KAT8/SIRT7-mediated Fascin-K41 acetylation/deacetylation regulates tumor metastasis in esophageal squamous cell carcinoma.

Fascin actin-bundling protein 1 (Fascin) is highly expressed in a variety of cancers, including esophageal squamous cell carcinoma (ESCC), working as an important oncogenic protein and promoting the migration and invasion of cancer cells by bundling F-actin to facilitate the formation of filopodia and invadopodia. However, it is not clear how exactly the function of Fascin is regulated by acetylation in cancer cells. Here, in ESCC cells, the histone acetyltransferase KAT8 catalyzed Fascin lysine 41 (K41) acetylation, to inhibit Fascin-mediated F-actin bundling and the formation of filopodia and invadopodia. Furthermore, NAD-dependent protein deacetylase sirtuin (SIRT) 7-mediated deacetylation of Fascin-K41 enhances the formation of filopodia and invadopodia, which promotes the migration and invasion of ESCC cells. Clinically, the analysis of cancer and adjacent tissue samples from patients with ESCC showed that Fascin-K41 acetylation was lower in the cancer tissue of patients with lymph node metastasis than in that of patients without lymph node metastasis, and low levels of Fascin-K41 acetylation were associated with a poorer prognosis in patients with ESCC. Importantly, K41 acetylation significantly blocked NP-G2-044, one of the Fascin inhibitors currently being clinically evaluated, suggesting that NP-G2-044 may be more suitable for patients with low levels of Fascin-K41 acetylation, but not suitable for patients with high levels of Fascin-K41 acetylation. © 2024 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

T cell infiltration mediates neurodegeneration and cognitive decline in Alzheimer's disease.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder with pathological features of ß-amyloid (Aß) and hyperphosphorylated tau protein accumulation in the brain, often accompanied by cognitive decline. So far, our understanding of the extent and role of adaptive immune responses in AD has been quite limited. T cells, as essential members of the adaptive immune system, exhibit quantitative and functional abnormalities in the brains of AD patients. Dysfunction of the blood-brain barrier (BBB) in AD is considered one of the factors leading to T cell infiltration. Moreover, the degree of neuronal loss in AD is correlated with the quantity of T cells. We first describe the differentiation and subset functions of peripheral T cells in AD patients and provide an overview of the key findings related to BBB dysfunction and how T cells infiltrate the brain parenchyma through the BBB. Furthermore, we emphasize the risk factors associated with AD, including Aß, Tau protein, microglial cells, apolipoprotein E (ApoE), and neuroinflammation. We discuss their regulation of T cell activation and proliferation, as well as the connection between T cells, neurodegeneration, and cognitive decline. Understanding the innate immune response is crucial for providing comprehensive personalized therapeutic strategies for AD.

A non-invasive artificial intelligence model for identifying axillary pathological complete response to neoadjuvant chemotherapy in breast cancer: a secondary analysis to multicenter clinical trial.

BACKGROUND: This study aims to develop a stacking model for accurately predicting axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) using longitudinal MRI in breast cancer. METHODS: We included patients with node-positive breast cancer who received NAC following surgery from January 2012 to June 2022. We collected MRIs before and after NAC, and extracted radiomics features from the tumour, peritumour, and ALN regions. The Mann-Whitney U test, least absolute shrinkage and selection operator, and Boruta algorithm were used to select features. We utilised machine learning techniques to develop three single-modality models and a stacking model for predicting ALN response to NAC. RESULTS: This study consisted of a training cohort (n = 277), three external validation cohorts (n = 313, 164, and 318), and a prospective cohort (n = 81). Among the 1153 patients, 60.62% achieved ypN0. The stacking model achieved excellent AUCs of 0.926, 0.874, and 0.862 in the training, external validation, and prospective cohort, respectively. It also showed lower false-negative rates (FNRs) compared to radiologists, with rates of 14.40%, 20.85%, and 18.18% (radiologists: 40.80%, 50.49%, and 63.64%) in three cohorts. Additionally, there was a significant difference in disease-free survival between high-risk and low-risk groups (p < 0.05). CONCLUSIONS: The stacking model can accurately predict ALN status after NAC in breast cancer, showing a lower false-negative rate than radiologists. TRIAL REGISTRATION NUMBER: The clinical trial numbers were NCT03154749 and NCT04858529.

Noninvasive Artificial Intelligence System for Early Predicting Residual Cancer Burden during Neoadjuvant Chemotherapy in Breast Cancer.

OBJECTIVE: To develop an artificial intelligence (AI) system for the early prediction of residual cancer burden (RCB) scores during neoadjuvant chemotherapy (NAC) in breast cancer. SUMMARY BACKGROUND DATA: RCB III indicates drug resistance in breast cancer, and early detection methods are lacking. METHODS: This study enrolled 1048 patients with breast cancer from four institutions, who were all receiving NAC. Magnetic resonance images were collected at the pre- and mid-NAC stages, and radiomics and deep learning features were extracted. A multitask AI system was developed to classify patients into three groups (RCB 0-I, II, and III ) in the primary cohort (PC, n=335). Feature selection was conducted using the Mann-Whitney U- test, Spearman analysis, least absolute shrinkage and selection operator regression, and the Boruta algorithm. Single-modality models were developed followed by model integration. The AI system was validated in three external validation cohorts. (EVCs, n=713). RESULTS: Among the patients, 442 (42.18%) were RCB 0-I, 462 (44.08%) were RCB II and 144 (13.74%) were RCB III. Model-I achieved an area under the curve (AUC) of 0.975 in the PC and 0.923 in the EVCs for differentiating RCB III from RCB 0-II. Model-II distinguished RCB 0-I from RCB II-III, with an AUC of 0.976 in the PC and 0.910 in the EVCs. Subgroup analysis confirmed that the AI system was consistent across different clinical T stages and molecular subtypes. CONCLUSIONS: The multitask AI system offers a noninvasive tool for the early prediction of RCB scores in breast cancer, supporting clinical decision-making during NAC.

Tanshinone IIA attenuates osteoarthritis via inhibiting aberrant angiogenesis in subchondral bone.

Excessive angiogenesis in subchondral bone is a pathological feature of osteoarthritis (OA). Tanshinone IIA (TIIA), an active compound found in Salvia miltiorrhiza, demonstrates significant anti-angiogenic properties. However, the effect of TIIA on abnormal subchondral angiogenesis in OA is still unclear. This study aims to investigate the mechanism of TIIA in modulating subchondral bone angiogenesis during OA and assess its therapeutic potential in OA. Our findings demonstrate that TIIA attenuated articular cartilage degeneration, normalized subchondral bone remodeling, and effectively suppressed aberrant angiogenesis within subchondral bone in monosodium iodoacetate (MIA)-induced OA mice. Additionally, the angiogenesis capacity of primary CD31hiEmcnhi endothelial cells was observed to be significantly reduced after treatment with TIIA in vitro. Mechanically, TIIA diminished the proportion of hypertrophic chondrocytes, ultimately leading to a substantial reduction in the secretion of vascular endothelial growth factor A (VEGFA). The supernatant of hypertrophic chondrocytes promoted the tube formation of CD31hiEMCNhi endothelial cells, whereas TIIA inhibited this process. Furthermore, TIIA effectively suppressed the expression of vascular endothelial growth factor receptor 2 (VEGFR2) along with its downstream MAPK pathway in CD31hiEmcnhi endothelial cells. In conclusion, our data indicated that TIIA could effectively inhibit the abnormal angiogenesis in subchondral bone during the progression of OA by suppressing the VEGFA/VEFGR2/MAPK pathway. These findings significantly contribute to our understanding of the abnormal angiogenesis in OA and offer a promising therapeutic target for OA treatment.

Arginine vasopressin induces ferroptosis to promote heart failure via activation of the V1aR/CaN/NFATC3 pathway.

Arginine vasopressin (AVP) is a key contributor to heart failure (HF), but the underlying mechanisms remain unclear. In the present study, a mouse model of HF and human cardiomyocyte (HCM) cells treated with dDAVP are generated in vivo and in vitro, respectively. Hematoxylin and eosin (HE) staining is used to evaluate the morphological changes in the myocardial tissues. A colorimetric method is used to measure the iron concentration, Fe 2+ concentration and malondialdehyde (MDA) level. Western blot analysis is used to examine the protein levels of the V1a receptor (V1aR), calcineurin (CaN), nuclear factor of activated T cells isoform C3 (NFATC3), glutathione peroxidase 4 (GPX4) and acyl-CoA synthase long chain family member 4 (ACSL4). Immunoprecipitation (IP) and luciferase reporter assays are performed to determine the interaction between NFATC3 and ACSL4. Both in vivo and in vitro experiments reveal that the V1aR-CaN-NFATC3 signaling pathway and ferroptosis are upregulated in HFs, which are verified by the elevated protein levels of V1aR, CaN, NFATC3 and ACSL4; reduced GPX4 protein level; and enhanced Fe 2+ and MDA levels. We further find that inhibiting NFATC3 by suppressing the V1aR/CaN/NFATC3 pathway via V1aR/CaN inhibitors or sh-NFATC3 not only alleviates HF but also inhibits AVP-induced ferroptosis. Mechanistically, sh-NFATC3 significantly reverses the increase in AVP-induced ACSL4 protein level, Fe 2+ concentration, and MDA level by directly interacting with ACSL4. Our results demonstrate that AVP enhances ACSL4 expression by activating the V1aR/CaN/NFATC3 pathway to induce ferroptosis, thus contributing to HF. This study may lead to the proposal of a novel therapeutic strategy for HF.

Wogonin preconditioning of MSCs improved their therapeutic efficiency for colitis through promoting glycolysis.

Inflammatory bowel diseases (IBDs) are prevalent and debilitating diseases with limited clinical treatment strategies. Mesenchymal stem cell (MSCs) are pluripotent stem cells with self-renewal capability and multiple immunomodulatory effects, which make them a promising therapeutic approach for IBDs. Thus, optimization of MSCs regimes is crucial for their further clinical application. Wogonin, a flavonoid-like compound with extensive immunomodulatory and adjuvant effects, has been investigated as a potential pretreatment for MSCs in IBD treatment. In this study, we employed the DSS-induced acute colitis mouse model to compare the therapeutic effectiveness of MSCs in pretreated with or without wogonin and further explore the underlying mechanism. Compared to untreated MSCs, MSCwogonin (pretreated with wogonin) showed greater effectiveness in the treatment of colitis. Further experiments revealed that wogonin treatment activated the AKT signaling pathway, resulting in higher cellular glycolysis. Inhibition of AKT phosphorylation by perifosine not only decreased glycolysis but impaired the therapeutic efficiency of MSCwogonin. Consistent with these results, qPCR data indicated that wogonin treatment induced the expression of immunomodulatory molecules IL-10, IDO, and AGR1, which were reduced by perifosine. Together, our data demonstrated that wogonin preconditioning strategy further augmented the therapeutic efficacy of MSCs via promoting glycolysis, which should be a promising strategy for optimizing MSCs therapy in IBDs.

From Research to Roach Traps: Practical Considerations for a Home-Based Asthma Program.

CONTEXT: Home-based asthma interventions have a significant evidence base as an effective means to address moderate and severe breathing concerns triggered by home conditions. However, the literature lacks logistical and staffing considerations necessary to successfully implement such a program at a governmental level. This practice report and process evaluation outlines practical details and lessons learned during a healthy homes pilot, and how they were addressed in the design of a permanent program. OBJECTIVE: To inform the creation of a permanent home-based asthma intervention at the Alexandria Health Department (AHD) (City of Alexandria, Virginia) and understand the tools and resources necessary for success. INTERVENTION: Participating households received a health and environmental assessment, followed by cleaning supplies, relevant education, and referrals to partners for services. AHD staff tracked challenges and insights at each step of the intervention. At the end of the pilot, staff worked with the community to identify solutions and design a permanent program. CONCLUSIONS: Although the pilot model was constructed based on existing case studies, technical assistance from national experts, and guidance documents, the team still experienced challenges around recruitment, staff support, home visit implementation, and impact evaluation. While pilots and existing literature can be instructive for identifying issues, work with residents and partners to develop a uniquely tailored community program was essential for practical success. IMPLICATIONS ON POLICY AND PRACTICE: Health departments developing new initiatives should consider both the staff and participant experience throughout the creation of administrative and programmatic processes. Testing out draft versions of these processes and materials using internal and external focus groups can identify potential bottlenecks and solutions upfront.

Exosome-Mediated lncRNA LINC01140 Attenuates Breast Cancer Progression by Regulating the Wnt/ß-Catenin Pathway.

Exosome-delivered long non-coding RNAs have a role in the cancer control. It is unknown how exosomal LINC01140 contributes to the breast cancer (BC) growth. The purpose of this investigation is to identify exosomal LINC01140's function in the development of breast cancer. Using quantitative reverse transcripion polymerase chain reaction, the expression of LINC01140 was measured. To investigate how LINC01140 overexpression impacts BC cell proliferation, CCK-8 as well as colony formation assays (CFA) were employed. The expression of apoptosis-related proteins (Bax and Bcl-2) and Wnt/ß-catenin signal pathway-related proteins (Wnt, C-myc, ß-catenin, and p-GSK-3ß) was assessed through Western blotting. Exosomes from BC cells were verified by western blotting to measure CD63 and CD9 levels. To examine how exosomal LINC01140 affects Wnt/ß-catenin signaling pathway and xenograft tumor in nude mice, BC cell exosomes that were overexpressing LINC01140 were obtained and co-cultured with BC cells. In BC, it was discovered that LINC01140 had poor expression. BC cell proliferation was inhibited by overexpressing LINC01140, and the levels of the proteins Bcl-2, ß-catenin, C-myc, and Wnt were lowered while Bax and p-GSK-3 were increased. In addition, exosomal LINC01140 hindered the activation of the Wnt/ß-catenin signaling pathway, leading to a decrease in the growth of breast cancer cells in vivo. The presence of exosomal LINC01140 impedes the initiation of Wnt/ß-catenin and reduces the cancerous characteristics of BC cells.

Characterization of pollen tube development in distant hybridization of Chinese cork oak (Quercus variabilis L.).

MAIN CONCLUSION: This work mainly found that the stigma and style of Q. variabilis did not completely lose the specific recognition towards heterologous pollen, a fact which is different from previous studies. Quercus is the foundation species in the Northern Hemisphere, with extreme prevalence for interspecific hybridization. It is not yet entirely understood whether or how the pollen tube-female tissue interaction contributes to the "extensive hybridization" in oaks. Pollen storage conditions correlate with distant hybridization. We conducted hybridization experiments with Q. variabilis as female and Q. variabilis and Q. mongolica as male parents. And the differences in pollen tube (PT) development between intra- and distant interspecific hybridization were studied by fluorescence microscopy and scanning electron microscopy (SEM). Our results showed that -20 °C allowed pollen of both species to maintain some viability. Both Q. variabilis and Q. mongolica pollen germinated profusely on the stigmas. SEM results indicated that in the intraspecific hybridization, Q. variabilis pollen started to germinate at 6 h after pollination (hap), PTs elongated significantly at 12 hap, and entered the stigma at 24 hap. By contrast, Q. mongolica pollen germinated at 15 hap, and the PTs entered the stigma at 27 hap. By fluorescence microscopical studies it was observed that some PTs of Q. variabilis gathered at the style-joining at 96 hap, unlike the Q. mongolica which reached the style junction at 144 hap. The above results indicate that the abundant germination of heterologous pollen (HP) on the stigma and the "Feeble specificity recognition" of the stigma and transmitting tract to HP may create opportunities for the "extensive hybridization" of oaks. This work provides a sexual developmental reference for clarifying the causes of Quercus "extensive hybridization".

Quercetin alleviates Mycoplasma gallisepticum-induced inflammatory damage and oxidative stress through inhibition of TLR2/MyD88/NF-κB pathway in vivo and in vitro.

Chronic respiratory disease (CRD) caused by Mycoplasma gallisepticum (MG) in chickens leads to enormous economic damage to the poultry industry yearly. The active components and mechanism of action of the traditional herbal remedy Ephedra houttuynia powder (EHP), which had been approved for clinical treatment against MG infection in China, remain unknown. In this study, the active components of EHP against MG were screened using a network pharmacological method, additionally, we studied the mechanism of action of the screened results (quercetin (QUE)). The findings demonstrated that QUE was an essential element of EHP against MG infection, effectively attenuating MG-induced oxidative stress and activation of the TLR2/MyD88/NF-κB pathway. Following QUE therapy, IL-1, IL-6, and TNF-α content and expression were downregulated, whereas IL-4 and IL-10 expression were upregulated, eventually suppressing the inflammatory response both in vitro and in vivo. Together, this study presents a strong rationale for using QUE as a therapeutic strategy to inhibit MG infection-induced inflammatory damage and oxidative stress.

Cocrystallization-Driven Double-Optimized Stratagem toward Directional Self-Assembly for the First Ternary Salt Cocrystal of Cardiotonic Drug Milrinone with Different Phenolic Acids Exhibits Optimal In Vitro/Vivo Biopharmaceutical Peculiarities.

The current research leverages the structural features and property superiorities along with benefits in protecting cardiovascular system of gallic acid (GLC) and gentisic acid (HGA) to optimize in vitro/vivo peculiarities of cardiotonic drug milrinone (MIL) through developing a stratagem of cocrystallization-driven double-optimized ternary salt cocrystal. This strategy assembles MIL ternary salt cocrystal by shaping a cocrystallization moiety relying on noncovalent interplays with GLC to obtain permeability advancement and molding a salt segment via the salification of proton transfer between HGA and MIL molecules to facilitate solubility enhancement. While the ameliorative in vitro properties further modulate the in vivo pharmacokinetic behaviors, thus fulfilling a dual optimization of MIL's biopharmaceutical characteristics on both in vitro and in vivo aspects. Along this line, the first MIL ternary salt cocrystal, viz., [HMIL+-GA-]-MIL-GLC-H2O (denoted as MTSC hereinafter), has been satisfactorily constructed and precisely structurally identified by diversified techniques. The single-crystal X-ray diffraction experiment validates that a molecular salt [HMIL+-GA-] species cocrystallizes with one neutral MIL, two GLC, and five solvent water molecules, among which the organic constituents compose laminated hydrogen bond networks, and then are self-assembled by water molecules to a 3D supramolecular structure. The unique structural feature and stacking pattern of MTSC make both the permeability and solubility be respectively enhanced by 9.69 times and 5.17- to 6.03-fold compared with the parent drug per se. The experimental outcomes are powerfully supported by associated calculations based on density functional theory. Intriguingly, these optimal in vitro physicochemical natures of MTSC have been potently converted into strengths of in vivo pharmacokinetics, showcasing the elevated drug plasma concentration, elongated half-life, alongside advanced bioavailability. Consequently, this presentation not just contributes a brand-new crystalline form with utility values, but ushers in a new dimension of ternary salt cocrystals for improving in vitro/vivo limitations of poor drug bioavailability.

Correction: Supramolecular self-assembly of amantadine hydrochloride with ferulic acid via dual optimization strategy establishes a precedent of synergistic antiviral drug-phenolic acid nutraceutical cocrystal.

Correction for 'Supramolecular self-assembly of amantadine hydrochloride with ferulic acid via dual optimization strategy establishes a precedent of synergistic antiviral drug-phenolic acid nutraceutical cocrystal' by Ling-Yang Wang et al., Analyst, 2021, 146, 3988-3999, https://doi.org/10.1039/D1AN00478F.

Influence of enhanced external counterpulsation on endothelial function: a meta-analysis of randomized controlled trials.

OBJECTIVES: Enhanced external counterpulsation (EECP) is an effective and noninvasive treatment for patients with refractory angina and chronic heart failure. However, previous studies evaluating the influence of EECP on endothelial function showed inconsistent results. This systematic review and meta-analysis was conducted to evaluate the effects of EECP on endothelial function measured by brachial artery flow-mediated dilation (FMD). DESIGN: PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases were searched for randomized controlled trials comparing the influence of EECP versus usual care on FMD in adult population. A random-effects model incorporating the potential influence of heterogeneity was used to pool the results. RESULTS: Nineteen studies with 1647 patients were included in the meta-analysis. Compared with usual care or conventional therapy, additional treatment with EECP for 3-7 weeks was associated with a significantly improved FMD (mean difference [MD]: 1.96%, 95% confidence interval [CI]: 1.57-2.36, p < 0.001, I2 = 52%). Subgroup analysis showed consistent results in patients with coronary artery disease and in patients with other diseases (p for subgroup difference = 0.21). Results of meta-regression analysis showed that the mean baseline FMD level was positively correlated with the influence of EECP on FMD (coefficient = 0.42, p < 0.001). Results of subgroup analysis suggested that the increment of FMD following EECP was larger in patients with baseline FMD ≥ 5% (MD: 2.69, 95% CI: 2.27-3.10, p < 0.001; I2 = 15%) compared to those with baseline FMD < 5% (MD: 1.49, 95% CI: 1.13-1.85, p < 0.001; I2 = 0%; p for subgroup difference < 0.001). CONCLUSIONS: EECP may be effective in improving endothelial function measured by FMD.

Systematic Proteome and Lysine Succinylome Analysis Reveals Enhanced Cell Migration by Hyposuccinylation in Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with poor therapeutic outcomes. However, the alterations in proteins and posttranslational modifications (PTMs) leading to the pathogenesis of ESCC remain unclear. Here, we provide the comprehensive characterization of the proteome, phosphorylome, lysine acetylome, and succinylome for ESCC and matched control cells using quantitative proteomic approach. We identify abnormal protein and PTM pathways, including significantly downregulated lysine succinylation sites in cancer cells. Focusing on hyposuccinylation, we reveal that this altered PTM was enriched on enzymes of metabolic pathways inextricably linked with cancer metabolism. Importantly, ESCC malignant behaviors such as cell migration are inhibited once the level of succinylation was restored in vitro or in vivo. This effect was further verified by mutations to disrupt succinylation sites in candidate proteins. Meanwhile, we found that succinylation has a negative regulatory effect on histone methylation to promote cancer migration. Finally, hyposuccinylation is confirmed in primary ESCC specimens. Our findings together demonstrate that lysine succinylation may alter ESCC metabolism and migration, providing new insights into the functional significance of PTM in cancer biology.

Clinical Efficacy of Fractional Flow Reserve-Guided Percutaneous Coronary Intervention in Coronary Heart Disease Patients with SYNTAX Score ≥33 and Euro Score ≥6: A Single-Center Retrospective Analysis.

OBJECTIVE: To observe clinical efficacy of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) in coronary heart disease patients with SYNTAX scores (SS) ≥33 and Euro Scores (ES) ≥6 who are unsuitable for or have declined coronary artery bypass graft (CABG). METHODS: A total of 117 patients with SS ≥33 and Euro Score (ES) ≥6 who were unsuitable for and/or who had declined CABG between Jan 2021 and June 2022 were enrolled in this retrospective analysis. All patients accepted optimal medical therapy and some accepted an FFR-guided PCI procedure. Patients who only underwent optimal medical therapy were divided into the optimal medical therapy group (OMT group) and patients who simultaneously underwent FFR-guided PCI procedure were divided into the PCI group in this retrospective analysis. All patients accepted follow-up for at least 12 months after discharge. RESULTS: SS and ES in the two groups were not statistically different (p > 0.05). Patients with chronic total occlusion accounted for a greater proportion in the PCI subgroup (31.3%, 5/16) than in other subgroups. Eighteen (18.6%, 18/97) cases in the PCI group developed major adverse cardiac and cerebrovascular events (MACCEs). There were 12 (60%, 12/20) cases of MACCEs in the OMT group, which was statistically different from the PCI group (p < 0.05). CONCLUSIONS: Based on optimal medical therapy, FFR-guided PCI can still have clinical benefit to coronary artery disease patients with SS ≥33 who were not suitable for CABG.

Risk Factors for Poor Prognosis in Acute Coronary Syndrome Admitted in the Emergency Department: A Retrospective Cohort Study.

BACKGROUND: In the present study, we aimed to identify risk factors of poor prognosis for patients with acute coronary syndrome in the emergency department. METHODS: The study included 2667 patients, who were admitted to the Emergency Department of Chest Pain Center, Fujian Provincial Hospital, due to chest pain from January 1, 2017 to March 31, 2020. Logistic regression was used to identify factors of poor prognosis for patients with ACS in the ED. Receiver operating characteristic (ROC) curve was plotted to assess the performance of the multivariate logistic regression model. Subgroup analysis was used to analyze the difference of SBP in ACS patients with different characteristics. RESULTS: The final analysis included 2667 patients, of whom 2,057 patients (77.8%) had poor prognosis. STEMI (compared with UA) (OR=20.139; 95% CI:12.448-32.581; P < 0.001), NSTEMI (compared with UA) (OR=7.430; 95% CI:5.159-10.700; P < 0.001), respiratory rate ≥20 bpm (compared with <20 bpm) (OR=1.334; 95% CI: 1.060-1.679; P = 0.014), and use of antiplatelets (OR=1.557; 95% CI:1.181-2.053; P = 0.002) was associated with increased likelihood of poor prognosis for ACS patients in ED. SBP ≥140 mmHg (compared with<140mmHg) (OR=0.574; 95% CI: 0.477-0.690; P < 0.001) was associated with decreased likelihood of poor prognosis for ACS patients in the ED. The area under curve (AUC) of the predictive efficacy of logistic regression model was 0.825 (95% CI: 0.795-0.833, P < 0.001). CONCLUSION: This study found that STEMI, NSTEMI, respiratory rate ≥20 bpm, and use of antiplatelets were associated with increased likelihood of poor prognosis for ACS patients in the ED. It also found that SBP≥140 was associated with decreased likelihood of poor prognosis. Our study may be useful for doctors to make clinical decisions for ACS patients.

Removal of an impacted apricot pit from a scarring duodenal stenosis using endoscopic retrograde cholangiopancreatography (ERCP) stone extraction technique.

A 66-year-old man presented with repeated vomiting for 5 days. Initial gastroscopy showed gastric retention while computed tomography (CT) revealed a 1.8*1.1 cm, oval-shaped, high-density object in the duodenum. Considering his past medical history of a surgical repair for duodenal ulcer perforation 20 years ago, a diagnosis of foreign body (FB) impaction causing gastric outlet obstruction was established. After gastric lavage, a second gastroscopy was performed. A brownish round FB impacted upon scarring stenoses at the junction of the 1st and 2nd part of duodenum was visualized after advancement of the scope with effort through a deformed pylorus. Attempts to capture the FB using a polypectomy snare failed because the snare loop could not be advanced across the stenotic impaction site to allow adequate opening. A grasper was also ineffective due to the smooth surface of the FB. Then the ERCP stone extraction technique was applied. Directed by the adjustable tip of a sphincterotome which was introduced through the same gastroscope, a guidewire passed with little resistance over the impaction site for an adequate length. Subsequently, an extraction balloon was advanced through the guidewire with slight inflation to avoid injury to the stenotic duodenal wall and fully inflated in the distal lumen. Gradual balloon deflation and withdrawal applied simultaneously achieved successful removal of the BF, which was identified as an apricot pit. The patient resumed his diet of soft food immediately after the procedure without complaint of any discomfort.

A database of modeled gridded dry deposition velocities for 45 gaseous species and three particle size ranges across North America.

The dry deposition process refers to the flux loss of an atmospheric pollutant due to uptake of the pollutant by the earth's surfaces. Dry deposition flux of a chemical species is typically calculated as the product of its surface-layer concentration and its dry deposition velocity (Vd). Field measurement based Vd data are very scarce or do not exist for many chemical species considered in chemistry transport models. In the present study, gaseous and particulate dry deposition schemes were applied to generate a database of hourly Vd for 45 gaseous species and three particle size ranges for two years (2016-2017) at a 15 km by 15 km horizontal resolution across North America. Hourly Vd of the 45 gaseous species ranged from < 0.001 to 4.6 cm/sec across the whole domain, with chemical species-dependent median (mean) values being in the range of 0.018-1.37 cm/sec (0.05-1.43 cm/sec). The spatial distributions of the two-year average Vd showed values higher than 1-3 cm/sec for those soluble and reactive species over certain land types. Soluble species have the highest Vd over water surfaces, while insoluble but reactive species have the highest Vd over forests. Hourly Vd of PM2.5 across the whole domain ranged from 0.039 to 0.75 cm/sec with median (mean) value of 0.18 (0.20) cm s-1, while the mean Vd for PM2.5-10 is twice that of PM2.5. Uncertainties in the modeled Vd are typically on the order of a factor of 2.0 or larger, which needs to be considered when applying the dataset in other studies.

Non-coding RNAs rewire cancer metabolism networks.

Non-coding RNAs (ncRNAs) are functional RNAs with limited or no protein-coding ability. These interact with their target molecules and participate in the precise regulation of disease development. Metabolic reprogramming is a hallmark in cancer, and is considered essential in meeting increased macromolecular biosynthesis and energy generation of tumors. Recent studies have revealed the involvement of ncRNAs in several metabolic regulations of cancer through direct modulation of metabolic enzyme activities or participation of metabolism-related signaling pathways. Elucidation of how ncRNAs regulate metabolic reprogramming of cancers has opened up a novel intention to understand the mechanism of metabolic rewiring and also the opportunities of utilizing ncRNA-based therapeutics for targeting the metabolism in cancer treatment.