Sieving-type Electric Double Layer with Hydrogen Bond Interlocking to Stable Zinc Metal Anode.

The stability of aqueous zinc metal batteries is significantly affected by side reactions and dendrite growth on the anode interface, which primarily originate from water and anions. Herein, we introduce a multi H-bond site additive, 2, 2'-Sulfonyldiethanol (SDE), into an aqueous electrolyte to construct a sieving-type electric double layer (EDL) by hydrogen bond interlock in order to address these issues. On the one hand, SDE replaces H2O and SO42- anions that are adsorbed on the zinc anode surface, expelling H2O/SO42- from the EDL and thereby reducing the content of H2O/SO42- at the interface. On the other hand, when Zn2+ are de-solvated at the interface during the plating, the strong hydrogen bond interaction between SDE and H2O/SO42- can trap H2O/SO42- from the EDL, further decreasing their content at the interface. This effectively sieves them out of the zinc anode interface and inhibits the side reactions. Moreover, the unique characteristics of trapped SO42- anions can restrict their diffusion, thereby enhancing the transference number of Zn2+ and promoting dendrite-free deposition and growth of Zn. Consequently, utilizing an SDE/ZnSO4 electrolyte enables excellent cycling stability in Zn//Zn symmetrical cells and Zn//MnO2 full cells with lifespans exceeding 3500 h and 2500 cycles respectively.

Increased glycolysis in skeletal muscle coordinates with adipose tissue in systemic metabolic homeostasis.

Insulin-independent glucose metabolism, including anaerobic glycolysis that is promoted in resistance training, plays critical roles in glucose disposal and systemic metabolic regulation. However, the underlying mechanisms are not completely understood. In this study, through genetically manipulating the glycolytic process by overexpressing human glucose transporter 1 (GLUT1), hexokinase 2 (HK2) and 6-phosphofructo-2-kinase-fructose-2,6-biphosphatase 3 (PFKFB3) in mouse skeletal muscle, we examined the impact of enhanced glycolysis in metabolic homeostasis. Enhanced glycolysis in skeletal muscle promoted accelerated glucose disposal, a lean phenotype and a high metabolic rate in mice despite attenuated lipid metabolism in muscle, even under High-Fat diet (HFD). Further study revealed that the glucose metabolite sensor carbohydrate-response element-binding protein (ChREBP) was activated in the highly glycolytic muscle and stimulated the elevation of plasma fibroblast growth factor 21 (FGF21), possibly mediating enhanced lipid oxidation in adipose tissue and contributing to a systemic effect. PFKFB3 was critically involved in promoting the glucose-sensing mechanism in myocytes. Thus, a high level of glycolysis in skeletal muscle may be intrinsically coupled to distal lipid metabolism through intracellular glucose sensing. This study provides novel insights for the benefit of resistance training and for manipulating insulin-independent glucose metabolism.

Characteristics and reference ranges of CD4+T cell subpopulations among healthy adult Han Chinese in Shanxi Province, North China.

BACKGROUND: Immunophenotyping of blood lymphocytes is an essential tool to evaluate the immune function of patients with immunodeficiency or autoimmunity. Predominately identified CD4+T cell subsets, Th1, Th2, Th17, as well as regulatory T (Treg) cells, play crucial roles in several immunological and pathological conditions. Considering the variations in cell counts among populations and ethnicities, specific CD4+T cell subset reference values need to be locally established to enable meaningful comparisons and accurate data interpretation in clinical and research settings. Therefore, the aim of this study was to establish distributions and reference ranges for blood CD4+T cell subpopulations in age- and sex-balanced healthy adults of a Han Chinese population in Shanxi Province, North China. METHODS: Peripheral blood CD4+T cell subsets were examined in 150 healthy volunteers (75 males, 75 females) aged 20-70 years with a four-color FACSCalibur flow cytometer. RESULTS: Reference value percentages (absolute counts, cells/µl) were defined as 95% of the population for cell types as follows: CD4+T, 23.78-51.07 (360-1127); Th1, 0.43-39.62 (2.64-276.21); Th2, 0.27-3.57 (1.80-27.14); Th17, 0.22-2.62 (1.10-19.54); and Treg, 2.17-7.94 (13.47-64.58). The ranges for the Th1:Th2 and Th17:Treg ratios were 0.59-52.37 and 0.04-0.76, respectively. Notably, a significant increase was observed in the values of Treg cells in older individuals, and the numbers of Treg cells in females also tended to decrease when compared to those in males. Therefore, we established the distribution and reference range of CD4+T cell subsets based on age and sex, demonstrating the lowest values of Treg cells in younger females. CONCLUSIONS: Collectively, our data provide population-, age-, and sex-specific distributions and reference ranges of circulating CD4+T cell subpopulations, which can be adopted to guide clinical decisions and interpretation of immunophenotyping data in the Han Chinese population in Taiyuan, Shanxi Province, China. In addition, the low expression of peripheral Treg cells in younger females may be associated with the predisposition of females to autoimmune diseases.

Sirolimus selectively increases circulating Treg cell numbers and restores the Th17/Treg balance in rheumatoid arthritis patients with low disease activity or in DAS28 remission who previously received conventional disease-modifying anti-rheumatic drugs.

OBJECTIVES: Regulatory T (Treg) cells are crucial players in the prevention of autoimmunity. Mechanistic target of rapamycin (mTOR) signalling negatively controls the development and function of Treg cells. The aim of the present study was to evaluate the effects of rapamycin, under the generic name sirolimus, on CD4+CD25+FoxP3+ Treg cells in rheumatoid arthritis (RA) patients with low disease activity or in DAS28 remission. METHODS: Fifty-five RA patients and 60 healthy controls were enrolled in this study. All patients had previously received conventional disease-modifying anti-rheumatic drugs (DMARDs) and were considered to have a low DAS28 score (≤3.2). Peripheral blood samples and clinical information were obtained at baseline and following 6 and 12 weeks of sirolimus treatment, or after 12 weeks of conventional treatment. Peripheral blood samples were also obtained from the healthy controls. The circulating levels of lymphocyte subpopulations were assessed by flow cytometry. RESULTS: Thirty-five patients received sirolimus and 20 patients continued treatment with conventional DMARDs. The absolute counts and proportions of CD4+CD25+FoxP3+ Treg cells were significantly lower in all RA patients with DAS28 ≤ 3.2 as compared with those in healthy controls. By contrast, the difference in circulating Th17 cell numbers was not significant. Sirolimus administration resulted in elevations in circulating Treg cell numbers and significant reductions in the Th17/Treg cell ratio, whereas the circulating level of Treg cells and the Th17/Treg cell ratio in patients under conventional treatment both showed a tendency of reduction. Furthermore, a greater proportion of patients under sirolimus treatment achieved DAS28-based remission at 12 weeks. CONCLUSIONS: Sirolimus can favourably expand Treg cells in RA patients with DAS28 ≤3.2, consequently restoring a healthy balance of Th17/Treg cells, which might improve the likelihood of long-term and sustained clinical remission and reduce the probability of disease flare-ups in RA.

p53 pathway is involved in cell competition during mouse embryogenesis.

The function of tumor suppressor p53 has been under intense investigation. Acute stresses such as DNA damage are able to trigger a high level of p53 activity, leading to cell cycle arrest or apoptosis. In contrast, the cellular response of mild p53 activity induced by low-level stress in vivo remains largely unexplored. Murine double minute (MDM)2 and MDM4 are two major negative regulators of p53. Here, we used the strategy of haploinsufficiency of Mdm2 and Mdm4 to induce mild p53 activation in vivo and found that Mdm2+/-Mdm4+/- double-heterozygous mice exhibited normal embryogenesis. However, closer examination demonstrated that the Mdm2+/-Mdm4+/- cells exhibited a growth disadvantage and were outcompeted during development in genetic mosaic embryos that contained wild-type cells. Further study indicated the out-competition phenotype was dependent on the levels of p53. These observations revealed that cells with mild p53 activation were less fit and exhibited altered fates in a heterotypic environment, resembling the cell competition phenomenon first uncovered in Drosophila By marking unfit cells for elimination, p53 may exert its physiological role to ensure organ and animal fitness.

Mouse Double Minute 2 Actively Suppresses p53 Activity in Oocytes during Mouse Folliculogenesis.

The p53 signaling network is indispensible in cellular stress responses and tumor suppression. Negative regulations of p53 by mouse double minute 2 (MDM2) and its homolog MDM4 are an integrated component of the network and have been implicated in regulating the stress responses and the maintenance of normal development and homeostasis of multiple somatic cell lineages. However, the regulatory role of MDM2 on p53 and stress responses in female germ cells remains undetermined. Here, we used the Cre-loxP system to delete Mdm2 in oocytes at different stages of folliculogenesis in mice. Mdm2 deletion resulted in a clear p53 nuclear accumulation in the oocytes and impeded fertilities with early follicular loss in mice, resembling human premature ovarian failure phenotypes. These phenotypes were fully rescued by concurrent deletion of p53 in mice. In addition, Nutlin-3, a small molecule compound that inhibited the binding of MDM2 to p53, also promoted p53-dependent oocyte death. Although cancer therapeutic agents 5-fluorouracil and doxorubicin could not induce a robust p53 activation in the wild-type oocytes, they induced p53 nuclear accumulation in the Mdm2 and Mdm4 double heterozygous oocytes. These results demonstrated a critical prosurvival role for MDM2 in the oocytes. Moreover, they suggested a more tightened and rigorous regulatory mode for the MDM2/MDM4-p53 network in female germ cells under stress situations.

Nurses' perception of knowledge, attitudes and reported practice towards patients with eating disorders: A concurrent mixed-methods study.

Eating disorders are complex disorders requiring specialised care, thus knowledge and attitudes are crucial for management. This study aims to examine nurses' knowledge, attitudes, reported practice, and perceptions towards patients with eating disorders in Singapore. A concurrent mixed-methods study was carried out in Southeast Asia's only psychiatric unit with eating disorders programme. Twenty nurses were recruited using census sampling. Quantitative data were analysed with descriptive and inferential statistics, while qualitative data were analysed with content and thematic analysis. Certain personal factors were associated with nurses' levels of perceived knowledge. Different attitudes towards managing these patients were identified during interview sessions.

Exploring predictors of medication adherence among inpatients with schizophrenia in Singapore's mental health settings: A non-experimental study.

Schizophrenia is a mental disorder, which is marked by frequent relapses. The main reason for relapse is nonadherence to antipsychotics. A cross-sectional, correlational research study was conducted with a convenience sample of 92 participants. The primary aim of this study was to explore the predictors of medication adherence among inpatients with schizophrenia hospitalised at tertiary hospitals in Singapore. Post-hoc analysis revealed that insight, religion, side effects, types of antipsychotics, social support from significant others, nurse-client relationship, were significant predictive factors. Results from this study added knowledge to the nursing literature about medication adherence of schizophrenia patients and in Singapore setting.

Knowledge, Attitudes and Challenges of Healthcare Professionals Managing People With Eating Disorders: A Literature Review.

This review consolidates findings regarding knowledge and attitudes of healthcare professionals, together with challenges faced while caring for patients with eating disorders. A rigorous and systematic approach was taken to identify 21 articles, which include 12 quantitative, 7 qualitative, and 2 mixed-method papers. Healthcare professionals' knowledge and attitudes toward patients with eating disorders will be discussed, while identifying if factors like age, gender, work experience or profession have an impact on these two variables. Challenges faced during care provision will also be examined. Methodological limitations and knowledge gaps from these articles will be discussed, together with implications of this review.

Factors Affecting Medication Adherence Among Adults with Schizophrenia: A Literature Review.

This review aimed to summarize empirical evidence concerning factors relating to medication adherence among patients with schizophrenia. A comprehensive search was implemented to recruit articles which met the present eligibility criteria. Twenty-five articles were included whereby only one was a qualitative study. Greater awareness of illness (insight), previous history of medication adherence, positive attitude toward medication, types of atypical antipsychotics, less severe psychotic symptoms, and social support were identified as factors of medication adherence. Knowledge gaps and methodological limitations were also identified. Implications to clinical practice include providing psychoeducation to patients by increasing their knowledge about illness and medication.

Lesion region inpainting: an approach for pseudo-healthy image synthesis in intracranial infection imaging.

The synthesis of pseudo-healthy images, involving the generation of healthy counterparts for pathological images, is crucial for data augmentation, clinical disease diagnosis, and understanding pathology-induced changes. Recently, Generative Adversarial Networks (GANs) have shown substantial promise in this domain. However, the heterogeneity of intracranial infection symptoms caused by various infections complicates the model's ability to accurately differentiate between pathological and healthy regions, leading to the loss of critical information in healthy areas and impairing the precise preservation of the subject's identity. Moreover, for images with extensive lesion areas, the pseudo-healthy images generated by these methods often lack distinct organ and tissue structures. To address these challenges, we propose a three-stage method (localization, inpainting, synthesis) that achieves nearly perfect preservation of the subject's identity through precise pseudo-healthy synthesis of the lesion region and its surroundings. The process begins with a Segmentor, which identifies the lesion areas and differentiates them from healthy regions. Subsequently, a Vague-Filler fills the lesion areas to construct a healthy outline, thereby preventing structural loss in cases of extensive lesions. Finally, leveraging this healthy outline, a Generative Adversarial Network integrated with a contextual residual attention module generates a more realistic and clearer image. Our method was validated through extensive experiments across different modalities within the BraTS2021 dataset, achieving a healthiness score of 0.957. The visual quality of the generated images markedly exceeded those produced by competing methods, with enhanced capabilities in repairing large lesion areas. Further testing on the COVID-19-20 dataset showed that our model could effectively partially reconstruct images of other organs.

A comparative study of spectral and luminescent properties of Eu3+-doped cation-deficient perovskite phosphors.

Eu3+ is not only a major red-emitting activator, but also an excellent spectral probe ion. This work reports the Eu3+-sites and luminescence in the cation-deficient perovskite tungstates, A-site deficient SrLa2(Mg2W2)O12 [Sr1/2□1/2La(MgW)O6] and B-site deficient Sr2La2(MgW2)O12 [SrLa(Mg1/2□1/2W)O6]. The 7F0→5D0 excitation spectra of Eu3+ activators in two lattices were measured via pulsed dye laser. In SrLa2(Mg2W2)O12:Eu3+, there is only one 7F0→5D0 transition, which could be related to the Eu3+ center on La3+ sites; while, two 7F0→5D0 transitions in Sr2La2(MgW2)O12 indicate Eu3+ ions occupy Sr2+ in addition to La3+, resulting in the luminescent centers related to heterovalent substitution defects. The different Eu3+ sites make two phosphors exhibit different red luminescence properties. SrLa2(Mg2W2)O12:Eu3+ shows higher luminescent efficiency and thermal quenching due to its regular distribution of the activators resulting in lower dispersion losses of the energy transfer. The experimental results show that rare earth ions occupy different crystallographic positions in A-site and B-site deficient perovskite oxides, and this microstructure can be important for the corresponding luminescent properties.

Association between dietary inflammatory index and gallstones in US adults.

Introduction: Previous studies have found that diet's inflammatory potential is related to various diseases. However, little is known about its relationship with gallstones. The present study aims to investigate the relationship between dietary inflammatory index (DII) and gallstones. Methods: Data were obtained from the 2003-2020 National Health and Nutrition Examination Survey (NHANES). We used the nearest neighbor propensity score matching (PSM) with a ratio of 1:1 to reduce selection bias. Logistic regression models estimated the association between DII and gallstones. The non-linear relationship was explored with restricted cubic splines (RCS). BMI subgroup stratification was performed to explore further the connection between DII and gallstones in different populations. Results: 10,779 participants were included. Before and after PSM, gallstone group individuals had higher DII scores than non-gallstone group individuals (p < 0.05). Matched logistic regression analysis showed that DII scores were positively correlated with gallstone risk (adjusted OR = 1.14, 95% CI 1.01, 1.29). The stratified analysis showed that this association was stronger in overweight or obese people (adjusted OR = 1.18, 95% CI 1.03, 1.34). RCS analysis suggested that DII and gallstones showed a "J"-shaped non-linear dose-response relationship (p non-linear <0.001). Conclusion: Higher DII score is positively associated with the risk of gallstones, particularly in overweight or obese population, and this relationship is a "J"-shaped non-linear relationship. These results further support that avoiding or reducing a pro-inflammatory diet can be an intervention strategy for gallstone management, particularly in the overweight or obese population.

Efficient synergism of concentric ring structures and carbon dots for enhanced methanol electro-oxidation.

Developing affordable and reliable electrocatalysts with high activity and stability is crucial for enhancing the practicality of direct methanol fuel cells (DMFCs). An effective and simple strategy of combining the carbon point of N-CDs (0.4 mg mL-1) with NiO/Ni for the fabrication of NiO/Ni-N-CDsV nanocomposites with a three-dimensional concentric core-shell structure was proposed to successfully prepare the electro-oxidation catalyst of methanol. The low cost of Ni-based materials and the conductive N-CDs that improve methanol catalytic performance make the composites an excellent choice as electrode materials for direct methanol fuel cells (DMFCs). The electrocatalytic behavior of methanol oxidation was studied using cyclic voltammetry and chronoamperometry. The results indicated that the catalytic activity of NiO/Ni-N-CDsV increased by 3.02 times, and the current density was stable during the operation for 83 hours, implying strong electrocatalytic stability. Furthermore, the electrocatalytic performance for ethanol, ethylene glycol, and glycerol electro-oxidation reactions was impressive. This study provides a novel foundation for the development of high-performance, cost-effective, non-noble metal catalysts for DMFC applications, contributing to the formation of commercially competitive electro-oxidation catalysts with enhanced efficiency and stability.

CRLF1 bridges AKT and mTORC2 through SIN1 to inhibit pyroptosis and enhance chemo-resistance in ovarian cancer.

Ovarian cancer, the second most leading cause of gynecologic cancer mortality worldwide, is challenged by chemotherapy resistance, presenting a significant hurdle. Pyroptosis, an inflammation-linked programmed cell death mediated by gasdermins, has been shown to impact chemoresistance when dysregulated. However, the mechanisms connecting pyroptosis to chemotherapy resistance in ovarian cancer are unclear. We found that cytokine receptor-like factor 1 (CRLF1) is a novel component of mTORC2, enhancing AKT Ser473 phosphorylation through strengthening the interaction between AKT and stress-activated protein kinase interacting protein 1 (SIN1), which in turn inhibits the mitogen-activated protein kinase kinase kinase 5 (ASK1)-JNK-caspase-3-gasdermin E pyroptotic pathway and ultimately confers chemoresistance. High CRLF1-expressing tumors showed sensitivity to AKT inhibition but tolerance to cisplatin. Remarkably, overexpression of binding-defective CRLF1 variants impaired AKT-SIN1 interaction, promoting pyroptosis and chemosensitization. Thus, CRLF1 critically regulates chemoresistance in ovarian cancer by modulating AKT/SIN1-dependent pyroptosis. Binding-defective CRLF1 variants could be developed as tumor-specific polypeptide drugs to enhance chemotherapy for ovarian cancer.

SNX8 enables lysosome reformation and reverses lysosomal storage disorder.

Lysosomal Storage Disorders (LSDs), which share common phenotypes, including enlarged lysosomes and defective lysosomal storage, are caused by mutations in lysosome-related genes. Although gene therapies and enzyme replacement therapies have been explored, there are currently no effective routine therapies against LSDs. During lysosome reformation, which occurs when the functional lysosome pool is reduced, lysosomal lipids and proteins are recycled to restore lysosome functions. Here we report that the sorting nexin protein SNX8 promotes lysosome tubulation, a process that is required for lysosome reformation, and that loss of SNX8 leads to phenotypes characteristic of LSDs in human cells. SNX8 overexpression rescued features of LSDs in cells, and AAV-based delivery of SNX8 to the brain rescued LSD phenotypes in mice. Importantly, by screening a natural compound library, we identified three small molecules that enhanced SNX8-lysosome binding and reversed LSD phenotypes in human cells and in mice. Altogether, our results provide a potential solution for the treatment of LSDs.

Effects of ferroptosis-related gene HSPB1 on acute myeloid leukemia.

INTRODUCTION: The purpose of this study was to investigate the effects and potential mechanisms of ferroptosis-related gene heat shock protein beta-1 (HSPB1) on acute myeloid leukemia (AML). METHODS: The RNA-seq and clinical data of AML samples were obtained from the Genomic Data Commons database, and the FerrDb database was used to screen the marker, drive and suppressor of ferroptosis. Besides, DESeq2 was applied for differential expression analysis on AML samples and screening for differentially expressed genes (DEGs). The screened DEGs were subjected to the intersection analysis with ferroptosis-related genes to identify the ferroptosis-related DEGs. Next, the functional pathways of ferroptosis-related DEGs were further be discussed by Gene Ontology as well as Kyoto Encyclopedia of Genes and Genomes enrichment analysis of DEGs. Additionally, lasso regression analysis was employed to determine the differential genes related to prognosis in patients with AML and the survival analysis was performed. Subsequently, quantitative real-time polymerase chain reaction and western blot assay were applied to detect the mRNA and protein expression levels of HSPB1 in normal/AML bone marrow tissues and human normal (HS-5)/AML (HL-60) bone marrow cells, respectively. Furthermore, HSPB1 was knocked down to assess the expression changes of glutathione peroxidase 4 and acyl-CoA synthetase long-chain family member 4. Ultimately, the viability and oxidative stress levels of HL-60 were analyzed by Cell Counting Kit-8 and biochemical detection. RESULTS: A total of 4986 DEGs were identified in AML samples, with 3324 up-regulated and 1662 down-regulated. The enrichment analysis illustrated that ferroptosis-related DEGs were significantly enriched in response to metal irons, oxidative stress, and other pathways. After lasso regression analysis, 17 feature genes related to the prognosis of patients with AML were obtained, with HSPB1 exhibiting a significant correlation. The reliability of our models was verified by Cox regression analysis and survival analysis of the hazard model. Furthermore, the outcomes of quantitative real-time polymerase chain reaction and western blot showed that mRNA and protein expression levels of HSPB1 were significantly increased in the AML Group and HL-60 cells. The knockdown of HSPB1 in HL-60 cells reduced the protein level of glutathione peroxidase 4, increased the protein level of acyl-CoA synthetase long-chain family member 4, decreased the cell viability, and aggravated oxidative stress. CONCLUSION: Ferroptosis-related gene HSPB1 is highly expressed in patients with AML. In addition, HSPB1 may be involved in the occurrence and development of AML by regulating oxidative stress and ferroptosis-related pathways. This study provides new clues for further understanding of AML molecular mechanisms. Also, HSPB1 is expected to be a potential therapeutic target for AML in the future.

Starvation-induced phosphorylation activates gasdermin A to initiate pyroptosis.

Pyroptosis, a pro-inflammatory form of programmed cell death, is crucial for host defense against pathogens and danger signals. Proteolytic cleavage of gasdermin proteins B-E (GSDMB-GSDME) is well established as a trigger for pyroptosis, but the intracellular activation mechanism of GSDMA remains elusive. Here, we demonstrate that severe starvation induces pyroptosis through phosphorylation-induced activation of GSDMA. Nutrient stresses stimulate GSDMA activation via phosphorylation mediated by Unc-51-like autophagy-activating kinase 1 (ULK1). Phosphorylation of Ser353 on human GSDMA by ULK1 or the phospho-mimetic Ser353Asp mutant of GSDMA liberates GSDMA from auto-inhibition, facilitating its membrane targeting and initiation of pyroptosis. To further validate the significance of GSDMA phosphorylation, we generated a constitutively active mutant Ser354Asp of mouse Gsdma, which induced skin inflammation and hyperplasia in mice, reminiscent of phenotypes with activated Gsdma. This study uncovers phosphorylation of GSDMA as a mechanism underlying pyroptosis initiation and cellular response to nutrient stress.

Reducing anxiety and enhancing satisfaction in thyroid patients with DietLens application during radioactive iodine therapy: A quasi-experimental study.

Hyperthyroidism and thyroid cancer significantly impact health, and often require Radioactive Iodine (RAI) therapy. Anxiety is common in patients undergoing RAI, particularly related to dietary compliance. This study aimed to assess the effectiveness of the mobile health application, DietLens in reducing anxiety and increasing satisfaction in patients preparing for RAI therapy, focusing on low-iodine diet (LID). A quasi-experimental study was conducted in a Singapore tertiary hospital outpatient department from March 13, 2019 to March 27, 2020, involving patients scheduled for their first RAI treatment. Participants were divided into a control group receiving standard care and an intervention group using DietLens alongside standard care. Anxiety levels were assessed using the Zung Self-Rating Anxiety Scale, and satisfaction levels were measured through self-reported questionnaires. In the study, 56 participants were initially divided into control (n = 28) and intervention (n = 28) groups. After accounting for dropouts, 50 participants finished the study, with each group comprising 25 individuals. Anxiety levels were similar between groups pre-intervention. Post-intervention, the intervention group displayed a significant decrease in anxiety levels compared to the control group (independent t-test: t (48) = 2.50, p = 0.02). The multivariate linear regression analysis indicated that being in the intervention group was significantly associated with a decrease in post-intervention anxiety score (ß = -4.03, 95 % CI: -7.33 to -0.72, p = 0.02). Fisher's Exact Test revealed a borderline significant difference in satisfaction with educational materials and the overall treatment process, with 100 % of the intervention group expressing satisfaction compared to 80 % in the control group, resulting in a p-value of 0.052 in both instances. DietLens was effective in reducing anxiety and enhancing satisfaction related to RAI therapy preparation, particularly in managing a LID, highlighting a beneficial role for digital interventions in healthcare settings.

Innate immune sensing of lysosomal dysfunction drives multiple lysosomal storage disorders.

Lysosomal storage disorders (LSDs), which are characterized by genetic and metabolic lysosomal dysfunctions, constitute over 60 degenerative diseases with considerable health and economic burdens. However, the mechanisms driving the progressive death of functional cells due to lysosomal defects remain incompletely understood, and broad-spectrum therapeutics against LSDs are lacking. Here, we found that various gene abnormalities that cause LSDs, including Hexb, Gla, Npc1, Ctsd and Gba, all shared mutual properties to robustly autoactivate neuron-intrinsic cGAS-STING signalling, driving neuronal death and disease progression. This signalling was triggered by excessive cytoplasmic congregation of the dsDNA and DNA sensor cGAS in neurons. Genetic ablation of cGAS or STING, digestion of neuronal cytosolic dsDNA by DNase, and repair of neuronal lysosomal dysfunction alleviated symptoms of Sandhoff disease, Fabry disease and Niemann-Pick disease, with substantially reduced neuronal loss. We therefore identify a ubiquitous mechanism mediating the pathogenesis of a variety of LSDs, unveil an inherent connection between lysosomal defects and innate immunity, and suggest a uniform strategy for curing LSDs.