Glucoconjugated monoterpene indole alkaloids with xanthine oxidase inhibitory activity from Ophiorrhiza japonica.

Continued interest in the bioactive alkaloids led to the isolation of five undescribed alkaloids (1-5), ophiorglucidines A-E, and seven known analogues (6-12) from the water-soluble fraction of Ophiorrhiza japonica. The structures were elucidated based on spectroscopic data and quantum calculations as well as X-ray crystallographic analysis. The structure of 1 was characterized as a hexacyclic skeleton including a double bridge linking the indole and the monoterpene moieties, which is the first report of a single crystal with this type of structure. Moreover, the inhibitory effect of zwitterionic indole alkaloid glycosides on xanthine oxidase was found for the first time. The alkaloids 2 and 3, both of which have a pentacyclic zwitterionic system, were more active than the reference inhibitor, allopurinol (IC50 = 11.1 µM) with IC50 values of 1.0 µM, and 2.5 µM, respectively. Structure-activity relationships analyses confirmed that the carbonyl group at C-14 was a key functional group responsible for the inhibitory effects of these alkaloids.

A Case of Squamous Cell Carcinoma Arising in Disseminated Superficial Porokeratosis.

Porokeratosis (PK), characterized by keratotic lesions with an atrophic center and a prominent peripheral ridge, with a typical histological hallmark, namely, the cornoid lamella, has two forms: disseminated and localized. While PK often converts into squamous cell carcinoma (SCC), conversion from disseminated superficial porokeratosis (DSP) alone is rarely reported except for one case in which DSP and LP coexisted and converted to SCC. Here, we report the case of a patient with SCC converted from DSP alone, presenting with coin-sized macules on the bottom right of his waist that developed into an ulcer at the center. The patient underwent radiation therapy, which effectively treated the SCC but did not resolve the PK. This article highlights regular follow-up and undergo comprehensive diagnosis, both of which are beneficial to enable early detection and management of DSP that has converted to into SCC; in addition, standardized medical treatment may help improve the treatment therapeutic effect of in similar diseases.

Effect of Clopidogrel combined with aspirin in the treatment of acute progressive cerebral infarction: A retrospective single-center analysis.

Objective: To explore the effect of clopidogrel combined with aspirin in the treatment of acute progressive cerebral infarction (APCI). Methods: We retrospectively analyzed the records of 190 patients with APCI admitted to Chengdu First People's Hospital from September 2020 to April 2023. The records were divided into an aspirin group (76 cases), a clopidogrel group (72 cases), and a clopidogrel plus aspirin group (42 cases) according to the treatment records. We compared the efficacy of the three treatment outcomes by analyzing the National Institutes of Health Stroke Scale (NIHSS) scores, and the levels of serum inflammatory factors (IL-8, TNF-α, and IL-1ß), cone like protein-1 (VILIP-1), and caveolin-1 (Cav-1). Results: The total efficacy of the combination group (97.62%) was significantly higher than those of the aspirin group (73.68%) or the clopidogrel group (79.17%) (p<0.05). After treatment, the NIHSS scores, inflammatory factor levels, serum VILIP-1 and Cav-1 levels were significantly lower than those before treatment in the three groups, but all the levels were significantly lower in the combination group (all p<0.05). Conclusions: Our results indicate that compared with aspirin alone or clopidogrel alone, the combination of aspirin and clopidogrel is more effective for the treatment of APCI. The combination regimen effectively lowers serum inflammatory factors (IL-8, TNF-α, and IL-1ß), as well as the VILIP-1 and Cav-1 levels.

RAD18 O-GlcNAcylation promotes translesion DNA synthesis and homologous recombination repair.

RAD18, an important ubiquitin E3 ligase, plays a dual role in translesion DNA synthesis (TLS) and homologous recombination (HR) repair. However, whether and how the regulatory mechanism of O-linked N-acetylglucosamine (O-GlcNAc) modification governing RAD18 and its function during these processes remains unknown. Here, we report that human RAD18, can undergo O-GlcNAcylation at Ser130/Ser164/Thr468, which is important for optimal RAD18 accumulation at DNA damage sites. Mechanistically, abrogation of RAD18 O-GlcNAcylation limits CDC7-dependent RAD18 Ser434 phosphorylation, which in turn significantly reduces damage-induced PCNA monoubiquitination, impairs Polη focus formation and enhances UV sensitivity. Moreover, the ubiquitin and RAD51C binding ability of RAD18 at DNA double-strand breaks (DSBs) is O-GlcNAcylation-dependent. O-GlcNAcylated RAD18 promotes the binding of RAD51 to damaged DNA during HR and decreases CPT hypersensitivity. Our findings demonstrate a novel role of RAD18 O-GlcNAcylation in TLS and HR regulation, establishing a new rationale to improve chemotherapeutic treatment.

Integrated Network Pharmacology Analysis and Experimental Validation to Elucidate the Mechanism of Acteoside in Treating Diabetic Kidney Disease.

Background: Acteoside, an active ingredient found in various medicinal herbs, is effective in the treatment of diabetic kidney disease (DKD); however, the intrinsic pharmacological mechanism of action of acteoside in the treatment of DKD remains unclear. This study utilizes a combined approach of network pharmacology and experimental validation to investigate the potential molecular mechanism systematically. Methods: First, acteoside potential targets and DKD-associated targets were aggregated from public databases. Subsequently, utilizing protein-protein interaction (PPI) networks, alongside GO and KEGG pathway enrichment analyses, we established target-pathway networks to identify core potential therapeutic targets and pathways. Further, molecular docking facilitated the confirmation of interactions between acteoside and central targets. Finally, the conjectured molecular mechanisms of acteoside against DKD were verified through experimentation on unilateral nephrectomy combined with streptozotocin (STZ) rat model. The underlying downstream mechanisms were further investigated. Results: Network pharmacology identified 129 potential intersected targets of acteoside for DKD treatment, including targets such as AKT1, TNF, Casp3, MMP9, SRC, IGF1, EGFR, HRAS, CASP8, and MAPK8. Enrichment analyses indicated the PI3K-Akt, MAPK, Metabolic, and Relaxin signaling pathways could be involved in this therapeutic context. Molecular docking revealed high-affinity binding of acteoside to PIK3R1, AKT1, and NF-κB1. In vivo studies validated the therapeutic efficacy of acteoside, demonstrating reduced blood glucose levels, improved serum Scr and BUN levels, decreased 24-hour urinary total protein (P<0.05), alongside mitigated podocyte injury (P<0.05) and ameliorated renal pathological lesions. Furthermore, this finding indicates that acteoside inhibits the expression of pyroptosis markers NLRP3, Caspase-1, IL-1ß, and IL-18 through the modulation of the PI3K/AKT/NF-κB pathway. Conclusion: Acteoside demonstrates renoprotective effects in DKD by regulating the PI3K/AKT/NF-κB signaling pathway and alleviating pyroptosis. This study explores the pharmacological mechanism underlying acteoside's efficacy in DKD treatment, providing a foundation for further basic and clinical research.

Diagnosis of Canine Tumours and the Value of Combined Detection of VEGF, P53, SF and NLRP3 for the Early Diagnosis of Canine Mammary Carcinoma.

The average life of a dog is generally maintained at ten to fifteen years, and tumours are the predominant reason that leads to the death of dogs, especially canine mammary carcinoma. Therefore, early diagnosis of tumours is very important. In this study, tumor size, morphology, and texture could be seen through general clinical examination, tumor metastasis could be seen through imaging examination, inflammatory reactions could be seen through hematological examination, and abnormal cell morphology could be seen through cytological and histopathological examination. In the 269 malignant cases and 179 benign cases, we randomly selected 30 cases each, and an additional 30 healthy dogs were selected for the experiment (healthy dogs: dogs in good physical condition without any tumor or other diseases). We used RT-qPCR and ELISA to determine the relative expression of vascular endothelial growth factor (VEGF), tumor protein P53 (P53), serum ferritin (SF), and NOD-like receptor protein 3 (NLRP3) in 30 healthy dogs, 30 dogs with benign mammary tumours, and 30 dogs with malignant mammary tumours. In the results, the same expression trend was obtained both in serum and tissues, and the expression of the four markers was the highest in malignant mammary tumours, with highly significant differences compared with the benign and healthy/paracancerous groups. By plotting the ROC curves, it was found that the results of combined tests were better than a single test and the combination of the four markers was the best for the early diagnosis. In conclusion, this can assist the clinical early diagnosis to a certain extent, and also provides some references and assistance for the development of tumor detection kits in clinical practice.

Impact of National Immunization Strategies on Vaccine-Preventable Diseases - China, 1950-2021.

What is already known about this topic?: The incidences of vaccine-preventable diseases (VPDs) included in the Expanded Program on Immunization in China have decreased significantly in recent decades. What is added by this report?: This study summarizes the national incidences of nine VPDs and the seroprevalence of hepatitis B surface antigen (HBsAg) under different immunization strategies from 1950 through 2021 in China. The sharpest decreases in VPD incidence and under-5-year HBsAg seroprevalence occurred during the latest stage of the National Immunization Program. The decreases in VPD incidence were most prominent among children under five years of age. What are the implications for public health practice?: These findings provide valuable insights for vaccine value assessment and emphasize the importance of implementing immunization strategies in targeted populations.

Synthesis of Cycloaliphatic Polyamides via Palladium-Catalyzed Hydroaminocarbonylative Polymerization.

Polyamides represent one class of materials that is important in modern society. Because of the numerous potential applications of polyamides in various fields, there is a high demand for new polyamide structures, which necessitates the development of new polymerization methods. Herein, we report a novel and efficient palladium-catalyzed hydroaminocarbonylative polymerization of dienes and diamines for the synthesis of cycloaliphatic polyamides. The method employs readily available starting materials, proceeds in an atom-economic manner, and creates a series of new functional polyamides in high yields and high molecular weights. In contrast with the traditional polyamides based on adipic acid, the cycloaliphatic polyamides have superior thermal resistance, higher glass-transition temperature, and better solubility in common organic solvents, thus probably featuring the merits of high-performance and good processability.

Complement C3aR signaling: Immune and metabolic modulation and its impact on Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia among the elderly population. Despite its widespread prevalence, our comprehension of the intricate mechanisms governing the pathogenesis of the disease remains incomplete, posing a challenge for the development of efficient therapies. Pathologically characterized by the presence of amyloid ß plaques and neurofibrillary tau tangles, AD is also accompanied by the hyperactivation of glial cells and the immune system. The complement cascade, the evolutionarily conserved innate immune pathway, has emerged as a significant contributor to AD. This review focuses on one of the complement components, the C3a receptor (C3aR), covering its structure, ligand-receptor interaction, intracellular signaling and its functional consequences. Drawing insights from cellular and AD mouse model studies, we present the multifaceted role of complement C3aR signaling in AD and attempt to convey to the readers that C3aR acts as a crucial immune and metabolic modulator to influence AD pathogenesis. Building on this framework, the objective of this review is to inform future research endeavors and facilitate the development of therapeutic strategies for this challenging condition.

Association between chronic pain and dementia: a systematic review and meta-analysis.

PURPOSE: Dementia and chronic pain (CP) are prevalent among older adults. However, no study has systematically reviewed the association between dementia and CP. Therefore, we performed this study to gather evidence about the potential relationship between the two. METHODS: Two authors independently searched PubMed, Embase, and Web of Science to identify all records published up to 1 September 2022 that explored the association between CP and dementia. The methodological quality of the studies was assessed using the Newcastle Ottawa Scale (NOS). A fixed or random-effects model was used to pool the risk estimates. RESULTS: Among the initial 3296 articles retrieved, 19 were included in the review (1 cross-sectional, and 18 cohort). The pooled result showed the risk of dementia was 1.42 times higher in CP patients (HR = 1.42, 95% CI 1.23-1.64, P < 0.001). dementia and CP subtypes, gender, and age did not significantly affect the results. CONCLUSION: Our study shows that people who suffered from CP are at an increased risk of developing dementia, regardless of gender, age, and dementia and CP subtypes.

Impaired synaptic plasticity and decreased glutamatergic neuron excitability induced by SIRT1/BDNF downregulation in the hippocampal CA1 region are involved in postoperative cognitive dysfunction.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication after anesthesia/surgery, especially among elderly patients, and poses a significant threat to their postoperative quality of life and overall well-being. While it is widely accepted that elderly patients may experience POCD following anesthesia/surgery, the exact mechanism behind this phenomenon remains unclear. Several studies have indicated that the interaction between silent mating type information regulation 2 homologue 1 (SIRT1) and brain-derived neurotrophic factor (BDNF) is crucial in controlling cognitive function and is strongly linked to neurodegenerative disorders. Hence, this research aims to explore how SIRT1/BDNF impacts cognitive decline caused by anesthesia/surgery in aged mice. METHODS: Open field test (OFT) was used to determine whether anesthesia/surgery affected the motor ability of mice, while the postoperative cognitive function of 18 months old mice was evaluated with Novel object recognition test (NORT), Object location test (OLT) and Fear condition test (FC). The expressions of SIRT1 and other molecules were analyzed by western blot and immunofluorescence staining. The hippocampal synaptic plasticity was detected by Golgi staining and Long-term potentiation (LTP). The effects of SIRT1 and BDNF overexpression as well as chemogenetic activation of glutamatergic neurons in hippocampal CA1 region of 18 months old vesicular glutamate transporter 1 (VGLUT1) mice on POCD were further investigated. RESULTS: The research results revealed that older mice exhibited cognitive impairment following intramedullary fixation of tibial fracture. Additionally, a notable decrease in the expression of SIRT1/BDNF and neuronal excitability in hippocampal CA1 glutamatergic neurons was observed. By increasing levels of SIRT1/BDNF or enhancing glutamatergic neuron excitability in the CA1 region, it was possible to effectively mitigate synaptic plasticity impairment and ameliorate postoperative cognitive dysfunction. CONCLUSIONS: The decline in SIRT1/BDNF levels leading to changes in synaptic plasticity and neuronal excitability in older mice could be a significant factor contributing to cognitive impairment after anesthesia/surgery.

Efficient photocatalytic nitrogen fixation via oxygen vacancies in Zr-MOFs at ambient conditions.

Photocatalytic nitrogen fixation is seen to be a potential technology for nitrogen reduction due to its eco-friendliness, low energy consumption, and environmental protection. In this study, photocatalysts with abundant oxygen vacancies (Zr-naphthalene dicarboxylic acid (Zr-NDC) and Zr-phthalic acid (Zr-BDC)) were designed using 1,4-naphthalene dicarboxylic acid (H2NDC) and 1,4-phthalic acid (H2BDC) as ligands. Since the structure of H2NDC includes one extra benzene ring than H2BDC, the charge density differential of the organic ligand is probably altered. The hypothesis is proved by density function theory (DFT) calculation. The abundant oxygen vacancies of the catalyst offer numerous active sites for nitrogen fixation. Concurrently, the process of ligand-metal charge transfer facilitates photo-electron transfer, creating an active center for nitrogen reduction. Additionally, the functionalization of ligand amplifies another pathway for charge transfer, broadening the light absorption range of Metal-organic framework (MOF) and increasing its capacity for nitrogen reduction. In contrast to H2BDC, the benzene ring added in H2NDC structure acts as an electron energy storage tank with a stronger electron density difference favorable for photogenerated electron-hole separation resulting in higher photocatalytic activity in Zr-NDC. The experimental results show that the nitrogen fixation efficiency of Zr-NDC is 163.7 µmol g-1h-1, which is significantly better than that of Zr-BDC (29.3 µmol g-1h-1). This work utilizes cost-effective and non-toxic ingredients to design highly efficient photocatalysts, thereby significantly contributing to the practical implementation of green chemistry principles.

Multi-omics delineate growth factor network underlying exercise effects in an Alzheimer's mouse model.

Physical exercise represents a primary defense against age-related cognitive decline and neurodegenerative disorders like Alzheimer's disease (AD). To impartially investigate the underlying mechanisms, we conducted single-nucleus transcriptomic and chromatin accessibility analyses (snRNA-seq and ATAC-seq) on the hippocampus of mice carrying AD-linked NL-G-F mutations in the amyloid precursor protein gene (APPNL-G-F) following prolonged voluntary wheel-running exercise. Our study reveals that exercise mitigates amyloid-induced changes in both transcriptomic expression and chromatin accessibility through cell type-specific transcriptional regulatory networks. These networks converge on the activation of growth factor signaling pathways, particularly the epidermal growth factor receptor (EGFR) and insulin signaling, correlating with an increased proportion of immature dentate granule cells and oligodendrocytes. Notably, the beneficial effects of exercise on neurocognitive functions can be blocked by pharmacological inhibition of EGFR and the downstream phosphoinositide 3-kinases (PI3K). Furthermore, exercise leads to elevated levels of heparin-binding EGF (HB-EGF) in the blood, and intranasal administration of HB-EGF enhances memory function in sedentary APPNL-G-F mice. These findings offer a panoramic delineation of cell type-specific hippocampal transcriptional networks activated by exercise and suggest EGF-related growth factor signaling as a druggable contributor to exercise-induced memory enhancement, thereby suggesting therapeutic avenues for combatting AD-related cognitive decline.

Valine induces inflammation and enhanced adipogenesis in lean mice by multi-omics analysis.

Introduction: The branched-chain amino acids (BCAAs) are essential to mammalian growth and development but aberrantly elevated in obesity and diabetes. Each BCAA has an independent and specific physio-biochemical effect on the host. However, the exact molecular mechanism of the detrimental effect of valine on metabolic health remains largely unknown. Methods and results: This study showed that for lean mice treated with valine, the hepatic lipid metabolism and adipogenesis were enhanced, and the villus height and crypt depth of the ileum were significantly increased. Transcriptome profiling on white and brown adipose tissues revealed that valine disturbed multiple signaling pathways (e.g., inflammation and fatty acid metabolism). Integrative cecal metagenome and metabolome analyses found that abundances of Bacteroidetes decreased, but Proteobacteria and Helicobacter increased, respectively; and 87 differential metabolites were enriched in several molecular pathways (e.g., inflammation and lipid and bile acid metabolism). Furthermore, abundances of two metabolites (stercobilin and 3-IAA), proteins (AMPK/pAMPK and SCD1), and inflammation and adipogenesis-related genes were validated. Discussion: Valine treatment affects the intestinal microbiota and metabolite compositions, induces gut inflammation, and aggravates hepatic lipid deposition and adipogenesis. Our findings provide novel insights into and resources for further exploring the molecular mechanism and biological function of valine on lipid metabolism.

Clinical Observation and Cause Analysis of Perioperative Superior Cluneal Neuralgia in Vertebral Augmentation.

BACKGROUND: In our clinical practice, we observed that some osteoporotic vertebral compression fracture patients undergoing vertebral augmentation exhibited pain in the iliac crest region. This pain aligned with the diagnostic criteria for superior cluneal neuralgia (SCN) and affected treatment satisfaction. OBJECTIVE: This study aims to clinically observe patients undergoing vertebral augmentation in a hospital setting and analyze the etiology and risk factors associated with SCN. STUDY DESIGN: Retrospective cohort study. SETTING: Inpatient population of a single center. METHODS: We retrospectively analyzed clinical data from 630 patients who underwent vertebral augmentation in our hospital from March 2022 to March 2023. Fifty-two patients enrolled in the study experienced pain that met the diagnostic criteria for superior cluneal neuralgia during the perioperative period of the vertebral augmentation procedures. Those patients were divided into 2 subgroups according to the conditions involved in the occurrence of SCN: Group A (26 patients) had either no preoperative SCN but developed it postoperatively, or had preoperative SCN that worsened or did not alleviate postoperatively. Group B (26 patients) had preoperative SCN that was relieved postoperatively. Additionally, 52 consecutive patients in March 2022 to March 2023. who did not experience SCN during the perioperative period were selected as the control group (Group C). Variables such as surgical segment, age, height, weight, body mass index, duration of hospitalization, chronic low back pain (CLBP), duration of pain, anesthesia, surgical approach, fracture pattern, preoperative visual analog scale (pre-op VAS) score, intraoperative VAS score, one-day VAS score, one-month VAS score, lumbar sacral angle, and sacral tilt angle were statistically described and analyzed. RESULTS: In our hospital, the incidence of SCN during the perioperative period of vertebral augmentation procedures is 8.25% (52/630). Among all the segments of patients who developed SCN during the perioperative period, the L1 segment had the highest proportion, which was 29.03% and 35.14% in Groups A and B, respectively. Group B and Group C showed significant differences in duration of hospitalization (P = 0.012), pre-op VAS scores (P = 0.026), and CLBP (P < 0.001). Group A had significantly higher VAS scores preoperatively (P = 0.026) and intraoperatively (P = 0.004) and in CLBP (P = 0.001) than did Group C. LIMITATIONS: This is a retrospective study. Single-center noncontrolled studies may introduce selection bias. The small sample size in each group might have also led to bias. CONCLUSION: Perioperative SCN associated with vertebral augmentation is significantly correlated with preoperative VAS scores and CLBP. In addition, intraoperative VAS scores might be a factor contributing to the nonalleviation or exacerbation of postoperative SCN.

A domain knowledge-based interpretable deep learning system for improving clinical breast ultrasound diagnosis.

BACKGROUND: Though deep learning has consistently demonstrated advantages in the automatic interpretation of breast ultrasound images, its black-box nature hinders potential interactions with radiologists, posing obstacles for clinical deployment. METHODS: We proposed a domain knowledge-based interpretable deep learning system for improving breast cancer risk prediction via paired multimodal ultrasound images. The deep learning system was developed on 4320 multimodal breast ultrasound images of 1440 biopsy-confirmed lesions from 1348 prospectively enrolled patients across two hospitals between August 2019 and December 2022. The lesions were allocated to 70% training cohort, 10% validation cohort, and 20% test cohort based on case recruitment date. RESULTS: Here, we show that the interpretable deep learning system can predict breast cancer risk as accurately as experienced radiologists, with an area under the receiver operating characteristic curve of 0.902 (95% confidence interval = 0.882 - 0.921), sensitivity of 75.2%, and specificity of 91.8% on the test cohort. With the aid of the deep learning system, particularly its inherent explainable features, junior radiologists tend to achieve better clinical outcomes, while senior radiologists experience increased confidence levels. Multimodal ultrasound images augmented with domain knowledge-based reasoning cues enable an effective human-machine collaboration at a high level of prediction performance. CONCLUSIONS: Such a clinically applicable deep learning system may be incorporated into future breast cancer screening and support assisted or second-read workflows.

Breast cancer is one of the most common cancers, and finding it early can greatly improve patients' chances of survival and recovery. We create a tool based on artificial intelligence (AI)­whereby computer software learns to perform tasks that normally require human thinking­called MUP-Net. MUP-Net can analyze medical images to predict a patient's risk of having breast cancer. To make this AI tool usable in clinical practice, we enabled doctors to see the reasoning behind the AI's predictions by visualizing the key image features it analyzed. We showed that our AI tool not only makes doctors more confident in their diagnosis but also helps them make better decisions, especially for less experienced doctors. With further testing, our AI tool may help clinicians to diagnose breast cancer more accurately and quickly, potentially improving patient outcomes.

Lipid metabolism disorder in diabetic kidney disease.

Diabetic kidney disease (DKD), a significant complication associated with diabetes mellitus, presents limited treatment options. The progression of DKD is marked by substantial lipid disturbances, including alterations in triglycerides, cholesterol, sphingolipids, phospholipids, lipid droplets, and bile acids (BAs). Altered lipid metabolism serves as a crucial pathogenic mechanism in DKD, potentially intertwined with cellular ferroptosis, lipophagy, lipid metabolism reprogramming, and immune modulation of gut microbiota (thus impacting the liver-kidney axis). The elucidation of these mechanisms opens new potential therapeutic pathways for DKD management. This research explores the link between lipid metabolism disruptions and DKD onset.

Stereochemical insights into enantioselective antiplasmodial lignanamides from the twigs and leaves of Solanum erianthum.

Stereochemical investigations on the twigs and leaves of Solanum erianthum afforded five pairs of lignanamide enantiomers and a previously undescribed phenolic amide (3). Particularly, two pairs of previously undescribed lignanamide racemates (1a/1b-2a/2b) represent the first case of natural products that feature an unreported 5/5-fused N/O-biheterocyclic core. Their structures, including the absolute configurations, were determined unambiguously by using spectroscopic analyses and electronic circular dichroism calculations. A speculative biogenetic pathway for 1-3 was proposed. Interestingly, these lignanamides exhibited enantioselective antiplasmodial activities against drug-sensitive Plasmodium falciparum 3D7 strain and chloroquine-resistant Plasmodium falciparum Dd2 strain, pointing out that chirality plays an important role in drug development.

Association between the frontoparietal network, clinical symptoms and treatment response in individuals with untreated anorexia nervosa.

Background: Anorexia nervosa (AN) has been characterised as a psychiatric disorder associated with increased control. Currently, it remains difficult to predict treatment response in patients with AN. Their cognitive abilities are known to be resistant to treatment. It has been established that the frontoparietal control network (FPCN) is the direct counterpart of the executive control network. Therefore, the resting-state brain activity of the FPCN may serve as a biomarker to predict treatment response in AN. Aims: The study aimed to investigate the association between resting-state functional connectivity (RSFC) of the FPCN, clinical symptoms and treatment response in patients with AN. Methods: In this case-control study, 79 female patients with AN and no prior treatment from the Shanghai Mental Health Center and 40 matched healthy controls (HCs) were recruited from January 2015 to March 2022. All participants completed the Questionnaire Version of the Eating Disorder Examination (version 6.0) to assess the severity of their eating disorder symptoms. Additionally, RSFC data were obtained from all participants at baseline by functional magnetic resonance imaging. Patients with AN underwent routine outpatient treatment at the 4th and 12th week, during which time their clinical symptoms were evaluated using the same measures as at baseline. Results: Among the 79 patients, 40 completed the 4-week follow-up and 35 completed the 12-week follow-up. The RSFC from the right posterior parietal cortex (PPC) and dorsolateral prefrontal cortex (dlPFC) increased in 79 patients with AN vs 40 HCs after controlling for depression and anxiety symptoms. By multiple linear regression, the RSFC of the PPC to the inferior frontal gyrus was found to be a significant factor for self-reported eating disorder symptoms at baseline and the treatment response to cognitive preoccupations about eating and body image, after controlling for age, age of onset and body mass index. The RSFC in the dlPFC to the middle temporal gyrus and the superior frontal gyrus may be significant factors in the treatment response to binge eating and loss of control/overeating in patients with AN. Conclusions: Alterations in RSFC in the FPCN appear to affect self-reported eating disorder symptoms and treatment response in patients with AN. Our findings offer new insight into the pathogenesis of AN and could promote early prevention and treatment.

Exercise activates interferon response of the liver via Gpld1 to enhance antiviral innate immunity.

Healthy behavioral patterns could modulate organ functions to enhance the body's immunity. However, how exercise regulates antiviral innate immunity remains elusive. Here, we found that exercise promotes type I interferon (IFN-I) production in the liver and enhances IFN-I immune activity of the body. Despite the possibility that many exercise-induced factors could affect IFN-I production, we identified Gpld1 as a crucial molecule, and the liver as the major organ to promote IFN-I production after exercise. Exercise largely loses the efficiency to induce IFN-I in Gpld1-/- mice. Further studies demonstrated that exercise-produced 3-hydroxybutanoic acid (3-HB) critically induces Gpld1 expression in the liver. Gpld1 blocks the PP2A-IRF3 interaction, thus enhancing IRF3 activation and IFN-I production, and eventually improving the body's antiviral ability. This study reveals that exercise improves antiviral innate immunity by linking the liver metabolism to systemic IFN-I activity and uncovers an unknown function of liver cells in innate immunity.