Effects of educational attainment on comorbidity of pain and depression in Chinese older adults.

Pain and depression comorbidity (PD) among older adults in China is common and significantly affects their physical and mental health. The psychosocial factors may affect people's feelings, understanding and expression of pain and depression, leading to inaccurate assessment of this condition. Educational attainment is thought to be associated with either pain or depression. However, we do not yet know the relationship between educational attainment and PD. Using data from the 2018 China Health and Retirement Longitudinal Study in 2018, we analyzed various variables in 7742 individuals aged 60 years and older. Our results indicate significant differences between the PD and non-PD populations in terms of social, lifestyle, and behavioral factors. We observed a significant decrease in the incidence of PD among older adults with higher levels of education (p < 0.001). This association appears to be partially mediated by cognitive ability, suggesting that educational attainment may mitigate the risk of PD through cognitive enhancement. In addition, our analysis shows that the effect of educational attainment on PD is moderated by additional psychosocial factors, including living environment and alcohol consumption patterns. Older adults with higher levels of education tend to live in urban areas and have better control over alcohol consumption, which may contribute to a lower incidence of PD. Therefore, interventions aimed at enhancing cognitive abilities, improving living environments, and promoting healthier lifestyles and habits among older adults could potentially reduce their burden of PD.

Elevated serum cholesterol levels during pregnancy as predictors for postpartum hypercholesterolemia: A prospective cohort study.

OBJECTIVE: To identify the associations between gestational cholesterol levels and the risk of postpartum hypercholesterolemia, and to establish trimester-specific reference values. METHODS: Serum lipids at gestational weeks 6-8, 16, 24, and 36, and 42 days postpartum were derived from 905 pregnant women of a prospective cohort. The major outcome was postpartum hypercholesterolemia. Logistic regression and restricted cubic splines were conducted to estimate the associations between cholesterol levels at specific gestational ages and postpartum hypercholesterolemia. Associations of the trend of changes in cholesterol levels during pregnancy with postpartum hypercholesterolemia were evaluated by linear mixed-effect model and linear or logistic regression. Reference values were computed by the receiver operating characteristic curves. RESULTS: Serum concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and the ratios of TC/HDL-C and LDL-C/HDL-C all increased during pregnancy and decreased at 42 days postpartum. The elevated levels of TC and LDL-C, decreased levels of HDL-C in pregnancy, and their rapid change rates were positively associated with higher risks of postpartum hypercholesterolemia. The established reference values from the first to the third trimester were below 5.47, 6.35, and 7.22 mmol/L for TC; below 2.83, 3.82, and 4.21 mmol/L for LDL-C; and more than 1.50, 1.55, and 1.50 mmol/L for HDL-C, respectively. CONCLUSION: Maternal cholesterol levels and their trend of change during pregnancy were predictors of postpartum hypercholesterolemia. Trimester-specific reference values were established in a Chinese population.

Taxonomic revision of Geotrichum and Magnusiomyces, with the descriptions of five new Geotrichum species from China.

The arthroconidial yeast-like species currently classified in the asexual genera Geotrichum and Saprochaete and the sexual genera Dipodascus, Galactomyces and Magnusiomyces are frequently associated with dairy and cosmetics production, fruit rot and human infection. However, the taxonomic system of these fungi has not been updated to accommodate the new nomenclature code adopting the "one fungus, one name" principle. Here, we performed phylogenetic analyses of these yeast-like species based on the sequences of the internal transcribed spacer (ITS) region and the D1/D2 domain of the large subunit of the rRNA gene. Two monophyletic groups were recognised from these species. One group contained Dipodascus, Galactomyces, and Geotrichum species and the other Magnusiomyces and Saprochaete species. We thus assigned the species in each group into one genus and selected the genus name Geotrichum for the first group and Magnusiomyces for the second one based on the principle of priority of publication. Five new Geotrichum species were identified from arthroconidial yeast strains recently isolated from various sources in China. The new species are described as Ge. dehoogii sp. nov., Ge. fujianense sp. nov., Ge. maricola sp. nov., Ge. smithiae sp. nov., and Ge. sinensis sp. nov.

Sarcopenia is attenuated by mairin in SAMP8 mice via the inhibition of FAPs fibrosis through the AMPK-TGF-ß-SMAD axis.

Sarcopenia has become a prominent health problem among the elderly because of its adverse consequence, including physical disabilities and death. Fibro-adipogenic progenitors (FAPs) exhibit adipogenic and fibrogenic potencies and regulate skeletal muscle development, which plays important role in sarcopenia. Mairin, as an ingredient of Astragalus membranaceus, has the effect of anti-fibrosis. Therefore, we predicted that mairin targeted the fibrosis of FAPs and then affected sarcopenia. To verify our ideas, mairin (30 mg/kg/day or 60 mg/kg/day) was given to senescence accelerated mouse-prone 8 (SAMP8) mice by oral administration. Aging led to loss of weight, skeletal muscle mass, strength, and function, and an increase in muscle atrophy and fibrosis, while mairin administration inhibited physiological decline caused by aging. Similarly, mairin (20 µM or 40 µM) treatment enhanced FAP proliferation but blocked the differentiation into fibroblasts. Mechanically, mairin played an anti-fibrotic role via AMP-activated protein kinase-transforming growth factor beta-drosophila mothers against decapentaplegic protein (AMPK-TGF-ß-SMAD) axis, as evidenced by increased phosphorylation of AMPKα and decreased TGF-ß and phosphorylated-SMAD2/3. In addition, the potential target genes of mairin were explored by mRNA sequencing in our study. In conclusion, mairin may interfere with the AMPK/TGF-ß/SMAD pathway to repress the fibrosis of FAPs and eventually ameliorate sarcopenia.

Study on diagnostic-sensitive markers of primary immune thrombocytopaenia in children based on plasma proteomics.

To use proteomic techniques to identify sensitive diagnostic biomarkers for paediatric immune thrombocytopenia (ITP). We selected children in ITP and control groups, using a four-dimensional data-independent acquisition approach (4D-DIA) to analyse its protein expression. The significantly differentially expressed proteins were selected for enzyme-linked immunosorbent assay (ELISA) validation in a cohort comprising 50 samples (13 healthy controls, 15 secondary thrombocytopenia controls and 22 children with ITP). Receiver operating characteristics (ROC) were generated to diagnose ITP and to assess the diagnostic effectiveness of this approach. Compared with the control group, 55 differentially expressed proteins (43 increased and 12 decreased) were determined in the ITP group. Matrix metalloproteinases-9 (MMP-9) and thrombospondin-1 (THBS1) were significantly expressed and selected for ELISA. The verification outcomes aligned with the findings from the proteomic examinations. In contrast to the control cohort, the ITP subjects exhibited markedly elevated plasma MMP-9 levels and reduced plasma THBS1 concentrations. Additionally, the ROC curves indicated the diagnostic value of these biomarkers. In conclusion, proteomics facilitates identifying the sensitive biomarkers for ITP diagnosis. We have preliminarily selected two differentially expressed proteins, MMP-9 and THBS1, whose potential role as biomarkers for diagnosing ITP requires further research.

Tetramerization of PKM2 Alleviates Traumatic Brain Injury by Ameliorating Mitochondrial Damage in Microglia.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Microglial activation and neuroinflammation are key cellular events that determine the outcome of TBI, especially neuronal and cognitive function. Studies have suggested that the metabolic characteristics of microglia dictate their inflammatory response. The pyruvate kinase isoform M2 (PKM2), a key glycolytic enzyme, is involved in the regulation of various cellular metabolic processes, including mitochondrial metabolism. This suggests that PKM2 may also participate in the regulation of microglial activation during TBI. Therefore, the present study aimed to evaluate the role of PKM2 in regulating microglial activation and neuroinflammation and its effects on cognitive function following TBI. A controlled cortical impact (CCI) mouse model and inflammation-induced primary mouse microglial cells in vitro were used to investigate the potential effects of PKM2 inhibition and regulation. PKM2 was significantly increased during the acute and subacute phases of TBI and was predominantly detected in microglia rather than in neurons. Our results demonstrate that shikonin and TEPP-46 can inhibit microglial inflammation, improving mitochondria, improving mouse behavior, reducing brain defect volume, and alleviating pathological changes after TBI. There is a difference in the intervention of shikonin and TEPP-46 on PKM2. Shikonin directly inhibits General PKM2; TEPP-46 can promote the expression of PKM2 tetramer. In vitro experiments, TEPP-46 can promote the expression of PKM2 tetramer, enhance the interaction between PKM2 and MFN2, improve mitochondria, alleviate neuroinflammation. General inhibition and tetramerization activation of PKM2 attenuated cognitive function caused by TBI, whereas PKM2 tetramerization exhibited a better treatment effect. Our experiments demonstrated the non-metabolic role of PKM2 in the regulation of microglial activation following TBI. Both shikonin and TEPP-46 can inhibit pro-inflammatory factors, but only TEPP-46 can promote PKM2 tetramerization and upregulate the release of anti-inflammatory factors from microglia.

Mature oocyte found during ovarian tissue cryopreservation in an early adolescent female. / 青春初期女性行卵巢组织冷冻过程中发现成熟卵母细胞一例.

A 15-year-old female with Hodgkin's lymphoma underwent ovarian tissue cryopreservation for preserving fertility in Reproductive Department of Sir Run Run Shaw Hospital, Zhejiang University School of Medical after receiving one course of chemotherapy. During the ovarian tissue cryopreservation, one MⅡmature oocyte and three germinal vesicle oocytes were found. The three immature oocytes underwent in vitro maturation but failed. Ultimately, one mature oocyte and 12 ovarian cortex slices were cryopreserved using vitrification. This case indicates that for patients with established gonadal axis feedback, ovarian tissue cryopreservation may not be the only method for fertility preservation. It is advisable to consider ovarian stimulation and oocyte retrieval for oocyte cryopreservation. Alternatively, for individuals in the ovulation phase of their menstrual cycle, attempting oocyte retrieval before ovarian tissue cryopreservation to obtain mature oocytes from the natural cycle, followed by oocyte cryopreservation, may enhance the likelihood of successful fertility preservation.

Nrf2/FSP1/CoQ10 axis-mediated ferroptosis is involved in sodium aescinate-induced nephrotoxicity.

Sodium aescinate (SA), an active compound found in horse chestnut seeds, is widely used in clinical practice. Recently, the incidence of SA-induced adverse events, particularly renal impairment, has increased. Our previous work demonstrated that SA causes severe nephrotoxicity via nephrocyte ferroptosis; however, the underlying mechanism remains to be fully elucidated. In the current study, we investigated additional molecular pathways involved in SA-induced nephrotoxicity. Our results showed that SA inhibited cell viability, disrupted cellular membrane integrity, and enhanced reactive oxygen species (ROS), ferrous iron (Fe2+), and malondialdehyde (MDA) levels, as well as lipid peroxidation in rat proximal renal tubular epithelial cell line (NRK-52E) cells. SA also depleted coenzyme Q10 (CoQ10, ubiquinone) and nicotinamide adenine dinucleotide (NADH) and reduced ferroptosis suppressor protein 1 (FSP1) and polyprenyltransferase (coenzyme Q2, COQ2) activity, triggering lipid peroxidation and ROS accumulation in mouse kidneys and NRK-52E cells. The overexpression of COQ2, FSP1, or CoQ10 (ubiquinone) supplementation effectively attenuated SA-induced ferroptosis, whereas iFSP1 or 4-formylbenzoic acid (4-CBA) pretreatment exacerbated SA-induced nephrotoxicity. Additionally, SA decreased nuclear factor-erythroid-2-related factor 2 (Nrf2) levels and inhibited Nrf2 binding to the -1170/-1180 bp ARE site in FSP1 promoter, resulting in FSP1 suppression. Overexpression of Nrf2 or its agonist dimethyl fumarate (DMF) promoted FSP1 expression, thereby improving cellular antioxidant capacity and alleviating SA-induced ferroptosis. These results suggest that SA-triggers renal injury through oxidative stress and ferroptosis, driven by the suppression of the Nrf2/FSP1/CoQ10 axis.

Species-level understanding of the bacterial community in Daqu based on full-length 16S rRNA gene sequences.

Daqu is used as the fermentation starter of Baijiu and contributes diversified functional microbes for saccharifying grains and converting sugars into ethanol and aroma components in Baijiu products. Daqu is mainly classified into three types, namely low (LTD), medium (MTD) and high (HTD) temperature Daqu, according to the highest temperatures reached in their fermentation processes. In this study, we used the PacBio small-molecule real-time (SMRT) sequencing technology to determine the full-length 16 S rRNA gene sequences from the metagenomes of 296 samples of different types of Daqu collected from ten provinces in China, and revealed the bacterial diversity at the species level in the Daqu samples. We totally identified 310 bacteria species, including 78 highly abundant species (with a relative abundance >0.1% each) which accounted for 91.90% of the reads from all the Daqu samples. We also recognized the differentially enriched bacterial species in different types of Daqu, and in the Daqu samples with the same type but from different provinces. Specifically, Lactobacillales, Enterobacterales and Bacillaceae were significantly enriched in the LTD, MTD and HTD groups, respectively. The potential co-existence and exclusion relationships among the bacteria species involved in all the Daqu samples and in the LTD, MTD and HTD samples from a specific region were also identified. These results provide a better understanding of the bacterial diversity in different types of Daqu at the species level.

L-valine derived from the gut microbiota protects sepsis-induced intestinal injury and negatively correlates with the severity of sepsis.

Background: The protective role of gut microbiota and its metabolites against intestinal damage in sepsis patients remain unclear. Methods: Fecal samples were acquired from patients categorized into sepsis and non-sepsis groups for analysis of microbial composition via 16S rRNA sequencing and untargeted metabolomics analysis. We assessed the impact of gut microbiota from sepsis patients on intestinal barriers in antibiotic-treated mice. Furthermore, We conducted spearman's correlation analysis to examine the relationship between metabolites and the severity of sepsis. Additionally, we performed animal experiments to validate the functionality of identified metabolites. Results: The diversity of intestinal flora is decreased in patients with sepsis compared to the control group. Through fecal microbiota transplantation experiments, it was discovered that the gut microbiota derived from sepsis patients could induce intestinal damage in antibiotic-treated mice. Metabolomics analysis of the microbiota revealed a significant enrichment of the Valine, leucine, and isoleucine biosynthesis pathway. Further analysis showed a significant decrease in the abundance of L-valine in sepsis patients, which was negatively correlated with APACHE-II and SOFA scores. In sepsis mouse experiments, it was found that L-valine could alleviate sepsis-induced intestinal damage. Conclusion: Alterations in microbial and metabolic features in the gut can affect the severity of sepsis. Furthermore, L-valine can protect against sepsis-induced intestinal injury.

Comparison of various doses of oral cannabidiol for treating refractory epilepsy indications: a network meta-analysis.

Aim: To evaluate the comparative efficacy and safety of various doses of oral cannabidiol (CBD) in treating refractory epilepsy indications, thus providing more informative evidence for clinical decision-making. Methods: A literature search of PubMed, Embase, the Cochrane library, and Web of Science (WoS) was performed to retrieve relevant randomized controlled trials (RCTs) that compared different doses of oral CBD with placebo or each other in refractory epilepsy indications. The search was limited from the inception of each database to January 3, 2023. Relative risk [RR] with a 95% confidence interval [CI] was used to express results. STATA/SE 14 was employed for network meta-analysis. Results: Six RCTs involving 972 patients were included in the final data analysis. Network meta-analysis showed that, CBD10 (10 mg/kg/day) (RR: 1.77, 95%CI: 1.28 to 2.44), CBD20 (20 mg/kg/day) (RR: 1.91, 95%CI: 1.49 to 2.46), CBD25 (25 mg/kg/day) (RR: 1.61, 95%CI: 0.96 to 2.70), and CBD50 (50 mg/kg/day) (RR: 1.78, 95%CI: 1.07 to 2.94) were associated with higher antiseizure efficacy although the pooled result for CBD25 was only close to significant. In addition, in terms of the risk of treatment-emergent adverse events (TEAEs), the difference between different doses is not significant. However, CBD20 ranked first in terms of antiseizure efficacy, followed by CBD50, CBD10, and CBD25. For TEAEs, CBD25 ranked first, followed by CBD10, CBD50, CBD5, and CBD20. Conclusion: For refractory indications, CBD20 may be optimal option for antiseizure efficacy; however, CBD25 may be best for TEAEs. Therefore, an appropriate dose of oral CBD should be selected based on the actual situation. Due to the limitations of eligible studies and the limited sample size, more studies are needed in the future to validate our findings.

Interleukin-11 Is Involved in Hyperoxia-induced Bronchopulmonary Dysplasia in Newborn Mice by Mediating Epithelium-Fibroblast Cross-talk.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a chronic lung disorder predominantly affecting preterm infants. Oxygen therapy, a common treatment for BPD, often leads to hyperoxia-induced pulmonary damage, particularly targeting alveolar epithelial cells (AECs). Crucially, disrupted lung epithelium-fibroblast interactions significantly contribute to BPD's pathogenesis. Previous studies on interleukin-11 (IL-11) in lung diseases have yielded conflicting results. Recent research, however, highlights IL-11 as a key regulator of fibrosis, stromal inflammation, and epithelial dysfunction. Despite this, the specific role of IL-11 in BPD remains underexplored. Our transcriptome analysis of normal and hyperoxia-exposed murine lung tissues revealed an increased expression of IL-11 RNA. This study aimed to investigate IL-11's role in modulating the disrupted interactions between AECs and fibroblasts in BPD. METHODS: BPD was modeled in vivo by exposing C57BL/6J neonatal mice to hyperoxia. Histopathological changes in lung tissue were evaluated with hematoxylin-eosin staining, while lung fibrosis was assessed using Masson staining and immunohistochemistry (IHC). To investigate IL-11's role in pulmonary injury contributing to BPD, IL-11 levels were reduced through intraperitoneal administration of IL-11RαFc in hyperoxia-exposed mice. Additionally, MLE-12 cells subjected to 95% oxygen were collected and co-cultured with mouse pulmonary fibroblasts (MPFs) to measure α-SMA and Collagen I expression levels. IL-11 levels in the supernatants were quantified using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Both IHC and Masson staining revealed that inhibiting IL-11 expression alleviated pulmonary fibrosis in neonatal mice induced by hyperoxia, along with reducing the expression of fibrosis markers α-SMA and collagen I in lung tissue. In vitro analysis showed a significant increase in IL-11 levels in the supernatant of MLE-12 cells treated with hyperoxia. Silencing IL-11 expression in MLE-12 cells reduced α-SMA and collagen I concentrations in MPFs co-cultured with the supernatant of hyperoxia-treated MLE-12 cells. Additionally, ERK inhibitors decreased α-SMA and collagen I levels in MPFs co-cultured with the supernatant of hyperoxia-treated MLE-12 cells. Clinical studies found increased IL-11 levels in tracheal aspirates (TA) of infants with BPD. CONCLUSION: This research reveals that hyperoxia induces IL-11 secretion in lung epithelium. Additionally, IL-11 derived from lung epithelium emerged as a crucial mediator in myofibroblast differentiation via the ERK signaling pathway, highlighting its potential therapeutic value in BPD treatment.

Roles of long non­coding RNA SNHG16 in human digestive system cancer (Review).

The incidence of tumors in the human digestive system is relatively high, including esophageal cancer, liver cancer, pancreatic cancer, gastric cancer and colorectal cancer. These malignancies arise from a complex interplay of environmental and genetic factors. Among them, long non­coding RNAs (lncRNAs), which cannot be translated into proteins, serve an important role in the development, progression, migration and prognosis of tumors. Small nucleolar RNA host gene 16 (SNHG16) is a typical lncRNA, and its relationship with digestive system tumors has been widely explored. The prevailing hypothesis suggests that the principal molecular mechanism of SNHG16 in digestive system tumors involves it functioning as a competitive endogenous RNA that interacts with other proteins, regulates various genes and influences a downstream target molecule. The present review summarizes recent research on the relationship between SNHG16 and numerous types of digestive system cancer, encompassing its biological functions, underlying mechanisms and potential clinical implications. Furthermore, it outlines the association between SNHG16 expression and pertinent risk factors, such as smoking, infection and diet. The present review indicated the promise of SNHG16 as a potential biomarker and therapeutic target in human digestive system cancer.

A Novel Ratiometric Photoelectrochemical Biosensor Based on Front and Back Illumination for Sensitive and Accurate Glutathione Sensing.

The ratiometric detection method has a strong attraction for photoelectrochemical bioanalysis due to its high reliability and real-time calibration. However, its implementation typically depends on the spatial resolution of equipment and the pairing of wavelength/potential with photoactive materials. In this paper, a novel ratiometric photoelectrochemical biosensor based on front and back illumination was prepared for the detection of glutathione (GSH). Unlike traditional ratio methods, this ratiometric biosensor does not require voltage and wavelength modulation, thereby avoiding potential crosstalk caused by voltage and wavelength modulation. Additionally, the formation of a heterojunction between mTiO2 and Ag2S is conducive to enhancing light absorption and promoting charge separation, thereby boosting the photocurrent signal. Apart from forming a heterojunction with TiO2, Ag2S also shows a specific affinity towards GSH, thus enhancing the selectivity of the mTiO2/Ag2S ratiometric photoelectrochemical biosensor. The results demonstrate that the ratiometric photoelectrochemical biosensor exhibits a good detection range and a low detection limit for GSH, while also possessing significant interference elimination capability. The GSH detection range is 0.01-10 mmol L-1 with a detection limit of 6.39 × 10-3 mmol·L-1. The relative standard deviation of 20 repeated detections is 0.664%. Impressively, the proposed novel ratiometric PEC biosensor demonstrates enviable universality, providing new insights for the design and construction of PEC ratiometric sensing platforms.

Effective recognition design in 8-ball billiards vision systems for training purposes based on Xception network modified by improved Chaos African Vulture Optimizer.

This research paper presents a comprehensive investigation into the utilization of color image processing technologies and deep learning algorithms in the development of a robot vision system specifically designed for 8-ball billiards. The sport of billiards, with its various games and ball arrangements, presents unique challenges for robotic vision systems. The proposed methodology addresses these challenges through two main components: object detection and ball pattern recognition. Initially, a robust algorithm is employed to detect the billiard balls using color space transformation and thresholding techniques. This is followed by determining the position of the billiard table through strategic cropping and isolation of the primary table area. The crucial phase involves the intricate task of recognizing ball patterns to differentiate between solid and striped balls. To achieve this, a modified convolutional neural network is utilized, leveraging the Xception network optimized by an innovative algorithm known as the Improved Chaos African Vulture Optimization (ICAVO) algorithm. The ICAVO algorithm enhances the Xception network's performance by efficiently exploring the solution space and avoiding local optima. The results of this study demonstrate a significant enhancement in recognition accuracy, with the Xception/ICAVO model achieving remarkable recognition rates for both solid and striped balls. This paves the way for the development of more sophisticated and efficient billiards robots. The implications of this research extend beyond 8-ball billiards, highlighting the potential for advanced robotic vision systems in various applications. The successful integration of color image processing, deep learning, and optimization algorithms shows the effectiveness of the proposed methodology. This research has far-reaching implications that go beyond just billiards. The cutting-edge robotic vision technology can be utilized for detecting and tracking objects in different sectors, transforming industrial automation and surveillance setups. By combining color image processing, deep learning, and optimization algorithms, the system proves its effectiveness and flexibility. The innovative approach sets the stage for creating advanced and productive robotic vision systems in various industries.

Genetic variations of IL10 and IL6R genes in acute anterior uveitis in Han Chinese.

BACKGROUND: Several autoimmune disorders have been linked to polymorphisms in IL10 and IL6R genes. This research aimed to study whether single nucleotide polymorphisms (SNPs) in the genes of IL10 and IL6R were associated with acute anterior uveitis (AAU) in Han Chinese. METHODS: Genotyping was carried out by the iPLEX Gold Genotyping Assay. Our study comprised 420 patients with AAU and 918 healthy subjects from Han Chinese. Using the chi-square (χ2) test, alleles and genotypes were analyzed between AAU subjects and healthy controls. RESULTS: All ten SNPs were successfully genotyped and four SNPs (IL10/rs1800871, IL10/rs3021094, IL10/rs2222202, IL6R/rs4845618) exhibited weak associations with AAU, as indicated by their Puncorr values. However, upon applying the Bonferroni correction, there was no significant association between AAU and the control subjects. Additionally, the haplotype analysis of the ten SNPs revealed no association with AAU. CONCLUSION: Our findings suggested that polymorphisms of the tested ten SNPs on the IL10 and IL6R genes did not show any association with the risk of developing AAU among the Han Chinese population.

Proteinase 3 depletion attenuates leukemia by promoting myeloid differentiation.

Hematopoietic stem and progenitor cells (HSPCs) that have impaired differentiation can transform into leukemic blasts. However, the mechanism that controls differentiation remains elusive. Here, we show that the genetic elimination of Proteinase 3 (PRTN3) in mice led to spontaneous myeloid differentiation. Mechanistically, our findings indicate that PRTN3 interacts with the N-terminal of STAT3, serving as a negative regulator of STAT3-dependent myeloid differentiation. Specifically, PRTN3 promotes STAT3 ubiquitination and degradation, while simultaneously reducing STAT3 phosphorylation and nuclear translocation during G-CSF-stimulated myeloid differentiation. Strikingly, pharmacological inhibition of STAT3 (Stattic) partially counteracted the effects of PRTN3 deficiency on myeloid differentiation. Moreover, the deficiency of PRTN3 in primary AML blasts promotes the differentiation of those cells into functional neutrophils capable of chemotaxis and phagocytosis, ultimately resulting in improved overall survival rates for recipients. These findings indicate PRTN3 exerts an inhibitory effect on STAT3-dependent myeloid differentiation and could be a promising therapeutic target for the treatment of acute myeloid leukemia.

QKL injection ameliorates Alzheimer's disease-like pathology by regulating expression of RAGE.

The onset of Alzheimer's disease is related to neuron damage caused by massive deposition of Aß in the brain. Recent studies suggest that excessive Aß in the brain mainly comes from peripheral blood, and BBB is the key to regulate Aß in and out of the brain. In this study, we explored the pathogenesis of AD from the perspective of Aß transport through the BBB and the effect of QKL injection in AD mice. The results showed that QKL could improve the cognitive dysfunction of AD mice, decrease the level of Aß and Aß transporter-RAGE, which was supported by the results of network pharmacology, molecular docking and molecular dynamics simulation. In conclusion, RAGE is a potential target for QKL's therapeutic effect on AD.