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Abstract Spatial transcriptomics is an emerging technology that enables the profiling of gene expression in tissues while preserving spatial location information. This innovative approach is anticipated to provide a comprehensive understanding of the spatial distribution of different cells within tissues and facilitate in-depth analysis of tissue structure. To accurately recognize spatial domains from spatial transcriptomics, we have introduced a generalized deep learning method called GAAEST (Graph Attention-based Autoencoder for Spatial Transcriptomics). Our proposed approach effectively integrates both spatial location information and gene expression data from spatial transcriptomics. Specifically, it leverages spatial location details to construct a neighborhood graph and employs a graph attention network-based encoder to embed gene expression information into a spatially informed space. At the same time, to further optimize the learned potential embedding, self-supervised contrastive learning is introduced to capture spatial information at three levels: local, global and contextual feature of spots. Finally, the decoder reconstructs gene expressions, which are then clustered to identify spatial domains with similar expression patterns and spatial proximity. Based on our experiments conducted on multiple datasets, GAAEST consistently outperforms existing state-of-the-art methods. The proposed GAAEST demonstrates excellent capabilities in spatial domain recognition, positioning it as an ideal tool for advancing spatial transcriptomics research.

In this work, a new method of near-infrared curing 3D printing sodium silicate sands (NIRC3DPSSS) driven by photovoltaic cells was proposed, and the Span-80 moisture resistance modifier was studied. NIRC3DPSSS had the advantages of high strength, rapid curing and low residual strength. However, the 24h storage strength would reduce because Na+ in the bonding bridges could absorb moisture. The experimental results showed that the strength of Span-80 modified sands molds reached 0.95MPa after 4 hours in a humidistat with 99%RH (relative humidity) containing 2.2% sodium silicate, an increase of 97.9% comparing to common sands molds. In air(80%RH), the strength reached 1.25MPa, an increase of 40.4%. The optimal effect of modification was achieved when Span-80 was 0.066% of the raw sands. Additionally, the bonding film and bridges in sodium silicate sands modified with Span-80 were more stable, smoother and free of cracks when observed using scanning electron microscopy (SEM) and energy dispersive spectroscopy(EDS).

Abstract Aryl hydrocarbon receptor (AhR) plays an important role in inflammation and immunity as a new therapeutic target for infectious disease and sepsis. Punicalagin (PUN) is a Chinese herbal monomer extract of pomegranate peel that has beneficial anti-inflammatory, antioxidant and anti-infective effects. However, whether PUN is a ligand of AhR, its effect on AhR expression, and its signaling pathway remain poorly understood. In this study, we found that PUN was a unique polyphenolic compound that upregulated AhR expression at the transcriptional level, and regulated the AhR nongenomic pathway. AhR expression in lipopolysaccharide-induced macrophages was upregulated by PUN in vitro and in vivo in a time- and dose-dependent manner. Using specific inhibitors and siRNA, induction of AhR by PUN depended on sequential phosphorylation of 90-kDa ribosomal S6 kinase (p90RSK), which was activated by the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) and phosphoinositide-dependent protein kinase (PDK)1 pathways. PUN promoted p90RSK-mediated activator protein-1 (AP-1) activation. AhR knockout or inhibitors reversed suppression of interleukin (IL)-6 and IL-1β expression by PUN. PUN decreased Listeria load and increased macrophage survival via AhR upregulation. In conclusion, we identified PUN as a novel selective AhR modulator involved in AhR expression via the MEK/ERK and PDK1 pathways targeting p90RSK/AP-1 in inflammatory macrophages, which inhibited macrophage inflammation and promoted bactericidal activity.

PurposeTo evaluate the predictive value of the Controlling Nutritional Status (CONUT) score and Injury Severity Score (ISS) in assessing physiological abnormalities and outcomes in trauma patients.MethodsA retrospective analysis was conducted on 354 trauma patients. Physiological parameters were assessed, including cardiovascular function, inflammatory response, liver and kidney function, and nutritional status. The CONUT score and ISS were calculated for each patient. Binary logistic regression was used to identify independent predictors of trauma severity. Receiver operating characteristic (ROC) curve analysis evaluated the predictive accuracy of the CONUT and ISS scores for adverse outcomes.ResultsSeverely injured patients exhibited more significant abnormalities in cardiovascular function, inflammatory response, liver and kidney function, and nutritional status compared to those with minor injuries. These patients had significantly higher CONUT scores. Logistic regression analysis identified white blood cell count, hemoglobin, and CONUT score as independent predictors of trauma severity. ROC analysis showed that both CONUT and ISS scores effectively predicted adverse outcomes, with ISS demonstrating better specificity.ConclusionThe CONUT and ISS scores are effective tools for predicting physiological abnormalities and adverse outcomes in trauma patients. Incorporating these scores into clinical practice may enhance prognostic assessments and improve management strategies for trauma patients.

As the key interface, the nitrate removal capacity of riparian zones is receiving close attention. Although naturally occurring organic compounds in this environment play a pivotal role in shaping microbial communities and influencing the nitrate removal capacity, the relevant research is inadequate. Given the complexity of riparian environments, in this study, we added representative natural organic matter (fulvic acid, butyric acid, naphthalene, starch, and sodium bicarbonate) as carbon conditions and incorporated magnetite to simulate riparian zone components. The study investigated the nitrate degradation efficiency and microbial responses under different natural carbon conditions in real iron-containing environments. Butyric acid exhibited the most efficient nitrate reduction, followed in descending order by naphthalene, starch, sodium bicarbonate, and humic acid. However, this did not imply that butyric acid efficiently removed nitrogen; instead, the nitrogen would circulate in the environment in the form of ammonium. Denitrification and DNRA were the primary drivers of nitrate reduction in each system, while naphthalene and humic acid systems also exhibited nitrification and mineralization. Nitrogen-fixing bacteria represent a unique microbial community in the butyrate system. Further, the synergistic degradation of naphthalene and nitrate demonstrated significant potential applications. High-throughput sequencing revealed that carbon conditions exerted selective pressure on microorganisms, driving Fe (Ⅱ)/Fe (Ⅲ) transformation by shaping the microbial community structure and influencing the nitrogen cycling process.

Increased blood-brain barrier (BBB) permeability can lead to cerebral vasogenic edema and hemorrhagic transformation (HT) after reperfusion with tissue plasminogen activator (tPA), the only United States Food and Drug Administration (FDA)-approved treatment for acute ischemia stroke (AIS). The therapeutic benefits of tPA after AIS are partially outweighed by a more than a six-fold increase in the risk of symptomatic intracerebral hemorrhage. Therefore, strategies to protect the integrity of BBB are urgently needed to reduce HT and vasogenic edema after tPA thrombolysis or endovascular thrombectomy. Interestingly, an NIH study showed that smokers treated with tPA had a significantly lower prevalence of brain hemorrhage than nonsmokers, suggesting that cigarette smoking may protect patients treated with tPA from the side effects of cerebral hemorrhage. Importantly, we recently showed that treatment with nicotine reduces AIS-induced BBB damage and that modulating α7nAChR by modulation could reduce ischemia/reperfusion-induced BBB damage, suggesting that α7nAChR could be a potential target to reduce BBB after AIS. In this review, we first provide an overview of stroke and the impact of α7nAChR activation on BBB damage. Next, we discuss the features and mechanism of BBB destruction after AIS. We then discuss the effect of nicotine effect on BBB integrity as well as the mechanism underlying those effects. Finally, we discuss the side effects and potential strategies for modulating α7nAChR to reduce AIS-induced BBB damage.

Abstract Oracle bone script is an ancient Chinese writing system engraved on turtle shells and animal bones, serving as a valuable resource for interpreting ancient culture, history, and language. We introduce the Oracle-MNIST dataset, comprising of 28 × 28 grayscale images of 30,222 ancient characters from 10 categories, designed for benchmarking pattern classification, with particular challenges related to image noise and distortion. The training set totally consists of 27,222 images, and the test set contains 300 images per class. Oracle-MNIST follows the same data format with the original MNIST dataset, enabling direct compatibility with all existing classifiers and systems, but it constitutes a more challenging classification task than MNIST. The images of ancient characters suffer from (1) extremely serious and unique noises caused by three-thousand years of burial and aging and (2) dramatically variant writing styles by ancient Chinese, which all make them realistic for machine learning research.

The blood–brain barrier (BBB) impairment plays a crucial role in the pathological processes of aging-accompanied neurological diseases (AAND). Meanwhile, circadian rhythms disruption and gut microbiota dysbiosis are associated with increased morbidity of neurological diseases in the accelerated aging population. Importantly, circadian rhythms disruption and gut microbiota dysbiosis are also known to induce the generation of toxic metabolites and pro-inflammatory cytokines, resulting in disruption of BBB integrity. Collectively, this provides a new perspective for exploring the relationship among circadian rhythms, gut microbes, and the BBB in aging-accompanied neurological diseases. In this review, we focus on recent advances in the interplay between circadian rhythm disturbances and gut microbiota dysbiosis, and their potential roles in the BBB disruption that occurs in AAND. Based on existing literature, we discuss and propose potential mechanisms underlying BBB damage induced by dysregulated circadian rhythms and gut microbiota, which would serve as the basis for developing potential interventions to protect the BBB in the aging population through targeting the BBB by exploiting its links with gut microbiota and circadian rhythms for treating AAND.

Background: Although immunotherapy has shown potential in cancer treatment, current immunotherapeutics for bladder cancer are limited by a low response rate. Therefore, it is necessary to investigate other suitable immunotherapeutic targets and strategies for bladder cancer. Methods: To evaluate whether CD47 could be a suitable target for bladder cancer immunotherapy, CD47 protein expression levels in 116 bladder cancer tissue samples were assessed by IHC staining. In vitro anti-tumor effect of blocking CD47 was examined by phagocytosis assays. In vivo anti-tumor effects of targeting CD47 and angiogenesis were experimented in the HSPCs-CDX model. Results: We find that CD47 is highly expressed in bladder cancer samples and is associated with poor prognosis. Blocking CD47 could enhance the human PBMC-derived macrophages’ phagocytosis of T24 (from 10.40% to 29.70%) and 5637 (from 5.31% to 33.52%) human bladder cancer cells, as well as demonstrate anti-tumor effects in the HSPCs-CDX model (tumor growth inhibition rate, TGI: 33.05%). During CD47 treatment, we observed that the level of angiogenesis increased after CD47 blockade, and it might undermine the effect of CD47 immunotherapy. We then combined CD47 blockade with anti-angiogenic drugs to treat bladder cancer and discovered that inhibiting angiogenesis could further improve the anti-tumor effect of CD47 blockade (TGI: 76.39%). Finally, we tested the anti-tumor effect of co-targeting CD47 and angiogenesis using a bispecific fusion protein, SIRPα-VEGFR1, which successfully inhibited tumor growth to a similar extent as a combination therapy. Conclusions: Our study suggests that targeting CD47 could inhibit the growth of bladder cancer by promoting macrophage-mediated anti-tumor immunity. Moreover, blocking CD47 and angiogenesis could achieve a potent anti-tumor effect and could be an effective immunotherapy strategy for bladder cancer.

The advancement of deep learning has resulted in significant improvements on various visual tasks. However, deep neural networks (DNNs) have been found to be vulnerable to well-designed adversarial examples, which can easily deceive DNNs by adding visually imperceptible perturbations to original clean data. Prior research on adversarial attack methods mainly focused on single-task settings, i.e., generating adversarial examples to fool networks with a specific task. However, real-world artificial intelligence systems often require solving multiple tasks simultaneously. In such multi-task situations, the single-task adversarial attacks will have poor attack performance on the unrelated tasks. To address this issue, the generation of multi-task adversarial examples should leverage the generalization knowledge among multiple tasks and reduce the impact of task-specific information during the generation process. In this study, we propose a multi-task adversarial attack method to generate adversarial examples from a multi-task learning network by applying attention distraction with gradient sharpening. Specifically, we first attack the attention heat maps, which contain more generalization information than feature representations, by distracting the attention on the attack regions. Additionally, we use gradient-based adversarial example-generating schemes and propose to sharpen the gradients so that the gradients with multi-task information rather than only task-specific information can make a greater impact. Experimental results on the NYUD-V2 and PASCAL datasets demonstrate that the proposed method can improve the generalization ability of adversarial examples among multiple tasks and achieve better attack performance.

Isoflavones are a class of natural products that exhibit a wide range of interesting biological properties, including antioxidant, hepatoprotective, antimicrobial, and anti-inflammatory activities. Scandenone (1), osajin (2), and 6,8-diprenylgenistein (3) are natural prenylated isoflavones that share the same polyphenol framework. In this research, the key intermediate 15 was used for the synthesis of the natural isoflavones 1–3, establishing a stereoselective synthetic method for both linear and angular pyran isoflavones. The antibacterial activities of 1–3 were also evaluated, and all of them displayed good antibacterial activity against Gram-positive bacteria. Among them, 2 was the most potent one against MRSA, with a MIC value of 2 μg/mL, and the SEM assay indicated that the bacterial cell membranes of both MRSA and E. faecalis could be disrupted by 2. These findings suggest that this type of isoflavone could serve as a lead for the development of novel antibacterial agents for the treatment of Gram-positive bacterial infections.

Soybean fermentation has a balancing effect on the regulation of intestinal flora. Relative research between fermented soybeans and intestinal microbiota is limited. Our aim was to explore the effects of soybean fermented fowder on lipopolysaccharide (LPS) induced intestinal microflora and corresponding functions in loach. 16S rDNA high-throughout sequencing was applied to estimate differences in the intestinal microbiota and predict genes function. Analysis of the overall of sequencing data showed that the ratio of Effective Tags in both the control group and the treatment group was greater than 80 %. Based on six major classifications involved in the phylum, class, order, family, genus, and species, we acquired the changes in the composition of intestinal microorganisms after the supplement of soybean fermented powder. These results showed that the dominant bacteria in the two groups were basically distinct at different levels. Alpha diversity analysis indicated that the microbial richness and uniformity of soybean fermented powder decreased compared to the control group. PICRUSt and Taxfun tools analysis of intestinal flora illustrated the functional genes of the six groups were mainly involved in metabolism, genetic information processing, cellular processes, environmental information processing, and human diseases at the level 1. These data clearly demonstrated the effect of soybean fermented powder on the gut microbiome. Not only that, it provides new ideas and insights for achieving high-quality utilization of soybean fermented powder. The potential mechanisms of soybean fermented powder to alter gut flora and intestinal microbiome function can further be explored.

Abstract Objective We aimed to estimate the prevalence of CRFs and investigate its associated social-economic factors among adults in coastal areas of Qinzhou, Guangxi. Methods A representative sample of 1836 participants aged 20 to 70 years was included in Qinzhou, Guangxi in 2020. Data were collected by the questionnaire, anthropometric and laboratory measurements. The prevalence of CRFs, including hypertension, dyslipidemia, diabetes, overweight or obesity, alcohol consumption, and smoking were calculated by standardization. The multivariate logistic regression analysis was performed to explore the independent factors associated with the presence of CRFs. Results The age-standardized prevalence of hypertension, dyslipidemia, diabetes, overweight or obesity alcohol consumption, and smoking was 42.7%, 39.5%, 0.9%, 38.5%, 18.4% and 15.7%, respectively. The prevalence of clustering of at least one and at least two cardiovascular disease risk factors were 82.2% and 45.3% in total. There were differences in the aggregation of cardiovascular risk factors among different age, education, and income levels. There appeared higher clustering of at least one and at least two CRFs among adults with lower education level, higher income level and those elderly. Conclusions Compared with other regions in China, a higher prevalence of CRFs exists among adults in Guangxi and several social-economic factors were associated with the presence of CRFs. These findings suggest that we should implement effective measures to control the CRFs, to reduce the risk of cardiovascular disease in adults.

Geological heritage is an important part of natural resources. Properly handling the relationship between protection and utilization of geological heritage in a high urbanization level area is one of the ecological measures to promote the high-quality development of new urbanization. However, the low level of geological heritage survey, unclear family background, lack of standard classification scheme and overall evaluation restrict the effective development of geological heritage protection and utilization in Tianjin. Based on the latest data of the whole Tianjin geological heritage survey, and through the integration of previous geological heritage survey results, this paper classifies the types of geological heritage according to the Specification for Geological Heritage Survey （DZ/T 0303—2017）. The scientific research value, ornamental value and protection value are qualitatively analyzed, and the quantitative evaluation and grade division are carried out by combining expert scoring and AHP. According to the classification scheme in the Specification for Geological Heritage Survey （DZ/T 0303—2017）, the important geological heritages in Tianjin are divided into 3 main categories: basic geological category, geomorphic landscape category and geological disasters, 7 categories: stratigraphic section, important rock and ore producing areas, rock and soil geomorphology, structural geomorphology, water geomorphology, coastal geomorphology and geological disaster heritages, 10 subclasses: stratotype (typical section), typical deposit outcrop, intrusive rock landform, clastic rock landform, carbonate rock landform, wetland, klippe, fault cliff, marine landform and land subsidence. The comprehensive evaluation and analysis indicate that there are 4 world-level, 3 national-level and 8 provincial-level geological heritages in Tianjin. The above research is expected to provide references for the protection and utilization of geological heritages in Tianjin.

The structural characteristics of karst conduit have an important influence on the rational use and protection of karst water resources and the safe construction of underground engineering. At present, when using tracer test curve to analyze the structural characteristics of karst conduit, there are some problems, such as curve superposition shape, blunt front shape, irregular rise and fall of curve, connection relationship between multiple karst conduit, location of underground lake and groundwater state. In this paper, the time concentration curve of tracer test is used to explain the structural characteristics of karst conduit through the numerical simulation of the karst conduit flow tracer test and the change of water flow state. The results are as follows: (1) The number of curve peaks corresponds to the number of karst conduit, and there are three models for the parallel curve of double pipelines due to the difference of the length and velocity of karst conduit runoff. (2) The number of single karst conduit curve decline gradients corresponds to the number of blue hole, and the relationship between the decline gradients and the number of blue hole should be analyzed for multiple karst conduit in combination with the number of karst conduit and the location of blue hole. There are four types of parallel karst conduits. (3) The rapid change of curve shape indicates the mutual transformation of surface flow and pressure flow.

Abstract Background Switchgrass (Panicum virgatum L.) is an important bioenergy and forage crop. The outcrossing nature of switchgrass makes it infeasible to maintain a genotype through sexual propagation. Current asexual propagation protocols in switchgrass have various limitations. An easy and highly-efficient vegetative propagation method is needed to propagate large natural collections of switchgrass genotypes for genome-wide association studies (GWAS). Results Micropropagation by node culture was found to be a rapid method for vegetative propagation of switchgrass. Bacterial and fungal contamination during node culture is a major cause for cultural failure. Adding the biocide, Plant Preservative Mixture (PPM, 0.2%), and the fungicide, Benomyl (5 mg/l), in the incubation solution after surface sterilization and in the culture medium significantly decreased bacterial and fungal contamination. In addition, “shoot trimming” before subculture had a positive effect on shoot multiplication for most genotypes tested. Using the optimized node culture procedure, we successfully propagated 330 genotypes from a switchgrass GWAS panel in three separate experiments. Large variations in shoot induction efficiency and shoot growth were observed among genotypes. Separately, we developed an in planta node culture method by stimulating the growth of aerial axillary buds into shoots directly on the parent plants, through which rooted plants can be generated within 6 weeks. By circumventing the tissue culture step and avoiding application of exterior hormones, the in planta node culture method is labor- and cost-efficient, easy to master, and has a high success rate. Plants generated by the in planta node culture method are similar to seedlings and can be used directly for various experiments. Conclusions In this study, we optimized a switchgrass node culture protocol by minimizing bacterial and fungal contamination and increasing shoot multiplication. With this improved protocol, we successfully propagated three quarters of the genotypes in a diverse switchgrass GWAS panel. Furthermore, we established a novel and high-throughput in planta node culture method. Together, these methods provide better options for researchers to accelerate vegetative propagation of switchgrass.

Abstract Background Systematic pelvic lymphadenectomy or whole pelvic irradiation is recommended for the patients with stage IB1 cervical cancer. However, the precise pattern of lymphatic tumor spread in cervical cancer is unknown. In the present study we evaluated the distribution of nodal metastases in stage IB1 cervical cancer to explore the possibilities for tailoring cancer treatment. Methods A total of 289 patients with cervical cancer of stage IB1, according to FIGO 2009, were retrospectively analyzed. All patients underwent laparoscopic radical hysterectomy (Querleu and Morrow type C2) and systematic pelvic lymphadenectomy with or without para-aortic lymphadenectomy (level 2 or level 3 according to Querleu and Morrow) from October 2014 to December 2017. Lymph nodes removed from 7 well-defined anatomical locations as well as other tissues were examined histopathologically, and typed, graded, and staged according to the WHO/IARC classification. Results Totally 8314 lymph nodes were analyzed with the average number of 31.88 ± 10.34 (Mean ± SD) lymph nodes per patient. Nodal metastases were present in 44 patients (15.22%). The incidence of lymphatic spread to different anatomic sites ranged from 0% (presacral) to 30.92% (obturator nodes). Tumor size above 2 cm, histologically proven lymphovascular space involvement (LVSI) and parametrial invasion were shown to be significantly correlated with the higher risk of lymphatic metastasis, while obesity (BMI ≥ 25) was independently negatively associated with lymphatic metastases. Conclusions The incidence of lymph node metastasis in patients with stage IB1 cervical cancer is low but prognostically relevant. Individual treatment could be considered for the selected low-risk patients who have smaller tumors and obesity and lack of the parametrial invasion or LVSI.

BackgroundHost-microbiota crosstalk has been implicated in multiple host metabolic pathway axes that regulate intestinal barrier function. Although constitutive cytochrome P4501A1 (CYP1A1) expression perturbs the microbiome-derived autoregulatory loop following enteric infection, little is known about the role of host CYP1A1 in modulating gut microbiome-mediated signaling during methicillin-resistant Staphylococcus aureus (MRSA)-induced abdominal sepsis and its effects on intestinal barrier integrity.MethodsAbdominal sepsis was induced by the intraperitoneal injection of MRSA in mice. The effect of CYP1A1 deficiency on gut barrier integrity was investigated using RNA sequencing, microbiome analyses, and targeted metabolomics. The microbiota-produced metabolites were validated in patients with sepsis and persistent MRSA infection.ResultsMice lacking CYP1A1 exhibited an altered gut microbiome, a reduced metabolic shift from lysine to cadaverine in the caecal contents and antimicrobial molecule production (Retnlb, Gbp7, and Gbp3), and they were protected against gut barrier disruption when subjected to MRSA challenge. These beneficial effects were validated in aryl hydrocarbon receptor (AHR) knockout (KO) mice by cohousing with CYP1A1 KO mice and abrogated after supplementation with cadaverine or Enterococcus faecalis, the primary microbiota genus for cadaverine synthesis. Antibiotic-driven gut dysbacteriosis impaired the survival benefit and disrupted the intestinal barrier integrity in CYP1A1 KO mice after MRSA infection. Furthermore, increased cadaverine levels in feces and serum were detected in critically ill patients with gut leakiness during persistent MRSA infection, whereas cadaverine was not detected in healthy controls. Additionally, microbiota-derived cadaverine induced enterocyte junction disruption by activating the histamine H4 receptor/nuclear factor-κB/myosin light-chain kinase signaling pathway.ConclusionThis study revealed the unexpected function of host CYP1A1 in microbiota-mediated cadaverine metabolism, with crucial consequences for dysbacteriosis following MRSA-induced abdominal sepsis, indicating that inhibiting CYP1A1 or blocking cadaverine-histamine H4 receptor signaling could be a potential therapeutic target against abdominal sepsis.Clinical Trial Registration[http://www.chictr.org.cn/index.aspx], identifier [ChiCTR1800018646].

A novel 4/8 subtype α-conotoxin, Vt1.27 (NCCMFHTCPIDYSRFNC-NH2), was identified from Conus vitulinus in the South China Sea by RACE methods. The peptide was synthesized and structurally characterized. Similar to other α-conotoxins that target neuronal nicotinic acetylcholine receptor (nAChR) subtypes, Vt1.27 inhibited the rat α3β2 nAChR subtype (IC50 = 1160 nM) and was inactive at voltage-gated sodium and potassium channels in rat sensory neurons. However, Vt1.27 inhibited high voltage-activated N-type (CaV2.2) calcium channels expressed in HEK293T cells with an IC50 of 398 nM. An alanine scan of the peptide showed that residues Phe5, Pro9, Ile10, and Ser13 contribute significantly to the inhibitory activity of Vt1.27. The molecular dockings indicate that Vt1.27 inhibits the transmembrane region of CaV2.2, which is different from that of ω-conotoxins. Furthermore, Vt1.27 exhibited potent anti-allodynic effect in rat partial sciatic nerve injury (PNL) and chronic constriction injury (CCI) pain models at 10 nmol/kg level with the intramuscular injection. The pain threshold elevation of Vt1.27 groups was higher than that of α-conotoxin Vc1.1 in CCI rat models. These findings expand our knowledge of targets of α-conotoxins and potentially provide a potent, anti-allodynic peptide for the treatment of neuropathic pain.

Battery storage is one of the important units in the optimal scheduling of integrated energy systems. To give full play to the advantages of battery storage in stabilizing power quality and smoothing the output of intermittent new energy generation, the battery life decay problem needs to be considered in optimal scheduling. In this paper, we studied the energy storage life decay model and established an electric–gas integrated energy system model considering energy storage life decay to minimize the economic cost of system operations and to compare the optimal dispatch results with and without energy storage life decay through simulation analysis to verify the rationality and economy of the energy storage life decay model used in this paper.

Polycyclic aromatic hydrocarbons (PAHs) such as naphthalene (Nap) and phenanthrene (Phe) are organic pollutants of concern owing to their toxicity, carcinogenicity, and teratogenicity. Biodegradation is considered the most economical and efficient process to remediate Nap and Phe. The riparian zone between a river and a riparian aquifer, which is rich in indigenous microorganisms, may be important for PAH remediation. However, few studies have evaluated the ability of indigenous microorganisms to remove Nap and Phe. In this study, focusing on the typical PAHs (Nap and Phe) as target pollutants, the genus-level community structure of Nap- and Phe-degrading bacteria was identified. Batch static and dynamic biodegradation experiments were conducted to explore the biodegradation mechanisms of Nap and Phe in the riparian zone and identify the factors influencing Nap and Phe biodegradation in the binary system (i.e., where Nap and Phe are simultaneously present). According to the genus-level community structure test results, the dominant bacterial genus in the binary system was mainly the Phe-degrading bacteria. The Nap and Phe-biodegradation percentages were 19.20% lower and 19.49% higher, respectively, in the binary system than in the unitary system. The results indicated that functional bacteria can degrade Nap and Phe, and that Nap weakly promoted Phe biodegradation. Additionally, the initial Nap and Phe concentration ratio, hydraulic gradient, and temperature affected Nap and Phe biodegradation. Dynamic biodegradation experiments showed that the biodegradation percentage decreased as the hydraulic gradient increased, and biodegradation percentage of Phe was always higher than that of Nap. According to the results of the dynamic laboratory experiments, the removal percentages of Nap and Phe by indigenous riparian-zone microorganisms were 6.21–16.73% and 13.95–24.45%, respectively. The findings in this study will be useful for alleviation of Nap and Phe pollution in groundwater and will facilitate determination of appropriate treatment measures for groundwater exposed to this type of pollution.

BackgroundCX3CL1 is a chemokine that may play important roles in cancer immune regulation. Its mechanism in bladder cancer (BCa) is poorly understood. The objective of the current study was to evaluate the association between CX3CL1 and BCa and the related biological mechanisms.MethodsA total of 277 patients with BCa were enrolled in the present study. The association between CX3CL1 expression and disease outcome was evaluated. In vitro and in vivo experiments were performed using the TCCSUP cell line to investigate the function of CX3CL1 in BCa.ResultsCompared with low expression, high expression of CX3CL1 was significantly associated with poorer progression-free survival (hazard ratio [HR]=2.03, 95% confidence interval [95% CI]: 1.26-3.27, P=0.006), cancer-specific survival (HR=2.16, 95% CI: 1.59-2.93, P

Face alignment is a crucial step in face recognition. Through making the position of face consistent, face alignment reduces intra-class variability due to factors such as lighting, background, pose, and perspective transformation, and further facilitating the recognition tasks. In this paper, we propose a new face alignment method for pose-invariant face recognition, called adaptive pose alignment (APA), which can greatly reduce the intra-class difference and correct the noise caused by the traditional method in the alignment process, especially in unconstrained settings. Instead of aligning all faces to the pre-defined, uniform frontal shape, we adaptively learn the alignment templates according to the facial poses and then align each face of training or testing sets to its related template. To further improve face recognition performance, we propose a simple, yet effective feature normalization method which can generate more discriminative feature representation of a face or a set of faces (template) combined with the APA method. Furthermore, we introduce a pose-invariant face recognition pipeline that sequentially applies APA-based alignment, deep representation by softmax or ArcFace loss function, and the effective feature normalization procedure. We empirically show that APA-based images can accelerate the training of deep face recognition model by aligning all the images to the optimal templates. Moreover, experimental results show that the proposed method achieves the state-of-the-art performance on popular challenging face datasets including IJB-A, IJB-C, and CPLFW datasets.

Feature extraction is vital for face recognition. In this paper, we focus on the general feature extraction framework for robust face recognition. We collect about 300 papers regarding face feature extraction. While some works apply handcrafted features, other works employ statistical learning methods. We believe that a general framework for face feature extraction consists of four major components: filtering, encoding, spatial pooling, and holistic representation. We analyze each component in detail. Each component could be applied in a task with multiple levels. Then, we provide a brief review of deep learning networks, which can be seen as a hierarchical extension of the framework above. Finally, we provide a detailed performance comparison of various features on LFW and FERET face database.

One major topic for robust face recognition could be the efficient encoding of facial descriptors. Among various encoders, Fisher vector (FV) is one of the probabilistic methods that yield promising results. However, its huge representation is fairly forbidding. In this paper, we present approaches to efficiently compress FV and retain its robustness. First, we put forward a new Compact FV (CFV) descriptor. The CFV is obtained by zeroing out small posteriors, calculating first-order statistics and reweighting its elements properly. Second, in light of Iterative Quantization (ITQ) scheme, we present a Generalized ITQ (GITQ) method to binarize our CFV. Finally, we apply our CFV and GITQ to encode convolutional activations of convolutional neural networks. We evaluate our methods on FERET, LFW, AR, and FRGC 2.0 datasets, and our experiments reveal the advantage of such a framework.

Application of the hashing method to large-scale image retrieval has drawn much attention because of the high efficiency and favorable accuracy of the method. Its related research generally involves two basic problems: similarity-preserving projection and information-preserving quantization. Most previous works focused on learning projection approaches, while the importance of quantization strategies was ignored. Although several hashing quantization models have been recently proposed to improve retrieval performance by assigning multiple bits to projected directions, these models still suffer from suboptimal results, as the critical information loss that occurs in the quantization procedure is not considered. In this paper, to construct an effective quantization model, we utilize rate-distortion theory in the hashing quantization procedure and minimize the distortion to reduce the information loss. Furthermore, combining principal component analysis with our quantization strategy, we present a quantization-based hashing method named distortion minimization hashing. Extensive experiments involving one synthetic data set and three image data sets demonstrate the superior performance of our proposed methods over several quantization techniques and state-of-the-art hashing methods.

Background: In our previous study, we found that periostin was upregulated in prostate cancer, and its expression could be modulated by TGF-β. TGF-β could upregulate periostin expression in some cells, and both TGF-β and periostin could induce epithelial mesenchymal transition (EMT). We aimed to study the effect of periostin in the process of TGF-β-induced EMT in prostate cancer cells. Methods: We constructed a lentivirus vector containing the periostin gene and transduced it into PC3 and DU145 cells. After confirming periostin overexpression by PCR and Western blotting, we used an MTT assay to establish a growth curve to measure cell proliferation. Additionally, we performed transwell and wound healing assays to measure cell invasion and migration, respectively. Lastly, we measured the expression of EMT associated factors using Western blot analysis to test the effect of periostin on EMT in prostate cancer cells. Results: PCR and Western blot analyses confirmed that periostin was upregulated after infection with the periostin lentiviral vector. Periostin overexpression promoted increased cell proliferation, invasion, and migration as measured by MTT, transwell, and wound healing assays, respectively. Western blot analysis illustrated that periostin overexpression increased the expression of EMT associated factors, and periostin overexpression activated Akt and GSK-3β, which could be inhibited using a PI3K inhibitor. Additionally, TGF-β increased the levels of STAT3, Twist1 and periostin, while both STAT3 shRNA and Twist1 shRNA inhibited periostin expression. However, STAT3 shRNA also decreased Twist1 expression. Although reduction of STAT3, Twist1 or periostin levels with shRNA inhibited TGF-β-induced overexpression of EMT associated factors, periostin overexpression could reverse such inhibition by interfering with STAT3 and Twist1. Similarly, periostin overexpression also reversed inhibition of cell invasion induced by interference of STAT3 and Twist1. Conclusion: Our findings indicate that periostin is an important mediator of TGF-β-induced EMT and suggest that periostin is a potential therapeutic target for suppressing the metastatic progression of prostate cancer.

In the present study, we synthesized and, structurally and functionally characterized a novel α4/7-conotoxin Mr1.7 (PECCTHPACHVSHPELC-NH2), which was previously identified by cDNA libraries from Conus marmoreus in our lab. The NMR solution structure showed that Mr1.7 contained a 310-helix from residues Pro7 to His10 and a type I β-turn from residues Pro14 to Cys17. Electrophysiological results showed that Mr1.7 selectively inhibited the α3β2, α9α10 and α6/α3β2β3 neuronal nicotinic acetylcholine receptors (nAChRs) with an IC50 of 53.1 nM, 185.7 nM and 284.2 nM, respectively, but showed no inhibitory activity on other nAChR subtypes. Further structure-activity studies of Mr1.7 demonstrated that the PE residues at the N-terminal sequence of Mr1.7 were important for modulating its selectivity, and the replacement of Glu2 by Ala resulted in a significant increase in potency and selectivity to the α3β2 nAChR. Furthermore, the substitution of Ser12 with Asn in the loop2 significantly increased the binding of Mr1.7 to α3β2, α3β4, α2β4 and α7 nAChR subtypes. Taken together, this work expanded our knowledge of selectivity and provided a new way to improve the potency and selectivity of inhibitors for nAChR subtypes.

Background Platinum-based agents are widely used in chemotherapy against solid tumors and insufficient intracellular drug accumulation is one of the leading causes of platinum resistance which is associated with poor survival of tumor patients. Thus, the detection of intracellular platinum is pivotal for studies aiming to overcome platinum resistance. In the present study, we aimed to establish a reliable graphite furnace atomic absorption spectrometry (GFAAS)-based assay to quantify the intracellular platinum content for cultured cells. Methods Several most commonly applied cell preparation methods, including 0.2% HNO3, 0.2% Triton X-100, concentrated nitric acid, RIPA combined with concentrated nitric acid and hydroxide, followed by GFAAS for platinum detection were compared in ovarian, cervical and liver cancer cell lines to obtain the optimal one, and parameters regarding linearity, accuracy, precision and sensitivity were evaluated. Influence of other metals on platinum detection and the storage conditions of samples were also determined. Results The treatment of cells with 0.2% HNO3 was superior to other approaches with fewer platinum loss and better repeatability. The recovery rate and precision of this method were 97.3%–103.0% and 1.4%–3.8%, respectively. The average recoveries in the presence of other metals were 95.1%–103.1%. The detection limit was 13.23 ug/L. The recovery rate of platinum remained acceptable even in cell samples stored in −20 °C or −80 °C for two months. Discussion After comparison, we found that 0.2% HNO3 was optimal for intracellular platinum quantification based on GFAAS, which presented values compatible with that of inductively-coupled plasma mass-spectrometry (ICP-MS), and this is partially attributed to the simplicity of this method. Moreover, the assay was proved to be accurate, sensitive, cost-effective and suitable for the research of platinum-based antitumor therapy.

The mobile terminals must be compensated for the Doppler effect in their moving communication. This special characteristic of mobile communication can be developed in some new applications. This paper proposes methods to realize mobile navigation calculation via Doppler shifts. It gives the theory of relationship between the motion parameters, like directions and speed, and frequency shifts caused by multibase stations. The simulation illustrates how to compute the movement parameters of numerical calculation and what should be care for the problem near angle 90 degree. It also gives an application with Google map and dynamical locating position and direction on a mobile phone by public wireless network. Given the simulation analysis and navigation test, the results show that this method has a good effect.

Quantitative real-time PCR (qPCR) is a powerful and reproducible method of gene expression analysis in which expression levels are quantified by normalization against reference genes. Therefore, to investigate the potential biomarkers and therapeutic targets for epithelial ovarian cancer by qPCR, it is critical to identify stable reference genes. In this study, twelve housekeeping genes (ACTB, GAPDH, 18S rRNA, GUSB, PPIA, PBGD, PUM1, TBP, HRPT1, RPLP0, RPL13A, and B2M) were analyzed in 50 ovarian samples from normal, benign, borderline, and malignant tissues. For reliable results, laser microdissection (LMD), an effective technique used to prepare homogeneous starting material, was utilized to precisely excise target tissues or cells. One-way analysis of variance (ANOVA) and nonparametric (Kruskal-Wallis) tests were used to compare the expression differences. NormFinder and geNorm software were employed to further validate the suitability and stability of the candidate genes. Results showed that epithelial cells occupied a small percentage of the normal ovary indeed. The expression of ACTB, PPIA, RPL13A, RPLP0, and TBP were stable independent of the disease progression. In addition, NormFinder and geNorm identified the most stable combination (ACTB, PPIA, RPLP0, and TBP) and the relatively unstable reference gene GAPDH from the twelve commonly used housekeeping genes. Our results highlight the use of homogeneous ovarian tissues and multiple-reference normalization strategy, e.g. the combination of ACTB, PPIA, RPLP0, and TBP, for qPCR in epithelial ovarian tissues, whereas GAPDH, the most commonly used reference gene, is not recommended, especially as a single reference gene.

Objectives. To summarize our experience of retroperitoneal laparoscopic ureterolithotomy for ureteral calculi and evaluate the safety and efficiency of this procedure. Methods. We conducted a retrospective analysis of 197 patients with proximal ureteral calculi who accepted retroperitoneal laparoscopic ureterolithotomy from June 2005 to June 2014. Results. All procedures were performed successfully and the mean operating time and estimated blood loss were 87 min and 64 mL. The clearance rate was 98.5% and the rates of urine leak and ureteral stricture were 2.5% and 1.0%. Conclusions. Retroperitoneal laparoscopic ureterolithotomy is a safe and effective procedure for patients with complex stones or anatomic abnormalities, and, with experience of high volume series, it is also a reasonable choice as the primary treatment for such selected patients.

BACKGROUND: Predicting the recurrence and progression of Non-muscle-invasive bladder cancer(NMIBC) is critical for urologist. Histological grade provides significant prognostic information, especially for prediction of progression. Currently, the 1973 and the 2004 WHO classification co-exist. Which system is better for predicting rumor recurrence and progression still a matter for debate. METHODOLOGY/PRINCIPAL FINDINGS: 348 patients diagnosed with Non-muscle invasive bladder cancer were enrolled in our retrospective study. Paraffin sections were assessed by an experienced urological pathologist according to both the 1973 and 2004 WHO classifications. Tumor recurrence and progression was followed-up in all patients. During follow-up, corresponding 5-year recurrence-free survival rates of G1, G2 and G3 were 82.1%, 55.9%, 32.1% and the 5-year progression-free survival rates were 95.9%, 84.4% and 43.3%, respectively. The 5-year recurrence-free survival rates of papillary urothelial neoplasm of low malignant potential (PUNLMP), low-grade papillary urothelial carcinoma(LGPUC) and high-grade papillary urothelial carcinoma (HGPUC) were 69.8%, 67.1% and 42.0% respectively and the 5-year progression-free survival rates were 100%, 90.9% and 54.8% respectively. In multivariate analysis, the 1973 WHO classification significantly associated with both tumor recurrence and progression(p=0.010 and p=0.022, respectively); the 2004 WHO classification correlated with tumor progression(p=0.019), while was not proved to be a variable that can predict the risk of recurrence(p=0.547). Kaplan-Meier plots showed that both the 1973 WHO and the 2004 WHO classifications were significantly associated with progression-free survival (p

Natural attenuation of naphthalene (NAP) in riverbank filtration zones is vital for maintaining water quality and is affected by dissolved organic matter (DOM) and iron minerals. However, the effects of DOM and iron minerals on the attenuation of NAP remain unclear. In this study, the attenuation mechanisms of NAP under the influence of DOM and iron minerals were explored in a riverside source area. Field dynamic monitoring data revealed that the NAP concentration in groundwater is mainly influenced by DOM, effective bound‑iron, and the intensity of river water infiltration recharge. Column experiments indicated that DOM with α-Fe 2 O 3 or α-FeO(OH) reduced medium permeability by 8.16 % or 6.85 %, respectively, increasing water retention time. However, they had different effects on the attenuation of NAP. The coexistence of α-Fe 2 O 3 and DOM enhanced NAP attenuation capacity by 9.13 %-45.91 %, while α-FeO(OH) and DOM reduced it by -13.25 % to -24.13 %. These effects were attributed to changes in the medium permeability, particle size, secondary mineral formation, and microbial community structure. Specifically, α-Fe 2 O 3 and DOM reduced medium permeability, increasing the adsorption and biodegradation reaction time of NAP, and promoted secondary mineral (FeCO 3 ) formation, increasing the adsorption capacity of medium for NAP, while α-FeO(OH) and DOM underwent cementation, resulting in larger particles and reduced adsorption capacity for NAP. Additionally, α-FeO(OH) and DOM promoted Shewanlla growth, inhibiting NAP attenuation by competing with NAP-degrading bacteria. These findings improve the understanding of the natural attenuation of polycyclic aromatic hydrocarbons (PAHs) in riverbank filtration, offering a basis for evaluating and controlling PAH pollution risks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Uncertainty assessment of parameters associated with non-point source pollution mechanism modeling are crucial for improving the effectiveness of pollution controlling. In this study, an approach based on Bayesian inference and integrated Markov chain Monte Carlo and multilevel factorial analysis has been developed, and it can not only apply straightforward Bayesian inference to assess parameter uncertainties, but also quantitatively investigate the main and interactive effects of multiple parameters on the model response variables by measuring the specific variations of model outputs. Its applicability and advantages are presented through the application of the Soil and Water Assessment Tool to Shitoukoumen Reservoir Catchment in northeast China. This study investigated the uncertainties of a set of sensitive parameters and their multilevel effects on model response variables, including average annual runoff (AAR), average annual sediment (AAS) and average annual total nitrogen (AAN). Results revealed that (i) soil conservation service runoff curve number for moisture condition II (CN2) had a positive effect on all response variables; (ii) available water capacity of the soil layer (SOL_AWC) had a negative effect on all response variables; (iii) the universal soil loss equation support practice (USLE_P) had a positive effect on AAS and AAN, and little effect on AAR; while the nitrate percolation coefficient (NPERCO) had a positive effect on AAN, and little effect on AAS and AAR; and (iv) the interactions amongst parameters had obvious interdependent effects on the model response variables, for example, the interaction between CN2 and SOL_AWC had a major impact on AAR. The above findings can improve the simulating and predicting capabilities of non-point source pollution mechanism model. Overall, this study highlights that the proposed approach represents a promising solution for uncertainty assessment of model parameters in non-point source pollution mechanism modeling., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)