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Abstract Liver cancer, specifically hepatocellular carcinoma (HCC), stands out as one of the most formidable solid tumors, characterized by a dauntingly low survival rate. At the forefront of the tumor microenvironment (TME) orchestrating the initiation and advancement of HCC are cancer-associated fibroblasts (CAFs). TGF-β, widely recognized as a potent activator of CAFs, not only regulates their activity but also assumes a pivotal role in the metastatic journey of the tumor. In our recent study, drawing from the GEO database, we identified two fibroblast subtypes in HCC through single-cell RNA sequencing (scRNA-seq) and explore the expression and distribution of TGF-β and its receptors in the TME of HCC. Subsequently, we investigated the interactions between tumor cells expressing high levels (TGFB1high) and low levels (TGFB1low) of TGF-β in the HCC TME and the two subtypes of CAFs. We also employed multi-color immunohistochemistry (mIHC) technology to examine the expressions of FAP, α-SMA, CD4, Foxp3, and TGF-β in HCC tissues within a tissue microarray. Additionally, we analyzed clinical associations, prognostic values, and the correlation of these molecules. These insights advance our understanding of the molecular mechanisms driving HCC progression and underscore the intricate interplay between tumor cells and the stromal components of the TME.

Abstract Type IA topoisomerases (TopoIAs) are present in all living organisms. They resolve DNA/RNA catenanes, knots and supercoils by breaking and rejoining single-stranded DNA/RNA segments and allowing the passage of another nucleic acid segment through the break. Topoisomerase III-β (TOP3B), the only RNA topoisomerase in metazoans, promotes R-loop disassembly and translation of mRNAs. Defects in TOP3B lead to severe neurological diseases. We present a series of cryo-EM structures of human TOP3B with its cofactor TDRD3 during cleavage and rejoining of DNA or RNA, thus elucidating the roles of divalent metal ions and key enzyme residues in each step of the catalytic cycle. We also obtained the structure of an open-gate configuration that addresses the long-standing question of the strand-passage mechanism. Our studies reveal how TOP3B catalyzes both DNA and RNA relaxation, while TOP3A acts only on DNA.

Abstract Filoviruses, including Ebola, Marburg, Sudan, and Taï Forest viruses, are zoonotic pathogens that can cause severe viral hemorrhagic fever and death. Developing vaccines that provide durable, broad immunity against multiple filoviruses is a high global health priority. In this Phase 1 trial, we enrolled 60 healthy U.S. adults and evaluated the safety, reactogenicity and immunogenicity of homologous and heterologous MVA-BN®-Filo and Ad26.ZEBOV prime-boost schedules followed in select arms by MVA-BN®-Filo boost at 1 year (NCT02891980). We found that all vaccine regimens had acceptable safety and reactogenicity. The heterologous prime-boost strategy elicited superior Ebola binding and neutralizing antibody, antibody-dependent cellular cytotoxicity (ADCC), and cellular responses compared to homologous prime-boost. The MVA-BN®-Filo boost administered at 1 year resulted in robust humoral and cellular responses that persisted through 6-month follow-up. Overall, our data demonstrated that a heterologous Ad26.ZEBOV/MVA-BN®-Filo prime-boost was safe and immunogenic and established immunologic memory primed to respond after re-exposure. Clinicaltrials.gov, NCT02891980, registered September 1, 2016.

Noise-induced hearing loss (NIHL) is primarily driven by inflammatory processes within the cochlea, where noise exposure triggers the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome, leading to an inflammatory cascade. The interaction between increased NLRP3 expression and NF-κB activity can further amplify cochlear inflammation. Our findings reveal that (R)-PFI-2 hydrochloride, a selective inhibitor of the SETD7 enzyme, effectively inhibits the activation of the cochlear NF-κB pathway, suppresses the release of pro-inflammatory factors, and prevents inflammasome assembly. This intervention disrupts the perpetuating cycle of inflammation, thereby alleviating damage to cochlear hair cells attributed to acoustic trauma. Consequently, (R)-PFI-2 hydrochloride emerges as a promising pharmacological candidate for NIHL, targeting and moderating the excessive immune and inflammatory responses implicated in the pathology of hearing loss.

Abstract Turbulent entrainment‐mixing processes profoundly influence the relationship between radar reflectivity factor and liquid water content (Z‐LWC) of cloud droplets. However, quantification of the entrainment‐mixing mechanisms based on the Z‐LWC relationship is still lacking. To address this gap, 12,218 entrainment‐mixing cases are simulated using the Explicit Mixing Parcel Model. We examine the variations of the parameters in the power‐law relationship Z = aLWCb, and the relationship between parameter b and homogeneous mixing degree (ψ), a measure quantifying entrainment‐mixing processes. The results indicate that parameter b distributes within the range of 1–2, with a positive correlation between parameter b and ψ. The b‐ψ relationship is fitted, which connects the Z‐LWC relationship for various entrainment‐mixing types. The results suggest the potential for employing a remote sensing approach to investigate the entrainment‐mixing mechanisms of non‐precipitating small cumulus/stratocumulus clouds, thereby overcoming the limitations of traditional observational studies that rely solely on aircraft observations.

Accurately aligning the same users on different flat social networks to merge user information and create more nuanced user profiles is critical. However, the current research in this area faces challenges related to low efficiency and inadequate alignment accuracy. To address these challenges, we introduce a cross-social network user alignment model based on multi-dimensional user features (MDUF). First, inspired by the principles of entity recognition and Hartley's association method, we employed a block matrix association algorithm to project the original dataset into different high-dimensional spaces. Second, we proposed a new inertia weight calculation method to improve the convergence speed from linear to nonlinear transformations. This method improves the performance of traditional particle swarm optimization algorithms. Finally, we utilize improved particle swarm optimization and residual connection techniques to optimize bidirectional long short-term memory networks. The experimental results show that our proposed model significantly outperforms traditional alignment models in terms of alignment efficiency and accuracy, which is highly practical and has the potential to inspire further research on social network user alignment.

Abstract O6‐methylguanine DNA methyltransferase (MGMT) removes alkyl adducts from the guanine O6 position (O6‐MG) and repairs DNA damage. High MGMT expression results in poor response to temozolomide (TMZ). However, the biological importance of MGMT and the mechanism underlying its high expression in pancreatic neuroendocrine tumors (PanNETs) remain elusive. Here, it is found that MGMT expression is highly elevated in PanNET tissues compared with paired normal tissues and negatively associated with progression‐free survival (PFS) time in patients with PanNETs. Knocking out MGMT inhibits cancer cell growth in vitro and in vivo. Ectopic MEN1 expression suppresses MGMT transcription in a manner that depends on β‐Catenin nuclear export and degradation. The Leucine 267 residue of MEN1 is crucial for regulating β‐Catenin‐MGMT axis activation and chemosensitivity to TMZ. Interference with β‐Catenin re‐sensitizes tumor cells to TMZ and significantly reduces the cytotoxic effects of high‐dose TMZ treatment, and MGMT overexpression counteracts the effects of β‐Catenin deficiency. This study reveals the biological importance of MGMT and a new mechanism by which MEN1 deficiency regulates its expression, thus providing a potential combinational strategy for treating patients with TMZ‐resistant PanNETs.

Abstract This paper presents a new method for accurately measuring the vocabulary size of second language (L2) learners. Traditional vocabulary size tests (VSTs) are limited in capturing a tester’s vocabulary and are often population-specific. To overcome these issues, we propose an intelligent vocabulary size measurement method that utilizes massive robot testers. They are equipped with randomized and word-frequency-based vocabularies to simulate L2 learners’ variant vocabularies. An intelligent vocabulary size test (IVST) is developed to precisely measure vocabulary size for any population. The robot testers “take” the IVST, which dynamically generates quizzes with varying levels of difficulty adapted to the estimated tester’s vocabulary size in real-time using an artificial neural network (ANN) through iterative learning. The effectiveness of the IVST is factually verified by their visible vocabularies. Additionally, we apply a long short-term memory (LSTM) model to further enhance the method’s performance. The proposed method has demonstrated high reliability and effectiveness, achieving accuracies of 98.47% for the IVST and 99.87% for the IVST with LSTM. This novel approach provides a more precise and reliable method for measuring vocabulary size in L2 learners compared to traditional VSTs, offering potential benefits to language learners and educators.

Abstract Background The procedure of total duodenum-preserving pancreatic head resection (DPPHRt) has been reported frequently, but rare in minimally invasive procedure, especially robotic-assisted operation. Here we share our experience and analyze the clinical outcomes of minimally invasive DPPHRt in the treatment of benign lesions or low-grade malignant tumors of the pancreatic head in this study. Materials and methods From October 2016 to January 2022, three patients received robot-assisted DPPHRt(RA-DPPHRt), and seventeen patients received laparoscopic DPPHRt(LDPPHRt). Data were retrospectively collected in terms of demographic characteristics (age, gender, body mass index, and pathological diagnosis), intraoperative variables (operative time, estimated blood loss), and post-operative variables (post-operative hospital stay, and complications). Results All 20 patients received minimally invasive total duodenum-preserving pancreatic head resection successfully without conversion, including 8 males and 12 females. Pathological diagnosis suggested 1 case of serous cystadenoma (SCA), 4 cases of intraductal papillary mucinous neoplasm (IPMN) ,5 cases of mucinous cystic neoplasm (MCN), 4 cases of pancreatic neuroendocrine neoplasm (PNET), 2 cases of chronic pancreatitis (CP),4 case of solid pseudopapillary tumor (SPT). The average operation time was (285.35 ± 95.13 min), ranging from 95 to 420 min. The average estimate blood loss was (196.50 ± 174.45ml) ,ranging from 10 to 600ml.The average post-operative hospital stay was(20.90 ± 14.44days),ranging from 8 to 54 days. Postoperative complications occurred in 10 patients (50%). A total of 5 patients (20%) suffered grade B or C pancreatic fistula. Two patients (10%) suffered from biliary fistula. Two patients (10%) suffered from delayed gastric emptying. One patient (5%) suffered from abdominal bleeding. The 90-day mortality was 0. No patient was observed tumor recurrence and new-onset diabetes but one developed diarrhea. Conclusion RA-DPPHRt or LDPPHRt provided a minimally invasive approach with good organ-preservation for patients with benign and low-grade malignant pancreatic head tumor. It is only recommended to be performed in high-volume pancreatic centers by experienced pancreatic surgeons.

Background Immune-based therapies are commonly employed to combat hepatocellular carcinoma (HCC). However, the presence of immune-regulating elements, especially regulatory T cells (Tregs), can dramatically impact the treatment efficacy. A deeper examination of the immune-regulation mechanisms linked to these inhibitory factors and their impact on HCC patient outcomes is warranted. Methods We employed multicolor fluorescence immunohistochemistry (mIHC) to stain Foxp3, cytokeratin, and nuclei on an HCC tissue microarray (TMA). Leveraging liver cancer transcriptome data from TCGA, we built a prognostic model focused on Treg-associated gene sets and represented it with a nomogram. We then sourced liver cancer single-cell RNA sequencing data (GSE140228) from the GEO database, selectively focusing on Treg subsets, and conducted further analyses, including cell-to-cell communication and pseudo-time trajectory examination. Results Our mIHC results revealed a more substantial presence of Foxp3 + Tregs in HCC samples than in adjacent normal tissue samples ( P < .001). An increased presence of Foxp3 + Tregs in HCC samples correlated with unfavorable patient outcomes ( HR = 1.722, 95% CI :1.023-2.899, P = .041). The multi-factorial prognosis model we built from TCGA liver cancer data highlighted Tregs as a standalone risk determinant for predicting outcomes ( HR = 3.84, 95% CI: 2.52-5.83, P < .001). Re-analyzing the scRNA-seq dataset (GSE140228) showcased distinctive gene expression patterns in Tregs from varying tissues. Interactions between Tregs and other CD4 + T cell types were predominantly governed by the CXCL13/CXCR3 signaling pathway. Communication pathways between Tregs and macrophages primarily involved MIF-CD74/CXCR4, LGALS9/CD45, and PTPRC/MRC1. Additionally, macrophages could influence Tregs via HLA-class II and CD4 interactions. Conclusion An elevated presence of Tregs in HCC samples correlated with negative patient outcomes. Elucidating the interplay between Tregs and other immune cells in HCC could provide insights into the modulatory role of Tregs within HCC tissues.

Retroviral integration is mediated by intasome nucleoprotein complexes wherein a pair of viral DNA ends are bridged together by a multimer of integrase (IN). Atomic-resolution structures of HIV-1 intasomes provide detailed insights into the mechanism of integration and inhibition by clinical IN inhibitors. However, previously described HIV-1 intasomes are highly heterogeneous and have the tendency to form stacks, which is a limiting factor in determining high-resolution cryo-EM maps. We have assembled HIV-1 intasomes in the presence of excess IN C-terminal domain protein, which was readily incorporated into the intasomes. The purified intasomes were largely homogeneous and exhibited minimal stacking tendencies. The cryo-EM map resolution was further improved to 2.01 Å, which will greatly facilitate structural studies of IN inhibitor action and drug resistance mechanisms. The C-terminal 18 residues of HIV-1 IN, which are critical for virus replication and integration in vitro, have not been well resolved in previous intasome structures, and its function remains unclear. We show that the C-terminal tail participates in intasome assembly, resides within the intasome core, and forms a small alpha helix (residues 271–276). Mutations that disrupt alpha helix integrity impede IN activity in vitro and disrupt HIV-1 infection at the step of viral DNA integration.

Abstract Green manufacture of steroid precursors from diosgenin by microbial replacing multistep chemical synthesis has been elusive. It is currently limited by the lack of strain and degradation mechanisms. Here, we demonstrated the feasibility of this process using a novel strain Mycolicibacterium sp. HK‐90 with efficiency in diosgenin degradation. Diosgenin degradation by strain HK‐90 involves the selective removal of 5,6‐spiroketal structure, followed by the oxygenolytic cleavage of steroid nuclei. Bioinformatic analyses revealed the presence of two complete steroid catabolic gene clusters, SCG‐1 and SCG‐2, in the genome of strain HK‐90. SCG‐1 cluster was found to be involved in classic phytosterols or cholesterol catabolic pathway through the deletion of key kstD1 gene, which promoted the mutant m‐∆kstD1 converting phytosterols to intermediate 9α‐hydroxyandrostenedione (9‐OHAD). Most impressively, global transcriptomics and characterization of key genes suggested SCG‐2 as a potential gene cluster encoding diosgenin degradation. The gene inactivation of kstD2 in SCG‐2 resulted in the conversion of diosgenin to 9‐OHAD and 9,16‐dihydroxy‐pregn‐4‐ene‐3,20‐dione (9,16‐(OH)2‐PG) in mutant m‐ΔkstD2. Moreover, the engineered strain mHust‐ΔkstD1,2,3 with a triple deletion of kstDs was constructed, which can stably accumulate 9‐OHAD by metabolizing phytosterols, and accumulate 9‐OHAD and 9,16‐(OH)2‐PG from diosgenin. Diosgenin catabolism in strain mHust‐ΔkstD1,2,3 was revealed as a progression through diosgenone, 9,16‐(OH)2‐PG, and 9‐OHAD to 9α‐hydroxytestosterone (9‐OHTS). So far, this work is the first report on genetically engineered strain metabolizing diosgenin to produce 21‐carbon and 19‐carbon steroids. This study presents a promising biosynthetic platform for the green production of steroid precursors, and provide insights into the complex biochemical mechanism of diosgenin catabolism.

Abstract Protein lattices that shift the structure and shape anisotropy in response to environmental cues are closely coupled to potential functionality. However, to design and construct shape‐anisotropic protein arrays from the same building blocks in response to different external stimuli remains challenging. Here, by a combination of the multiple, symmetric interaction sites on the outer surface of protein nanocages and the tunable features of phenylalanine‐phenylalanine interactions, a protein engineering approach is reported to construct a variety of superstructures with shape anisotropy, including 3D cubic, 2D hexagonal layered, and 1D rod‐like crystalline protein nanocage arrays by using one single protein building block. Notably, the assembly of these crystalline protein arrays is reversible, which can be tuned by external stimuli (pH and ionic strength). The anisotropic morphologies of the fabricated macroscopic crystals can be correlated with the Å‐to‐nm scale protein arrangement details by crystallographic elucidation. These results enhance the understanding of the freedom offered by an object's symmetry and inter‐object π−π stacking interactions for protein building blocks to assemble into direction‐ and shape‐anisotropic biomaterials.

Abstract Background Laparoscopic surgery (LS) has been increasingly applied in perihilar cholangiocarcinoma (pCCA). In this study, we intend to compare the short-term outcomes of LS versus open operation (OP) for pCCA in a multicentric practice in China. Methods This real-world analysis included 645 pCCA patients receiving LS and OP at 11 participating centers in China between January 2013 and January 2019. A comparative analysis was performed before and after propensity score matching (PSM) in LS and OP groups, and within Bismuth subgroups. Univariate and multivariate models were performed to identify significant prognostic factors of adverse surgical outcomes and postoperative length of stay (LOS). Results Among 645 pCCAs, 256 received LS and 389 received OP. Reduced hepaticojejunostomy (30.89% vs 51.40%, P = 0.006), biliary plasty requirement (19.51% vs 40.16%, P = 0.001), shorter LOS (mean 14.32 vs 17.95 d, P 0.05 for all). After PSM, the short-term outcomes of two surgical methods were similar, except for shorter LOS in LS compared with OP (mean 15.19 vs 18.48 d, P = 0.0007). A series subgroup analysis demonstrated that LS was safe and had advantages in shorting LOS. Conclusion Although the complex surgical procedures, LS generally seems to be safe and feasible for experienced surgeons. Trial registration NCT05402618 (date of first registration: 02/06/2022).

Abstract Background RNA binding proteins (RBPs) have been implicated in oncogenesis and progression in various cancers. However, the potential value of RBPs as prognostic indicators and therapeutic targets in colorectal cancer (CRC) requires further investigation. Methods Four thousand eighty two RBPs were collected from literature. The weighted gene co-expression network analysis (WGCNA) was performed to identify prognosis-related RBP gene modules based on the data attained from the TCGA cohorts. LASSO algorithm was conducted to establish a prognostic risk model, and the validity of the proposed model was confirmed by an independent GEO dataset. Functional enrichment analysis was performed to reveal the potential biological functions and pathways of the signature and to estimate tumor immune infiltration. Potential therapeutic compounds were inferred utilizing CMap database. Expressions of hub genes were further verified through the Human Protein Atlas (HPA) database and RT-qPCR. Results One thousand seven hundred thirty four RBPs were differently expressed in CRC samples and 4 gene modules remarkably linked to the prognosis were identified, based on which a 12-gene signature was established for prognosis prediction. Multivariate Cox analysis suggested this signature was an independent predicting factor of overall survival (P

Abstract Background As an oncogene, SETD8 can promote tumour growth and tumour cell proliferation. This study aims to reveal the relationship between SETD8 and ferroptosis in pancreatic cancer and its role in pancreatic cancer to provide a possible new direction for the comprehensive treatment of pancreatic cancer. Methods The downstream targets were screened by RNA sequencing analysis. Western blot, Real-time Quantitative PCR (qPCR) and immunohistochemistry showed the relationship between genes. Cell proliferation analysis and cell metabolite analysis revealed the function of genes. Chromatin immunoprecipitation (CHIP) assays were used to study the molecular mechanism. Results The potential downstream target of SETD8, RRAD, was screened by RNA sequencing analysis. A negative correlation between SETD8 and RRAD was found by protein imprinting, Real-time Quantitative PCR (qPCR) and immunohistochemistry. Through cell proliferation analysis and cell metabolite analysis, it was found that RRAD can not only inhibit the proliferation of cancer cells but also improve the level of lipid peroxidation of cancer cells. At the same time, chromatin immunoprecipitation analysis (CHIP) was used to explore the molecular mechanism by which SETD8 regulates RRAD expression. SETD8 inhibited RRAD expression. Conclusions SETD8 interacts with the promoter region of RRAD, which epigenetically silences the expression of RRAD to reduce the level of lipid peroxidation in pancreatic cancer cells, thereby inhibiting ferroptosis in pancreatic cancer cells and resulting in poor prognosis of pancreatic cancer.

Multi-direction impact forging (MDIF) was applied to the as-extruded ZK60 Mg alloy, and the microstructure, texture evolution and yield strength symmetry were investigated in the current study. The results showed that the average grain size of forged piece was greatly refined to 5.3 µm after 120 forging passes, which was ascribed to the segmenting effect of {10–12} twins and the subsequent multiple rounds of dynamic recrystallization (DRX). A great deal of {10–12} twins were activated at the beginning of MDIF process, which played an important role in grain refinement. With forging proceeding, continuous and discontinuous DRX were successively activated, resulting in the fully DRXed microstructure. Meanwhile, the forged piece exhibited a unique four-peak texture, and the initial //ED fiber texture component gradually evolved into multiple texture components composed of //FFD (first forging direction) and //FFD texture. The special strain path was the key to the formation of the unique four-peak texture. The {10–12} twinning and basal slip were two dominant factors to the evolution of texture during MDIF process. Grain strengthening and dislocation strengthening were two main strengthening mechanisms of the forged piece. Besides, the symmetry of yield strength was greatly improved by MDIF process.

Abstract Background Although some factors that predict the prognosis in pancreatic neuroendocrine tumor (pNET) have been confirmed, the predictive value of lymph node metastasis (LNM) in the prognosis of pNETs remains conflicting and it is not clear whether regional lymphadenectomy should be performed in all grades of tumors. Methods We included pNET patients undergoing surgery in Shanghai pancreatic cancer institute (SHPCI). The risk factors for survival were investigated by the Kaplan–Meier method and Cox regression model. We evaluated the predictors of LNM using Logistic regression. Results For 206 patients in the SHPCI series, LNM was an independent prognostic factor for entire cohort suggested by multivariate Cox regression analysis. LNM (P = 0.002) predicted poorer overall survival (OS) in grade 2/3 cohort, but there is no significant association between LNM and OS in grade 1 cohort. Grade (P 4 cm tumors. On the other way, LNM was seems to be not associated with prognosis in patients with grade 1 tumors less than 4 cm. Moreover, tumor grade and tumor size seem to act as independent predictors of LNM. Thus, regional lymphadenectomy should be performed in grade 2/3 patients but was not mandatory in grade 1 tumors

Ferroptosis is a new form of regulatory cell death that is closely related to the balance of redox reactions and the occurrence and development of cancer. There is increasing evidence that inducing ferroptosis in cells has great potential in the treatment of cancer. Especially when combined with traditional therapy, it can improve the sensitivity of cancer cells to traditional therapy and overcome the drug resistance of cancer cells. This paper reviews the signaling pathways regulating ferroptosis and the great potential of ferroptosis and radiotherapy (RT) in cancer treatment and emphasizes the unique therapeutic effects of ferroptosis combined with RT on cancer cells, such as synergy, sensitization and reversal of drug resistance, providing a new direction for cancer treatment. Finally, the challenges and research directions for this joint strategy are discussed.

Proxy signature schemes safely ensure that an original signer transfers the signing right to a proxy signer, and a variety of these schemes have been developed for secure applications. Constructions of proxy signature schemes vary; recently developed schemes utilize lattices to safeguard against quantum attacks. However, existing lattice-based proxy schemes proved secure in the standard model have many public system parameters, reducing the efficiency of these schemes. To solve this problem, we utilize an admissible hash function with compatible algorithms (AHFwCA) and lattice trapdoors as an initial framework to propose a new lattice-based proxy signature scheme. While maintaining a similar key and signature size as prior schemes, this new proxy signature scheme requires fewer public system parameters. Compared with requiring linear basic matrices as public system parameters found in other standard model schemes, the proposed new scheme depends upon logarithmic basic matrices. Under the standard inhomogeneous short integer solution (ISIS) assumption, we prove that the scheme is existentially unforgeable against chosen message attacks and chosen warrant attacks (EUF-CMA-CWA) in the standard model by using the generalized partitioning proof technique. Thus, this paper partially solves the many parameters problem existed in the standard model lattice-based signature schemes.

Short message services (SMS), microblogging tools, instant message apps, and commercial websites produce numerous short text messages every day. These short text messages are usually guaranteed to reach mass audience with low cost. Spammers take advantage of short texts by sending bulk malicious or unwanted messages. Short texts are difficult to classify because of their shortness, sparsity, rapidness, and informal writing. The effectiveness of the hidden Markov model (HMM) for short text classification has been illustrated in our previous study. However, the HMM has limited capability to handle new words, which are mostly generated by informal writing. In this paper, a hybrid model is proposed to address the informal writing issue by weighting new words for fast short text filtering with high accuracy. The hybrid model consists of an artificial neural network (ANN) and an HMM, which are used for new word weighting and spam filtering, respectively. The weight of a new word is calculated based on the weights of its neighbor, along with the spam and ham (i.e., not spam) probabilities of short text message predicted by the ANN. Performance evaluations on benchmark datasets, including the SMS message data maintained by University of California, Irvine; the movie reviews, and the customer reviews are conducted. The hybrid model operates at a significantly higher speed than deep learning models. The experiment results show that the proposed hybrid model outperforms other prominent machine learning algorithms, achieving a good balance between filtering throughput and accuracy.

The structure and assembly properties of ferritin derived from aquatic products remain to be explored. Constructing diverse three-dimensional (3D) protein architectures with the same building blocks has important implications for nutrient delivery, medicine and materials science. Herein, ferritin from Asterias forbesii (AfFer) was prepared, and its crystal structure was resolved at 1.91 Å for the first time. Notably, different from the crystal structure of other reported ferritin, AfFer exhibited a BCT lattice arrangement in its crystals. Bioinspired by the crystal structure of AfFer, we described an effective approach for manufacturing 3D porous, crystalline nanoarchitectures by redesigning the shared protein interface involved in different 3D protein arrays. Based on this strategy, two 3D superlattices of body-centered tetragonal and simple cubicwere constructed with ferritin molecules as the building blocks. This study provided a potentially generalizable strategy for constructing different 3D protein-based crystalline biomaterials with the same building blocks.

COVID-19 vaccination during pregnancy protects infants against symptomatic COVID-19. Vaccination of lactating mothers may offer additional protection, but our understanding of immune responses in breast milk is limited. We, therefore, performed a single-center prospective cohort study of lactating mothers who received a COVID-19 mRNA primary vaccine series to evaluate the durability, breadth, and neutralizing capacity of the antibody responses in breast milk. Spike IgG- and IgA-binding antibodies of ancestral SARS-CoV-2 in serum and breast milk were quantified over 9 months using Meso Scale Discovery (MSD) V-PLEX assays, and ancestral titers were compared to four variants of concern (Alpha, Beta, Delta, Gamma) at a single time point. Neutralizing antibodies against ancestral SARS-CoV-2 and Omicron BA.4/5 were compared before and after vaccination using a pseudovirus-neutralization assay. Eleven lactating mothers received either Pfizer BNT162b2 (7/11) or Moderna mRNA-1273 (4/11) vaccine primary series. IgG and IgA titers increased in serum and breast milk following each dose, peaking 1–4 weeks after series completion. Titers remained significantly elevated for 7–9 months, except for in breast milk IgA which returned to baseline within 1 month. Furthermore, binding antibodies against all included variants were detected in breast milk collected 1–3 weeks after series completion. However, while vaccination induced a strong neutralizing response against ancestral SARS-CoV-2 in serum and more modest response in breast milk, it did not induce neutralizing antibodies against Omicron BA.4/5 in either specimen type. This study demonstrates that maternal COVID-19 mRNA vaccination may enhance immune protection for infants through breast milk via increased IgG- and IgA-binding-and-neutralizing antibodies; although, variant-specific boosters may be required to optimize immune protection.

BackgroundThere are few studies comparing the oncological outcomes of laparoscopic pancreaticoduodenectomy (LPD) and open pancreaticoduodenectomy (OPD) for distal cholangiocarcinoma (DCC). Our objective was to assess the short-term efficacy and long-term survival of LPD and OPD in patients with DCC.MethodsThe data of 124 DCC patients who underwent LPD or OPD at the Third Affiliated Hospital of Soochow University from May 2010 to May 2021 were retrospectively analyzed. Propensity score matching was performed to balance the two groups of baseline characteristics. After 1:1 matching, the overall survival (OS) of the two groups was compared by the Kaplan−Meier method. Univariate and multivariate Cox regression analyses were used to identify independent predictors of OS.ResultsThe original cohort consisted of 124 patients. Nineteen patients were excluded because of incomplete baseline or follow-up data, and the remaining 105 patients were divided into two cohorts (45 in the LPD group and 60 in the OPD group). The LPD group showed more favorable results in OS analysis (LPD vs. OPD, 56.4 [46.2-66.5] vs. 48.9 [36.4-61.4], months, P=0. 01). PSM analysis identified 30 pairs of patients, and differences between matching groups were still significant (LPD vs. OPD, 67.9[58.2-77.6] vs. 47.4[31.4-67.5], months, P=0.002). Moreover, the LPD group experienced less intraoperative bleeding (LPD vs. OPD, 292.67 vs. 519.17 mL, P=0.002). Univariate analysis showed that surgical modality (P=0.012), carbohydrate antigen 19-9 (P=0.043), carcinoembryonic antigen (P=0.003), neutrophil-to-lymphocyte ratio (P=0.012), blood transfusion (P=0.031), clinically relevant postoperative pancreatic fistula (P0.05).ConclusionsFor DCC patients, LPD may be a more recommended procedure because of its advantages over OPD in terms of intraoperative bleeding and long-term survival.

Bacterial resistance is becoming increasingly serious, the present study aimed to investigate the mechanism of antibacterial sensitization effect of DHA27 combined with tobramycin in tobramycin-resistant Pseudomonas aeruginosa (PA). We found that DHA27 combined with aminoglycosides had an antibacterial sensitization effect on PA. Tobramycin, owing to its lower toxic and side effects, was selected to further study the molecular mechanism of drug combination. A sublethal-dose bacterial challenge/sepsis mouse model was established to study the protective effect of DHA27 plus tobramycin. Scanning electron microscopy was used to investigate whether DHA27 exerts the antibacterial sensitization effect by directly affecting bacterial morphology. The effect of DHA27 on daunorubicin accumulation in bacteria was studied, and quantitative reverse transcription PCR was used to study the effect of DHA27 plus tobramycin on 16S rRNA methyltransferase and aminoglycoside-modifying enzyme mRNA expression. Twenty clinical isolates of PA were found to be tobramycin resistant; DHA27 plus tobramycin had a significant antibacterial sensitization effect on many of these resistant strains. DHA27 plus tobramycin reduced the bacterial load in the spleen and lungs of sepsis model mice and levels of proinflammatory cytokines interleukin-1β (IL-1β) and interferon-γ (IFN-γ). DHA27 plus tobramycin significantly inhibited the mRNA expression of aminoglycoside-modifying enzymes in bacteria. DHA27 combined with AGs had an antibacterial sensitization effect on PA; the molecular mechanism underlying this effect is closely related to the inhibition of the mRNA expression of aminoglycoside-modifying enzymes, especially aac(3)-II.

Analysis of traffic flow signals plays an important role in traffic prediction and management. As an intrinsic property, the singular point of a traffic flow signal labels a new nonsteady status. Therefore, detecting the singular point is an effective approach to determine the moment of traffic flow prediction. In this paper, an improved wavelet transform is proposed to detect singular points of real-time traffic flow signals. The number of detected singular points is output via the heuristic selection of multiple scales. Then, a weighted similarity measurement of historical traffic flow signals is utilized to predict the next singular point. The position of the next singular point decides the duration of prediction adaptively. The detected and predicted singular points are applied to dynamically update the unequal interval prediction of traffic flow. Furthermore, a Vasicek model is used to predict the traffic flow by minimizing the sum of the relative mean standard error (RMSE) between the traffic flow increment in the predicted interval and the sampled increments of previous intervals. A decomposition method is used to solve the unequal matrix problem. Based on the scenario and traffic flow imported from the real-world map, the simulation results show that the proposed algorithm outperforms existing approaches with high prediction accuracy and much lower computing cost.

BackgroundThe four major pathways in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) including chromatin remodeling, DNA damage repair, activation of mTOR signaling, and telomere maintenance were mediated by some critical molecules and constituted critical processes of regulation in cancer-causing processes. However, the interplay and potential role of these pathway-related molecules in the tumor microenvironment of the primary and metastatic site remained unknown.MethodsWe systematically evaluated the mRNA expression of 34 molecules associated with the four pathways in 227 GEP−NEN samples from 5 datasets. We assigned the samples into two expression patterns of pathway-related molecules by an unsupervised clustering method. Subsequently, we explored the specific cell-related molecules, especially immune and stromal cells using the WGCNA method, based on differentially expressed genes (DEGs) responsible for the different patterns of pathway-related molecules, which provided a new method to qualify the pathway-related subtypes of individual tumors, then the PC_Score and PI_Score scoring systems were also constructed using obtained specific cell-related molecules. Furthermore, we performed the association of pathway-related subtypes with characteristics of immune landscape in primary and metastatic GEP-NENs.ResultsWe demonstrated that the specific pathway-related molecules (SMARCA4, MLH1, TSC1, ATRX, and ATR) were associated with cytolytic activity. Then we identified the two distinct patterns of pathway-related molecules, which were characteristic with a significantly distinct immune landscape. Using WGCNA, we also identified the fibroblast-related molecules, including ASPN, COL10A1, COL3A1, EDNRA, MYL9, PRELP, RAB31, SPARC, and THBS2, and immune-related molecules including CASP1, CCL5, CTSS, CYBRD1, PMP22, and TFEC. Based on these specific markers, we identified four distinct pathway-related subtypes, characterized by immune and fibrotic enriched (I/FE), immune enriched (IE), fibrotic enriched (FE), and immune and fibrotic desert (I/FD), of which I/FE was characteristic with the highest PC_Score and PI_Score whereas I/FD presents the opposite trend. I/FE was positively correlated with immune landscape of T-cell activation and immunosuppression. Furthermore, the I/FE marked GEP-NENs with increased immune activation scores (T-cell costimulation, MHC I presentation, and APC costimulation). Importantly, the four distinct pathway-related subtypes were not conserved in different tumor sites, because I/FE was lacking in the liver metastatic site even though IE, FE, and I/FD also could be observed in the metastatic site.ConclusionsThis study was the first to perform a comprehensive analysis of the four major pathways in GEP-NENs. We demonstrated the potential function of these pathway-related molecules in immune landscapes. Our findings indicated that the primary and metastatic GEP-NENs had distinct antitumor phenotypes. This work highlighted the interplay and potential clinical utility of these pathway-related molecules in GEP-NENs.

AimsTo investigate the clinical efficacy and prognostic factors of primary gallbladder cancer (GBC) treated by radical surgery.MethodsThe clinical and pathological data of 168 patients with primary gallbladder cancer admitted and treated in the Third Affiliated Hospital of Soochow University from January 1st, 2010 to December 31st, 2018 were analyzed retrospectively. Kaplan Meier method was used to draw the survival curve and evaluate the survival rate. Chi-square test was used for univariate analysis and binary logistic regression was used for multivariate analysis.Results94 cases showed symptoms of abdominal pain and abdominal distension. 7 cases showed symptoms of fatigue and weight loss. Jaundice occurred in 10 patients. Fever occurred in 6 patients. 51 patients had no symptoms at all. The median survival time of 168 patients was 35.0 (1.0 ~ 142.0) months. The overall 1-, 2- and 3-year cumulative survival rates were 69.6%, 55.4% and 48.8% respectively. The univariate analysis indicated that preoperative bilirubin, tumor size, tumor location, pathological type, degree of differentiation, liver invasion, nerve invasion, vascular invasion, surgical margin, filtration depth and N staging were significant factors influencing prognosis of patients with primary GBC (P

Introduction Pancreatic cancer is one of the deadliest cancers and pancreaticoduodenectomy (PD) is recommended as the optimal operation for resectable pancreatic head cancer. Minimally invasive surgery, which initially emerged as hybrid-laparoscopy and recently developed into total laparoscopy surgery, has been widely used for various abdominal surgeries. However, controversy persists regarding whether laparoscopic PD (LPD) is inferior to open PD (OPD) for resectable pancreatic ductal adenocarcinoma (PDAC) treatment. Further studies, especially randomised clinical trials, are warranted to compare these two surgical techniques.Methods and analysis The TJDBPS07 study is designed as a prospective, randomised controlled, parallel-group, open-label, multicentre noninferiority study. All participating pancreatic surgical centres comprise specialists who have performed no less than 104 LPDs and OPDs, respectively. A total of 200 strictly selected PD candidates diagnosed with PDAC will be randomised to receive LPD or OPD. The primary outcome is the 5-year overall survival rate, whereas the secondary outcomes include overall survival, disease-free survival, 90-day mortality, complication rate, comprehensive complication index, length of stay and intraoperative indicators. We hypothesise that LPD is not inferior to OPD for the treatment of resectable PDAC. The enrolment schedule is estimated to be 2 years and follow-up for each patient will be 5 years.Ethics and dissemination This study received approval from the Tongji Hospital Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology, and monitor from an independent third-party organisation. Results of this trial will be presented in international meetings and published in a peer-reviewed journal.Trial registration number NCT03785743.

With the growing popularity of autonomous electric vehicles (AEVs), optimizing their path-planning and charging strategy has become a critical research area. However, the dynamic nature of transport networks presents a significant challenge when ensuring their efficient operation. The use of vehicle-to-everything (V2X) communication in vehicular ad hoc networks (VANETs) has been proposed to tackle this challenge. However, establishing efficient communication and optimizing dynamic paths with charging selection remain complex problems. In this paper, we propose a joint push–pull communication mode to obtain real-time traffic conditions and charging infrastructure information (i.e., charging stations and energy segments). We also analyze the selection of relay vehicles in multi-hop communication routing, considering factors such as link stability, vehicle distance, and reputation values. Furthermore, we formulate a dynamic optimization problem based on real-time information to minimize travel and charging costs. Our proposed algorithm enables AEVs to obtain charging services from charging stations and conduct dynamic wireless charging via energy segments. We present a dynamic real-time A* algorithm to solve the path-optimization problem and a dynamic real-time charging selection algorithm based on dynamic path optimization when the state of charge is lower than the charging threshold. Extensive simulations demonstrate that the proposed joint push-pull communication mode can provide vehicles the up-to-date information and the developed optimization algorithms effectively reduce travel and charging costs.

Objective: Sufferers of tinnitus, especially of the prolonged type, frequently suffer from comorbid depression and anxiety. From the perspective of the network model, this comorbidity is thought to be an interacting system of these two symptoms. In our study, we conducted a network analysis of depression and anxiety comorbidity in tinnitus sufferers, aiming to identify the central and bridge symptoms and make informed suggestions for clinical interventions and psychotherapy. Method: A total of 566 tinnitus sufferers were enrolled in our study. The Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder 7-Item Questionnaire (GAD-7) were selected to evaluate depression and anxiety symptoms, respectively, followed by network analysis to construct the interacting networks. Results: The findings identified six edges of strongest regularized partial correlations in this network. Of these, three were depression symptoms and three were anxiety symptoms. The anxiety symptoms “Unable to control worry” and “Relaxation difficulty” and the depression symptom “Feeling depressed or hopeless” had the highest expected influence centrality. The analysis results also revealed three bridge symptoms: “Afraid something awful might happen”, “Feeling of worthlessness”, and “Trouble concentrating”. As for “Suicidal ideation”, the direct relations between this symptom and “Afraid something awful might happen” and “Feeling depressed or hopeless” were the strongest. Conclusions: The central and bridge symptoms of the interacting network of depression and anxiety symptoms in tinnitus sufferers can be considered a significant transdiagnostic intervention target for the management of this comorbidity. In particular, clinical prevention and psychotherapy should be implemented, targeting the symptoms that have the strongest associations with suicidal ideation.

The porosity of porous media is a key factor affecting cement slurry diffusion. In this paper, a theoretical model of cement slurry diffusion in porous media considering the variation of porosity is proposed. The model is validated through comparison with the experimental results in the literature. The influence of injection parameters (i.e., the water–cement ratio and the pore fractal dimension) on the porosity and strength of porous media is analyzed. The results indicate that: under the same pore fractal dimension, the porosity of the specimen increases gradually with the increase in diffusion distance, and the rate increases rapidly in the later stage. However, when the fractal dimension of porosity increases to 2.1, the porosity of the consolidated body after grouting does not change with the diffusion distance. The water–cement ratio also affects the porosity of the sample. At a distance below 1.0 m, the sample porosity is larger at a larger water–cement ratio of 1.5. When the distance is more than 1.0 m, the smaller the porosity decreases with increasing water–cement ratios. With the increase in distance, the compressive strength of the specimen first decreases slowly, and then rapidly from 90 kPa to 0 kPa. This is further verified by the pore variation law obtained by SEM. The model is applied to selecting grouting parameter design in road maintenance. The pavement deflection after grouting is effectively reduced, verifying the theoretical model’s applicability.

Abstract Mitogen‐activated protein kinase (MAPK) signaling plays a significant role in reactive oxygen species (ROS) production. The authors have previously shown that Brahma‐related gene 1 (BRG1), a chromatin remodeling protein, contributes to hepatic ROS accumulation in multiple animal and cellular models of liver injury. Here it is reported that DNA damage‐induced transcript 4 (DDIT4) is identified as a direct transcriptional target for BRG1. DDIT4 overexpression overcomes BRG1 deficiency to restore ROS production whereas DDIT4 knockdown phenocopies BRG1 deficiency in suppressing ROS production in vitro and in vivo. Mechanistically, DDIT4 coordinates the assembly of the p38‐MAPK signaling complex to drive ROS production in an S‐nitrosylation dependent manner. Molecular docking identifies several bioactive DDIT4‐inteacting compounds including imatinib, nilotinib, and nateglinide, all of which are confirmed to attenuate hepatic ROS production, dampen p38‐MAPK signaling, and ameliorate liver injury by influencing DDIT4 S‐nitrosylation. Importantly, positive correlation between ROS levels and BRG1/DDIT4/S‐nitrosylated DDIT4 levels is detected in human liver biopsy specimens. In conclusion, the data reveal a transcription‐based signaling cascade that contributes to ROS production in liver injury.

The search for a preventive vaccine against HIV infection remains an ongoing challenge, indicating the need for novel approaches. Parainfluenza virus 5 (PIV5) is a paramyxovirus replicating in the upper airways that is not associated with any animal or human pathology. In animal models, PIV5-vectored vaccines have shown protection against influenza, RSV, and other human pathogens. Here, we generated PIV5 vaccines expressing HIV envelope (Env) and SIV Gag and administered them intranasally to macaques, followed by boosting with virus-like particles (VLPs) containing trimeric HIV Env. Moreover, we compared the immune responses generated by PIV5-SHIV prime/VLPs boost regimen in naïve vs a control group in which pre-existing immunity to the PIV5 vector was established. We demonstrate for the first time that intranasal administration of PIV5-based HIV vaccines is safe, well-tolerated and immunogenic, and that boosting with adjuvanted trimeric Env VLPs enhances humoral and cellular immune responses. The PIV5 prime/VLPs boost regimen induced robust and durable systemic and mucosal Env-specific antibody titers with functional activities including ADCC and neutralization. This regimen also induced highly polyfunctional antigen-specific T cell responses. Importantly, we show that diminished responses due to PIV5 pre-existing immunity can be overcome in part with VLP protein boosts. Overall, these results establish that PIV5-based HIV vaccine candidates are promising and warrant further investigation including moving on to primate challenge studies.

Objective To analyse potential risk factors for postoperative pancreatic fistula (POPF). Methods A retrospective study on risk factors for POPF was conducted in patients undergoing laparoscopic pancreatoduodenectomy. Basic characteristics, and preoperative, intraoperative and postoperative patient data were collected and analysed. Results A total of 268 patients were enrolled in this study, including 54 patients with POPF following surgery (POPF incidence, 20.15%). Univariate analysis indicated that patient’s age, body mass index (BMI), preoperative bilirubin level, pancreas texture, and drainage fluid amylase level on day 1 following surgery were associated with POPF. Multiple logistic regression analysis indicated that preoperative bilirubin level ≥170 µmol/l, soft pancreas texture, BMI ≥25, and age ≥65 years were independent risk factors associated with POPF. Conclusions For patients with preoperative bilirubin level ≥170 µmol/l, soft pancreas texture, BMI ≥25 and age ≥65 years, clinically relevant measures should be taken as early as possible for the prophylaxis of POPF.

The mesoporous silica modified by salicylaldimine was prepared through a co-condensation method. Through the bridge effect from metal ion (copper ion, zinc ion, manganese ion), the model drug-avermectin was supported on the metal-Schiff base functionalized mesoporous silica (M-MCM-41) to form a highly efficient adsorbents for pesticidedelivery and removal. The experimental results showed that the sequence in adsorption capacity (AC) for avermectin (AVM) of various mesoporous silica in different adsorption time was Zn-MCM-41 > Cu-MCM-41 > Mn-MCM-41 > MCM-41 > SA-MCM-41. The AC of Zn-MCM-41 was 151 mg/g, while the MCM-41 was 78 mg/g which increased nearly 100 % after modification due to its strongest coordination ability. The FT-IR and XPS results confirmed the existence of coordination bond between SA-MCM-41 and metal ions as well as the coordination bond between M-MCM-41 and avermectin. The kinetic data and the equilibrium isotherms are modeled by three kinetic models, the pseudo-first-order, the pseudo-second-order and intraparticle diffusion, and two isotherm models, Langmuir and Freundlich, respectively. The kinetic mechanism of the adoption changed from physical adsorption to the intraparticle diffusion due to the stronger interaction between avermectin and the mesoporous silica through coordination. Adsorption isotherm of the samples were well-represented by Freundlich model which indicated that the adsorption was reversible.

Background/Aims: We aimed to study the involvement of circZMYM2 (hsa_circ_0099999) in pancreatic cancer (PC) cell proliferation, apoptosis and invasion and to figured out the underlying mechanism of circZMYM2 regulating miR-335-5p and JMJD2C. Methods: CircRNA differential expressions in twenty PC samples and paired normal tissue samples were analyzed using Arraystar Human CircRNA microarray V1. CircZMYM2 expression level was determined via qRT-PCR. The effects of circZMYM2 inhibition and overexpression on cell proliferation, cell apoptosis and cell invasion were investigated by CCK-8 assays, Flow cytometry assays and Transwell assays. An animal experiment on nude mice was put forward to test the influence of circZMYM2 knockdown on tumor growth. The relationship between circZMYM2, miR-335 and JMJD2C was verified by RNA pull down, dual-luciferase reporter assays and rescue experiment. The effect of circZMYM2 and miR-335-5p on the expression of JMJD2C protein was detected by western blot. Results: CircZMYM2 overexpression was observed in both PC tissues and cells. Knockdown of circZMYM2 inhibited proliferation, induced apoptosis, and weakened invasion ability of cancer cells. Tumor growth was restrained in vivo. CircZMYM2 repressed the expression of its target miR-335-5p. MiR-335-5p attenuated pancreatic cancer development via inhibition of JMJD2C. Conclusion: Our study demonstrated that circZMYM2 promoted PC progression. CircZMYM2 had a sponge effect on miR-335-5p and modulated the downstream oncogene JMJD2C.

Understanding the effect of thermal treatment on the physical and chemical properties of protein and its mechanisms has important theoretical implications in food science. Pea seed ferritin (PSF) is an iron storage protein naturally occurring in pea seeds, which represents a promising iron supplement. However, how thermal processing affects the structure and function of PSF remains unknown. In this work, during the production of pea seed milk, we investigated the effect of thermal treatments at boiling temperature for two different times (5 and 10 min), respectively, on the structure and function of PSF. The results demonstrated that thermal treatment resulted in a pronounced change in the primary, secondary, and tertiary structure, iron content, and iron oxidation activity of PSF. However, the shell-like structure of PSF can be kept during the processing of pea seed milk. Interestingly, upon thermal treatment, both thermal-treated samples exhibit larger higher iron absorption rate by Caco-2 than untreated PSF at the same protein concentration. Such an investigation provides a better understanding of the relationship between the structure and function of food protein, as affected by thermal treatment.

Trans-differentiation of quiescent hepatic stellate cells (HSC) to myofibroblasts is a hallmark event in liver fibrosis. Previous studies have led to the discovery that myocardin-related transcription factor A (MRTF-A) is a key regulator of HSC trans-differentiation or, activation. In the present study we investigated the interplay between MRTF-A and c-Abl (encoded by Abl1), a tyrosine kinase, in this process. We report that hepatic expression levels of c-Abl were down-regulated in MRTF-A knockout (KO) mice compared to wild type (WT) littermates in several different models of liver fibrosis. MRTF-A deficiency also resulted in c-Abl down-regulation in freshly isolated HSCs from the fibrotic livers of mice. MRTF-A knockdown or inhibition repressed c-Abl in cultured HSCs in vitro. Further analyses revealed that MRTF-A directly bound to the Abl1 promoter to activate transcription by interacting with Sp1. Reciprocally, pharmaceutical inhibition of c-Abl suppressed MRTF-A activity. Mechanistically, c-Abl activated extracellular signal-regulated kinase (ERK), which in turn phosphorylated MRTF-A and promoted MRTF-A nuclear trans-localization. In conclusion, our data suggest that a c-Abl-MRTF-A positive feedback loop contributes to HSC activation and liver fibrosis.

In this paper, a deep neural network hidden Markov model (DNN-HMM) is proposed to detect pipeline leakage location. A long pipeline is divided into several sections and the leakage occurs in different section that is defined as different state of hidden Markov model (HMM). The hybrid HMM, i.e., DNN-HMM, consists of a deep neural network (DNN) with multiple layers to exploit the non-linear data. The DNN is initialized by using a deep belief network (DBN). The DBN is a pre-trained model built by stacking top-down restricted Boltzmann machines (RBM) that compute the emission probabilities for the HMM instead of Gaussian mixture model (GMM). Two comparative studies based on different numbers of states using Gaussian mixture model-hidden Markov model (GMM-HMM) and DNN-HMM are performed. The accuracy of the testing performance between detected state sequence and actual state sequence is measured by micro F1 score. The micro F1 score approaches 0.94 for GMM-HMM method and it is close to 0.95 for DNN-HMM method when the pipeline is divided into three sections. In the experiment that divides the pipeline as five sections, the micro F1 score for GMM-HMM is 0.69, while it approaches 0.96 with DNN-HMM method. The results demonstrate that the DNN-HMM can learn a better model of non-linear data and achieve better performance compared to GMM-HMM method.

Identity-based signature (IBS) which is a paradigm built on public key cryptography has played a significant role in light-weight authentication. With the advent of the post quantum era, the lattice has become a main mathematical tool to construct quantum-immune cryptographic schemes. By utilizing an admissible hash function with compatible algorithms and lattice trapdoors as basic building blocks, we propose a new IBS scheme over lattices. The scheme is proved existentially unforgeable against adaptive identity attacks and chosen message attacks in the standard model under inhomogeneous short integer solution assumption via the generalized partitioning proof technique. Moreover, the scheme needs only logarithmic basic matrices as master public key while keeping the same private key size and signature size as those of other standard model lattice-based IBS schemes. This construction is the first adaptive-ID secure standard model IBS scheme over lattice with such space efficiency.

Purpose: This phase II/III, non-randomized clinical trial aimed to determine the efficacy and safety of the combination of radiofrequency ablation (RFA) and cytokine-induced killer (CIK) cells transfusion for patients with colorectal liver metastases (CRLMs). Experimental Design: A total of 60 eligible patients with CRLMs were enrolled and divided into Group A (RFA alone, n = 30) and Group B (RFA plus CIK, n = 30), and following enzyme-linked immunosorbent spot assay was performed in 8 patients with CEA > 50 ng/mL pre-RFA and 7 days post-RFA and CIK treatment, respectively. Results: The median progression-free survival (PFS) times of Group A and Group B were 18.5 months and 23 months, respectively (P = 0.0336). The 3-year progression-free rates were 13.3% in Group A and 20.3% in Group B, respectively. The median overall survival time was 43 months in Group A, and not reached in Group B. The 3-year survival rates were 64.6% in Group A and 81.0% in Group B, respectively (P = 0.1187). Among the 8 patients with CEA > 50ng/mL, 6 had increase of circulating CEA-specific T cells after RFA (P = 0.010). After CIK cell therapy, the number of CEA-specific T cells increased in all the 8 patients comparing with that pre-treatment (P = 0.001) and in 7 patients comparing with that post-RFA (P = 0.028). Conclusions: We firstly confirm that the combination of RFA and CIK cells boosts CEA-specific T cell response and shows to be an efficacious and safe treatment modality for patients with CRLMs.

Respiratory syncytial virus (RSV) causes substantial lower respiratory tract disease in children and at-risk adults. Though there are no effective anti-viral drugs for acute disease or licensed vaccines for RSV, palivizumab prophylaxis is available for some high risk infants. To support anti-viral and vaccine development efforts, we developed an RSV virus-like particle (VLP) platform to explore the role RSV F and G protein interactions in disease pathogenesis. Since VLPs are immunogenic and a proven platform for licensed human vaccines, we also considered these VLPs as potential vaccine candidates. We developed two RSV VLP platforms, M+P and M+M2-1 that had F and G, F and a G peptide, or a truncated F and G on their surface. Immunoblots of sucrose gradient purified particles showed co-expression of M, G, and F with both VLP platforms. Electron microscopy imaging and immunogold labeling confirmed VLP-like structures with surface exposed projections consistent with F and G proteins. In mice, the VLPs induced both anti-F and -G protein antibodies and, on challenge, reduced lung viral titer and inflammation. These data show that these RSV VLP platforms provide a tool to study the structure of F and G and their interactions and flexible platforms to develop VLP vaccines in which all components contribute to RSV-specific immune responses.

Many machine learning methods have been applied for short messaging service (SMS) spam detection, including traditional methods such as naïve Bayes (NB), vector space model (VSM), and support vector machine (SVM), and novel methods such as long short-term memory (LSTM) and the convolutional neural network (CNN). These methods are based on the well-known bag of words (BoW) model, which assumes documents are unordered collection of words. This assumption overlooks an important piece of information, i.e., word order. Moreover, the term frequency, which counts the number of occurrences of each word in SMS, is unable to distinguish the importance of words, due to the length limitation of SMS. This paper proposes a new method based on the discrete hidden Markov model (HMM) to use the word order information and to solve the low term frequency issue in SMS spam detection. The popularly adopted SMS spam dataset from the UCI machine learning repository is used for performance analysis of the proposed HMM method. The overall performance is compatible with deep learning by employing CNN and LSTM models. A Chinese SMS spam dataset with 2000 messages is used for further performance evaluation. Experiments show that the proposed HMM method is not language-sensitive and can identify spam with high accuracy on both datasets.

The stress wave reflection method is widely used in the detection of structure size and integrity due to its advantages of low environmental impact and convenience. The detection accuracy depends on the accurate extraction of the stress wave reflection period. The traditional peak–peak method (PPM) measures the time interval between the first two peaks of the reflected waves to extract the reflection period. However, human interpretation is not avoidable for identifying the weak peak due to signal energy leaks into the surrounding environment. This paper proposes an algorithm for automatic extraction of the stress wave reflection period based on image processing to avoid human interference. The image is the short-time Fourier transform (STFT) spectrogram of the reflected wave signal after applying wavelet denoising and quadratic self-correlation operations. The edge detection method of image processing is used to extract the periodically occurring trough in the image. Graying and filtering are performed to eliminate interference. The frequency of the trough distribution is calculated by using the fast Fourier transform (FFT), and then the reflection period of the stress wave is obtained. The effectiveness and accuracy of the proposed method are validated by measuring the different lengths of two buried metal piles in soil. Comparing with the existing method of extracting the stress wave reflection period, this new algorithm comprehensively utilizes the time–frequency domain information of the stress wave reflection signal.

Molybdenum disulfide (MoS2) has been recognized as one of the most promising catalysts to replace Pt for hydrogen evolution reaction (HER) electrocatalysis because of the elemental abundance, excellent catalytic potential, and stability. However, its HER efficiency is still below that of Pt. Recent research advances have revealed that the modification of pristine MoS2 is a very effective approach to boost its HER performance, including improving the intrinsic activity of sites, increasing the number of edges, and enhancing the electrical conductivity. In this review, we focus on the recent progress on the modification strategies of MoS2 for enhanced electrocatalytic hydrogen evolution. Moreover, some urgent challenges in this field are also discussed to realize the large-scale application of the modified-MoS2 catalysts in industry.

HIV-specific antibodies (Abs) can reduce viral burden by blocking new rounds of infection or by destroying infected cells via activation of effector cells through Fc–FcR interaction. This latter process, referred to as antibody-dependent cellular cytotoxicity (ADCC), has been associated with viral control and improved clinical outcome following both HIV and SIV infections. Here we describe an HIV viral-like particle (VLP)-based sorting strategy that led to identification of HIV-specific memory B cells encoding Abs that mediate ADCC from a subtype A-infected Kenyan woman at 914 days post-infection. Using this strategy, 12 HIV-envelope-specific monoclonal antibodies (mAbs) were isolated and three mediated potent ADCC activity when compared to well-characterized ADCC mAbs. The ADCC-mediating Abs also mediated antibody-dependent cell-mediated virus inhibition (ADCVI), which provides a net measure of Fc receptor-triggered effects against replicating virus. Two of the three ADCC-mediating Abs targeted a CD4-induced (CD4i) epitope also bound by the mAb C11; the third antibody targeted the N-terminus of V3. Both CD4i Abs identified here demonstrated strong cross-clade breadth with activity against 10 of 11 envelopes tested, including those from clades A, B, C, A/D and C/D, whereas the V3-specific antibody showed more limited breadth. Variants of these CD4i, C11-like mAbs engineered to interrupt binding to FcγRs inhibited a measurable percentage of the donor's ADCC activity starting as early as 189 days post-infection. C11-like antibodies also accounted for between 18–78% of ADCC activity in 9 chronically infected individuals from the same cohort study. Further, the two CD4i Abs originated from unique B cells, suggesting that antibodies targeting this epitope can be commonly produced. Taken together, these data provide strong evidence that CD4i, C11-like antibodies develop within the first 6 months of infection and they can arise from unique B-cell lineages in the same individual. Further, these mAbs mediate potent plasma IgG-specific ADCC breadth and potency and contribute to ADCC activity in other HIV-infected individuals.

Purpose: This paper investigates the dynamic interaction between the real estate market and the macroeconomic environment of China by use of dynamic coherence function based on co-spectral analysis. Design/methodology/approach: Through a theoretical perspective, the dynamic interrelationship among economic variables at different time intervals (both long and short terms) is analyzed. Findings: The empirical results show that China’s real estate market features a high coherence with the change of the long-term interest rate, employment rate and money supply, while there is a moderate coherence between the real estate market and the inflation rate and economic growth rate, and the coherence between the short-term rate of interest and the real estate market is the lowest. Research implications: Previous researches have some shortcomings. They do not consider the dependence between nonlinear series, but the latter is crucial to avoid the deviation of results. In this paper, we proposed a new method of experience to overcome these shortcomings. Originality/value: The paper provides a reasonable explanation accordingly to different coherences between the real estate market and the macroeconomic variables.