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Summary: Background: Ultrasound is a critical non-invasive test for preoperative diagnosis of ovarian cancer. Deep learning is making advances in image-recognition tasks; therefore, we aimed to develop a deep convolutional neural network (DCNN) model that automates evaluation of ultrasound images and to facilitate a more accurate diagnosis of ovarian cancer than existing methods. Methods: In this retrospective, multicentre, diagnostic study, we collected pelvic ultrasound images from ten hospitals across China between September 2003, and May 2019. We included consecutive adult patients (aged ≥18 years) with adnexal lesions in ultrasonography and healthy controls and excluded duplicated cases and patients without adnexa or pathological diagnosis. For DCNN model development, patients were assigned to the training dataset (34 488 images of 3755 patients with ovarian cancer, 541 442 images of 101 777 controls). For model validation, patients were assigned to the internal validation dataset (3031 images of 266 patients with ovarian cancer, 5385 images of 602 with benign adnexal lesions), external validation datasets 1 (486 images of 67 with ovarian cancer, 933 images of 268 with benign adnexal lesions), and 2 (1253 images of 166 with ovarian cancer, 5257 images of 723 benign adnexal lesions). Using these datasets, we assessed the diagnostic value of DCNN, compared DCNN with 35 radiologists, and explored whether DCNN could augment the diagnostic accuracy of six radiologists. Pathological diagnosis was the reference standard. Findings: For DCNN to detect ovarian cancer, AUC was 0·911 (95% CI 0·886–0·936) in the internal dataset, 0·870 (95% CI 0·822–0·918) in external validation dataset 1, and 0·831 (95% CI 0·793–0·869) in external validation dataset 2. The DCNN model was more accurate than radiologists at detecting ovarian cancer in the internal dataset (88·8% vs 85·7%) and external validation dataset 1 (86·9% vs 81·1%). Accuracy and sensitivity of diagnosis increased more after DCNN-assisted diagnosis than assessment by radiologists alone (87·6% [85·0–90·2] vs 78·3% [72·1–84·5], p

In order to improve mechanical properties of TiAlNb alloys, different contents of silicon were added into Ti48Al6Nb alloy. The Ti48Al6NbxSi (x=0, 0.1, 0.2, 0.3, 0.4 and 0.5, at.%) alloys were prepared by vacuum arc melting. The phase constitution, microstructure evolution and mechanical properties of the alloys were studied. Results show that the Ti48Al6NbxSi alloys consist of γ-TiAl phase, α2-Ti3Al phase and B2 phase, and Ti5Si3 silicide phase is formed when the addition of silicon is higher than 0.3at.%. The addition of silicon leads to the decrease in γ phase and increase in α2 phase. The formation of silicide decreases the amount of Nb dissolved in the TiAl matrix, and therefore decreases B2 phase. Compressive tests show that the ultimate strength of the alloys increases from 2,063 MPa to 2,281 MPa with an increase in silicon from 0 to 0.5at.%, while the fracture strain decreases from 34.7% to 30.8%. The increase of compressive strength and decrease of fracture strain can be attributed to the decrease of B2 phase and the formation of Ti5Si3 phase by the addition of silicon. The strengthening mechanism is changed from solid solution strengthening when the addition of silicon is less than 0.3at.% to combination of solid solution strengthening and secondary phase strengthening when the addition of silicon is higher than 0.3at.%.

With the increase in the power receiving proportion and an insufficient peak regulation capacity of the local units, the receiving-end power grid struggles to achieve peak regulation in valley time. To solve this problem while considering the potential of the large-scale charge load of electric vehicles (EVs), an aggregator-based demand response (DR) mechanism for EVs that are participating in the peak regulation in valley time is proposed in this study. In this aggregator-based DR mechanism, the profits for the power grid’s operation and the participation willingness of the EV owners are considered. Based on the characteristics of the EV charging process and the day-ahead unit generation scheduling, a rolling unit commitment model with the DR is established to maximize the social welfare. In addition, to improve the efficiency of the optimization problem solving process and to achieve communication between the independent system operator (ISO) and the aggregators, the clustering algorithm is utilized to extract typical EV charging patterns. Finally, the feasibility and benefits of the aggregator-based DR mechanism for saving the costs and reducing the peak-valley difference of the receiving-end power grid are verified through case studies.

Abstract Objective circular RNAs (circRNAs) have been reported to be essential regulators of multiple malignant cancers. However, the functions of circRNAs in ovarian cancer need to be further explored. The aim of our study is to explore the role of circRNA-UBAP2 in ovarian cancer and its mechanism. Results circRNA-UBAP2 was upregulated in ovarian cancer tissues and cell lines. Knockdown of circRNA-UBAP2 inhibited cell proliferation and promoted cell apoptosis, but circRNA-UBAP2 overexpressed got opposite results. In addition, circRNA-UBAP2 targeted miR-382-5p and downregulated its expression, PRPF8 was a target gene of miR-382-5p. Furthemore, circRNA-UBAP2/miR-382-5p/PRPF8 axis affected the proliferation, apoptosis and cell cycle of ovarian cancer through the mechanism of competing endogenous RNAs (ceRNA). Conclusion circRNA-UBAP2 acted as a ceRNA to sponged miR-382-5p, increased the expression level of PRPF8, and prompted proliferation and inhibited apoptosis in ovarian cancer cells.

An effective vaccine for human papillomavirus (HPV) needs to protect from several genotypes. Here, Wang et al. provide a strategy to produce single capsomere-hybrid virus-like particle (chVLP) composed of capsomers of different genotypes and show that a nona-type chVLP induces similar levels of neutralizing antibodies as an approved HPV vaccine.

In our previous studies, enhancer of zeste homolog 2 (EZH2) has been proven to be a key oncogenic driver in oral squamous cell carcinoma (OSCC). However, the regulatory mechanisms on EZH2 remain poorly understood in OSCC. Here, through multi-transcriptomics, bioinformatics analysis, and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), the co-expression network of long noncoding RNA RC3H2 (RC3H2), microRNA-101-3p (miR-101-3p), and EZH2 were screened and validated as a competing endogenous RNA (ceRNA) mechanism in OSCC. Silencing of RC3H2 inhibited OSCC cell proliferation, colony formation, migration, and invasion in vitro and reduced the expression of EZH2 and H3K27Me3, whereas RC3H2 overexpression significantly promoted OSCC cell growth, colony formation, migration, invasion, and xenograft tumor growth in vivo and increased the expression of EZH2 and H3K27Me3. A fluorescence in situ hybridization (FISH) assay verified that RC3H2 was predominately localized to the cytoplasm. RNA pull-down and luciferase activity assays showed that miR-101-3p was physically bound to RC3H2 as well as EZH2, and its inhibitor reversed the inhibitory effect of RC3H2 knockdown on progression of OSCC. Taken together, our findings demonstrate that RC3H2 as completive endogenous RNA sponging miR-101-3p targets EZH2 and facilitates OSCC cells’ malignant behavior.

Abstract Purpose As a potential tool for the biodegradation of nitrogen contaminants, including nitrate, nitrite, and ammonium, in pickled foods with high salinity, the halophilic and denitrifying archaeal strain Halomicrobium sp. ZPS1 was isolated from edible salt particles. Methods Under anaerobic and static culture conditions, Halomicrobium sp. ZPS1 could simultaneously degrade nitrate, nitrite, and ammonium in liquid medium with 18% salinity and generate N2O. To gain insight into these physiological characteristics, the complete genome of Halomicrobium sp. ZPS1 was sequenced to reveal the mechanism of nitrogen metabolism associated with salt-tolerance. Result The complete genome sequencing revealed a genome size of 3,094,203 bp with a circular chromosome and a GC content of 65.64%. Based on gene annotation, 3191 CDSs, 6 rRNA genes, and 76 tRNA genes were identified. Moreover, 28 genes were annotated as related to salt tolerance, ammonium assimilation, and a truncated denitrification pathway. Conclusion The annotated functional genes indicate that Halomicrobium sp. ZPS1 could be a candidate strain for the simultaneous removal of nitrate, nitrite, and ammonia in extremely high salt environments.

Nitrogen is widely used to prevent the spontaneous combustion of coal in underground coal mines. A spontaneous combustion-prone coal seam was studied to investigate the restraining effect of nitrogen on coal oxidation in different oxidation stages, based on non-isothermal thermogravimetry-differential scanning calorimetry (TG-DSC) and electron paramagnetic resonance (EPR) experiments. We found that the key feature temperatures grow steadily with increasing nitrogen in the oxidation environment, resulting in longer oxidation stages. The most significant finding is that there is a stagnation of the inhibitory effect of nitrogen on coal oxidation in the range of 85.0–95.0% nitrogen in the slow and the rapid oxidation stages, owing to the competitive adsorption of coal by nitrogen and oxygen. However, the restraining effect cannot be reflected by the kinetic parameters of the coal before it reaches the thermal decomposition and combustion stage. Nitrogen can also affect free radical types and free radical concentrations during coal oxidation: the higher the concentration of nitrogen in the oxidation environment, the greater the number of free radical types and the lower the free radical concentration. This experimental study improves the understanding of the restraining effect of nitrogen on coal oxidation in different oxidation stages and provides an important reference for coal fire prevention in spontaneous combustion-prone coal seams.

The giant panda (Ailuropoda melanoleuca) is one of the world’s most endangered mammals and remains threatened as a result of intense environmental and anthropogenic pressure. The transformation and specialization of the giant panda’s diet into a herbivorous diet have resulted in unique adaptabilities in many aspects of their biology, physiology and behavior. However, little is known about their adaptability at the molecular level. Through comparative analysis of the giant panda’s genome with those of nine other mammalian species, we found some genetic characteristics of the giant panda that can be associated with adaptive changes for effective digestion of plant material. We also found that giant pandas have similar genetic characteristics to carnivores in terms of olfactory perception but have similar genetic characteristics to herbivores in terms of immunity and hydrolytic enzyme activity. Through the analysis of gene family expansion, 3752 gene families were found, which were enriched in functions such as digestion. A total of 93 genes under positive selection were screened out and gene enrichment identified these genes for the following processes: negative regulation of cellular metabolic process, negative regulation of nitrogen compound metabolic process, negative regulation of macromolecule metabolic process and negative regulation of metabolic process. Combined with the KEGG pathway, it was found that genes such as CREB3L1, CYP450 2S1, HSD11B2, LRPAP1 play a key role in digestion. These genes may have played a key role in the pandas’ adaptation to its bamboo diet.

In recent years, active queue management (AQM) has gained more and more attention as an important part of network congestion control. Although there are many AQM algorithms, these algorithms show weaknesses to detect and control congestion due to the complexity and dynamics of the networks. Hence, this paper proposes a new AQM algorithm based on model predictive control (MPC) theory which has been widely applied in nonlinear and time-delay systems. In order to adjust the parameters of the MPC-based AQM algorithm adaptively according to network scenario variations, the adaptive mechanism is introduced into the new algorithm, named PHAQM, by using the Hebb learning rules from the neural network control theory. The simulation results show that the algorithm is effective in avoiding network congestion. Compared to the traditional AQM schemes, such as PI, REM, and GPC algorithm, the PHAQM has a faster convergence rate and smaller queue length fluctuations and outperforms especially under dynamically changing network situations.

Corn flour has been stored at different moisture content (without and with 10 % water) and temperatures (–20, 4 and 25 °C). A modified quick, easy, cheap, effective, rugged and safe (QuEChERS) method was applied to determine the degradation rate of five common pesticides (imidacloprid, carbendazim, triadimefon, acetochlor and metolachlor) during the stored process using high-performance liquid chromatography with a diode array detector and gas chromatography with an electron capture detector. The results showed that there was almost no degradation on five pesticides at –20°C in corn flour whether with or without water, and the half-life was 69.3–693.2 days. The degradation rate ranged from 1.7 to 7.8 % after ten days of application. Under 25°C and 10 % moisture content, the half-life was sharply reduced to 5.8–14.4 days. Under this condition, the degradation rate ranged from 40.6 to 68.4 % after ten days of application, and the sequence from high to low of the five pesticides. The degradation rates were as follows: carbendazim, imidacloprid, acetochlor, metolachlor and triadimefon. Therefore, low temperature and drying were beneficial to the storage of corn flour, but unfavorable to the degradation of pesticides in corn flour.

In order to investigate the effect of nano polymer materials on the UV aged performance of asphalt binder, a nano PA modifying agent was selected to prepare modified asphalt. Under the effect of UV radiation, the modifying effect of nano PA on the rheological properties of asphalt was studied. With the extension of UV ageing time, the microstructure variation of PA modified asphalt was characterized by using a focused ion beam scanning electron microscope (FIB-SEM). The thermophysical properties of PA modified asphalt were investigated by thermogravimetric analysis (TG). Furthermore, the functional group compositions of PA modified asphalt were investigated by dynamic FTIR. The results showed that with the extension of UV ageing time, the PA modifier could mitigate the ageing effect of UV radiation on the asphalt binder. PA modifier could achieve an increasing effect on the viscoelasticity of asphalt during the UV ageing process. PA modifier suppressed the generation of microcracks in the surface microzone of UV aged asphalt samples. PA modifier could promote the thermal stability improvement of asphalt binder when subjected to UV radiation. The generation of carbonyl and sulfoxide groups in asphalt was inhibited during the UV ageing period, which indicated that the UV induced reaction of asphalt could be postponed by the PA modifying agent.

The ground motion records obtained by the CDSMON during the Ms6.4 earthquake in Yangbi, Yunnan Province, on May 21, 2021, were subjected to routine processing such as baseline correction and filtering. The nonstationary time-frequency characteristics of ground motion signals were analysed by the wavelet transform, and the acceleration response spectrum characteristics of typical stations under different epicentral distances, magnitudes, and site conditions were analysed. Finite element software was used to establish a model to analyse the seismic response of a typical three-span continuous beam bridge. The maximum peak ground acceleration (PGA) of this earthquake (720.29 gal) was obtained from 53YBX in the NS direction at the epicentral distance of 8.6 km. The energy at station 53YBX was mainly concentrated in 0–15 Hz range, and the low-frequency component energy caused great damage to buildings with natural frequencies in this frequency band. The Sa value near the origin of the earthquake is relatively large, as the distance from the epicentre increases, the predominant period of Sa also gradually increases, and the high-frequency component diminishes. With the increase in earthquake magnitude, the Sa peak increased, and the long-period component became more obvious. The soil station had more obvious long-period components than the bedrock station, which is consistent with the amplification result of the response spectrum of overburden thickness to surface acceleration. The earthquake had little influence on the pier displacement of the three-span continuous beam bridge with a fundamental period of 0.77 s but had a great influence on the bending moment at the bottom of the piers.

The WHO recommends Artemisinin-based combination therapy (ACTs) as the first-line treatment for malaria. This meta-analysis aims to analyze the effects of artemisinin and its derivatives as well as non-artemisinin drugs on the gametophytes in the host during the treatment of falciparum malaria. Fourteen studies were included in this analysis, and the artemisinin combination drugs involved were: artemether-lumefantrine (AL), artemisinin (AST), artemether-benflumetol (AB), dihydroartemisinin-piperaquine + trimethoprim + primaquine (CV8), amodiaquine + sulfadoxine-pyrimethamine (ASP), pyronaridine-phosphate + dihydroartemisinin (PP-DHA), dihydroartemisinin (DHA), and mefloquine + artesunate (MA), with 1702 patients. The control intervention measures involved the following: sulfadoxine-pyrimethamine (SP), mefloquine (MQ), atovaquone-proguanil (AT-PG), chloroquine + sulfadoxine-pyrimethamine (C-SP), quinine (Q), pyronaridine-phosphate (PP), pyronaridine (PN), and mefloquine + primaquine (MP), with 833 patients. The effect of ACTs was more obvious (OR = 0.37, 95%CI: 0.22–0.62, p < 0.05). In the control group of second malaria attacks, the difference between the two groups was not statistically significant (RD = 1.16, 95%CI: 0.81–1.66, p < 0.05); there was no significant difference in treatment failure during follow-up (RD = -0.01, 95%CI: 0.04–0.03, p < 0.05). There were also very few serious adverse events in both groups. ACTs showed good therapeutic effects in preventing gametocythemia but did not control the recrudescence rate and overall cure, which indicated the effectiveness of the combination of antimalarial drugs. Further research is required to explore which compatibility method is most conducive to the development of clinical malaria control.

Previous studies evaluating the association between skipping breakfast and hypertension in adult population showed inconsistent results. We performed a meta-analysis to systematically evaluate the association. Observational studies which evaluated the relationship between skipping breakfast and hypertension in adult population with multivariate analyses were identified by systematic search of PubMed, Embase, and Web of Science databases. A random-effect model which incorporated the potential intrastudy heterogeneity was used for the meta-analysis. A total of six observational studies with 14189 adults were included, and 3577 of them were breakfast skippers. Pooled results showed that skipping breakfast was independently associated with hypertension in these populations (adjusted odds ratio (OR): 1.20, 95% confidence interval: 1.08 to 1.33, P0.10). In conclusion, skipping breakfast is associated with hypertension in the adult population.

Metal laminated composites are widely used in industrial and commercial applications due to their excellent overall performance. In this study, the copper/graphene-aluminum-copper/graphene (Cu/Gr-Al-Cu/Gr) laminated composites were prepared by ingenious hot pressing design. Raman, optical microscope (OM), scanning electron microscope (SEM), van der Pauw (vdP), and X-Ray Diffractometer (XRD) were used to investigate the graphene status, interface bonding, diffusion layer thickness, electrical conductivity, Miller indices and secondary phases, respectively. The results demonstrate that the Cu-Al interfaces in the Cu/Gr-Al-Cu/Gr composites were free of pores, cracks and other defects and bonded well. The number of graphene layers was varied by regulating the thickness of the Cu/Gr layer, with the Cu/Gr foils fabricated by chemical vapor deposition (CVD). The electrical conductivity of the composite was significantly improved by the induced high-quality interfaces Cu/Gr structure. The increased number of graphene layers is beneficial for enhancing the electrical conductivity of the Cu/Gr-Al-Cu/Gr composite, and the highest conductivity improved by 20.5% compared to that of raw Al.

Background Anemia or low hemoglobin can increase the risk of stroke. However, the association between hemoglobin and outcomes after stroke is uncertain. In this study, we aimed to investigate the association between hemoglobin and clinical outcomes, including mortality, poor functional outcome, stroke recurrence, and composite vascular events at 1 year. Methods and Results We included the patients diagnosed with acute ischemic stroke or transient ischemic attack from the Third China National Stroke Registry. We used the Cox model for mortality, stroke recurrence, and composite vascular events and the logistic model for the poor functional outcome to examine the relationship between hemoglobin and clinical outcomes. In addition, we used the restricted cubic spline to evaluate the nonlinear relationship. This study included 14 159 patients with acute ischemic stroke or transient ischemic attack. After adjusted for potential cofounders, both anemia and high hemoglobin were associated with the higher risk of mortality (hazard ratio [HR], 1.73; 95% CI, 1.39–2.15; HR, 2.71; 95% CI, 1.95–3.76) and poor functional outcome (odds ratio [OR], 1.36; 95% CI, 1.18–1.57; OR, 1.42; 95% CI, 1.07–1.87). High hemoglobin, but not anemia, increased the risk of stroke recurrence (HR, 1.37; 95% CI, 1.05–1.79) and composite vascular events (HR, 1.41; 95% CI, 1.08–1.83). There was a U‐shaped relationship between hemoglobin and mortality and poor functional outcome. Conclusions Abnormal hemoglobin was associated with a higher risk of all‐cause mortality, poor functional outcome, stroke recurrence, and composite vascular events. More well‐designed clinical studies are needed to confirm the relationship between hemoglobin and clinical outcomes after stroke.

Poly ADP-ribose polymerase inhibitor (PARPi) has become an important maintenance therapy for ovarian cancer after surgery and cytotoxic chemotherapy, which has changed the disease management model of ovarian cancer, greatly decreased the risk of recurrence, and made the prognosis of ovarian cancer better to certain extent. The three PARPis currently approved by the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of ovarian cancer are Olaparib, Niraparib and Rucaparib. With the incremental results from new clinical trials, the applicable population of PARPi for ovarian cancer have expanded to population with non-BRCA mutations. Although BRCA mutated population are still the main beneficiaries of PARPi, recent clinical trials indicated PARPis’ therapeutic potential in non-BRCA mutated population, especially in homologous recombination repair deficiency (HRD) positive population. However, lack of unified HRD status detection method poses a challenge for the accurate selection of PARPi beneficiaries. The reversal of homologous recombination (HR) function during the treatment will not only cause resistance to PARPis, but also reduce the accuracy of the current method to determine HRD status. Therefore, the development of reliable HRD status detection methods to determine the beneficiary population, as well as rational combination treatment are warranted. This review mainly summarizes the latest clinical trial results and combination treatment of PARPis in ovarian cancer with non-BRCA mutations, and discusses the application prospects, including optimizing combination therapy against drug resistance, developing unified and accurate HRD status detection methods for patient selection and stratification. This review further poses an interesting topic: the efficacy and safety in patients retreated with PARPis after previous PARPi treatment---“PARPi after PARPi”.

In order to reduce the impacts caused by large-scale renewable energy resources accessing the utility grid, the micro-energy grid system, as a natural extension of the microgrid in the energy internet era, is proposed and developed to provide a new solution for the optimal utilization of renewable energy resources. In this paper, a multi-energy integrated micro-energy system is proposed which contains wind, PV, bedrock energy storage, magnetic levitation electric refrigeration, solid oxide fuel cell, solar thermal collector, energy storage, and V2G technologies, and detailed models of the energy generation/conversion/storage devices are formulated. Besides this, the uncertainties of renewable energy resources and cold/heat/electricity loads are considered, and the optimal dispatch problem of the micro-energy system is established from day-ahead and real-time time scales based on a model predictive control method. The day-ahead optimal scheduling aims at economic optimization and guides real-time scheduling, and real-time scheduling utilizes rolling optimization and a feedback correction mechanism to effectively correct the deviation of renewable energy generations and loads at a real-time horizon, which improves the optimization control accuracy, follows the day-ahead dispatch plan, and ensures the economics of real-time scheduling at the same time.

Objective To investigate the care needs of dying patients and their family caregivers in hospice and palliative care in mainland China.Methods A search for English and Chinese quantitative and qualitative studies was performed using the following English databases: PubMed (Medline), CINAHL and PsycINFO, as well as Chinese databases: SinoMed and CNKI. The records were independently screened by two reviewers and critiqued using Joanna Briggs Institute Critical Appraisal tools. All quantitative data were transformed into qualitative data, which were converted into textual descriptions. Due to the diversity of included studies, a three-step analysis was performed: narrative summary, thematic analysis and presentation of integrated results in a narrative form. The qualitative findings were pooled using the meta-aggregation approach.Results The literature search identified 2964 papers after removing duplicates, from which 18 were included (9 quantitative and 9 qualitative studies). All studies were conducted in mainland China. Quantitative studies involved cross-sectional surveys, and qualitative studies involved interviews for data collection. Two synthesised results of patients’ needs were identified, including needs to be comfortable and experience a good death. Another two synthesised results of family caregivers’ needs included needs to care for and improve the quality of life of patients, and to care for themselves well.Conclusion This study identified that patients and family caregivers have an increasing demand for professional care at the end of life. Professionals, especially nurses, should enact a patients’ demand-centred practice to overcome the challenges of organisation, education, emotion and communication to provide high-quality end-of-life care.

ObjectiveThe concentrations of complement proteins (adipsin, C3a, and C5a) and soluble endoglin (sENG) in the plasma were measured in this study, and their value as early-pregnancy predictors and potential diagnostic marker of preeclampsia was assessed, respectively.Experimental DesignPlasma samples were obtained from healthy and preeclampsia pregnant women before delivery for a cross-sectional study. Plasma samples were collected from healthy and preeclampsia pregnant women throughout pregnancy and postpartum for a follow-up study. Enzyme-linked immunosorbent assays were used to detect plasma levels of several complement proteins (adipsin, C3a, and C5a) and sENG.ResultsThe plasma levels of adipsin, C5a, and sENG were significantly increased before delivery in pregnant women with preeclampsia. During pregnancy, the plasma adipsin, C5a, and sENG levels were increased from the third trimester in healthy pregnant women; plasma adipsin levels remained stable after delivery, while C3a levels increased in the second trimester and remained stable afterward. Furthermore, levels of adipsin, C5a, and sENG were higher in preeclampsia patients at different stages of pregnancy; the C3a level presents a similar change and no difference was found in the third trimester. In the first trimester, receiver-operating curve (ROC) curve analysis showed that adipsin (AUC, 0.83 ± 0.06, P=0.001) and sENG (AUC, 0.74 ± 0.09, P=0.021) presented high value as predictors of early pregnancy.ConclusionsAdipsin is likely a novel plasma biomarker to monitor the increased risk of preeclampsia in early pregnancy. Moreover, the increased plasma levels of adipsin, C5a, and sENG before delivery may be associated with preeclampsia.

ABSTRACT Iron is an essential element for the growth and survival of pathogenic bacteria; however, it is not fully understood how bacteria sense and respond to iron deficiency or excess. In this study, we show that xfeA in Xanthomonas oryzae pv. oryzicola senses extracytoplasmic iron and changes the hydrogen bonding network of ligand channel domains by adenosine-to-inosine (A-to-I) RNA editing. The frequency of A-to-I RNA editing during iron-deficient conditions increased by 76.87%, which facilitated the passage of iron through the XfeA outer membrane channel. When bacteria were subjected to high iron concentrations, the percentage of A-to-I editing in xfeA decreased, which reduced iron transport via XfeA. Furthermore, A-to-I RNA editing increased expression of multiple genes in the chemotaxis pathway, including methyl-accepting chemotaxis proteins (MCPs) that sense concentrations of exogenous ferrienterobactin (Fe-Ent) at the cytoplasmic membrane. A-to-I RNA editing helps X. oryzae pv. oryzicola move toward an iron-rich environment and supports our contention that editing in xfeA facilitates entry of a ferric siderophore. Overall, our results reveal a new signaling mechanism that bacteria use to adjust to iron concentrations. IMPORTANCE Adenosine-to-inosine (A-to-I) RNA editing, which is catalyzed by the adenosine deaminase RNA-specific family of enzymes, is a frequent posttranscriptional modification in metazoans. Research on A-to-I editing in bacteria is limited, and the importance of this editing is underestimated. In this study, we show that bacteria may use A-to-I editing as an alternative strategy to promote uptake of metabolic iron, and this form of editing can quickly and precisely modify RNA and subsequent protein sequences similar to an “on/off” switch. Thus, bacteria have the capacity to use a rapid switch-like mechanism to facilitate iron uptake and improve their competitiveness.

Ulcerative colitis (UC) is an inflammatory bowel disease. The intake of African Garcinia Kola nuts has been reported as a therapy for diarrhea and dysentery in the African population. However, the mechanism of action through which Garcinia Kola nuts act to ameliorates UC remains unknown. GB1a is the main active component of Garcinia Kola nuts. In this study, we explored the therapeutic effects and underlying mechanism of GB1a on dextran sodium sulfate (DSS)-induced UC. Human Colonic Epithelial Cells (HCoEpic) were challenged with TNF-α to test the effects of GB1a in protecting against oxidative stress and inflammation in vitro. Our data showed that GB1a significantly attenuated DSS-induced colonic inflammatory injury manifested as reversed loss of body weight and disease activity index (DAI) scores in UC mice. We also showed that GB1a improved the permeability of the intestinal epithelium by modulating the expression of tight junction proteins (ZO-1, Occludin). Mechanistically, GB1a may activate the Nrf2 antioxidant signaling pathway and suppress the nuclear translocation of NF-κB in reduced oxidative stress and expression of inflammatory genes induced by TNF-α in HCoEpic cells. Our study suggests that GB1a alleviates inflammation, oxidative stress and the permeability of the colonic epithelial mucosa in UC mice via the repression of NF-κB and activation of Nrf2 signaling pathway.

A flexible electrochemical sensor based on the carbon felt (CF) functionalized with Bisphenol A (BPA) synthetic receptors was developed. The artificial Bisphenol A receptors were grafted on the CF by a simple thermal polymerization molecular imprinting process. Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and electrochemical characterizations were used to analyze the receptors. Characterization results demonstrated that the Bisphenol A synthetic receptors successfully formed on the CFs surface. Because the synthetic receptor and the porous CFs were successfully combined, the sensor displayed a better current response once Bisphenol A was identified. The sensor’s linear range was determined to be from 0.5 to 8.0 nM and 10.0 to 300.0 nM, with a detection limit of 0.36 nM. Even after being bent and stretched repeatedly, the electrode’s performance was unaffected, demonstrating the robustness, adaptability and viability of installing the sensor on flat or curved surfaces for on-site detection. The designed electrochemical sensor has been used successfully to identify Bisphenol A in milk samples with satisfactory results. This work provided a promising platform for the design of implantable, portable and miniaturized sensors.

Heavy metal ions (HMIs) pose a serious threat to the environment and human body because they are toxic and non-biodegradable and widely exist in environmental ecosystems. It is necessary to develop a rapid, sensitive and convenient method for HMIs detection to provide a strong guarantee for ecology and human health. Ion-imprinted electrochemical sensors (IIECSs) based on nanomaterials have been regarded as an excellent technology because of the good selectivity, the advantages of fast detection speed, low cost, and portability. Electrode surfaces modified with nanomaterials can obtain excellent nano-effects, such as size effect, macroscopic quantum tunneling effect and surface effect, which greatly improve its surface area and conductivity, so as to improve the detection sensitivity and reduce the detection limit of the sensor. Hence, the present review focused on the fundamentals and the synthetic strategies of ion-imprinted polymers (IIPs) and IIECSs for HMIs detection, as well as the applications of various nanomaterials as modifiers and sensitizers in the construction of HMIIECSs and the influence on the sensing performance of the fabricated sensors. Finally, the potential challenges and outlook on the future development of the HMIIECSs technology were also highlighted. By means of the points presented in this review, we hope to provide some help in further developing the preparation methods of high-performance HMIIECSs and expanding their potential applications.

The ongoing spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused hundreds of millions of cases and millions of victims worldwide with serious consequences to global health and economies. Although many vaccines protecting against SARS-CoV-2 are currently available, constantly emerging new variants necessitate the development of alternative strategies for prevention and treatment of COVID-19. Inhibitors that target the main protease (Mpro) of SARS-CoV-2, an essential enzyme that promotes viral maturation, represent a key class of antivirals. Here, we showed that a peptidomimetic compound with benzothiazolyl ketone as warhead, YH-53, is an effective inhibitor of SARS-CoV-2, SARS-CoV, and MERS-CoV Mpros. Crystal structures of Mpros from SARS-CoV-2, SARS-CoV, and MERS-CoV bound to the inhibitor YH-53 revealed a unique ligand-binding site, which provides new insights into the mechanism of inhibition of viral replication. A detailed analysis of these crystal structures defined the key molecular determinants required for inhibition and illustrate the binding mode of Mpros from other coronaviruses. In consideration of the important role of Mpro in developing antivirals against coronaviruses, insights derived from this study should add to the design of pan-coronaviral Mpro inhibitors that are safer and more effective.

Cisplatin is widely used as a chemotherapeutic drug to treat various solid tumors. However, it often induces severe side effects, including nephrotoxicity, which limits its application in clinical settings. Furthermore, the underlying mechanisms of action are unclear. Here, we applied whole-transcriptome RNA sequencing to a cisplatin-induced acute kidney injury (CP-AKI) mouse model to evaluate competing endogenous RNA (ceRNA) networks. We found 4460 mRNAs, 1851 long non-coding RNAs, 101 circular RNAs, and 102 microRNAs significantly differentially expressed between CP-AKI and control mice. We performed gene set enrichment analysis to reveal the biological functions of the mRNAs and constructed non-coding RNA-associated ceRNA networks in CP-AKI mice. Two ceRNA regulatory pathways, Lhx1os-203/mmu-miR-21a-3p/Slc7a13 and circular RNA_3907/mmu-miR-185-3p/Ptprn, were validated using quantitative real-time PCR. The protein–protein interaction network indicated that Il6, Cxcl1, Cxcl2, and Plk1 serve as hub genes and are highly connected with the inflammatory response or DNA damage. Transcription factors, such as Stat3, Cebpb, and Foxm1, regulate gene expression levels in CP-AKI. Our study provides insight into non-coding RNA-associated ceRNA networks and mRNAs in CP-AKI and identifies potential treatment targets.

The purpose of geographic location selection is to make the best use of space. Geographic location selection contains a large amount of spatiotemporal data and constraints, resulting in too many solutions. Therefore, this paper adopts the ant colony algorithm in the meta-heuristic search method combined with the incomplete quadtree to improve the searchability of the space. This paper proposes an improved ant colony algorithm in nonuniform space to solve the P-center facility location problem. The geographic space is divided by the incomplete quadtree, and the ant colony path is constructed on the level of the quadtree division. Ant colonies can leave pheromones on multiple search paths, and optimized quadtree encoding in nonuniform space stores pheromone matrices and distance matrices. The algorithm proposed in this paper improves the pheromone diffusion algorithm and the optimization objective at the same time to update the pheromone in the nonuniform space and obtain the ideal solution. The results show that the algorithm has excellent performance in solving the location problem with good convergence accuracy and calculation time.

Objective: This meta-analysis aimed to systematically assess the therapeutic efficacy and safety of Qinghao Biejia decoction combined with conventional chemical medicine in patients with systemic lupus erythematosus (SLE), and to provide reference for clinical medication.Methods: Multiple databases were retrieved by computer for randomized controlled trials (RCTs) of treating SLE with Qinghao Biejia decoction combining chemical medicine, from the establishment of the database to January 2021. Study screening, data collection, and quality assessment were performed independently by two reviewers. RevMan 5.4 and Stata 15.1 software were used for Meta-analysis.Results: Nine eligible studies, involving 655 SLE participants, were included. Meta-analysis showed that the additional use of Qinghao Biejia decoction superior to chemical medicine alone in people with SLE in improving the overall response rate (RR = 1.30, 95% CI [1.19, 1.41], p < 0.00001, heterogeneity p = 0.61, I2 = 0%), and can decrease SLE Disease Activity Index (SLEDAI) and TCM symptom scores, improve immunological indexes (C3, C4, IgG, IgA, IFN-γ, IL-4, Th1/Th2), reduce the occurrence of adverse events in treatment (P ≤ 0.05).Conclusion: Based on this meta-analysis, the additional use of Qinghao Biejia decoction has more advantages in the treatment of SLE than conventional chemical medication alone, which could enhance the efficacy and reduce adverse reactions, and is worthy of clinical promotion. However, more and higher quality RCTs are still need to confirm our findings.

PurposeThis study aimed to identify the exact definition of the concept of compensatory belief (CB) and to help clinicians and caregivers to distinguish patients who tend to form such beliefs.MethodsThis study is a conceptual analysis based on the strategy of Walker and Avant (2014). We retrieved studies from existing literature using databases such as PubMed, CINAHL, Wiley, and Web of Science, and extracted information from the results. No date limitations were applied.ResultsA total of 35 articles were sourced for data extraction. The identified attributes of CB were as follows: cognitive coping strategy, pleasure without guilt, compensatory behaviors, automatic motivated self-regulatory process, and implicit cognition. The observed antecedents were: failure to resist desire, reluctance, a conflicting motivational state, seeking appropriate balance, and self-image maintenance. The consequences of CB were lower health-related intentions, justification of unhealthy choices, relief from cognitive dissonance, continued existence of conflict feeling, and poor long-term health.ConclusionCompensatory belief stems from motivational dissonance or confliction. Despite causing feelings of pleasure and relief, it can negatively impact long-term health. Although CB is crucial to establish healthy behaviors, it is easily ignored in medical work.

Malaria, one of the most serious parasitic diseases, kills thousands of people every year, especially in Africa. São Tomé and Príncipe are known to have stable transmission of malaria. Indoor residual spraying (IRS) of insecticides and long-lasting insecticidal nets (LLIN) are considered as an effective malaria control interventions in these places. The resistance status of Anopheles gambiae s.s. from Agua Grande, Caue, and Lemba of São Tomé and Príncipe to insecticides, such as dichlorodiphenyltrichloroethane (DDT) (4.0%), deltamethrin (0.05%), permethrin (0.75%), fenitrothion (1.0%), and malathion (5.0%), were tested according to the WHO standard protocol. DNA extraction, species identification, as well as kdr and ace-1R genotyping were done with the surviving and dead mosquitoes post testing. They showed resistance to cypermethrin with mortality rates ranging from 89.06% to 89.66%. Mosquitoes collected from Agua Grande, Caue, and Lemba displayed resistance to DDT and fenitrothion with mortality rates higher than 90%. No other species were detected in these study localities other than Anopheles gambiae s.s. The frequency of L1014F was high in the three investigated sites, which was detected for the first time in São Tomé and Príncipe. No ace-1R mutation was detected in all investigated sites. The high frequency of L1014F showed that kdr L1014F mutation might be related to insecticide resistance to Anopheles gambiae s.s. populations from São Tomé and Príncipe. Insecticide resistance status is alarming and, therefore, future malaria vector management should be seriously considered by the government of São Tomé and Príncipe.

Background: Mass drug administration with artemisinin-piperaquine (AP-MDA) is being considered for elimination of residual foci of malaria in Democratic Republic of São Tomé and Principe.Methods: Three monthly rounds of AP-MDA were implemented from July to October 2019. Four zones were selected. A and B were selected as a study site and a control site, respectively. C and D were located within 1.5 and 1.5 km away from the study site, respectively. Parasite prevalence, malaria incidence, and the proportion of the Plasmodium falciparum malaria cases were evaluated.Results: After 3 monthly rounds of AP-MDA, the parasite prevalence and the gametocyte carriage rate of P. falciparum in zone A decreased from 28.29(‰) to 0 and 4.99(‰) to 0, respectively. Compared to zone B, the relative risk for the population with Plasmodium falciparum malaria in zone A was lower (RR = 0.458, 95% CI: 0.146–1.437). Malaria incidence fell from 290.49(‰) (the same period of the previous year) to 15.27(‰) (from the 29th week in 2019 to the 14th week in 2020), a decrease of 94.74% in zone A, and from 31.74 to 5.46(‰), a decline of 82.80% in zone B. Compared to the data of the same period the previous year, the cumulative number of P. falciparum malaria cases were lower, decreasing from 165 to 10 in zone A and from 17 to 4 in zone B. The proportion of the P. falciparum malaria cases on the total malaria cases of the country decreased of 90.16% in zone A and 71.34% in zone C.Conclusion: AP-MDA greatly curbed malaria transmission by reducing malaria incidence in the study site and simultaneously creating a knock-on effect of malaria control within 1.5 km of the study site and within the limited time interval of 38 weeks.

Background: To evaluate the associations of pre-conception body mass index (BMI), fasting plasma glucose (FPG) alone and their combination with pre-term birth (PTB) risk.Methods: We conducted a population-based retrospective cohort study with 4,987,129 reproductive-aged women, who participated in National Free Pre-Pregnancy Checkups Project in 2013–2016 and had a singleton delivery before December 2017 in China. All data analyses were conducted in 2018–2021.Results: A total of 339,662 (6.81%) women had pre-term deliveries. Compared with women with normal weight and normal glucose, underweight and normal weight were associated with PTB among hypoglycemia women, the adjusted odd ratios (aORs) were 1.24 (95% CI: 1.05–1.48) and 1.16 (95% CI: 1.07–1.25), respectively; underweight, overweight and obesity were associated with PTB among women with normal glucose, the aORs were 1.09 (95% CI: 1.08–1.10), 1.06 (95% CI: 1.05–1.07) and 1.08 (95% CI: 1.05–1.12), respectively; all the BMI groups were significantly associated with PTB among women with pre-diabetes or diabetes (P < 0.05). The dose-response relationships of BMI with PTB varied in different FPG level, with U-shaped curve in normal glucose and pre-diabetes women, J-shaped in diabetes women, L-shaped in hypoglycemia women. For FPG with PTB, the dose-response relationships were U-shaped in normal weight, overweight, and obesity women, and L-shaped in underweight women.Conclusion: We found that the associations of PTB with BMI varied with levels of FPG, and associations of PTB with FPG varied with levels of BMI. There was a synergistic effect on PTB risk due to abnormal weight and glycemia besides a conventional main effect derived from either of them. Achieving desirable weight and glucose control before conception should be advised.

Abstract Background The lncRNA LINC00460 plays crucial roles in several epithelial cancers, although its mechanisms of action differ greatly in different cellular contexts. In this study, we aimed to determine the potential clinical applications of LINC00460 and elucidate the mechanisms by which LINC00460 affects the development and progression of head and neck squamous cell carcinoma (HNSCC). Methods The biological functions of LINC00460 were assessed in several epithelial cancer cell lines. The subcellular localization of LINC00460 was evaluated by cell nuclear/cytoplasmic fractionation and fluorescence in situ hybridization. RNA pull-down assays, LS-MS/MS analysis, and RNA and chromatin immunoprecipitation assays were performed to identify the molecular mechanism by which LINC00460 promotes HNSCC progression. The clinical pathological features of LINC00460 and PRDX1 were evaluated in HNSCC tissues and paired adjacent normal tissues. Results LINC00460 enhanced HNSCC cell proliferation and metastasis in vitro and in vivo and induced epithelial–mesenchymal transition (EMT). LINC00460 primarily localized within the cytoplasm of HNSCC cells, physically interacted with PRDX1 and facilitated PRDX1 entry into the nucleus. PRDX1 promoted the transcription of LINC00460, forming a positive feedback loop. In addition, PRDX1 also promoted the transcription of EMT-related genes (such as ZEB1, ZEB2 and VIM) through enrichment on gene promoters in the nucleus. LINC00460 effectively induced HNSCC cell EMT in a PRDX1-dependent manner, and PRDX1 mainly mediated the EMT-promoting effect of LINC00460. High levels of LINC00460 and PRDX1 expression were positively associated with lymph metastasis, pathological differentiation and tumor size in HNSCC patients. Conclusions LINC00460 promoted EMT in HNSCC cells by facilitating PRDX1 entry into the nucleus. LINC00460 and PRDX1 are promising candidate prognostic predictors and potential targets for cancer therapy for HNSCC.

Abstract Background Head and neck cancer (HNC) is one of the most common deadly diseases worldwide. An increasing number of studies have recently focused on the malignant functions of cancer-associated fibroblasts (CAFs) in numerous cancers. However, the underlying mechanisms by which CAF-derived exosomes promote tumor progression need to be further elucidated. This study aims to determine whether the loss of specific miRNAs in CAF-derived exosomes may be involved in the malignant transformation of HNC. Methods MiRNA array and real-time PCR assays were used to analyze the differential expression of miRNAs in exosomes from normal fibroblasts (NFs) and CAFs. Cell proliferation, EdU incorporation, colony formation, apoptosis, cell cycle distribution and xenograft assays were performed to examine the effects of miR-3188 on HNC in vitro and in vivo. Real-time PCR, western blotting and luciferase reporter assays were used to identify the target genes of miR-3188. Furthermore, tumor-bearing mouse models were used to prove the potential therapeutic value of miR-3188-loaded exosomes in HNC. Results Our results showed that miR-3188 expression is reduced in exosomes and their parental CAFs from HNC tissues. In addition, miR-3188 can be transferred from fibroblasts to HNC cells by exosomes. Further exploration demonstrated that exosomal miR-3188 can influence the proliferation and apoptosis of HNC cells by directly targeting B-cell lymphoma 2 (BCL2) in vitro and in vivo. More importantly, we also found that miR-3188-loaded exosomes significantly inhibited tumor growth in vivo. Conclusions Our findings revealed that CAF-derived exosomes contain lower miR-3188 levels than NFs, and the loss of miR-3188 in exosomes contributes to the malignant phenotypes of HNC cells through the derepression of BCL2. Furthermore, these data suggest the potential therapeutic value of exosomal miR-3188 for inhibiting HNC growth.

The mold filling process of titanium alloy in a thin-walled cylinder cavity under vertical centrifugal casting process was studied by means of the hydraulic simulation experiments. Results show that the filling mode of the melt in the cylinder cavity varies with casting wall-thickness. When the casting wall-thickness is less than or equal to the thickness of the first layer during the filling process, the melts fill the cavity from the bottom to the top. When the casting wall-thickness is greater than the thickness of the first layer during the filling process, the melts first fill the largest radius parts of the cavity with a certain thickness of the first layer from the bottom to the top of the cavity, and then they fill the cavity from the larger radius part to the smaller radius part. The melt filling ability increases with the increment of the mold rotational speed and the pouring temperature. In another aspect, the melt filling ability rises with the decrement of the melt viscosity, and the melt with the better filling ability is prone to fill the cylinder cavity layer by layer.

Abstract Background Acetate, an economical industrial chemical, which is also the precursor of acetyl-CoA, could serve as an alternative substrate for biomanufacturing. This nontraditional substrate can be widely produced from syngas via hydrolysis or pyrolysis of the cellulosic biomass, chemical or microbial catalysis, anaerobic fermentation in treated wastewater, etc. However, the toxicity of acetate to microorganisms has held back its utilization, especially for the eukaryotes that are good hosts for production of complicated pharmaceuticals or chemicals. This study seeks to improve acetate utilization in a widely used yeast host, Komagataella phaffii (previously Pichia pastoris), by metabolic engineering of acetate tolerance, transport, and metabolism. Results A kinase-deficient library of K. phaffii was firstly used to screen acetate-resistant kinases. The HRK1 knockout strain was sensitive to acetate and overexpression of this gene improved acetate tolerance and cell growth of the strain. Also, overexpression of HRK1 caused a 55% productivity improvement of acetyl-CoA-dependent 6-methylsalicylic acid (6-MSA). However, activation of Hrk1 on membrane H(+)-ATPase Pma1 seemed not to work in the engineered strain. Acetate transporter gene ScFPS1* was further overexpressed, despite of not improving 6-MSA biosynthesis. To enhance acetate metabolism, acetyl-CoA synthesizing related genes, yeast PpACS1, ScACS1*, and E. coli ackA/pta were overexpressed separately. Introduction of PpACS1 and ScACS1* each increased biosynthesis of 6-MSA by approximately 20% on 20 mM acetate. Finally, co-overexpression of HRK1 and ScACS1* improved 6-MSA productivity by 51% on 20 mM acetate, despite that a low expression level of HRK1 happened when genes were expressed under the same promoter. Conclusions HRK1 screened by K. phaffii kinase-deficient library played an important role in acetate tolerance and was proved to profit the biosynthesis of acetyl-CoA-derived chemicals. It could be a potential target for metabolic engineering of acetate utilization in other eukaryotic hosts as well. A combined strategy of introducing genes for acetate tolerance and metabolism further improved biosynthesis of acetyl-CoA derived reporter compound in K. phaffii. This makes it a good choice for acetyl-CoA-derived chemicals with acetate as substrate or precursor in K. phaffii, which would also extend the use of this chassis host.

This work presents a novel method for the sensitive and selective detection of atmospheric hydroxyl radicals (OH). After activation by a hydrothermal method in the presence of sodium citrate, carbon fiber paper (CFP) with good conductivity and hydrophilicity was impregnated with salicylic acid (SA) and used as a detector to monitor OH. The impregnated SA can trap atmospheric OH, producing 2,5-dihydroxybenzoic acid (2,5-DHBA), an electroactive species. The concentration of 2,5-DHBA was quantified using a simple electrochemical method to estimate the number of OH radicals that have participated in the reaction. This method provided a linear correlation for 2,5-DHBA concentrations from 1.0 × 10−13 to 3.0 × 10−10 M with a detection limit of 2.09 × 10−14 M, which corresponds to an OH range from 1.0 × 105 to 3.0 × 108 molecules/cm3 with a detection limit of 2.1 × 104 molecules/cm3. This method has been used to measure the atmospheric OH levels in Yangzhou. Keywords: Salicylic acid, Impregnated, Carbon fiber paper, Hydroxyl radical, Electrochemical

One-sided exponential exponentially weighted moving average (EWMA) charts are useful tools for monitoring high-quality processes. Average run length ($ARL$ ) is usually used as the only criterion to evaluate the performance of a control chart. However, the shapes of the run length ($RL$ ) distributions of the one-sided exponential EWMA charts are highly skewed, and furthermore, are affected by the number of Phase I samples used to estimate the process parameters. This results in some confusion in the interpretation of control charts based on $ARL$ for practitioners. Fortunately, the median run length ($MRL$ ), which is more intuitional for users, could be employed as a good alternative measure. Based on these, the $MRL$ -based one-sided exponential EWMA charts are investigated in this paper, by taking the effect of estimated parameters into account. The performances of control charts are investigated through a Markov chain approach. An optimal design procedure is developed for the one-sided exponential EWMA charts with estimated parameters based on $MRL$ . Finally, an illustrative example is presented to show the implementation of the exponential EWMA chart when process parameters are estimated.

Abstract Background Cisplatin resistance is a major challenge for advanced head and neck cancer (HNC). Understanding the underlying mechanisms and developing effective strategies against cisplatin resistance are highly desired in the clinic. However, how tumor stroma modulates HNC growth and chemoresistance is unclear. Results We show that cancer-associated fibroblasts (CAFs) are intrinsically resistant to cisplatin and have an active role in regulating HNC cell survival and proliferation by delivering functional miR-196a from CAFs to tumor cells via exosomes. Exosomal miR-196a then binds novel targets, CDKN1B and ING5, to endow HNC cells with cisplatin resistance. Exosome or exosomal miR-196a depletion from CAFs functionally restored HNC cisplatin sensitivity. Importantly, we found that miR-196a packaging into CAF-derived exosomes might be mediated by heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1). Moreover, we also found that high levels of plasma exosomal miR-196a are clinically correlated with poor overall survival and chemoresistance. Conclusions The present study finds that CAF-derived exosomal miR-196a confers cisplatin resistance in HNC by targeting CDKN1B and ING5, indicating miR-196a may serve as a promising predictor of and potential therapeutic target for cisplatin resistance in HNC.

BackgroundTo develop and validate nomogram models for the preoperatively prediction of the histologic grade of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to provide appropriate treatments.MethodsA total of 1014 participants, including 211 healthy controls, 293 patients with benign diseases, 299 patients with cancers, and 211 patients with GEP-NETs were included in the final analysis. Their sociodemographic and laboratory information, including serum tumor markers such as AFP, CEA, CA19-9, CA72-4, Cyfra21-1 and NSE were collected. Nomogram models were developed to preoperatively predict histologic grades of GEP-NETs.ResultsAmong six serum tumor markers, only NSE was found to have a statistically significant association with the histologic grades in GEP-NETs (G1 vs. G2: p < 0.05; G2 vs. G3: p < 0.001; G1 vs. G3: p < 0.0001), which was combined with sex and age to develop the nomogram models. The first nomogram (to differentiate grade 1(G1) and grade 2/3 tumor (G2/G3)) showed a strong association to differentiate with an AUC of 0.747 (95% CI: 0.663-0.832) and 0.735 (95% CI: 0.624-0.847) in the training and validation datasets, respectively. The second nomogram (to differentiate G1/G2 and G3 tumors) showed a strong association to differentiate with an AUC of 0.827 (95% CI: 0.744-0.911) and 0.847 (95% CI: 0.744-0.950) in the training and validation datasets, respectively. The ROC, area under ROC curve (AUC), calibration curve and decision curve analysis (DCA) demonstrated the clinical usefulness of both models.ConclusionsWe proposed two novel nomogram models based on sex, age and serum NSE levels to preoperatively predict the histologic grades in GEP-NETs to assist the clinical decision-making.

Objectives To develop a model of in-hospital mortality using medical record front page (MRFP) data and assess its validity in case-mix standardisation by comparison with a model developed using the complete medical record data.Design A nationally representative retrospective study.Setting Representative hospitals in China, covering 161 hospitals in modelling cohort and 156 hospitals in validation cohort.Participants Representative patients admitted for acute myocardial infarction. 8370 patients in modelling cohort and 9704 patients in validation cohort.Primary outcome measures In-hospital mortality, which was defined explicitly as death that occurred during hospitalisation, and the hospital-level risk standardised mortality rate (RSMR).Results A total of 14 variables were included in the model predicting in-hospital mortality based on MRFP data, with the area under receiver operating characteristic curve of 0.78 among modelling cohort and 0.79 among validation cohort. The median of absolute difference between the hospital RSMR predicted by hierarchical generalised linear models established based on MRFP data and complete medical record data, which was built as ‘reference model’, was 0.08% (10th and 90th percentiles: −1.8% and 1.6%). In the regression model comparing the RSMR between two models, the slope and intercept of the regression equation is 0.90 and 0.007 in modelling cohort, while 0.85 and 0.010 in validation cohort, which indicated that the evaluation capability from two models were very similar.Conclusions The models based on MRFP data showed good discrimination and calibration capability, as well as similar risk prediction effect in comparison with the model based on complete medical record data, which proved that MRFP data could be suitable for risk adjustment in hospital performance measurement.

Abstract INTRODUCTION: Artemisinin-based combination therapy (ACT), such as artemisinin-piperaquine (AP), dihydroartemisinin-piperaquine (DP), and artemether-lumefantrine (AL), is the first-line treatment for malaria in many malaria-endemic areas. However, we lack a detailed evaluation of the cardiotoxicity of these ACTs. This study aimed to analyze the electrocardiographic effects of these three ACTs in malaria patients. METHODS: We analyzed the clinical data of 89 hospitalized patients with falciparum malaria who had received oral doses of three different ACTs. According to the ACTs administered, these patients were divided into three treatment groups: 27 treated with AP (Artequick), 31 with DP (Artekin), and 31 with AL (Coartem). Electrocardiograms and other indicators were recorded before and after the treatment. The QT interval was calculated using Fridericia’s formula (QTcF) and Bazett’s formula (QTcB). RESULTS: Both QTcF and QTcB interval prolongation occurred in all three groups. The incidence of such prolongation between the three groups was not significantly different. The incidence of both moderate and severe prolongation was not significantly different between the three groups. The ΔQTcF and ΔQTcB of the three groups were not significantly different. The intra-group comparison showed significant prolongation of QTcF after AL treatment. CONCLUSIONS: Clinically recommended doses of DP, AL, and AP may cause QT prolongation in some malaria patients but do not cause torsades de pointes ventricular tachycardia or other arrhythmias.

The role of Ly49+CD8 T-cells in the immune system is not clear. Previously, several papers suggested Ly49+CD8 T-cells as immunosuppressors, while multiple studies also suggested their role as potent participants of the immune response. The mechanism of Ly49 expression on CD8 T-cells is also not clear. We investigated phenotype, functions, and regulation of Ly49 expression on murine CD8 T-cells in both normal state and during LCMV infection. CD8 T-cells express different Ly49 receptors compared with NK-cells. In intact mice, Ly49+CD8 T-cells have a phenotype similar to resting central memory CD8 T-cells and do not show impaired proliferation and cytokine production. Conventional CD8 T-cells upregulate Ly49 receptors during TCR-induced stimulation, and IL-2, as well as IL-15, affect it. At the same time, Ly49+CD8 T-cells change the Ly49 expression profile dramatically upon re-stimulation downregulating inhibitory and upregulating activating Ly49 receptors. We observed the expression of Ly49 receptors on the virus-specific CD8 T-cells during LCMV infection, especially marked in the early stages, and participation of Ly49+CD8 T-cells in the anti-viral response. Thus, CD8 T-cells acquire Ly49 receptors during the T-cell activation and show dynamic regulation of Ly49 receptors during stimulation.

BackgroundThis study aimed to establish a traumatic hemorrhagic shock (THS) model in swine and examine pathophysiological characteristics in a dry-heat environment.MethodsForty domestic Landrace piglets were randomly assigned to four study groups: normal temperature non-shock (NS), normal temperature THS (NTHS), desert dry-heat non-shock (DS), and desert dry-hot THS (DTHS) groups. The groups were exposed to either normal temperature (25°C) or dry heat (40.5°C) for 3 h. To induce THS, anesthetized piglets in the NTHS and DTHS groups were subjected to liver trauma and hypovolemic shock until death, and piglets in the NS and DS groups were euthanized at 11 h and 4 h, respectively. Body temperature, blood gas, cytokine production, and organ function were assessed before and after environmental exposure at 0 h and at every 30 min after shock to death. Hemodynamics was measured post exposure and post-shock at 0 h and at every 30 min after shock to death.ResultsSurvival, body temperature, oxygen delivery, oxygen consumption, and cardiac output were significantly different for traumatic hemorrhagic shock in the dry-heat groups compared to those in the normal temperature groups. Lactic acid and IL-6 had a marked increase at 0.5 h, followed by a progressive and rapid increase in the DTHS group.ConclusionsOur findings suggest that the combined action of a dry-heat environment and THS leads to higher oxygen metabolism, poorer hemodynamic stability, and earlier and more severe inflammatory response with higher mortality.