One-year results of the flowdynamics dense mesh stent for residual dissection after proximal repair of stanford type a or type b aortic dissection: a multicenter, prospective and randomized study.

OBJECTIVE: Negative remodeling of the distal aorta following proximal repair for acute aortic dissection has garnered growing attention. This clinical scenario has spurred the development of techniques and devices. A multicenter, prospective, and randomized controlled study was conducted with the aim of confirming the safety and effectiveness of a newly-designed flowdynamics dense mesh stent for the treatment of residual dissection after proximal repair. METHODS: Patients with nonchronic residual dissection affecting visceral branches were prospectively enrolled at three centers and randomly allocated to either the FDMS group or the control group. Primary endpoints encompassed all-cause and aortic-related mortality, while the patency of branch arteries is indeed a key focal metric. Morphological changes (diameter, area, and volume) were analyzed to demonstrate the therapeutic effect. RESULTS: 112 patients were recruited in the clinical trial, and 103 patients completed the 12-month follow-up. The rate of freedom from all-cause and aortic-related death in the FDMS group was 94.64% and 100%, respectively. All visceral branches remained patent. The FDMS group exhibited a substantial expansion in TL and a notable shrinkage in FL at the planes below renal arteries (ΔArea TL: FDMS vs. Control, 0.74±0.46 vs. 0.34±0.66 cm2, P<0.001; ΔArea FL: FDMS vs. Control, -0.72±1.26 vs. -0.12±0.86 cm, P = 0.01) and 5 cm below renal arteries (ΔArea TL: FDMS vs. Control, 1.06±0.75 vs. 0.16±0.63 cm2, P<0.001; ΔArea FL: FDMS vs. Control, -0.53±1.43 vs. -0.25±1.00 cm, P = 0.27). Meanwhile, the FDMS group demonstrated an increase of 22.55±11.14 cm3 in TL (P<0.001) and a corresponding reduction of 21.94±11.77 cm3 in FL (P=0.08). CONCLUSIONS: This newly-designed FDMS for endovascular repair of residual dissection following the proximal repair is demonstrated to be safe and effective at 12 months.

Interlayer-Coupling-Driven High-Temperature Superconductivity in La_{3}Ni_{2}O_{7} under Pressure.

The newly discovered high-temperature superconductivity in La_{3}Ni_{2}O_{7} under pressure has attracted a great deal of attention. The essential ingredient characterizing the electronic properties is the bilayer NiO_{2} planes coupled by the interlayer bonding of 3d_{z^{2}} orbitals through the intermediate oxygen atoms. In the strong coupling limit, the low-energy physics is described by an intralayer antiferromagnetic spin-exchange interaction J_{∥} between 3d_{x^{2}-y^{2}} orbitals and an interlayer one J_{⊥} between 3d_{z^{2}} orbitals. Taking into account Hund's rule on each site and integrating out the 3d_{z^{2}} spin degree of freedom, the system reduces to a single-orbital bilayer t-J model based on the 3d_{x^{2}-y^{2}} orbital. By employing the slave-boson approach, the self-consistent equations for the bonding and pairing order parameters are solved. Near the physically relevant 1/4-filling regime (doping δ=0.3∼0.5), the interlayer coupling J_{⊥} tunes the conventional single-layer d-wave superconducting state to the s-wave one. A strong J_{⊥} could enhance the interlayer superconducting order, leading to a dramatically increased T_{c}. Interestingly, there could exist a finite regime in which an s+id state emerges.

Coordination polymer derived Fe-N-C electrocatalysts with high performance for the oxygen reduction reaction in Zn-air batteries.

Developing high performance noble-metal-free electrocatalysts as an alternative to Pt-based catalysts for the oxygen reduction reaction (ORR) in energy conversion devices is highly desirable. We report herein the preparation of a coordination-polymer (CP)-derived Fe/CP/C composite as an electrocatalyst for the ORR with excellent activity and stability both in solution and in Zn-air batteries. The Fe/CP/C catalyst was obtained from the pyrolysis of an iron porphyrin Fe(TPP)Cl (5,10,15,20-tetraphenyl-21H,23H-porphyrin iron(III) chloride) grafted Zn-coordination polymer with dangling functional groups 4,4'-oxybisbenzoic acid and 4,4'-bipyridine ligands. The Fe/CP/C catalyst showed much higher ORR activity with a half-wave potential (E1/2) of 0.90 V (vs. RHE) than the Fe/C catalyst (E1/2 = 0.85 V) derived from the carbon-black-supported Fe porphyrins in 0.1 M KOH solution. When Fe/CP/C was used as the cathode electrocatalyst in Zn-air batteries (ZABs), the ZABs achieved a significantly higher open circuit voltage (OCV = 1.43 V) and maximum power density (Pmax = 142.8 mW cm-2) compared with Fe/C (OCV = 1.38 V, Pmax = 104.5 mW cm-2) and commercial 20 wt% Pt/C (OCV = 1.41 V, Pmax = 117.6 mW cm-2). Using dangling functional groups in CP to increase the loading efficiency of iron porphyrins offered a facile method to prepare high-performance noble-metal-free electrocatalysts for the ORR, which may provide promising applications to energy conversion devices.

MOTS-c is an effective target for treating streptozotocin induced painful diabetic neuropathy through induction of AMPK/PGC-1α -mediated mitochondrial biogenesis.

Painful Diabetic Neuropathy (PDN) is a common diabetes complication that frequently causes severe hyperalgesia and allodynia and presents treatment challenges. MOTS-c, a novel mitochondrial-derived peptide, has been shown to regulate glucose metabolism, insulin sensitivity, and inflammatory responses. This study aimed to evaluate the effects of MOTS-c in streptozocin (STZ)-induced PDN model and investigate the putative underlying mechanisms. We found that endogenous MOTS-c levels in plasma and spinal dorsal horn were significantly lower in STZ-treated mice than in control animals. Accordingly, MOTS-c treatment significantly improves STZ-induced weight loss, elevation of blood glucose, mechanical allodynia, and thermal hyperalgesia; however, these effects were blocked by dorsomorphin, an AMPK inhibitor. In addition, MOTS-c treatment significantly enhanced AMPKα1/2 phosphorylation and PGC-1α expression in the lumbar spinal cord of PDN mice. Mechanistic studies indicated that MOTS-c significantly restored mitochondrial biogenesis, inhibited microglia activation, and decreased the production of pro-inflammatory factors, which contributed to the alleviation of pain. Moreover, MOTS-c decreased STZ-induced pain hypersensitivity in PDN mice by activating AMPK/PGC-1α signaling pathway. This provides the pharmacological and biological evidence for developing mitochondrial peptide-based therapeutic agents for PDN.

Rapid Screening of 34 Emerging Contaminants in Surface Water by UHPLC-Q-TOF-MS.

OBJECTIVES: To establish a rapid screening method for 34 emerging contaminants in surface water by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF-MS). METHODS: The pretreatment conditions of solid phase extraction (SPE) were optimized by orthogonal experimental design and the surface water samples were concentrated and extracted by Oasis® HLB and Oasis® MCX SPE columns in series. The extracts were separated by Kinetex® EVO C18 column, with gradient elution of 0.1% formic acid aqueous solution and 0.1% formic acid methanol solution. Q-TOF-MS 'fullscan' and 'targeted MS/MS' modes were used to detect 34 emerging contaminants and to establish a database with 34 emerging contaminants precursor ion, product ion and retention times. RESULTS: The 34 emerging contaminants exhibited good linearity in the concentration range respectively and the correlation coefficients (r) were higher than 0.97. The limit of detection was 0.2-10 ng/L and the recoveries were 81.2%-119.2%. The intra-day precision was 0.78%-18.70%. The method was applied to analyze multiple surface water samples and 6 emerging contaminants were detected, with a concentration range of 1.93-157.71 ng/L. CONCLUSIONS: The method is simple and rapid for screening various emerging contaminants at the trace level in surface water.

Function and mechanism of exosomes derived from different cells as communication mediators in colorectal cancer metastasis.

Colorectal cancer (CRC) ranks as the second leading cause of cancer-related mortality, with metastasis being the primary determinant of poor prognosis in patients. Investigating the molecular mechanisms underlying CRC metastasis is currently a prominent and challenging area of research. Exosomes, as crucial intercellular communication mediators, facilitate the transfer of metabolic and genetic information from cells of origin to recipient cells. Their roles in mediating information exchange between CRC cells and immune cells, fibroblasts, and other cell types are pivotal in reshaping the tumor microenvironment, regulating key biological processes such as invasion, migration, and formation of pre-metastatic niche. This article comprehensively examines the communication function and mechanism of exosomes derived from different cells in cancer metastasis, while also presenting an outlook on current research advancements and future application prospects. The aim is to offer a distinctive perspective that contributes to accurate diagnosis and rational treatment strategies for CRC.

Evaluation of the prognostic performance of different cutoff values of lymph node ratio staging system for stage III colorectal cancer.

This study attempted to compare the prognostic performance of lymph node ratio (LNR) staging system with different cutoff values relative to American Joint Committee on Cancer (AJCC) pN staging system in stage III colorectal cancer (CRC). Overall, 45,069 patients from the SEER dataset and 69 patients from the Second Affiliated Hospital of Nanjing Medical University (the External set) who underwent surgical resection of the primary tumor and were diagnosed with stage III CRC by postoperative pathology were included. Patients were divided into three subgroups based on the LNR cutoff used in previous studies, Kaplan-Meier curves were plotted, and log-rank test was used to compare the differences among groups in terms of cancer-specific survival (CSS). Cox regression model was applied for survival analysis. To evaluate the discriminatory power of different lymph node staging systems, Harrell's C statistic(C-index) and Akaike's Information Criterion (AIC) were applied. A set of optimal cutoff values (0.11; 0.36; 0.66) of LNR staging system with the most considerable discriminatory power to the prognosis in patients with stage III CRC (SEER set: C-index = 0.714; AIC = 58,942.46, External set: C-index = 0.809; AIC = 164.36) were obtained, and both were superior to the AJCC pN staging system (SEER set: C-index = 0.708; AIC = 59,071.20, External set: C-index = 0.788; AIC = 167.06). For evaluating the prognostic efficacy of patients with stage III colorectal cancer, the cutoff value (0.11; 0.36; 0.66) of LNR staging system had the best discrimination and prognostic ability, which was superior to LNR staging system under other cutoff values and AJCC pN staging system.

Interfacial Engineering of P2-Type Ni/Mn-Based Layered Oxides by a Facile Water-Washing Method for Superior Sodium-Ion Batteries.

Owing to the strong basicity and reactivity, residual sodium compounds (RSCs) on the surface of Na-based layered oxides for sodium-ion batteries (SIBs) cause the deterioration of the electrochemical performance and processability of the oxide cathode materials. Herein, considering P2-type Na0.66Ni0.26Zn0.07Mn0.67O2 as the model material, the water-washing treatment is proven to be a facile, economic, and highly efficient method to improve the electrochemical performance of P2-type Ni/Mn-based layered oxides. Experimental results show that RSCs on material surfaces can be effectively removed by water washing without causing severe damage to the bulk structure. Notably, water washing triggers the formation of an ultrathin (2-3 nm thick) Na-poor disordered interfacial layer on the surface of Na0.66Ni0.26Zn0.07Mn0.67O2. This layer plays a passivating role in further enhancing the material's resistance to water and reduces the reactivity of the material surface with the electrolyte. These compositional and structural optimizations for P2-type Na0.66Ni0.26Zn0.07Mn0.67O2 effectively suppress the release of gaseous CO2, formation of thick cathode-electrolyte interphase films, and consumption of active Na+, enabling good Na+ transport kinetics during cycling. The water-washed Na0.66Ni0.26Zn0.07Mn0.67O2 exhibits significantly improved cycling stability with a capacity retention of 89.1% at 100 mA g-1 after 100 cycles and rate capability with a discharge capacity of 76.3 mA g-1 at 2000 mA g-1; these values are higher than those of the unwashed Na0.66Ni0.26Zn0.07Mn0.67O2 (83.3%, 71.4 mA h g-1). This work provides fundamental insights into the detrimental effect of RSCs on the electrochemical performance of layered oxides and highlights the importance of regulating interfacial compositions for developing high-performance layered-oxide cathode materials for SIBs.

Nomogram predicting the efficacy of transurethral surgery in benign prostatic hyperplasia patients.

PURPOSE: This study aimed to develop and validate a nomogram for predicting the efficacy of transurethral surgery in benign prostatic hyperplasia (BPH) patients. METHODS: Patients with BPH who underwent transurethral surgery in the West China Hospital and West China Shang Jin Hospital were enrolled. Patients were retrospectively involved as the training group and were prospectively recruited as the validation group for the nomogram. Logistic regression analysis was utilized to generate nomogram for predicting the efficacy of transurethral surgery. The discrimination of the nomogram was assessed using the area under the receiver operating characteristic curve (AUC) and calibration plots were applied to evaluate the calibration of the nomogram. RESULTS: A total of 426 patients with BPH who underwent transurethral surgery were included in the study, and they were further divided into a training group (n = 245) and a validation group (n = 181). Age (OR 1.07, 95% CI 1.02-1.15, P < 0.01), the compliance of the bladder (OR 2.37, 95% CI 1.20-4.67, P < 0.01), the function of the detrusor (OR 5.92, 95% CI 2.10-16.6, P < 0.01), and the bladder outlet obstruction (OR 2.21, 95% CI 1.07-4.54, P < 0.01) were incorporated in the nomogram. The AUC of the nomogram was 0.825 in the training group, and 0.785 in the validation group, respectively. CONCLUSION: The nomogram we developed included age, the compliance of the bladder, the function of the detrusor, and the severity of bladder outlet obstruction. The discrimination and calibration of the nomogram were confirmed by internal and external validation.

Simulation training of laparoscopic biliary-enteric anastomosis with a 3D-printed model leads to better skill transfer: a randomized controlled trial.

AIM: A new simulation model and training curriculum for laparoscopic bilioenteric anastomosis has been developed. Currently, this concept lacks evidence for the transfer of skills from simulation to clinical settings. This study was conducted to determine whether training with a 3D bilioenteric anastomosis model result in greater transfer of skills than traditional training methods involving video observation and a general suture model. METHODS: Fifteen general surgeons with no prior experience in laparoscopic biliary-enteric anastomosis were included in this study and randomised into three training groups: video observation only, practice using a general suture model, and practice using a 3D printed biliary-enteric anastomosis model. Following five training sessions, each surgeon was asked to perform a laparoscopic biliary-enteric anastomosis procedure on an isolated swine organ model. The operative time and performance scores of the procedure were recorded and compared among the three training groups. RESULTS: The operation time in the 3D printed model group was significantly shorter than the suture and video observation groups (P=0.040). Furthermore, the performance score of the 3D printed model group was significantly higher than those of the suture and video observation groups (P=0.001). Finally, the goal score for laparoscopic biliary-enteric anastomosis in the isolated swine organ model was significantly higher in the 3D model group than in the suture and video observation groups (P=0.004). CONCLUSIONS: The utilisation of a novel 3D-printed model for simulation training in laparoscopic biliary-enteric anastomosis facilitates improved skill acquisition and transferability to an animal setting compared with traditional training techniques.

Double-branched stent graft and four-stage deployment in total arch repair: safety and feasibility evaluation in porcine models.

OBJECTIVES: The primary objective of this research was to evaluate the safety and feasibility of an innovative double-branched stent graft system employing four-stage deployment technology for aortic arch repair in porcine models. METHODS: The double-branched stent graft system consisted of a proximal polyester artificial blood vessel, the main and double-branched stent grafts and a delivery system. We utilized 12 healthy pigs as experimental animals (6 per group). Postimplantation, samples were collected at 90 and 180 days after the operations. Preoperative and postoperative imaging and intraoperative arterial blood gas analyses were performed. After the pigs were euthanized, the implanted product, surrounding tissue and major organs were collected for pathological analysis. RESULTS: The technical success rate of the stent graft implants was 100% (12/12). All animals survived to the experimental end point. Perioperative assessments showed intact stent grafts, and imaging features at the end of the follow-up period revealed neither endoleak nor device migration. No major adverse cardiovascular events were observed during the postoperative follow-up period. Pathological examinations confirmed the satisfactory biocompatibility of the stent graft. CONCLUSIONS: This innovative double-branched stent graft system with four-stage deployment technology was affirmed as a safe and feasible option for aortic arch repair in accordance with our preclinical evaluation with porcine models.

Therapeutic Application of Dendrobium fimbriatum Hook for Retinopathy Caused by Ultraviolet Radiation and Chemotherapy Using ARPE-19 Cells and Mouse Retina.

Retinopathy caused by ultraviolet radiation and cancer chemotherapy has increased dramatically in humans due to rapid environmental and social changes. Therefore, it is very important to develop therapeutic strategies to effectively alleviate retinopathy. In China, people often choose dendrobium to improve their eyesight. In this study, we explored how Dendrobium fimbriatum extract (DFE) protects ARPE-19 cells and mouse retinal tissue from damage of ultraviolet (UV) radiation and chemotherapy. We evaluated the antioxidant capacity of DFE using the 1,1-diphenyl-2-trinitophenylhydrazine (DPPH) assay. The protective effects of DEF from UV- and oxaliplatin (OXA)-induced damage were examined in ARPE-19 cells using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and immunofluorescence (IF) stains, and in mouse retinal tissue using immunohistochemistry (IHC) stains. Our results show that DFE has excellent antioxidant capacity. The ARPE-19 cell viability was decreased and the F-actin cytoskeleton structure was damaged by UV radiation and OXA chemotherapy, but both were alleviated after the DFE treatment. Furthermore, DFE treatment can alleviate OXA chemotherapy-induced reduced expressions of rhodopsin and SOD2 and increased expressions of TNF-α and caspase 3 in mouse retinal tissue. Thus, we suggest that DFE can act as suitable treatment for retinopathy through reducing oxidative stress, inflammation, and apoptosis.

ACADL-YAP axis activity in non-small cell lung cancer carcinogenicity.

BACKGROUND: The role of Acyl-CoA dehydrogenase long chain (ACADL) in different tumor types had different inhibiting or promoting effect. However, its role in non-small cell lung cancer (NSCLC) carcinogenicity is not clear. METHOD: In this study, we utilized The Cancer Genome Atlas (TCGA) database to analyze ACADL expression in NSCLC and its correlation with overall survival. Furthermore, we investigated the function of ACADL on cellular proliferation, invasion, colony, apoptosis, cell cycle in vitro with NSCLC cells. Mechanistically, we evaluated the regulatory effect of ACADL expression on its downstream factor yes-associated protein (YAP) by assessing YAP phosphorylation levels and its cellular localization. Finally, we verified the tumorigenic effect of ACADL on NSCLC cells through xenograft experiments in vivo. RESULTS: Compared to adjacent non-cancerous samples, ACADL significantly down-regulated in NSCLC. Overexpression of ACADL, effectively reduced the proliferative, colony, and invasive capabilities of NSCLC cells, while promoting apoptosis and inducing cell cycle arrest. Moreover, ACADL overexpression significantly enhanced YAP phosphorylation and hindered its nuclear translocation. However, the inhibitory effect of the overexpression of ACADL in NSCLC cells mentioned above can be partially counteracted by YAP activator XMU-MP-1 application both in vitro and in vivo. CONCLUSION: The findings suggest that ACADL overexpression could suppress NSCLC development by modulating YAP phosphorylation and limiting its nuclear shift. This role of ACADL-YAP axis provided novel insights into NSCLC carcinogenicity and potential therapeutic strategies.

Tumor necrosis factor α-induced protein 8-like-2 controls microglia phenotype via metabolic reprogramming in BV2 microglial cells and responses to neuropathic pain.

Microglial are major players in neuroinflammation that have recently emerged as potential therapeutic targets for neuropathic pain. Glucose metabolic programming has been linked to differential activation state and function in microglia. Tumor necrosis factor α-induced protein 8-like-2 (TNFAIP8L2) is an important component in regulating the anti-inflammatory response. However, the role of TNFAIP8L2 in microglia differential state during neuropathic pain and its interplay with glucose metabolic reprogramming in microglia has not yet been determined. Thus, we aimed to investigate the role of TNFAIP8L2 in the status of microglia in vitro and in vivo. BV2 microglial cells were treated with lipopolysaccharides plus interferon-gamma (LPS/IFNγ) or interleukin-4 (IL-4) to induce the two different phenotypes of microglia in vitro. In vivo experiments were conducted by chronic constriction injury of the sciatic nerve (CCI). We investigated whether TNFAIP8L2 regulates glucose metabolic programming in BV2 microglial cells. The data in vitro showed that TNFAIP8L2 lowers glycolysis and increases mitochondrial oxidative phosphorylation (OXPHOS) in inflammatory microglia. Blockade of glycolytic pathway abolished TNFAIP8L2-mediated differential activation of microglia. TNFAIP8L2 suppresses inflammatory microglial activation and promotes restorative microglial activation in BV2 microglial cells and in spinal cord microglia after neuropathic pain. Furthermore, TNFAIP8L2 controls differential activation of microglia and glucose metabolic reprogramming through the MAPK/mTOR/HIF-1α signaling axis. This study reveals that TNFAIP8L2 plays a critical role in neuropathic pain, providing important insights into glucose metabolic reprogramming and microglial phenotypic transition, which indicates that TNFAIP8L2 may be used as a potential drug target for the prevention of neuropathic pain.

Novel Three-Dimensional Artificial Neural Network Based on an Eight-Layer Vertical Memristor with an Ultrahigh Rectify Ratio (>107) and an Ultrahigh Nonlinearity (>105) for Neuromorphic Computing.

In recent years, memristors have successfully demonstrated their significant potential in artificial neural networks (ANNs) and neuromorphic computing. Nonetheless, ANNs constructed by crossbar arrays suffer from cross-talk issues and low integration densities. Here, we propose an eight-layer three-dimensional (3D) vertical crossbar memristor with an ultrahigh rectify ratio (RR > 107) and an ultrahigh nonlinearity (>105) to overcome these limitations, which enables it to reach a >1 Tb array size without reading failure. Furthermore, the proposed 3D RRAM shows advanced endurance (>1010 cycles), retention (>104 s), and uniformity. In addition, several synaptic functions observed in the human brain were mimicked. On the basis of the advanced performance, we constructed a novel 3D ANN, whose learning efficiency and recognition accuracy were enhanced significantly compared with those of conventional single-layer ANNs. These findings hold promise for the development of highly efficient, precise, integrated, and stable VLSI neuromorphic computing systems.

Regulation of PDGFRα+ cells and ICC in progesterone-mediated slow colon transit in pregnant mice.

Background: Progesterone can inhibit intestinal smooth muscle contraction; however, the specific mechanism remains unclear. Besides smooth muscle cells, smooth muscle has two important mesenchymal cells, namely interstitial cells of Cajal (ICC) and PDGFRα+ cells, which induce the contraction and relaxation of smooth muscles. We aimed to explore the regulation of PDGFRα+ cells and ICC in progesterone-mediated colon slow transit in pregnant mice. Methods: Colon transit experiments were performed in vivo and in vitro to observe slow colon transit. The expression of PDGFRα and c-KIT was detected by Western blot, RT-PCR, and immunofluorescence. An isometric tension experiment was performed to investigate smooth muscle contractions. Results: The colon transit time in pregnant mice was longer than that in non-pregnant mice. Progesterone significantly blocks colonic smooth muscle contractions. However, when the relaxation and contraction of PDGFRα+ cells and ICC are blocked, progesterone cannot inhibit smooth muscle contraction. When the function of only PDGFRα+ cells are blocked, progesterone has a more obvious inhibitory effect on smooth muscle in the non-pregnant group than that in the pregnant group. However, when ICC alone was blocked, progesterone inhibited smooth muscle contractions more clearly in pregnant mice. The protein and mRNA expression of PDGFRα was higher and c-KIT was lower in pregnant mice. PDGFRα+ cells and ICC from smooth muscle all co-localize progesterone receptors. Conclusions: Under the regulation of progesterone, the relaxation function of PDGFRα+ cells is enhanced and the contraction function of ICC is weakened, leading to the slow colon transit of pregnant mice.

Characterization of Heat-labile Uracil-DNA Glycosylase from Oncorhynchus mykiss and its Application for Carry-over Contamination Control in RT-qPCR.

BACKGROUND: Heat-labile uracil-DNA glycosylase (HL-UDG) is commonly employed to eliminate carry-over contamination in DNA amplifications. However, the prevailing HL-UDG is markedly inactivated at 50°C, rendering it unsuitable for specific one-step RT-qPCR protocols utilizing reverse transcriptase at an optimal temperature of 42°C. OBJECTIVE: This study aimed to explore novel HL-UDG with lower inactivation temperature and for recombinant expression. METHODS: The gene encoding an HL-UDG was cloned from the cold-water fish rainbow trout (Oncorhynchus mykiss) and expressed in Escherichia coli with high yield. The thermostability of the enzyme and other enzymatic characteristics were thoroughly examined. The novel HL-UDG was then applied for controlling carry-over contamination in one-step RT-qPCR. RESULTS: This recombinantly expressed truncated HL-UDG of rainbow trout (OmUDG) exhibited high amino acids similarity (84.1% identity) to recombinant Atlantic cod UDG (rcUDG) and was easily denatured at 40°C. The optimal pH of OmUDG was 8.0, and the optimal concentrations of both Na+ and K+ were 10 mM. Since its inactivation temperature was lower than that of rcUDG, the OmUDG could be used to eliminate carry-over contamination in one-step RT-qPCR with moderate reverse transcription temperature. CONCLUSION: We successfully identified and recombinantly expressed a novel HL-UDG with an inactivation temperature of 40°C. It is suitable for eliminating carry-over contamination in one-step RT-qPCR.

CPXM1 correlates to poor prognosis and immune cell infiltration in gastric cancer.

Background: Gastric cancer (GC) is the fourth most common cause of cancer-related death and the fifth most frequent malignant cancer, especially advanced GC. Carboxypeptidase X member 1 (CPXM1) is an epigenetic factor involved in many physiological processes, including osteoclast differentiation and adipogenesis. Several studies have shown the association of CPXM1 with multiple tumors; however, the mechanism of CPXM1 involvement in the progression of GC is yet to be characterized. Method: CPXM1 expression data were obtained from the Tumor Immune Estimation Resource. The Cancer Genome Atlas and the Gene Expression Omnibus databases were used to obtain patient-matched clinicopathological information, and the Kaplan-Meier plot database was utilized for the prognosis analysis of GC patients. The Catalog of Somatic Mutations in Cancer and cBioportal databases were adopted to study CPXM1 mutations in tumors. Next, we utilized the Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis for mechanism research. Furthermore, we performed tumor microenvironment and immune infiltration analysis based on CPXM1. Finally, we predicted sensitivity to several targeted drugs in GC patients based on CPXM1.CPXM1 is upregulated in GC and is correlated with poor prognosis, gender, and tumor stage in GC patients. Gene enrichment analysis suggested that CPXM1 may regulate the occurrence and progression of GC via the PI3K-AKT and TGF-ß pathway. Moreover, CPXM1 expression results in an increase in the proportion of immune and stromal cells. Additionally, the proportion of plasma cells was inversely related to the expression of CPXM1, whereas macrophage M2 expression was proportionate to CPXM1 expression. Finally, six small-molecule drugs that showed notable variations in IC50 between two groups were screened. Conclusion: These results suggested that CPXM1 regulates the progression of GC and may represent a novel target for the detection and treatment of GC.

Integrating network pharmacology, molecular docking and simulation approaches with machine learning reveals the multi-target pharmacological mechanism of Berberis integerrima against diabetic nephropathy.

Diabetic nephropathy (DN) is one of the most feared complications of diabetes and key cause of end-stage renal disease (ESRD). Berberis integerrima has been widely used to treat diabetic complications, but exact molecular mechanism is yet to be discovered. Data on active ingredients of B. integerrima and target genes of both diabetic nephropathy and B.integerrima were obtained from public databases. Common results between B. integerrima and DN targets were used to create protein-protein interaction (PPI) network using STRING database and exported to Cytoscape software for the selection of hub genes based on degree of connectivity. Future, PPI network between constituents and overlapping targets was created using Cytoscape to investigate the network pharmacological effects of B. integerrima on DN. KEGG pathway analysis of core genes exposed their involvement in excess glucose-activated signaling pathway. Then, expression of core genes was validated through machine learning classifiers. Finally, PyRx and AMBER18 software was used for molecular docking and simulation. We found that Armepavine, Berberine, Glaucine, Magnoflorine, Reticuline, Quercetin inhibits the growth of diabetic nephropathy by affecting ICAM1, PRKCB, IKBKB, KDR, ALOX5, VCAM1, SYK, TBXA2R, LCK, and F3 genes. Machine learning revealed SYK and PRKCB as potential genes that could use as diagnostic biomarkers against DN. Furthermore, docking and simulation analysis showed the binding affinity and stability of the active compound with target genes. Our study revealed that B. integerrima has preventive effect on DN by acting on glucose-activated signaling pathways. However, experimental studies are needed to reveal biosafety profiles of B. integerrima in DN.Communicated by Ramaswamy H. Sarma.