Relationship of Retinal Nerve Fiber Layer Thickness and Retinal Vessel Calibers with Cognitive Impairment in the Asymptomatic Polyvascular Abnormalities Population.

Objective: Cognitive impairment (CI) in older individuals has a high morbidity rate worldwide, with poor diagnostic methods and susceptible population identification. This study aimed to investigate the relationship between different retinal metrics and CI in a particular population, emphasizing polyvascular status. Methods: We collected information from the Asymptomatic Polyvascular Abnormalities Community Study on retinal vessel calibers, retinal nerve fiber layer (RNFL) thickness, and cognitive function of 3,785 participants, aged 40 years or older. Logistic regression was used to analyze the relationship between retinal metrics and cognitive function. Subgroups stratified by different vascular statuses were also analyzed. Results: RNFL thickness was significantly thinner in the CI group (odds ratio: 0.973, 95% confidence interval: 0.953-0.994). In the subgroup analysis, the difference still existed in the non-intracranial arterial stenosis, non-extracranial carotid arterial stenosis, and peripheral arterial disease subgroups ( P < 0.05). Conclusion: A thin RNFL is associated with CI, especially in people with non-large vessel stenosis. The underlying small vessel change in RNFL and CI should be investigated in the future.

Advances in zeolitic-imidazolate-framework-based catalysts for photo-/electrocatalytic water splitting, CO2 reduction and N2 reduction applications.

Harnessing electrical or solar energy for the renewable production of value-added fuels and chemicals through catalytic processes (such as photocatalysis and electrocatalysis) is promising to achieve the goal of carbon neutrality. Owing to the large number of highly accessible active sites, highly porous structure, and charge separation/transfer ability, as well as excellent stability against chemical and electrochemical corrosion, zeolite imidazolate framework (ZIF)-based catalysts have attracted significant attention. Strategic construction of heterojunctions, and alteration of the metal node and the organic ligand of the ZIFs effectively regulate the binding energy of intermediates and the reaction energy barriers that allow tunable catalytic activity and selectivity of a product during reaction. Focusing on the currently existing critical issues of insufficient kinetics for electron transport and selective generation of ideal products, this review starts from the characteristics and physiochemical advantages of ZIFs in catalytic applications, then introduces promising regulatory approaches for advancing the kinetic process in emerging CO2 reduction, water splitting and N2 reduction applications, before proposing perspective modification directions.

Minimally invasive surgical removal of bilateral impacted mandibular supernumerary teeth using 3D surgical guide template: a case report.

Impacted supernumerary teeth are defined as the presence of one or more teeth in a patient's upper and lower jaws in addition to the normal number of teeth in the dental arch. It has an incidence rate of approximately 1%-14% and more frequently occurs in males than females, may be single or multiple, unilateral or bilateral, erupted or impacted. In this article, we describe the case of a patient with two supernumerary teeth between the roots of the mandibular second premolar and the first molar, which influenced the effectiveness of the first orthodontic treatment. The special anatomical position of the complex supernumerary teeth made tooth extraction challenging. Given the higher risk status of surgery, we implemented a novel tooth extracting technique for this patient. Thus, in this study, we describe a case of minimally invasive extraction of bilateral mandibular impacted supernumerary teeth using a digital 3D positioning guide plate.

The Potential Transcriptomic and Metabolomic Mechanisms of ATO and ATRA in Treatment of FLT3-ITD Acute Myeloid Leukemia.

BACKGROUND: Acute myeloid leukemia (AML) with Fms-like tyrosine kinase 3 gene internal tandem duplication (FLT3-ITD) mutations has a poor prognosis. The combination of arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) has a synergistic killing effect on leukemia cells with FLT3-ITD mutation. However, the mechanism, especially the changes of gene expression and metabolic activity remain unclear. Here we explore the transcriptome and metabolomics changes of FLT3-ITD AML cells treated with ATO/ATRA. METHODS: RNA-seq was used to identify differential expressed genes (DEGs), and ultra-high performance liquid chromatography-quadrupole electrostatic field orbital trap mass spectrometry (UHPLC-QE-MS) nontargeted metabolomics method was used to screen out the differential metabolites in FLT3-ITD mutant cell lines treated with ATRA and ATO. KEGG pathway database was utilized for pathway exploration and Seahorse XF24 was used to detect extracellular acidification rate (ECAR). Metabolic polymerase chain reaction (PCR) array and real-time quantitative PCR (RT-qPCR) were used to detect mRNA levels of key metabolic genes of glycolysis and fatty acid after drug treatment. RESULTS: A total of 3873 DEGs were identified and enriched in 281 Gene Ontology (GO) terms, among which 210 were related to biological processes, 43 were related to cellular components, and 28 were related to molecular functions. Besides, 1794 and 927 differential metabolites were screened in positive and negative ion mode separately, and 59 different metabolic pathways were involved, including alanine-aspartate-glutamate metabolic pathway, arginine, and proline metabolic pathway, glycerophospholipid metabolic pathways, etc. According to KEGG Pathway analysis of transcriptome combined with metabolome, glycolysis/gluconeogenesis pathway and fatty acid metabolism pathway were significantly founded enriched. ATRA + ATO may inhibit the glycolysis of FLT3-ITD AML cells by inhibiting FLT3 and its downstream AKT/HK2-VDAC1 signaling pathway. CONCLUSIONS: The gene transcription profile and metabolites of FLT3-ITD mutant cells changes significantly after treatment, which might be related to the anti-FLT3-ITD AML effect. The screened DEGs, differential metabolites pathway are helpful in studying the mechanism of anti-leukemia effects and drug targets.

Dopamine regulates colonic glial cell-derived neurotrophic factor secretion through cholinergic dependent and independent pathways.

BACKGROUND AND PURPOSE: Glial cell-derived neurotrophic factor (GDNF) maintains gut homeostasis. Dopamine promotes GDNF release in astrocytes. We investigated the regulation by dopamine of colonic GDNF secretion. EXPERIMENTAL APPROACH: D1 receptor knockout (D1 R-/- ) mice, adeno-associated viral 9-short hairpin RNA carrying D2 receptor (AAV9-shD2 R)-treated mice, 6-hydroxydopamine treated (6-OHDA) rats and primary enteric glial cells (EGCs) culture were used. Incubation fluid from colonic submucosal plexus and longitudinal muscle myenteric plexus were collected for GDNF and ACh measurements. KEY RESULTS: D2 receptor-immunoreactivity (IR), but not D1 receptor-IR, was observed on EGCs. Both D1 receptor-IR and D2 receptor-IR were co-localized on cholinergic neurons. Low concentrations of dopamine induced colonic GDNF secretion in a concentration-dependent manner, which was mimicked by the D1 receptor agonist SKF38393, inhibited by TTX and atropine and eliminated in D1 R-/- mice. SKF38393-induced colonic ACh release was absent in D1 R-/- mice. High concentrations of dopamine suppressed colonic GDNF secretion, which was mimicked by the D2 receptor agonist quinpirole, and absent in AAV-shD2 R-treated mice. Quinpirole decreased GDNF secretion by reducing intracellular Ca2+ levels in primary cultured EGCs. Carbachol ( ACh analogue) promoted the release of GDNF. Quinpirole inhibited colonic ACh release, which was eliminated in the AAV9-shD2 R-treated mice. 6-OHDA treated rats with low ACh and high dopamine content showed decreased GDNF content and increased mucosal permeability in the colon. CONCLUSION AND IMPLICATIONS: Low concentrations of dopamine promote colonic GDNF secretion via D1 receptors on cholinergic neurons, whereas high concentrations of dopamine inhibit GDNF secretion via D2 receptors on EGCs and/or cholinergic neurons.

Case Report: CD19 and CD20 monoclonal antibodies with sequential chemotherapy for refractory acute B-lymphocytic leukemia in children.

Objective: This paper observes the efficacy of chemotherapy combined with CD19 and CD20 monoclonal antibodies in clearing minimal residual disease (MRD) and bridging transplantation for refractory acute B-lymphoblastic leukemia (B-ALL) in children and reviews the literature. Methods: A 4-year-old boy diagnosed with B-ALL in our hospital was treated with the SCCLG-ALL-2016 protocol. MRD and gene quantification decreased after induction but remained persistently positive, with poor efficacy. After this patient received three cycles of consolidation chemotherapy combined with blinatumomab and rituximab, MRD and fusion gene quantification became negative, and he received allogeneic hematopoietic stem cell transplantation (allo-HSCT). Results: During the use of monoclonal antibodies, neurotoxicity, CRS, or other side effects did not occur. Before transplantation, MRD became negative, and the bone marrow had been in complete remission since transplantation (13 months). Conclusion: Chemotherapy combined with blinatumomab for refractory B-ALL in children can bring a better remission rate for patients and is a means of bridging transplantation. Nevertheless, sequential CD20 monoclonal antibody therapy is the first report , and no adverse effects were observed in our case. It is well tolerated and can be used as one of the treatments for refractory B-ALL.

Long-term outcome of children with acute promyelocytic leukemia: a randomized study of oral versus intravenous arsenic by SCCLG-APL group.

Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine mainly containing Realgar (As4S4), is highly effective in treating adult acute promyelocytic leukemia (APL). However, the treatment efficacy and safety of RIF have not been verified in pediatric patients. SCCLG-APL group conducted a multicenter randomized non-inferiority trial to determine whether intravenous arsenic trioxide (ATO) can be substituted by oral RIF in treating pediatric APL. Of 176 eligible patients enrolled, 91 and 85 were randomized to ATO and RIF groups, respectively. Patients were treated with the risk-adapted protocol. Induction, consolidation, and 96-week maintenance treatment contained all-trans-retinoic acid and low-intensity chemotherapy, and either ATO or RIF. The primary endpoint was 5-year event-free survival (EFS). The secondary endpoints were adverse events and hospital days. After a median 6-year follow-up, the 5-year EFS was 97.6% in both groups. However, the RIF group had significantly shorter hospital stays and lower incidence of infection and tended to have less cardiac toxicity. All 4 relapses occurred within 1.5 years after completion of maintenance therapy. No long-term arsenic retentions were observed in either group. Substituting oral RIF for ATO maintains treatment efficacy while reducing hospitalization and adverse events in treating pediatric APL patients, which may be a future treatment strategy for APL.

The effect of long-term moderate exercise on myocardial metabolome in rats.

Regular moderate physical exercise is beneficial for the cardiovascular system. Our prior study has demonstrated a long-term moderate exercise (4-week of 60-min 74.0% V̇O2max treadmill running) is optimal in protecting from exhaustive exercise-induced cardiac ischemic injury. This study is aimed to investigate the effect of long-term moderate exercise on myocardial metabolome in rats. Thirteen male Sprague-Dawley rats were randomly assigned into the control group (C) and the long-term moderate exercise group (E). The targeted metabolomics of the myocardium was analyzed by ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system. Results showed that the metabolites categories of bile acids (BAs), fatty acids (FAs), and phenylpropanoic acids were significantly decreased. The biosynthesis of unsaturated FAs pathway was significantly downregulated. The altered metabolites in the E Group included decreased FAs (pentadecanoic acid, 10Z-heptadecenoic acid, dihomo-gamma-linolenic acid, docosahexaenoic acid, docosapentaenoic acid, and 10Z-nonadecenoic acid), decreased BAs (chenodeoxycholic acid and beta-muricholic acid), decreased organic acids (glycolic acid and 2-hydroxyglutaric acid), decreased carbohydrate (N-acetylneuraminic acid, Neu5Ac), decreased amino acids (α-aminobutyric acid and norvaline), decreased phenylpropanoic acids (hydroxyphenyllactic acid), and benzoic acids (4-hydroxybenzoic acid and phthalic acid). The results indicated that long-term moderate exercise has promoted lipids utilization in myocardium while exerted little influence on carbohydrate metabolism and diminished many detrimental metabolites. Notably, decrease of myocardial carbohydrate Neu5Ac after long-term moderate exercise might predict a prospective metabolomics biomarker for cardioprotection. This research has displayed the effect of long-term moderate exercise on myocardial metabolomic profiling in rats and indicated some promising metabolites which can be applied for exercise benefits in future.

Nomogram model of functional outcome for endovascular treatment in patients with acute basilar artery occlusion.

Background and purpose: The efficacy and safety of endovascular treatment (EVT) in acute basilar artery occlusion (ABAO) has been confirmed by four randomized clinical trials. Nevertheless, the predictors of a 90-day favorable outcome after EVT have not been elucidated. We attempted to establish a nomogram for the prediction of a 90-day favorable outcome in ABAO patients with EVT. Methods: Clinical data of ABAO patients with EVT were obtained from two nationwide clinical trial registries in China. Factors associated with a 90-day favorable outcome were screened by multivariable step-wise regression on the basis of univariable analysis. A nomogram was established to predict 90-day favorable outcome after EVT. Results: The proportion of ABAO patients with a favorable outcome was 41.53% (157/378). Seven variables, including baseline National Institutes of Health Stroke Scale (NIHSS) <20 [odds ratio (OR): 8.330; P-value < 0.0001], posterior circulation Alberta Stroke Program Early CT (pc-ASPECT) score ≥7 (OR: 1.948; P-value = 0.0296), Pons-Midbrain Index (PMI) score < 2 (OR: 2.108; P-value = 0.0128), Posterior Circulation Collateral Score (PC-CS) ≥5 (OR: 3.288; P-value < 0.0001), local anesthesia (OR: 0.389; P-value = 0.0017), time from onset to recanalization (OTR) <330 min (OR: 2.594; P-value = 0.0013), and no occurrence of early neurological deterioration (END; OR: 0.039; P-value < 0.0001) were included into the nomogram, with C-index values of 0.8730 and 0.8857 in the training and the internal validation set, respectively. Conclusions: The proposed nomogram provided a reliable prognostic scale, which can be employed in clinical settings for the selection and clinical management of ABAO patients. Registration: https://www.clinicaltrials.gov, identifier: NCT03370939.

[Clinical Characteristics and Prognosis of Patients with Primary Testicular Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To analyze the clinical manifestations, therapeutic response and prognosis of patients with primary testicular diffuse large B-cell lymphoma (PT-DLBCL). METHODS: Thirty-eight patients with PT-DLBCL were enrolled, who hospitalized from January 2010 to April 2021, and their clinical characteristics, treatment regimen and efficacy were collected and analyzed retrospectively. RESULTS: The median age of the patients was 56 years old (ranged from 38 to 79 years). There were 4 cases (10.5%) with bilateral lesions, 13 cases (34.2%) with left lesions, and 21 cases (55.3%) right lesions. There were 2 cases(5.3%) with B symptoms, 6 cases (15.8%) of germinal center B-cell-like(GCB) subtype and 32 cases(84.2%) of non-GCB subtype. Efficacy was evaluated in 36 cases, including 10 cases with CHOP regimen, 21 cases with R-CHOP regimen (7 cases were treated with rituximab combined with high-dose methotrexate injection chemotherapy at intervals of R-CHOP regimen), and 5 cases with other regimens. In 36 patients, the efficacy evaluation of initial chemotherapy showed that the overall response rate (ORR) was 86.1%, 29 cases (80.6%) reached complete response (CR), and 2 cases (5.5%) reached partial response (PR). The R-CHOP group was superior to CHOP group in ORR (95.2% vs 60.0%, P=0.027) and CR (90.4% vs 50.0%, P=0.022). Of the 36 patients, 7 cases had central nervous system(CNS) recurrence and 4 cases had contralateral testicular recurrence. Compared with the CHOP group, the CNS recurrence rate in the R-CHOP group was significantly lower (4.8% vs 50.0%, P=0.007), and the testicular recurrence rate in the R-CHOP group was also lower than the CHOP group, but the difference was not statistically significant (4.8% vs 30.0%, P=0.087). The median follow-up time was 27(3-135) months, and the 5-year PFS and OS were 71% and 74%, respectively. Kaplan-Meier univariate analysis showed that the R-CHOP regimen significantly improved the patients' PFS (P=0.024) and OS (P=0.025) compared with the CHOP regimen. CONCLUSION: PT-DLBCL is mainly treated with comprehensive treatment. Compared with CHOP regimen, R-CHOP regimen can improve the CR rate and ORR, reduce CNS recurrence and contralateral testicular recurrence, and improve the patients' survival. Patients may benefit from high-dose methotrexate combined with rituximab interlaced with R-CHOP regimen.

A possible genetic association between obesity and colon cancer in females.

Object: There is mounting clinical evidence that an increase in obesity is linked to an increase in cancer incidence and mortality. Although studies have shown a link between obesity and colon cancer, the particular mechanism of the interaction between obesity and colon cancer in females remains unknown. The goal of this work is to use bioinformatics to elucidate the genetic link between obesity and colon cancer in females and to investigate probable molecular mechanisms. Methods: GSE44076 and GSE199063 microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. In the two microarray datasets and healthy controls, the online tool GEO2R was utilized to investigate the differential genes between obesity and colon cancer. The differential genes (DEGs) identified in the two investigations were combined. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment studies were performed on the DEGs. The STRING database and Cytoscape software were then used to build protein-protein interaction (PPI) networks to discover hub genes. NetworkAnalyst was also used to build networks of target microRNAs (miRNAs) and hub genes, as well as networks of transcriptions. Results: Between the two datasets, 146 DEGs were shared. The DEGs are primarily enriched in inflammatory and immune-related pathways, according to GO analysis and KEGG. 14 hub genes were identified via PPI building using the Cytoscape software's MCODE and CytoNCA plug-ins: TYROBP, CD44, BGN, FCGR3A, CD53, CXCR4, FN1, SPP1, IGF1, CCND1, MMP9, IL2RG, IL6 and CTGF. Key transcription factors for these hub genes include WRNIP1, ATF1, CBFB, and NR2F6. Key miRNAs for these hub genes include hsa-mir-1-3p, hsa-mir-26b-5p, hsa-mir-164a-5p and hsa-mir-9-5p. Conclusion: Our research provides evidence that changed genes are shared by female patients with colon cancer and obesity. Through pathways connected to inflammation and the immune system, these genes play significant roles in the emergence of both diseases. We created a network between hub genes and miRNAs that target transcription factors, which may offer suggestions for future research in this area.

Synergistic material modification-induced optimization of interfacial charge transfer and surface hydrogen adsorption.

Being chemically stable, low cost and made from abundant resources, titanium dioxide (TiO2) possesses the most desired advantages for photocatalytic applications. However, the intrinsic limits of high surface hydrogen adsorption energy, wide band gap, low separation rate and rapid recombination of the photogenerated charge carriers greatly hamper its utilization. To address these issues, the present work combines density functional theory (DFT) calculations with rational modifications of TiO2 with nickel doping and an ultra-thin shield of fluorinated carbon (FNT) for application in the photocatalytic hydrogen evolution reaction (HER). Comprehensive studies imply that the synergistic modifications not only optimize the surface H adsorption, but also facilitate the interfacial charge transfer and simultaneously prevent the photochemical and chemical corrosion of the catalysts. In good agreement with the theoretical predictions, the resulting FNT photocatalysts demonstrate an optimal HER efficiency of 13.0 mmol g-1 h-1, nearly 33-times and over three-times beyond that of the pristine TiO2 (0.4 mmol g-1 h-1) and the Ni-doped TiO2 (4.2 mmol g-1 h-1), respectively. Moreover, the composite also exhibits excellent stability with a well-reproducible HER performance over a 66-hour cyclic HER test of 15 cycles.

Effect of vitamin D3 supplementation in winter on physical performance of university students: a one-month randomized controlled trial.

BACKGROUND: There is epidemiological evidence which suggests an association between 25-hydroxyvitamin D [25(OH)D] levels and bone and muscle function; however, it is unclear whether vitamin D supplementation has an added benefit beyond bone health. Here, we investigated the effects of vitamin D3 supplementation (1 month) on physical performance in Chinese university students in winter. METHODS: One hundred and seventeen eligible subjects with 25(OH)D (19.2 ± 7.8 ng/mL) were randomly assigned to either vitamin D3 supplement (N = 56; 1000 IU/day) or the control (N = 61) group for 1 month. Pre- and post-measurements included: 1) serum levels of 25(OH)D; 2) musculoskeletal and pulmonary function [vertical jump height (VJH) and right handgrip strength (RHS), forced vital capacity (FVC), and forced expiratory volume at 1s (FEV1)]; 3) bone turnover markers [parathyroid hormone (PTH), n-terminal osteocalcin (N-MID), and calcium]; 4) hemoglobin-related parameters [hemoglobin (Hb), hematocrit (HCT), red blood cells (RBC), and red cell distribution width (RDW)]; 5) lipid parameters [total triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)]; 6) Fatigue-related indicators [serum creatine kinase (CK), lactate dehydrogenase (LDH), and total testosterone (T)]. In addition, aerobic capacity was assessed by measuring maximal oxygen uptake (VO2max) at baseline. RESULTS: During wintertime, supplementation with 1000 IU/d of vitamin D3 significantly increased serum 25(OH)D levels (from 18.85 ± 7.04 to 26.98 ± 5.88 ng/mL, p < 0.05), accompanied by a decrease of PTH (p < 0.05). However, vitamin D3 supplementation did not significantly impact the physical performance, serum lipid parameters, and bone turnover markers of students. Furthermore, 25(OH)D was found to be positively correlated with VJH and negatively correlated with PTH and TC at the beginning and end of the study (p < 0.05). In addition, the multiple linear regression analysis showed that 25(OH)D combined with athletic, gender, height, weight, Hb, and FVC could account for 84.0% of the VO2max value. CONCLUSIONS: The study demonstrated that one-month of 1000 IU/d of vitamin D3 supplementation during the winter had beneficial effects on 25(OH)D status and PTH. However, vitamin D3 intervention was not sufficient to improve physical performance. Furthermore, 25(OH)D levels combined with athletic, Hb and FVC could be a predictor of VO2max.

Surface Modification in CsPb0.5Sn0.5I2Br Inorganic Perovskite Solar Cells: Effects of Bifunctional Dipolar Molecules on Photovoltaic Performance.

Inorganic tin-lead binary perovskites have piqued the interest of researchers as effective absorbers for thermally stable solar cells. However, the nonradiative recombination originating from the surface undercoordinated Sn2+ cations and the energetic offsets between different layers cause an excessive energy loss and deteriorate the perovskite device's performance. In this study, we investigated two thioamide derivatives that differ only in the polar part connected to their common benzene ring, namely, benzenecarbothioamide and 4-fluorophenylcarbothioamide (F-TBA). These two molecules were implemented as modifiers onto the inorganic tin-lead perovskite (CsPb0.5Sn0.5I2Br) surface in the perovskite solar cells. Modifiers that carry C═S and NH2 functional groups, equipped with lone electron pairs, can autonomously associate with surface Sn2+ through coordination and electrostatic attraction mechanisms. This interaction serves effectively to passivate the surface. In addition, due to the permanent dipole moment of the intermediate layer, an interfacial dipole field appears at the PCBM/CsPb0.5Sn0.5I2Br interface, reducing the electron extraction potential barrier. Consequently, the planar solar cell with an ITO/PEDOT:PSS/CsPb0.5Sn0.5I2Br/PCBM/BCP/Ag layered structure featuring an F-TBA surface post-treatment demonstrated a noteworthy power conversion efficiency of 14.01%. Simultaneously, after being stored for 1000 h in an inert atmosphere glovebox, the non-encapsulated CsPb0.5Sn0.5I2Br solar cells managed to preserve 94% of their original efficiency.

[Inhibitory Effect of Cinobufotalin on Macrophage Inflammatory Factor Storm and Its Mechanism].

OBJECTIVE: To investigate the inflammatory effects of Cinobufotalin on monocytes in resting state and macrophages in activated state and its molecular mechanism. METHODS: THP-1 cells were stimulated with Phorbol 12-myristate 13-acetate to induce differentiation into macrophages. Lipopolysaccharides was added to activate macrophages in order to establish macrophage activation model. Cinobufotalin was added to the inflammatory cell model for 24 h as a treatment. CCK-8 was used to detect cell proliferation, Annexin V /PI double staining flow cytometry was used to detect cell apoptosis, flow cytometry was used to detect macrophage activation, and cytometric bead array was used to detect cytokines. Transcriptome sequencing was used to explore the gene expression profile regulated by Cinobufotalin. Changes in the significantly regulated molecules were verified by real-time quantitative polymerase chain reaction and Western blot. RESULTS: 1∶25 concentration of Cinobufotalin significantly inhibited the proliferation of resting monocytes(P<0.01), and induced apoptosis(P<0.01), especially the activated macrophages(P<0.001, P<0.001). Cinobufotalin significantly inhibited the activation of macrophages, and significantly down-regulated the inflammatory cytokines(IL-6, TNF-α, IL-1ß, IL-8) released by activated macrophages(P＜0.001). Its mechanism was achieved by inhibiting TLR4/MYD88/P-IκBa signaling pathway. CONCLUSION: Cinobufotalin can inhibit the inflammatory factors produced by the over-activation of macrophages through TLR4/MYD88/P-IκBa pathway, which is expected to be applied to the treatment and research of diseases related to the over-release of inflammatory factors.

The ubiquitin-binding protein MdRAD23D1 mediates drought response by regulating degradation of the proline-rich protein MdPRP6 in apple (Malus domestica).

RAD23 (RADIATION SENSITIVE23) proteins are a group of UBL-UBA (ubiquitin-like-ubiquitin-associated) proteins that shuttle ubiquitylated proteins to the 26S proteasome for breakdown. Drought stress is a major environmental constraint that limits plant growth and production, but whether RAD23 proteins are involved in this process is unclear. Here, we demonstrated that a shuttle protein, MdRAD23D1, mediated drought response in apple plants (Malus domestica). MdRAD23D1 levels increased under drought stress, and its suppression resulted in decreased stress tolerance in apple plants. Through in vitro and in vivo assays, we demonstrated that MdRAD23D1 interacted with a proline-rich protein MdPRP6, resulting in the degradation of MdPRP6 by the 26S proteasome. And MdRAD23D1 accelerated the degradation of MdPRP6 under drought stress. Suppression of MdPRP6 resulted in enhanced drought tolerance in apple plants, mainly because the free proline accumulation is changed. And the free proline is also involved in MdRAD23D1-mediated drought response. Taken together, these findings demonstrated that MdRAD23D1 and MdPRP6 oppositely regulated drought response. MdRAD23D1 levels increased under drought, accelerating the degradation of MdPRP6. MdPRP6 negatively regulated drought response, probably by regulating proline accumulation. Thus, "MdRAD23D1-MdPRP6" conferred drought stress tolerance in apple plants.

The regulatory network of the chemokine CCL5 in colorectal cancer.

The chemokine CCL5 plays a potential role in the occurrence and development of colorectal cancer (CRC). Previous studies have shown that CCL5 directly acts on tumor cells to change tumor metastatic rates. In addition, CCL5 recruits immune cells and immunosuppressive cells into the tumor microenvironment (TME) and reshapes the TME to adapt to tumor growth or increase antitumor immune efficacy, depending on the type of secretory cells releasing CCL5, the cellular function of CCL5 recruitment, and the underlying mechanisms. However, at present, research on the role played by CCL5 in the occurrence and development of CRC is still limited, and whether CCL5 promotes the occurrence and development of CRC and its role remain controversial. This paper discusses the cells recruited by CCL5 in patients with CRC and the specific mechanism of this recruitment, as well as recent clinical studies of CCL5 in patients with CRC.Key MessagesCCL5 plays dual roles in colorectal cancer progression.CCL5 remodels the tumor microenvironment to adapt to colorectal cancer tumor growth by recruiting immunosuppressive cells or by direct action.CCL5 inhibits colorectal cancer tumor growth by recruiting immune cells or by direct action.

Network pharmacology to explore the mechanism of scutellarin in the treatment of brain ischaemia and experimental verification of JAK2/STAT3 signalling pathway.

Scutellarin is used to treat brain ischaemia. However, its underlying mechanism of action remains unclear. This study aimed to elucidate the potential mechanism of action of scutellarin in brain ischaemia through network pharmacology and experimental verification. The JAK2/STAT3 signalling pathway was identified and experimentally verified. Expression of JAK2/STAT3 signalling related proteins in TNC-1 astrocytes with BV-2 microglia-conditioned medium (CM), CM + lipopolysaccharide (LPS) (CM + L), and CM pretreated with scutellarin + LPS (CM + SL) was analysed by Western Blot and immunofluorescence staining. Expression levels of JAK2, p-JAK2, STAT3, and p-STAT3 were evaluated in astrocytes pre-treated with AG490. Middle cerebral artery occlusion (MCAO) in rats was performed in different experimental groups to detect expression of the above biomarkers. Network pharmacology suggested that the JAK2/STAT3 signalling pathway is one of the mechanisms by which scutellarin mitigates cerebral ischaemic damage. In TNC-1 astrocytes, p-JAK2 and p-STAT3 expression were significantly up-regulated in the CM + L group. Scutellarin promoted the up-regulation of various markers and AG490 neutralised the effect of scutellarin. In vivo, up-regulation of p-JAK2 and p-STAT3 after ischaemia is known. These results are consistent with previous reports. Scutellarin further enhanced this upregulation at 1, 3, and 7 d after MCAO. Scutellarin exerts its therapeutic effects on cerebral ischaemia by activating the astrocyte JAK2/STAT3 signalling, which provides a firm experimental basis for its clinical application.

Helicobacter pylori regulates stomach diseases by activating cell pathways and DNA methylation of host cells.

One of the most prevalent malignant tumors of the digestive tract is gastric cancer (GC). Age, high salt intake, Helicobacter pylori (H. pylori) infection, and a diet deficient in fruits and vegetables are risk factors for the illness. A significant risk factor for gastric cancer is infection with H. pylori. Infecting gastric epithelial cells with virulence agents secreted by H. pylori can cause methylation of tumor genes or carcinogenic signaling pathways to be activated. Regulate downstream genes' aberrant expression, albeit the precise mechanism by which this happens is unclear. Oncogene, oncosuppressor, and other gene modifications, as well as a number of different gene change types, are all directly associated to the carcinogenesis of gastric cancer. In this review, we describe comprehensive H. pylori and its virulence factors, as well as the activation of the NF-κB, MAPK, JAK/STAT signaling pathways, and DNA methylation following infection with host cells via virulence factors, resulting in abnormal gene expression. As a result, host-related proteins are regulated, and gastric cancer progression is influenced. This review provides insight into the H. pylori infection, summarizes a series of relevant papers, discusses the complex signaling pathways underlying molecular mechanisms, and proposes new approach to immunotherapy of this important disease.

Metachronous urothelial carcinoma in the renal pelvis, bladder, and urethra: A case report.

BACKGROUND: Urothelial carcinoma (UC) is a common malignancy of the urinary system that can occur anywhere from the renal pelvis to the proximal urethra. Most UCs are in the bladder and have multifocal growth. Upper urinary tract UC (UTUC), which occurs in the renal pelvis or ureter, accounts for only 5% to 10% of UCs. CASE SUMMARY: In March 2015, a 70-year-old male who initially presented to a local hospital with a complaint of painless hematuria was diagnosed with UTUC of the right renal pelvis. The doctors administered radical nephroureterectomy and bladder cuff excision. Although the doctors recommended intravesical chemotherapy and regular follow-up, he rejected this advice. In December 2016, the patient presented at our hospital with dysuria. We identified UC in the residual bladder and administered radical cystectomy and left cutaneous ureterostomy. In November 2021, he presented again with urethral bleeding. We detected urethral UC as the cause of urethral orifice bleeding and administered radical urethrectomy. Since then, he has visited regularly for 6-mo follow-ups, and was in stable condition as of December 2022. CONCLUSION: UTUC is prone to seeding and recurrence. Adjuvant instillation therapy and intense surveillance are crucial for these patients.