Glycyrrhetinic acid triggers a protective autophagy by inhibiting the JAK2/STAT3 pathway in cerebral ischemia/reperfusion injury.

Cerebral ischemia/reperfusion injury (CIRI) is a common feature of ischemic stroke leading to a poor prognosis. Effective treatments targeting I/R injury are still insufficient. The study aimed to investigate the mechanisms, by which glycyrrhizic acid (18ß-GA) in ameliorates CIRI. Our results showed that 18ß-GA significantly decreased the infarct volume, neurological deficit scores, and pathological changes in the brain tissue of rats after middle cerebral artery occlusion. Western blotting showed that 18ß-GA inhibited the expression levels of phosphorylated JAK2 and phosphorylated STAT3. Meanwhile, 18ß-GA increased LC3-II protein levels in a reperfusion duration-dependent manner, which was accompanied by an increase in the Bcl-2/Bax ratio. Inhibition of 18ß-GA-induced autophagy by 3-methyladenine (3-MA) enhanced apoptotic cell death. In addition, 18ß-GA inhibited the JAK2/STAT3 pathway, which was largely activated in response to oxygen-glucose deprivation/reoxygenation. However, the JAK2/STAT3 activator colivelin TFA abolished the inhibitory effect of 18ß-GA, suppressed autophagy, and significantly decreased the Bcl-2/Bax ratio. Taken together, these findings suggested that 18ß-GA pretreatment ameliorated CIRI partly by triggering a protective autophagy via the JAK2/STAT3 pathway. Therefore might be a potential drug candidate for treating ischemic stroke.

Microplastics in soil affect the growth and physiological characteristics of Chinese fir and Phoebe bournei seedlings.

Pot experiments were conducted using Chinese fir (Cunninghamia lanceolata (Lamb.) Hook.) and Phoebe bournei (Hemsl.) Yang) to investigate whether soil microplastics adversely affect the nurturing and renewal of plantations. Microplastics composed of polyethylene and polypropylene with a size of 48 µm were used. The treatments included a control group (without microplastics) and groups treated with microplastic concentrations of 1% and 2% (w/w). The effects of microplastics on the growth, photosynthetic pigments in leaves, antioxidant systems, and osmotic regulation substances of the seedlings were analysed by measuring the seedling height, ground-line diameter growth, chlorophyll (chlorophyll a, chlorophyll b, and total chlorophyll) contents, antioxidant enzyme (superoxide dismutase, peroxidase, catalase) activities, and malondialdehyde, soluble sugar, and soluble protein levels. The results indicated that treatment with 1% polyethylene microplastics increased the chlorophyll a, total chlorophyll, and soluble protein contents in the leaves of both types of seedlings while inhibiting superoxide dismutase and peroxidase activities in P. bournei seedlings. Treatment with 2% polyethylene or polypropylene microplastics suppressed the chlorophyll a, chlorophyll b, and total chlorophyll contents; superoxide dismutase, peroxidase, and catalase activities; and soluble sugar and soluble protein levels in the leaves of both types of seedlings, resulting in reduced growth in terms of height and ground-line diameter. The physiological effects of polyethylene microplastics were more evident than those of polypropylene at the same concentration. The results demonstrated that microplastics can affect photosynthesis, the antioxidant system, and osmotic regulation in Chinese fir and P. bournei seedlings, thereby inhibiting their normal growth and development. Exposure to 1% (w/w) microplastics triggered stress responses in seedlings, whereas 2% (w/w) microplastics impeded seedling growth.

Motor adaptation is reduced by symbolic compared to sensory feedback.

Motor adaptation - the process of reducing motor errors through feedback and practice - is an essential feature of human competence, allowing us to move accurately in dynamic and novel environments. Adaptation typically results from sensory feedback, with most learning driven by visual and proprioceptive feedback that arises with the movement. In humans, motor adaptation can also be driven by symbolic feedback. In the present study, we examine how implicit and explicit components of motor adaptation are modulated by symbolic feedback. We conducted three reaching experiments involving over 400 human participants to compare sensory and symbolic feedback using a task in which both types of learning processes could be operative (Experiment 1) or tasks in which learning was expected to be limited to only an explicit process (Experiments 2 and 3). Adaptation with symbolic feedback was dominated by explicit strategy use, with minimal evidence of implicit recalibration. Even when matched in terms of information content, adaptation to rotational and mirror reversal perturbations was slower in response to symbolic feedback compared to sensory feedback. Our results suggest that the abstract and indirect nature of symbolic feedback disrupts strategic reasoning and/or refinement, deepening our understanding of how feedback type influences the mechanisms of sensorimotor learning.

MiR-4465-modified mesenchymal stem cell-derived small extracellular vesicles inhibit liver fibrosis development via targeting LOXL2 expression. / MiR-4465修饰的间质干细胞来源的小细胞外囊泡通过靶向LOXL2表达抑制肝纤维化的进展.

Liver fibrosis is a significant health burden, marked by the consistent deposition of collagen. Unfortunately, the currently available treatment approaches for this condition are far from optimal. Lysyl oxidase-like protein 2 (LOXL2) secreted by hepatic stellate cells (HSCs) is a crucial player in the cross-linking of matrix collagen and is a significant target for treating liver fibrosis. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) have been proposed as a potential treatment option for chronic liver disorders. Previous studies have found that MSC-sEV can be used for microRNA delivery into target cells or tissues. It is currently unclear whether microRNA-4465 (miR-4465) can target LOXL2 and inhibit HSC activation. Additionally, it is uncertain whether MSC-sEV can be utilized as a gene therapy vector to carry miR-4465 and effectively inhibit the progression of liver fibrosis. This study explored the effect of miR-4465-modified MSC-sEV (MSC-sEVmiR-4465) on LOXL2 expression and liver fibrosis development. The results showed that miR-4465 can bind specifically to the promoter of the LOXL2 gene in HSC. Moreover, MSC-sEVmiR-4465 inhibited HSC activation and collagen expression by downregulating LOXL2 expression in vitro. MSC-sEVmiR-4465 injection could reduce HSC activation and collagen deposition in the CCl4-induced mouse model. MSC-sEVmiR-4465 mediating via LOXL2 also hindered the migration and invasion of HepG2 cells. In conclusion, we found that MSC-sEV can deliver miR-4465 into HSC to alleviate liver fibrosis via altering LOXL2, which might provide a promising therapeutic strategy for liver diseases.

Single-pixel Fresnel incoherent correlation holography compressed imaging using a Trumpet network.

Fresnel incoherent correlation holography (FINCH) can achieve high-precision and non-scanning 3D imaging. However, as a holographic imaging technology, the huge bandwidth requirements and the amount of holographic data transmitted have always been one of the important factors limiting its application. In addition, the hardware cost of pixel array-based CCD or CMOS imaging is very high under high resolution or specific wavelength conditions. Accordingly, a single-pixel Fresnel incoherent correlation holography (SP-FINCH) compressed imaging method is proposed, which replaces pixel array detector with single-pixel detector and designs a Trumpet network to achieve low-cost and high-resolution imaging. Firstly, a modified FINCH imaging system is constructed and data acquisition is carried out using a single-pixel detector. Secondly, a Trumpet network is constructed to directly map the relationship between one-dimensional sampled data and two-dimensional image in an end-to-end manner. Moreover, by comparing the reconstructed images using neural network with that using commonly used single-pixel reconstruction methods, the results indicate that the proposed SP-FINCH compressed imaging method can significantly improve the quality of image reconstruction at lower sampling rate and achieve imaging without phase-shifting operation. The proposed method has been shown to be feasible and advantageous through numerical simulations and optical experiment results.

Knockdown of ATRX enhances radiosensitivity in glioblastoma.

BACKGROUND: Glioblastoma are highly malignant type of primary brain tumors. Treatment for glioblastoma multiforme (GBM) generally involves surgery combined with chemotherapy and radiotherapy. However, the development of tumoral chemo- and radioresistance induces complexities in clinical practice. Multiple signaling pathways are known to be involved in radiation-induced cell survival. However, the role of alpha-thalassemia X-linked mutant retardation syndrome (ATRX), a chromatin remodeling protein, in GBM radioresistance remains unclear. METHODS: In the present study, the ATRX mutation rate in patients with glioma was obtained from The Cancer Genome Atlas, while its expression analyzed using bioinformatics. Datasets were also obtained from the Gene Expression Omnibus, and ATRX expression levels following irradiation of GBM were determined. The effects of ATRX on radiosensitivity were investigated using a knockdown assays. RESULTS: The present study demonstrated that the ATRX mutation rate in patients with GBM was significantly lower than that in patients with low-grade glioma, and that patients harboring an ATRX mutation exhibited a prolonged survival, compared with to those harboring the wild-type gene. Single-cell RNA sequencing demonstrated that ATRX counts increased 2 days after irradiation, with ATRX expression levels also increasing in U-251MG radioresistant cells. Moreover, the results of in vitro irradiation assays revealed that ATRX expression was increased in U-251MG cells, while ATRX knockdown was associated with increased levels of radiosensitivity. CONCLUSIONS: High ATRX expression levels in primary GBM may contribute to high levels of radioresistance. Thus ATRX is a potential target for overcoming the radioresistance in GBM.

Glutamine Protects against Mouse Abdominal Aortic Aneurysm through Modulating VSMC Apoptosis and M1 Macrophage Activation.

Glutamine (Gln), known as the most abundant free amino acid, is widely spread in human body. In this study, we demonstrated the protective effects of glutamine against mouse abdominal aortic aneurysm (AAA) induced by both angiotensin II (AngII) and calcium phosphate (Ca3(PO4)2) in vivo, which was characterized with lower incidence of mouse AAA. Moreover, histomorphological staining visually presented more intact elastic fiber and less collagen deposition in abdominal aortas of mice treated by glutamine. Further, we found glutamine inhibited the excessive production of reactive oxide species (ROS), activity of matrix metalloproteinase (MMP), M1 macrophage activation, and apoptosis of vascular smooth muscle cells (VSMCs) in suprarenal abdominal aortas of mice, what's more, the high expressions of MMP-2 protein, MMP-9 protein, pro-apoptotic proteins, and IL-6 as well as TNF-α in protein and mRNA levels in cells treated by AngII were down-regulated by glutamine. Collectively, these results revealed that glutamine protected against mouse AAA through inhibiting apoptosis of VSMCs, M1 macrophage activation, oxidative stress, and extracellular matrix degradation.

De novo transcriptome assembly database for 100 tissues from each of seven species of domestic herbivore.

Domesticated herbivores are an important agricultural resource that play a critical role in global food security, particularly as they can adapt to varied environments, including marginal lands. An understanding of the molecular basis of their biology would contribute to better management and sustainable production. Thus, we conducted transcriptome sequencing of 100 to 105 tissues from two females of each of seven species of herbivore (cattle, sheep, goats, sika deer, horses, donkeys, and rabbits) including two breeds of sheep. The quality of raw and trimmed reads was assessed in terms of base quality, GC content, duplication sequence rate, overrepresented k-mers, and quality score distribution with FastQC. The high-quality filtered RNA-seq raw reads were deposited in a public database which provides approximately 54 billion high-quality paired-end sequencing reads in total, with an average mapping rate of ~93.92%. Transcriptome databases represent valuable resources that can be used to study patterns of gene expression, and pathways that are related to key biological processes, including important economic traits in herbivores.

Ultrahigh extinction ratio and a low power silicon thermo-optic switch.

The silicon thermo-optic switch (TOS) is one of the most fundamental and crucial blocks in large-scale silicon photonic integrated circuits (PICs). An energy-efficient silicon TOS with ultrahigh extinction ratio can effectively mitigate cross talk and reduce power consumption in optical systems. In this Letter, we demonstrate a silicon TOS based on cascading Mach-Zehnder interferometers (MZIs) with spiral thermo-optic phase shifters. The experimental results show that an ultrahigh extinction ratio of 58.8 dB is obtained, and the switching power consumption is as low as 2.32 mW/π without silicon air trench. The rise time and fall time of the silicon TOS are about 10.8 and 11.2 µs, respectively. Particularly, the figure of merit (FOM) has been improved compared with previously reported silicon TOS. The proposed silicon TOS may find potential applications in optical switch arrays, on-chip optical delay lines, etc.

Endobronchial ultrasound-guided transbronchial needle aspiration for diagnosing thoracic lesions: a retrospective cohort study.

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive technique for biopsy of lung, peri-pulmonary tissue and lymph nodes under real-time ultrasound-guided biopsy. It is used in the diagnosis and/or staging of benign and malignant pulmonary and non-pulmonary diseases. Our study is based on a large sample size, in a diversified population which provides a representative real-world cohort for analysis. Methods: Patients who underwent EBUS-TBNA procedure between September 2019 and August 2022 were included in this retrospective study. For cases diagnosed as benign and unclassified lesions by EBUS-TBNA, the final diagnosis was determined by further invasive surgery or a combination of therapy and clinical follow-up for at least 6 months. Results: A total of 618 patients were included in the study, including 182 females (29.4%) and 436 males (70.6%). The mean age of all patients was 61.9 ± 10.5 years. These patients were successfully punctured by EBUS-TBNA to obtain pathological results. The pathological diagnosis results of EBUS-TBNA were compared with the final clinical diagnosis results as follows: 133 cases (21.5%) of benign lesions and 485 cases (78.5%) of malignant lesions were finally diagnosed. Among them, the pathological diagnosis was obtained by EBUS-TBNA in 546 patients (88.3%) (464 malignant lesions and 82 benign conditions), while EBUS-TBNA was unable to define diagnosis in 72 patients (11.6%). 20/72 non-diagnostic EBUS-TBNA were true negative. The overall diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of EBUS-TBNA were 91.3%, 100%, 100%, 27.8%, and 91.6% [95% confidence interval (CI): 89.1-93.6%], respectively. In this study, only one case had active bleeding without serious complications during the EBUS-TBNA procedure. Conclusion: Given its low invasiveness, high diagnostic accuracy, and safety, EBUS-TBNA is worth promoting in thoracic lesions.

The effect of acute sleep deprivation on cortisol level: a systematic review and meta-analysis.

Acute sleep deprivation has aroused widespread concern and the relationship between acute sleep deprivation and cortisol levels is inconsistent. This study aimed to explore additional evidence and details. The PubMed, Web of Science, EMBASE, CLINAHL and Cochrane databases were searched for eligible studies published up to June 7, 2023. All analyses were performed using Review Manager 5.4 and Stata/SE 14.0. A total of 24 studies contributed to this meta-analysis. There was no significant difference in cortisol levels between participants with acute sleep deprivation and normal sleep in 21 crossover-designed studies (SMD = 0.18; 95% CI: -0.11, 0.45; p = 0.208) or 3 RCTs (SMD = 0.26; 95% CI: -0.22, 0.73; p = 0.286). Subgroup analysis revealed that the pooled effects were significant for studies using serum as the sample (SMD = 0.46; 95%CI: 0.11, 0.81; p = 0.011). Studies reporting cortisol levels in the morning, in the afternoon and in the evening did not show significant difference (p > 0.05). The pooled effects were statistically significant for studies with multiple measurements (SMD = 0.28; 95%CI: 0.03, 0.53; p = 0.027) but not for studies with single cortisol assessments (p = 0.777). When the serum was used as the test sample, the cortisol levels of individuals after acute sleep deprivation were higher than those with normal sleep.

MiR-4465-modified mesenchymal stem cell-derived small extracellular vesicles inhibit liver fibrosis development via targeting LOXL2 expression. / MiR-4465修饰的间质干细胞来源的小细胞外囊泡通过靶向LOXL2表达抑制肝纤维化的进展.

Liver fibrosis is a significant health burden, marked by the consistent deposition of collagen. Unfortunately, the currently available treatment approaches for this condition are far from optimal. Lysyl oxidase-like protein 2 (LOXL2) secreted by hepatic stellate cells (HSCs) is a crucial player in the cross-linking of matrix collagen and is a significant target for treating liver fibrosis. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) have been proposed as a potential treatment option for chronic liver disorders. Previous studies have found that MSC-sEV can be used for microRNA delivery into target cells or tissues. It is currently unclear whether microRNA-4465 (miR-4465) can target LOXL2 and inhibit HSC activation. Additionally, it is uncertain whether MSC-sEV can be utilized as a gene therapy vector to carry miR-4465 and effectively inhibit the progression of liver fibrosis. This study explored the effect of miR-4465-modified MSC-sEV (MSC-sEVmiR-4465) on LOXL2 expression and liver fibrosis development. The results showed that miR-4465 can bind specifically to the promoter of the LOXL2 gene in HSC. Moreover, MSC-sEVmiR-4465 inhibited HSC activation and collagen expression by downregulating LOXL2 expression in vitro. MSC-sEVmiR-4465 injection could reduce HSC activation and collagen deposition in the CCl4-induced mouse model. MSC-sEVmiR-4465 mediating via LOXL2 also hindered the migration and invasion of HepG2 cells. In conclusion, we found that MSC-sEV can deliver miR-4465 into HSC to alleviate liver fibrosis via altering LOXL2, which might provide a promising therapeutic strategy for liver diseases.

Effectiveness of gonadotropin-releasing hormone agonists for ovarian function suppression in premenopausal patients with hormone receptor-positive breast cancer: a retrospective single-center real-world study.

PURPOSE: This study evaluated the effectiveness of ovarian function suppression (OFS) of various gonadotropin-releasing hormone agonists (GnRHa) combined with aromatase inhibitors (AI) in premenopausal patients with hormone receptor-positive (HR-positive) breast cancer. Potential risk factors associated with insufficient OFS were analyzed. PATIENTS AND METHODS: Premenopausal HR-positive breast cancer patients who had received AI with GnRHa were studied retrospectively. Patients were divided into different groups according to monthly or trimonthly GnRHa schedules they received, and the effectiveness of OFS was compared between groups. Insufficient OFS was defined as at least one instance of estradiol ≥ 30 pg/ml. Patient data was gathered from medical records for this comparison. RESULTS: Of the 264 patients enrolled in this study, 117 were administered 3.6 mg of goserelin monthly (goserelin 1 M group), 63 received 3.75 mg of leuprorelin monthly (leuprorelin 1 M group) and 84 were given 11.25 mg of leuprorelin every three months (leuprorelin 3 M group). Overall, 7.20% experienced insufficient OFS. The incidence rates in the three GnRHa depot groups were 7.69%, 6.35%, and 7.14%, respectively, without a significant statistical difference (P = 0.900). Notably, younger patients exhibited a higher likelihood of insufficient OFS [OR = 0.900, 95%CI (0.824-0.982), P = 0.018]. CONCLUSION: Insufficient OFS remains a concern during GnRHa and AI treatment. The effectiveness of the three GnRHa depots commonly used in China seems comparable. Younger patients face a heightened risk of insufficient OFS.

Realizing Ultrathin LiSn Alloy Anode by Tuning the Wettability of Molten Li for High-Energy-Density Batteries.

Despite being heralded as the "holy grail" of anodes for their high theoretical specific capacity, lithium (Li) metal anodes still face practical challenges due to difficulties in fabricating ultrathin Li with controllable thickness and suppressing Li dendrites growth. Herein, we introduce a simple and cost-effective dip-coating method to fabricate ultrathin lithium-tin (LiSn) anode with adjustable thicknesses ranging from 4.5 to 45 µm. The in situ formation of Li22Sn5 alloy improves the wettability of the molten Li, enabling the casting of ultrathin Li metal layers on different substrates. More importantly, the abundant Li22Sn5 lithiophilic sites significantly lower the nucleation overpotential, inducing uniform Li deposition and accelerating the electrochemical reaction at the interface. As a result, the symmetric cell assembled with LiSn-Cu electrodes can cycle stably for more than 120 h with a charge/discharge depth of 50%, which is 1.5 times longer than the lifespan of the pure Li anode. In the full cells paired with NCM cathode, the discharge specific capacity is improved from 13.84 to 70.31 mA h g-1 with the LiSn-Cu anode at 8 C. The LiSn-Cu||NCM full cell realized a high energy density of 724.9 Wh kg-1 at the active material level with an N/P ratio of 1.4.

Increased TMEM166 Level in Patients with Postoperative Stroke after Carotid Endarterectomy.

Postoperative stroke is a challenging and potentially devastating complication after elective carotid endarterectomy (CEA). We previously demonstrated that transmembrane protein 166 (TMEM166) levels were directly related to neuronal damage after cerebral ischemia-reperfusion injury in rats. In this subsequent clinical study, we aimed to evaluate the prognostic value of TMEM166 in patients suffering from post-CEA strokes. Thirty-five patients undergoing uncomplicated elective CEA and 8 patients who suffered ischemic strokes after CEA were recruited. We evaluated the protein level and expression of TMEM166 in patients diagnosed with postoperative strokes and compared it to those in patients who underwent uncomplicated elective CEA. Blood samples and carotid artery plaques were collected and analyzed. High expressions of TMEM166 were detected by immunofluorescence staining and Western Blot in carotid artery plaques of all patients who underwent CEA. Furthermore, circulating TMEM166 concentrations were statistically higher in post-CEA stroke patients than in patients allocated to the control group. Mean plasma concentrations of inflammatory markers, including interleukin 6 (IL-6) and C-reactive protein (CRP), were also elevated in patients with postoperative strokes. Therefore, based on these findings, we hypothesize that elevated TMEM166 levels, accompanied by a strong inflammatory response, serve as a useful biomarker for risk assessment of postoperative stroke following CEA.

Trajectories of depressive symptom and its association with air pollution: evidence from the Mr. OS and Ms. OS Hong Kong cohort study.

BACKGROUND: Depression is a global health priority. Maintaining and delaying depressive symptoms in older adults is a key to healthy aging. This study aimed to identify depressive symptom trajectories, predictors and mortality, while also exploring the relationship between air quality and depressive symptoms in older adults in the Hong Kong community over 14 years. METHODS: This study is a longitudinal study in Hong Kong. The target population was community-dwelling older adults over age 65. Depressive symptoms were measured by the Geriatric Depression Scale (GDS-15). Group-based trajectory model was used to identify heterogeneity in longitudinal changes over 14 years and examine the associations between baseline variables and trajectories for different cohort members using multinomial logistic regression. The Kaplan-Meier method was employed to conduct survival analysis and explore the variations in survival probabilities over time among different trajectory group. Linear mixed model was used to explore the relationship between air quality and depressive symptoms. RESULTS: A total of 2828 older adults were included. Three different trajectories of depressive symptoms in older people were identified: relatively stable (15.4%), late increase (67.1%) and increase (17.5%). Female, more number of chronic diseases, poor cognitive function, and poor health-related quality of life (HRQOL) were significantly associated with other less favorable trajectories compared with participants with stable levels of depressive symptoms. The late increase group had a lower mortality rate than the relatively stable and increased groups. Lower baseline ambient air pollutant exposure to NO2 over 14 years was significantly associated with fewer depressive symptoms. CONCLUSIONS: In this study, we found that a late increase in depressive symptoms was the predominant trend in older Chinese people in Hong Kong. Poorer HRQOL was predictive of less favorable trajectories of depressive symptoms. Ambient air pollution was associated with depressive symptoms. This novel observation strengthens the epidemiological evidence of longitudinal changes in depressive symptoms and associations with late-life exposure to air pollution.

Multi-center study of COVID-19 infection in elderly patients with lymphoma: on behalf of Jiangsu Cooperative Lymphoma Group (JCLG).

Elderly patients with lymphoproliferative diseases (LPD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we retrospectively described the clinical features and outcomes of the first time infection of Omicron SARS-CoV-2 in 364 elderly patients with lymphoma enrolled in Jiangsu Cooperative Lymphoma Group (JCLG) between November 2022 and April 2023 in China. Median age was 69 years (range 60-92). 54.4% (198/364) of patients were confirmed as severe and critical COVID-19 infection. In univariable analysis, Age > 70 years (OR 1.88, p = 0.003), with multiple comorbidities (OR 1.41, p = 0.005), aggressive lymphoma (OR 2.33, p < 0.001), active disease (progressive or relapsed/refractory, OR 2.02, p < 0.001), and active anti-lymphoma therapy (OR 1.90, p < 0.001) were associated with severe COVID-19. Multiple (three or more) lines of previous anti-lymphoma therapy (OR 3.84, p = 0.021) remained an adverse factor for severe COVID-19 in multivariable analysis. Moreover, CD20 antibody (Rituximab or Obinutuzumab)-based treatments within the last 6 months was associated with severe COVID-19 in the entire cohort (OR 3.42, p < 0.001). Continuous BTK inhibitors might be protective effect on the outcome of COVID-19 infection (OR 0.44, p = 0.043) in the indolent lymphoma cohort. Overall, 7.7% (28/364) of the patients ceased, multiple lines of previous anti-lymphoma therapy (OR 3.46, p = 0.016) remained an adverse factor for mortality.

VSP-2 attenuates secretion of inflammatory cytokines induced by LPS in BV2 cells by mediating the PPARγ/NF-κB signaling pathway.

Neuroinflammation, characterized by microglial activation and the subsequent secretion of inflammatory cytokines, plays a pivotal role in neurodegenerative diseases and brain injuries, often leading to neuronal damage and death. Alleviating neuroinflammation has thus emerged as a promising strategy to protect neurons and ameliorate neurodegenerative disorders. While peroxisome proliferator-activated receptor gamma (PPARγ) agonists have demonstrated potential therapeutic actions on neuroinflammation, their prolonged use, such as with rosiglitazone, can lead to cardiac risks and lipid differentiation disorders. In this study, we investigated the effects of a newly synthesized PPARγ agonist, VSP-2, on secretion of inflammatory cytokines in BV2 cells. Treatment with VSP-2 significantly reduced the mRNA and protein levels of proinflammatory cytokines such as interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α). Furthermore, VSP-2 attenuated the phosphorylation of nuclear factor kappa B (NF-κB) (65 kD) and IκBα, as well as the nuclear translocation of NF-κB (65 kD). Additionally, the use of PPARγ small interfering RNA was able to attenuate the effects of VSP-2 on proinflammatory cytokines and the NF-κB pathway. In conclusion, our findings suggest that VSP-2 effectively suppressed the expressions of IL-1ß, IL-6, and TNF-α via the PPARγ/NF-κB signaling pathway. Given its potential therapeutic benefits, VSP-2 may emerge as a promising candidate for the treatment of neurodegenerative diseases or brain injuries associated with neuroinflammation.

Biological characteristics of molecular subtypes of ulcerative colitis characterized by ferroptosis and neutrophil infiltration.

Clinical ulcerative colitis (UC) is a heterogeneous condition. Moreover, medical interventions are nonspecific, and thus, treatment responses are inconsistent. The aim of this study was to explore the molecular subtypes and biological characteristics of UC based on ferroptosis and neutrophil gene sets. Multiple intestinal mucosa gene expression profiles of UC patients in the Gene Expression Omnibus (GEO) database were downloaded. Unsupervised clustering methods were used to identify potential molecular subtypes based on ferroptosis and neutrophil gene sets. Multiple immune infiltration algorithms were used to evaluate the biological characteristics of the molecular subtypes. Machine learning identifies hub genes for molecular subtypes and analyses their diagnostic efficacy for UC and predictive performance for drug therapy. The relevant conclusions were verified by clinical samples and animal experiments. Four molecular subtypes were identified according to the ferroptosis and neutrophil gene sets: neutrophil, ferroptosis, mixed and quiescent. The subtypes have different biological characteristics and immune infiltration levels. Multiple machine learning methods jointly identified four hub genes (FTH1, AQP9, STEAP3 and STEAP4). Receiver operating characteristic (ROC) curve analysis revealed that the four hub genes could be used as diagnostic markers for UC. The clinical response profile data of infliximab treatment patients showed that AQP9 and STEPA4 were reliable predictors of infliximab treatment response. In human samples the AQP9 and STEAP4 protein were shown to be increased in UC intestinal samples. In animal experiments, the ferroptosis and neutrophil phenotype were confirmed. Dual analysis of ferroptosis and neutrophil gene expression revealed four subgroups of UC patients. The molecular subtype-associated hub genes can be used as diagnostic markers for UC and predict infliximab treatment response.