Amide Proton Transfer-Weighted Imaging in Assessing the Aggressive and Proliferative Potential of Bladder Cancer.

BACKGROUND: Ki-67 and human epidermal growth factor receptor 2 (HER2) are known oncogenes involved in bladder cancer (BCa) patient risk stratification. Preoperative assessment of their expression level can assist in clinical treatment decision-making. Recently, amide proton transfer-weighted (APTw) MRI has shown promising potential in the diagnosis of several malignancies. However, few studies reported the value of APTw imaging in evaluating Ki-67 and HER2 status of BCa. PURPOSE: To investigate the feasibility of APTw MRI in assessing the aggressive and proliferative potential regarding the expression levels of Ki-67 and HER2 in BCa. STUDY TYPE: Retrospective. SUBJECTS: 114 patients (mean age, 64.78 ± 11.93 [SD] years; 97 men) were studied. FIELD STRENGTH/SEQUENCE: APTw MRI acquired by a three-dimensional fast-spin-echo sequence at 3.0 T MRI system. ASSESSMENT: Patient pathologic findings, included histologic grade and the expression status of Ki-67 and HER2, were reviewed by one uropathologist. The APTw values of BCa were independently measured by two radiologists and were compared between high-/low-tumor grade group, high-/low-Ki-67 expression group, and high-/low-HER2 expression group. STATISTICAL TESTS: The interclass correlation coefficient, independent sample t-test, Mann-Whitney U test, Spearman's rank correlation, and receiver operating characteristic curve (ROC) analysis were used. P < 0.05 was considered statistically significant. RESULTS: Significantly higher APTw values were found in high-grade BCa patients (7.72% vs. 4.29%, P < 0.001), high-Ki-67 expression BCa patients (8.40% vs. 3.25%, P < 0.001) and HER2 positive BCa patients (8.24% vs. 5.40%, P = 0.001). APTw values were positively correlated with Ki-67 (r = 0.769) and HER2 (r = 0. 356) expression status. The area under the ROC curve of the APTw values for detecting Ki-67 and HER2 expression status were 0.883 (95% CI: 0.790-0.945) and 0.713 (95% CI: 0.592-0.816), respectively. DATA CONCLUSIONS: APTw MRI is a potential method to assess the biological and proliferation potential of BCa. TECHNICAL EFFICACY: Stage 2.

Characteristics and comparative study of medicinal materials between China and India based on data mining from literatures.

ETHNOPHARMACOLOGICAL RELEVANCE: China and India have unique traditional medicine systems with vast territory and rich medical resources. Traditional medicines in China include traditional Chinese medicine, Tibetan medicine, Mongolian medicine, Uyghur medicine, Dai medicine, etc. In the third national survey of Chinese medicine resources, 12694 medicinal materials were identified. Traditional medicines in India include Ayurveda, Unani, Siddha, Homoeopathy, etc. There are 7263 medicinal materials in India. AIM OF THE STUDY: To reveal the characteristics of medicinal materials between China and India respectively, and to compare the similarities and differences in terms of properties, tastes, medicinal parts and therapeutic uses and to promote the exchange of traditional medicine between China and India and the international trade of traditional medicine industry. METHODS: The information of medicinal materials between China and India was extracted from The Chinese Traditional Medicine Resource Records and Pharmacopoeia of the People's Republic of China, as well as from 71 Indian herbal monographs. The information of each medicinal material, such as types, families, genera, properties, distribution, medicinal parts, efficacy, therapeutic uses, dosage form and dosage, was recorded in Excel for statistical analysis and visual comparison. RESULTS: A total of 12694 medicinal materials in China and 5362 medicinal materials in India were identified. The medicinal materials were mostly distributed in Southwest China and northern India. Plants were the main sources of medicinal materials. The common medicinal parts in China were whole medicinal materials, roots and rhizomes, and India used more renewable fruits, seeds and leaves. They are commonly used in the treatment of digestive system diseases. There were 1048 medicinal materials used by both China and India, which were distributed in 188 families and 685 genera. The Chinese and Indian pharmacopoeias had a total of 80 species of medicinal materials used by both China and India. CONCLUSIONS: The characteristics of medicinal materials between China and India were somewhat different, which was conducive to provide a reference basis for traditional medicine in China or India to increase the medicinal parts and indications when using a certain medicinal material, as well as to expand the source of medicine and introduce new resources. However, there were certain similarities and shared medicinal materials, which can tap the potential of bilateral trade of medicinal materials between China and India, so as to promote the medical cultural exchange and economic and trade cooperation between the two countries.

Phellodendron chinense C.K.Schneid: an in vitro study on its anti-Helicobacter pylori effect.

ETHNOPHARMACOLOGICAL RELEVANCE: Phellodendron chinense C.K.Schneid(P. chinense Schneid) is known in TCM as Huang Bo, is traditionally used to support gastrointestinal function and alleviate stomach-related ailments, including gastric ulcer bleeding and symptoms of gastroesophageal reflux disease. Helicobacter pylori (H. pylori) is classified by the WHO as a Group 1 carcinogen. However, the specific activity and mechanism of action of P. chinense Schneid against H. pylori infection remain unclear. It has been noted that Huangjiu processing may alter the bitter and cold properties of P. chinense Schneid, but its effect on antimicrobial activity requires further investigation. Additionally, it remains uncertain whether berberine is the sole antimicrobial active component of P. chinense Schneid. AIM OF STUDY: This study aims to elucidate the anti-H. pylori infection activity of P. chinense Schneid, along with its mechanism of action and key antimicrobial active components. MATERIALS AND METHODS: Phytochemical analysis was carried out by UPLC-MS/MS. HPLC was employed to quantify the berberine content of the extracts. Antimicrobial activity was assessed using the micro broth dilution method. Morphology was observed using SEM. The impact on urease activity was analyzed through in vitro urease enzyme kinetics. RT-qPCR was employed to detect the expression of virulence genes, including adhesin, flagellum, urease, and cytotoxin-related genes. The adhesion effect was evaluated by immunofluorescence staining and agar culture. RESULTS: P. chinense Schneid exhibited strong antimicrobial activity against both antibiotic-sensitive and resistant H. pylori strains, with MIC ranging from 40-160 µg/mL. Combination with amoxicillin, metronidazole, levofloxacin, and clarithromycin did not result in antagonistic effects. P. chinense Schneid induced alterations in bacterial morphology and structure, downregulated the expression of various virulence genes, and inhibited urease enzyme activity. In co-infection systems, P. chinense Schneid significantly attenuated H. pylori adhesion and urease relative content, thereby mitigating cellular damage caused by infection. Huangjiu processing enhanced the anti-H. pylori activity of P. chinense Schneid. Besides berberine, P. chinense Schneid contained seven other components with anti-H. pylori activity, with palmatine exhibiting the strongest activity, followed by jatrorrhizine. CONCLUSIONS: This study sheds light on the potential therapeutic mechanisms of P. chinense Schneid against H. pylori infection, demonstrating its capacity to disrupt bacterial structure, inhibit urease activity, suppress virulence gene transcription, inhibit adhesion, and protect host cells. The anti-H. pylori activity of P. chinense Schneid was potentiated by Huangjiu processing, and additional components beyond berberine were identified as possessing strong anti-H. pylori activity. Notably, jatrorrhizine, a core component of P. chinense Schneid, exhibited significant anti-H. pylori activity, marking a groundbreaking discovery.

Label-free Raman spectroscopy reveals tumor microenvironmental changes induced by intermittent fasting for the prevention of breast cancer in animal model.

The development of tools that can provide a holistic picture of the evolution of the tumor microenvironment in response to intermittent fasting on the prevention of breast cancer is highly desirable. Here, we show, for the first time, the use of label-free Raman spectroscopy to reveal biomolecular alterations induced by intermittent fasting in the tumor microenvironment of breast cancer using a dimethyl-benzanthracene induced rat model. To quantify biomolecular alterations in the tumor microenvironment, chemometric analysis of Raman spectra obtained from untreated and treated tumors was performed using multivariate curve resolution-alternative least squares and support vector machines. Raman measurements revealed remarkable and robust differences in lipid, protein, and glycogen content prior to morphological manifestations in a dynamically changing tumor microenvironment, consistent with the proteomic changes observed by quantitative mass spectrometry. Taken together with its non-invasive nature, this research provides prospective evidence for the clinical translation of Raman spectroscopy to identify biomolecular variations in the microenvironment induced by intermittent fasting for the prevention of breast cancer, providing new perspectives on the specific molecular effects in the tumorigenesis of breast cancer.

ABA-mediated regulation of rice grain quality and seed dormancy via the NF-YB1-SLRL2-bHLH144 Module.

Abscisic acid (ABA) plays a crucial role in promoting plant stress resistance and seed dormancy. However, how ABA regulates rice quality remains unclear. This study identifies a key transcription factor SLR1-like2 (SLRL2), which mediates the ABA-regulated amylose content (AC) of rice. Mechanistically, SLRL2 interacts with NF-YB1 to co-regulate Wx, a determinant of AC and rice quality. In contrast to SLR1, SLRL2 is ABA inducible but insensitive to GA. In addition, SLRL2 exhibits DNA-binding activity and directly regulates the expression of Wx, bHLH144 and MFT2. SLRL2 competes with NF-YC12 for interaction with NF-YB1. NF-YB1 also directly represses SLRL2 transcription. Genetic validation supports that SLRL2 functions downstream of NF-YB1 and bHLH144 in regulating rice AC. Thus, an NF-YB1-SLRL2-bHLH144 regulatory module is successfully revealed. Furthermore, SLRL2 regulates rice dormancy by modulating the expression of MFT2. In conclusion, this study revealed an ABA-responsive regulatory cascade that functions in both rice quality and seed dormancy.

A prospective randomized controlled clinical trial investigating the efficacy of low-dose olanzapine in preventing nausea and vomiting associated with oxaliplatin-based and irinotecan-based chemotherapy.

OBJECTIVE: The aim of this study is to assess the clinical efficacy of a 5 mg dosage of olanzapine in preventing chemotherapy-induced nausea and vomiting (CINV) associated with moderately emetogenic chemotherapy (MEC) among female patients diagnosed with gastrointestinal tract tumors. METHODS: Patients undergoing the oxaliplatin/irinotecan chemotherapy regimen were enrolled in this prospective controlled study. The olanzapine group received a 5 mg dosage of olanzapine along with palonosetron and dexamethasone, while the control group received a standard two-combination regimen consisting of dexamethasone and palonosetron. The primary endpoints included the total protection (TP) rates for the entire age group and the subgroup aged 60 years and above. Secondary endpoints encompassed the total protection rates during the acute and delayed phases within the two age brackets, as well as the total control (TC) rates and complete remission (CR) rates across all three phases (total, acute, and delayed). Additionally, the study involved the assessment of quality of life and the collection of adverse events associated with the interventions. RESULTS: 1) Regarding the primary endpoint, the total phase TP rates within both the entire age group and the age group exceeding 60 years demonstrated superiority in the olanzapine group when compared to the control group (66.7% vs 37.25%, P = 0.003; 68.8% vs 44.4%, P = 0.044). 2) In terms of secondary endpoints, the olanzapine group exhibited superior acute phase TP rates in both age brackets when compared to the control group (P < 0.05). The olanzapine group also demonstrated higher delayed-phase TP rates, TC rates across all three phases, and CR rates within the two age brackets, although the differences were not statistically significant (P > 0.05). Furthermore, the quality of life in the olanzapine group surpassed that of the control group for both age brackets (P < 0.05), characterized by enhanced appetite and a higher incidence of drowsiness in the patients treated with olanzapine when compared to those in the control group (P < 0.05). CONCLUSION: Olanzapine can enhance CINV induced by MEC regimen in female patients across all age groups, including the elderly, and therefore improve the quality of life for these patients. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/index.html , identifier: ChiCTR20000368269, 25/08/2020.

The role of the immunoproteasome in cardiovascular disease.

The ubiquitinproteasome system (UPS) is the main mechanism responsible for the intracellular degradation of misfolded or damaged proteins. Under inflammatory conditions, the immunoproteasome, an isoform of the proteasome, can be induced, enhancing the antigen-presenting function of the UPS. Furthermore, the immunoproteasome also serves nonimmune functions, such as maintaining protein homeostasis and regulating signalling pathways, and is involved in the pathophysiological processes of various cardiovascular diseases (CVDs). This review aims to provide a comprehensive summary of the current research on the involvement of the immunoproteasome in cardiovascular diseases, with the ultimate goal of identifying novel strategies for the treatment of these conditions.

Current applications of intestinal organoids: a review.

In the past decade, intestinal organoid technology has paved the way for reproducing tissue or organ morphogenesis during intestinal physiological processes in vitro and studying the pathogenesis of various intestinal diseases. Intestinal organoids are favored in drug screening due to their ability for high-throughput in vitro cultivation and their closer resemblance to patient genetic characteristics. Furthermore, as disease models, intestinal organoids find wide applications in screening diagnostic markers, identifying therapeutic targets, and exploring epigenetic mechanisms of diseases. Additionally, as a transplantable cellular system, organoids have played a significant role in the reconstruction of damaged epithelium in conditions such as ulcerative colitis and short bowel syndrome, as well as in intestinal material exchange and metabolic function restoration. The rise of interdisciplinary approaches, including organoid-on-chip technology, genome editing techniques, and microfluidics, has greatly accelerated the development of organoids. In this review, VOSviewer software is used to visualize hot co-cited journal and keywords trends of intestinal organoid firstly. Subsequently, we have summarized the current applications of intestinal organoid technology in disease modeling, drug screening, and regenerative medicine. This will deepen our understanding of intestinal organoids and further explore the physiological mechanisms of the intestine and drug development for intestinal diseases.

Comparison of allo-SCT, auto-SCT and chemotherapy for the treatment of patients with low- or intermediate-risk acute myeloid leukemia: a network meta-analysis.

BACKGROUND: The therapeutic status of allogeneic stem cell transplantation (allo-SCT) as a post-remission treatment for patients with high-risk acute myeloid leukemia (AML) was well-accepted. However, the optimal treatment for patients with low/favorable- or intermediate-risk AML who achieve complete remission has remained controversial. Therefore, we conducted a network meta-analysis to discuss this disputed problem. METHODS: We compared the effects of treatment strategies including allo-SCT, autologous stem cell transplantation (auto-SCT) and consolidation chemotherapy (CT) for patients with low/favorable- or intermediate-risk AML. The pooled HRs and 95% CIs for overall survival and disease-free survival were estimated with Stata12 and R software. Thirty clinical studies with 6682 patients were included in the meta-analysis. RESULTS: The results indicated that the treatment outcome of allo-SCT was the best, followed by auto-SCT, and CT was likely the worst in the total AML patients. In patients with low/favorable-risk AML, the treatment outcome of auto-SCT was likely ranked first, followed by allo-SCT, and CT was the worst. In patients with intermediate-risk AML, the treatment outcome of haploidentical stem cell transplantation (haplo-SCT) was the best, followed by allo-SCT (excluding haplo-SCT), and auto-SCT and CT were the worst. However, the median age of the haplo-SCT group was much younger than that of the control group, which may be one of the reasons for the better prognosis of the haplo-SCT group. CONCLUSIONS: Patients with low/favorable- and intermediate-risk (non-high-risk) AML should prioritize allo-SCT if they are eligible for transplantation, and auto-SCT is optional. However, in the subgroup analysis, auto-SCT was the optimal treatment choice for patients with low/favorable-risk AML, and allo-SCT was the priority selection for patients with intermediate-risk AML, especially young patients. These findings could provide references for clinical practice.

Astragaloside IV alleviates renal fibrosis by inhibiting renal tubular epithelial cell pyroptosis induced by urotensin II through regulating the cAMP/PKA signaling pathway.

OBJECTIVE: To explore the molecular mechanism of Astragaloside IV (AS-IV) in alleviating renal fibrosis by inhibiting Urotensin II-induced pyroptosis and epithelial-mesenchymal transition of renal tubular epithelial cells. METHODS: Forty SD rats were randomly divided into control group without operation: gavage with 5ml/kg/d water for injection and UUO model group: gavage with 5ml/kg/d water for injection; UUO+ AS-IV group (gavage with AS-IV 20mg/kg/d; and UUO+ losartan potassium group (gavage with losartan potassium 10.3mg/kg/d, with 10 rats in each group. After 2 weeks, Kidney pathology, serum Urotensin II, and cAMP concentration were detected, and the expressions of NLRP3, GSDMD-N, Caspase-1, and IL-1ß were detected by immunohistochemistry. Rat renal tubular epithelial cells were cultured in vitro, and different concentrations of Urotensin II were used to intervene for 24h and 48h. Cell proliferation activity was detected using the CCK8 assay. Suitable concentrations of Urotensin II and intervention time were selected, and Urotensin II receptor antagonist (SB-611812), inhibitor of PKA(H-89), and AS-IV (15ug/ml) were simultaneously administered. After 24 hours, cells and cell supernatants from each group were collected. The cAMP concentration was detected using the ELISA kit, and the expression of PKA, α-SMA, FN, IL-1ß, NLRP3, GSDMD-N, and Caspase-1 was detected using cell immunofluorescence, Western blotting, and RT-PCR. RESULTS: Renal tissue of UUO rats showed renal interstitial infiltration, tubule dilation and atrophy, renal interstitial collagen fiber hyperplasia, and serum Urotensin II and cAMP concentrations were significantly higher than those in the sham operation group (p <0.05). AS-IV and losartan potassium intervention could alleviate renal pathological changes, and decrease serum Urotensin II, cAMP concentration levels, and the expressions of NLRP3, GSDMD-N, Caspase-1, and IL-1ß in renal tissues (p <0.05). Urotensin II at a concentration of 10-8 mol/L could lead to the decrease of cell proliferation, (p<0.05). Compared with the normal group, the cAMP level and the PKA expression were significantly increased (p<0.05). After intervention with AS-IV and Urotensin II receptor antagonist, the cAMP level and the expression of PKA were remarkably decreased (p<0.05). Compared with the normal group, the expression of IL-1ß, NLRP3, GSDMD-N, and Caspase-1 in the Urotensin II group was increased (p<0.05), which decreased in the AS-IV and H-89 groups. CONCLUSION: AS-IV can alleviate renal fibrosis by inhibiting Urotensin II-induced pyroptosis of renal tubular epithelial cells by regulating the cAMP/PKA signaling pathway.

In-depth characterization of cycloartane triterpenoids and discovery of species-specific markers from three Cimicifuga species guided by a strategy that integrates in-source fragment elimination, diagnostic ion recognition, and feature-based molecular networking.

Characterization studies of the plant metabolome are crucial for revealing plant physiology, developing functional foods, and controlling quality. Mass spectrometry-based metabolite profiling allows unprecedented qualitative coverage of complex biological extract composition. However, the electrospray ionization used in metabolite profiling generates multiple artifactual signals for a single analyte, which makes it challenging to filter out redundant signals and organize the signals corresponding to abundant constituents. This study proposed a strategy integrating in-source fragments elimination, diagnostic ions recognition, and feature-based molecular networking (ISFE-DIR-FBMN) to simultaneously characterize cycloartane triterpenoids (CTs) from three medicinal Cimicifuga species. The results showed that 63.1 % of the measured ions were redundant. A total of 184 CTs were annotated, with 27.1 % being reported for the first time. It presents a promising approach to assess the composition of natural extracts, thus facilitating new ingredient registrations or natural-extracts-based drug discovery campaigns. Besides, chemometrics analysis of the three Cimicifuga species identified 32 species-specific markers, highlighting significant differences among them. The valuable information can enhance the sustainable utilization and further development of Cimicifuga resources. The codes involved in ISFE-DIR-FBMN are freely available on GitHub (https://github.com/LHJ-Group/ISFE-DIR-FBMN.git).

ß-Glucan Subverts the Function of Myeloid Cells in Neonates.

ß-Glucan is the main component of the cell wall of pathogen-associated molecular patterns (PAMPs) including various yeast, fungi, or certain bacteria. Previous reports demonstrated that ß-glucan was widely investigated as a potent immunomodulators to stimulate innate and adaptive immune responses, which indicated that it could be recommended as an effective adjuvant in immunotherapy. However, the detailed effects of ß-glucan on neonatal immunity are still largely unknown. Here, we found that ß-glucan did not affect the frequencies and numbers of myeloid cells in the spleen and bone marrow from neonates. Functional assay revealed that ß-glucan from neonates compromised the immunosuppressive function of immature myeloid cells, which were myeloid-derived suppressor cells (MDSCs). Flow cytometry or gene expression analysis revealed that ß-glucan-derived polymorphonuclear (PMN)-MDSCs produced lower level of reactive oxygen species (ROS) and arginase-1 (Arg1) in neonatal mice. Furthermore, ß-glucan administration significantly decreased the frequency and ROS level of PMN-MDSCs in vitro. These observations suggest that ß-glucan facilitates the maturation of myeloid cells in early life, which may contribute to its beneficial effects against immune disorders later in life.

Rational construction of genome-minimized Streptomyces host for the expression of secondary metabolite gene clusters.

Streptomyces offer a wealth of naturally occurring compounds with diverse structures, many of which possess significant pharmaceutical values. However, new product exploration and increased yield of specific compounds in Streptomyces have been technically challenging due to their slow growth rate, complex culture conditions and intricate genetic backgrounds. In this study, we screened dozens of Streptomyces strains inhabiting in a plant rhizosphere for fast-growing candidates, and further employed CRISPR/Cas-based engineering techniques for stepwise refinement of a particular strain, Streptomyces sp. A-14 that harbors a 7.47 Mb genome. After strategic removal of nonessential genomic regions and most gene clusters, we reduced its genome size to 6.13 Mb, while preserving its growth rate to the greatest extent. We further demonstrated that cleaner metabolic background of this engineered strain was well suited for the expression and characterization of heterologous gene clusters, including the biosynthetic pathways of actinorhodin and polycyclic tetramate macrolactams. Moreover, this streamlined genome is anticipated to facilitate directing the metabolic flux towards the production of desired compounds and increasing their yields.

The Barthel Index predicts surgical textbook outcomes following hepatectomy for elderly patients with hepatocellular carcinoma: A multicenter cohort study.

BACKGROUND: The burgeoning demand for hepatectomy in elderly patients with hepatocellular carcinoma (HCC) necessitates improved perioperative care. Geriatric populations frequently experience functional decline and frailty, predisposing them to adverse postoperative outcomes. The Barthel Index serves as a reliable measure for assessing functional capacity, and this study evaluates its impact on surgical textbook outcomes (TOs) in elderly HCC patients. METHODS: A multicenter retrospective cohort study analyzed elderly patients (≥70 years) following hepatectomy for HCC between 2013 and 2021. Utilizing a Barthel Index cut-off value of 85, patients were divided into two groups: with and without preoperative functional decline and frailty. The primary outcome was the rate of TO, encompassing seven criteria. TO rates were compared between groups, and multivariate logistic regression analyses identified independent risks for achieving TOs. RESULTS: Of 497 elderly patients, 157 (31.6 â€‹%) exhibited preoperative functional decline and frailty (Barthel Index score <85). The overall TO rate was 58.6 â€‹%. Patients with preoperative Barthel Index score <85 had significantly lower TO rates compared to patients with score ≥85 (29.3 â€‹% vs. 72.1 â€‹%, P â€‹< â€‹0.001). Multivariate analysis revealed preoperative Barthel Index score <85 as an independent risk for achieving TO (odds ratio 3.413, 95 â€‹% confidence interval 1.879-6.198, P â€‹< â€‹0.001). Comparable results were observed in the subgroups of patients undergoing open and laparoscopic hepatectomy. CONCLUSION: Preoperative Barthel Index-based assessment of functional decline and frailty significantly predicts TOs following hepatectomy in elderly HCC patients, enabling identification of high-risk patients and informing preoperative management and postoperative care within geriatric oncology.

Cobalt based bimetallic catalysts for heterogeneous electro-Fenton adapting to vary pH for HEDP and MIT degradation.

Most of the materials studied as catalysts in the electro-Fenton system are variants of iron oxide or iron hydroxide. However, iron-based catalysts often exhibit weak catalytic capabilities under neutral and alkaline conditions. In this work, we synthesized three cobalt based bimetallic oxides, Co2CuOx, Co2AlOx, and Co2NiOx, using hydrothermal method and evaluated them as catalysts for the heterogeneous electro-Fenton system to remove 1-hydroxyethylidene-1,1-diphosphonic acid (HEDP) and Methylisothiazolinone [2-methyl-4-isothiazolin-3-one] (MIT). Co2NiOx has the highest catalytic degradation activity for HEDP, and Co2CuOx has the best catalytic degradation effect for MIT. Based on characterization results of the catalysts, the reasons for the differences in the pollutant removal efficiency were analysed, and the optimal pH for the three cobalt based oxides to remove HEDP and MIT was investigated. The results showed that the optimal pH values of the three cobalt based bimetallic oxides are not only influenced by the second metal type, but also by the properties of pollutants. Therefore, suitable cobalt based catalysts can be selected based on the different properties of pollutants, or the composition of cobalt based catalysts can be adjusted to meet the different pH requirements of target wastewater. The three cobalt based bimetallic oxides exhibited good degradation of HEDP and MIT under neutral conditions, which to some extent solved the problem of narrow pH range in the practical application of the electro-Fenton process.

PRDX1 Interfering Peptide Disrupts Amino Acids 70-90 of PRDX1 to Inhibit the TLR4/NF-κB Signaling Pathway and Attenuate Neuroinflammation and Ischemic Brain Injury.

Ischemic stroke ranks among the leading causes of death and disability in humans and is accompanied by motor and cognitive impairment. However, the precise mechanisms underlying injury after stroke and effective treatment strategies require further investigation. Peroxiredoxin-1 (PRDX1) triggers an extensive inflammatory cascade that plays a pivotal role in the pathology of ischemic stroke, resulting in severe brain damage from activated microglia. In the present study, we used molecular dynamics simulation and nuclear magnetic resonance to detect the interaction between PRDX1 and a specific interfering peptide. We used behavioral, morphological, and molecular experimental methods to demonstrate the effect of PRDX1-peptide on cerebral ischemia-reperfusion (I/R) in mice and to investigate the related mechanism. We found that PRDX1-peptide bound specifically to PRDX1 and improved motor and cognitive functions in I/R mice. In addition, pretreatment with PRDX1-peptide reduced the infarct area and decreased the number of apoptotic cells in the penumbra. Furthermore, PRDX1-peptide inhibited microglial activation and downregulated proinflammatory cytokines including IL-1ß, IL-6, and TNF-α through inhibition of the TLR4/NF-κB signaling pathway, thereby attenuating ischemic brain injury. Our findings clarify the precise mechanism underlying PRDX1-induced inflammation after ischemic stroke and suggest that the PRDX1-peptide can significantly alleviate the postischemic inflammatory response by interfering with PRDX1 amino acids 70-90 and thereby inhibiting the TLR4/NF-κB signaling pathway. Our study provides a theoretical basis for a new therapeutic strategy to treat ischemic stroke.

Structural characterization and immunostimulant activities of polysaccharides fractionated by gradient ethanol precipitation method from Panax ginseng C. A. Meyer.

Panax ginseng C. A. Meyer is a dual-purpose plant for medicine and food, its polysaccharide is considered as an immune enhancer. Four polysaccharides, WGP-20-F, WGP-40-F, WGP-60-F and WGP-80-F were obtained from ginseng via water extraction and gradient ethanol precipitation with different molecular weights (Mw) of 1.720 × 106, 1.434 × 106, 4.225 × 104 and 1.520 × 104 Da, respectively. WGP-20-F and WGP-40-F which with higher Mw and a triple-helix structure are glucans composed of 4-ɑ-Glcp, do not show remarkable immunoregulatory effects. WGP-60-F and WGP-80-F are heteropolysaccharides mainly composed of 4-ɑ-Glcp and also contain t-ɑ-Araf, 5-ɑ-Araf and 3,5-ɑ-Araf. They are spherical branched conformations without a triple-helix structure and can effectively increase the index of immune organs, lymphocyte proliferation, activate macrophages to regulate the immune system in mice and further enhance immune functions by improving delayed-type hypersensitivity reaction and antibody response. These results indicated that WGP-60-F and WGP-80-F could be used as potential immune enhancers, and gradient ethanol precipitation can be applied for the preparation of ginseng bioactive polysaccharide.

Identification of SOCS3 and PTGS2 as new biomarkers for the diagnosis of gout by cross-species comprehensive analysis.

Background: Gout is the most common inflammatory arthritis in adults. Gout is an arthritic disease caused by the deposition of monosodium urate crystal (MSU) in the joints, which can lead to acute inflammation and damage adjacent tissue. Hyperuricemia is the main risk factor for MSU crystal deposition and gout. With the increasing burden of gout disease, the identification of potential biomarkers and novel targets for diagnosis is urgently needed. Methods: For the analysis of this subject paper, we downloaded the human gout data set GSE160170 and the gout mouse model data set GSE190138 from the GEO database. To obtain the differentially expressed genes (DEGs), we intersected the two data sets. Using the cytohubba algorithm, we identified the key genes and enriched them through GO and KEGG. The gene expression trends of three subgroups (normal control group, intermittent gout group and acute gout attack group) were analyzed by Series Test of Cluster (STC) analysis, and the key genes were screened out, and the diagnostic effect was verified by ROC curve. The expression of key genes in dorsal root nerve and spinal cord of gout mice was analyzed. Finally, the clinical samples of normal control group, hyperuricemia group, intermittent gout group and acute gout attack group were collected, and the expression of key genes at protein level was verified by ELISA. Result: We obtained 59 co-upregulated and 28 co-downregulated genes by comparing the DEGs between gout mouse model data set and human gout data set. 7 hub DEGs(IL1B, IL10, NLRP3, SOCS3, PTGS2) were screened out via Cytohubba algorithm. The results of both GO and KEGG enrichment analyses indicate that 7 hub genes play a significant role in regulating the inflammatory response, cytokine production in immune response, and the TNF signaling pathway. The most representative hub genes SOCS3 and PTGS2 were screened out by Series Test of Cluster, and ROC analysis results showed the AUC values were both up to 1.000. In addition, we found that PTGS2 expression was significantly elevated in the dorsal root ganglia and spinal cord in monosodium urate(MSU)-induced gout mouse model. The ELISA results revealed that the expression of SOCS3 and PTGS2 was notably higher in the acute gout attack and intermittent gout groups compared to the normal control group. This difference was statistically significant, indicating a clear distinction between the groups. Conclusion: Through cross-species comprehensive analysis and experimental verification, SOCS3 and PTGS2 were proved to be new biomarkers for diagnosing gout and predicting disease progression.

Correlation between Mitochondria-Associated Endoplasmic Reticulum Membrane-Related Genes and Cellular Senescence-Related Genes in Osteoarthritis.

BACKGROUND: The role of mitochondria-associated endoplasmic reticulum membrane (MAM) formation in the development of osteoarthritis (OA) is yet unclear. METHODS: A mix of bioinformatics methods and in vitro experimental methodologies was used to study and corroborate the role of MAM-related genes and cellular senescence-related genes in the development of OA. The Gene Expression Omnibus database was used to obtain the microarray information that is relevant to the OA. Several bioinformatic methods were employed to carry out function enrichment analysis and protein-protein correlation analysis, build the correlation regulatory network, and investigate potential relationships between MAM-related genes and cellular senescence-related genes in OA. These methods also served to identify the MAM-related and OA-related genes (MAM-OARGs). RESULTS: For the additional functional enrichment analysis, a total of 13 MAM-OARGs were detected. The correlation regulatory network was also created. Hub MAM-OARGs were shown to have a strong correlation with genes relevant to cellular senescence in OA. Results of in vitro experiments further demonstrated a positive correlation between MAM-OARGs (PTPN1 and ITPR1) and cellular senescence-related and OA-related genes. CONCLUSIONS: As a result, our findings can offer new insights into the investigations of MAM-related genes and cellular senescence-related genes, which could be linked to the OA as well as brand-new potential treatment targets.