Fractional amplitude of low-frequency fluctuations in sensory-motor networks and limbic system as a potential predictor of treatment response in patients with schizophrenia.

BACKGROUND: Previous investigations have revealed substantial differences in neuroimaging characteristics between healthy controls (HCs) and individuals diagnosed with schizophrenia (SCZ). However, we are not entirely sure how brain activity links to symptoms in schizophrenia, and there is a need for reliable brain imaging markers for treatment prediction. METHODS: In this longitudinal study, we examined 56 individuals diagnosed with 56 SCZ and 51 HCs. The SCZ patients underwent a three-month course of antipsychotic treatment. We employed resting-state functional magnetic resonance imaging (fMRI) along with fractional Amplitude of Low Frequency Fluctuations (fALFF) and support vector regression (SVR) methods for data acquisition and subsequent analysis. RESULTS: In this study, we initially noted lower fALFF values in the right postcentral/precentral gyrus and left postcentral gyrus, coupled with higher fALFF values in the left hippocampus and right putamen in SCZ patients compared to the HCs at baseline. However, when comparing fALFF values in brain regions with abnormal baseline fALFF values for SCZ patients who completed the follow-up, no significant differences in fALFF values were observed after 3 months of treatment compared to baseline data. The fALFF values in the right postcentral/precentral gyrus and left postcentral gyrus, and the left postcentral gyrus were useful in predicting treatment effects. CONCLUSION: Our findings suggest that reduced fALFF values in the sensory-motor networks and increased fALFF values in the limbic system may constitute distinctive neurobiological features in SCZ patients. These findings may serve as potential neuroimaging markers for the prognosis of SCZ patients.

A Zn2+ cross-linked sodium alginate/epigallocatechin gallate hydrogel scaffold for promoting skull repair.

The optimal material for repairing skull defects should exhibit outstanding biocompatibility and mechanical properties. Specifically, hydrogel scaffolds that emulate the microenvironment of the native bone extracellular matrix play a vital role in promoting osteoblast adhesion, proliferation, and differentiation, thereby yielding superior outcomes in skull reconstruction. In this study, a composite network hydrogel comprising sodium alginate (SA), epigallocatechin gallate (EGCG), and zinc ions (Zn2+) was developed to establish an ideal osteogenic microenvironment for bone regeneration. Initially, physical entanglement and hydrogen bonding between SA and EGCG resulted in the formation of a primary network hydrogel known as SA-EGCG. Subsequently, the inclusion of Zn2+ facilitated the creation of a composite network hydrogels named SA-EGCG-Zn2+ via dynamic coordination bonds with SA and EGCG. The engineered SA-EGCG2 %-Zn2+ hydrogels offered an environment mimicking the native extracellular matrix (ECM). Moreover, the sustained release of Zn2+ from the hydrogel effectively enhanced cell adhesion, promoted proliferation, and stimulated osteoblast differentiation. In vitro experiments have shown that SA-EGCG2 %-Zn2+ hydrogels greatly enhance the attachment and growth of osteoblast precursor cells (MC3T3-E1), while also increasing the expression of genes related to osteogenesis in these cells. Additionally, in vivo studies have confirmed that SA-EGCG2 %-Zn2+ hydrogels promote new bone formation and accelerate the regeneration of bone in situ, indicating promising applications in the realm of bone tissue engineering.

Physical exercise frequency and cognition: a multicenter cross-sectional cohort study.

Background and aims: Dementia imposes a heavy burden on society and families, therefore, effective drug treatments, exploring and preventing factors associated with dementia, are paramount. To provide reference points for the best frequency of physical exercise (physical exercise), we investigated the association between frequency of PE and cognition in Chinese old adults. Methods: 16,181 Chinese participants aged 65 years or older were included in this study. Associations between PE and cognition were estimated multivariate logistic and linear regression analyses. Associations were further investigated across dementia subtypes (Alzheimer dementia, vascular dementia, and other types of dementia). Subgroup analyses were performed in different age groups, in populations with and without stroke, and those with and without hypertension. Results: PE associated with dementia after adjusting for full covariates (OR: 0.5414, 95% CI: 0.4536-0.6491, p < 0.001). Exercise performed at ≥3 times/week associated with lower risk of dementia (OR: 0.4794-0.6619, all p value <0.001). PE was associated with improved cognition (ß: 12851, p < 0.001), and any PE frequency contributed to cognitive improvement (p values for exercise performed ≥1 time/week were <0.001). Similar conclusions were identified when we repeated analyses in different dementia subtypes and age groups. Subgroup analyses suggested that the cognition of individuals without hypertension also benefitted from exercising 1-2 times/week (OR: 0.6168, 95% CI: 0.4379-0.8668, p = 0.005). Conclusion: The best exercise frequency is exercising ≥3 times/week for individuals from different dementia subtypes and age groups. While for those without hypertension, PE at 1-2 times /week is also beneficial.

Pharmacological approaches for targeting lysosomes to induce ferroptotic cell death in cancer.

Lysosomes are crucial organelles responsible for the degradation of cytosolic materials and bulky organelles, thereby facilitating nutrient recycling and cell survival. However, lysosome also acts as an executioner of cell death, including ferroptosis, a distinctive form of regulated cell death that hinges on iron-dependent phospholipid peroxidation. The initiation of ferroptosis necessitates three key components: substrates (membrane phospholipids enriched with polyunsaturated fatty acids), triggers (redox-active irons), and compromised defence mechanisms (GPX4-dependent and -independent antioxidant systems). Notably, iron assumes a pivotal role in ferroptotic cell death, particularly in the context of cancer, where iron and oncogenic signaling pathways reciprocally reinforce each other. Given the lysosomes' central role in iron metabolism, various strategies have been devised to harness lysosome-mediated iron metabolism to induce ferroptosis. These include the re-mobilization of iron from intracellular storage sites such as ferritin complex and mitochondria through ferritinophagy and mitophagy, respectively. Additionally, transcriptional regulation of lysosomal and autophagy genes by TFEB enhances lysosomal function. Moreover, the induction of lysosomal iron overload can lead to lysosomal membrane permeabilization and subsequent cell death. Extensive screening and individually studies have explored pharmacological interventions using clinically available drugs and phytochemical agents. Furthermore, a drug delivery system involving ferritin-coated nanoparticles has been specifically tailored to target cancer cells overexpressing TFRC. With the rapid advancements in understandings the mechanistic underpinnings of ferroptosis and iron metabolism, it is increasingly evident that lysosomes represent a promising target for inducing ferroptosis and combating cancer.

Investigator-blinded, controlled, and randomized comparative study on 1565 nm non-ablative fractional laser versus 5% minoxidil for treatment of androgenetic alopecia.

BACKGROUND: Characterized by progressive hair loss due to an excessive response to androgens, androgenetic alopecia (AGA) affects up to 50% of males and females. Minoxidil is one of approved medications for AGA but inadequate responses occur in many patients. AIMS: To determine whether 1565 nm non-ablative fractional laser (NAFL) could yield better therapeutic benefits for patients with AGA as compared with 5% minoxidil. METHODS: Thirty patients with AGA were enrolled; they were randomly assigned into the laser or minoxidil treatment groups. For the laser treatment group, patients were treated by 1565 nm NAFL at 10 mJ, 250 spots/cm2 with 2 weeks intervals for 4 sessions in total. For the minoxidil treatment group, 1-milliliter of topical 5% minoxidil solution was applied to hair loss area twice a day. RESULTS: The primary outcomes were the changes in numerous hair growth indexes at the Week 10 as compared with the baselines. Both 1565 nm NAFL and 5% minoxidil led to significantly greater hair densities and diameters in patients at the Week 10 than the baselines (p < 0.01). As compared with 5% minoxidil, 1565 nm NAFL showed significantly greater improvements in total hair number, total hair density (hair/cm2), terminal hair number, terminal hair density (hair/cm2), number of hair follicle units, and average hair number/number of hair follicle units. CONCLUSIONS: Our data demonstrate that 1565 nm NAFL exhibits superior clinical efficacy in some aspects of hair growth to the topical minoxidil. It is a safe and effective modality in treating AGA.

Decreased expression of hsa_circ_0112879 in oral squamous cell carcinoma and its clinicopathological implications.

Background: To identify differently expressed circular RNA (circRNA) in oral squamous cell carcinoma (OSCC) and adjacent normal tissue, construct a hsa_circ_0112879-related microRNAs (miRNAs) prognostic model, and discuss the circRNA as a biomarker for early diagnosis of OSCC. Methods: The expression of hsa_circ_0112879 in OSCC cell lines and tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR). A receiver operating characteristic (ROC) curve was plotted to estimate its clinical significance. The potential miRNA and messenger RNA (mRNA) binding to hsa_circ_009755 were predicted by R software edgeR package. Based on the median value of the risk score in the all-sample cohort, all the included patients with OSCC were divided into either high- or low-risk groups, and Kaplan-Meier analysis was performed. The ROC curve was used to verify the accuracy of the risk signature in predicting the prognosis of OSCC. By univariable Cox, least absolute shrinkage and selection operator (LASSO), and multivariable Cox analyses, we constructed a hsa_circ_0112879-related miRNAs risk model to forecast the prognosis of OSCC. Results: The expression of hsa_circ_0112879 was significantly downregulated in the OSCC tissues and cell lines. The expression level was statistically correlated with the pathological differentiation of OSCC tumors (P=0.0285). Furthermore, 141 differentially expressed hsa_circ_0112879-related miRNAs were obtained [|log2FC| >1, false discovery rate (FDR) <0.05], of which 70 miRNAs were up-regulated in OSCC tissues, whereas 71 miRNAs were down-regulated in OSCC tissues. The area under the ROC curve (AUC) at 1-, 3-, and 5-year in the all-sample cohort was 0.591, 0.689, and 0.618, respectively. The toll-like receptor signaling pathway, Janus tyrosine kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway, nucleotide-binding and oligomerization domain (NOD)-like receptor signaling pathway, and T-cell receptor (TCR) signaling pathway were mainly enriched in the high-risk group. Conclusions: The model and nomogram constructed herein has the ability to discriminate the prognosis of OSCC patients. Hsa_circ_0112879 may serve as a novel biomarker in the diagnosis and prognosis of OSCC.

Clinical value of Cyclin D1 and P21 in the differential diagnosis of papillary thyroid carcinoma.

BACKGROUND: With the continuous discovery of new borderline thyroid lesions and benign and malignant "gray areas", coupled with the limitations of traditional immune indicators, the differential diagnosis of papillary thyroid carcinoma (PTC) has become more difficult. Cyclin D1 and P21 are cell cycle regulators involved in the occurrence and metastasis of multiple tumors, including PTC, but their specific functions are unclear. METHODS: In our study, immunohistochemical staining was used to explore the expression of Cyclin D1 and P21 in PTC, paracancerous tissue, follicular adenoma (FA) and papillary thyroid hyperplasia. In addition, their relationship with the clinicopathological features of PTC and their differential diagnostic value in distinguishing between intralymph node PTC metastases and intralymph node ectopic thyroid tissue were studied. RESULTS: Among 200 primary PTC lesions, Cyclin D1 and P21 were found to be expressed in 186 (93.00%) and 177 (88.50%), respectively, and their expression levels were significantly higher in PTC tissue than in adjacent tissue, FA tissue and papillary thyroid hyperplasia tissue (P < 0.05). The expression levels of Cyclin D1 and P21 were positively correlated with tumor size and lymph node metastasis (P < 0.05) but not with sex, age, number of tumor lesions, histological subtype, chronic lymphocytic thyroiditis or TNM stage (P < 0.05). The expression levels of Cyclin D1 and P21 were significantly correlated (P < 0.05). The positivity rates of Cyclin D1 and P21 in intralymph node PTC metastases were 97.96% (48/49) and 89.80% (44/49), respectively, which were significantly higher than those in intralymph node ectopic thyroid tissue (P < 0.05). The sensitivity (Se) and negative predictive value (NPV) of Cyclin D1 and P21 detection alone or in combination were higher than those of the combined detection of the classical antibody markers CK19, HBME-1 and Galectin-3. Besides, the Se, Sp, PPV and NPV of Cyclin D1 and P21 in differentiating intralymph node PTC metastases and intralymph node ectopic thyroid tissue were higher. CONCLUSIONS: The results of our study show that Cyclin D1 and P21 are highly sensitive and specific markers for the diagnosis of PTC that are superior to traditional classical antibodies. And, these two markers are of great value in the differential diagnosis of intralymph node PTC metastases and intralymph node ectopic thyroid tissue.

Deviant spontaneous neural activity as a potential early-response predictor for therapeutic interventions in patients with schizophrenia.

Objective: Previous studies have established significant differences in the neuroimaging characteristics between healthy controls (HCs) and patients with schizophrenia (SCZ). However, the relationship between homotopic connectivity and clinical features in patients with SCZ is not yet fully understood. Furthermore, there are currently no established neuroimaging biomarkers available for the diagnosis of SCZ or for predicting early treatment response. The aim of this study is to investigate the association between regional homogeneity and specific clinical features in SCZ patients. Methods: We conducted a longitudinal investigation involving 56 patients with SCZ and 51 HCs. The SCZ patients underwent a 3-month antipsychotic treatment. Resting-state functional magnetic resonance imaging (fMRI), regional homogeneity (ReHo), support vector machine (SVM), and support vector regression (SVR) were used for data acquisition and analysis. Results: In comparison to HCs, individuals with SCZ demonstrated reduced ReHo values in the right postcentral/precentral gyrus, left postcentral/inferior parietal gyrus, left middle/inferior occipital gyrus, and right middle temporal/inferior occipital gyrus, and increased ReHo values in the right putamen. It is noteworthy that there was decreased ReHo values in the right inferior parietal gyrus after treatment compared to baseline data. Conclusion: The observed decrease in ReHo values in the sensorimotor network and increase in ReHo values in the right putamen may represent distinctive neurobiological characteristics of patients with SCZ, as well as a potential neuroimaging biomarker for distinguishing between patients with SCZ and HCs. Furthermore, ReHo values in the sensorimotor network and right putamen may serve as predictive indicators for early treatment response in patients with SCZ.

Andrographolide causes p53-independent HCC cell death through p62 accumulation and impaired DNA damage repair.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly lethal cancer characterized by dominant driver mutations, including p53. Consequently, there is an urgent need to search for novel therapeutic agents to treat HCC. Andrographolide (Andro), a clinically available anti-inflammatory phytochemical agent, has shown inhibitory effects against various types of cancer, including HCC. However, the underlying molecular mechanisms of its action remain poorly understood. PURPOSE: This study aims to investigate the molecular mechanisms by which p53 and p62 collectively affect Andro-induced HCC cell death, using both in vitro and in vivo models. METHODS: In vitro cellular experiments were conducted to examine the effects of Andro on cell viability and elucidate its mechanisms of action. In vivo xenograft experiments further validated the anti-cancer effects of Andro. RESULTS: Andro induced dose- and time-dependent HCC cell death while sparing normal HL-7702 hepatocytes. Furthermore, Andro caused DNA damage through the generation of reactive oxygen species (ROS), a critical event leading to cell death. Notably, HCC cells expressing p53 exhibited greater resistance to Andro-induced cell death compared to p53-deficient cells, likely due to the ability of p53 to induce G2/M cell cycle arrest. Additionally, Andro-induced p62 aggregation led to the proteasomal degradation of RAD51 and 53BP1, two key proteins involved in DNA damage repair. Consequently, silencing or knocking out p62 facilitated DNA damage repair and protected HCC cells. Importantly, disruption of either p53 or p62 did not affect the expression of the other protein. These findings were further supported by the observation that xenograft tumors formed by p62-knockout HCC cells displayed increased resistance to Andro treatment. CONCLUSION: This study elucidates the mechanistic basis of Andro-induced HCC cell death. It provides valuable insights for repurposing Andro for the treatment of HCC, regardless of the presence of functional p53.

Automatic depression diagnosis through hybrid EEG and near-infrared spectroscopy features using support vector machine.

Depression is a common mental disorder that seriously affects patients' social function and daily life. Its accurate diagnosis remains a big challenge in depression treatment. In this study, we used electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) and measured the whole brain EEG signals and forehead hemodynamic signals from 25 depression patients and 30 healthy subjects during the resting state. On one hand, we explored the EEG brain functional network properties, and found that the clustering coefficient and local efficiency of the delta and theta bands in patients were significantly higher than those in normal subjects. On the other hand, we extracted brain network properties, asymmetry, and brain oxygen entropy as alternative features, used a data-driven automated method to select features, and established a support vector machine model for automatic depression classification. The results showed the classification accuracy was 81.8% when using EEG features alone and increased to 92.7% when using hybrid EEG and fNIRS features. The brain network local efficiency in the delta band, hemispheric asymmetry in the theta band and brain oxygen sample entropy features differed significantly between the two groups (p < 0.05) and showed high depression distinguishing ability indicating that they may be effective biological markers for identifying depression. EEG, fNIRS and machine learning constitute an effective method for classifying depression at the individual level.

Arthritis of the hip caused by arteriovenous malformations: A case report.

BACKGROUND Arthritis of the hip caused by arteriovenous malformations (AVMs) has been rarely reported. Therefore, total hip replacement (THR) in patients with AVM-induced arthritis of the hip is challenging. CASE SUMMARY We report a 44-year-old woman with aggravated right hip pain during the past decade. The patient presented with severe pain and a functional disorder of the right hip. X-ray examination revealed severely narrowed right hip joint space and abnormal trabecular bone loss in the femoral neck and trochanter area. Doppler ultrasound, magnetic resonance imaging and computed tomography angiography revealed AVMs surrounding the right hip, along with erosion. To ensure the safety of THR, we performed vascular embolization and temporary balloon occlusion of the iliac artery three times during the operation. However, serious hemorrhage occurred, which was rescued by the multimodality blood conservation strategy. THR was successfully performed, and the patient was discharged 8 d later for rehabilitation. Postoperative pathological examination showed osteonecrosis of the femoral head with malformed thick-walled vessels and focal granulomatous inflammation of the surrounding soft tissues. The Harris Hip Scale score increased from 31 to 82 at 3 mo of follow-up. The patient was followed up for 1 year, and all her clinical symptoms were significantly alleviated. CONCLUSION Arthritis of the hip caused by AVMs is rare in clinical practice. The activity and function of the involved hip joint can be effectively treated with THR after comprehensive imaging and multidisciplinary consultation.

Differences and correlations of biochemical index levels in patients with bipolar disorder and major depressive disorder during a stable period.

The differences and correlation of biochemical indexes between bipolar disorder (BPD) and major depressive disorder (MDD) in stable stage were analyzed and discussed. Patients diagnosed with BPD and MDD in the Third People's Hospital of Foshan from January 2019 to December 2021 were selected as the research subjects, with 200 cases in each. Fasting serum was collected from patients and then detected regarding TC, TG, high-density lipoprotein, low-density lipoprotein (LDL), aspartate aminotransferase, lactic dehydrogenase, creatine kinase, creatine kinase-MB, urea, creatinine, uric acid, alanine aminotransferase, glucose (GLU), hemoglobin A1c, prolactin, high-sensitivity C-reactive protein, homocysteine. The results showed that the mean age and serum LDL, GLU, and HbAc1 levels of the MDD group were significantly higher than those of the BPD group (P < .05), while there was no significant difference in other indexes (P > .05). The prevalence of BPD was significantly negatively correlated with patient age (r = -0.164, P = .020), LDL (r = -0.150, P = .034), GLU (r = -0.140, P = .048), and HbAc1 (r = -0.215, P = .002) (P < .05). There were no significant differences in serum Hcy and high-sensitivity C-reactive protein levels between the BPD and MDD groups. The age, fasting blood glucose, glycosylated hemoglobin, and LDL of BPD patients were negatively correlated with their incidence.

Amygdala signal abnormality and cognitive impairment in drug-naïve schizophrenia.

BACKGROUND: Recently studies had showed that the amygdala may take part in the cognitive impairment in schizophrenia (SC). However, the mechanism is still unclear, so we explored the relationship between the amygdala resting state magnetic resonance imaging (rsMRI) signal and cognitive function, to provide a reference for the follow-up study. METHODS: We collected 59 drug-naïve SCs and 46 healthy controls (HCs) from the Third People's Hospital of Foshan. The rsMRI technique and automatic segmentation tool were used to extract the volume and functional indicators of the SC's amygdala. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of the disease, and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to assess cognitive function. Pearson correlation analysis was used to compare the relationship between the structural and functional indicators of the amygdala and PANSS and RBANS. RESULTS: (1) There was no significant difference between SC and HC in age, gender and years of education. Compared with HC, the PANSS score of SC increased and the RBANS score decreased significantly. Meanwhile, the left amygdala volume decreased (t=-3.675, p < 0.001), and the Fractional amplitude of low-frequency fluctuations (FALFF) values of bilateral amygdala increased (tL=3.916, p < 0.001; tR=3.131, p = 0.002). (2) The volumes of the left amygdala were negatively correlated with the PANSS score (rL=-0.243, p = 0.039). While the FALFF values of the bilateral amygdala were positively correlated with the PANSS score (rL=0.257, p = 0.026; rR=0.259, p = 0.026). Bilateral amygdala volumes and FALFF values were positively correlated (rL=0.445, p < 0.001; rR=0.326, p = 0.006) and negatively correlated with RBANS score (rL=-0.284, p = 0.014; rR=-0.272, p = 0.020), respectively. CONCLUSION: The abnormal volume and function of the amygdala play important roles in the disease process of SC, and are closely related to cognitive impairment.

Mesenchymal Stem Cell Aggregation-Released Extracellular Vesicles Induce CD31+ EMCN+ Vessels in Skin Regeneration and Improve Diabetic Wound Healing.

The blood vessel system is essential for skin homeostasis and regeneration. While the heterogeneity of vascular endothelial cells has been emergingly revealed, whether a regeneration-relevant vessel subtype exists in skin remains unknown. Herein, a specialized vasculature in skin featured by simultaneous CD31 and EMCN expression contributing to the regeneration process is identified, the decline of which functionally underlies the impaired angiogenesis of diabetic nonhealing wounds. Moreover, enlightened by the developmental process that mesenchymal condensation induces angiogenesis, it is demonstrated that mesenchymal stem/stromal cell aggregates (CAs) provide an efficacious therapy to enhance regrowth of CD31+ EMCN+ vessels in diabetic wounds, which is surprisingly suppressed by pharmacological inhibition of extracellular vesicle (EV) release. It is further shown that CAs promote secretion of angiogenic protein-enriched EVs by proteomic analysis, which directly exert high efficacy in boosting CD31+ EMCN+ vessels and treating nonhealing diabetic wounds. These results add to the current knowledge on skin vasculature and help establish feasible strategies to benefit wound healing under diabetic condition.

Disrupted interhemispheric coordination of sensory-motor networks and insula in major depressive disorder.

Objective: Prior researches have identified distinct differences in neuroimaging characteristics between healthy controls (HCs) and patients with major depressive disorder (MDD). However, the correlations between homotopic connectivity and clinical characteristics in patients with MDD have yet to be fully understood. The present study aimed to investigate common and unique patterns of homotopic connectivity and their relationships with clinical characteristics in patients with MDD. Methods: We recruited 42 patients diagnosed with MDD and 42 HCs. We collected a range of clinical variables, as well as exploratory eye movement (EEM), event-related potentials (ERPs) and resting-state functional magnetic resonance imaging (rs-fMRI) data. The data were analyzed using correlation analysis, support vector machine (SVM), and voxel-mirrored homotopic connectivity (VMHC). Results: Compared with HCs, patients with MDD showed decreased VMHC in the insula, and increased VMHC in the cerebellum 8/vermis 8/vermis 9 and superior/middle occipital gyrus. SVM analysis using VMHC values in the cerebellum 8/vermis 8/vermis 9 and insula, or VMHC values in the superior/middle occipital gyrus and insula as inputs can distinguish HCs and patients with MDD with high accuracy, sensitivity, and specificity. Conclusion: The study demonstrated that decreased VMHC in the insula and increased VMHC values in the sensory-motor networks may be a distinctive neurobiological feature for patients with MDD, which could potentially serve as imaging markers to discriminate HCs and patients with MDD.

AFM negatively regulates the infiltration of monocytes to mediate sepsis-associated acute kidney injury.

Background: Sepsis is organ dysfunction due to the host's deleterious response to infection, and the kidneys are one of the organs damaged in common sepsis. Sepsis-associated acute kidney injury (SA-AKI) increases the mortality in patients with sepsis. Although a substantial volume of research has improved the prevention and treatment of the disease, SA-SKI is still a significant clinical concern. Purpose: Aimed to use weighted gene co-expression network analysis (WGCNA) and immunoinfiltration analysis to study SA-AKI-related diagnostic markers and potential therapeutic targets. Methods: Immunoinfiltration analysis was performed on SA-AKI expression datasets from the Gene Expression Synthesis (GEO) database. A weighted gene co-expression network analysis (WGCNA) analysis was performed on immune invasion scores as trait data, and modules associated with immune cells of interest were identified as hub modules. Screening hub geneset in the hub module using protein-protein interaction (PPI) network analysis. The hub gene was identified as a target by intersecting with significantly different genes screened by differential expression analysis and validated using two external datasets. Finally, the correlation between the target gene, SA-AKI, and immune cells was verified experimentally. Results: Green modules associated with monocytes were identified using WGCNA and immune infiltration analysis. Differential expression analysis and PPI network analysis identified two hub genes (AFM and GSTA1). Further validation using additional AKI datasets GSE30718 and GSE44925 showed that AFM was significantly downregulated in AKI samples and correlated with the development of AKI. The correlation analysis of hub genes and immune cells showed that AFM was significantly associated with monocyte infiltration and hence, selected as a critical gene. In addition, Gene single-enrichment analysis (GSEA) and PPI analyses results showed that AFM was significantly related to the occurrence and development of SA-AKI. Conclusions: AFM is inversely correlated with the recruitment of monocytes and the release of various inflammatory factors in the kidneys of AKI. AFM can be a potential biomarker and therapeutic target for monocyte infiltration in sepsis-related AKI.

Deficiency of IRG1/ itaconate aggravates endotoxemia-induced acute lung injury by inhibiting autophagy in mice.

Itaconate, produced by aconitate decarboxylase 1 (ACOD1), which is encoded by immune-responsive gene 1 (Irg1), is one of the metabolites derived from the tricarboxylic acid cycle. It has been reported that exogenous itaconate plays an anti-inflammatory role in the progression of multiple diseases and pathological processes, including activated macrophage, ischemia-reperfusion injury, and acute lung injury. However, the role and specific mechanism of endogenous itaconate in endotoxemia-induced acute lung injury (ALI) remain unclear. The animal model of ALI in wild-type and Irg1-/- mice was constructed by LPS intraperitoneal injection. Ultrahigh-performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) analysis was performed to measure the quantity of endogenous itaconate. The protective effect of itaconate was investigated by the behavioral assessment and the levels of inflammatory cytokines. Acute lung injury was assessed by hematoxylin and eosin staining, total protein in BALF, and Evans blue leakage. Western blotting was used to detect the IRG1 expression and autophagic protein in the lung. We demonstrated that IRG1 was highly expressed in ALI and that endogenous itaconate was produced simultaneously and was 100 times higher. Using Irg1-/- mice, we found that endogenous itaconate was likely to exert an anti-inflammatory effect by activating NRF2 and promoting autophagy. Furthermore, autophagy was restrained by LPS but enhanced by 4-octyl itaconate (4-OI) pretreatment. Our study illustrated that a deficiency of IRG1/Itaconate aggravates ALI and that the IRG1/itaconate pathway protects against ALI. The protective mechanisms could be related to the facilitation of autophagy. Such findings may provide a theoretical foundation for the treatment of endotoxemia-induced ALI.

ipaQTL-atlas: an atlas of intronic polyadenylation quantitative trait loci across human tissues.

Functional interpretation of disease-associated non-coding variants remains a significant challenge in the post-GWAS era. Our recent study has identified 3'UTR alternative polyadenylation (APA) quantitative trait loci (3'aQTLs) and connects APA events with QTLs as a major driver of human traits and diseases. Besides 3'UTR, APA events can also occur in intron regions, and increasing evidence has connected intronic polyadenylation with disease risk. However, systematic investigation of the roles of intronic polyadenylation in human diseases remained challenging due to the lack of a comprehensive database across a variety of human tissues. Here, we developed ipaQTL-atlas (http://bioinfo.szbl.ac.cn/ipaQTL) as the first comprehensive portal for intronic polyadenylation. The ipaQTL-atlas is based on the analysis of 15 170 RNA-seq data from 838 individuals across 49 Genotype-Tissue Expression (GTEx v8) tissues and contains ∼0.98 million SNPs associated with intronic APA events. It provides an interface for ipaQTLs search, genome browser, boxplots, and data download, as well as the visualization of GWAS and ipaQTL colocalization results. ipaQTL-atlas provides a one-stop portal to access intronic polyadenylation information and could significantly advance the discovery of APA-associated disease susceptibility genes.

Observational study on obesity: Insights from middle-aged and elderly college staff in Beijing.

Obesity poses a serious global public health challenge, particularly among middle-aged, and elderly college staff. This study aims to explore the associated factors of obesity by analyzing the metabolic indicators of 1756 university staff from Minzu University of China, Beijing. Venous blood samples were collected, and blood metabolic indicators were analyzed. The results indicate that middle-aged faculty members are more susceptible to obesity compared to their younger counterparts. Multiple linear regression analysis revealed that BMI values increase with age (B = 0.074, P < .001), uric acid (B = 0.008, P < .001), alanine transaminase (B = 0.043, P < .001), low-density lipoprotein (B = 1.941, P < .001), triglycerides (B = 0.544, P < .001), total cholesterol (TC, B = -1.582, P < .001), and other factors, while decreasing with the increase of high-density lipoprotein (B = -1.493, P < .001). In light of these findings, it is recommended that middle-aged and elderly college staff undergo regular blood indicator checks and enhance weight management to mitigate the risk of obesity and promote their overall health.