Wnt5a deficiency in osteocalcin-expressing cells could not alleviate the osteoarthritic phenotype in a mouse model of post-traumatic osteoarthritis.

Objectives: Wnt5a, which regulates the activities of osteoblasts and osteoclasts, is reportedly overexpressed in osteoarthritis (OA) tissues. The purpose of this study was to elucidate its role in the development of OA by deleting Wnt5a in osteocalcin (OCN)-expressing cells. Materials and Methods: Knee OA was induced by anterior cruciate ligament transection (ACLT) in OCN-Cre;Wnt5afl/fl knockout (Wnt5a-cKO) mice and control littermates. Eight weeks after surgery, histological changes, cell apoptosis, and matrix metabolism of cartilage were evaluated by toluidine blue, TUNEL staining, and im-immunohistochemistry analyses, respectively. In addition, the subchondral bone microarchitecture of mice was examined by micro-computed tomography (micro-CT). Results: Histological scores show substantial cartilage degeneration occurred in ACLT knees, coupled with decreased collagen type II expression and enhanced matrix metalloproteinase 13 expression, as well as higher proportions of apoptotic cells. Micro-CT results show that ACLT resulted in decreased bone mineral density, bone volume/trabecular volume, trabecular number, and structure model index of subchondral bones in both Wnt5a-cKO and control littermates; although Wnt5a-cKO mice display lower BMD and BV/TV values, no significant difference was observed between Wnt5a-cKO and control mice for any of these values. Conclusion: Our findings indicate that Wnt5a deficiency in OCN-expressing cells could not prevent an osteoarthritic phenotype in a mouse model of post-traumatic OA.

Joint-tissue integrative analysis identifies high-risk genes for Parkinson's disease.

The loss of dopaminergic neurons in the substantia nigra and the abnormal accumulation of synuclein proteins and neurotransmitters in Lewy bodies constitute the primary symptoms of Parkinson's disease (PD). Besides environmental factors, scholars are in the early stages of comprehending the genetic factors involved in the pathogenic mechanism of PD. Although genome-wide association studies (GWAS) have unveiled numerous genetic variants associated with PD, precisely pinpointing the causal variants remains challenging due to strong linkage disequilibrium (LD) among them. Addressing this issue, expression quantitative trait locus (eQTL) cohorts were employed in a transcriptome-wide association study (TWAS) to infer the genetic correlation between gene expression and a particular trait. Utilizing the TWAS theory alongside the enhanced Joint-Tissue Imputation (JTI) technique and Mendelian Randomization (MR) framework (MR-JTI), we identified a total of 159 PD-associated genes by amalgamating LD score, GTEx eQTL data, and GWAS summary statistic data from a substantial cohort. Subsequently, Fisher's exact test was conducted on these PD-associated genes using 5,152 differentially expressed genes sourced from 12 PD-related datasets. Ultimately, 29 highly credible PD-associated genes, including CTX1B, SCNA, and ARSA, were uncovered. Furthermore, GO and KEGG enrichment analyses indicated that these genes primarily function in tissue synthesis, regulation of neuron projection development, vesicle organization and transportation, and lysosomal impact. The potential PD-associated genes identified in this study not only offer fresh insights into the disease's pathophysiology but also suggest potential biomarkers for early disease detection.

Genome-wide identification of JAZ gene family in sugarcane and function analysis of ScJAZ1/2 in drought stress response and flowering regulation.

The JASMONATE ZIM DOMAIN (JAZ) proteins are a key inhibitors of the jasmonic acid (JA) signaling pathway that play an important role in the regulation of plant growth and development and environmental stress responses. However, there is no systematic identification and functional analysis of JAZ gene family members in sugarcane. In this study, a total of 49 SsJAZ genes were identified from the wild sugarcane species Saccharum spontaneum genome that were unevenly distributed on 13 chromosomes. Phylogenetic analysis showed that all SsJAZ members can be divided into six groups, and most of the SsJAZ genes contained photoreactive and ABA-responsive elements. RNA-seq analysis revealed that SsJAZ1-1/2/3/4 and SsJAZ7-1 were significantly upregulated under drought stress. The transcript level of ScJAZ1 which is the homologous gene of SsJAZ1 in modern sugarcane cultivars was upregulated by JA, PEG, and abscisic acid (ABA). Moreover, ScJAZ1 can interact with three other JAZ proteins to form heterodimers. The spatial and temporal expression analysis showed that SsJAZ2-1/2/3/4 were highly expressed in different tissues and growth stages and during the day-night rhythm between 10:00 and 18:00. Overexpression of ScJAZ2 in Arabidopsis accelerated flowering through activating the expression of AtSOC1, AtFT, and AtLFY. Moreover, the transcription level of ScJAZ2 was about 30-fold in the early-flowering sugarcane variety than that of the non-flowering variety, indicating ScJAZ2 positively regulated flowering. This first systematic analysis of the JAZ gene family and function analysis of ScJAZ1/2 in sugarcane provide key candidate genes and lay the foundation for sugarcane breeding.

Hierarchical Self-assembly of Multidimensional Functional Materials from Sequence-defined Peptoids.

Hierarchical self-assembly represents a powerful strategy for the fabrication of functional materials across various length scales. However, achieving precise formation of functional hierarchical assemblies remains a significant challenge and requires a profound understanding of molecular assembly interactions. In this study, we present a molecular-level understanding of the hierarchical assembly of sequence-defined peptoids into multidimensional functional materials, including twisted nanotube bundles serving as a highly efficient artificial light harvesting system. By employing synchrotron-based powder X-ray diffraction and analyzing single crystal structures of model compounds, we elucidated the molecular packing and mechanisms underlying the assembly of peptoids into multidimensional nanostructures. Our findings demonstrate that incorporating aromatic functional groups, such as tetraphenyl ethylene (TPE), at the termini of assembling peptoid sequences promotes the formation of twisted bundles of nanotubes and nanosheets, thus enabling the creation of a highly efficient artificial light harvesting system. This research exemplifies the potential of leveraging sequence-defined synthetic polymers to translate microscopic molecular structures into macroscopic assemblies. It holds promise for the development of functional materials with precisely controlled hierarchical structures and designed functions.

Gut microbiota plays a significant role in gout.

With the development of social economy, the incidence of gout is increasing, which is closely related to people's increasingly rich diet. Eating a diet high in purine, fat, sugar and low-fibre for a long time further aggravates gout by affecting uric acid metabolism. The renal metabolism mechanism of uric acid has been thoroughly studied. To find a new treatment method for gout, increasing studies have recently been conducted on the mechanism of intestinal excretion, metabolism and absorption of uric acid. The most important research is the relationship between intestinal microbiota and the risk of gout. Gut microbiota represent bacteria that reside in a host's gastrointestinal tract. The composition of the gut microbiota is associated with protection against pathogen colonization and disease occurrence. This review focuses on how gut microbiota affects gout through uric acid and discusses the types of bacteria that may be involved in the occurrence and progression of gout. We also describe potential therapy for gout by restoring gut microbiota homeostasis and reducing uric acid levels. We hold the perspective that changing intestinal microbiota may become a vital method for effectively preventing or treating gout.

Recognition of Human Lower Limb Motion and Muscle Fatigue Status Using a Wearable FES-sEMG System.

Functional electrical stimulation (FES) devices are widely employed for clinical treatment, rehabilitation, and sports training. However, existing FES devices are inadequate in terms of wearability and cannot recognize a user's intention to move or muscle fatigue. These issues impede the user's ability to incorporate FES devices into their daily life. In response to these issues, this paper introduces a novel wearable FES system based on customized textile electrodes. The system is driven by surface electromyography (sEMG) movement intention. A parallel structured deep learning model based on a wearable FES device is used, which enables the identification of both the type of motion and muscle fatigue status without being affected by electrical stimulation. Five subjects took part in an experiment to test the proposed system, and the results showed that our method achieved a high level of accuracy for lower limb motion recognition and muscle fatigue status detection. The preliminary results presented here prove the effectiveness of the novel wearable FES system in terms of recognizing lower limb motions and muscle fatigue status.

Development of a new Cox model for predicting long-term survival in hepatitis cirrhosis patients underwent transjugular intrahepatic portosystemic shunts.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) placement is a procedure that can effectively treat complications of portal hypertension, such as variceal bleeding and refractory ascites. However, there have been no specific studies on predicting long-term survival after TIPS placement. AIM: To establish a model to predict long-term survival in patients with hepatitis cirrhosis after TIPS. METHODS: A retrospective analysis was conducted on a cohort of 224 patients who underwent TIPS implantation. Through univariate and multivariate Cox regression analyses, various factors were examined for their ability to predict survival at 6 years after TIPS. Consequently, a composite score was formulated, encompassing the indication, shunt reasonability, portal venous pressure gradient (PPG) after TIPS, percentage decrease in portal venous pressure (PVP), indocyanine green retention rate at 15 min (ICGR15) and total bilirubin (Tbil) level. Furthermore, the performance of the newly developed Cox (NDC) model was evaluated in an internal validation cohort and compared with that of a series of existing models. RESULTS: The indication (variceal bleeding or ascites), shunt reasonability (reasonable or unreasonable), ICGR15, postoperative PPG, percentage of PVP decrease and Tbil were found to be independent factors affecting long-term survival after TIPS placement. The NDC model incorporated these parameters and successfully identified patients at high risk, exhibiting a notably elevated mortality rate following the TIPS procedure, as observed in both the training and validation cohorts. Additionally, in terms of predicting the long-term survival rate, the performance of the NDC model was significantly better than that of the other four models [Child-Pugh, model for end-stage liver disease (MELD), MELD-sodium and the Freiburg index of post-TIPS survival]. CONCLUSION: The NDC model can accurately predict long-term survival after the TIPS procedure in patients with hepatitis cirrhosis, help identify high-risk patients and guide follow-up management after TIPS implantation.

Facial Physiological Characteristics and Skin Microbiomes Changes are Associated with Body Mass Index (BMI).

Background: Overweight and obesity have become public health problems worldwide. An increasing number of research works are focusing on skin physiology and the manifestations of obesity-associated skin diseases, but little is known about the correlations between body mass index (BMI), facial skin physiological parameters, and the facial skin microbiome in healthy women. Objective: To investigate the correlations between BMI, facial skin physiological parameters and facial bacteria and fungi in 198 women aged 18 to 35 years in Shanghai. Methods: According to the international BMI standard and Chinese reference standard, subjects were divided into three groups, "lean" B1, "normal" B2 and "overweight" B3, and the physiological parameters of facial skin were measured by non-invasive instrumental methods, and the skin microbiota was analyzed by 16S rRNA and ITS high-throughput sequencing. Results: Compared with the skin physiological parameters of the normal group, those of the overweight group exhibited a significant increase in trans-epidermal water loss (TEWL), which indicated that the skin barrier was impaired. The skin haemoglobin content was significantly increased, and skin surface pH was significant decreased in those with a high BMI. Furthermore, α-diversity, analysed using the Shannon, Chao, Sobs, and Ace indexes, was increased in the overweight group, suggesting that the diversity and species abundance of facial bacterial and fungal microbiota were also increased. Moreover, the overweight group had higher abundances of Streptococcus, Corynebacterium, Malassezia, and Candida. Notably, skin surface pH was significantly and negatively correlated with the relative abundances of Malassezia, Candida, and Cladosporium. Besides, the abundance of Malassezia was positively associated with the abundances of Staphylococcus and Corynebacterium. Conclusion: These results indicate that BMI is associated with differences in the biophysical properties and microbiome of the facial skin. A high BMI affects the integrity of skin barrier and changes the skin flora diversity and species composition.

Gestational diabetes mellitus aggravates adverse perinatal outcomes in women with intrahepatic cholestasis of pregnancy.

PURPOSE: To evaluate the effect of intrahepatic cholestasis of pregnancy (ICP) with gestational diabetes mellitus (GDM) on perinatal outcomes and establish a prediction model of adverse perinatal outcomes in women with ICP. METHODS: This multicenter retrospective cohort study included the clinical data of 2,178 pregnant women with ICP, including 1,788 women with ICP and 390 co-occurrence ICP and GDM. The data of all subjects were collected from hospital electronic medical records. Univariate and multivariate logistic regression analysis were used to compare the incidence of perinatal outcomes between ICP with GDM group and ICP alone group. RESULTS: Baseline characteristics of the population revealed that maternal age (p < 0.001), pregestational weight (p = 0.01), pre-pregnancy BMI (p < 0.001), gestational weight gain (p < 0.001), assisted reproductive technology (ART) (p < 0.001), and total bile acid concentration (p = 0.024) may be risk factors for ICP with GDM. Furthermore, ICP with GDM demonstrated a higher association with both polyhydramnios (OR 2.66) and preterm labor (OR 1.67) compared to ICP alone. Further subgroup analysis based on the severity of ICP showed that elevated total bile acid concentrations were closely associated with an increased risk of preterm labour, meconium-stained amniotic fluid, and low birth weight in both ICP alone and ICP with GDM groups. ICP with GDM further worsened these outcomes, especially in women with severe ICP. The nomogram prediction model effectively predicted the occurrence of preterm labour in the ICP population. CONCLUSIONS: ICP with GDM may result in more adverse pregnancy outcomes, which are associated with bile acid concentrations.

Inertial Measuring System to Evaluate Gait Parameters and Dynamic Alignments for Lower-Limb Amputation Subjects.

The study aims to construct an inertial measuring system for the application of amputee subjects wearing a prosthesis. A new computation scheme to process inertial data by installing seven wireless inertial sensors on the lower limbs was implemented and validated by comparing it with an optical motion capture system. We applied this system to amputees to verify its performance for gait analysis. The gait parameters are evaluated to objectively assess the amputees' prosthesis-wearing status. The Madgwick algorithm was used in the study to correct the angular velocity deviation using acceleration data and convert it to quaternion. Further, the zero-velocity update method was applied to reconstruct patients' walking trajectories. The combination of computed walking trajectory with pelvic and lower limb joint motion enables sketching the details of motion via a stickman that helps visualize and animate the walk and gait of a test subject. Five participants with above-knee (n = 2) and below-knee (n = 3) amputations were recruited for gait analysis. Kinematic parameters were evaluated during a walking test to assess joint alignment and overall gait characteristics. Our findings support the feasibility of employing simple algorithms to achieve accurate and precise joint angle estimation and gait parameters based on wireless inertial sensor data.

Preclinical pharmacokinetic investigation of the bioavailability and skin distribution of HY-072808 ointment, a novel drug candidate for the treatment of atopic dermatitis, in minipigs by a newly LC-MS/MS method.

HY-072808 is a novel phosphodiesterase 4 inhibitor clinically used for topical atopic dermatitis treatment. Cytochrome P450 enzymes are involved in transforming it into major metabolite ZZ-24. An efficient UPLC-MS/MS method was established to detect HY-072808 and ZZ-24 in plasma and skin tissues of minipigs.One-step protein precipitation was performed with acetonitrile. Subsequently, elution was served with a methanol and water gradient containing 0.1% formic acid for 3.5 min. The plasma and skin tissue concentrations of HY-072808 and ZZ-24 showed good linearity from 0.200 to 200 ng/mL.The experimental minipigs exhibited low systemic exposure and bioavailability of 3.1-7.6% after transdermal application of 1-4% HY-072808 ointment. Multiple topical administrations over seven consecutive days showed a minor accumulation in systemic exposure, with accumulation factors of 2.3 and 4.0 for HY-072808 and ZZ-24, respectively.The distribution of HY-072808 ointment among different cortical layers in minipigs was studied for the first time. Following transdermal application of 2% HY-072808 ointment, the concentration in plasma and skin tissues in the order of epidermis > dermis > subcutaneous tissue ≈ subcutaneous muscle ≈ plasma; at 48 h after the administration, the epidermis and dermis still had a high concentration of the drug.

Divergent Total Syntheses of Lycorine Alkaloids via a Sequential C-H Functionalization Strategy.

A Pd-catalyzed one-pot sequential C-H functionalization strategy was utilized to prepare four lycorine alkaloids and one pseudo-lycorine alkaloid from the common intermediate 4. By switching the followed oxidative conditions of air, DMSO/H2O/I2, and DMSO/O2, based on the Pd(PPh3)4/K2CO3/toluene catalytic system, three key intermediates 12a, 12b, and 12c with different substitution patterns could be obtained in a well-controlled manner. As a result, four natural products γ-lycorane, hippadine, anhydrolycorinone, and anhydrolycorine as well as a pseudo-lycorine alkaloid Δ(4a,10b)-6-oxodihydrolycorine were successfully synthesized within 10 steps through this divergent route.

Tunable Neuromorphic Switching Dynamics via Porosity Control in Mesoporous Silica Diffusive Memristors.

In response to the growing need for efficient processing of temporal information, neuromorphic computing systems are placing increased emphasis on the switching dynamics of memristors. While the switching dynamics can be regulated by the properties of input signals, the ability of controlling it via electrolyte properties of a memristor is essential to further enrich the switching states and improve data processing capability. This study presents the synthesis of mesoporous silica (mSiO2) films using a sol-gel process, which enables the creation of films with controllable porosities. These films can serve as electrolyte layers in the diffusive memristors and lead to tunable neuromorphic switching dynamics. The mSiO2 memristors demonstrate short-term plasticity, which is essential for temporal signal processing. As porosity increases, discernible changes in operating currents, facilitation ratios, and relaxation times are observed. The underlying mechanism of such systematic control was investigated and attributed to the modulation of hydrogen-bonded networks within the porous structure of the silica layer, which significantly influences both anodic oxidation and ion migration processes during switching events. The result of this work presents mesoporous silica as a unique platform for precise control of neuromorphic switching dynamics in diffusive memristors.

Biomimetic Total Synthesis of Bimagnolignan: A Natural Anti-Breast Cancer Agent.

A short scalable biomimetic route to bioactive natural product bimagnolignan (1) was accomplished. Compound 1 was successfully prepared through a three-step metal-free synthesis from honokiol (2). Alternatively, 1 was also synthesized by biomimetic transformations that mimic tyrosinase in four steps. The key reactions feature a regioselective acetylation, a highly efficient C(sp2)-H oxidation, a cascade aerobic oxidative cyclization/coupling, and a Cu-catalyzed direct oxidative coupling. In addition, cell-based assays validate that 1 is a promising natural lead for HER2-positive breast cancer treatment.

Predictive nomograms of repeat intrahepatic recurrence and overall survival after radiofrequency ablation of recurrent colorectal liver metastases.

OBJECTIVES: This study was conducted to develop nomograms for predicting repeat intrahepatic recurrence (rIHR) and overall survival (OS), after radiofrequency ablation (RFA), treatment in patients with recurrent colorectal liver metastases (CLMs) after hepatectomy based on clinicopathologic features. METHODS: A total of 160 consecutive patients with recurrent CLMs after hepatectomy who were treated with ultrasound-guided percutaneous RFA from 2012 to 2022 were retrospectively included. Patients were randomly divided into a training cohort and a validation cohort, with a ratio of 8:2. Potential prognostic factors associated with rIHR and OS, after RFA, were identified by using the competing-risks and Cox proportional hazard models, respectively, and were used to construct the nomogram. The nomogram was evaluated by Harrell's C-index and a calibration curve. RESULTS: The 1-, 2-, and 3-year rIHR rates after RFA were 58.8%, 70.2%, and 74.2%, respectively. The 1-, 3- and 5-year OS rates were 96.3%, 60.4%, and 38.5%, respectively. In the multivariate analysis, mutant RAS, interval from hepatectomy to intrahepatic recurrence ≤ 12 months, CEA level >5 ng/ml, and ablation margin <5 mm were the independent predictive factors for rIHR. Mutant RAS, largest CLM at hepatectomy >3 cm, CEA level >5 ng/ml, and extrahepatic disease were independent predictors of poor OS. Two nomograms for rIHR and OS were constructed using the respective significant variables. In both cohorts, the nomogram demonstrated good discrimination and calibration. CONCLUSIONS: The established nomograms can predict individual risk of rIHR and OS after RFA for recurrent CLMs and contribute to improving individualized management.

Design, Synthesis, and Biological Evaluation of Pierardine Derivatives as Novel Brain-Penetrant and In Vivo Potent NMDAR-GluN2B Antagonists for Ischemic Stroke Treatment.

A series of structurally novel GluN2B NMDAR antagonists were designed, synthesized, and biologically evaluated as anti-stroke therapeutics by optimizing the chemical structure of Pierardine, the active ingredient of traditional Chinese medicine Dendrobium aphyllum (Roxb.) C. E. Fischer identified via in silico screening. The systematic structure-activity relationship study led to the discovery of 58 with promising NMDAR-GluN2B binding affinity and antagonistic activity. Of the two enantiomers, S-58 exhibited significant inhibition (IC50 = 74.01 ± 12.03 nM) against a GluN1/GluN2B receptor-mediated current in a patch clamp assay. In addition, it displayed favorable specificity over other subtypes and off-target receptors. In vivo, S-58 exerted therapeutic efficacy comparable to that of the approved GluN2B NMDAR antagonist ifenprodil and excellent safety profiles. In addition to the attractive in vitro and in vivo potency, S-58 exhibited excellent brain exposure. In light of these merits, S-58 has been advanced to further preclinical investigation as a potential anti-stroke candidate.

Discovery of the novel and potent histamine H1 receptor antagonists for treatment of allergic diseases.

Desloratadine, a second-generation histamine H1 receptor antagonist, has established itself as a first-line drug for the treatment of allergic diseases. Despite its effectiveness, desloratadine exhibits an antagonistic effect on muscarinic M3 receptor, which can cause side effects such as dry mouth and urinary retention, ultimately limiting its clinical application. Herein, we describe the discovery of compound Ⅲ-4, a novel H1 receptor antagonist with significant H1 receptor antagonistic activity (IC50 = 24.12 nM) and enhanced selectivity towards peripheral H1 receptor. In particular, Ⅲ-4 exhibits reduced M3 receptor inhibitory potency (IC50 > 10,000 nM) and acceptable hERG inhibitory activity (17.6 ± 2.1 µM) compare with desloratadine. Additionally, Ⅲ-4 exhibits favorable pharmacokinetic properties, as well as in vivo efficacy and safety profiles. All of these reveal that Ⅲ-4 has potential to emerge as a novel H1 receptor antagonist for the treatment of allergic diseases. More importantly, the compound Ⅲ-4 (HY-078020) has recently been granted clinical approval.

Design, synthesis, antibacterial evaluation of isopropylamine linked with different substituted phenol and piperazine novel derivatives.

BACKGROUND: Xanthomonas oryzae pv. oryzae (Xoo) is often considered one of the most destructive bacterial pathogens causing bacterial leaf blight (BLB), resulting in significant yield and cost losses in rice. In this study, a series of novel derivatives containing the isopropanolamine moiety linked to various substituted phenols and piperazines were designed, synthesized and screened. RESULTS: Antibacterial activity results showed that most compounds had good inhibitory effects on Xoo, among which compound W2 (EC50 = 2.74 µg mL-1 ) exhibited the most excellent inhibitory activity, and W2 also had a certain curative effect (35.89%) on rice compared to thiodiazole copper (TC) (21.57%). Scanning electron microscopy (SEM) results indicated that compound W2 could cause rupture of the Xoo cell membrane. Subsequently, proteomics and quantitative real-time polymerase chain reaction revealed that compound W2 affected the physiological processes of Xoo and may exert antibacterial activity by targeting the two-component system pathway. Interestingly, W2 upregulated Xoo's methyltransferase to impact on its pathogenicity. CONCLUSION: The present study offers a promising phenolic-piperazine-sopropanolamine compound as an innovative antibacterial strategy by specifically targeting the two-component system pathway and inducing upregulation of methyltransferase to effectively impact Xoo's pathogenicity. © 2024 Society of Chemical Industry.

ISR inhibition reverses pancreatic ß-cell failure in Wolfram syndrome models.

Pancreatic ß-cell failure by WFS1 deficiency is manifested in individuals with wolfram syndrome (WS). The lack of a suitable human model in WS has impeded progress in the development of new treatments. Here, human pluripotent stem cell derived pancreatic islets (SC-islets) harboring WFS1 deficiency and mouse model of ß cell specific Wfs1 knockout were applied to model ß-cell failure in WS. We charted a high-resolution roadmap with single-cell RNA-seq (scRNA-seq) to investigate pathogenesis for WS ß-cell failure, revealing two distinct cellular fates along pseudotime trajectory: maturation and stress branches. WFS1 deficiency disrupted ß-cell fate trajectory toward maturation and directed it towards stress trajectory, ultimately leading to ß-cell failure. Notably, further investigation of the stress trajectory identified activated integrated stress response (ISR) as a crucial mechanism underlying WS ß-cell failure, characterized by aberrant eIF2 signaling in WFS1-deficient SC-islets, along with elevated expression of genes in regulating stress granule formation. Significantly, we demonstrated that ISRIB, an ISR inhibitor, efficiently reversed ß-cell failure in WFS1-deficient SC-islets. We further validated therapeutic efficacy in vivo with ß-cell specific Wfs1 knockout mice. Altogether, our study provides novel insights into WS pathogenesis and offers a strategy targeting ISR to treat WS diabetes.

Film before aggregates: an operando GISAXS study on electrochemically assisted surfactant assembly.

The process of electrochemically assisted surfactant assembly was followed in real time by grazing incidence small angle X-ray scattering with the aim to deconvolute the formation of mesoporous silica film and unwanted porous particles. The X-ray technique proved to be useful for the characterisation of this process, as it takes place at a very dynamic, solid/liquid interface. This paper shows the electrochemically driven onset and evolution of silica/surfactant structures. Additional control experiments indicate the formation of vertically aligned structures without the use of an electric field, although it seems to be beneficial for increased pore ordering.