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Abstract Meat intake, particularly from oily fish, has been associated with various chronic diseases. However, its relationship with acne has always been controversial. Therefore, we have adopted Mendelian randomization (MR) analysis to investigate the causal relationship between different types of meat intake and acne. The exposure and outcome datasets for this study were obtained from the Integrative Epidemiology Unit (IEU) Open GWAS project. Seven datasets on meat intake were included, which consisted of non‐oily fish, oily fish, lamb/mutton, poultry, pork, beef, and processed meat. The main methods used for MR analysis were inverse variance weighted, weighted median, and MR‐egger. To ensure the accuracy of the results, heterogeneity, pleiotropy, and Mendelian randomization pleiotropy residual sum and outlier (MR‐PRESSO) analyses were conducted. Additionally, an analysis of four risk factors (fasting insulin, insulin resistance, total testosterone level, and estradiol level) was performed to investigate the underlying mechanisms linking statistically significant meat intake to acne. Oily fish intake was found to be a protective factor for acne (OR: 0.22, 95% CI: 0.10–0.49, p

Abstract Introduction Premature ejaculation (PE), a common male sexual dysfunction, often accompanies by abnormal psychological factors, such as depression. Recent neuroimaging studies have revealed structural and functional brain abnormalities in PE patients. However, there is limited neurological evidence supporting the comorbidity of PE and depression. This study aimed to explore the topological changes of the functional brain networks of PE patients with depression. Methods Resting‐state functional magnetic resonance imaging (rs‐fMRI) data were acquired from 60 PE patients (30 with depression and 30 without depression) and 29 healthy controls (HCs). Functional brain networks were constructed for all participants based on rs‐fMRI data. The nodal parameters including nodal centrality and efficiency were calculated by the method of graph theory analysis and then compared between groups. In addition, the results were corrected for multiple comparisons by family‐wise error (FWE) (p

Abstract A blood test identifying patients at increased risk of pulmonary hypertension (PH) could streamline the investigative pathway. The prospective, multicenter CIPHER study aimed to develop a microRNA‐based signature for detecting PH in breathless patients and enrolled adults with a high suspicion of PH who had undergone right heart catheterization (RHC). The CIPHER‐MRI study was added to assess the performance of this CIPHER signature in a population with low probability of having PH who underwent cardiac magnetic resonance imaging (cMRI) instead of RHC. The microRNA signature was developed using a penalized linear regression (LASSO) model. Data were modeled both with and without N‐terminal pro‐brain natriuretic peptide (NT‐proBNP). Signature performance was assessed against predefined thresholds (lower 98.7% CI bound of ≥0.73 for sensitivity and ≥0.53 for specificity, based on a meta‐analysis of echocardiographic data), using RHC as the true diagnosis. Overall, 926 CIPHER participants were screened and 888 were included in the analysis. Of 688 RHC‐confirmed PH cases, approximately 40% were already receiving PH treatment. Fifty microRNA (from 311 investigated) were algorithmically selected to be included in the signature. Sensitivity [97.5% CI] of the signature was 0.85 [0.80–0.89] for microRNA‐alone and 0.90 [0.86–0.93] for microRNA+NT‐proBNP, and the corresponding specificities were 0.33 [0.24–0.44] and 0.28 [0.20–0.39]. Of 80 CIPHER‐MRI participants with evaluable data, 7 were considered PH‐positive by cMRI whereas 52 were considered PH‐positive by the microRNA signature. Due to low specificity, the CIPHER miRNA‐based signature for PH (either with or without NT‐proBNP in model) did not meet the prespecified diagnostic threshold for the primary analysis.

Abstract Loss of E‐cadherin (ECAD) is required in tumor metastasis. Protein degradation of ECAD in response to oxidative stress is found in metastasis of hepatocellular carcinoma (HCC) and is independent of transcriptional repression as usually known. Mechanistically, protein kinase A (PKA) senses oxidative stress by redox modification in its β catalytic subunit (PRKACB) at Cys200 and Cys344. The activation of PKA kinase activity subsequently induces RNF25 phosphorylation at Ser450 to initiate RNF25‐catalyzed degradation of ECAD. Functionally, RNF25 repression induces ECAD protein expression and inhibits HCC metastasis in vitro and in vivo. Altogether, these results indicate that RNF25 is a critical regulator of ECAD protein turnover, and PKA is a necessary redox sensor to enable this process. This study provides some mechanistic insight into how oxidative stress‐induced ECAD degradation promotes tumor metastasis of HCC.

Abstract Aim The purpose of this study was to provide a comprehensive understanding of the attitudes and experiences of the medical staff regarding the hospital bed‐sharing model. Design The present research was a qualitative study. Methods This qualitative study used in‐depth individual interviews with 7 doctors, 10 clinical nurses and 3 head nurses, which were then transcribed and analysed thematically. Results The study identified six overall themes. Issues were raised about the efficient utilization of hospital bed resources, greater challenges for nursing work, adjustment of doctors' work modes, barriers to communication between doctors, nurses, and patients, potential medical risks, and differentiation of patients' medical experience. Implications for Nursing Management Hospital administrators and nurse managers should work together to solve the challenges that medical staff face, including strengthening nursing training, improving medical–nursing collaboration models, standardizing and effective communication strategies, and improving patient experiences.

Abstract In this article, a prediction model based on spatiotemporal stacked ResNet (Res‐STS) for hourly temperature prediction is designed. On the timescale, the Res‐STS removes the gate structure of the long short‐term memory (LSTM) model, and the data of multiple consecutive time nodes are stacked together to preserve all temporal characteristics of the data. A point‐to‐point data mapping relationship is developed on the spatial scale to maximize the impact of large‐scale environmental background field characteristics on a single grid point. Based on the historical gridded data from the China Meteorological Administration land data assimilation system (CLDAS) and the optimal factor dataset of the European Centre for Medium‐Range Weather Forecasts Integrated Forecasting System (ECMWF‐IFS) from 2017 to 2020, hourly temperature prediction models based on convolutional long short‐term memory (ConvLSTM) and Res‐STS model are developed, respectively. Furthermore, the prediction results of the two models in 2021 are compared with the ECMWF‐IFS. The results show that the root mean square error (RMSE) of the prediction results by ConvLSTM and Res‐STS models are both smaller than that of ECMWF‐IFS. Specially, the Res‐STS model performs best: it reduces the RMSE by 20.8% (24.5%) compared with the ConvLSTM (ECMWF‐IFS). Specifically, the RMSE peaks in the afternoon when the daily maximum temperature occurs, while it is relatively smaller at night. Res‐STS demonstrates a significant improvement in forecast performance compared with ECMWF‐IFS, while ConvLSTM's correction during the period of maximum temperature occurrence has been enhanced. Moreover, the forecast performance of the Res‐STS model is least affected by terrain compared with those of the ConvLSTM and ECMWF‐IFS. For the regions with terrain height greater than 1 km, the model Res‐STS evidently improves the RMSE.

Abstract Interlayer charge‐transfer (CT) in 2D atomically thin vertical stacks heterostructures offers an unparalleled new approach to regulation of device performance in optoelectronic and photonics applications. Despite the fact that the saturable absorption (SA) in 2D heterostructures involves highly efficient optical modulation in the space and time domain, the lack of explicit SA regulation mechanism at the nanoscale prevents this feature from realizing nanophotonic modulation. Here, the enhancement of SA response via CT in WS2/graphene vertical heterostructure is proposed and the related mechanism is demonstrated through simulations and experiments. Leveraging this mechanism, CT‐induced SA enhancement can be expanded to a wide range of nonlinear optical modulation applications for 2D materials. The results suggest that CT between 2D heterostructures enables efficient nonlinear optical response regulation.

Abstract Nanotransfer printing of colloidal nanoparticles is a promising technique for the fabrication of functional materials and devices. However, patterning nonplanar nanostructures pose a challenge due to weak adhesion from the extremely small nanostructure‐substrate contact area. Here, the study proposes a thermal‐assisted nonplanar nanostructure transfer printing (NP‐NTP) strategy for multiscale patterning of polystyrene (PS) nanospheres. The printing efficiency is significantly improved from ≈3.1% at low temperatures to ≈97.2% under the glass transition temperature of PS. Additionally, the arrangement of PS nanospheres transitioned from disorder to long‐range order. The mechanism of printing efficiency enhancement is the drastic drop of Young's modulus of nanospheres, giving rise to an increased contact area, self‐adhesive effect, and inter‐particle necking. To demonstrate the versatility of the NP‐NTP strategy, it is combined with the intaglio transfer printing technique, and multiple patterns are created at both micro and macro scales at a 4‐inch scale with a resolution of ≈2757 pixels per inch (PPI). Furthermore, a multi‐modal anti‐counterfeiting concept based on structural patterns at hierarchical length scales is proposed, providing a new paradigm of imparting multiscale nanostructure patterning into macroscale functional devices.

Abstract This study aimed to evaluate the effectiveness and safety of an oral sequential triple combination therapy with selexipag after dual combination therapy with endothelin receptor antagonist (ERA) and phosphodiesterase‐5 inhibitor (PDE5I)/riociguat in pulmonary arterial hypertension (PAH) patients. A total of 192 PAH patients from 10 centers had received oral sequential selexipag therapy after being on dual‐combination therapy with ERA and PDE5i/riociguat for a minimum of 3 months. Clinical data were collected at baseline and after 6 months of treatment. The study analyzed the event‐free survival at 6 months and all‐cause death over 2 years. At baseline, the distribution of patients among the risk groups was as follows: 22 in the low‐risk group, 35 in the intermediate‐low‐risk group, 91 in the intermediate‐high‐risk group, and 44 in the high‐risk group. After 6 months of treatment, the oral sequential triple combination therapy resulted in reduced NT‐proBNP levels (media from 1604 to 678 pg/mL), a decline in the percentage of WHO‐FC III/IV (from 79.2% to 60.4%), an increased in the 6MWD (from 325 ± 147 to 378 ± 143 m) and a rise in the percentage of patients with three low‐risk criteria (from 5.7% to 13.5%). Among the low‐risk group, there was an improvement in the right heart remodeling, marked by a decrease in right atrium area and eccentricity index. The intermediate‐low‐risk group exhibited significant enhancements in WHO‐FC and tricuspid annular plane systolic excursion. For those in the intermediate‐high and high‐risk groups, there were marked improvements in activity tolerance, as reflected by WHO‐FC and 6MWD. The event‐free survival rate at 6 months stood at 88%. Over the long‐term follow‐up, the survival rates at 1 and 2 years were 86.5% and 86.0%, respectively. In conclusion, the oral sequential triple combination therapy enhanced both exercise capacity and cardiac remodeling across PAH patients of different risk stratifications.

Abstract BRAF V600E attracts wide attention in the treatment of colorectal cancer (CRC) as stratifying and predicting a refractory classification of CRC. Recent evidence indicates that Wnt/β‐catenin signaling is broadly activated and participates in the refractoriness of BRAF V600E CRC, but the underlying molecular mechanism needs to be elucidated. Here, heat shock 70 kDa protein 8 (HSPA8), an essential regulator in chaperone‐mediated autophagy (CMA), is identified as a potential therapeutic target for advanced BRAF V600E CRC. These results show that HSPA8 is transcriptionally upregulated in BRAF V600E CRC, which promotes CMA‐dependent degradation of caveolin‐1 (CAV1) to release β‐catenin into the nucleus and thus activates the Wnt/β‐catenin pathway, contributing to metastasis and progression of BRAF V600E CRC. Of note, HSPA8 directly interacts with the KIFSN motif on CAV1, the interaction can be enhanced by p38 MAPK‐mediated CAV1 S168 phosphorylation. Furthermore, pharmacological targeting HSPA8 by VER155008 exhibits synergistic effects with BRAF inhibitors on CRC mouse models. In summary, these findings discover the important role of the HSPA8/CAV1/β‐catenin axis in the development of refractory BRAF V600E CRC and highlight HSPA8 as a predictive biomarker and therapeutic target in clinical practice.

Abstract Emerging evidence indicates that cancer cells can mimic characteristics of embryonic development, promoting their development and progression. Cancer cells share features with embryonic development, characterized by robust proliferation and differentiation regulated by signaling pathways such as Wnt, Notch, hedgehog, and Hippo signaling. In certain phase, these cells also mimic embryonic diapause and fertilized egg implantation to evade treatments or immune elimination and promote metastasis. Additionally, the upregulation of ATP‐binding cassette (ABC) transporters, including multidrug resistance protein 1 (MDR1), multidrug resistance‐associated protein 1 (MRP1), and breast cancer‐resistant protein (BCRP), in drug‐resistant cancer cells, analogous to their role in placental development, may facilitate chemotherapy efflux, further resulting in treatment resistance. In this review, we concentrate on the underlying mechanisms that contribute to tumor development and progression from the perspective of embryonic development, encompassing the dysregulation of developmental signaling pathways, the emergence of dormant cancer cells, immune microenvironment remodeling, and the hyperactivation of ABC transporters. Furthermore, we synthesize and emphasize the connections between cancer hallmarks and embryonic development, offering novel insights for the development of innovative cancer treatment strategies.

Abstract Candida albicans (C. albicans), a ubiquitous polymorphic fungus in humans, causes different types of candidiasis, including oral candidiasis (OC) and vulvovaginal candidiasis (VVC), which are physically and mentally concerning and financially costly. Thus, developing alternative antifungals that prevent drug resistance and induce immunity to eliminate Candida biofilms is crucial. Herein, a novel membrane‐targeted aggregation‐induced emission (AIE) photosensitizer (PS), TBTCP‐QY, is developed for highly efficient photodynamic therapy (PDT) of candidiasis. TBTCP‐QY has a high molar absorption coefficient and an excellent ability to generate 1O2 and •OH, entering the interior of biofilms due to its high permeability. Furthermore, TBTCP‐QY can efficiently inhibit biofilm formation by suppressing the expression of genes related to the adhesion (ALS3, EAP1, and HWP1), invasion (SAP1 and SAP2), and drug resistance (MDR1) of C. albicans, which is also advantageous for eliminating potential fungal resistance to treat clinical infectious diseases. TBTCP‐QY‐mediated PDT efficiently targets OC and VVC in vivo in a mouse model, induces immune response, relieves inflammation, and accelerates the healing of mucosal defects to combat infections caused by clinically isolated fluconazole‐resistant strains. Moreover, TBTCP‐QY demonstrates excellent biocompatibility, suggesting its potential applications in the clinical treatment of OC and VVC.

Abstract The application potential of aluminium conductor composite core (ACCC) conductors in the 1000‐kV power transmission line project deserves to be investigated. Its economic evaluation is a contentious issue. This paper proposes a method for selecting the type of conductors based on the life cycle cost (LCC) of a transmission line, which includes the initial investments, operation costs, maintenance costs, failure costs, and discard costs. The mathematical model of electromagnetic loss differs due to the various operational circumstances surrounding a transmission line; therefore, a novel three‐dimensional electromagnetic–fluid–thermal coupling model based on the finite element method (FEM) was proposed. The simulation error of ACCC and aluminium conductor steel reinforced (ACSR) conductors is 2.56% and 0.5%, respectively, compared to the experimental value. Subsequently, the LCC model is applied in the economic analysis of a 1000‐kV transmission line, and the costs of ACCC conductors and ACSR conductors under different annual power load utilization hours are calculated. The results indicate that the overhead power transmission line with ACCC conductors saves at least 2 × 106 ¥/km compared with ACSR when annual utilization hours reach 3500 h; meanwhile, energy saving benefits are achieved.

Mouse bone marrow mesenchymal stem cells (mBM‐MSCs) are important for preclinical tissue regeneration and repair studies. In the present study, we isolated mBM‐MSCs using three easy‐to‐perform methods (whole bone marrow‐adherent culture, density‐gradient centrifugation, and bone digestion), and then compared the morphology, proliferation, differentiation, and paracrine factor profiles of the isolated mBM‐MSCs. Of these three isolation methods, the bone digestion method resulted in the highest quantity of mBM‐MSCs with high growth potential and moderate differentiation. Conversely, the mBM‐MSCs isolated through the whole bone marrow‐adherent method exhibited the lowest potency for proliferation and differentiation. The differentially expressed factors between mBM‐MSCs were primarily those involved in immune responses. The highly expressed secreted factors included cytokines/members of the chemokine family, growth factors, and protein binding/proteinase activity. These findings provide a fundamental reference for development of MSC isolation methods.

Abstract Lung endothelial permeability is a key pathological feature of acute respiratory distress syndrome. Hyaluronic acid (HA), a major component of the glycocalyx layer on the endothelium, is generated by HA synthase (HAS) during inflammation and injury and is critical for repair. We hypothesized that administration of exogenous high molecular weight (HMW) HA would restore protein permeability across human lung microvascular endothelial cells (HLMVEC) injured by an inflammatory insult via upregulation of HAS by binding to CD44. A transwell coculture system was used to study the effects of HA on protein permeability across HLMVEC injured by cytomix, a mixture of IL‐1β, TNFα, and IFNγ, with or without HMW or low molecular weight (LMW) HA. Coincubation with HMW HA, but not LMW HA, improved protein permeability following injury at 24 h. Fluorescence microscopy demonstrated that exogenous HMW HA partially prevented the increase in “actin stress fiber” formation. HMW HA also increased the synthesis of HAS2 mRNA expression and intracellular HMW HA levels in HLMVEC following injury. Pretreatment with an anti‐CD44 antibody or 4‐methylumbelliferone, a HAS inhibitor, blocked the therapeutic effects. In conclusion, exogenous HMW HA restored protein permeability across HLMVEC injured by an inflammatory insult in part through upregulation of HAS2.

Abstract Aim To determine the tolerance and acceptance of hepatic venous pressure gradient (HVPG) measurements in patients with liver cirrhosis. Methods This prospective international multicenter study included 271 patients with cirrhosis who were scheduled to undergo HVPG measurement between October 2019 and June 2020. Data related to the tolerance and acceptance of HVPG measurements were collected using descriptive questionnaires. Results HVPG measurements were technically successful in all 271 patients, with 141 (52.0%) undergoing HVPG measurement alone. The complication rate was 0.4%. Postoperative pain was significantly lower than preoperative expected pain (p

Objectives. The goal of this retrospective study was to reveal the prevalence, angiographic characteristics, clinical presentation, and long-term outcomes of non-ST-segment elevation myocardial infarction (NSTEMI) patients with Wellens’ syndrome. Background. Procedural results for percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) have improved in recent years. However, there is still a paucity of available clinical trial data for Wellens’ syndrome even though it is a well-known high-risk ACS. Methods. Among a total of 3528 patients with ACS who underwent angioplasty from 2017 to 2019 at the Cardiovascular Center of Beijing Friendship Hospital, 476 NSTEMI patients with culprit left anterior descending (LAD) vessels were enrolled in this study. According to electrocardiographic criteria of Wellens’ syndrome, the patients were divided into a Wellens group (n = 138) and a non-Wellens group (n = 338). The primary endpoint was cardiac death; the secondary endpoints were main adverse cardiovascular and cerebrovascular events (MACCEs), a composite of all-cause death, cardiac death, heart failure, target lesion revascularization, recurrent myocardial infarction, and stroke. All of the medical and follow-up data were obtained from our institutional database. Results. The incidence of Wellens’ syndrome in all ACS patients was 5.7% (200 of 3528). Among the 200 patients with Wellens’ syndrome, 138 had NSTEMI, for a proportion of 69%. There was a significant decrease in the percentage of preexisting coronary heart disease (CHD), prior myocardial infarction, and previous PCI (P

Objectives To assess the efficiency, safety, and accuracy of S2 (IS) screw fixation using a robot‐assisted method compared with a freehand method. Methods This is a retrospective clinical study. We analyzed the patients treated with S2 IS screw fixation for unstable pelvic fractures from January 2016 to January 2019 in our institution. Sixty‐three patients (17 men and 46 women) aged between 21 and 55 years (with an average age of 39.22 ± 9.28) were included in this study. According to the Tile classification, there were 26 (41.3%) type B fractures and 37 (58.7%) type C fractures. All patients were divided into robot‐assisted (RA) group (38 patients) or the traditional freehand (FH) group (25 patients). In RA group, the S2 IS screws were implanted with a robot‐assisted technique. And S2 IS screws were implanted with a traditional freehand technique in FH group. The screw‐related complications were recorded during and after the surgery. The position of all screws and fracture reduction was assessed by postoperative CT scans according to the Gras classification. The number of guide wire attempts and the radiation exposure for S2 screw implantation during operation were also recorded. Finally, the Matta standard was used to evaluate the fracture reduction of the IS joint. Results A total of 89 IS screws were implanted into S2 iliosacral joint. Fifty‐four screws were placed by RA (38 patients) and 35 screws were by FH (25 patients). There was no difference between the two groups with respect to demographic data. There was no screw‐related complications or revision surgery in any group. In terms of screw placement, the excellent and good rate was 100% in the RA group, better than that in the FH group where it was only 85.7% (P

Abstract Redox biology is at the core of life sciences, accompanied by the close correlation of redox processes with biological activities. Redox homeostasis is a prerequisite for human health, in which the physiological levels of nonradical reactive oxygen species (ROS) function as the primary second messengers to modulate physiological redox signaling by orchestrating multiple redox sensors. However, excessive ROS accumulation, termed oxidative stress (OS), leads to biomolecule damage and subsequent occurrence of various diseases such as type 2 diabetes, atherosclerosis, and cancer. Herein, starting with the evolution of redox biology, we reveal the roles of ROS as multifaceted physiological modulators to mediate redox signaling and sustain redox homeostasis. In addition, we also emphasize the detailed OS mechanisms involved in the initiation and development of several important diseases. ROS as a double‐edged sword in disease progression suggest two different therapeutic strategies to treat redox‐relevant diseases, in which targeting ROS sources and redox‐related effectors to manipulate redox homeostasis will largely promote precision medicine. Therefore, a comprehensive understanding of the redox signaling networks under physiological and pathological conditions will facilitate the development of redox medicine and benefit patients with redox‐relevant diseases.

Abstract Glioblastoma (GBM) is the main form of primary brain malignancies with a dismal prognosis partly due to its invasive growth and rapid relapse. GBM frequently developed resistance to current standard‐of‐care therapeutic modalities, including surgery, radiation and chemotherapy, of which temozolomide (TMZ) is the most widely used first‐line anti‐GBM drug. Despite the intense efforts of the past decades, the underlying mechanisms of GBM resistance to TMZ remain largely unclear. Here we show that the long noncoding RNA (lncRNA) PSMG3‐AS1 is significantly upregulated in GBM and its expression correlates with the grade of glioma, with the highest level observed in GBM (Grade IV glioma). We also demonstrated that PSMG3‐AS1 mediates the resistance of GBM to TMZ, as knockdown of PSMG3‐AS1 remarkably increased the sensitivity whereas overexpression of PSMG3‐AS1 in sensitive GBM cell line induced a resistance phenotype to TMZ. Mechanistically, PSMG3‐AS1 directly binds to c‐Myc and thus stabilizes c‐Myc in the nucleus to promote the survival of GBM cells under treatment of TMZ. Our data demonstrated an unreported role of PSMG3‐AS1 in TMZ resistance and provide a potential novel target to tackle TMZ resistance in GBM.

Abstract Despite advantages of arsenic trioxide (ATO) in oncological practice, its clinical applications have been hampered by severe cardiotoxicity. The general mechanism of ATO‐induced cardiotoxicity has been attributed to its damage to mitochondria, resulting in cardiac remodeling. Honokiol (HKL) is a naturally occurring compound derived from Magnolia bark. Previous studies have demonstrated that HKL exerts cardio‐protective effects on ischemia/reperfusion (I/R) or chemical‐induced cardiotoxicity by counteracting the toxic effects on mitochondria. The present study was conducted to investigate whether HKL pretreatment protects against ATO‐induced cardiac oxidative damage and cell death. For the in vitro study, we evaluated the effects of ATO and/or Honokiol on reactive oxygen species (ROS) production and apoptosis induction in primary cultured cardiomyocytes; for the in vivo study, BALB/c mice were administrated with ATO and/or HKL for a period of 4 weeks, myocardial apoptosis, cardiac function, and cardiac remodeling (cardiac hypertrophy and cardiac fibrosis) were assessed at the end of administration. Our results demonstrated Honokiol pretreatment alleviated the ATO‐induced boost in ROS concentration and the following apoptosis induction in primary cultured cardiomyocytes. In the mouse model, Honokiol pretreatment ameliorated ATO‐induced myocardial apoptosis, cardiac dysfunction, and cardiac remodeling. Collectively, these results indicated that Honokiol provide a protection against ATO‐induced cardiotoxicity by reducing mitochondrial damage. In addition, given that Honokiol has shown considerable suppressive effects on leukemia cells, our data also imply that ATO and Honokiol combination may possibly be a superior avenue in leukemia therapy.

Pancreatic cancer (PC) is one of the most common human malignancies worldwide and remains a major clinical challenge. Here, we found that benproperine phosphate (BPP), a cough suppressant, showed a significant anticancer effect on PC both in vitro and in vivo via the induction of autophagy‐mediated cell death. Mechanistic studies revealed that BPP triggered AMPK/mTOR‐mediated autophagy initiation and disturbed Ras‐related protein Rab‐11A (RAB11A)‐mediated autophagosome–lysosome fusion, resulting in excessive accumulation of autophagosomes. Inhibition of autophagy or overexpression of RAB11A partially reversed BPP‐induced growth inhibition in PC cells, suggesting that BPP might induce lethal autophagy arrest in PC cells. In conclusion, our results identify BPP as a potent antitumor agent for PC via the induction of autophagy arrest, therefore providing a new potential therapeutic strategy for the treatment of PC.

Phthalanilic acid is widely used in wheat and oilseed rape fields in China, but there is no analysis method to detect its residues in wheat and oilseed rape substrates. To accurately evaluate the health and environmental impact of phthalanilic acid residues on wheat gains and rapeseeds, it is urgent to establish a reliable analytical method for its detection. In this study, a rapid and sensitive method was developed based on QuEChERS and LC-MS/MS to detect phthalanilic acid in cereals (wheat, rice, corn, and millet), wheat straw, and rapeseeds. Optimization of the detection conditions showed that the mobile phase of acetonitrile-0.1% formic acid solution had the best chromatographic resolution and sensitivity. The average recovery rates of phthalanilic acid in cereals, wheat straw, and rapeseeds ranged from 88% to 113% with relative standard deviations (RSDs) of 1%–6%. There were good linear relationships with the correlation coefficients (r) higher than 0.9990 at concentrations of 0.01–5 mg L−1. The limits of quantification (LOQ) for phthalanilic acid in cereals, wheat straw, and rapeseeds were 0.01 mg kg−1, 0.05 mg kg−1, and 0.02 mg kg−1, respectively. These results show that the method established in this study is convenient and reliable for routine monitoring of phthalanilic acid in cereals, wheat straw, and rapeseeds.

Origanum majorana belongs to the Lamiaceae family as a famous spice plant in Egypt, which is used to treat arthritis, allergies, fever, flu, hypertension, respiratory infections, migraine, and asthma. In our studies, it was found that the ethanol extract of O. marjoram could significantly reduce NO release at 200 (P

The pathogenesis of CRSwNP is complex and unclear. CRSwNP is subdivided into two types based on the infiltration of EOSs: eCRSwNP and noeCRSwNP. This study was designed to seek the role of autophagy, mitophagy, and Akt/mTOR pathway in these two subtypes of CRSwNP. This study included 29 patients with CRSwNP and 9 controls. The levels of autophagy, mitophagy, and Akt/mTOR pathway-related proteins in nasal tissues were quantified using western blot analysis. Levels of eosinophilic inflammation-related cytokines in nasal tissues were quantified by enzyme-linked immunosorbent assay. Immunohistochemistry was also used to evaluate autophagy, mitophagy, and Akt/mTOR pathway-related protein expression and distribution in nasal polyps and control tissues. Transmission electron microscopy was used to detect the formation of autophagosomes and mitochondrial autophagosomes. Masson’s trichrome and periodic acid–Schiff Alcian blue staining were used to evaluate the severity of tissue remodeling. The expression of p-Akt/Akt and p-mTOR/mTOR was upregulated in patients with eCRSwNP or noeCRSwNP. Beclin 1, PINK1, BNIP3, and FUNDC1 levels were significantly reduced in the nasal polyps of patients with eCRSwNP or noeCRSwNP. Autophagosomes and mitochondrial autophagosomes formed less frequently in the nasal polyps of patients with eCRSwNP or noeCRSwNP. Levels of IL-4, IL-5, IL-13, and ECP and the eotaxins CCL11, CCL24, and CCL26 were elevated in the nasal polyps of patients with eCRSwNP or noeCRSwNP. Tissue remodeling is enhanced in patients with eCRSwNP or noeCRSwNP. The Akt/mTOR pathway, eosinophilic inflammation, and tissue remodeling are activated in the nasal polyps of patients with eCRSwNP or noeCRSwNP. The downregulation of autophagy and mitophagy is also observed in eosinophilic and noneosinophilic nasal polyps. The targeting of mitophagy may provide new therapeutic options for different endotypes of CRSwNP.

Objective. To explore the application effects of chain nursing process in the nursing of elderly inpatients with implantable venous infusion port. Methods. 81 elderly inpatients who were treated with implantable venous infusion port in the hospital were selected between February 2018 and December 2021, and they were divided into the routine group (given routine nursing of implantable venous infusion port, n = 40) and the study group (given chain nursing process intervention on the basis of the routine group, n = 41) according to the random number table method. The patients in both groups were intervened for 1 month. The catheter-related indicators and incidence rates of adverse events (drug extravasation, local hematoma, infusion port blockage, catheter-related infection) were compared between the two groups of patients. Generalized Anxiety Disorder 7-item scale (GAD-7) and Athens Insomnia Scale (AIS) were used to compare the psychological states of the two groups before and after intervention, and Newcastle Satisfaction with Nursing Scale (NSNS) was adopted to compare the nursing satisfaction of patients before and after intervention. Results. After intervention, the catheter maintenance operation time in the study group was shorter than that in the routine group (P0.05). The incidence rate of adverse reactions of 2.44% in the study group was lower than 15.00% in the routine group (P0.05). After intervention, the NSNS scores in the study group were higher than those in the routine group (P

The object of this paper is to establish a new model with strategy transformational barriers for a class of generalized multileader multifollower multiple objective games (GMLMFMOG) and further deduce some new results of the weakly Pareto-Nash equilibrium (WPNE) with strategy transformational barriers for the GMLMFMOG. First, we investigate the existence of the WPNE with strategy transformational barriers for the GMLMFMOG by using the Kakutani-Fan-Glicksberg fixed point theory. Next, we study the generic stability of the GMLMFMOG with strategy transformational barriers in Hausdorff space. Finally, we obtain that the majority of the WPNE with strategy transformational barriers for the GMLMFMOG are essential on the meaning of Baire’s category. In addition, we demonstrate that there is at least an essential component for the GMLMFMOG with strategy transformational barriers.

To investigate the stress-strain relationship of fiber reinforced phosphogypsum (PG) under uniaxial compression, a total of twenty-seven PG prism specimens were fabricated and tested. The influences of the content of admixture, content of fiber, and water-solid ratio on the stress-strain curve of the specimens were investigated. Three kinds of failure modes were summarized by observing the experimental phenomena; they were called “compaction failure,” “tension failure,” and “mixed stress failure,” respectively. Through in-depth analysis of the test data, it was found that decreasing the water-solid ratio can lead to increasing the peak stress and secant modulus of specimens; increasing the fiber content can lead to improving the mechanical property of PG mixture specimens. However, adjusting the contents of the cement and quicklime has no significant effect on the mechanical property of specimens. In addition, according to the test data and the characteristics of stress-strain curves, the stress-strain curve of PG specimens was divided into four parts, and a mathematical model was developed to predict the stress-strain curve of PG specimens. The validations of the model showed that the curves calculated by the proposed model were well in agreement with the test data of this study and previous studies.

In this paper, we consider the following fourth order elliptic Kirchhoff-type equation involving the critical growth of the form Δ2u−a+b∫ℝN∇u2dxΔu+Vxu=Iα∗Fufu+λu2∗∗−2u,in ℝN,u∈H2ℝN, where a>0, b≥0, λ is a positive parameter, α∈N−2,N, 5≤N≤8, V:ℝN⟶ℝ is a potential function, and Iα is a Riesz potential of order α. Here, 2∗∗=2N/n−4 with N≥5 is the Sobolev critical exponent, and Δ2u=ΔΔu is the biharmonic operator. Under certain assumptions on Vx and fu, we prove that the equation has ground state solutions by variational methods.

The consistent tanh expansion (CTE) method is successfully applied to the coupled integrable dispersionless (CID) system. A nonauto-Bäcklund transformation (BT) theorem includes two fields f and v1 is obtained by using the CTE method. One obtains the consistent condition in the nonauto-BT theorem by means of the relation between the fields f and v1. The CID system possesses the CTE solvability property by some detailed analysis. Many interactions between one soliton and multiple resonant solitons, and between one soliton and cnoidal waves are generated by using the nonauto-BT theorem. The types of bright and gray two front waves are shown by some figures. In the meanwhile, the nonlocal symmetry is obtained by the truncated Painlevé method and the Möbious invariant form. The initial value problem and an auto-BT are constructed by the localization procedure.

Background. To investigate the efficacy of high-quality nursing service for the patients during the anesthesia recovery period. Methods. We used the National Library of Medicine (PubMed), Cochrane Library of Excerpta Medica Database (EMBASE), China National Knowledge Infrastructure (CNKI), Wanfang, and very important person (VIP) databases for conducting a systematic literature study. We employed the fixed-effects model for evaluating the standardized mean differences (SMDs) with 95% confidence intervals (CIs). The sensitivity and publication bias were estimated for determining the efficacy of high-quality nursing services during the recovery period of anesthesia. Results. In our study, the result showed that the efficiency of recovery time of spontaneous respiration was significantly improved in the experimental group (SMD=−1.48, 95%CI=−1.62,−1.34). In this analysis, the extubation time of the experimental group was lower than that of the control group. In control group [WMD=−15.54, 95% CI (-21.24, -9.83), P

The endothelial dysfunction, associated with inflammation and vascular permeability, remains the key event in the pathogenesis of cerebral ischemic stroke. Angiogenesis is essential for neuroprotection and neural repair following stroke. The neuroinflammatory reaction plays a vital role in stroke, and inhibition of inflammation contributes to establishing an appropriate external environment for angiogenesis. Exosomes are the heterogeneous population of extracellular vesicles which play critical roles in intercellular communication through transmitting various proteins and nucleic acids to nearby and distant recipient cells by body fluids and circulation. Recent reports have shown that exosomal therapy is a valuable and potential treatment strategy for stroke. In this review, we discussed the exosomes in complex interaction mechanisms of angiogenesis and inflammation following stroke as well as the challenges of exosomal studies such as secretion, uptake, modification, and application.

Abstract Isolation of viable circulating tumor cells (CTC) holds the promise for improving screening, early diagnosis, and personalized treatment of lymphoma. In this study, we isolated and characterized spontaneously immortalized B‐lymphocyte (SIBC) lines from HIV‐infected patients with and without Non‐Hodgkin's Lymphoma (AIDS‐NHL). A total of 22 SIBC lines was isolated from peripheral blood mononuclear cells (PBMC) of HIV‐infected patients with (n = 40) and without (n = 77) clinically detectable NHL, but not from healthy individuals (n = 34). Of these, 8 SIBC lines named HIV‐SIBC were generated from HIV‐infected patients without AIDS‐NHL (10%, 8/77), while 14 SIBCs named AIDS‐NHL‐SIBC were from 13 of the AIDS‐NHL patients (32.5%, 13/40). Among the 14 AIDS‐NHL‐SIBCs, 12 were derived from AIDS‐NHL patients with poor prognoses (survival time less than 1 year). SIBCs displayed markers typical of memory B cells (CD3‐CD20+CD27+) with EBV infection. Moreover, AIDS‐NHL‐SIBCs were representative of CTC as evidenced by monoclonal Ig gene rearrangement, abnormal chromosomal karyotype, and the formation of xenograft tumors, while HIV‐SIBCs generated harbored some features of tumor cells, none had the capacity of xenograft tumor formation, suggesting HIV‐SIBC present the precursor of CTC. These results indicate that SIBCs is associated with poor prognosis in AIDS‐NHL patients and can be isolated from HIV‐infected patients with NHL and without NHL. This findings point to the need for further molecular characterization and functional studies of SIBCs, which may prove the value of SIBCs in the diagnosis, prognoses, and screening for NHL among HIV‐infected patients.