A novel protein encoded by circINSIG1 reprograms cholesterol metabolism by promoting the ubiquitin-dependent degradation of INSIG1 in colorectal cancer.

BACKGROUND: Hypoxia is a hallmark of solid tumors and leads to the metabolic reprogramming of cancer cells. The role of epigenetic regulation between hypoxia and aberrant cholesterol metabolism in colorectal cancer (CRC) remains elusive. METHODS: Hypoxia-responsive circular RNAs (circRNAs) were identified by high throughput RNA sequencing between CRC cells cultured under normoxia or hypoxia. The protein-coding potential of circINSIG1 was identified by polysome profiling and LC-MS. The function of circINSIG1 was validated in vitro and in vivo by gain or loss of function assays. Mechanistic results were concluded by immunoprecipitation analyses. RESULTS: A novel hypoxia-responsive circRNA named circINSIG1 was identified, which was upregulated in CRC tissues and correlated with advanced clinical stages and poor survival. Mechanistically, circINSIG1 encoded a 121 amino acid protein circINSIG1-121 to promote K48-linked ubiquitination of the critical cholesterol metabolism regulator INSIG1 at lysine 156 and 158 by recruiting CUL5-ASB6 complex, a ubiquitin E3 ligase complex, thereby inducing cholesterol biosynthesis to promote CRC proliferation and metastasis. The orthotopic xenograft tumor models and patient-derived xenograft models further identified the role of circINSIG1 in CRC progression and potential therapeutic target of CRC. CONCLUSIONS: circINSIG1 presents an epigenetic mechanism which provides insights into the crosstalk between hypoxia and cholesterol metabolism, and provides a promising therapeutic target for the treatment of CRC.

Comparison of multi-mode Hong-Ou-Mandel interference and multi-slit interference.

Hong-Ou-Mandel (HOM) interference of multi-mode frequency entangled states plays a crucial role in quantum metrology. However, as the number of modes increases, the HOM interference pattern becomes increasingly complex, making it challenging to comprehend intuitively. To overcome this problem, we present the theory and simulation of multi-mode-HOM interference (MM-HOMI) and compare it to multi-slit interference (MSI). We find that these two interferences have a strong mapping relationship and are determined by two factors: the envelope factor and the details factor. The envelope factor is contributed by the single-mode HOM interference (single-slit diffraction) for MM-HOMI (MSI). The details factor is given by sin (Nx)/sin (x) ([sin (Nv)/sin (v)]2) for MM-HOMI (MSI), where N is the mode (slit) number and x (v) is the phase spacing of two adjacent spectral modes (slits). As a potential application, we demonstrate that the square root of the maximal Fisher information in MM-HOMI increases linearly with the number of modes, indicating that MM-HOMI is a powerful tool for enhancing precision in time estimation. We also discuss multi-mode Mach-Zehnder interference, multi-mode NOON-state interference, and the extended Wiener-Khinchin theorem. This work may provide an intuitive understanding of MM-HOMI patterns and promote the application of MM-HOMI in quantum metrology.

Spatial-spectral mapping to prepare frequency entangled qudits.

Entangled qudits, the high-dimensional entangled states, play an important role in the study of quantum information. How to prepare entangled qudits in an efficient and easy-to-operate manner is still a challenge in quantum technology. Here, we demonstrate a method to engineer frequency entangled qudits in a spontaneous parametric downconversion process. The proposal employs an angle-dependent phase-matching condition in a nonlinear crystal, which forms a classical-quantum mapping between the spatial (pump) and spectral (biphotons) degrees of freedom. In particular, the pump profile is separated into several bins in the spatial domain, and thus shapes the down-converted biphotons into discrete frequency modes in the joint spectral space. Our approach provides a feasible and efficient method to prepare a high-dimensional frequency entangled state. As an experimental demonstration, we generate a three-dimensional entangled state by using a homemade variable slit mask.

Common pathogenic bacteria-induced reprogramming of the host proteinogenic amino acids metabolism.

Apart from cancer, metabolic reprogramming is also prevalent in other diseases, such as bacterial infections. Bacterial infections can affect a variety of cells, tissues, organs, and bodies, leading to a series of clinical diseases. Common Pathogenic bacteria include Helicobacter pylori, Salmonella enterica, Mycobacterium tuberculosis, Staphylococcus aureus, and so on. Amino acids are important and essential nutrients in bacterial physiology and support not only their proliferation but also their evasion of host immune defenses. Many pathogenic bacteria or opportunistic pathogens infect the host and lead to significant changes in metabolites, especially the proteinogenic amino acids, to inhibit the host's immune mechanism to achieve its immune evasion and pathogenicity. Here, we review the regulation of host metabolism, while host cells are infected by some common pathogenic bacteria, and discuss how amino acids of metabolic reprogramming affect bacterial infections, revealing the potential adjunctive application of amino acids alongside antibiotics.

[Discussion on discipline of herbalism].

Since the emergence of the term "materia medica", scholars have proposed different opinions on its concept. This term has been used to refer to traditional Chinese medicines, or medical books, or traditional pharmacology. Due to the differences in the concept of materia medica, scholars also have controversies about the concept of herbalism. Herbalism is usually understood as traditional Chinese pharmacology. After years of evolution, the term "herbalism" has now possessed the characteristics of an independent discipline, which can be defined as an applied basic discipline that comprehensively utilizes traditional and modern technological methods to study the formation, development, and changes of traditional pharmacology and reveal the basic theories and application laws of traditional medicine. At present, the research content of herbalism mainly includes three aspects: materia medica history, materia medica literature, and traditional pharmacology. This study explores the disciplinary concepts and main research content of herbalism based on a systematic review of the literature about the concepts of materia medica and herbalism, with the aim of attracting more attention to promote the establishment and development of the discipline of herbalism.

Disrupted resting-state interhemispheric functional connectivity in systemic lupus erythematosus patients with and without neuropsychiatric lupus.

PURPOSE: The aim of the study is to explore interhemispheric homotopic functional connectivity alterations in systemic lupus erythematosus (SLE) patients with and without neuropsychiatric lupus (NPSLE and non-NPSLE, respectively) and their potential correlations with clinical characteristics and neuropsychological performance. METHODS: Based on resting-state functional MRI (rs-fMRI) data collected from SLE patients and matched healthy controls (HCs), the voxel-mirrored homotopic connectivity (VMHC) analysis was conducted to measure functional homotopy. Subsequently, correlations between altered functional homotopy and clinical/neuropsychological data were analyzed. RESULTS: Compared with the HC group, both NPSLE and non-NPSLE groups showed attenuated homotopic connectivity in middle temporal gyrus (MTG), cuneus (CUN), middle occipital gyrus (MOG), angular gyrus (ANG), and postcentral gyrus (PoCG). NPSLE patients also exhibited decreased homotopic connectivity in inferior parietal gyrus (IPG) and middle frontal gyrus (MFG). Compared with non-NPSLE patients, NPSLE patients showed weaker interhemispheric homotopic functional connectivity in MOG. Decreased homotopic functional connectivity in PoCG, IPG, and MOG were associated with the anxiety state of SLE patients. CONCLUSIONS: Our findings revealed attenuated functional homotopy in both NPSLE and non-NPSLE groups compared to the HC group, which appeared to be more severe in patients with comorbid neuropsychiatric lupus. Interhemispheric homotopy dysconnectivity may participate in the neuropathology of anxiety symptoms in SLE.

Control of pathogenic fungi on Panax notoginseng by volatile oils from the food ingredients Allium sativum and Foeniculum vulgare.

To screen natural drugs with strong inhibitory effects against pathogenic fungi related to P. notoginseng, the antifungal activities of garlic and fennel EOs were studied by targeting P. notoginseng disease-associated fungi, and the possible action mechanisms of garlic and fennel EOs as plant fungicides were preliminarily discussed. At present, the antifungal mechanism of EOs has not been fully established. Therefore, understanding the antifungal mechanism of plant EOs is helpful to address P. notoginseng diseases continuous cropping disease-related obstacles and other agricultural cultivation problems. First, the Oxford cup method and chessboard were used to confirm that the EOs and oxamyl had a significant inhibitory effect on the growth of Fusarium oxysporum. F. oxysporum is the main pathogen causing root rot of P. notoginseng and the preliminary study on the antifungal mechanisms of the EOs against F. oxysporum showed that the inhibition of EOs mainly affects cell membrane permeability and cell processes and affects the enzyme activities of micro-organism, to achieve antifungal effects. Finally, an in vivo model verified that both two EOs could significantly inhibit the occurrence of root rot caused by F. oxysporum.

Establishment and application of a TaqMan probe-based qPCR for the detection of Enterocytozoon hepatopenaei in shrimp Litopenaeus vannamei.

Enterocytozoon hepatopenaei (EHP) is a common parasite that invades the epithelial cytoplasm in the hepatopancreas of shrimp Litopenaeus vannamei and results in slow growth of the host shrimps to cause significant economic loss in shrimp aquaculture. In this study, a TaqMan probe-based qPCR for quantitative detection of EHP was established. A pair of specific primers and a TaqMan probe were designed based on the sequence of cysteine desulfurase gene (NFS1) of EHP. The standard curve between cycle threshold (Ct) and the logarithmic starting quantity (SQ) of the template was determined as Ct = - 3.231 lg (SQ) + 40.638, with a correlation coefficient (R2) of 0.998 and an amplification efficiency of 103.9%. The lower limit of quantification was 1.67 × 101 copies/µL for this TaqMan probe-based qPCR and 1.67 × 103 copies/µL for the conventional PCR. The TaqMan probe-based qPCR established in the research was 100 times more sensitive than the conventional PCR method. In addition, the results of clinical sample detection indicated that the present technique was efficient in detecting EHP in the hepatopancreas, feces, water, and pond bottom mud samples. Therefore, the established TaqMan probe-based qPCR is a suitable technique for detecting EHP in both shrimp and aquatic environment samples.

A novel NF-κB regulator encoded by circPLCE1 inhibits colorectal carcinoma progression by promoting RPS3 ubiquitin-dependent degradation.

BACKGROUND: Constitutive activation of nuclear factor-κB (NF-κB) signaling plays a key role in the development and progression of colorectal carcinoma (CRC). However, the underlying mechanisms of excessive activation of NF-κB signaling remain largely unknown. METHODS: We used high throughput RNA sequencing to identify differentially expressed circular RNAs (circRNAs) between normal human intestinal epithelial cell lines and CRC cell lines. The identification of protein encoded by circPLCE1 was performed using LC-MS. The function of novel protein was validated in vitro and in vivo by gain or loss of function assays. Mechanistic results were concluded by immunoprecipitation analyses. RESULTS: A novel protein circPLCE1-411 encoded by circular RNA circPLCE1 was identified as a crucial player in the NF-κB activation of CRC. Mechanistically, circPLCE1-411 promoted the ubiquitin-dependent degradation of the critical NF-κB regulator RPS3 via directly binding the HSP90α/RPS3 complex to facilitate the dissociation of RPS3 from the complex, thereby reducing NF-κB nuclear translocation in CRC cells. Functionally, circPLCE1 inhibited tumor proliferation and metastasis in CRC cells, as well as patient-derived xenograft and orthotopic xenograft tumor models. Clinically, circPLCE1 was downregulated in CRC tissues and correlated with advanced clinical stages and poor survival. CONCLUSIONS: circPLCE1 presents an epigenetic mechanism which disrupts NF-κB nuclear translocation and serves as a novel and promising therapeutic target and prognostic marker.

Mitochondrial Damage-Associated Molecular Patterns Exacerbate Lung Fluid Imbalance Via the Formyl Peptide Receptor-1 Signaling Pathway in Acute Lung Injury.

OBJECTIVES: To investigate the effect of mitochondrial damage-associated molecular patterns on the lung fluid homeostasis in experimental acute lung injury. DESIGN: Experimental study. SETTING: Research laboratory. SUBJECTS: Patients with acute respiratory distress syndrome and control subjects, wild-type C57BL/6 and formyl peptide receptor-1 gene knockout mice, and primary rat alveolar epithelial type II cells. INTERVENTIONS: Samples of bronchoalveolar lavage fluid and serum were obtained from patients and control subjects. Mice were intratracheally instilled with lipopolysaccharide and mitochondrial damage-associated molecular patterns. The primary rat alveolar epithelial type II cells were isolated and incubated with mitochondrial damage-associated molecular patterns. MEASUREMENTS AND MAIN RESULTS: Patients were divided into direct (pulmonary) and indirect (extrapulmonary) injury groups based on etiology. The release of mitochondrial peptide nicotinamide adenine dinucleotide dehydrogenase 1 in both bronchoalveolar lavage fluid and serum was induced in patients and was associated with etiology. In the lipopolysaccharide-induced lung injury, administration of mitochondrial damage-associated molecular patterns exacerbated the lung fluid imbalance, which was mitigated in formyl peptide receptor-1 knockout mice. Proteomic analysis of mouse lung tissues revealed the involvement of ion channels and tight junction proteins in this process. Treatment with mitochondrial damage-associated molecular patterns decreased the expression of epithelial sodium channel α, zonula occludens-1, and occludin via the formyl peptide receptor-1/p38 pathway in the primary rat alveolar epithelial type II cells. CONCLUSIONS: Mitochondrial damage-associated molecular patterns exacerbate lung fluid imbalance in the experimental acute lung injury model through formyl peptide receptor-1 signaling, the inhibition of which may prevent exacerbation of lung fluid imbalance induced by mitochondrial damage-associated molecular patterns. Thus, formyl peptide receptor-1 is a potential therapeutic target for acute respiratory distress syndrome.

Ischemic postconditioning attenuates acute kidney injury following intestinal ischemia-reperfusion through Nrf2-regulated autophagy, anti-oxidation, and anti-inflammation in mice.

Intestinal ischemia-reperfusion (IIR) often occurs during and following major cardiovascular or gut surgery and causes significant organ including kidney injuries. This study was to investigate the protective effect of intestinal ischemic postconditioning (IPo) on IIR-induced acute kidney injury (AKI) and the underling cellular signaling mechanisms with focus on the Nrf2/HO-1. Adult C57BL/6J mice were subjected to IIR with or without IPo. IIR was established by clamping the superior mesenteric artery (SMA) for 45 minutes followed by 120 minutes reperfusion. Outcome measures were: (i) Intestinal and renal histopathology; (ii) Renal function; (iii) Cellular signaling changes; (iv) Oxidative stress and inflammatory responses. IPo significantly attenuated IIR-induced kidney injury. Furthermore, IPo significantly increased both nuclear Nrf2 and HO-1 expression in the kidney, upregulated autophagic flux, inhibited IIR-induced inflammation and reduced oxidative stress. The protective effect of IPo was abolished by the administration of Nrf2 inhibitor (Brusatol) or Nrf2 siRNA. Conversely, a Nrf2 activator t-BHQ has a similar protective effect to that of IPo. Our data indicate that IPo protects the kidney injury induced by IIR, which was likely mediated through the Nrf2/HO-1 cellular signaling activation.

Lp-PLA2 inhibition prevents Ang II-induced cardiac inflammation and fibrosis by blocking macrophage NLRP3 inflammasome activation.

Macrophage-mediated inflammation plays an important role in hypertensive cardiac remodeling, whereas effective pharmacological treatments targeting cardiac inflammation remain unclear. Lipoprotein-associated phospholipase A2 (Lp-PLA2) contributes to vascular inflammation-related diseases by mediating macrophage migration and activation. Darapladib, the most advanced Lp-PLA2 inhibitor, has been evaluated in phase III trials in atherosclerosis patients. However, the role of darapladib in inhibiting hypertensive cardiac fibrosis remains unknown. Using a murine angiotensin II (Ang II) infusion-induced hypertension model, we found that Pla2g7 (the gene of Lp-PLA2) was the only upregulated PLA2 gene detected in hypertensive cardiac tissue, and it was primarily localized in heart-infiltrating macrophages. As expected, darapladib significantly prevented Ang II-induced cardiac fibrosis, ventricular hypertrophy, and cardiac dysfunction, with potent abatement of macrophage infiltration and inflammatory response. RNA sequencing revealed that darapladib strongly downregulated the expression of genes and signaling pathways related to inflammation, extracellular matrix, and proliferation. Moreover, darapladib substantially reduced the Ang II infusion-induced expression of nucleotide-binding oligomerization domain-like receptor with pyrin domain 3 (NLRP3) and interleukin (IL)-1ß and markedly attenuated caspase-1 activation in cardiac tissues. Furthermore, darapladib ameliorated Ang II-stimulated macrophage migration and IL-1ß secretion in macrophages by blocking NLRP3 inflammasome activation. Darapladib also effectively blocked macrophage-mediated transformation of fibroblasts into myofibroblasts by inhibiting the activation of the NLRP3 inflammasome in macrophages. Overall, our study identifies a novel anti-inflammatory and anti-cardiac fibrosis role of darapladib in Lp-PLA2 inhibition, elucidating the protective effects of suppressing NLRP3 inflammasome activation. Lp-PLA2 inhibition by darapladib represents a novel therapeutic strategy for hypertensive cardiac damage treatment.

[Hotspots and trends of Ophiopogonis Radix based on CiteSpace knowledge map].

Ophiopogonis Radix is an important Yin-nourishing drug in traditional Chinese medicine(TCM), with the effects of nourishing Yin, promoting fluid production, clearing away heart-fire, and relieving restlessness. It is widely used in clinical practice due to its multiple chemical components and pharmacological effects. The technique "mapping knowledge domains" is an effective tool to quantitatively and objectively visualize the development frontiers and trends of certain disciplines. In this study, TCM research papers related to Ophiopogonis Radix were retrieved from Web of Science(WoS) and CNKI, and the research institutions, journals, and keywords involved were visualized and analyzed using the scientometric software CiteSpace. The co-occurrence network of related research on Ophiopogonis Radix was constructed, and the Ophiopogonis Radix-disease-target network was plotted using Cytoscape 3.8.2. The hot topics in Chinese and English papers were analyzed and the shortcomings in the research on Ophiopogonis Radix were summed up. Furthermore, the development trends were discussed. A total of 1 403 Chinese papers and 292 English papers were included in this study. The analysis of research institutions showed that Beijing University of Chinese Medicine and China Pharmaceutical University were the two research institutions with the largest numbers of papers published. The analysis of journals showed that Hebei Journal of Traditional Chinese Medicine and Journal of Asian Natural Products Research were the two journals with the highest numbers of papers concerning Ophiopogonis Radix. The keyword analysis showed that the research contents of Chinese papers focused on the analysis of medication regularity and clinical observation trials, while the English papers focused on component analysis and pharmacological investigation. Data mining and apoptosis-based pharmacological mechanism might be the research trends in the future.

Catalytic Asymmetric Halogenation/Semipinacol Rearrangement of 3-Hydroxyl-3-vinyl Oxindoles: A Stereodivergent Kinetic Resolution Process.

A highly enantioselective halogenation/semipinacol rearrangement of isatin-derived allylic alcohols has been developed with a chiral N,N'-dioxide/ScIII complex as catalyst. This strategy involved a pivotal stereodivergent kinetic resolution process and provided a facile and efficient entry to optically active halo-substituted quinolone derivatives and quinoline alkaloids with a quaternary stereocenter simultaneously under mild reaction conditions. Based on the control experiments together with kinetic studies and DFT calculations, a possible catalytic cycle was proposed to illustrate the reaction process and enantiocontrol.

Biological Activities of Two Essential Oils from Pogostemon cablin and Eupatorium fortunei and Their Major Components against Fungi Isolated from Panax notoginseng.

Panax notoginseng (Burkill) F.H.Chen (Araliaceae), of which the dry root and rhizome are precious traditional Chinese medicine, suffers severely from diseases during planting. Essential oils (EOs) with antimicrobial activity are a possibility for the development of green pesticides. We extracted EOs from Pogostemon cablin (Blanco) Benth. and Eupatorium fortunei Turcz., respectively and tested their inhibitory rates on fungi isolated from diseased P. notoginseng by the Oxford cup method. The compounds of the EO were identified by GC/MS and the minimum inhibitory concentrations (MICs) of the EOs and their main components were evaluated by the 96-well plate method. We also mixed P. cablin EO, E. fortunei EO and hymexazol in pairs to explore whether their combinations produce stronger antifungal effects than individual components. Finally, we evaluated the effects of the EOs against Fusarium oxysporum in vivo. P. cablin EO and E. fortunei EO exhibited different antifungal activities against fungi, with the inhibitory rates of 21.02 %-100 % and 54.84 %-100 % and MICs of 0.07-0.88 mg/mL and 0.20-1.17 mg/mL, respectively. Pogostone (24.96 %) and thymol (15.64 %) were the major compounds of P. cablin EO and E. fortunei EO, respectively, and they exhibited stronger antifungal activities than EOs, with MICs of 0.008-0.078 mg/mL and 0.12-0.31 mg/mL, respectively. Moreover, hymexazol was mixed with E. fortunei EO, and the inhibitory effect against Cylindrocarpon destructans was enhanced with a synergistic effect. The disease incidence and disease index of EO treatments decreased significantly in vivo. Based on our study, P. cablin EO and E. fortunei EO have great potential to be developed into green fungicides for use in agriculture to control diseases of P. notoginseng.

[Predictive Factors of Early Weight Loss after Laparoscopic Sleeve Gastrectomy].

Objective To explore the clinical factors that can be used to predict the early weight loss after laparoscopic sleeve gastrectomy(LSG).Methods The clinical data of 64 obese patients undergoing LSG in Peking Union Medical College Hospital from August 2015 to January 2018 were retrospectively analyzed.We analyzed the relationship between different clinical factors and early weight loss,determined the independent predictors based on Logistic models,and estimated their test power by using the receiver operating characteristic(ROC)curves.Results Correlation analysis indicated that preoperative body mass index(P=0.000,P=0.000,P=0.000),waist circumference(WC)(P=0.000,P=0.000,P=0.000),whole body fat volume(P=0.000,P=0.006,P=0.003),homeostatic model assessment for insulin resistance(HOMA-IR)(P=0.000,P=0.000,P=0.002),and hypersensitive C-reactive protein(hsCRP)(P=0.004,P=0.002,P=0.025)were negatively correlated with excess weight loss percentage(EWL %) after 3,6 and 12 months.Also,hsCRP after 6 months showed negative correlation with EWL % after 1 year(P=0.029).Binary Logistic regression analysis showed that WC was an independent predictor of early weight loss(P=0.018).ROC analysis showed that when the optimal cutoff value is 142.5 cm for WC,Youden index was highest,with a sensitivity of 80% and a specificity of 87%.Patients were further divided into low WC group and high WC group based on this optimal cutoff value.The low WC group had significantly higher EWL% than the high WC group 3 months(t=6.677,P=0.000),6 months(t=6.157,P=0.000),and 1 year(t=4.006,P=0.000)after surgery.The low WC group also had significantly lower hsCRP than high WC group 6 months after surgery(z=-3.510,P=0.000).HOMA-IR showed no significant difference between these two groups(z=-0.821,P=0.412).Conclusions WC is an independent predictor of weight loss early after LSG.The patients with low WC have better weight loss effectiveness.

[History, Recent Advancements, and Prospects in Bariatric/Metabolic Surgery].

Bariatric/metabolic surgery is the most effective method to treat morbid obesity and its complications. Tracing its origin back to jejunoileal bypass in 1950s, bariatric/metabolic surgery has been continuously improved after more than 60 years of development. At present, the mainstream surgical procedures include sleeve gastrectomy, Roux-en-Y gastric bypass, biliopancreatic diversion/duodenal switch, and mini gastric bypass. In addition, new procedures such as single-anastomosis duodenal switch, duodenal-jejunal bypass with sleeve gastrectomy, laparoscopic greater curvature plication and endoscopic surgeries have been developed. This article reviews the history, status quo, and prospects of bariatric/metabolic surgery.

SIKVAV promotion proliferation of vascular endothelial cells and related mechanisms.

BACKGROUND: Vascular endothelial injury, a key factor in diabetic foot ulcers (DFUs) pathogenesis, is linked to the impaired proliferation and migration of vascular endothelial cells, modulated by hypoxia-inducible factor, growth factors, and inflammatory elements. OBJECTIVE: The present study assesses the role of SIKVAV (Ser-Ile-Lys-Val-Ala-Val), a peptide shown to enhance cell proliferation and migration, on mouse aortic endothelial cell (MAEC) and the corresponding molecular mechanisms. METHODS: MAEC were treated with SIKVAV at 0, 100, 200, 400, and 600 µg/mL for 0, 24, 48, and 72 h. Cell viability was tested using the CCK-8 assay. Proliferating cell nuclear antigen (PCNA), extracellular signal-regulated kinase 1/2 (ERK1/2), and protein kinase B (Akt) levels were measured by qRT-PCR and western blot. RESULTS: SIKVAV augmented PCNA mRNA expression and stimulated vascular endothelial cell proliferation in a concentration and time-dependent fashion. Furthermore, it amplified the expression of p-ERK1/2 and p-Akt, pivotal components of the mitogen-activated protein kinase (MAPK)/ERK1/2 and phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathways. The inhibition of these pathways suppressed PCNA mRNA expression, cell proliferation rate, and decreased p-ERK1/2 and p-Akt levels, highlighting SIKVAV's role in promoting vascular endothelial cell proliferation via these pathways. CONCLUSION: The results of this study confirmed that SIKVAV grafted onto scaffolds can accelerate the proliferation of vascular endothelial cells for the therapy of skin wounds, and provide a theoretical basis for its application in ischemic disease as synthesized biomaterials scaffolds of tissue engineering.

Diurnal variation of postoperative delirium in elderly patients undergoing esketamine anesthesia for elective noncardiac surgery: a randomized clinical trial.

BACKGROUND: Postoperative delirium (POD) is a serious and common complication. The aim of present study is to investigate the diurnal variation of POD and the effects of esketamine in elderly patients. METHODS: A randomized, double-blind, placebo-controlled clinical trial with factorial design was conducted. Patients (aged 65 to 85 years) with normal Mini-Mental State Examination (MMSE) score were stratified by age (≤70 vs. >70) and American Society of Anesthesiologists physical status classification (Ⅱ vs. Ⅲ), then randomly assigned to either morning (08:00-12:00) or afternoon (14:00-18:00) noncardiac operation under general anesthesia with or without esketamine administration (0.2 mg/kg). The primary outcome was the incidence of POD (3-Minute Diagnostic Interview for Confusion Assessment Method-defined Delirium, 3D-CAM) on postoperative days 1, 3, and 7. The secondary outcomes were the scores of MMSE and Hospital Anxiety and Depression Scale. The intention-to-treat analysis of the outcomes were performed by generalized estimating equation. RESULTS: Six patients who did not receive an intervention because of canceled operation were excluded after randomization. The datasets containing 426 cases were analyzed following the intention-to-treat principle after handling missing data via multiple imputation method. The incidence of POD declined from about 55% on postoperative day 1 to 31 and 18% on postoperative days 3 and 7, respectively. Afternoon operation [B=-0.583, OR (95% CI) 0.558 (0.319-0.976); P=0.041], but not esketamine, significantly decreased the incidence of POD. Both esketamine and operation time failed to significantly affect MMSE, HAD, and NRS score. There was no interaction among operation time, esketamine, and follow up time. CONCLUSION: Elderly patients undergoing elective noncardiac surgery in the afternoon displayed lower POD incidence than those operated in the morning. A single low-dose of esketamine before general anesthesia induction failed to significantly decrease the risk of POD but decrease the risk of intraoperative hypotension and emergence agitation.

Deep Learning-based 12-Lead Electrocardiogram for Low Left Ventricular Ejection Fraction Detection in Patients.

BACKGROUND: Reduced left ventricular ejection fraction (LVEF) initiates heart failure, and promptly identifying low ejection fraction is crucial for managing progression and averting mortality. This study developed an artificial intelligence-enabled electrocardiogram (AI-ECG) algorithm to identify patients with low ejection fraction and predict LVEF values. METHODS: The ECG data were used as input, and the algorithm generated the probability of the patient suffering a low ejection fraction as well as estimating the LVEF value. A 5-year follow-up study on a group of individuals who initially had normal LVEF values was also performed. Furthermore, external validation of the algorithm performance was conducted using the Medical Information Mart for Intensive Care (MIMIC-IV) database. RESULTS: The algorithm's performance on the test set yielded an area under the curve (AUC) of 0.965 for detecting LVEF ≤ 50%. The algorithm had an accuracy of 92.8%, sensitivity of 88.8%, and specificity of 92.9%. For LVEF regression, the method showed a mean absolute error (MAE) of 5.28 (95% CI: 5.23 - 5.33) for the testing set. Additionally, the algorithm obtained an AUC value of 0.848 and an MAE value of 9.56 during external validation. Patients with false-positive results had a significantly greater likelihood of developing a low ejection fraction compared to patients who received true negative results (26.2% vs. 2.0%, P < 0.0001). CONCLUSIONS: The AI-ECG algorithm is capable of identifying low ejection fraction in patients with high accuracy. The AI-ECG algorithm is an efficient, prompt, and cost-effective screening tool for early heart failure.