2.9 and 1.7 at 3, 6, and 12 months. At baseline, all patients received steroids at a mean (SD) prednisone equivalent dose of 31.0 (18.2) mg/day, which decreased to 19.4 (10.8) mg/day at month 3, 12.6 (7.2) mg/day at month 6 and 6.7 (5.3) mg/day at month 12. The symptoms and immunological indicators were also significantly improved. CONCLUSION: This is the first and largest sample size prospective clinical intervention study of cSLE patients treated with belimumab in China. LLDAS and CR were attainable treat-to-target of belimumab plus SoC therapy in cSLE.

Comparison Between the Clinical Effect of Percutaneous Kyphoplasty for Osteoporosis Vertebral Compression Fracture Patient with or Without Sarcopenia: A Retrospective Cohort Study.

Background: Sarcopenia and osteoporosis vertebral compression fractures (OVCF) are common diseases that increase with age. This study aimed to investigate the effects of sarcopenia on OVCF patients after percutaneous kyphoplasty (PKP). Methods: Data of 101 patients who were treated with single-level PKP between January 2021 and March 2022 at Ningbo No.6 Hospital were enrolled. Forty-five OVCF patients with sarcopenia who met our inclusion criteria were included in the Sarcopenia-PKP group (SPKP group), and 56 patients in the Normal-PKP group (NPKP group). All clinical and radiological data were collected from medical records. Baseline characteristics, operation-related parameters (operation time, time to ambulation, hospital stay, surgery segment), clinical outcomes (visual analog score [VAS], Oswestry Disability Index [ODI], Japanese Orthopaedic Association Scores [JOA] of lumber), radiological outcomes (vertebral anterior height rate and local kyphosis angle), Macnab score, and complications were evaluated and compared. Results: There were no significant differences in age, sex, surgical segment preoperative VAS score, ODI, or JOA between the two groups (P > 0.05). The SPKP group had a significantly lower body mass index (BMI), bone mineral density (BMD), and smooth muscle index (SMI) than the NPKP group (P < 0.05). Significantly longer hospital stays and time to ambulation in SPKP group than NPKP group (3.7±0.8 vs 3.4±0.5 and 2.0±0.8 vs 1.6±0.5, P < 0.05). In SPKP group, significantly better clinical outcomes at 6- and 12-months follow-up were observed in NPKP group than SPKP group (P < 0.05), and NPKP group showed significantly better in vertebral anterior height rates than SPKP group after 6-month follow-up (P < 0.05). Moreover, there were significantly more cases of complications in the SPKP group (P < 0.05). Conclusion: Sarcopenia could reduce the clinical effect of percutaneous kyphoplasty, and furthermore. Related studies are needed to verify the effect of sarcopenia on OVCF patients.

Bartter syndrome type III with glomerular dysplasia and chronic kidney disease: A case report.

Background: Bartter syndrome (BS) type III is a rare autosomal recessive genetic disease. Its clinical features are polyuria, hypokalemia, hypochloremia, metabolic alkalosis, and hyperreninaemia. A few BS type III can be complicated with chronic kidney disease. Case presentation: We report a 14-year-old boy with Bartter syndrome caused by a c.1792C > T (p.Q598*) mutation in the CLCNKB gene. He was a no deafness and full-term baby, and he had renal dysplasia and chronic kidney disease (CKD). In addition, we summarize all cases of BS type III complicated with CKD. Conclusions: We report a case of Bartter syndrome complicated by chronic kidney disease caused by a new mutation of CLCNKB. As we all know, BS type IV is usually combined with chronic kidney disease, and BS type III can also integrate with CKD. We don't find BS type III with glomerular dysplasia in the literature. So renal damage in BS type III is not only FSGS; clinicians must also be aware of glomerular dysplasia.

Clinical features and familial mutations in the coexistence of Wilson's disease and Alport syndrome: A case report.

Background: Alport syndrome (AS) and Wilson's disease (WD) are genetic diseases that could lead to kidney damage. Herein, we report the clinical features and gene variants in a patient with WD and X-linked AS. Case presentation: The proband was a 12-year-old boy diagnosed with AS coexisting with WD at the age of 11 years. The patient underwent a medical check-up when he was 4 years and 8 months. Laboratory tests revealed elevated liver enzymes, decreased serum ceruloplasmin, increased 24-h urinary copper excretion, and one variant in the ATP7B gene. Then, the patient was diagnosed with WD. After 2 months of treatment with D-penicillamine and zinc salt, his liver function had recovered to normal levels, but he presented with microscopic hematuria. The hematuria did not resolve after switching to dimercaptosuccinic acid from D-penicillamine. In addition, he presented with proteinuria 3 years later. A renal biopsy was performed more than 6 years after the patient was diagnosed with WD, and electron microscopy showed that the basement membrane thickness was uneven, layered, and focal torn. Copper staining was negative. A genetic analysis identified a hemizygous variant (c.1718G > A, p. Gly573Asp) in COL4A5 and a homozygous variant (c.2975C > T, p. Pro992leu) in ATP7B. The patient's urine protein-creatinine ratio was less than 1.0 mg/mg after a 1 year of follow-up, after enalapril was administered for treating AS. Conclusion: This case highlights a lack of improvement in renal function after conventional treatment provides a possible indication for performing renal biopsy or genetic testing to determine the etiology in order to facilitate subsequent clinical management. Clinicians should prevent the occurrence of diagnostic inaccuracies caused by diagnostic anchoring because an accurate diagnosis is essential for achieving precise treatment and improved prognosis.

Diffusive excitonic bands from frustrated triangular sublattice in a singlet-ground-state system.

Magnetic order in most materials occurs when magnetic ions with finite moments arrange in a particular pattern below the ordering temperature. Intriguingly, if the crystal electric field (CEF) effect results in a spin-singlet ground state, a magnetic order can still occur due to the exchange interactions between neighboring ions admixing the excited CEF levels. The magnetic excitations in such a state are spin excitons generally dispersionless in reciprocal space. Here we use neutron scattering to study stoichiometric Ni2Mo3O8, where Ni2+ ions form a bipartite honeycomb lattice comprised of two triangular lattices, with ions subject to the tetrahedral and octahedral crystalline environment, respectively. We find that in both types of ions, the CEF excitations have nonmagnetic singlet ground states, yet the material has magnetic order. Furthermore, CEF spin excitons from the tetrahedral sites form a dispersive diffusive pattern around the Brillouin zone boundary, likely due to spin entanglement and geometric frustrations.

Dent disease manifesting as nephrotic syndrome.

Dent disease is an X-linked recessive renal tubular disorder, which is mainly caused by mutations of the CLCN5 gene and OCRL gene. It is characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis or nephrolithiasis, and progressive renal failure. Nephrotic syndrome is a glomerular disorder characterized by massive proteinuria, hypoalbuminemia, edema, and hyperlipidemia. In this study, we report two cases of Dent disease manifesting as nephrotic syndrome. Two patients were initially diagnosed with nephrotic syndrome due to edema, nephrotic range proteinuria, hypoalbuminemia, and hyperlipidemia, and responded to prednisone and tacrolimus therapy. Genetic testing revealed mutations in the OCRL and CLCN5 genes. They were eventually diagnosed with Dent disease. Nephrotic syndrome is a rare and insidious phenotype of Dent disease, and its pathogenesis is not fully understood. Patients with nephrotic syndrome are recommended to routinely undergo urinary protein classification and urinary calcium testing, especially those with frequently recurrent nephrotic syndrome and poor response to steroid and immunosuppressive therapy. To date, there is no effective drug treatment for Dent disease. About 30% to 80% of patients progress to end-stage renal disease at the age of 30-50.