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Objectives To investigate whether APETx2, a potent and selective inhibitor of ASIC3, regulates intestinal motility and visceral sensitivity in post-infectious irritable bowel syndrome (PI-IBS) mice through the 5-HT signalling pathway. Methods The PI-IBS model was established by Trichinella spiralis infection of NIH mice. APETx2(120 µg/kg) was administrated to PI-IBS mice by intraperitoneal injection once a day, lasting for 7 days. The gastrointestinal function of mice was assessed by the time of the first dark stool and the number of pellets defecated within 2 h. The visceral sensitivity was tested via abdominal withdrawal reflex. The protein levels of 5-HT and CRF in colon tissues were detected by immunohistochemistry. The changes in serum 5-HT and colon CRF contents were detected by ELISA. The mRNA levels of colon 5-HT4R and CRF were detected by RT-qPCR. The protein levels of colon 5-HT4R and dorsal root ganglion (DRG) ASIC3 were detected by Western blotting. Key findings The results indicated that APETx2 could markedly improve gastrointestinal function and visceral sensitivity in mice. Moreover, APETx2 could reduce the expression level of ASIC3 protein in the DRG of PI-IBS mice. APETx2 could increase the expression levels of 5-HT in serum and colon, CRF and 5-HT4R in the colon, and 5-HT4R in brain tissue in PI-IBS mice. Conclusions APETx2 can improve visceral sensitivity and intestinal motility in PI-IBS through 5-HT signalling pathway.

A novel reactive flame retardant based on L-cysteines containing P, N and S flame retardant elements was synthesized and used to improve the flame resistance of a density board made of poplar wood. The outcomes demonstrated the excellent flame retardancy and catalytic carbon formation of the poplar density board treated with the flame retardant. The thermogravimetric infrared coupler (TG-FTIR) test and thermal cracking gas mass spectrometer (Py-GC-MS) test both revealed that the flame retardant modified the thermal decomposition pathway of the wood, forming many residues and producing only a small amount of combustible gas. The ultimate oxygen index (LOI) of poplar density board treated with 20% cysteine-based flame retardant was as high as 60.9%. Scanning electron microscopy (SEM) images revealed that the surface of the treated wood powder was rough and that the wood powder particles were interconnected by the flame retardant. This suggests that the flame-retardant molecules have a bridging effect on the inner structure of the density board. Moreover, the cone calorimetry (CONE) experiments showed that with the flame retardant treatment, there was significant reduction of total heat release (THR) and heat release rate (HRR) of the density board. These findings demonstrate the effectiveness of the cysteine-based flame retardant.

ObjectivesWe aimed to identify the factors associated with necrotizing enterocolitis (NEC) and to assess the associations of the initial empirical antibiotic therapy (IEAT) duration and antibiotic therapy duration/hospital stay ratio (A/H ratio) before NEC with subsequent NEC in very low birth weight (VLBW) infants with gestational age less than 32 weeks without proven sepsis.MethodsA retrospective study was conducted at the NICU of the First Affiliated Hospital of Medical University of Anhui province from June 2015 to May 2022, and 567 VLBW infants with gestational age less than 32 weeks were included in the study. We divided the VLBW infants into those with and without NEC according to modified Bell’s criteria. We then used descriptive statistics to identify the factors associated with NEC and multivariate analyses to evaluate the associations of IEAT duration and A/H ratio with the occurrence of NEC.ResultsOf the 567 VLBW neonates admitted to our center, 547 survived and reached the normal discharge criteria. Fifty-one infants (8.99%) were diagnosed as showing NEC. Infants with NEC had a longer total parenteral nutrition time, total enteral nutrition time, and IEAT duration, as well as a higher A/H ratio than those without NEC. In multivariate analyses adjusted for the other factors, IEAT duration was associated with an increased odds of NEC [odds ratio (OR) = 1.267; 95% confidence interval (CI), 1.128–1.423], and the A/H ratio was also associated with increased odds of NEC (OR = 8.718; 95% CI, 2.450–31.030). For the A/H ratio, the area under the curve (AUC) was 0.767 and the ideal cutoff was 0.357, and the sensitivity and specificity were 0.843 and 0.645, respectively.ConclusionProlonged antibiotic therapy may increase the risk of NEC in VLBW infants with a gestational age of fewer than 32 weeks and should be used with caution.

Gastric cancer is the fifth most common cancer and the third leading cause of cancer death worldwide, posing a severe threat to human health. Surgical resection remains the most preferred option for gastric cancer treatment. However, for advanced gastric cancer, the curative effect of surgical resection is usually limited by the local recurrence, peritoneal carcinomatosis, or distal metastasis. Intraoperative chemotherapy is an attractive in situ adjuvant treatment strategy to reduce the recurrence and metastasis after surgical resection. Here, we designed a 5-fluorouracil (5-FU) and

Background The H5 subtype avian influenza virus (AIV) has caused huge economic losses to the poultry industry and is a threat to human health. A rapid and simple test is needed to confirm infection in suspected cases during disease outbreaks. Methods In this study, we developed a reverse transcription recombinase-aided amplification (RT-RAA) assay for the detection of H5 subtype AIV. Assays were performed at a single temperature (39 °C), and the results were obtained within 20 min. Results The assay showed no cross-detection with Newcastle disease virus or infectious bronchitis virus. The analytical sensitivity was 103 RNA copies/μL at a 95% confidence interval according to probit regression analysis, with 100% specificity. Compared with published reverse transcription quantitative real-time polymerase chain reaction assays, the κ value of the RT-RAA assay in 420 avian clinical samples was 0.983 (p Conclusions These results indicated that our RT-RAA assay may be a valuable tool for detecting H5 subtype AIV.

Wood is favored by furniture and decorative materials due to its beautiful color and texture, lightweight and high strength, but the thermal stability and flame retardants of wood have not been well solved. In this paper, metal salt-doped ammonium polyphosphate silicon gel (Cu, Mn/APP/Gel) was trapped in the wood cell wall and cell cavity by vacuum-pressure infusion method and vacuum drying method. Compared with unmodified wood, Cu, Mn/APP/Gel impregnated wood can rapidly enhance the flame retardant and smoke suppression capability of wood due to the catalysis of Cu2+ and Mn2+, and the total heat release rate, heat release rate peak value, mean heat release rate, smoke produce rate, total smoke release, CO and CO2 yield (YCO, YCO2) are obviously reduced. The electronic microscope picture of the burned carbon layer shows that the Cu, Mn/APP/Gel doped wood no longer has a clear and beautiful carbon layer formed by cell structure, but completely forms a whole. It is this dense and firm carbon layer structure that effectively inhibits the thermal decomposition of wood and has a role in flame retardant and smoke suppression. This study proposed an environment-friendly and green scheme for flame retardant modification of wood.

With the development of information and network technology, a new type of manufacturing paradigm, known as a service-oriented Cloud Manufacturing (CMfg), is emerged. In the CMfg paradigm, geographically distributed various manufacturing resources authorized by different companies are encapsulated as different manufacturing services (MSs) supported by the enabling technologies, such as cloud computing, Industrial Internet of Things, virtualization technologies, etc. MSs are provided according to the demands of manufacturing tasks (MTs) presented by various customers via the IoT (Internet of Things) in CMfg paradigm. Generally, one MS may complete one MT, but mostly one MT needs more MSs to complete it cooperatively. Furthermore, these MSs are perhaps controlled and managed by different enterprises. As an autonomous entity, each MS generally makes decision in light of its own interests, and their own interests generally have conflicts with the others' and the collective ones. To solve the conflicts through MSs' cooperation is an efficient and low-cost method to maximize both individual and collective interests. Hence, the influences of individual decision-making behaviors on cooperation are explored and discussed in CMfg paradigm. The evolutionary game theory and agent-based modeling and simulating method are employed to model and simulate individual behaviors of MSs during the process of forming the coalition for completing MTs. In addition, the learning mechanism of MSs is discussed in the decision-making process. The simulation results show that decision behaviors of MSs are positively influenced by the information transparency of the CMfg environment and the learning mechanism of MSs effects on the cooperative emergence.

Purpose Management response to consumer comments has become a widely adopted marketing strategy to address the undesirable effects caused by negative remarks. Yet, when and what management response is more effective and under what circumstances remains under-researched. This study aims to fill this gap. Design/methodology/approach In three experiments using five different products, the authors manipulate psychological construal level (psychological distance: distant vs proximal) and management response (response of primary vs secondary features) and thereafter assess their bearings on consumer psychological and behavioral reaction toward products of two distinctive natures (hedonic vs utilitarian). Findings At a psychological distance, consumers show a preferable reaction to management response of primary over secondary features. In contrast, when the psychological distance is proximal, consumers react more positively to management response of secondary than primary features. In addition, these effects vary as a function of product nature, hedonic vs utilitarian. Research limitations/implications The findings of this research bring a significant contribution to marketing communication literature and extend the construal level theory. Practical implications A better understanding of the relative effectiveness of distinct types of management response to negative consumer comments is essential for more targeted and effective marketing strategies. Originality/value Little research has documented the effects of distinct types of management response. How psychological distance might underpin these effects has not been explored. In addition, whether the interaction effect of management response and psychological distance varies with differences in product nature, namely, hedonic and utilitarian, remains unanswered until this research.

In this study, sulfonated carbon was obtained by sulfonating pine carbon with fuming sulfuric acid. Characterized by elemental analyzer, fourier transform infrared spectroscopy and X-ray photoelectron spectrometry, it showed that –SO3H was successfully bonded onto the pine carbon’ skeleton in the sulfonation reaction. The effects of pine carbon and sulfonated carbon on the catalytic carbonization and smoke suppression of sawdust boards, and its flame-retardant mechanism were investigated by cone calorimetry, thermogravimetric analysis, scanning electron microscopy, and pyrolysis–gas chromatography–mass spectrometry. And the results demonstrated that sawdust boards containing sulfonated carbon showed superior performance, determined by comparing the peak heat release rate, total heat release, smoke release rate, and total smoke product. Furthermore, with the addition of sulfonated carbon, a carbon layer was formed with a strong oxygen-containing hybrid structure and carbohydrate structure, the pyrolysis of sawdust boards was inhibited, and its char yield was increased.

Remanufacturing helps to protect the environment and reduce the manufacturing cost by making full use of end-of-life products, and it has been paid much attention nowadays. Disassembly, which is the key step of remanufacturing, is always manually executed due to the uncertainties faced in disassembly process. Recently, robotic disassembly is the research hotspot of remanufacturing research field and it helps to promote the automatic and intelligent developments of disassembly process. Cloud manufacturing helps to improve manufacturing efficiency by encapsulating manufacturing resources into services. Combined with cloud manufacturing and robotic disassembly, the framework and enabling technologies of cloud robotic disassembly (CRD) is proposed in this paper. The enabling technologies of CRD are introduced from the perspective of perception methods, modeling and data storage, planning and controlling services, service scheduling and interaction methods. This paper could provide guidelines to build the CRD.

To expand our understanding of the epidemiology of pigeon paramyxovirus type 1 (PPMV-1) in China, risk-based active surveillance was undertaken with pigeon swabs collected from live bird markets in 2014-2021. Seventy-six PPMV-1 strains were isolated from 12 provinces (60%) of the 20 provinces surveyed, and the positive rates of PPMV-1 varied from 0.50% to 3.19% annually. The complete genomic sequences of 18 representative viruses were analyzed, revealing a genome of 15,192 nucleotides, with the gene order 3'-NP-P-M-F-HN-L-5'. All isolates contained the

To observe the application effect of high-flow nasal canula oxygen therapy (HFNC) after extubation in patients with mechanical ventilation (MV) in the intensive care unit (ICU).A prospective study was conducted. From January 2018 to June 2020, 163 MV patients admitted to Yijishan Hospital of Wannan Medical College were enrolled, and they were divided into HFNC group (82 cases) and traditional oxygen therapy group (81 cases) according to the oxygen therapy model. The patients included in the study were given conventional treatment according to their condition. In the HFNC group, oxygen was inhaled by a nasal high-flow humidification therapy instrument. The gas flow was gradually increased from 35 L/min to 60 L/min according to the patient's tolerance, and the temperature was set at 34-37 centigrade. The fraction of inspiration oxygen (FiOThere was no significant differences in MV duration before extubation (days: 4.33±3.83 vs. 4.15±3.03), tracheal intubation duration (days: 4.34±1.87 vs. 4.20±3.35), ICU mortality [4.9% (4/82) vs. 3.7% (3/81)] and in-hospital stay [days: 28.93 (15.00, 32.00) vs. 27.69 (15.00, 38.00)] between HFNC group and traditional oxygen therapy group (all P0.05). The total MV duration in the HFNC group (days: 4.48±2.43 vs. 5.67±3.84) and ICU stay [days: 6.57 (4.00, 7.00) vs. 7.74 (5.00, 9.00)] were significantly shorter than those in the traditional oxygen therapy group, the reintubation duration of the HFNC group was significantly longer than that of the traditional oxygen therapy group (hours: 35.75±10.15 vs. 19.92±13.12), and the weaning failure rate was significantly lower than that of the traditional oxygen therapy group [4.9% (4/82) vs. 16.0% (13/81), all P0.05]. Among the reasons for weaning failure traditional oxygen therapy group had lower ability of airway secretion clearance than that of the HFNC group [8.64% (7/81) vs. 0% (0/82), P0.05], there was no statistically differences in the morbidity of heart failure, respiratory muscle weakness, hypoxemia, and change of consciousness between the two groups.For MV patients in the ICU, the sequential application of HFNC after extubation can reduce the rate of weaning failure and the incidence of adverse events, shorten the length of ICU stay.

A cage is the 1-skeleton of a convex polytope in ℝ3. A cage is said to hold a set if the set cannot be continuously moved to a distant location, remaining congruent to itself and disjoint from the cage. In how many positions can (compact 2-dimensional) unit discs be held by a tetrahedral cage? We completely answer this question for all tetrahedra.

This paper is about cages for compact convex sets. A cage is the 1-skeleton of a convex polytope in ?$\mathbb{R}^3$?. A cage is said to hold a set if the set cannot be continuously moved to a distant location, remaining congruent to itself and disjoint from the cage. In how many ''truly different'' positions can (compact 2-dimensional) discs be held by a cage? We completely answer this question for all tetrahedra. Moreover, we present pentahedral cages holding discs in a large number (57) of positions. Članek govori o kletkah za kompaktne konveksne množice. Kletka je 1-skelet konveksnega politopa v ?$\mathbb{R}^3$?. Pravimo, da kletka zadržuje množico, če se množice ne da zvezno premakniti na oddaljeno lokacijo tako, da bi ves čas ostala sama sebi kongruentna in disjunktna s kletko. Na koliko ''zares različnih'' položajih lahko kletka zadržuje (kompaktni 2-dimenzionalni) disk? Na to vprašanje popolnoma odgovorimo za vse tetraedre. Poleg tega predstavimo pentaederske kletke, ki zadržujejo diske na velikem številu (57) položajev.

In this study we employed self-designed PDLLA-PEG-PDLLA (PLEL) thermosensitive hydrogel to blend with norcantharidin (NCTD), a hydrophilic chemotherapeutic drug possessing curative effect on primary hepatocellular carcinoma (HCC) and adverse effects, then utilized the composite in HCC interstitial chemotherapy. PLEL copolymer was synthesized by ring-opening polymerization, NCTD-loaded PLEL hydrogel was prepared in a simple and reasonable way. The addition of NCTD had no significant effect on the temperature-dependent rheological properties of PLEL hydrogel. The pH values of NCTD-loaded gel solutions (13 wt%) and free NCTD solutions with three drug concentrations of 0.4 mg/mL, 0.8 mg/mL and 1.2 mg/mL under different storage conditions met the pH requirement of small-volume injection. There was no significant difference among the drug release behaviors of NCTD-loaded gels with drug concentrations of 0.4 mg/mL, 0.8 mg/mL and 1.2 mg/mL, they fitted first-order dynamics, exhibited significantly slower drug release than free drug solutions and the release was mainly based on drug diffusion. Drug-loaded gel solution (13 wt%) could evenly distribute throughout tumor tissue before converting into gel after being intratumorally injected and was able to significantly prolong retention time of the drug in tumor compared to free drug solution. The sustained-release performance of NCTD-loaded gel (13 wt%) was confirmed from the perspective of pharmacodynamics in vitro. The in vivo evaluation demonstrated that intratumoral injection of NCTD-loaded PLEL gel (13 wt%) was capable of improving curative effect of the drug and reducing its toxicity.

Let F be a family of sets in R d . A set M ⊂ R d is called F -convex if for any pair of distinct points x , y ∈ M , there is a set F ∈ F such that x , y ∈ F and F ⊂ M . A family F of compact sets is called complete if F contains all compact F -convex sets. Generalizing the definition in Yuan and Zamfirescu (2016), a compact set K will be called selfish, if the family F K of all sets similar to K contains all compact F K -convex sets. In this paper, we investigate the selfishness of rectangles, isosceles triangles, regular n -gons, and some finite sets.

The problem of finding short paths avoiding obstacles in a packing was extensively studied. Similar question concerning coverings received less attention. Here we consider locally finite coverings of the plane (i) by discs of radius 1, (ii) by squares of area 1. Given two discs (squares resp.) centered at x and $$x'$$ one can ask for the least number of discs (squares) needed to connect the given discs (squares resp.). Estimates of type $$(C + o(1)) d(x,x')$$ as the Euclidean distance $$ d(x,x') \rightarrow \infty $$ will be given. For discs we prove $$C= \frac{2}{\sqrt{3}} \thickapprox 1.15 \dots $$, for squares we prove $$C = 2\sqrt{2}$$. The latter constant turns out to be the best possible.

Pancreatic cancer is one of the most devastating cancers with poor prognosis and no significant change in the survival rate over the past decades. Localized targeted drug delivery through interventional endoscopic ultrasonography-guided fine-needle injection (EUS-FNI) is an attractive and minimally invasive strategy for inoperable pancreatic cancer. An injectable in-situ formed long-lasting drug delivery system is a promising alternative for the localized treatment of pancreatic cancer via EUS-FNI. Here, a biodegradable thermo-sensitive copolymer hydrogel for the co-delivery of anticancer agents gemcitabine (GEM) and cis-platinum (DDP) was developed. This hydrogel is a free flowable liquid at room temperature that changes into a semi-solid hydrogel following injection in response to the physiological temperature. Both in vitro and in vivo drug release behaviors indicate sustained drug release of this delivery system. Synergistic cellular proliferation inhibition and desirable apoptosis promotion have been found when pancreatic cancer Bxpc-3 cells were co-cultured with this GEM-DDP/hydrogel system. After a single intratumoral injection, the dual-drug loaded hydrogel formulation exhibited superior anti-tumor efficacy and minimized systemic side effect on pancreatic cancer xenograft mouse model in comparison to the intravenously injected free GEM and DDP combination. In addition, a strong synergistic therapeutic effect of the GEM-DDP/hydrogel system against pancreatic cancer has been found in vitro and in vivo compared to the single-drug loaded hydrogel composites. The obtained findings suggest this developed thermo-sensitive copolymer hydrogel system as a potential universal carrier for the localized targeted delivery of multi-drugs, for use in a variety of inoperable solid tumors.

Adenomyomatous polyps (APs) of the uterus (also termed polypoid adenomyomas and pedunculated adenomyomas) are exophytic proliferations composed of myomatous stroma admixed with endometrial glands. APs can be diagnostically challenging, mimicking polypoid neoplasms such as atypical polypoid adenomyoma and adenosarcoma. The purpose of this study was to describe the clinicopathological, morphologic, and molecular features of APs, as well as to raise awareness of this entity as a potential source of diagnostic confusion. We identified APs diagnosed at Brigham and Women's Hospital from 2000 to 2015. We reviewed histologic slides and obtained archival tissue for immunohistochemical and molecular studies. APs seen in consultation were associated with a broad differential, including adenosarcoma, atypical polypoid adenomyoma, and endometrial neoplasia. We performed a histologic review of 84 APs diagnosed at our institution and identified 2 distinct morphologic types of APs, which we have termed type 1 (with vaguely fascicular myomatous stroma intimately admixed with glands) and type 2 (containing a well-defined stalk of smooth muscle entrapping glands). Most APs exhibited CD10-positive (100%; 72/72) and desmin-positive (97%; 70/72) stroma. Diffuse caldesmon positivity was present in 97% (28/29) of type 2 polyps compared with 8% (3/39) of type 1 APs. APs did not harbor mutations in exon 2 of MED12. APs are not uncommon in routine practice and may be misinterpreted as more worrisome lesions. We identified 2 types of APs with distinct morphology and immunophenotype. The absence of MED12 exon 2 mutations suggests that the pathogenesis of APs is separate from uterine leiomyomas.

For each positive integer m and any convex body K , denote by γ m ( K ) the smallest positive number γ so that the boundary of K can be covered by m translates of γ K . It is proved that, for each positive integer m , γ m ( K ) is Lipschitz continuous on the space of affine equivalence classes of n -dimensional convex bodies endowed with the Banach–Mazur metric. Exact values of γ m ( K ) for particular choices of planar convex bodies K and positive integers m are also obtained. Moreover, a general way to estimate γ m ( K ) for centrally symmetric convex bodies is presented.

Breast cancer has become the most commonly diagnosed cancer type in the world. A combination of chemotherapy and photothermal therapy (PTT) has emerged as a promising strategy for breast cancer therapy. However, the intricacy of precise delivery and the ability to initiate drug release in specific tumor sites remains a challenging puzzle. Therefore, to ensure that the therapeutic agents are synchronously delivered to the tumor site for their synergistic effect, a multifunctional nanoparticle system (PCRHNs) is developed, which is grafted onto the prussian blue nanoparticles (PB NPs) by reduction-responsive camptothecin (CPT) prodrug copolymer, and then modified with tumor-targeting peptide cyclo(Asp- d -Phe-Lys-Arg-Gly) (cRGD) and hyaluronic acid (HA). PCRHNs exhibited nano-sized structure with good monodispersity, high load efficiency of CPT, triggered CPT release in response to reduction environment, and excellent photothermal conversion under laser irradiation. Furthermore, PCRHNs can act as a photoacoustic imaging contrast agent-guided PTT. In vivo studies indicate that PCRHNs exhibited excellent biocompatibility, prolonged blood circulation, enhanced tumor accumulation, allow tumor-specific chemo-photothermal therapy to achieve synergistic antitumor effects with reduced systemic toxicity. Moreover, hyperthermia-induced upregulation of heat shock protein 70 in the tumor cells could be inhibited by CPT. Collectively, PCRHNs may be a promising therapeutic way for breast cancer therapy.

Uterine carcinoma (UC) is the most common gynecologic malignancy in the United States. TP53 mutant UCs cause a disproportionate number of deaths due to limited therapies for these tumors and the lack of mechanistic understanding of their fundamental vulnerabilities. Here we sought to understand the functional and therapeutic relevance of TP53 mutations in UC. We functionally profiled targetable TP53 dependent DNA damage repair and cell cycle control pathways in a panel of TP53 mutant UC cell lines and patient-derived organoids. There were no consistent defects in DNA damage repair pathways. Rather, most models demonstrated dependence on defective G2/M cell cycle checkpoints and subsequent upregulation of Aurora kinase-LKB1-p53-AKT signaling in the setting of baseline mitotic defects. This combination makes them sensitive to Aurora kinase inhibition. Resistant lines demonstrated an intact G2/M checkpoint, and combining Aurora kinase and WEE1 inhibitors, which then push these cells through mitosis with Aurora kinase inhibitor-induced spindle defects, led to apoptosis in these cases. Overall, this work presents Aurora kinase inhibitors alone or in combination with WEE1 inhibitors as relevant mechanism driven therapies for TP53 mutant UCs. Context specific functional assessment of the G2/M checkpoint may serve as a biomarker in identifying Aurora kinase inhibitor sensitive tumors.

Simple Summary Cancers arising from the lining of the uterus, endometrial cancers, are the most common gynecologic malignancy in the United States. Once endometrial cancer escapes the uterus and grows in distant locations, there are limited therapeutic options. The most aggressive and lethal endometrial cancers carry alterations in the protein p53, which is a critical guardian of many cellular functions. The role of these p53 alterations in endometrial cancer is not well understood. The goal of this work was to use p53 altered models of endometrial cancer to understand which, if any, therapeutically targetable vulnerabilities these p53 alterations may confer in endometrial cancer. Here we show that many of these p53 altered cells have problems with cell division which can be targeted with novel single and combination therapies. These discoveries may lead to relevant new therapies for difficult to treat advanced stage endometrial cancers. Abstract Uterine carcinoma (UC) is the most common gynecologic malignancy in the United States. TP53 mutant UCs cause a disproportionate number of deaths due to limited therapies for these tumors and the lack of mechanistic understanding of their fundamental vulnerabilities. Here we sought to understand the functional and therapeutic relevance of TP53 mutations in UC. We functionally profiled targetable TP53 dependent DNA damage repair and cell cycle control pathways in a panel of TP53 mutant UC cell lines and patient-derived organoids. There were no consistent defects in DNA damage repair pathways. Rather, most models demonstrated dependence on defective G2/M cell cycle checkpoints and subsequent upregulation of Aurora kinase-LKB1-p53-AKT signaling in the setting of baseline mitotic defects. This combination makes them sensitive to Aurora kinase inhibition. Resistant lines demonstrated an intact G2/M checkpoint, and combining Aurora kinase and WEE1 inhibitors, which then push these cells through mitosis with Aurora kinase inhibitor-induced spindle defects, led to apoptosis in these cases. Overall, this work presents Aurora kinase inhibitors alone or in combination with WEE1 inhibitors as relevant mechanism driven therapies for TP53 mutant UCs. Context specific functional assessment of the G2/M checkpoint may serve as a biomarker in identifying Aurora kinase inhibitor sensitive tumors.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China, and rapidly spread worldwide. This new emerging pathogen is highly transmittable and can cause fatal disease. More than 35 million cases have been confirmed and the fatality was about 2.9% up to October 9 2020. However, the original and intermediate hosts of SARS-CoV-2 remain unknown. Here, a total of 3160 poultry samples collected from 14 provinces between September and December 2019 in China were tested for the purpose of traceable surveillance for SARS-CoV-2 infection. The results indicated that all samples were SARS-CoV-2 negative, and a total of 593 avian coronaviruses were detected, including 485 avian infectious bronchitis viruses, 72 duck coronaviruses and 36 pigeon coronaviruses. The positive rates of avian infectious bronchitis virus, duck coronavirus, and pigeon coronavirus were 15.35%, 2.28% and 1.14%, respectively. Our surveillance demonstrated the diversities of avian coronaviruses in China, and higher prevalence were also recognized in some regions. The possibility of SARS-CoV-2 originating from the known avian-origin coronaviruses can be preliminarily ruled out. More surveillance and research on avian coronaviruses should be strengthened for better understanding the diversity, distribution, cross-species transmission and clinical significance of these viruses.

The diagnosis of malignant tumors is essential for informing clinical decisions regarding therapeutic options. Current imaging and pathological diagnostic methods do not provide quantitative molecular information that is important in tumor identification. Moreover, pathological tissue analysis is dependent on unevenly distributed pathological features. The tumor microenvironment has been documented to have hydrogen peroxide (H

The H5 subtype Avian Influenza Virus has caused huge economic losses to the poultry industry and is a threat to human health. A rapid and simple test is needed to confirm infection in suspected cases during disease outbreaks. In this study, we developed a reverse-transcription recombinase-aided amplification assay for the detection of H5 subtype avian influenza virus. Assays were performed at a single temperature (39°C), and the results were obtained within 20 min. The assay showed no cross-detection with Newcastle disease virus or infectious bronchitis virus. The analytical sensitivity was 103 RNA copies per reaction at a 95% confidence interval according to probit regression analysis, with 100% specificity. Compared with published reverse-transcription quantitative real-time polymerase chain reaction assays, the κ value of the reverse transcription recombinase-aided amplification assay in 365 avian clinical samples was 0.970 (p < 0.001). The sensitivity for avian clinical sample detection was 94.44% (95%CI, 70.63% - 99.71%), and the specificity was 100% (95%CI, 98.64% - 100%). These results indicated that our reverse-transcription recombinase-aided amplification assay may be a valuable tool for detecting H5 subtype avian influenza virus.

Background: Rotavirus infection is still the leading cause of acute viral gastroenteritis in children under five years of age worldwide. It is also a serious public health concern in China. Objectives: This study aimed to obtain information about rotavirus diarrhea among hospitalized children in Hefei City, Anhui Province, China, in recent years. Methods: We conducted a retrospective study over four years (2015 - 2018) examining hospital admission records of rotavirus infections at the First Affiliated Hospital of Anhui Medical University in Hefei City of Anhui Province, China. Results: A total of 1,095 cases with acute viral gastroenteritis requiring hospital admission from January 2015 to December 2018 were analyzed. Among them, 276 cases were positive for rotavirus A infection, accounting for 25.21% of the total number of children suffering from acute diarrhea. The detection rate of rotavirus A was the highest in children aged 1 - 2 years. The peak month for rotavirus infection during 2015 - 2018 was December and January. The hospitalized children with rotavirus infection showed dehydration, electrolyte disorder, liver function abnormality, and myocardial enzyme abnormality. Conclusions: Rotavirus is still the first pathogen of acute viral diarrhea in children in Hefei, especially children < 2 years of age, which highlights the need for widespread rotavirus immunization in young children.

Most of the existing Chinese entity relation extraction models have adopted methods which are based on character or word input. However, the word-based input method ignores potential word information in the sentence, and the method based on word input will be affected by the spread of word segmentation errors. In order to solve these problem, we introduce a lattice model that can merge words and characters input and use BiGRU instead of BiLSTM. After comparative experiments, our model achieves better results.

An efficient Simaese network(SiaNet) with Phash for video vibration detection in the paper were formed, such a network can transform the images to feature vectors and by caculating the distance between two consecutive picture vectors to judge whether the video is in stable or vibrating state. The proposed SiaNet takes the network with excellent feature extraction performance such as vgg as the base network branch, Uses Phash to preprocess the images that previous frame and current frame of the input network to screen out the simple samples, and adds the SPP layer before the decision layer to increase the applicability and robustness of the network. Then, a technique called Contrasive Loss of Loss function was used in this article to reduce the distance between positive sample pairs and increase the distance between negative sample pairs. Finally, some experiments for the the SiaNet on 16000 electric meter pictures which were collected in the subway station machine room are utilized to demonstrate the validity of the proposed SiaNet with Phash.

Erlotinib (ERT), oral administration agents, is one of the most pivotal targeted drugs in the treatment of non‐small cell lung cancer (NSCLC); however, its poor solubility, low oral bioavailability, and capricious toxicity limit broader clinical applications. In this paper, a novel injectable matrix is prepared based on hollow mesoporous silica nanoparticles (HMSNs) and thermosensitive poly(d,l‐lactide)‐poly(ethylene glycol)‐poly(d,l‐lactide) (PDLLA‐PEG‐PDLLA, PLEL) hydrogel to encapsulate and localize the sustained release of ERT for improved efficacy against NSCLC. The test‐tube‐inversion method shows that this ERT‐loaded hydrogel composite (ERT@HMSNs/gel) presents as an injectable flowing solution under room temperature and transfers into a physically crosslinked non‐flowing gel structure at physiological temperature.The ERT@HMSNs/gel composite shows a much longer intratumoral and peritumoral drug retention by in vivo imaging study. Notably, this injectable drug delivery system (DDS) provides an impressive balance between antitumor efficacy and systemic safety in a mice xenograft model. The novel ERT loaded HMSNs/gel system may be a promising candidate for the in situ treatment of NSCLC. Moreover, this study provides a prospective platform for the design and fabrication of a nano‐scaled delivery system for localized anticancer therapies., A novel injectable composite is developed based on hollow mesoporous silica nanoparticles (HMSNs) and thermosensitive hydrogelpoly(d,l‐lactide)‐poly(ethylene glycol)‐poly(d,l‐lactide) (PDLLA‐PEG‐PDLLA, PLEL) via mixing them in proportion at room temperature. The obtained in situ drug delivery platform (HMSNs/gel) can gelate under body temperature, and is employed for localized and sustained delivery of small molecule, erlotinib (ERT), to significantly promote its therapeutic efficacy and ameliorate drug‐related toxicity.

Let K be a convex body in $${\mathbb {R}} ^d$$, with $$d = 2,3$$. We determine sharp sufficient conditions for a set E composed of 1, 2, or 3 points of $$\mathrm{bd}K$$, to contain at least one endpoint of a diameter of K. We extend this also to convex surfaces, with their intrinsic metric. Our conditions are upper bounds on the sum of the complete angles at the points in E. We also show that such criteria do not exist for $$n\ge 4$$ points.

With the development of network technology, the Internet has brought great convenience to people's daily lives. However, due to the rapid increase in the number of people using the Internet and the explosion of data volume, the server needs to handle high concurrent access and large amounts of data, which also brings great challenges to the performance of the network server. Server clusters and load balancing technologies have emerged at the historic moment, and have optimized the server performance in terms of hardware and software. Nginx, as an open source, lightweight and high-performance server, has been widely used in recent years for its high performance and ease of expansion. By learning the source code of Nginx, each module, the processing flow of HTTP, and the load balancing algorithms in Nginx, it was found that the algorithms of Nginx cannot feedback the real-time performance of the server, and dynamically adjust the server weight to suit the server performance. Therefore, a dynamic load balancing algorithm based on Nginx is proposed, which collects server load information in real time and dynamically adjusts weights.

With the development of society, many industries and professions are more comprehensive and intersecting. Different industries have their own requirements for students with comprehensive backgrounds. For graduates, they may not know the skills required for various occupations, or what kind of jobs and occupations they can take based on their existing knowledge and skills, even how to acquire these abilities after they know the requirements of the jobs they want. In this chapter, authors combine the existing method to predict hot jobs with the analysis of knowledge map, aiming to achieve accurate recommendation of learning path for those who want to find a job. This chapter will help job hunters gradually master skills, and ultimately achieve the goal of optimizing resource allocation and saving social resources.

Deoxynivalenol (DON) is a type B trichothecene mycotoxin that exerts multiple toxic effects on plants, animals and humans. Several reports have shown that DON leads to G2/M cell cycle arrest. However, its molecular mechanism is still unclear. In this study, we showed that DON induced strong G2/M cell cycle arrest in HepG2 cells, and the cell cycle-inhibitory protein p21 was highly upregulated by DON. Further analysis showed that the cell cycle regulating gene EGR1 was highly induced by DON and that EGR1 knockdown abolished the upregulation of p21 and G2/M cell cycle arrest. Furthermore, we showed that the induction of EGR1 was regulated by the stress-responsive transcription factor ATF3. ATF3ΔZip2a/2b, which is a DNA binding domain truncated isoform of ATF3, was upregulated by DON. ATF3 knockdown weakened the expression induction of EGR1 and G2/M cell cycle arrest by DON. Moreover, the upregulation of ATF3ΔZip2a/2 highly depended on the enhanced presence of histones H3K9ac and H3K27ac. H3K9ac and H3K27ac were enriched at the promoter region of ATF3 following the DON treatment, and the knocking down of the genes responsible for H3K9ac and H3K27ac abolished the upregulation of ATF3 by DON. In summary, we found that DON induced G2/M cell cycle arrest by sequentially inducing the expression of ATF3ΔZip2a/2b, EGR1 and p21, and EGR1 played an essential role in this process, which is a novel molecular mechanism of cell cycle arrest by DON and is important for understanding its toxicology.

Transdermal drug delivery refers to a means of delivering drugs through the surface of the skin for local or systemic treatment. The drug functions after absorption through the skin into the systemic circulation via capillary action at a certain rate. Use of traditional physical and chemical enhancers to improve the transdermal permeation rate by increasing drug solubility, diffusion coefficient, and reservoir effect is not feasible owing to the toxic side effects of the overuse of chemical penetration enhancers. Nano-formulations generally vary in size and range from 10 nm to 100 nm. The smaller particle size leads to increased drug permeability, stability, retention, and targeting, making nano-formulations suitable for transdermal drug delivery. The different applications of nano-formulations (vesicles or nanoparticles and nanoemulsions) have been widely studied. Here, the classification, characteristics, transdermal mechanism, and application of the most popular nano-formulations in transdermal drug delivery system are reviewed.

We say that a polytope has the Rupert property if we can make a hole large enough in to permit another copy of to pass through. In this article, we show that among the 13 Archimedean solids, 8 have...

Petroleum exploration has found that the Baiyun deep-water area of the Pearl River Mouth Basin (PRMB), China, holds abundant oil and gas resources with great prospects. However, conditions restricting offshore drilling in this area present significant challenges to the investigation of source rocks. Core samples are lacking, and any cuttings obtained are generally highly contaminated by drilling mud. As a result, the identification and evaluation of hydrocarbon sources in deep-water areas would be greatly aided by new techniques capable of reliably obtaining the geochemical characteristics of potential source rocks. This study combines catalytic hydropyrolysis (HyPy) and gas chromatography–isotope ratio mass spectrometry (GC–IRMS) to determine the carbon isotope composition of individual n-alkanes covalently bound in kerogen framework. Furthermore, it reconstructs the source and depositional environment of sedimentary organic matter in potential source rocks from the Baiyun deep-water area of the PRMB. The results indicate that the optimized degassing (i.e., degassing under high vacuum at 250 °C for 24 h) can effectively eliminate hydrocarbon contaminants in the kerogen. Determination by GC–IRMS of bound n-alkanes released from the degassed kerogen by HyPy can provide the molecular carbon isotope characteristics of the original organic matter in cuttings contaminated by drilling mud. The results improve the understanding of potential hydrocarbon source rocks in the Baiyun deep-water area of the PRMB.