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Abstract Background This study aims to investigate the relationships between the Chinese Healthy Eating Index (CHEI), psychological balance, depressive symptoms, and cognitive function in the rural older population. Additionally, it examines the impact of CHEI on cognitive function and the potential chain mediating roles of psychological balance and depressive symptoms. Methods The study utilized data from 2,552 rural older adults aged 65 and above, drawn from the Chinese Longitudinal Healthy Longevity Study (CLHLS). The CHEI was self-reported, with scores ranging from 0 to 50, representing adherence to healthy eating habits. Psychological balance was assessed using status and personality-emotion characteristics recorded in the database, with scores ranging from 6 to 30. Cognitive function was measured using the Mini-Mental State Examination (MMSE), with scores ranging from 0 to 30; higher scores indicated better cognitive function. Depressive symptoms were evaluated using the 10-item Center for Epidemiologic Studies Depression Scale (CESD-10), with scores ranging from 0 to 30, where higher scores reflected more severe depressive symptoms. Results The median CHEI score was 40.0 (IQR: 34.0–45.0), reflecting moderate adherence to healthy dietary practices. The median Psychological Balance score was 19.0 (IQR: 17.0–21.0), and the median Depressive Symptoms score was 13.0 (IQR: 10.0–15.0), indicating mild depressive symptoms among participants. Additionally, the median Cognitive Function score was 28.0 (IQR: 27.0–29.0), suggesting relatively stable cognitive abilities within the sample. Correlational analysis revealed the following: (1) Depressive symptoms were negatively correlated with both cognitive function (rs = -0.100, p

[Objective] In the process of URT (urban rail transit) asset formation, there are challenges in the smooth transmission of asset information, leading to issues such as ′inconsistency between accounts and reality,′ difficulties in equipment maintenance and replacement due to untraceable information during the operation-maintenance phase. To address these issues, it is essential to strengthen the management of asset information throughout the entire lifecycle and construct an asset information system for URT, thereby enhancing the asset management efficiency in URT enterprises. [Method] By reviewing existing research on asset management value, summarizing the value of URT asset management, and using this as a guide, the deficiencies in the existing URT asset information system are identified. Based on this analysis and utilizing axiomatization design theory, asset management value is integrated into the dynamic management process of the whole life cycle of assets. Demand research for asset information users is conducted, and the findings are incorporated into the top-level design of the information system. [Result & Conclusion] The value of URT asset management is reflected in reliability, functionality, effectiveness, and sustainability. Taking Nanjing Metro as the research object, a top-level information system for URT assets is constructed, consisting of an asset information classification system, a coding system and information templates.

Summary: Altered myeloid inflammation and lymphopenia are hallmarks of severe infections. We identified the upregulated EN-RAGE gene program in airway and blood myeloid cells from patients with acute lung injury from SARS-CoV-2 or other causes across 7 cohorts. This program was associated with greater clinical severity and predicted future mechanical ventilation and death. EN-RAGEhi myeloid cells express features consistent with suppressor cell functionality, including low HLA-DR and high PD-L1. Sustained EN-RAGE program expression in airway and blood myeloid cells correlated with clinical severity and increasing expression of T cell dysfunction markers. IL-6 upregulated many EN-RAGE program genes in monocytes in vitro. IL-6 signaling blockade by tocilizumab in a placebo-controlled clinical trial led to rapid normalization of EN-RAGE and T cell gene expression. This identifies IL-6 as a key driver of myeloid dysregulation associated with worse clinical outcomes in COVID-19 patients and provides insights into shared pathophysiological mechanisms in non-COVID-19 ARDS.

Colorectal cancer (CRC) is a malignant digestive tumor mostly prevalent among adolescents and has great proliferation potential. Baicalin is a flavonoid derived from the dried root of Scutellaria baicalensis, it has tumor-suppressing effects on various kinds of tumors. Although baicalin has been shown to regulate genes associated with CRC, its role in cancer proliferation remains poorly illustrated. In this work, we evaluated the effect of baicalin on the proliferative ability of three CRC cell lines using a cell counting kit-8 assay. Furthermore, we screened for differentially expressed genes in HCT-116 cells using baicalin-treated samples and control samples on a gene expression profile microarray. We identified 19 genes were identified significantly downregulated by baicalin, which may potentially play an indispensable role in the proliferation of HCT-116 cells. High-content screening evaluated whether silencing the 19 genes affected HCT-116 cell growth. The results showed that knocking down ARRDC4 exhibited the most potent inhibition of cell proliferation. ARRDC4 expression was knocked down by transfecting CRC cells with lentiviral shRNA. MTT assay, Caspase-Glo 3/7 assay and immunohistochemistry analysis were performed to explore the effects of baicalin on proliferation and apoptosis of CRC cells. Besides, RT-PCR showed that the expression levels of ARRDC4 mRNA decreased significantly in HCT-116 cells after baicalin treatment. In conclusion, these findings indicated that baicalin may attenuated the expression of ARRDC4 via regulating the levels of LCN2, Claudin-2 and GSTA4 to inhibit HCT-116 cell proliferation. The theoretical underpinnings for the investigation of the pharmacological effects of baicalin in the treatment of human CRC were also established in this study.

Abstract Purpose The aim of this study is to explore the factors associated with the fall risk in type 2 diabetes (T2D) patients with a lacunar stroke. Materials and methods We compiled data of 146 T2D patients (mean age 68 years), including the Morse fall scale data (MFS), nutrition score, self-care scale, laboratory data, and data from continuous glucose monitoring system (CGMS) from 2019 to 2021 in Shanghai Pudong Hospital. Thereby, we evaluated the associations between MFS and other clinical parameters. Results The analyses showed that there were significantly increased size and numbers of lacunar infarction (p 0.05). The correlational study revealed the higher score of MFS was associated with the age (r = 0.41), number of lacunar infarction (r = 0.18), nutrition score (r = 0.20), self-care score (r = − 0.43), serum creatine level (r = 0.19), eGFR (r = − 0.26) (p

Abstract Background Insulin has been demonstrated to play an important role in the occurrence and development of Alzheimer’s disease, especially in those with diabetes. β cells are important insulin-producing cells in human pancreas. This study aimed to investigate the association between β-cell dysfunction and cognitive impairment among patients over 40-year-old with abnormal glucose metabolism in Chinese rural communities. Methods A sample of 592 participants aged 40 years or older from the China National Stroke Prevention Project (CSPP) between 2015 and 2017 were enrolled in this study. Abnormal glucose metabolism was defined when hemoglobin Alc ≥ 5.7%. Cognitive function was assessed by the Beijing edition of the Montreal Cognitive Assessment scale. Homeostasis assessment of β-cell function was performed and classified into 4 groups according to the quartiles. A lower value of HOMA-β indicated a worse condition of β-cell function. Multivariate logistic regression was used to analyze the association between β-cell function and cognitive impairment. Results In a total of 592 patients with abnormal glucose metabolism, the average age was 60.20 ± 7.63 years and 60.1% patients had cognitive impairment. After adjusting for all potential risk factors, we found the first quartile of β-cell function was significantly associated with cognitive impairment (OR: 2.27, 95%CI: 1.32–3.92), especially at the domains of language (OR: 1.64, 95%CI: 1.01–2.65) and abstraction (OR: 2.29, 95%CI: 1.46–3.58). Conclusions Our study showed that worse β-cell function is associated with cognitive impairment of people over 40-year-old with abnormal glucose metabolism in Chinese rural communities, especially in the cognitive domains of abstraction and language.

PurposeThe Distribution of Co-Care Activities Scale was adapted into Chinese for the purposes of this study, and then the psychometric characteristics of the Chinese version of the DoCCA scale were confirmed in chronic conditions.MethodsA total of 434 patients with chronic diseases were recruited from three Chinese cities. A cross-cultural adaptation procedure was used to translate the Distribution of Co-Care Activities Scale into Chinese. Cronbach's alpha coefficient, split-half reliability, and test-retest reliability were used to verify the scale's reliability. Content validity indices, exploratory factor analysis, and confirmatory factor analysis were used to confirm the scale's validity.ResultsThe Chinese DoCCA scale includes five domains: demands, unnecessary tasks, role clarity, needs support, and goal orientation. The S-CVI was 0.964. Exploratory factor analysis yielded a five-factor structure that explained 74.952% of the total variance. According to the confirmatory factor analysis results, the fit indices were within the range of the reference values. Convergent and discriminant validity both met the criteria. Also, the scale's Cronbach's alpha coefficient is 0.936, and the five dimensions' values range from 0.818 to 0.909. The split-half reliability was 0.848, and the test-retest reliability was 0.832.ConclusionsThe Chinese version of the Distribution of Co-Care Activities Scale had high levels of validity and reliability for chronic conditions. The scale can assess how patients with chronic diseases feel about their service of care and provide data to optimize their personalized chronic disease self-management strategies.

ObjectiveThe purpose of this study was to translate and verify the reliability and validity of the Chinese version of the self-care scale for older adults undergoing hip fracture surgery.MethodsA total of 502 older adult/adults patients after hip fracture surgery were recruited from Liaoning, Shanxi, and Beijing, China. The reliability of the Chinese version of the scale was measured by internal consistency, split-half reliability, and retest reliability, and the validity was evaluated by the content validity index and structure validity index.ResultsThe Chinese version of the HFS-SC scale had a Cronbach's alpha coefficient of 0.848, and the Cronbach's alpha coefficients for the five dimensions ranged from 0.719 to 0.780. The split-half reliability of the scale was 0.739, and the retest reliability was 0.759. The content validity index (S-CVI) was 0.932. The five-factor structure, supported by the eigenvalues, total variance explained, and the scree plot accounted for 66.666% of the total variance. In confirmatory factor analysis, the model fit results were as follows, X2/df = 1.847, GFI = 0.914, AGFI = 0.878, PGFI = 0.640, IFI = 0.932, TLI = 0.912, CFI = 0.931, RMSEA = 0.058, PNFI = 0.679. The indicators of the model's fit were within reasonable bounds.ConclusionThe Chinese version of the self-care scale for older adults undergoing hip fracture surgery has suitable reliability and validity. The scale can be used to assess the level of older adult/adults self-care in China following hip replacement surgery and serves as a useful benchmark for identifying potential intervention targets to raise the level of older adult/adults self-care following hip replacement surgery.

Abstract Background Small nucleolar RNA host gene (SNHG) long noncoding RNAs (lncRNAs) are frequently dysregulated in human cancers and involved in tumorigenesis and progression. SNHG17 has been reported as a candidate oncogene in several cancer types, however, its regulatory role in colorectal cancer (CRC) is unclear. Methods SNHG17 expression in multiple CRC cohorts was assessed by RT-qPCR or bioinformatic analyses. Cell viability was evaluated using Cell Counting Kit-8 (CCK-8) and colony formation assays. Cell mobility and invasiveness were assessed by Transwell assays. Tumor xenograft and metastasis models were applied to confirm the effects of SNHG17 on CRC tumorigenesis and metastasis in vivo. Immunohistochemistry staining was used to measure protein expression in cancer tissues. RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, and dual luciferase assays were used to investigate the molecular mechanism of SNHG17 in CRC. Results Using multiple cohorts, we confirmed that SNHG17 is aberrantly upregulated in CRC and correlated with poor survival. In vitro and in vivo functional assays indicated that SNHG17 facilitates CRC proliferation and metastasis. SNHG17 impedes PES1 degradation by inhibiting Trim23-mediated ubiquitination of PES1. SNHG17 upregulates FOSL2 by sponging miR-339-5p, and FOSL2 transcription activates SNHG17 expression, uncovering a SNHG17-miR-339-5p-FOSL2-SNHG17 positive feedback loop. Conclusions We identified SNHG17 as an oncogenic lncRNA in CRC and identified abnormal upregulation of SNHG17 as a prognostic risk factor for CRC. Our mechanistic investigations demonstrated, for the first time, that SNHG17 promotes tumor growth and metastasis through two different regulatory mechanisms, SNHG17-Trim23-PES1 axis and SNHG17-miR-339-5p-FOSL2-SNHG17 positive feedback loop, which may be exploited for CRC therapy.

Abstract Heart failure (HF) and cardiac arrhythmias share overlapping pathological mechanisms that act cooperatively to accelerate disease pathogenesis. Cardiac fibrosis is associated with both pathological conditions. Our previous work identified a link between phytosterol accumulation and cardiac injury in a mouse model of phytosterolemia, a rare disorder characterized by elevated circulating phytosterols and increased cardiovascular disease risk. Here, we uncover a previously unknown pathological link between phytosterols and cardiac arrhythmias in the same animal model. Phytosterolemia resulted in inflammatory pathway induction, premature ventricular contractions (PVC) and ventricular tachycardia (VT). Blockade of phytosterol absorption either by therapeutic inhibition or by genetic inactivation of NPC1L1 prevented the induction of inflammation and arrhythmogenesis. Inhibition of phytosterol absorption reduced inflammation and cardiac fibrosis, improved cardiac function, reduced the incidence of arrhythmias and increased survival in a mouse model of phytosterolemia. Collectively, this work identified a pathological mechanism whereby elevated phytosterols result in inflammation and cardiac fibrosis leading to impaired cardiac function, arrhythmias and sudden death. These comorbidities provide insight into the underlying pathophysiological mechanism for phytosterolemia-associated risk of sudden cardiac death.

Abstract Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses tumor progression, potentially displaying opposing effects on therapeutic outcomes. Chronic inflammation facilitates tumor progression and treatment resistance, whereas induction of acute inflammatory reactions often stimulates the maturation of dendritic cells (DCs) and antigen presentation, leading to anti-tumor immune responses. In addition, multiple signaling pathways, such as nuclear factor kappa B (NF-kB), Janus kinase/signal transducers and activators of transcription (JAK-STAT), toll-like receptor (TLR) pathways, cGAS/STING, and mitogen-activated protein kinase (MAPK); inflammatory factors, including cytokines (e.g., interleukin (IL), interferon (IFN), and tumor necrosis factor (TNF)-α), chemokines (e.g., C-C motif chemokine ligands (CCLs) and C-X-C motif chemokine ligands (CXCLs)), growth factors (e.g., vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β), and inflammasome; as well as inflammatory metabolites including prostaglandins, leukotrienes, thromboxane, and specialized proresolving mediators (SPM), have been identified as pivotal regulators of the initiation and resolution of inflammation. Nowadays, local irradiation, recombinant cytokines, neutralizing antibodies, small-molecule inhibitors, DC vaccines, oncolytic viruses, TLR agonists, and SPM have been developed to specifically modulate inflammation in cancer therapy, with some of these factors already undergoing clinical trials. Herein, we discuss the initiation and resolution of inflammation, the crosstalk between tumor development and inflammatory processes. We also highlight potential targets for harnessing inflammation in the treatment of cancer.

Zhang et al. present the cryo-EM structure of ATP-binding cassette transporters ABCG5/G8 in complex with the Fab fragments from two monoclonal antibodies at 3.3 Å resolution. This study provides structural insights into the transport cycle and potential epitopes for therapeutic interventions that control cholesterol homeostasis.

Abstract Background Accumulating evidences have shown that long noncoding RNAs (lncRNAs) play key roles in many diseases, including cancer. Several studies reported that MCM3AP antisense RNA 1 (MCM3AP‐AS1) was associated with the tumorigenesis and progression. However, the specific function and mechanism of MCM3AP‐AS1 in colorectal cancer (CRC) have not been fully understood. Methods The expression of MCM3AP‐AS1 was detected by quantitative reverse transcription PCR (RT‐qPCR) in CRC tissues and matched noncancerous tissues (NCTs). CCK‐8 assay, colony formation assay, transwell assay, xenograft and lung metastasis mouse models were used to examine the tumor‐promoting function of MCM3AP‐AS1 in vitro and in vivo. The binding relationship between MCM3AP‐AS1, miR‐193a‐5p and sentrin‐specific peptidase 1 (SENP1) were screened and identified by databases, RT‐qPCR, dual luciferase reporter assay and western blot. Results In the present study, we got that the expression of MCM3AP‐AS1 was higher in CRC tissues than in paired NCTs, and increased MCM3AP‐AS1 expression was associated with adverse outcomes in CRC patients. Functional experiments in vitro revealed that silencing of MCM3AP‐AS1 could inhibit the proliferation, colony formation, migratory, and invasive abilities of CRC cells. The mouse models of xenograft and lung metastasis further confirmed that in vivo silencing MCM3AP‐AS1 could significantly inhibit the growth and metastasis of CRC. Further mechanism studies indicated that MCM3AP‐AS1 could sponge miR‐193a‐5p and inhibit the activity of it. What is more, SENP1 was proved to be a novel target of miR‐193a‐5p and could be upregulated by MCM3AP‐AS1. At last, we observed that SENP1 overexpression in CRC tissues was closely related to unfavorable prognosis. Conclusion Taken together, we identified in CRC the MCM3AP‐AS1/miR‐193a‐5p/SENP1 regulatory axis, which affords a therapeutic possibility for CRC.

Cognitive radio (CR) is a candidate for opportunistic spectrum implementation in wireless communications, allowing secondary users (SUs) to share the spectrum with primary users (PUs). In this paper, a robust adaptive target power allocation strategy for cognitive nonorthogonal multiple access (NOMA) networks is proposed, which involves the maximum transmission power of each SU and interference power threshold under PU constraints. By introducing the signal-to-interference-plus-noise ratio (SINR) adjustment factor, the strategy enables single-station communication to achieve energy efficiency (EE) or high throughput (HT), thus making the target function more flexible. In the same communication scenario, different cognitive users can choose different communication targets that meet their needs. Different QoS can be selected by the same cognitive user at different times. In the case of imperfect channel state information (CSI), semi-infinite (SI) constraints with bounded uncertainty sets are transformed into an optimization problem under the worst case, which is solved by the dual decomposition method. Simulation results show that this strategy has good adaptive selectivity and robustness.

Abstract Self-reported skin discomfort is a common problem during pregnancy, but it is not clear whether skin barrier function is altered in the process. Few studies have described the skin barrier function during pregnancy. In this work, we used highly sensitive and high-resolution ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) to distinguish skin surface lipid (SSL) combined with multivariate analysis of lipids and metabolic changes to determine the relationship between SSL changes and skin physiology during pregnancy in order to better understand the skin condition of pregnant women. The results showed a significant reduction in the total lipid content in pregnant women. A total of 2270 lipids were detected, and the relative abundances of fatty acyls and glycerolipids were significantly reduced, while glycerophospholipids (GPs), sphingolipids, and saccharolipids was significantly increased in the pregnancy group. Multivariate data analysis indicated that 23 entities constituted the most important individual species responsible for the discrimination and phosphatidylcholine was the most abundant lipid in pregnancy group. In addition, compared to SSL profile of control group, it was observed that the average chain length of ceramides and fatty acids both decreased in SSL profile of pregnancy group. The main and most commonly affected pathway was that of GP pathways. These findings indicate that skin lipids are significantly altered in mid-pregnancy compared to the control group. Changes in ostrogen during pregnancy also make the skin more susceptible to inflammatory factors and lead to more fragile and susceptible skin, weakening the skin barrier along with the lipid alterations.

OBJECTIVE: This study examined the psychological impact of the coronavirus disease 2019 (COVID-2019) outbreak on medical staff in China. MATERIALS AND METHODS: In February 2020, an online survey was carried out by using an online survey tool (WeChat) to evaluate the effects of the outbreak on the mental health of medical staff in China. RESULTS: A total of 11,118 medical staff responded to the survey. About 4.98% of the respondents reported middle and high levels of anxiety, while 13.47% of the respondents reported middle and high levels of depression since the COVID-19 outbreak. Nurses, frontline medical staff, and younger medical staff were more likely to have anxiety and depression than physicians, nonfrontline medical staff, and older medical staff. CONCLUSIONS: Although the serious psychological impact of COVID-19 is not so common in medical staff in China, programs are needed to protect them against the negative impacts of COVID-19.

Abstract Background Secondary brain damage caused by the innate immune response and subsequent proinflammatory factor production is a major factor contributing to the high mortality of intracerebral haemorrhage (ICH). Nucleotide-binding oligomerization domain 1 (NOD1)/receptor-interacting protein 2 (RIP2) signalling has been reported to participate in the innate immune response and inflammatory response. Therefore, we investigated the role of NOD1/RIP2 signalling in mice with collagenase-induced ICH and in cultured primary microglia challenged with hemin. Methods Adult male C57BL/6 mice were subjected to collagenase for induction of ICH model in vivo. Cultured primary microglia and BV2 microglial cells (microglial cell line) challenged with hemin aimed to simulate the ICH model in vitro. We first defined the expression of NOD1 and RIP2 in vivo and in vitro using an ICH model by western blotting. The effect of NOD1/RIP2 signalling on ICH-induced brain injury volume, neurological deficits, brain oedema, and microglial activation were assessed following intraventricular injection of either ML130 (a NOD1 inhibitor) or GSK583 (a RIP2 inhibitor). In addition, levels of JNK/P38 MAPK, IκBα, and inflammatory factors, including tumour necrosis factor-α (TNF-α), interleukin (IL)-1β, and inducible nitric oxide synthase (iNOS) expression, were analysed in ICH-challenged brain and hemin-exposed cultured primary microglia by western blotting. Finally, we investigated whether the inflammatory factors could undergo crosstalk with NOD1 and RIP2. Results The levels of NOD1 and its adaptor RIP2 were significantly elevated in the brains of mice in response to ICH and in cultured primary microglia, BV2 cells challenged with hemin. Administration of either a NOD1 or RIP2 inhibitor in mice with ICH prevented microglial activation and neuroinflammation, followed by alleviation of ICH-induced brain damage. Interestingly, the inflammatory factors interleukin (IL)-1β and tumour necrosis factor-α (TNF-α), which were enhanced by NOD1/RIP2 signalling, were found to contribute to the NOD1 and RIP2 upregulation in our study. Conclusion NOD1/RIP2 signalling played an important role in the regulation of the inflammatory response during ICH. In addition, a vicious feedback cycle was observed between NOD1/RIP2 and IL-1β/TNF-α, which could to some extent result in sustained brain damage during ICH. Hence, our study highlights NOD1/RIP2 signalling as a potential therapeutic target to protect the brain against secondary brain damage during ICH.

Stroke is a disease with high morbidity, disability and mortality, which seriously endangers the life span and quality of life of people worldwide. Angiogenesis and neuroprotection are the key to the functional recovery of penumbra function after acute cerebral infarction. In this study, we used the middle cerebral artery occlusion (MCAO) model to investigate the effects of 1α,25-dihydroxyvitamin D3 (1,25-D3) on transforming growth factor-β (TGF-β)/Smad2/3 signaling pathway. Cerebral infarct volume was measured by TTC staining. A laser speckle flow imaging system was used to measure cerebral blood flow (CBF) around the ischemic cortex of the infarction, followed by platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) and isolectin-B4 (IB4) immunofluorescence. The expression of vitamin D receptor (VDR), TGF-β, Smad2/3, p-Smad2, p-Smad3, and vascular endothelial growth factor (VEGF) was analyzed by western blot and RT-qPCR. Results showed that compared with the sham group, the cerebral infarction volume was significantly increased while the CBF was reduced remarkably in the MCAO group. 1,25-D3 reduced cerebral infarction volume, increased the recovery of CBF and expressions of VDR, TGF-β, p-Smad2, p-Smad3, and VEGF, significantly increased IB4+ tip cells and CD31+ vascular length in the peri-infarct area compared with the DMSO group. The VDR antagonist pyridoxal-5-phosphate (P5P) partially reversed the neuroprotective effects of 1,25-D3 described above. In summary, 1,25-D3 plays a neuroprotective role in stroke by activating VDR and promoting the activation of TGF-β, which in turn up-regulates the TGF-β/Smad2/3 signaling pathway, increases the release of VEGF and thus promotes angiogenesis, suggesting that this signaling pathway may be an effective target for ischemic stroke treatment. 1,25-D3 is considered to be a neuroprotective agent and is expected to be an effective drug for the treatment of ischemic stroke and related diseases.

LCAT converts free cholesterol to cholesteryl esters in the process of reverse cholesterol transport. Familial LCAT deficiency (FLD) is a genetic disease that was first described by Kaare R. Norum and Egil Gjone in 1967. This report is a summary from a 2017 symposium where Dr. Norum recounted the history of FLD and leading experts on LCAT shared their results. The Tesmer laboratory shared structural findings on LCAT and the close homolog, lysosomal phospholipase A2. Results from studies of FLD patients in Finland, Brazil, Norway, and Italy were presented, as well as the status of a patient registry. Drs. Kuivenhoven and Calabresi presented data from carriers of genetic mutations suggesting that FLD does not necessarily accelerate atherosclerosis. Dr. Ng shared that LCAT-null mice were protected from diet-induced obesity, insulin resistance, and nonalcoholic fatty liver disease. Dr. Zhou presented multiple innovations for increasing LCAT activity for therapeutic purposes, whereas Dr. Remaley showed results from treatment of an FLD patient with recombinant human LCAT (rhLCAT). Dr. Karathanasis showed that rhLCAT infusion in mice stimulates cholesterol efflux and suggested that it could also enhance cholesterol efflux from macrophages. While the role of LCAT in atherosclerosis remains elusive, the consensus is that a continued study of both the enzyme and disease will lead toward better treatments for patients with heart disease and FLD.

Forsythia suspensa (Thunb.) Vahl (F. suspensa) is a traditional Chinese medical herb and only its fruit is currently used in clinical therapies. However, the discarded parts like leaves also contain a large number of active components. In this study, we used macroporous adsorption resin to enrich the effective components from F. suspensa leaves. The separated active compounds were then identified and quantified by ultra-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC/Q-TOF MS) and high-performance liquid chromatography Active components with antibacterial properties extracted from F. suspensa leaves were confirmed in vitro and the corresponding mechanisms were explored. In sum, a stable and effective method for extracting antibacterial active components from F. suspensa leaves was established in this study, which proved the practicability of F. suspensa leaves as traditional Chinese medicine and is conducive to the more comprehensive utilization of the plant.

Lithium–sulfur (Li–S) batteries are considered as promising candidates for future-generation energy storage systems due to their prominent theoretical energy density. However, their application is still hindered by several critical issues, e.g., the low conductivity of sulfur species, the shuttling effects of soluble lithium polysulfides, volumetric expansion, sluggish redox kinetics, and uncontrollable Li dendritic formation. Considerable research efforts have been devoted to breaking through the obstacles that are preventing Li–S batteries from realizing practical application. Recently, benefiting from the no additives/binders, buffer of volume change, high sulfur loading and suppression of lithium dendrites, nanoarray (NA) structures have have emerged as efficient and durable electrodes in Li–S batteries. In this work, recent advances in the design, synthesis and application of NA structures in Li–S batteries are reviewed. First, the multifunctional merits and typical synthetic strategies of employing NA structure electrodes for Li–S batteries are outlined. Second, the applications of NA structures in Li–S batteries are discussed comprehensively. Finally, the challenge and rational design of NA structure for Li–S batteries are analyzed in depth, with the aim of providing promising orientations for the commercialization of high-energy-density Li–S batteries.

The emergence and advancement of flexible electronics have great potential to lead development trends in many fields, such as “smart electronic skin” and wearable electronics. By acting as intermediates to detect a variety of external stimuli or physiological parameters, flexible sensors are regarded as a core component of flexible electronic systems and have been extensively studied. Unlike conventional rigid sensors requiring costly instruments and complicated fabrication processes, flexible sensors can be manufactured by simple procedures with excellent production efficiency, reliable output performance, and superior adaptability to the irregular surface of the surroundings where they are applied. Here, recent studies on flexible sensors for sensing humidity and strain/pressure are outlined, emphasizing their sensory materials, working mechanisms, structures, fabrication methods, and particular applications. Furthermore, a conclusion, including future perspectives and a short overview of the market share in this field, is given for further advancing this field of research.

Colorectal cancer (CRC) is one of the most common malignancies globally. Increasing evidence indicates that circular RNAs (circRNAs) play a pivotal role in various cancers. The present study focused on exploring the role of a functionally unknown circRNA, hsa_circ_0062682 (circ_0062682), in CRC. By online analyses and experimental validations, we showed that circ_0062682 expression was aberrantly increased in CRC tissues compared with paired normal tissues. Increased expression of circ_0062682 in CRC notably correlated with a poor prognosis and advanced tumor stage. Functional experiments showed that circ_0062682 knockdown reduced CRC growth both in vitro and in vivo. Mechanistically, we revealed that circ_0062682 could sponge miR-940 and identified D-3-phosphoglycerate dehydrogenase (PHGDH), a key oxidoreductase involved in serine biosynthesis, as a novel target of miR-940. Silencing miR-940 expression could mimic the inhibitory effect of circ_0062682 knockdown on CRC proliferation. The expression of PHGDH was downregulated in circ_0062682-depleted or miR-940 overexpressing CRC cells at both the mRNA and protein levels. Circ_0062682 knockdown suppressed CRC growth by decreasing PHGDH expression and serine production via miR-940. Taken together, these data demonstrate, for the first time, that circ_0062682 promotes serine metabolism and tumor growth in CRC by regulating the miR-940/PHGDH axis, suggesting circ_0062682 as a potential novel therapeutic target for CRC.

Pulsatilla chinensis (Bunge) Regel is a commonly used Chinese medicine for clearing away heat and detoxification, cooling blood, stopping dysentery, and anti-inflammatory effects. Pulsatilla chinensis saponins (PRS) have been identified to be responsible for producing these pharmacological activities. Studies have shown that Pulsatilla decoction has a good therapeutic effect on ulcerative colitis (UC), however, the therapeutic effect of PRS on UC has not been reported. Therefore, the purpose of this study was to investigate the possible anti-UC activity of PRS using a dextran sulfate sodium (DSS)-induced rat model, and further study the mechanism of PRS in the treatment of UC. The fecal and colon samples were collected from rats to monitor the changes in the composition and diversity of the intestinal flora, and pathological colon sections were also made to examine the mesenteric hemorheological characteristics. The results showed that PRS significantly reduced the mesenteric blood flow in UC rats and significantly alleviated the inflammatory response, which indicates that saponins are involved in the anti-UC effects of PRS. At the same time, it is also suggested that the regulation of intestinal flora by Pulsatilla chinensis saponins is an important pathway for its anti-UC activity, which may be ascribed to the increase in beneficial bacteria like norank_F_Muribaculaceae and norank_F_norank_O_Clostridia_UCG-014, and decrease in the harmful Bacteroides.

The use of a cognitive radio power allocation algorithm is an effective method to improve spectral utilization. However, there are three problems with traditional cognitive radio power allocation algorithms: (1) based on the ideal channel model analysis, channel fluctuation is not considered; (2) they do not consider fairness among cognitive users; and (3) some algorithms are complex and locating the optimal power allocation scheme is not an easy task. For the above problems, this study establishes a robust model which adds the cognitive user transmission rate variance constraint to solve the maximum channel capacity time power allocation scheme by considering the worst-case channel transmission model, and finally solves this complex non-convex optimization problem by using the hybrid particle swarm algorithm. Simulation results show that the algorithm has good robustness, improves the fairness among the cognitive users, makes full use of the channel resources under the constraints, and has a simple algorithm, fast convergence, and good optimization results.

Although integrin subunit genes (ITGs) have been reported to be associated with some human cancer types, a systematic assessment of ITGs across human cancers is lacking. Hence, we performed comprehensive analyses to investigate mRNA expression, copy number variation (CNV), DNA methylation, mutation, and clinical landscapes of ITGs in more than 8000 cancer patients from The Cancer Genome Atlas (TCGA) dataset. Landscapes of ITGs were established across 20 human cancer types. We observed that ITGs are extensively dysregulated with heterogeneity in different system cancer types, part of which are driven by CNV, DNA hypomethylation or mutation. Furthermore, dysregulated prognosis-related ITGs were systematically identified in each cancer type, including ITGA11 in stomach adenocarcinoma (STAD). The models based on dysregulated ITGs with clinical relevance and TNM staging indexes are good indicators in STAD and head and neck squamous cell carcinoma. Finally, ITGA11 is overexpressed and associated with poor survival in STAD cases from the TCGA and additionally Gene Expression Omnibus cohorts. Functionally, ITGA11 knockdown inhibits malignant phenotypes in STAD cell lines AGS and MKN45, demonstrating the oncogenic role of ITGA11 in STAD. Together, this study highlights the important roles of ITGs in tumorigenesis as potential prognostic biomarkers, and provide an effective resource that identifies cancer-related genes of ITGs in human cancers.

FFAs display pleiotropic functions in human diseases. Short-chain FAs (SCFAs), medium-chain FAs, and long-chain FAs are derived from different origins, and precise quantification of these FFAs is critical for revealing their roles in biological processes. However, accessing stable isotope-labeled internal standards is difficult, and different chain lengths of FFAs challenge the chromatographic coverage. Here, we developed a metabolomics strategy to analyze FFAs based on isotope-free LC-MS-multiple reaction monitoring integrated with dual derivatization. Samples and dual derivatization internal standards were synthesized using 2-dimethylaminoethylamine or dansyl hydrazine as a “light” label and N,N-diethyl ethylene diamine or N,N-diethyldansulfonyl hydrazide as a “heavy” label under mild and efficient reaction conditions. General multiple reaction monitoring parameters were designed to analyze these FFAs. The limit of detection of SCFAs varied from 0.5 to 3 nM. Furthermore, we show that this approach exhibits good linearity (R2 = 0.99374–0.99929), there is no serious substrate interference, and no quench steps are required, confirming the feasibility and reliability of the method. Using this method, we successfully quantified 15 types of SCFAs in fecal samples from hepatocellular carcinoma patients and healthy individuals; among these, propionate, butyrate, isobutyrate, and 2-methylbutyrate were significantly decreased in the hepatocellular carcinoma group compared with the healthy control group. These results indicate that the integrated LC-MS metabolomics with isotope-free and dual derivatization is an efficient approach for quantifying FFAs, which may be useful for identifying lipid biomarkers of cancer.

In this work, a covalent-organic framework with high carbon and nitrogen content microstructures (named COF-LZU1), assisted by 3D nitrogen-containing kenaf stem composites (represented as COF-LZU1/3D-KSCs), was constructed. Moreover, it was utilized for immobilizing acetylcholinesterase (AChE) for identifying trichlorfon, a commonly applied organophosphorus (OP) pesticide. The development of COF-LZU1/3D-KSC was affirmed by SEM, PXRD, and EDXS. The findings confirmed that COF-LZU1 microstructures were uniformly developed on 3D-KSC holes using a one-step synthesis approach, which can substantially enhance the effective surface area. Also, the COF-LZU1/3D-KSC composite contains not only the nitrogen element in COF-LZU1 but also the nitrogen element in 3D-KSC, which will greatly improve the biocompatibility of the material. The AChE/COF-LZU1/3D-KSC integrated electrode was fabricated by directly fixing a large amount of AChE on the composite. At the same time, the integrated electrode had good detection efficiency for trichlorfon. Improved stabilization, a wide-linear-range (0.2–19 ng/mL), and a lower detection limit (0.067 ng/mL) have been displayed by the sensor. Therefore, this sensor can be used as an important platform for the on-site detection of OP residue.

Background: The prevalence of cognitive impairment is growing and higher in rural areas. The association between carotid plaque and cognitive impairment remains uncertain, and few studies focused on the cognitive function of the rural population. We designed this study to investigate the association between carotid plaque and cognitive impairment in a rural community.Methods: We enrolled 3,336 participants who underwent carotid ultrasound and cognitive function measurements, free of cerebrovascular diseases, and without neurological deficits, from the China National Stroke Screen Survey program. Cognitive function was evaluated by the Montreal Cognitive Assessment (Beijing version). We used multivariable logistic regression to assess the association between asymptomatic carotid plaques and the presence of cognitive impairment.Results: Nine hundred seventy-six participants had cognitive impairment in this study. After adjustment for potential confounding factors, asymptomatic carotid plaques (odds ratio was 1.35; 95% confidence interval, 1.15–1.58), especially vulnerable carotid plaques (odds ratio was 1.54; 95% confidence interval, 1.28–1.85), were associated with cognitive impairment.Conclusion: In this community-based and observational study, asymptomatic vulnerable carotid plaque is an independent and significant risk factor for cognitive impairment in rural residents.

Noise generated from wind turbines is a big challenge for the wind energy industry to develop further onshore wind energy. The traditional way of reducing noise is to design low noise wind turbine airfoils and blades. A wind turbine operating under wind shear and in yaw produces periodic changes of blade loading, which intensifies the amplitude modulation (AM) of the generated noise, and thus can give more annoyance to the people living nearby. In this paper, the noise emission from a wind turbine under wind shear and yaw is modelled with an advanced fluid-structure-acoustics framework, and then controlled with a pitch control strategy. The numerical tool used in this study is the coupled Navier–Stokes/Actuator Line model EllipSys3D/AL, structure model FLEX5, and noise prediction model (Brooks, Pope and Marcolini: BPM) framework. All simulations and tests were made on the NM80 wind turbine equipped with three blades made by LM Wind Power. The coupled code was first validated against field load measurements under wind shear and yaw, and a fairly good agreement was obtained. The coupled code was then used to study the noise source control of the turbine under wind shear and yaw. Results show that in the case of a moderate wind shear with a shear exponent of 0.3, the pitch control strategy can reduce the mean noise emission about 0.4 dB and reduce slightly the modulation depth that mainly occurs in the low-frequency region.

LCAT is intimately involved in HDL maturation and is a key component of the reverse cholesterol transport (RCT) pathway which removes excess cholesterol molecules from the peripheral tissues to the liver for excretion. Patients with loss-of-function LCAT mutations exhibit low levels of HDL cholesterol and corneal opacity. Here we report the 2.65 Å crystal structure of the human LCAT protein. Crystallization required enzymatic removal of N-linked glycans and complex formation with a Fab fragment from a tool antibody. The crystal structure reveals that LCAT has an α/β hydrolase core with two additional subdomains that play important roles in LCAT function. Subdomain 1 contains the region of LCAT shown to be required for interfacial activation, while subdomain 2 contains the lid and amino acids that shape the substrate binding pocket. Mapping the naturally occurring mutations onto the structure provides insight into how they may affect LCAT enzymatic activity.

Elevated triglyceride (TG) and cholesterol levels are risk factors for cardiovascular disease and are often associated with diabetes and metabolic syndrome. Recent reports suggest that fibroblast growth factor (FGF)19 and FGF21 can dramatically improve metabolic dysfunction, including hyperglycemia, hypertriglyceridemia, and hypercholesterolemia. Due to their similar receptor specificities and co-receptor requirements, FGF19 and FGF21 share many common properties and have been thought to be interchangeable in metabolic regulation. Here we directly compared how pharmacological administration of recombinant FGF19 or FGF21 proteins affect metabolism in B6.V-Lepob/J leptin-deficient mice. FGF19 and FGF21 equally improved glucose parameters; however, we observed increased serum TG and cholesterol levels after treatment with FGF19 but not with FGF21. Increases in serum TGs were also observed after a 4-day treatment with FGF19 in C57BL6/J mice on a high-fat diet. This is in contrast to many literature reports that showed significant improvements in hyperlipidemia after chronic treatment with FGF19 or FGF21 in high-fat diet models. We propose that FGF19 has lipid-raising and lipid-lowering actions mediated through different FGF receptors and target tissues, and the results described here provide a potential mechanism that may explain the inconsistency in the reported effects of FGF19 on lipid metabolism.

Cognitive radio networks (CRNs) is a technology that can alleviate the scarcity of radio resources, improve communication efficiency, and reduce electromagnetic radiation pollution. However, traditional research mostly concentrates on a single optimization function, which is too constrained to achieve global consideration. We suggest a multi-objective optimization problem (MOP) with the objectives of transmission rate and power efficiency. Then, we introduce a fairness factor with the minimum protection rate to ensure the quality of data transfer for each secondary user (SU). We use the ellipsoid set to characterize the uncertain parameters under the actual channel state information (CSI). In the worst case, the semi-infinite programming (SIP) problem is transformed into a secondorder cone programming (SOCP) problem. The original problem is linearly combined using the weighted-sum method to construct a single objective problem (SOP), which is then turned into a solvable convex optimization problem and resolved using the Lagrange dual algorithm and sub-gradient method. The simulation results demonstrate the ability of our proposed algorithm to balance power and transmission rate optimization by adjusting the weighting values, while maintaining good robustness. [ABSTRACT FROM AUTHOR]