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Abstract In this study, nonaxisymmetric endwall contouring technology is employed as a passive control strategy to enhance the stable operating range of a centrifugal compressor with an asymmetric volute. The endwall contouring method is applied to the hub‐side wall of the vaned diffuser within a centrifugal compressor stage. Instead of utilizing a flat hub as the baseline diffuser, various diffuser configurations featuring hub‐side contoured endwalls are explored, with adjustments in the peak radial position and peak height of the convex and concave profiles. Numerical simulations are conducted to evaluate the performance of the centrifugal compressor stage with both the baseline and contoured vaned diffusers. The investigation explores the underlying flow control mechanisms and establishes the effective endwall contouring guidelines. The findings highlight the effectiveness of endwall contouring in enhancing the stable operating range of centrifugal compressors. Notably, a substantial enhancement of 15.1% in the stable operating range is achieved by employing the contoured diffuser with the peak radial position near the vane leading edge (LE) and the peak height at 20% of the vane height. The endwall contoured diffusers reduce the positive LE incidence angles to direct the fluid toward the suction side (SS), and increase the radial velocity near the SS to suppress the hub‐suction corner separations in the diffuser passages near the volute tongue. These improvements collectively contribute to the enhancement of diffuser flow characteristics. Finally, a set of effective endwall contouring guidelines is proposed to guide the endwall contouring design for enhancing the stable operating range of centrifugal compressors.

Abstract Acute pancreatitis (AP) is a multifaceted inflammatory disorder stemming from the aberrant activation of trypsin within the pancreas. Despite the contribution of various factors to the pathogenesis of AP, such as trypsin activation, dysregulated increases in cytosolic Ca2+ levels, inflammatory cascade activation, and mitochondrial dysfunction, the precise molecular mechanisms underlying the disease are still not fully understood. Mitophagy, a cellular process that preserves mitochondrial homeostasis under stress, has emerged as a pivotal player in the context of AP. Research suggests that augmenting mitophagy can mitigate pancreatic injury by clearing away malfunctioning mitochondria. Elucidating the role of mitophagy in AP may pave the way for novel therapeutic strategies. This review article aims to synthesize the current research findings on mitophagy in AP and underscore its significance in the clinical management of the disorder.

Abstract The newly identified XBB.1.16‐containing sublineages, including XBB.1.5, have become the prevailing severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variant in circulation. Unlike previous Omicron XBB variants (e.g., XBB.1.5 and XBB.1.9) harboring the F486P substitution, XBB.1.16 also carries a T478R substitution in the receptor‐binding domain (RBD). Numerous researchers have delved into the high transmissibility and immune evasion of XBB.1.16 subvariant. Therefore, developing a new vaccine targeting XBB.1.16, including variants of concern (VOCs), is paramount. In our study, we engineered a recombinant protein by directly linking the S‐RBD sequence of the XBB.1.16 strain of SARS‐CoV‐2 to the sequences of two heptad repeat sequences (HR1 and HR2) from the SARS‐CoV‐2 S2 subunit. Named the recombinant RBDXBB.1.16‐HR/trimeric protein, this fusion protein autonomously assembles into a trimer. Combined with an MF59‐like adjuvant, the RBDXBB.1.16‐HR vaccine induces a robust humoral immune response characterized by high titers of neutralizing antibodies against variant pseudovirus and authentic VOCs and cellular immune responses. Additionally, a fourth heterologous RBDXBB.1.16‐HR vaccine enhances both humoral and cellular immune response elicited by three‐dose mRNA vaccines. These findings demonstrate that the recombinant RBDXBB.1.16‐HR protein, featuring the new T478R mutation, effectively induces solid neutralizing antibodies to combat newly emerged XBB variants.

The spatial disparity of air pollutants is one of the key influential factors for environmental inequality. We quantitatively evaluated the evolution of PM2.5 spatial disparity in China during 2013–2020, and investigated the associations between PM2.5 spatial disparity and economic indicators. Differences in PM2.5 between more- and less-polluted cities declined over time, suggesting decreased absolute disparity. However, the more polluted cities in 2013 remained so in 2017 and 2020, and vice versa, indicating persistent relative disparity. PM2.5 pollution levels increased with higher GDP per capita in less-developed areas of China, but such negative effects weakened over time, while economic development tended to promote cleaner air in developed areas of China. Therefore, policies to improve air quality and promote economic development simultaneously are needed in China to reduce the disparity of air pollution and promote all people to enjoy environmental equality.

Abstract Urgent research into innovative severe acute respiratory coronavirus‐2 (SARS‐CoV‐2) vaccines that may successfully prevent various emerging emerged variants, particularly the Omicron variant and its subvariants, is necessary. Here, we designed a chimeric adenovirus‐vectored vaccine named Ad5‐Beta/Delta. This vaccine was created by incorporating the receptor‐binding domain from the Delta variant, which has the L452R and T478K mutations, into the complete spike protein of the Beta variant. Both intramuscular (IM) and intranasal (IN) vaccination with Ad5‐Beta/Deta vaccine induced robust broad‐spectrum neutralization against Omicron BA.5‐included variants. IN immunization with Ad5‐Beta/Delta vaccine exhibited superior mucosal immunity, manifested by higher secretory IgA antibodies and more tissue‐resident memory T cells (TRM) in respiratory tract. The combination of IM and IN delivery of the Ad5‐Beta/Delta vaccine was capable of synergically eliciting stronger systemic and mucosal immune responses. Furthermore, the Ad5‐Beta/Delta vaccination demonstrated more effective boosting implications after two dosages of mRNA or subunit recombinant protein vaccine, indicating its capacity for utilization as a booster shot in the heterologous vaccination. These outcomes quantified Ad5‐Beta/Delta vaccine as a favorable vaccine can provide protective immunity versus SARS‐CoV‐2 pre‐Omicron variants of concern and BA.5‐included Omicron subvariants.

Abstract Indoor air conditioning systems play a crucial role in regulating the environmental conditions of enclosed spaces. The noise generated by such systems can significantly impact human comfort. The multiblade centrifugal fan, as a crucial component of indoor air conditioners, has a significant impact on the performance of the air conditioner. The vortex, which is the primary noise source inside the fan, hinders the aerodynamic noise reduction of the indoor unit. During experimental research and numerical simulation of the indoor unit, the researchers identified the presence of a vortex flow at the outlet of the multiblade centrifugal fan. By analyzing the velocity vector of different cross‐sections in the fan, the researchers determined the formation mechanism and influencing factors of the vortex at the fan's outlet. The addition of fairing sheet plates on the volute wall was explored as a vortex suppression method, which proved effective in weakening and suppressing the vortex. The test results showed that under the same air volume, the noise reduction amplitude of the fan equipped with fairing sheet blades was 1.2 dB at an outlet static pressure of 30 Pa and 0.7 dB at an outlet static pressure of 100 Pa. The research findings suggest that the addition of the fairing sheet can effectively reduce the vortex's intensity, improve the performance of the multiblade centrifugal fan, and reduce the noise.

Abstract Background/aims To investigate the clinical situation, treatment methods, and clinical predictors of surgical intervention in children with magnetic foreign bodies in the digestive tract. Materials and methods From January 2019 to June 2022, we retrospectively analyzed the clinical data of 72 children who ingested magnetic foreign bodies inadvertently in our hospital, including their general information, admissions, clinical manifestations, and treatment methods, as well as pertinent literature and statistical data. Following software processing, univariate and multivariate logistic regression analyses were conducted to determine the independent risk factors of this study. Results In this study, 16 patients (22.2%) were discharged smoothly following conservative treatment and 19 patients (26.4%) were cured by gastroscopy. The remaining 37 patients (51.4%) were underwent surgery, in which 26 cases developed gastrointestinal perforation. There were statistical differences between surgery group and non- surgery group in the days of eating by mistake, clinical manifestations (nausea and vomiting, intermittent abdominal pain, abdominal muscle tension) and movement trajectory by every 24-h radiograph (P

Abstract Background To illuminate the precise roles of MOB Kinase Activator 1 A (MOB1A) in the development of ovarian cancer (OC). Methods MOB1A expression and clinical data of OC were obtained from the public database on gene expression and proteomics. Meanwhile, verification of expression was carried out in Gene Expression Omnibus, the Human Protein Atlas, and OC cell lines. The prognosis of MOB1A was explored in the Kaplan-Meier plotter. RNA interference and lentivirus vectors were applied to construct knockdown and overexpressed cell models. Changes in the malignant behaviors of OC cells were detected by cholecystokinin octopeptide cell counting kit, wound healing, colony formation assay, transwell, flow cytometry assays, and in vivo experiments. Changes in proteins in the PI3K and autophagy-related makers were detected by western blot analysis. Results The expression of MOB1A was significantly upregulated and accompanied by an inferior survival rate in OC. Knockdown of MOB1A inhibited the proliferation, invasion, migration, and cell cycle of OC cells, whereas induced cell autophagy. MOB1A upregulation had the opposite effects. In addition, bioinformatics analysis and western blot experiments showed that MOB1A plays an important role in the PI3K/AKT/mTOR pathway. Conclusions Our findings indicated that MOB1A is highly expressed and related to poor prognosis in OC. MOB1A plays a role in promoting the malignant biological behavior of tumor cells through PI3K/AKT/mTOR signaling pathway.

Abstract Owing to the limitations of conventional cancer therapies, including chemotherapy, radiotherapy, and surgery, gene therapy has become a prominent strategy for cancer treatment over the past few decades. Gene therapy is a medical approach for targeting and destroying cancer cells by delivering exogenous genes into the target cancerous cells or surrounding tissues. However, successful delivery of foreign genes into target cells and tissues remains a key issue in such therapy. Efficient gene delivery systems would undoubtedly be important for improving the medical outcomes of gene therapy. With genetic modifications, viral vectors can target specific cells with high gene transduction efficiency, thus, the use of viral vectors is a promising technology for improving foreign gene delivery. Currently, four viral vectors—adenovirus, adeno‐associated virus, herpes simplex virus, and retrovirus—are dominantly being investigated and used in preclinical and clinical trials. In this review, we provide an overview of the mechanisms and latest applications of the four above‐mentioned viral vectors, and summarize the current development of several other viral vectors. In addition, we discuss the challenges and provide insights into future development of viral vectors in cancer treatment.

CO2 reduction (CO2RR) with selective benzyl alcohol (BA) oxidation in a single photoredox reaction can simultaneously utilize photogenerated electrons and holes to realize efficient production of fuels and value‐added chemicals. Herein, a unique 2D/1D ZnIn2S4/In2O3 (ZIS/In2O3) heterostructure is developed displaying outstanding performance for photoredox catalysis. As is unequivocally illustrated by various advanced ex situ/in situ characterizations and theoretic calculations, the notable catalytic performances originate from the built‐in interfacial electric field within the ZIS/In2O3 heterostructure, which strongly ameliorates the separation and transport of charge carriers. Remarkably, the catalytic activity can further be boosted after coupling the additional thermal treatments, and the product selectivity is highly temperature dependent. Thereby, the precise formation of targeted products, which can serve as valuable industrial products and fuels can be controlled by changing the reaction temperatures, including obtaining the syngas with different H2/CO ratios from CO2 reduction, as well as benzaldehyde, hydrogenated benzoin, and dibenzyl ether (never reported for BA during photocatalysis) from the BA conversion. This study offers a constructive and inspiring contribution to reasonably developing photoredox catalysts, which can fully utilize photogenerated electrons and holes, as well as demonstrate how to controllably yield the targeted products by coupling thermo‐ and photoredox catalysis.

Abstract Emerging SARS-CoV-2 variants, particularly the Omicron variant and its sublineages, continually threaten the global public health. Small molecule antivirals are an effective treatment strategy to fight against the virus. However, the first-generation antivirals either show limited clinical efficacy and/or have some defects in pharmacokinetic (PK) properties. Moreover, with increased use of these drugs across the globe, they face great pressure of drug resistance. We herein present the discovery and characterization of a new generation antiviral drug candidate (SY110), which is a potent and selective inhibitor of SARS-CoV-2 main protease (Mpro). This compound displayed potent in vitro antiviral activity against not only the predominant SARS-CoV-2 Omicron sublineage BA.5, but also other highly pathogenic human coronaviruses including SARS-CoV-1 and MERS-CoV. In the Omicron-infected K18-hACE2 mouse model, oral treatment with SY110 significantly lowered the viral burdens in lung and alleviated the virus-induced pathology. Importantly, SY110 possesses favorable PK properties with high oral drug exposure and oral bioavailability, and also an outstanding safety profile. Furthermore, SY110 exhibited sensitivity to several drug-resistance Mpro mutations. Collectively, this investigation provides a promising new drug candidate against Omicron and other variants of SARS-CoV-2.

Reporting the crystal structure of the N-terminal domain of the viral nucleocapsid protein in complex with the ubiquitin-like domain 1 of Nsp3 in SARS-CoV-2

Few national studies have systemically examined the effects of criteria air pollutants on cardiovascular morbidity. This study aimed to investigate the associations between all criteria air pollutants and hospitalization of cause-specific cardiovascular diseases (CVD) in China. We obtained data on CVD hospitalization events of four major categories and 12 specific diseases from 153 hospitals distributed in 20 provincial-level regions from 2013 to 2020. We adopted a time-stratified case-crossover study design using individual cases to capture the effect of short-term exposure to six criteria air pollutants on CVD hospitalizations, using conditional logistic regression models. More than 1.1 million CVD hospitalization events were included. The lag pattern exploration demonstrated the largest effect for six air pollutants on lag 0–1 day. PM2.5, PM10, NO2, and CO were significantly associated with increased hospitalization from ischemic heart diseases, cerebrovascular diseases, other heart diseases, and five specific causes of CVD. The effect estimates of NO2 were the most robust when adjusting for co-pollutants. The concentration-response curves were positive and linear for most pollutant–endpoint pairs (except for O3), and these positive associations remained even below the 24-h levels recommended by WHO Air Quality Guidelines and China Air Quality Standards. This nationwide case-crossover study in China demonstrated that short-term exposure to multiple ambient air pollutants may significantly increase the risk of cause-specific CVD hospitalizations even under the most stringent air quality regulations, striking an alert for potential CVD patients against these environmental risk factors.

Song, Zeng, Yan et al. validate the E1L3N monoclonal antibody for the detection of PD-L1 in NSCLC samples. The authors show that PD-L1 scores assessed with E1L3N are concordant with the 22C3 assay and are associated with response to first-line pembrolizumab monotherapy.

Summary: Proton-dependent oligopeptide transporters (POTs) are promiscuous transporters of the major facilitator superfamily that constitute the main route of entry for a wide range of dietary peptides and orally administrated peptidomimetic drugs. Given their clinical and pathophysiological relevance, several POT homologs have been studied extensively at the structural and molecular level. However, the molecular basis of recognition and transport of diverse peptide substrates has remained elusive. We present 14 X-ray structures of the bacterial POT DtpB in complex with chemically diverse di- and tripeptides, providing novel insights into the plasticity of the conserved central binding cavity. We analyzed binding affinities for more than 80 peptides and monitored uptake by a fluorescence-based transport assay. To probe whether all 8400 natural di- and tripeptides can bind to DtpB, we employed state-of-the-art molecular docking and machine learning and conclude that peptides with compact hydrophobic residues are the best DtpB binders.

Abstract Lysine‐specific histone demethylase 1 (LSD1) is an attractive target for malignancies therapy. Nevertheless, its role in hepatocellular carcinoma (HCC) progression and the potential of its inhibitor in HCC therapy remains unclear. Here, we show that LSD1 overexpression in human HCC tissues is associated with HCC progression and poor patient survival. ZY0511, a highly selective and potent inhibitor of LSD1, suppressed human HCC cell proliferation in vitro and tumor growth in cell‐derived and patient‐derived HCC xenograft models in vivo. Mechanistically, ZY0511 induced mRNA expression of growth arrest and DNA damage‐inducible gene 45beta (GADD45B) by inducing histone H3 at lysine 4 (H3K4) methylation at the promoter of GADD45B, a novel target gene of LSD1. In human HCC tissues, LSD1 level was correlated with a decreased level of GADD45B, which was associated with HCC progression and predicted poor patient survival. Moreover, co‐administration of ZY0511 and DTP3, which specifically enhanced the pro‐apoptotic effect of GADD45B, effectively inhibited HCC cell proliferation both in vitro and in vivo. Collectively, our study revealed the potential value of LSD1 as a promising target of HCC therapy. ZY0511 is a promising candidate for HCC therapy through upregulating GADD45B, thereby providing a novel combinatorial strategy for treating HCC.

Abstract To improve the stable operating range of centrifugal compressor stage, endwall contouring technology is introduced on the hub‐side wall of the vaned diffuser for NASA CC3 centrifugal compressor as a promising technique to redistribute the flow field near the endwall in this paper. The main contents of this paper are listed as follows. First, a specific parameterized endwall contouring guideline is developed based on sinusoidal function and Bézier curve, and three factors are considered, namely, peak height, peak radial position, and frequency coefficient. Then, centrifugal compressor stages with baseline diffuser and contoured endwall diffusers are numerically investigated to reveal the influence of endwall contouring on the stable operating range. Results show that endwall contouring is an effective method to achieve stability enhancement with no evident reduction in stage performance on the design point. CEW13‐12 has the most successful combination of endwall contouring parameters, and stall margin is increased by up to 40% for CEW13‐12. Finally, the influence mechanism of endwall contouring on the stable operating range is discussed. At the near stall condition, the contouring endwall forces the fluid within the semi vaneless space to deflect toward the suction side to increase the momentum of low‐energy fluid in the suction surface boundary layer and reduce the adverse pressure gradient on the suction side, which delay the development of flow separation on the vane leading edge near the shroud side to suppress the onset of rotating stall. At the near choke condition, the contouring endwall has more potential to increase the throat area, resulting in a decrease of throat blockage to improve choke margin. The results show that the endwall contouring technology is a reliable method to achieve stability enhancement of centrifugal compressor stage.

Abstract Purpose The role of neoadjuvant chemotherapy (NACT) and primary debulking surgery (PDS) in advanced epithelial ovarian cancer (EOC) remains controversial. This study aimed to investigate the prognosis between NACT and PDS in advanced EOC. We also investigated the prognostic effect of the residual tumor (RT) after NACT and PDS. Methods Patients with stage III‐IV EOC diagnosed between 2010 and 2017 were included from the Surveillance, Epidemiology, and End Results (SEER) database. Chi‐square test, multivariate logistic regression analysis, Kaplan–Meier curves, and Cox proportional hazards model were used for statistical analyses. Results A total of 5522 women patients were identified, 2017 (36.5%) and 3505 (63.5%) patients received NACT and PDS, respectively. There were 2971 (53.8%), 1637 (29.6%), and 914 (16.6%) patients who had no residual tumor, RT ≤1 cm, and RT >1 cm, respectively. There were 25.5% of patients receiving NACT in 2010 and 48.4% in 2017 (p 1 cm (p = 0.442). In those receiving PDS, the CSS was decreased with a RT increase (p

BackgroundThe relationships between short-term ozone exposure and the acute exacerbations of asthma in adults have not been fully studied. Existing studies commonly ignored the effects of ozone on mild or early asthma exacerbations.ObjectiveTo investigate the associations between short-term ozone exposure and asthma exacerbations in Chinese adults.MethodsWe administered health management for adult asthma patients through the Respiratory Home Platform and required them to monitor their lung function every morning and evening by themselves. Finally, a total of 4,467 patients in 18 Chinese cities were included in the current analyses, with 79,217 pairs of lung function records. The maximum daily 8-h average ozone concentrations were collected from fixed-site air quality monitoring stations. We calculated diurnal peak expiratory flow (PEF) variation using morning and evening measurements of PEF and then defined different severity of asthma exacerbations with diurnal PEF variations >10, 15, and 20%, respectively. A binomial distributed generalized additive mixture model combined with distribution non-linear models was applied to examine the association of ozone with asthma exacerbations. We further conducted stratified analyses by sex, age, season of lung function tests, and region.Measurements and resultsWe found that short-term ozone exposure was independently associated with an elevated risk of asthma exacerbations defined by lung function and the effects could last for about 2 days. At lag 0–2 days, each 10 μg/m3 increment in ozone concentration was associated with odds ratios of 1.010 [95% confidence interval (CI): 1.003, 1.017], 1.014 (95% CI: 1.005, 1.023), and 1.017 (95% CI: 1.006, 1.028) for asthma exacerbations that were defined by diurnal PEF variation over 10, 15, and 20%, respectively. The associations remained significant after adjusting for other pollutants, and became unstable when using 24-h average ozone concentration. We also found that the associations were relatively stronger in males, those aged 45 years and older, and in the warm season.ConclusionsOur results suggest that short-term ozone exposure can increase the risk of asthma exacerbations, even in the early stage of exacerbation. Male and older asthma patients may be more vulnerable to ozone air pollution, especially in the warm season.

The emergence of drug-resistant genes and concerns about food safety caused by the overuse of antibiotics are becoming increasingly prominent. There is an urgent need for effective alternatives to antibiotics in the fields of livestock production and human medicine. Antimicrobial peptides can effectively replace antibiotics to kill pathogens and enhance the immune functions of the host, and pathogens cannot easily produce genes that are resistant to them. The ability of antimicrobial peptides (AMPs) to kill pathogens is associated with their structure and physicochemical properties, such as their conformation, electrical charges, hydrophilicity, and hydrophobicity. AMPs regulate the activity of immunological cells and stimulate the secretion of inflammatory cytokines via the activation of the NF-κB and MAPK signaling pathways. However, there are still some limitations to the application of AMPs in the fields of livestock production and human medicine, including a restricted source base, high costs of purification and expression, and the instability of the intestines of animals and humans. This review summarizes the information on AMPs as effective antibiotic substitutes to improve the immunological functions of the host through suppressing pathogens and regulating inflammatory responses. Potential challenges for the commercial application of AMPs in animal husbandry and human medicine are discussed.

Background: Non-optimum ambient temperature has not been widely perceived as an important environmental risk factor for asthma, and the association between ambient temperature and pulmonary function is rarely explored. Our study aimed to investigate the associations between non-optimum ambient temperature and pulmonary function among asthmatic adult patients. Methods: We performed a longitudinal study among 4,992 eligible adult asthmatic patients in 25 cities of China from 2017 to 2020. The patients were required to complete pulmonary function test every day in the morning and evening. Linear mixed-effects models and distributed lag non-linear models were used to evaluate the associations between ambient temperature and pulmonary function. Results: We evaluated 298,396 records of pulmonary function tests. We found inversely J-shaped exposure–response relationship curves for ambient temperature and pulmonary function. The effects of extreme low temperature occurred at lag 0 h and vanished at lag 72 h (almost 3 days). Compared with referent temperature (29.5 °C), extreme low temperature (−9.4 °C) was associated with decreases of 60.4 mL in FEV1, 299.7 mL/s in PEF, and 101.5 mL in FVC. Extreme high temperature (34.2 °C) was associated with decreases of 26.0 mL in FEV1, 35.8 mL/s in PEF, and 23.4 mL in FVC. Patients of male, overweight, and elder ages were vulnerable populations, and cold effects were more prominent in the south and in areas without central heating. Conclusions: Both extreme low and high ambient temperatures were associated with decreased pulmonary function in adult asthmatic patients. The effect could last for almost 3 days and low temperature was more harmful.

Abstract Background Precise quantification of microRNA is challenging since circulating mRNA and rRNA in the blood are usually degraded. Therefore, it is necessary to identify specific biomarkers for ovarian cancer. This study aimed to investigate candidate circular RNAs (circRNAs) involved in the pathogenic process of ovarian cancer after inhibition of chromodomain helicase DNA binding protein 1-like (CHD1L) and the corresponding mechanism. Methods CHD1L mRNA-targeted siRNA was designed and induced a decreased level of CHD1L function in SK-OV-3 and OVCAR-3 cells observed via transwell and wound healing assays and assessment of epithelial–mesenchymal transition (EMT)-related protein expression by immunofluorescence (IF) and western blotting (WB). After decreasing the level of CHD1L, RNA-seq was conducted, and the circRNA expression profiles were obtained. cirRNAs were then selected and validated by PCR together with Sanger sequencing, fluorescent in situ hybridization (FISH), and reverse transcriptase-quantitative PCR (RT-qPCR). Selected circRNA function in vitro was adjusted via interference and overexpression and assessed via transwell assay, tube formation, and EMT-related protein assay by IF and WB; tumor formation in vivo was followed via hematoxylin and eosin (HE) staining and immunohistochemistry of EMT-related proteins. Based on the competing endogenous RNA prediction of circRNA targets, candidate miRNAs were found, and their downstream mRNAs targeted by the selected miRNA were identified and validated by luciferase assay. The functions of these selected miRNA and mRNA were then further investigated through transwell and WB assay of EMT-related proteins. Results CHD1L was significantly upregulated in ovarian cancer tissues and patients with higher expression of CHD1L had a shorter relapse-free survival (P

Abstract Background To investigate the potential molecular mechanism of ovarian cancer (OC) evolution and immunological correlation using the integrated bioinformatics analysis. Methods Data from the Gene Expression Omnibus was used to gain differentially expressed genes (DEGs). Gene Ontology and Kyoto Encyclopedia of Gene and Genome pathway analysis were completed by utilizing the Database for Annotation, Visualization, and Integrated Discovery. After multiple validations via The Cancer Genome Atlas (TCGA), Genotype‐Tissue Expression (GTEx) projects, the Human Protein Atlas, Kaplan–Meier (KM) plotter, and immune logical relationships of the key gene SOBP were evaluated based on Tumor Immune Estimation Resource, and Gene Set Enrichment Analysis (GSEA) software. Finally, the lncRNAs‐miRNAs‐mRNAs subnetwork was predicted by starBase, TargetScan, miRBD, and LncBase, individually. Correlation of expression and prognosis for mRNAs, miRNAs, and lncRNAs were confirmed by TCGA, Gene Expression Profiling Interactive Analysis 2 (GEPIA 2), starBase, and KM. Results A total of 192 shared DEGs were discovered from the four data sets, including 125 upregulated and 67 downregulated genes. Functional enrichment analysis presented that they were mainly enriched in cartilage development, pathway in PI3 K‐Akt signaling pathway. Lower expression of SOBP was the independent prognostic factor for inferior prognosis in OC patients. The downregulation of SOBP enhanced the infiltration levels of B cells, CD8+ T cells, Macrophage, Neutrophil, and Dendritic cells. GSEA also disclosed low SOBP showed a significantly associated with the activation of various immune‐related pathways. Finally, we first reported that the MEG8/miR‐378d/SOBP axis was linked to the development and prognosis of OC through regulating the cytokines pathway. Conclusions Our study establishes a novel MEG8/miR‐378d/SOBP axis in the development and prognosis of OC, and the triple subnetwork probably affects the progression of the OC by regulating the cytokines pathway.

Abstract Background We aim to assess the value of locoregional treatment (LRT) including breast‐conserving surgery (BCS), mastectomy (MAST), and radiotherapy (RT) in patients with de novo stage IV breast cancer. Methods Patients with de novo stage IV breast cancer were retrospectively identified from the Surveillance, Epidemiology, and End Results database between 2004 and 2014. Kaplan‐Meier analysis, log‐rank tests, propensity score matching (PSM), and the multivariate Cox proportional model were used for statistical analysis. Results A total of 5798 patients were identified including 849 (14.6%), 763 (13.2%), 2338 (40.3%), and 1848 (31.9%) who received BCS alone, BCS+RT, MAST alone, and MAST+RT, respectively. The proportions of receiving BCS decreased from 35.9% in 2004 to 26.2% in 2014 (p = 0.002), and the probability of patients receiving MAST increased from 64.1% in 2004 to 74.8% in 2014 (p = 0.002). Before PSM, there was a significant difference in breast cancer‐specific survival (BCSS) among the treatment arms. Patients who received RT had better BCSS, the 5‐year BCSS was 40.5%, 52.3%, 41.5%, and 47.7% in patients treated with BCS alone, BCS+RT, MAST alone, and MAST+RT, respectively (p

Here the authors report binary phase supercritical lenses by patterning monolayer TMD materials. Through placement of atomic thin 2D TMD with sufficient absorption, a spot of critical coupling is created to facilitate a π phase jump and subdiffraction focusing over bandwidth of 150 nm in visible range.

Background: Few studies have evaluated long-term cardiovascular effects of fine particulate matter (PM2.5) and its constituents in countries with high air pollution levels. We aimed to investigate the associations of long-term exposure to PM2.5 and constituents with cardiovascular mortality in China. Methods: We conducted a prospective cohort study of 90,672 adults ≥ 18 years from 2010 to 2017 in 161 districts/counties across China. The residential annual-average exposure to PM2.5 and 6 main components from 2011 to 2017 were estimated by satellite-based and chemical transport models. Associations of PM2.5 and constituents with cardiovascular mortality were analyzed by competing-risk Cox proportional hazards regression. Results: The average PM2.5 exposure throughout the whole period was 46 ± 22 μg/m3. The hazard ratios of mortality (95% confidence intervals) per 10 μg/m3 increase in PM2.5 concentrations were 1.02 (1.00, 1.05) for overall cardiovascular disease, 1.05 (1.01, 1.09) for ischemic heart disease, 1.03 (1.00, 1.06) for overall stroke, 0.99 (0.94, 1.04) for hemorrhagic stroke, and 1.11 (1.04, 1.19) for ischemic stroke. PM2.5 constituents from fossil fuel combustion (i.e., black carbon, organic matter, nitrate, ammonium, and sulfate) showed larger hazard ratios than PM2.5 total mass, while soil dust showed no risks. Conclusions: This nationwide cohort study demonstrated associations of long-term exposure to PM2.5 and its constituents with increased risks of cardiovascular mortality in the general population of China. Our study highlighted the importance of PM2.5 constituents from fossil fuel combustion in the long-term cardiovascular effects of PM2.5 in China.

Abstract The newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a global human health crisis. The CoV nucleocapsid (N) protein plays essential roles both in the viral genomic RNA packaging and the regulation of host cellular machinery. Here, to contribute to the structural information of the N protein, we describe the 2.0 Å crystal structure of the SARS-CoV-2 N protein C-terminal domain (N-CTD). The structure indicates an extensive interaction dimer in a domain-swapped manner. The interface of this dimer was first thoroughly illustrated. Also, the SARS-CoV-2 N-CTD dimerization form was verified in solution using size-exclusion chromatography. Based on the structural comparison of the N-CTDs from alpha-, beta-, and gamma-CoVs, we demonstrate the common and specific characteristics of the SARS-CoV-2 N-CTD. Furthermore, we provide evidence that the SARS-CoV-2 N-CTD possesses the binding ability to single-stranded RNA, single-stranded DNA as well as double-stranded DNA in vitro. In conclusion, this study could potentially accelerate research to understand the complete biological functions of the new CoV N protein.

Purpose: The 8th edition of the American Joint Committee on Cancer (AJCC) pathological staging system for breast cancer considers biologic factors in addition to the anatomical features included in the previous systems. The purpose of this study was to determine the validity of the 8th AJCC staging system for T1-2N1 breast cancer and to assess the effect of additional chemotherapy and radiotherapy according to the new pathologic stages. Methods: The cohort included patients from the Surveillance, Epidemiology, and End Results program (2010–2012) who had stage T1-2N1 invasive breast carcinoma and underwent mastectomy. All patients were restaged using the 8th AJCC staging system. The Kaplan–Meier method, Cox proportional hazards regression, and competing risks models were used for data analysis. Results: We identified 9908 patients including 3022 (30.5%), 3131 (31.6%), 1940 (19.6%), 1194 (12.1%), and 621 (6.3%) were classified with stage IA, IB, IIA, IIB, and IIIA disease, respectively. The 5-year breast cancer-specific survival (BCSS) was 97.3%, 94.3%, 88.3%, 84.0%, and 71.1% for stage IA, IB, IIA, IIB, and IIIA disease, respectively. Higher pathological stage was associated with a significantly higher risk of breast cancer-related death. Chemotherapy was associated with better BCSS regardless of the pathological stage, but radiotherapy was only associated with better BCSS in stage IIIA disease. Conclusions: The 8th AJCC pathological staging system provides more refined stratification for T1-2N1 breast cancer patients after mastectomy and may meet the needs of the current trend of individualized decision making for chemotherapy and radiotherapy in this patient subset.

Abstract Background In Ethiopia, cervical cancer is the second most frequent cancer among women aged 15 to 44 years old. Cervical cancer screening is an effective measure to enhance the early detection of cervical cancer for prevention. However, the magnitude of cervical cancer screening is less than 1%. This study aimed to determine the influence of sociodemographic characteristics and related factors on screening. Method A hospital-based cross-sectional study has been conducted from July to September 2017. Data have been collected using interviewer-administered questioner among 425 women (18–49 years age) who visited the family health department at St. Paul’s Hospital. Descriptive statistics, chi-square, univariate and multivariate logistic regression were used for data analysis. Result Of the 425 study participants, only 12.2% of women have been screened within the past 3 years. Women in the age range of 40–49 years old were more likely to be screened (36.1%) than women age 18–29 years (8%). Women living in urban were more likely to be screened (15.9%) than women living in rural (3.9%). Other factors including low monthly income, unlikely chance of having cancer, lack of knowledge, and fear test outcome were significantly associated with the low uptake of screening. Conclusion This study revealed that the uptake of cervical cancer screening was low. Women in the potential target population of cervical cancer screening were just a proportion of all studied age groups and screening in them was more common than in younger women. Besides, rural residence, low monthly income, and lack of knowledge were important predictors for low utilization of cervical cancer screening practice.

Abstract Background T3N0 breast cancer might be a distinct clinical and biological entity, with higher heterogeneity and presenting diverse responses to locoregional and systemic therapy. The aim of the current study was to validate the prognostic effect and assess the treatment decision‐making of the American Joint Committee on Cancer (AJCC) eighth pathological prognostic staging in T3N0 breast cancer after mastectomy. Methods We retrospectively included 2465 patients with stage T3N0 breast cancer who had undergone mastectomy between 2010 and 2014 using the data from Surveillance, Epidemiology, and End Results program. The primary endpoint of this study was breast cancer–specific survival (BCSS). Results Of the entire cohort, 76.0% of patients in the seventh AJCC staging system were restaged to the eighth AJCC pathological prognostic staging system. A total of 1431 (58.1%) and 1175 (47.7%) of them received chemotherapy and postmastectomy radiotherapy (PMRT), respectively. Pathological staging was an independent prognostic factor for BCSS. Using pathological prognostic stage IA as the reference, BCSS gradually became worse with increased hazard ratios. The 5‐years BCSS was 96.9%, 95.5%, 91.1%, 85.6%, and 75.5% in pathological prognostic stage IA, IB, IIA, IIB, and IIIA breast cancers, respectively (P

The short-term associations of fine particulate matter (PM2.5) and coarse particulate matter (PM2.5-10) with pulmonary function were inconsistent and rarely evaluated by dynamic measurements. Our study aimed to investigate the associations of PM2.5 and PM2.5–10 with real-time pulmonary function. We conducted a longitudinal study based on dynamic pulmonary function measurements among adult asthmatic patients in 25 cities of 19 provincial regions of China from 2017 to 2020. Linear mixed-effects models combined with polynomial distributed lag models were used for statistical analysis. A total of 298,396 records among 4,992 asthmatic patients were evaluated. We found generally inverse associations of PM2.5 and PM2.5–10 with 16 pulmonary function indicators that were independent of gaseous pollutants. The associations occurred at lag 1 d, became the strongest at lag 4 d, and vanished a week later. PM2.5-10 had stronger associations than PM2.5, especially in southern China. Nationally, an interquartile increase in PM2.5-10 (28.0 μg/m3) was significantly associated with decreases in forced expiratory volume in 1 s (FEV1, 41.6 mL), the ratio of FEV1 in forced vital capacity (1.1%), peak expiratory flow (136.9 mL/s), and forced expiratory flow at 25–75% of forced vital capacity (54.3 mL/s). We observed stronger associations in patients of male, BMI ≥ 25 kg/m2, age ≥ 45 years old, and during warm seasons. In conclusion, this study provided robust evidence for impaired pulmonary function by short-term exposure to PM2.5 and PM2.5-10 in asthmatic patients using the largest dataset of dynamic monitoring. The associations can last for one week and PM2.5-10 may be more hazardous.

Supercritical lens can create a sub-diffraction-limited focal spot in the far field, providing a promising route for the realization of label-free super-resolution imaging through the point scanning mechanism. However, all of the reported supercritical lenses have circular shape configurations, and produce isotropic sub-diffraction-limited focal spots in the focal plane. Here, we propose and experientially demonstrate a sub-diffraction transverse optical needle by using an elliptical supercritical lens. Through breaking the circular symmetry and introducing ellipticity to the lens, a uniform sub-diffractive transverse optical needle with lateral length and width of 6λ/NA and 0.45λ/NA, respectively, was successfully created in the focal plane. Further, elliptical sector-shape cutting with an optimized apex angle of 60 degrees can lead to suppressed subsidiary focusing for improved uniformity and condensed field intensity of the transverse optical needle. The demonstration of sub-diffractive transverse optical needle with a high aspect ratio (length to width ratio) of 13:1 may find potential applications in line-scanning microscopy for video-rate label-free super-resolution imaging, and also enable advances in the fields from laser manufacturing to optical manipulation.

BackgroundActual long-term survival rates for advanced epithelial ovarian cancer (EOC) are rarely reported. ObjectiveThis study aimed to assess the role of histological subtypes in predicting the prognosis among long-term survivors (≥5 years) of advanced EOC. MethodsWe performed a retrospective analysis of data among patients with stage III-IV EOC diagnosed from 2000 to 2014 using the Surveillance, Epidemiology, and End Results cancer data of the United States. We used the chi-square test, Kaplan–Meier analysis, and multivariate Cox proportional hazards model for the analyses. ResultsWe included 8050 patients in this study, including 6929 (86.1%), 743 (9.2%), 237 (2.9%), and 141 (1.8%) patients with serous, endometrioid, clear cell, and mucinous tumors, respectively. With a median follow-up of 91 months, the most common cause of death was primary ovarian cancer (80.3%), followed by other cancers (8.1%), other causes of death (7.3%), cardiac-related death (3.2%), and nonmalignant pulmonary disease (3.2%). Patients with the serous subtype were more likely to die from primary ovarian cancer, and patients with the mucinous subtype were more likely to die from other cancers and cardiac-related disease. Multivariate Cox analysis showed that patients with endometrioid (hazard ratio [HR] 0.534, P

As a pioneer tropical pasture legume, stylo (Stylosanthes guianensis) is well adapted to growth-limiting factors in acid soils. Considering the importance of stylo, there is a need to improve Agrobacterium-mediated genetic transformation to enable development of elite cultivars. In this study, S. guianensis cv. RY5 was used to systematically optimize Agrobacterium-mediated transformation based on its plant regeneration. Results showed that Murashige and Skoog (MS) medium containing 0.2 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D) and 2 mg/L 6-benzylaminopurine (6-BA) was the optimal callus induction medium. MS medium supplemented with 2 mg/L 6-BA was suitable for shoot regeneration from cotyledon-derived calluses, and 0.5 mg/L indole-3-acetic acid (IAA) and 0.5 mg/L indole-3-butyric acid (IBA) applications were beneficial for rooting. The highest transformation efficiency (67%) was obtained at an Agrobacterium concentration of optical density = 0.6 combined with an infection time of 15 min and 3 days of co-cultivation. Furthermore, 200 mg/mL carbenicillin (Carb) and 0.6 mg/L Basta® supplements were effective in eliminating excess bacterial growth and selecting transgenic plants, respectively. Subsequent polymerase chain reaction (PCR) analysis confirmed that the β-glucuronidase (GUS) and BAR genes were successfully integrated into the stylo genome. Wider testing of this improved protocol as a means of enhancing genetic improvement and gene function analysis of stylo seems warranted.

Background: Ovarian cancer (OC) is the most deadly tumor in gynecology and there is no effective biomarker for diagnosis and treatment. The role of Transmembrane Protein 98 (TMEM98) in ovarian cancer is still unclear. Methods: The expression and prognostic effect of TMEM98 in OC were analyzed using the public database. Cell Counting Kit-8 proliferation experiment, scratch experiment, Transwell invasion experiment, flow cytometry, TUNEL staining, and in vivo and vitro experiment were used. Results: TMEM98 was significantly downregulated in OC tissues and cell lines compared to the normal ovarian tissue and cells lines. In addition, patients with lower TMEM98 levels exhibited inferior survival. Low expression of the TMEM98 promoted proliferation, migration, invasion, vasculogenic mimicry, and inhibited apoptosis in OC cells. The expression of Caspase-3 was significantly downregulated and the expression of Bcl-2 was significantly increased in the silencing-TMEM98 group. Moreover, low expression of TMEM98 promotes OC development in vivo. Bioinformatics analysis showed that TMEM98 expression was negatively correlated with poly ADP-ribose polymerase expression. Conclusions: This study demonstrates that TMEM98 is low expressed in OC and impacts the prognosis of OC patients. TMEM98 inhibits proliferation and promotes apoptosis and finally exerts a certain tumor-suppressor effect on OC.

Background: As a central organ of energy metabolism, the liver is closely related to selenium for its normal function and disease development. However, the underlying roles of mitochondrial energy metabolism and mitophagy in liver fibrosis associated with selenium remain unclear. Methods: 28 rats were randomly divided into normal, low-selenium, nano-selenium supplement-1, and supplement-2 groups for a 12-week intervention. We observed pathological and ultrastructural changes in the liver and analyzed the effects of selenium deficiency and nano-selenium supplementation on liver metabolic activities and crucial proteins expression of mammalian target of the rapamycin (mTOR) signaling pathway. Results: Selenium deficiency caused liver pathological damage and fibrosis with the occurrence of mitophagy by disrupting normal metabolic activities; meanwhile, the mTOR signaling pathway was up-regulated to enhance mitophagy to clear damaged mitochondria. Furthermore, nano-selenium supplements could reduce the severity of pathological damage and fibrosis in livers and maintain normal energy metabolic activity. With the increased concentrations of nano-selenium supplement, swelling mitochondria and mitophagy gradually decreased, accompanied by the higher expression of mTOR and phosphorylation-modified mTOR proteins and lower expression of unc-51 like autophagy activating kinase 1 (ULK1) and phosphorylation-modified ULK1 proteins. Conclusions: Mitophagy regulated by the mTOR signaling pathway plays a dual protective role on low-selenium inducing liver fibrosis and nano-selenium supplements preventing liver fibrosis. Mitochondrial energy metabolism plays an important role in these processes as well.

PurposeTo validate the 8th edition of the American Joint Committee on Cancer (AJCC) pathological prognostic staging system for breast cancer patients with internal mammary lymph nodes (IMN) metastasis (N3b disease, stage IIIC in 7th AJCC anatomical staging).MethodsBreast cancer patients with IMN metastasis diagnosed between 2010 and 2014 were retrieved from the Surveillance, Epidemiology, and End Results program. Chi-squared test, Log-rank test, Kaplan-Meier method, and Cox proportional hazard analysis were applied to statistical analysis.ResultsWe included 678 patients with N3b disease in this study. Overall, 68.4% of patients were downstaged to IIIA and IIIB diseases from the 7th anatomical staging to 8th pathological prognostic staging. The new pathological prognostic staging system had better discriminatory value on prognosis prediction among IMN-metastasized breast cancer patients, with a 5-year breast cancer-specific survival (BCSS) of 92.7, 77.4, and 66.0% in stage IIIA, IIIB, and IIIC diseases, respectively (P

Leafy sweet potato is rich in total phenolics (TP) which play key roles in health protection, the chlorogenic acid (CGA) constitutes the major components of phenolic compounds in leafy sweet potato. Unfortunately, the mechanism of CGA biosynthesis in leafy sweet potato is unclear. To dissect the mechanisms of CGA biosynthesis, we performed transcriptome, small RNA (sRNA) and degradome sequencing of one low-CGA content and one high-CGA content genotype at two stages. A total of 2,333 common differentially expressed genes (DEGs) were identified, and the enriched DEGs were related to photosynthesis, starch and sucrose metabolism and phenylpropanoid biosynthesis. The functional genes, such as CCR, CCoAOMT and HCT in the CGA biosynthetic pathway were down-regulated, indicating that the way to lignin was altered, and two possible CGA biosynthetic routes were hypothesized. A total of 38 DE miRNAs were identified, and 1,799 targets were predicated for 38 DE miRNAs by using in silico approaches. The target genes were enriched in lignin and phenylpropanoid catabolic processes. Transcription factors (TFs) such as apetala2/ethylene response factor (AP2/ERF) and Squamosa promoter binding protein-like (SPL) predicated in silico were validated by degradome sequencing. Association analysis of the DE miRNAs and transcriptome datasets identified that miR156 family negatively targeted AP2/ERF and SPL. Six mRNAs and six miRNAs were validated by qRT-PCR, and the results showed that the expression levels of the mRNAs and miRNAs were consistent with the sequencing data. This study established comprehensive functional genomic resources for the CGA biosynthesis, and provided insights into the molecular mechanisms involving in this process. The results also enabled the first perceptions of the regulatory roles of mRNAs and miRNAs, and offered candidate genes for leafy sweet potato improvements.

IntroductionTo investigate the prognostic and predictive effect of the American Joint Committee on Cancer (AJCC) 8th edition pathological prognostic staging system in patients with T1-2N1micM0 breast cancer who underwent mastectomy.MethodsData from T1-2N1micM0 breast cancer patients who underwent mastectomy from 2010–2014 were obtained from the Surveillance, Epidemiology, and End Results program. The chi-square test, binomial logistics regression, receiver-operating characteristics curve, competing-risk regression model, Cox proportional hazards regression model, and proportional hazard assumption were used for statistical analyses.ResultsWe identified 4,729 patients, including 1,062 patients were received postmastectomy radiotherapy (PMRT). Stage change occurred in 88.2% of the patients, of which 84.4% were downstaged and 3.7% were upstaged. Patients with higher pathological prognostic stages were independently predicted to receive PMRT. The 5-year breast cancer-specific survival (BCSS) was 97.5, 93.7, 90.1, 86.0, and 73.5% in disease stages IA, IB, IIA, IIB, and IIIA, respectively, according to the 8th edition criteria (P < 0.001). The AJCC 8th edition demonstrated moderate discriminative ability, and it had a significantly better ability to predict the BCSS than the AJCC 7th edition criteria (P < 0.001). The multivariate prognostic analysis showed that the new pathological prognostic staging was an independent prognostic factor affecting the BCSS. The BCSS worsened with an increase in the stage. The PMRT did not affect the BCSS regardless of the pathological prognostic stage. Similar trends were found using the competing-risks regression model.ConclusionsThe 8th AJCC breast cancer pathological prognostic staging system downstaged 84.4% of patients with T1-2N1micM0 disease and the survival outcome prediction with this staging system was more accurate than the AJCC 7th edition system. Our study does not support using the prognostic stage as a guideline to escalate of PMRT.

Sweet potato is a hexaploid heterozygote with a complex genetic background, self-pollination infertility, and cross incompatibility, which makes genetic linkage analysis quite difficult. Genome-wide association studies (GWAS) provide a new strategy for gene mapping and cloning in sweet potato. Storage root flesh color (SRFC) is an important sensory evaluation, which correlates with storage root flesh composition, such as starch, anthocyanin, and carotenoid. We performed GWAS using SRFC data of 300 accessions and 567,828 single nucleotide polymorphism (SNP) markers. Furthermore, we analyzed transcriptome data of different SRFC varieties, and conducted real-time quantitative PCR (qRT-PCR) to measure the expression level of the candidate gene in purple and non-purple fleshed sweet potato genotypes. The results showed that five unique SNPs were significantly (−log10P > 7) associated with SRFC. Based on these trait-associated SNPs, four candidate genes, g55964 (IbF3′H), g17506 (IbBAG2-like), g25206 (IbUGT-73D1-like), and g58377 (IbVQ25-isoform X2) were identified. Expression profiles derived from transcriptome data and qRT-PCR analyses showed that the expression of g55964 in purple-fleshed sweet potato was significantly (p < 0.01) higher than that of non-purple fleshed sweet potato. By combining the GWAS, transcriptomic analysis and qRT-PCR, we inferred that g55964 is the key gene related to purple formation of storage root in sweet potato. Our results lay the foundation for accelerating sweet potato genetic improvement of anthocyanin through marker-assisted selection.

IntroductionTo investigate the effect of local treatment strategy on survival outcome in de novo stage IV breast cancer patients who received chemotherapy.MethodsWe identified stage IV breast cancers that presented with synchronous metastasis from the Surveillance, Epidemiology, and End Results database. Binomial logistic regression, Kaplan–Meier survival curves, propensity score matching (PSM), and multivariate Cox regression model were used for statistical analyses.ResultsWe identified 5,374 patients in total, including 2,319 (43.2%), 2,137 (39.8%), and 918 (17.1%) patients who received surgery alone, surgery+radiotherapy, and radiotherapy alone, respectively. The probability of patients receiving surgery alone decreased over time, and the probability of patients receiving radiotherapy alone increased over time. However, no significant difference was observed in the probability of patients receiving postoperative radiotherapy (P = 0.291). The 3-year breast cancer-specific survival (BCSS) in patients treated with surgery alone, radiotherapy alone, and surgery+radiotherapy was 57.1, 35.9, and 63.9%, respectively (P < 0.001). The local treatment strategy was the independent prognostic factor related to BCSS. Using surgery alone as the reference, radiotherapy alone was related to lower BCSS (P < 0.001), while additional radiotherapy after surgery improved BCSS (P < 0.001). Similar results were observed using PSM.ConclusionsCompared to radiotherapy alone, surgery to the primary site may confer a survival benefit in stage IV breast cancer with synchronous metastasis, and additional postoperative radiotherapy further improves outcome after primary tumor removal. Local treatment can only be an option in highly selected patients with de novo stage IV disease in the treatment guidelines. More prospective studies are needed to investigate the role of local management for this patient subset.

Karstic-fault oil pools are a new type of carbonate reservoirs which is consisted of groups of large caves with high oil storage potential. In this study’s examinations of high-yielding wells, it was found that many valuable reservoirs relate to the drilling wells through fractures or karst caves, and it was not possible to determine the reservoir depths through the method of seismic prospecting precisely due to its poor vertical resolution. The conventional logs cannot be run in the case of no mud circulation due to leaking to the caves. If the depths of the reservoirs cannot be determined, then it becomes difficult to achieve long term and stable development of the oil resources in the reservoirs. The heat transfer between wellbore and formation during oil production processes was simulated by CFD. The Horner method was used for estimating the flow temperature during the stable production stage using the temperature curve measured after shut-in. This research presented a scheme which could be used to effectively determine the depths of karstic-fault reservoirs by static and flow temperature logs. The proposed method was applied to a well located in the Tahe Oilfield of the Tarim Basin. The application of the method will aid in deepening our understanding of the distribution of fault-karst reservoirs, as well as in supporting the future stable and sustainable high-yielding oilfield production of similar reservoirs.

Chemokine-like factor (CKLF)-like MARVEL transmembrane members (CMTMs) represent a novel protein family linking the chemokine and transmembrane-4 superfamily families, which potentially play several roles in diverse physiological and pathological processes. The detailed functions and underlying molecular mechanisms of CMTMs remain elusive in breast cancer. Herein, we performed a comprehensive bioinformatic analysis to investigate the prognostic effect, potential functions, and biomolecular regulatory network of CMTMs in breast cancer. The mRNA expression level of CMTM5, in particular, was significantly downregulated in breast cancer; moreover, high mRNA expression level of CMTM5 was significantly associated with better relapse-free survival. DNA promoter hypermethylation of CMTM5 was negatively correlated with its mRNA expression levels. Furthermore, CMTM5 strongly associated with pathway in MARVEL domains, chemotaxis, cytokines, transmembrane structures, and integral component of membrane. For example, genes related to MARVEL domains, transmembrane structures, and chemokines were significantly enriched. Our findings indicate that CMTM5 can be used as a prognostic biomarker and potential therapeutic target for breast cancer.

Abstract Background Metastatic colorectal cancer (mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promising anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC. Methods Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), quality-of-life (QoL), and safety. Results Between July 18, 2012 and Jan 22, 2014, a total of 167 patients were screened, and 154 patients were randomized in a 2:1 ratio to receive either famitinib (n = 99) or placebo (n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups (hazard ratio = 0.60, 95% confidence interval = 0.41–0.86, P = 0.004). The DCR was 59.8% and 31.4% (P = 0.002) and the ORR was 2.2% and 0.0% (P = 0.540) in the famitinib and placebo groups, respectively. The most frequent grade 3–4 adverse events were hypertension (11.1%), hand-foot syndrome (10.1%), thrombocytopenia (10.1%), and neutropenia (9.1%). Serious adverse events occurred in 11 (11.1%) patients in the famitinib group and 5 (9.1%) in the placebo group (P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months (P = 0.657). Conclusion Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability. Trial registration This study was registered on ClinicalTrials.gov (NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal Symposium

Abstract Cysteine-rich peptides (CRPs) of 2–6 kDa are generally thermally and proteolytically stable because of their multiple cross-bracing disulfide bonds. Here, we report the discovery and characterization of two novel cystine-stapled CRPs, designated lybatide 1 and 2 (lyba1 and lyba2), from the cortex of Lycium barbarum root. Lybatides, 32 to 33 amino acids in length, are hyperstable and display a novel disulfide connectivity with a cysteine motif of C-C-C-C-CC-CC which contains two pairs of adjacent cysteines (-CC-CC). X-ray structure analysis revealed the presence of a single cystine-stabilized (α + π)-helix in lyba2, a rare feature of CRPs. Together, our results suggest that lybatides, one of the smallest four-disulfide-constrained plant CRPs, is a new family of CRPs. Additionally, this study provides new insights into the molecular diversity of plant cysteine-rich peptides and the unusual lybatide scaffold could be developed as a useful template for peptide engineering and therapeutic development.