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We gave the Hardy type identities and inequalities for the divergence type operator $ L_{f, V} $ on smooth metric measure spaces. Additionally, we improved a Rellich type inequality by using the improved Hardy type inequality. Our results improved and included many previously known results as special cases.

Protective vaccines are crucial for preventing and controlling coronavirus disease 2019 (COVID-19). Updated vaccines are needed to confront the continuously evolving and circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. These vaccines should be safe, effective, amenable to easily scalable production, and affordable. Previously, we developed receptor binding domain (RBD) dimer-based protein subunit vaccines (ZF2001 and updated vaccines) in mammalian cells. In this study, we explored a strategy for producing RBD-dimer immunogens in Pichia pastoris. We found that wild-type P. pastoris produced hyperglycosylated RBD-dimer protein containing four N-glycosylation sites in P. pastoris. Therefore, we engineered the wild type P. pastoris (GS strain) into GSΔOCH1pAO by deleting the OCH1 gene (encoding α-1,6-mannosyltransferase enzyme) to decrease glycosylation, as well as by overexpressing the HIS4 gene (encoding histidine dehydrogenase) to increase histidine synthesis for better growth. In addition, RBD-dimer protein was truncated to remove the R328/F329 cleavage sites in P. pastoris. Several homogeneous RBD-dimer proteins were produced in the GSΔOCH1pAO strain, demonstrating the feasibility of using the P. pastoris expression system. We further resolved the cryo-EM structure of prototype-Beta RBD-dimer complexed with the neutralizing antibody CB6 to reveal the completely exposed immune epitopes of the RBDs. In a murine model, we demonstrated that the yeast-produced RBD-dimer induces robust and protective antibody responses, which is suitable for boosting immunization. This study developed the yeast system for producing SARS-CoV-2 RBD-dimer immunogens, providing a promising platform and pipeline for the future continuous updating and production of SARS-CoV-2 vaccines.

Abstract The acute myeloid leukemia (AML) patients obtain limited benefits from current immune checkpoint blockades (ICBs), although immunotherapy have achieved encouraging success in numerous cancers. Here, we found that V-domain Ig suppressor of T cell activation (VISTA), a novel immune checkpoint, is highly expressed in primary AML cells and associated with poor prognosis of AML patients. Targeting VISTA by anti-VISTA mAb boosts T cell-mediated cytotoxicity to AML cells. Interestingly, high expression of VISTA is positively associated with hyperactive STAT3 in AML. Further evidence showed that STAT3 functions as a transcriptional regulator to modulate VISTA expression by directly binding to DNA response element of VISTA gene. We further develop a potent and selective STAT3 inhibitor W1046, which significantly suppresses AML proliferation and survival. W1046 remarkably enhances the efficacy of VISTA mAb by activating T cells via inhibition of STAT3 signaling and down-regulation of VISTA. Moreover, combination of W1046 and VISTA mAb achieves a significant anti-AML effect in vitro and in vivo. Overall, our findings confirm that VISTA is a potential target for AML therapy which transcriptionally regulated by STAT3 and provide a promising therapeutic strategy for immunotherapy of AML.

Abstract Benefitting from the maximum atom utilization efficiency, special size quantum effects and tailored active sites, single‐atom catalysts (SACs) have been promising candidates for bifunctional catalysts toward water splitting. Besides, due to the unique structure and properties, some amorphous materials have been found to possess better performance than their crystalline counterparts in electrocatalytic water splitting. Herein, by combining the advantages of ruthenium (Ru) single atoms and amorphous substrates, amorphous molybdenum‐based oxide stabilized single‐atomic‐site Ru (Ru SAs‐MoO3−x/NF) catalysts are conceived as a self‐supported electrode. By virtue of the large surface area, enhanced intrinsic activity and fast reaction kinetics, the as‐prepared Ru SAs‐MoO3−x/NF electrode effectively drives both oxygen evolution reaction (209 mV @ 10 mA cm−2) and hydrogen evolution reaction (36 mV @ 10 mA cm−2) in alkaline media. Impressively, the assembled electrolyzer merely requires an ultralow cell voltage of 1.487 V to deliver the current density of 10 mA cm−2. Furthermore, such an electrode also exhibits a great application potential in alkaline seawater electrolysis, achieving a current density of 100 mA cm−2 at a low cell voltage of 1.759 V. In addition, Ru SAs‐MoO3−x/NF only has very small current density decay in the long‐term constant current water splitting test.

Conventional membership inference attacks usually require a large number of queries of the target model when training shadow models, and this task becomes extremely difficult when the number of queries is limited. Aiming at the problem of insufficient training data for shadow models due to the limited number of queries, we propose a membership inference attack method based on generative adversarial networks (GAN). First, we use generative adversarial networks to augment the samples obtained by a small number of queries to expand the training data of the model; Secondly, we use the improved CNN to obtain shadow models that have a higher degree of fitting on different target model structures; Finally, we evaluate the accuracy of the proposed algorithm on XgBoost, Logistic, and neural network models using public datasets MNIST and CIFAR10 in a black-box setting, and the results show that our model has an average attack accuracy of 62% and 83%, respectively. It can be seen that, compared with the existing research methods, our model can obtain better attack effects under the condition of significantly reducing the number of queries, which shows the feasibility of our proposed method in membership inference attacks.

Abstract Background Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) of the pancreas are extremely rare. Their pathogenesis and molecular landscape are largely unknown. Here, we report a case of mixed pancreatic intraductal papillary mucinous neoplasm (IPMN) and well-differentiated neuroendocrine tumor (NET) and identify its genetic alterations by next-generation sequencing (NGS). Case presentation A fifty-year-old male was admitted into the hospital for evaluation of a pancreatic lesion detected during a routine examination. Abdominal ultrasound indicated a hypoechoic mass of 2.6 cm at the head of the pancreas. Malignancy was suspected and partial pancreatectomy was performed. Thorough histopathological examination revealed a mixed IPMN-NET. In some areas, the two components were relatively separated, whereas in other areas IPMN and NET grew in a composite pattern: The papillae were lined with epithelial cells of IPMN, and there were clusters of NET nests in the stroma of papillary axis. NGS revealed shared somatic mutations (KRAS, PCK1, MLL3) in both components. The patient has been uneventful 21 months after the surgery. Conclusions Our case provides evidence of a common origin for mixed IPMN-NET with composite growth features. Our result and literature review indicate that KRAS mutation might be a driver event underlying the occurrence of MiNEN. We also recommend the inclusion of mixed non-invasive exocrine neoplasms and neuroendocrine neoplasms into MiNEN.

Introduction: Composite pheochromocytoma/paraganglioma (CP) is a rare neoplasm with most cases presented as single reports. Little is known about its pathogenesis and relationship with ordinary pheochromocytoma (PCC) or paraganglioma (PGL). Our study is aimed at analyzing the status of SDH and ATRX and identifying novel genetic changes in CP. Methods: Eighteen CP cases were collected. SDH and ATRX status was screened by immunohistochemistry. Targeted region sequencing (TRS) was successfully performed on formalin-fixed paraffin-embedded tissues in two cases within 3 years. Based on the TRS result, Sanger sequencing of BRAF and HRAS was performed in fifteen cases (including the two cases with TRS performed), with three cases excluded due to the limited amount of tissue. Results: Histopathologically, all the cases were composite PCC/PGL-ganglioneuroma (GN). The GN components were either closely admixed or juxtapos ed with the PCC/PGL components, with a highly variable percentage (10–80%). All cases stained positive for SDHB and ATRX. HRAS and BRAF mutations were identified during TRS. In the subsequent Sanger sequencing, 20.0% (3/15) harbored BRAF mutations (K601E and K601N) and 46.7% (7/15) harbored HRAS mutations (Q61R, Q61L, G13R). The mutation rates were both significantly higher than reported in ordinary PCC/PGL. Conclusions: We demonstrated that composite PCC/PGL-GN might be a unique entity with frequent HRAS and BRAF mutations rather than genetic changes of SDH and ATRX. Our findings revealed the possible pathogenesis of composite PCC/PGL -GN and provided clues for potential treatment targets.

In this paper, we consider the following fractional equation with a gradient term $$(-\Delta)^{s} u(x)= f(x,u (x), \nabla u (x)),$$ in a bounded domain and the upper half space. Firstly, we prove the monotonicity and uniqueness of solutions to the fractional equation in a bounded domain by the sliding method. In order to obtain maximum principle on unbounded domain, we need to estimate the singular integrals define the fractional Laplacians along a sequence of approximate maximum points by using a generalized average inequality. Then we prove monotonicity and uniqueness of solutions to fractional equation in $\mathbb{R}^n_+$ by the sliding method. In order to solve the difficulties caused by the gradient term, some new techniques are developed. The paper may be considered as an extension of Berestycki and Nirenberg [J. Geom. Phys. 5(1988), 237–275].

Abstract Designing synergistic heterogeneous catalytic interfaces is the key to developing highly compatible pH‐universal electrocatalysts for complex chemical environments. Our theoretical calculation results demonstrate that the Ru‐Ru2P heterointerface can not only promote the redistribution of charges, but also reduce the d‐band center, and then enhances the adsorption capacity of the key intermediate. However, in situ and facile synthesis of Ru‐Ru2P heterostructures is severely limited by thermodynamic obstacles. Herein, we propose a molten salt‐assisted catalytic synthesis scheme, and successfully build a series of homologous metallic Ru‐Ru2P heterostructure catalysts with different molar ratios of Ru to P under atmospheric pressure and low‐temperature (400°C). The resultant Ru‐Ru2P with rich heterostructures show the Pt‐like HER performance in different pH media. Particularly, it is prominent under alkaline conditions (18 mV @ 10 mA cm−2), which outperforms the Pt catalyst (37 mV @ 10 mA cm−2). Furthermore, Ru‐Ru2P heterostructures also show certain potential in the electrolysis of seawater to produce hydrogen. This work represents a significant supplement of high‐efficiency pH‐universal HER catalysts, and provides a new light on interface engineering in energy technology fields and beyond.

This research was performed to obtain a safe and highly immunogenic Listeria strain and evaluate the biological characteristics of the deletion mutant. Based on homologous recombination technology, we constructed a deletion mutant Lm90-ΔinlB of L. monocytogenes. Meanwhile, we characterized its safety and protective efficacy against listeriosis infection in mice. The results showed that the virulence of Lm90-ΔinlB could significantly decrease compared with the parental strain (Lm90). The deletion strain retained hemolytic activity and induced CD8+ T cell response comparable to that of Lm90. Mice immunized with Lm90-ΔinlB were capable of stimulating specific CD8+ T cells to the listerial epitopes LLO91-99 and P60217-225 at levels equivalent to Lm90. Importantly, immunization of mice with Lm90-ΔinlB displayed good protection against listeriosis. In conclusion, strain Lm90-ΔinlB is a vaccine candidate with the potential to be more immunogenic yet considerably less toxic than the parental strain.

Abstract The rational construction of earth‐abundant and advanced electrocatalysts for oxygen evolution reaction (OER) is extremely desired and significant to seawater electrolysis. Herein, by directly etching Ni3S2 nanosheets through potassium ferricyanide, a novel self‐sacrificing template strategy is proposed to realize the in situ growth of NiFe‐based Prussian blue analogs (NiFe PBA) on Ni3S2 in an interfacial redox reaction. The well‐designed Ni3S2@NiFe PBA composite as precursor displays a unique spherical magic cube architecture composed of nanocubes, which even maintains after a phosphating treatment to obtain the derived Ni3S2/Fe‐NiPx on nickel foam. Specifically, in alkaline seawater, the Ni3S2/Fe‐NiPx as OER precatalyst marvelously realizes the ultralow overpotentials of 336 and 351 mV at large current densities of 500 and 1000 mA cm–2, respectively, with remarkable durability for over 225 h, outperforming most reported advanced OER electrocatalysts. Experimentally, a series of characterization results confirm the reconstruction behavior in the Ni3S2/Fe‐NiPx surface, leading to the in situ formation of Ni(OH)2/Ni(Fe)OOH with abundant oxygen vacancies and grain boundaries, which constructs the Ni3S2/Fe‐NiPx reconstruction system responsible for the remarkable OER catalytic activity. Theoretical calculation results further verify the enhanced OER activity for Ni3S2/Fe‐NiPx reconstruction system, and unveil that the Fe‐Ni2P/FeOOH as active origin contributes to the central OER activity.

Abstract Hitherto, there are almost no reports on the complete reconstruction in hydrogen evolution reaction (HER). Herein, the authors develop a new type of reconfigurable fluoride (such as CoF2) pre‐catalysts, with ultra‐fast and in‐depth self‐reconstruction, substantially promoting HER activity. By experiments and density functional theory (DFT) calculations, the unique surface structure of fluorides, alkaline electrolyte and bias voltage are identified as key factors for complete reconstruction during HER. The enrichment of F atoms on surface of fluorides provides the feasibility of spontaneous and continuous reconstruction. The alkaline electrolyte triggers rapid F− leaching and supplies an immediate complement of OH− to form amorphous α‐Co(OH)2 which rapidly transforms into β‐Co(OH)2. The bias voltage promotes amorphous crystallization and accelerates the reconstruction process. These endow the generation of mono‐component and crystalline β‐Co(OH)2 with a loose and defective structure, leading to an ultra‐low overpotential of 54 mV at 10 mA cm−2 and super long‐term stability exceeding that of Pt/C. Moreover, DFT calculations confirm that F− leaching optimizes hydrogen and water adsorption energies, boosting HER kinetics. Impressively, the self‐reconstruction is also applicable to other non‐noble transition metal fluorides. The work builds the fundamental comprehension of complete self‐reconstruction during HER and provides a new perspective to conceive advanced catalysts.

Abstract Hydrogen, a renewable and outstanding energy carrier with zero carbon dioxide emission, is regarded as the best alternative to fossil fuels. The most preferred route to large-scale production of hydrogen is by water electrolysis from the intermittent sources (e.g., wind, solar, hydro, and tidal energy). However, the efficiency of water electrolysis is very much dependent on the activity of electrocatalysts. Thus, designing high-effective, stable, and cheap materials for hydrogen evolution reaction (HER) could have a substantial impact on renewable energy technologies. Recently, single-atom catalysts (SACs) have emerged as a new frontier in catalysis science, because SACs have maximum atom-utilization efficiency and excellent catalytic reaction activity. Various synthesis methods and analytical techniques have been adopted to prepare and characterize these SACs. In this review, we discuss recent progress on SACs synthesis, characterization methods, and their catalytic applications. Particularly, we highlight their unique electrochemical characteristics toward HER. Finally, the current key challenges in SACs for HER are pointed out and some potential directions are proposed as well.

Abstract The exact solutions of the Riemann problem for a symmetric system of Keyfitz–Kranzer type are obtained in fully explicit forms. Furthermore, the global solutions of the double Riemann problems are also constructed explicitly when the initial data are taken to be three piecewise constant states. During the process of constructing the global solutions, all occurring wave interactions have been dealt with in detail by using the method of characteristics. In addition, it is shown that the Riemann solutions are stable with respect to the specific small perturbations of the Riemann initial data.

Zika virus (ZIKV)-specific T cells are activated by different peptides derived from virus structural and nonstructural proteins, and contributed to the viral clearance or protective immunity. Herein, we have depicted the profile of CD8+ and CD4+ T cell immunogenicity of ZIKV proteins in C57BL/6 (H-2b) and BALB/c (H-2d) mice, and found that featured cellular immunity antigens were variant among different murine alleles. In H-2b mice, the proteins E, NS2, NS3 and NS5 are recognized as immunodominant antigens by CD8+ T cells, while NS4 is dominantly recognized by CD4+ T cells. In contrast, in H-2d mice, NS1 and NS4 are the dominant CD8+ T cell antigen and NS4 as the dominant CD4+ T cell antigen, respectively. Among the synthesized 364 overlapping polypeptides spanning the whole proteome of ZIKV, we mapped 91 and 39 polypeptides which can induce ZIKV-specific T cell responses in H-2b and H-2d mice, respectively. Through the identification of CD8+ T cell epitopes, we found that immunodominant regions E294-302 and NS42351-2360 are hotspots epitopes with a distinct immunodominance hierarchy present in H-2b and H-2d mice, respectively. Our data characterized an overall landscape of the immunogenic spectrum of the ZIKV polyprotein, and provide useful insight into the vaccine development.

Objectives. Mixed neuroendocrine–non-neuroendocrine neoplasms (MiNENs) are rare gallbladder neuroendocrine neoplasms (GB-NENs). This study is aimed at investigating the clinicopathological features of GB-NENs and identifying prognostic factors related to overall survival (OS) of GB-MiNENs. Methods. The clinical data and pathological features of 13 patients with GB-NENs in our hospital were retrospectively reviewed. Additionally, 41 GB-MiNENs cases reported in English literature were reviewed and survival analysis was performed. Results. The mean age of thirteen patients (6 males and 7 females) with GB-NENs was 57.2 years (range: 35-75 years). Two patients were diagnosed with NET grade 1 (G1), two patients with NEC (large cell/small cell=1/1), and nine patients with MiNENs. Of these 9 patients with MiNENs, 8 had composite tumors and 1 had amphicrine carcinoma. Microscopically, the adenocarcinoma component was located in the surface mucosa, and the neuroendocrine component was in the area of deep invasion, liver infiltration, and lymph node metastasis. Total analysis of 41 GB-MiNENs showed that patients were mainly elderly women (female/male ratio, 2.4 : 1.0; median age, 60 years). Kaplan-Meier’s analysis demonstrated that liver metastasis and TNM stage III-IV were associated with decreased OS (P

Summary: Efficient electrocatalyst toward hydrogen evolution/oxidation reactions (HER/HOR) and oxygen reduction reaction (ORR) is desirable for water splitting, fuel cells, etc. Herein, we report an advanced platinum phosphide (PtP2) material with only 3.5 wt % Pt loading embedded in phosphorus and nitrogen dual-doped carbon (PNC) layer (PtP2@PNC). The obtained catalyst exhibits robust HER, HOR, and ORR performance. For the HER, a much low overpotential of 8 mV is required to achieve the current density of 10 mA cm−2 compared with Pt/C (22 mV). For the HOR, its mass activity (MA) at an overpotential of 40 mV is 2.3-fold over that of the Pt/C catalyst. Interestingly, PtP2@PNC also shows exceptional ORR MA which is 2.6 times higher than that of Pt/C and has robust stability in alkaline solutions. Undoubtedly, this work reveals that PtP2@PNC can be employed as nanocatalysts with an impressive catalytic activity and stability for broad applications in electrocatalysis.

Purpose: This study aimed to determine whether detecting elastic fibers in tumor stroma (EFTS) could be used as a new method for predicting the prognosis of gastric cancer (GC) patients.Materials and Methods: EFTS expression was determined by histochemistry in 160 GC patients who underwent gastrectomy. Based on the staining results, the patients were divided into three groups according to their EFTS expression level: low (n = 57), moderate (n = 50), and high (n = 53). The clinicopathological data and 6-year survival data were analyzed among different EFTS groups.Results: The expression of EFTS was closely related to lymphovascular invasion (P = 0.010), blood transfusion in operation (P < 0.001), recurrence rate (P < 0.001), and motility (P < 0.001). High expression of EFTS was also correlated with recurrence-free survival (RFS) and overall survival (OS) in GC patients by Kaplan–Meier curve (P < 0.001 for RFS and P < 0.001 for OS).Conclusions: Multivariate analysis showed that EFTS was an independent prognostic factor for RFS and OS. In conclusion, detecting EFTS to predict the prognosis of GC patients is effective and highly feasible.

Blood-brain barrier (BBB) characteristics are induced and maintained by cross-talk between brain microvessel endothelial cells and neighbouring elements of the neurovascular unit. It plays a primary role in a selective diffusion barrier at the level of the cerebral microvascular endothelium. Here, we have developed and characterized an in vitro model of the blood-brain barrier by seeding primary brain microvascular endothelial cells (BMECs) and astrocyte cells (ACs) from sheep on a polyester Transwell cell culture membrane with 0.4-μm pores, and conducted transepithelial electrical resistance measurements (TEER), leakage tests and assays for the permeability of horseradish peroxidase (HRP). The results of TEER and 4-h leakage assay showed that the new syngeneic BBB model had a characteristic of BBB in vivo. The HRP permeability test showed that the BBB model had good barrier function. Results showed that our model may be a valuable tool in the study of the mechanisms of brain invasion mediated by internalins of Listeria monocytogenes.

The high-altitude ecosystem of the Tibetan Plateau in China is a biodiversity hotspot that provides unique habitats for endemic and relict species along an altitudinal gradient at the eastern edge. Acquiring biodiversity information in this area, where the average altitude is over 4000 m, has been difficult but has been aided by recent developments in non-invasive technology, including infrared-triggered camera trapping. We used camera trapping to acquire a substantial number of photographic wildlife records in Wolong National Nature Reserve, Sichuan, China, from 2013 to 2016. We collected information of the habitat surrounding the observation sites, resulting in a dataset covering 37 species and 12 environmental factors. We performed a multivariate statistical analysis to discern the dominant environmental factors and cluster the mammals and birds of the ecosystem in order to examine environmental factors contributing to the species’ relative abundance. Species were generalized into three main types, i.e., cold-resistant, phyllophilic, and thermophilic, according to the identified key environmental drivers (i.e., temperature and vegetation) for their abundances. The mammal species with the highest relative abundance were bharal (Pseudois nayaur), Moupin pika (Ochotona thibetana), and Himalayan marmot (Marmota himalayana). The bird species with highest relative abundance were snow partridge (Lerwa lerwa), plain mountain finch (Leucosticte nemoricola), Chinese monal (Lophophorus lhuysii), and alpine accentor (Prunella collaris).

Rural human settlements are an integral part of a rural system. The evaluation of public feedback based on farmers’ satisfaction is a crucial way to understand the current situation of rural human settlements. This paper establishes a framework to evaluate local dwellers’ satisfaction towards the environment of rural human settlements in northwest China from six dimensions involving living conditions, the environment, physical infrastructure, public service, governance, and culture. The empirical study was conducted in Yanchi County, which demonstrates the applicability of this evaluating method. This study shows that the overall degree of satisfaction towards the environment of rural human settlements is relatively high, with a figure of 77.38. However, the satisfaction scores for the six dimensions are uneven, and there are significant differences between the villages. Further, these villages can be divided into three types according to the residents’ satisfaction, and viable strategies are suggested correspondingly. To sustain rural settlement development, the authors argue that more efforts should be put into technology advancement, public participation incentives, and the subsequent maintenance of projects in the long run.

Abstract In this paper we consider the following system of fractional nonlinear equations in the half space R + n ${R^{n}_{+}}$ : 1 { ( − Δ ) α 2 u 1 ( x ) = x n γ u 1 α 1 ( x ) u 2 β 1 ( x ) , x ∈ R + n , ( − Δ ) α 2 u 2 ( x ) = x n γ u 1 α 2 ( x ) u 2 β 2 ( x ) , x ∈ R + n , u 1 ( x ) = u 2 ( x ) = 0 , x ∉ R + n , $$ \textstyle\begin{cases} (-\Delta)^{\frac{\alpha}{2}}u_{1}(x)=x^{\gamma}_{n}u_{1}^{\alpha _{1}}(x)u_{2}^{\beta_{1}}(x), &\mbox{$ x \in R^{n}_{+}$},\\ (-\Delta)^{\frac{\alpha}{2}}u_{2}(x)=x^{\gamma}_{n}u_{1}^{\alpha _{2}}(x)u_{2}^{\beta_{2}}(x), &\mbox{$x \in R^{n}_{+}$},\\ u_{1}(x)=u_{2}(x)=0, &\mbox{$x \notin R^{n}_{+}$}, \end{cases} $$ where γ ≥ 0 $\gamma\geq0$ , 0 < α < 2 $0 0 $\beta_{i} >0$ , i = 1 , 2 $i=1,2$ . First, we use the Kelvin transform and the method of moving planes in integral forms to prove that (1) is equivalent to the following system of integral equations with 1 < α i + β i ≤ n + α + 2 γ n − α $1

Multiple human papillomavirus (HPV) genotypes often coexist within the cervical epithelia and are frequently detected together in various grades of the cervical neoplasia. To date, only a few reports exist on multiple HPV infections of HPV in Xinjiang Uygur Autonomous Region (XUAR). In the present study, we investigated the prevalence of High-Risk HPV (HR-HPV) genotypes and multiple infections. Cervical cytology samples were collected from 428 women who presented cervical abnormalities. Genotyping of HPV was performed by polymerase chain reaction-sequencing based typing (PCR-SBT) using consensus primers and specific primers. Of them, 166 samples were positive for HPV according to PCR results using the consensus primers. These samples contained cervical abnormalities enriched with inflammation (n = 107), cervical intraepithelial neoplasia (CIN) I (n = 19), CINII-III (n = 9) and cervical cancer (n = 31). Of the 166 HPV positive samples as determined by PCR analysis, 151 were further typed by PCR-SBT using 19 pairs of genotype-specific primers. Using this method, 17 different HR-HPV genotypes were identified. The most frequently observed HPV genotypes were HPV16 (44.0%, 73/166), 53 (28.9%, 48/166), 52 (25.3%, 42/166), 58 (22.3%, 37/166) and 35 (17.5%, 29/166). The proportions of single and multiple infections in the HPV-positive specimens were 34.9% and 65.1%, respectively. Multiple HPV types were most prevalent in the inflammatory state (63.0%), followed by cervical cancer (24.1%), CINI (11.1%), and CINII-III (1.9%). The results of our data analyses suggested that i) multiple HPV infection is not necessarily correlated with the severity of cervical abnormalities; and ii) among the multiple HPV infections, double infections combined with HPV16 is the most common. In addition, L1 full-length sequences of the top five high-risk HPV genotypes were amplified and sequenced. According to the L1 sequence of the epidemic genotypes that were amplified, we found that these genotypes contained the sequence point mutation, and that some of these genotypes further showed amino acid modifications. These results provide a basis for the construction of a polyvalent vaccine that is suitable for use in the XUAR, even in economically challenged communities located in China.

BACKGROUND:Dengue is the most prevalent arthropod-borne viral illness in humans with half of the world's population at risk. During early infancy, severe dengue can develop after a primary dengue virus infection. There has been a clinical observation that severe dengue during the first year of life is seen only in chubby infants. METHODOLOGY/PRINCIPAL FINDINGS:We examined the associations between the development of severe dengue and adipose tissue accumulation patterns during the first year of life in a prospective observational clinical study of infants and dengue virus infections. We found that adipose tissue contains two potential targets for dengue virus infection and production- adipocytes and adipose tissue macrophages. During the first year of life, total body adiposity and visceral adipose tissue stores were at their highest levels in early infancy. Early infancy was also characterized by a relative decrease in alternatively activated (anti-inflammatory) macrophages, and a relative increase in circulating pro-inflammatory cytokines. CONCLUSIONS/SIGNIFICANCE:The data has been used to propose a model where the adipose tissue accumulation pattern and pro-inflammatory environment during early infancy provide the conditions for the potential development of severe dengue in immune-susceptible infants.

Foot-and-mouth disease virus (FMDV) is an economically devastating viral disease leading to a substantial loss to the swine industry worldwide. A novel alternative strategy is to develop pigs that are genetically resistant to infection. Here, we produce transgenic (TG) pigs that constitutively expressed FMDV-specific short interfering RNA (siRNA) derived from small hairpin RNA (shRNA). In vitro challenge of TG fibroblasts showed the shRNA suppressed viral growth. TG and non-TG pigs were challenged by intramuscular injection with 100 LD50 of FMDV. High fever, severe clinical signs of foot-and-mouth disease and typical histopathological changes were observed in all of the non-TG pigs but in none of the high-siRNA pigs. Our results show that TG shRNA can provide a viable tool for producing animals with enhanced resistance to FMDV.

Urotensin II (UII), a somatostatin-like cyclic peptide, is involved in tumor progression due to its mitogenic effect. Our previous study demonstrated that UII and its receptor UT were up-regulated in human hepatocellular carcinoma (HCC), and exogenous UII promoted proliferation of human hepatoma cell line BEL-7402. Hepatic progenitor cell (HPCs) are considered to be one of the origins of liver cancer cells, but their relationship with UII remains unclear. In this work, we aimed to investigate the effect of UII on ROS generation in HPCs and the mechanisms of UII-induced ROS in promoting cell proliferation. Human HCC samples were used to examine ROS level and expression of NADPH oxidase. Hepatic oval cell line WB-F344 was utilized to investigate the underlying mechanisms. ROS level was detected by dihydroethidium (DHE) or 2', 7'-dichlorofluorescein diacetate (DCF-DA) fluorescent probe. For HCC samples, ROS level and expression of NADPH oxidase were significantly up-regulated. In vitro, UII also increased ROS generation and expression of NADPH oxidase in WB-F344 cells. NADPH oxidase inhibitor apocynin pretreatment partially abolished UII-increased phosphorylation of PI3K/Akt and ERK, expression of cyclin E/cyclin-dependent kinase 2. Cell cycle was then analyzed by flow cytometry and UII-elevated S phase proportion was inhibited by apocynin pretreatment. Finally, bromodeoxyuridine (Brdu) incorporation assay showed that apocynin partially abolished UII induced cell proliferation. In conclusion, this study indicates that UII-increased ROS production via the NADPH oxidase pathway is partially associated with activation of the PI3K/Akt and ERK cascades, accelerates G1/S transition, and contributes to cell proliferation. These results showed that UII plays an important role in growth of HPCs, which provides novel evidence for the involvement of HPCs in the formation and pathogenesis of HCC.

Abstract By using bioinformatics computer programs, all foot-and-mouth disease virus (FMDV) genome sequences in public-domain databases were analyzed. Based on the results of homology analysis, 2 specific small interfering RNA (siRNA) targeting homogenous 3D and 2B1 regions of 7 serotypes of FMDV were prepared and 2 siRNA-expression vectors, pSi-FMD2 and pSi-FMD3, were constructed. The siRNA-expressing vectors were used to test the ability of siRNAs to inhibit virus replication in baby hamster kidney (BHK-21) cells and suckling mice, a commonly used small animal model. The results demonstrated that transfection of BHK-21 cells with siRNA-expressing plasmids significantly weakened the cytopathic effect (CPE). Moreover, BHK-21 cells transiently transfected with short hairpin RNA (shRNA)-expressing plasmids were specifically resistant to the infection of the FMDV serotypes A, O, and Asia I and this the antiviral effects persisted for almost 48 hours. We measured the viral titers, the 50% tissue culture infective dose (TCID50) in cells transfected with anti-FMDV siRNAs was found to be lower than that of the control cells. Furthermore, subcutaneous injection of siRNA-expressing plasmids in the neck of the suckling mice made them less susceptible to infection with O, and Asia I serotypes of FMDV.

In this paper, we consider the following nonlinear fractional Kirchhoff equation... where 0 < s < 1, a > 0 and b = 0. We first establish a maximum principle for anti-asymmetric functions on any half space, and then obtain a Liouville theorem to the above nonlinear fractional Kirchhoff equations in the whole space. In particular, we derive key ingredients for proving the symmetry and monotonicity of positive solutions to the nonlinear fractional Kirchhoff equations, which indicate that fractional Kirchhoff De Giorgi conjecture is valid under some conditions. We believe that the results obtained here can be conveniently applied to study a variety of properties for solutions to fractional Kirchhoff equations. [ABSTRACT FROM AUTHOR]