Search

Abstract The preservation of the left colic artery (LCA) during rectal cancer resection remains a topic of controversy, and there is a notable absence of robust evidence regarding the outcomes associated with LCA preservation. And the advantages of robotic-assisted laparoscopy (RAL) surgery in rectal resection remain uncertain. The objective of this study was to assess the influence of LCA preservation surgery and RAL surgery on intraoperative and postoperative complications of rectal cancer resection. Patients who underwent laparoscopic (LSC) or RAL with or without LCA preservation resection for rectal cancer between April 2020 and May 2023 were retrospectively assessed. The patients were categorized into two groups: low ligation (LL) which with preservation of LCA and high ligation (HL) which without preservation of LCA. A one-to-one propensity score-matched analysis was performed to decrease confounding. The primary outcome was operative findings, operative morbidity, and postoperative genitourinary function. A total of 612 patients were eligible for this study, and propensity score matching yielded 139 patients in each group. The blood loss of the LL group was significantly less than that of the HL group (54.42 ± 12.99 mL vs. 65.71 ± 7.37 mL, p

ObjectiveIn order to design and optimize the typical orthogonally stiffened plates commonly used in naval architecture and ocean engineering, it is necessary to investigate the influence of different stiffener configurations on the intrinsic dynamic characteristics of orthogonally stiffened plates.MethodsThe natural frequencies and mode shapes of orthogonally, obliquely and curvilinearly stiffened plates are calculated using the finite element method under clamped boundary conditions. Comparative and analogy analyses of the intrinsic dynamic characteristics of the three types of stiffened plates reveals the influence of stiffener configurations on their dynamic coupling behavior and intrinsic dynamic characteristics.ResultsThe numerical results show that the natural frequency of obliquely stiffened plates can be increased by 9% compared to that of orthogonally stiffened plates, while the stiffness distributions of obliquely stiffened plates and curvilinearly stiffened plates are more homogeneous than that of orthogonally stiffened plates, and the dynamic stiffness homogenization effect of curvilinearly stiffened plates is more significant. In the frequency range below 900 Hz, the stronger the reinforcement, the greater the influence of the stiffener configuration on the dynamic characteristics of stiffened plates.ConclusionThe results of this study can provide valuable references for the design of structures composed of orthogonally stiffened plates.

This paper studies a dual-hop Simultaneous Wireless Information and Power Transfer (SWIPT)-based multi-relay network with a direct link. To achieve high throughput in the network, a novel protocol is first developed, in which the network can switch between a direct transmission mode and a Single-Relay-Selection-based Cooperative Transmission (SRS-CT) mode that employs dynamic decode-and-forward relaying accomplished with Rateless Codes (RCs). Then, under this protocol, an optimization problem is formulated to jointly optimize the network operation mode and the resource allocation in the SRS-CT mode. The formulated problem is difficult to solve because not only does the noncausal Channel State Information (CSI) cause the problem to be stochastic, but also the energy state evolution at each relay is complicated by network operation mode decision and resource allocation. Assuming that noncausal CSI is available, the stochastic optimization issue is first to be addressed by solving an involved deterministic optimization problem via dynamic programming, where the complicated energy state evolution issue is addressed by a layered optimization method. Then, based on a finite-state Markov channel model and assuming that CSI statistical properties are known, the stochastic optimization problem is solved by extending the result derived for the noncausal CSI case to the causal CSI case. Finally, a myopic strategy is proposed to achieve a tradeoff between complexity and performance without the knowledge of CSI statistical properties. The simulation results verify that our proposed SRS-and-RC-based design can achieve a maximum of approximately 40% throughput gain over a simple SRS-and-RC-based baseline scheme in SWIPT-based multi-relay networks.

Abstract Background The unfolded protein response (UPR) is associated with immune cells that regulate the biological behavior of tumors. This article aims to combine UPR-associated genes with immune cells to find a prognostic marker and to verify its connection to the UPR. Methods Univariate cox analysis was used to screen prognostically relevant UPRs and further screened for key UPRs among them by machine learning. ssGSEA was used to calculate immune cell abundance. Univariate cox analysis was used to screen for prognostically relevant immune cells. Multivariate cox analysis was used to calculate UPR_score and Tumor Immune Microenvironment score (TIME_score). WGCNA was used to screen UPR-Immune-related (UI-related) genes. Consensus clustering analysis was used to classify patients into molecular subtype. Based on the UI-related genes, we classified colon adenocarcinoma (COAD) samples by cluster analysis. Single-cell analysis was used to analyze the role of UI-related genes. We detected the function of TIMP1 by cell counting and transwell. Immunoblotting was used to detect whether TIMP1 was regulated by key UPR genes. Results Combined UPR-related genes and immune cells can determine the prognosis of COAD patients. Cluster analysis showed that UI-related genes were associated with clinical features of COAD. Single-cell analysis revealed that UI-related genes may act through stromal cells. We defined three key UI-related genes by machine learning algorithms. Finally, we found that TIMP1, regulated by key genes of UPR, promoted colon cancer proliferation and metastasis. Conclusions We found that TIMP1 was a prognostic marker and experimentally confirmed that TIMP1 was regulated by key genes of UPR.

Metabolic reprogramming occurs when tumor cells replenish themselves with nutrients required for growth to meet their metabolic needs. Cancer-associated fibroblasts (CAFs) are activated fibroblasts involved in building the c (TME) to promote tumor progression and metastasis. Metabolic reprogramming of CAFs can interact with cancer cells to generate metabolic crosstalk. Furthermore, CAF metabolic reprogramming has great potential as a new field of tumor treatment. This review summarizes the role of CAFs in TME and the mechanisms by which metabolic reprogramming of CAFs causes cancer progression and metastasis, demonstrating the great potential of CAF metabolic reprogramming in cancer chemotherapy and immunotherapy treatment. Furthermore, we provide an outlook for future CAF metabolic reprogramming for cancer treatment.

Abstract Metastasis poses a major challenge in colorectal cancer (CRC) treatment and remains a primary cause of mortality among patients with CRC. Recent investigations have elucidated the involvement of disrupted gut microbiota homeostasis in various facets of CRC metastasis, exerting a pivotal influence in shaping the metastatic microenvironment, triggering epithelial-mesenchymal transition (EMT), and so on. Moreover, therapeutic interventions targeting the gut microbiota demonstrate promise in enhancing the efficacy of conventional treatments for metastatic CRC (mCRC), presenting novel avenues for mCRC clinical management. Grounded in the “seed and soil” hypothesis, this review consolidates insights into the mechanisms by which imbalanced gut microbiota promotes mCRC and highlights recent strides in leveraging gut microbiota modulation for the clinical prevention and treatment of mCRC. Emphasis is placed on the considerable potential of manipulating gut microbiota within clinical settings for managing mCRC.

Technological advances are crucial for the optimization of gastric cancer surgery, and the success of any gastric cancer surgery is based on the correct and precise anatomical determination of the primary tumour and tissue structures. Real-time imaging-guided surgery is showing increasing potential and utility, mainly because it helps to aid intraoperative decision-making. However, intraoperative imaging faces many challenges in the field of gastric cancer. This article summarizes and discusses the following clinical applications of real-time optical imaging and fluorescence-guided surgery for gastric cancer: (1) the potential of quantitative fluorescence imaging in assessing tissue perfusion, (2) vascular navigation and determination of tumour margins, (3) the advantages and limitations of lymph node drainage assessment, and (4) identification of peritoneal metastases. In addition, preclinical study of tumour-targeted fluorescence imaging are discussed.

The use of recycled asphalt mixtures in regions with seasonal freeze-thaw cycles is becoming more popular. However, strict requirements for low-temperature cracking resistance limit their widespread application. This study designed thirteen types of recycled asphalt mixtures to explore factors affecting low-temperature performance in seasonal freeze-thaw regions and potential optimization methods. The three-point bending test assessed the low-temperature cracking performance of mixtures with varying recycled asphalt pavement (RAP) content, asphalt-aggregate ratios, asphalt types, and gradations under both conventional and freeze-thaw conditions. Results show that destructive strain and fracture energy decrease with higher RAP content, but increase with higher asphalt-aggregate ratios and 4.75 mm sieve passing rates. Adding rubber powder significantly enhances both destructive strain and fracture energy. Furthermore, the destructive strain remains insensitive to factors under both and freeze-thaw conditions, while fracture energy effectively distinguishes differences in low-temperature crack resistance. Analysis of variance reveals that RAP content, asphalt-aggregate ratio, asphalt type, and gradation significantly affect fracture energy after freeze-thaw cycles. Optimizing gradation is recommended to improve low-temperature performance of recycled asphalt mixtures in freeze-thaw regions.

Deep learning methods like convolution neural networks (CNNs) and transformers are successfully applied in hyperspectral image (HSI) classification due to their ability to extract local contextual features and explore global dependencies, respectively. However, CNNs struggle in modeling long-term dependencies, and transformers may miss subtle spatial-spectral features. To address these challenges, this paper proposes an innovative hybrid HSI classification method aggregating hierarchical spatial-spectral features from a CNN and long pixel dependencies from a transformer. The proposed aggregation multi-hierarchical feature network (AMHFN) is designed to capture various hierarchical features and long dependencies from HSI, improving classification accuracy and efficiency. The proposed AMHFN consists of three key modules: (a) a Local-Pixel Embedding module (LPEM) for capturing prominent spatial-spectral features; (b) a Multi-Scale Convolutional Extraction (MSCE) module to capture multi-scale local spatial-spectral features and aggregate hierarchical local features; (c) a Multi-Scale Global Extraction (MSGE) module to explore multi-scale global dependencies and integrate multi-scale hierarchical global dependencies. Rigorous experiments on three public hyperspectral image (HSI) datasets demonstrated the superior performance of the proposed AMHFN method.

Abstract Background CHF (Congenital hepatic fibrosis) is a rare hereditary disease characterized by periportal fibrosis and ductal plate malformation. Little is known about the clinical presentations and outcome in CHF patients with an extraordinary complication with biliary sepsis. Case summary Our case described a 23-year-old female diagnosed as CHF combined with biliary sepsis. Her blood culture was positive for KP (Klebsiella pneumoniae), and with a high level of CA19-9 (> 1200.00 U/ml, ref: G (p. V1287G) and c.9059T > C (p. L3020P) in PKHD1 gene. After biliary sepsis relieved, her liver function test was normal, and imaging examination results showed no significant difference with the results harvested during her biliary sepsis occurred. Conclusion The diagnosis of CHF complicated with biliary sepsis in the patient was made. Severely biliary sepsis due to KP infection may not inevitably aggravate congential liver abnormality in young patients. Our case provides a good reference for timely treatment of CHF patients with biliary sepsis.

A new design of intelligent reflecting surface (IRS)-aided mobile edge computing (MEC) system was studied, which consisted of a hybrid access point (HAP) connected with an MEC server, an IRS equipped with radio-frequency (RF) energy harvesting (EH) circuits, and a user side with random task arrival.To reduce energy consumption at the user, a novel protocol was proposed first, in which the system was enabled to select a proper operation mode among an EH mode, an IRS-aided task offloading mode, and an IRS-inactive task offloading mode.Then, based on the proposed protocol, an optimization problem was formulated, which aimed at minimizing the amount of consumed energy at the user by optimizing the selection of system operation mode and the resource allocation in each mode.Lyapunov optimization framework was employed to solve the problem to achieve a low-complexity and efficient optimization algorithm.Simulation results show that the proposed scheme can save 50% to 90% of energy consumption for the MEC system as compared with the existing baseline schemes.

[Objective] Orthogonally stiffened plates with different plate-to-beam bending stiffness ratios are taken as the research objects to uncover the dynamic coupling characteristics of the beam and plate components of orthogonally stiffened plates, and reveal the mechanism and influence of dynamic coupling between the construction members on their intrinsic dynamic characteristics. [Method] The natural frequencies and mode shapes of numerical models under free boundary conditions and clamped boundary conditions are calculated using the finite element method. Through an analysis of variations in the natural frequencies and mode shapes of an orthogonally stiffened plate against the plate-to-beam bending stiffness ratio, the intrinsic dynamic characteristics of an orthogonally stiffened plate with different bending stiffness ratios are discussed, and the dynamic coupling characteristics between the beam and plate are analyzed. [Results] The numerical results show that with the variation of the plate-to-beam bending stiffness ratios, the dynamic behaviour of the orthogonally stiffened plate transforms between two kinds of characteristics: one dominated by the plate and the other one coupled by the beam and plate. The critical plate-to-beam bending stiffness ratios and the criterion for determining them are presented in this paper. [Conclusion] The dynamic coupling between the beam and plate changes the variation rate of the natural frequencies with the plate-to-beam bending stiffness ratio, leading to the dislocation and distortion of the mode shapes of orthogonally stiffened plates.

Abstract Cancer is a major cause of high morbidity and mortality worldwide. Several environmental, genetic and lifestyle factors are associated with the development of cancer in humans and result in suboptimal treatment. The human microbiota has been implicated in the pathophysiological process of cancer and has been used as a diagnostic, prognostic and risk assessment tool in cancer management. Notably, both extratumoural and intratumoural microbiota are important components of the tumor microenvironment, subtly influencing tumorigenesis, progression, treatment and prognosis. The potential oncogenic mechanisms of action of the intratumoural microbiota include induction of DNA damage, influence on cell signaling pathways and impairment of immune responses. Some naturally occurring or genetically engineered microorganisms can specifically accumulate and replicate in tumors and then initiate various anti-tumor programs, ultimately promoting the therapeutic effect of tumor microbiota and reducing the toxic and side effects of conventional tumor treatments, which may be conducive to the pursuit of accurate cancer treatment. In this review, we summarise evidence revealing the impact of the intratumoural microbiota on cancer occurrence and progress and potential therapeutic and diagnostic applications, which may be a promising novel strategy to inhibit tumor development and enhance therapeutic efficacy. Video Abstract

This study employed small-angle X-ray scattering (SAXS) to characterize the microstructure of asphalt and investigated the evolving patterns of microstructure during the aging process of asphalt. Furthermore, by utilizing Fourier transform infrared (FTIR) spectroscopy, a detailed explanation of the intrinsic mechanisms governing microstructural changes in asphalt during aging was provided. The study demonstrated that the unified power-law exponential equation is more suitable for analyzing the SAXS curve of asphalt compared to model-dependent analyses. This equation not only exhibits a strong fit to the SAXS curve of asphalt but also yields crucial parameters about asphalt's microstructure, including the scattering coefficient (P) of asphaltene clusters, the scattering coefficient (Ps) of micelles, and the radius of gyration (Rs) of micelles. The SAXS experiments indicate the presence of asphaltene clusters with a surface fractal structure in asphalt, by a size exceeding 100 nm. The asphaltene clusters exhibit a propensity for ''phase separation'' with the aging of asphalt. Furthermore, asphalt aging leads to an increase in the Rs of the micelles and alters the Ps of the micelles. These changes are attributed to both the aggregation of the micelles and alterations in the manner in which micelles aggregate, which are primarily caused by the excessive aging of the maltene fraction. To analyse the effect of microstructural changes on macroscopic properties during asphalt aging, the changes in high and low temperature properties of asphalt during aging were tested in this study using the multiple stress creep and recovery (MSCR) test and the bending beam rheometer (BBR) test, respectively. It was found that the changes in macro properties of asphalt during aging are not entirely due to the changes in microstructure. This study expands the application of SAXS for microstructural analysis of asphalt and contributes to a profound comprehension of the aging mechanism of asphalt from a microstructural perspective.

Abstract Metastasis, the spread of a tumor or cancer from the primary site of the body to a secondary site, is a multi-step process in cancer progression, accounting for various obstacles in cancer treatment and most cancer-related deaths. Metabolic reprogramming refers to adaptive metabolic changes that occur in cancer cells in the tumor microenvironment (TME) to enhance their survival ability and metastatic potential. Stromal cell metabolism also changes to stimulate tumor proliferation and metastasis. Metabolic adaptations of tumor and non-tumor cells exist not only in the TME but also in the pre-metastatic niche (PMN), a remote TME conducive for tumor metastasis. As a novel mediator in cell-to-cell communication, small extracellular vesicles (sEVs), which have a diameter of 30–150 nm, reprogram metabolism in stromal and cancer cells within the TME by transferring bioactive substances including proteins, mRNAs and miRNAs (microRNAs). sEVs can be delivered from the primary TME to PMN, affecting PMN formation in stroma rewriting, angiogenesis, immunological suppression and matrix cell metabolism by mediating metabolic reprogramming. Herein, we review the functions of sEVs in cancer cells and the TME, how sEVs facilitate PMN establishment to trigger metastasis via metabolic reprogramming, and the prospective applications of sEVs in tumor diagnosis and treatment. Video Abstract

Abstract Presenting with a poor prognosis, gastric cancer (GC) remains one of the leading causes of disease and death worldwide. Long non-coding RNAs (lncRNAs) regulate tumor formation and have been long used to predict tumor prognosis. N7-methylguanosine (m7G) is the most prevalent RNA modification. m7G-lncRNAs regulate GC onset and progression, but their precise mechanism in GC is unclear. The objective of this research was the development of a new m7G-related lncRNA signature as a biomarker for predicting GC survival rate and guiding treatment. The Cancer Genome Atlas database helped extract gene expression data and clinical information for GC. Pearson correlation analysis helped point out m7G-related lncRNAs. Univariate Cox analysis helped in identifying m7G-related lncRNA with predictive capability. The Lasso-Cox method helped point out seven lncRNAs for the purpose of establishing an m7G-related lncRNA prognostic signature (m7G-LPS), followed by the construction of a nomogram. Kaplan–Meier analysis, univariate and multivariate Cox regression analysis, calibration plot of the nomogram model, receiver operating characteristic curve and principal component analysis were utilized for the verification of the risk model’s reliability. Furthermore, q-PCR helped verify the lncRNAs expression of m7G-LPS in-vitro. The study subjects were classified into high and low-risk groups based on the median value of the risk score. Gene enrichment analysis confirmed the constructed m7G-LPS’ correlation with RNA transcription and translation and multiple immune-related pathways. Analysis of the clinicopathological features revealed more progressive features in the high-risk group. CIBERSORT analysis showed the involvement of m7G-LPS in immune cell infiltration. The risk score was correlated with immune checkpoint gene expression, immune cell and immune function score, immune cell infiltration, and chemotherapy drug sensitivity. Therefore, our study shows that m7G-LPS constructed using seven m7G-related lncRNAs can predict the survival time of GC patients and guide chemotherapy and immunotherapy regimens as biomarker.

ObjectivesIn order to explore the relationship and difference between the intrinsic dynamic characteristics of the orthogonally stiffened plate of different dimensions, the scale effect of the intrinsic dynamic characteristics of the construction members, such as the beam and the plate, as well as the dynamically coupled structure of the two construction members, the orthogonally stiffened plate, was analyzed and discussed. MethodsTaking the models of the beam, the plate and the orthogonally stiffened plate as research objects, the natural frequencies and mode shapes of the above-mentioned models of different sizes were calculated by the finite element method. The influence of boundary conditions on the scale effect is discussed in terms of the similarities and differences between the natural frequencies of the beam model and the plate model of the unit scale under the free boundary conditions with those of the models under the simply supported boundary conditions. The influence of dynamic coupling between the construction members of the beam and the plate on the size effect of the intrinsic dynamic characteristics of the orthogonally stiffened plate was investigated by discussing the similarities and differences between the natural frequencies and mode shapes of the orthogonally stiffened plate of unit scale with those of the beam model and the plate model of unit scale. ResultsNumerical results show that the variation of the natural frequencies of the model of unit scale against the size of the model under free boundary conditions no longer strictly follows the law that the natural frequencies are inversely proportional to the square of the size, but it is generally similar, or close to, the law. ConclusionsThe dynamic coupling between the construction members of the beam and the plate, results in the transformation of the variation of the natural frequencies against the size of the orthogonally stiffened plate of unit scale from a rapid decrease to a gradual increase. It also leads to dislocation and distortion of the mode shape of specified orders of the orthogonally stiffened plate, which contrasts with the classical pattern and regular lattice distribution of mode shapes of the unstiffened plate.

In order to further improve the spectral efficiency of intelligent reflecting surface (IRS)-assisted millimeter wave non-orthogonal multiple access (NOMA) system, a joint design scheme of user clustering, successive interference cancellation (SIC) decoding order, transmit power allocation, analog beam selection and IRS phase shifting was investigated, under the transmit power constraint, SIC decoding rate constraint, beam selection constraint, SIC decoding order constraint, user rate constraint, and IRS phase shift constraint, aiming at maximizing system sum rate.Because of the coupling of discrete variables, combinatorial variables and continuous variables in objective function and constraints, the formulated optimization problem was difficult to solve by traditional optimization methods.To solve it, first the SIC decoding sequence variables were transformed into binary discrete variables through a query table, then the discrete variables and continuous variables were decoupled based on the hybrid whale optimization algorithm, and delt with the optimization constraints based on the penalty function method, and the non-convex optimization problem was transformed into a heuristic problem for iterative solution.Simulation results verify the effectiveness of the proposed scheme.

Colorectal cancer (CRC) is the third most common cancer in the world, and its incidence rate and mortality are on the rise in many countries. In recent years, with the improvement of economic conditions, people’s living habits have changed, including lack of physical activity, poor diet patterns and circadian rhythm disorder. These risk factors can change the colon environment and the composition of intestinal microbiota. This state is called intestinal imbalance, which increases the risk of cancer. Probiotics, a class of microorganisms that help maintain gut microbial homeostasis and alleviate dysbiosis, may help prevent inflammation and colorectal cancer. These probiotics inhibit or ameliorate the effects of dysbiosis through the production of short-chain fatty acids (SCFAs), modulation of immunity, maintenance of the intestinal epithelial barrier, pro-apoptotic mechanisms, and other mechanisms. This review aims to explain the interaction between probiotics, the gut microenvironment and the gut microbiota, and summarize reports on the possibility of probiotics in the prevention and treatment of colorectal cancer.

Abstract Experimental colitis can persist as a chronic disease, accompanied with an underlying risk of development into colorectal cancer. Metastasis-associated protein 1 (MTA1), as a chromatin modifier, exerts notable association with multiple diseases, including colitis. The current study aims to investigate the mechanism of MTA1/HIF1A/AQP4 axis in experimental colitis in mice. First, experimental colitis mouse models were established using dextran sulfate sodium (DSS) and in vitro colonic epithelial cells FHC inflammation models were with lipopolysaccharide (LPS) for determination of MTA1 and HIF1A expressions. It was found that MTA1 and HIF1A were both highly-expressed in experimental colitis samples. Results of dual-luciferase reporter gene assay and ChIP assay further revealed that MTA1 activated HIF1A, and subsequently induced AQP4 transcription to up-regulate AQP4 in experimental colitis. Following loss- and gain-function, the effects of MTA1/HIF1A/AQP4 axis on apoptosis and viability of colon epithelial cells were detected by a combination of TUNEL staining and flow cytometry, and CCK-8 assay. It was observed that silencing of MAT1 in the FHC and NCM460 cells reduced IL-1β and TNF-α expressions induced by LPS. Meanwhile, AQP4 promoted LPS-induced inflammation, and exacerbated apoptosis of colon epithelial cells and augmented experimental colitis development in mice. In vivo experiments further verified that TGN-020 treatment effectively alleviated DSS-induced experimental colitis in mice and diminished apoptosis of colon epithelial cells. Altogether, MTA1 may promote AQP4 transcription by activating HIF1A, thus exacerbating DSS-induced experimental colitis in mice, which provides a novel direction for the treatment of experimental colitis.

Although increasing studies have confirmed the distinction between emotion-label words (words directly label emotional states) and emotion-laden words (words evoke emotions through connotations), the existing evidence is inconclusive, and their embodiment is unknown. In the current study, the emotional categorization task was adopted to investigate whether these two types of emotion words are embodied by directly comparing how they are processed in individuals’ native language (L1) and the second language (L2) among late Chinese-English bilinguals. The results revealed that apart from L2 negative emotion-laden words, both types of emotion words in L1 and L2 produced significant emotion effects, with faster response times and/or higher accuracy rates. In addition, processing facilitation for emotion-label words over emotion-laden words was observed irrespective of language operation; a significant three-way interaction between the language, valence and emotion word type was noted. Taken together, this study suggested that the embodiment of emotion words is modulated by the emotion word type, and L2 negative emotion-laden words tend to be affectively disembodied. The disassociation between emotion-label and emotion-laden words is confirmed in both L1 and L2 and therefore, future emotion word research should take the emotion word type into account.

Black tea is a healthy and popular tea beverage. However, its main bioactive compounds (theaflavins and thearubigins) are not easily absorbed. The aim of this study was to investigate the modulation of intestinal microbiota by the nonabsorptive components of Keemun black tea (KBT) and Dianhong black tea (DBT), and fructooligosaccharide (FOS) was selected for use in the control group. KBT, DBT, and FOS significantly increased total short-chain acid production. Specifically, FOS treatment predominantly increased the production of acetic acids and black tea treatments increased the production of acetic, propionic, and butyric acids at similar rates. Moreover, FOS exerted a strong bifidogenic effect after 24 h of fermentation; KBT and DBT increased the abundance of the beneficial genus Bacteroides and Roseburia. In summary, the nonabsorptive components of KBT and DBT could serve as novel prebiotics, the underlying mechanisms of which are quite different from those of FOS.

Abstract Inflammatory bowel disease (IBD) comprises a group of chronic inflammatory disorders of the gastrointestinal tract. Accumulating evidence shows that the development of IBD is always accompanied by the dysbiosis of the gut microbiota (GM), causing a decrease in prebiotic levels and an increase in harmful metabolite levels. This leads to persistent immune response and inflammation in the intestine, greatly impairing the physiological function of the gastrointestinal tract. Short-chain fatty acids (SCFAs) are produced by probiotic gut bacteria from a fiber-rich diet that cannot be digested directly. SCFAs with significant anti-inflammatory functions regulate immune function and prevent an excessive immune response, thereby delaying the clinical progression of IBD. In this review, we summarize the generation of SCFAs and their potential therapeutic effects on IBD. Furthermore, we suggest that SCFAs may modulate innate immune recognition and cytokine production to intervene in the progression of IBD. Additional randomized controlled trials and prospective cohort studies should also investigate the clinical impact of SCFA. Video Abstract

Abstract Pancreatic cancer is a highly malignant tumor and, is extremely difficult to diagnose and treat. Metastasis is one of the critical steps in the development of cancer and uses cell to cell communication to mediate changes in the microenvironment. Small extracellular vesicles (sEVs)-carry proteins, nucleic acids and other bioactive substances, and are important medium for communication between cells. There are two primary steps in sVEs-mediated metastasis: communication between pancreatic cancer cells and their surrounding microenvironment; and the communication between primary tumor cells and distant organ cells in distant organs that promotes angiogenesis, reshaping extracellular matrix, forming immunosuppressive environment and other ways to form appropriate pre-metastasis niche. Here, we explore the mechanism of localization and metastasis of pancreatic cancer and use sEVs as early biomarkers for the detection and treatment of pancreatic cancer. Graphical Abstract Video Abstract

Abstract Pancreatic cancer is one of the most common malignancies. Unfortunately, the lack of effective methods of treatment and diagnosis has led to poor prognosis coupled with a very high mortality rate. So far, the pathogenesis and progression mechanisms of pancreatic cancer have been poorly characterized. Exosomes are small vesicles secreted by most cells, contain lipids, proteins, and nucleic acids, and are involved in diverse functions such as intercellular communications, biological processes, and cell signaling. In pancreatic cancer, exosomes are enriched with multiple signaling molecules that mediate intercellular communication with control of immune suppression, mutual promotion between pancreas stellate cells and pancreatic cancer cells, and reprogramming of normal cells. In addition, exosomes can regulate the pancreatic cancer microenvironment and promote the growth and survival of pancreatic cancer. Exosomes can also build pre-metastatic micro-ecological niches and facilitate the targeting of pancreatic cancer. The ability of exosomes to load cargo and target allows them to be of great clinical value as a biomarker mediator for targeted drugs in pancreatic cancer. Video Abstract

Background: Growing evidence suggests the links between moyamoya disease (MMD) and autoimmune diseases. However, the molecular mechanism from genetic perspective remains unclear. This study aims to clarify the potential roles of autoimmune-related genes (ARGs) in the pathogenesis of MMD.Methods: Two transcription profiles (GSE157628 and GSE141025) of MMD were downloaded from GEO databases. ARGs were obtained from the Gene and Autoimmune Disease Association Database (GAAD) and DisGeNET databases. Differentially expressed ARGs (DEARGs) were identified using “limma” R packages. GO, KEGG, GSVA, and GSEA analyses were conducted to elucidate the underlying molecular function. There machine learning methods (LASSO logistic regression, random forest (RF), support vector machine-recursive feature elimination (SVM-RFE)) were used to screen out important genes. An artificial neural network was applied to construct an autoimmune-related signature predictive model of MMD. The immune characteristics, including immune cell infiltration, immune responses, and HLA gene expression in MMD, were explored using ssGSEA. The miRNA-gene regulatory network and the potential therapeutic drugs for hub genes were predicted.Results: A total of 260 DEARGs were identified in GSE157628 dataset. These genes were involved in immune-related pathways, infectious diseases, and autoimmune diseases. We identified six diagnostic genes by overlapping the three machine learning algorithms: CD38, PTPN11, NOTCH1, TLR7, KAT2B, and ISG15. A predictive neural network model was constructed based on the six genes and presented with great diagnostic ability with area under the curve (AUC) = 1 in the GSE157628 dataset and further validated by GSE141025 dataset. Immune infiltration analysis showed that the abundance of eosinophils, natural killer T (NKT) cells, Th2 cells were significant different between MMD and controls. The expression levels of HLA-A, HLA-B, HLA-C, HLA-DMA, HLA-DRB6, HLA-F, and HLA-G were significantly upregulated in MMD. Four miRNAs (mir-26a-5p, mir-1343-3p, mir-129-2-3p, and mir-124-3p) were identified because of their interaction at least with four hub DEARGs.Conclusion: Machine learning was used to develop a reliable predictive model for the diagnosis of MMD based on ARGs. The uncovered immune infiltration and gene-miRNA and gene-drugs regulatory network may provide new insight into the pathogenesis and treatment of MMD.

Background: There are few models to predict the survival of patients of different ethnicities initially diagnosed with metastatic gastric cancer (mGC). Therefore, the aim of this study was to construct a nomogram to predict the cancer-specific survival (CSS) of these patients. Methods: Data for 994 patients initially diagnosed with mGC between 2000 and 2013 were extracted from the Surveillance, Epidemiology, and End Results database. Patients were randomly classified into a training (n = 696) or internal validation (n = 298) cohort, and a cohort of 133 patients from Fudan cohort was used for external validation. A nomogram to predict the CSS of mGC patients was derived and validated using a concordance index (C-index), calibration curves, and decision-curve analysis (DCA). Results: Multivariate Cox regression indicated that five factors were independent predictors of CSS: differentiation grade, T stage, N stage, metastatic site at diagnosis, and with or without chemotherapy. Thus, these factors were integrated into the nomogram model. The C-index value of the nomogram model was 0.63 (95% CI: 0.60–0.65), and those of the internal and external validation cohorts were 0.60 (95%: CI 0.55–0.64) and 0.63 (95%: CI 0.57–0.69), respectively. The calibration curves showed good consistency between the actual and predicted survival rates in both the internal and external validation cohorts. The DCA also showed the clinical utility of the nomogram model. Conclusions: We established a practical nomogram to predict the CSS of patients initially diagnosed with mGC. The nomogram can be used for individualized prediction of survival and to guide clinicians in making treatment decisions.

The large number of microbes found in the gut are involved in various critical biological processes in the human body and have dynamic and complex interactions with the immune system. Disruptions in the host’s gut microbiota and the metabolites produced during fermentation promote the development of intestinal inflammation and colorectal cancer (CRC). Toll-like receptors (TLRs) recognize specific microbial-associated molecular patterns specific to microorganisms whose signaling is involved in maintaining intestinal homeostasis or, under certain conditions, mediating dysbiosis-associated intestinal inflammation. The signaling pathways of TLRs are described first, followed by a discussion of the interrelationship between gut microbes and TLRs, including the activation of TLRs by gut microbes and the effect of TLRs on the distribution of gut microbiota, particularly the role of microbes in colorectal carcinogenesis via TLRs. Finally, we discuss the potential roles of various TLRs in colorectal cancer.

The discovery of immune checkpoint inhibitors (ICIs) has ushered a new era for immunotherapy against malignant tumors through the killing effects of cytotoxic T lymphocytes in the tumor microenvironment (TME), resulting in long-lasting tumor suppression and regression. Nevertheless, given that ICIs are highly dependent on T cells in the TME and that most tumors lack T-cell infiltration, promoting the conversion of such immunosuppressive “cold” tumors to “hot” tumors is currently a key challenge in tumor immunotherapy. Herein, we systematically outlined the mechanisms underlying the formation of the immunosuppressive TME in cold tumors, including the role of immunosuppressive cells, impaired antigen presentation, transforming growth factor-β, STAT3 signaling, adenosine, and interferon-γ signaling. Moreover, therapeutic strategies for promoting cold tumors to hot tumors with adequate T-cell infiltration were also discussed. Finally, the prospects of therapeutic tools such as oncolytic viruses, nanoparticles, and photothermal therapy in restoring immune activity in cold tumors were thoroughly reviewed.

During the operation of underground water-sealed oil storage caverns, a large amount of oil vapor is generated due to volatilization. Oil vapor can easily leak into the surrounding rock, and fractures in the surrounding rock are usually the dominant channels for oil vapor leakage. To study the influence of fractures on oil vapor leakage and migration in underground water-sealed oil storage caverns during the oil storage period, a gas–liquid two-phase flow model of the fracture–pore dual medium in fractured rock mass was established. The program was implemented on the COMSOL platform by using weak-form PDE (partial differential equation). Then, taking an underground water-sealed cavern of an oil reserve as an example, the influence of the characteristic parameters of a single fracture on the evolution process of oil vapor leakage and migration during the oil storage period of the underground water-sealed oil storage cavern was studied. The results were further applied to the Huangdao underground oil depot project. The results show that the spatial distribution of oil vapor leakage is mainly affected by fractures. Through parameter sensitivity analysis, it was found that the geometric characteristic parameters of fractures will have a certain impact on the migration field of oil vapor leakage in underground caverns. Specifically, fracture permeability (kf), fracture width (df), and fracture inclination (θ) are positively correlated with oil vapor leakage parameters (oil vapor leakage range and leakage volume), while the distance between the fracture and the middle cavern (s) is negatively correlated with oil vapor leakage parameters (oil vapor leakage range and leakage volume). The relative influence of fracture geometry parameters on the migration process of oil vapor leakage during the oil storage period of the underground water-sealed oil storage cavern is in the following order: kf> df> s > θ. Engineering application shows that the existence of fractures affects the spatial distribution of oil vapor leakage and migration, and the relationship between oil vapor leakage parameters and oil storage operation time is a positive power function. The gas–liquid two-phase flow model of the fracture–pore dual medium in fractured rock mass developed in this study could offer a numerical simulation tool to assess and mitigate the risk of oil vapor leakage. The research conclusions can provide some references for related problems encountered in similar projects.

BackgroundGastric metastasis from lung cancer (GMLC) is a rare occurrence. The clinicopathological characteristics, outcomes, and prognostic factors remain largely elusive.MethodsWe conducted a systematic review on case reports and case series of GMLC by scanning MEDLINE, Embase, and ISI Web of Knowledge. Data involving the clinicopathological features, treatment, and outcomes were extracted and analyzed. Survival analysis was performed using Kaplan–Meier method. The Cox proportional hazards regression model was used to identify potential prognostic factors associated with survival. Furthermore, a case of metastatic gastric adenocarcinoma of pulmonary origin with epidermal growth factor receptor (EGFR) L858R+T790M mutation was also described and included.ResultsSeventy-eight records involving 114 cases (including ours) were finally included. The median age on admission was 65 years with a male predominance of 79.8%. Lung adenocarcinoma (42.1%), located in the right upper lobe (30.3%), was the most frequent primary tumor. Bleeding (36.7%) and abdominal pain (35.8%) were the two most common symptoms. Endoscopically, gastric lesions were typically presented as elevated lesions with or without volcano-like ulceration, or ulcerative lesions, mostly involving the gastric corpus. The median overall survival time and survival time after diagnosis of metastatic cancer were 11 months [95% confidence interval (CI): 7–14] and 4.5 months (95% CI: 3–9), respectively. The survival analyses revealed that surgical interventions (including lung surgery and/or abdominal surgery) and systemic therapy (including chemotherapy, radiotherapy, and/or targeted therapy) seemed to be positive prognostic factors for both overall survival and survival after diagnosis of metastatic cancer.ConclusionsClinicians should be alerted to the occurrence of gastric metastasis in lung cancer patients. Comprehensive evaluation and appropriate treatment for specific patients may improve the survival rate of GMLC patients.

The human gut microbiome is important for human health. The development of stable microbial communities in the gastrointestinal tract is closely related to the early growth and development of host immunity. After the birth of a baby, immune cells and the gut microbiome mature in parallel to adapt to the complex gut environment. The gut microbiome is closely linked to the immune system and influences each other. This interaction is associated with various diseases in infants and young children, such as asthma, food allergies, necrotizing colitis, obesity, and inflammatory bowel disease. Thus, the composition of the infant gut microbiome can predict the risk of disease development and progression. At the same time, the composition of the infant gut microbiome can be regulated in many ways and can be used to prevent and treat disease in infants by modulating the composition of the infant gut microbiome. The most important impacts on infant gut microbiota are maternal, including food delivery and feeding. The differences in the gut microbiota of infants reflect the maternal gut microbiota, which in turn reflects the gut microbiota of a given population, which is clinically significant.

The diazabicyclooctane (DBO) scaffold is the backbone of non-β-lactam-based second generation β-lactamase inhibitors. As part of our efforts, we have synthesized a series of DBO derivatives A1–23 containing amidine substituents at the C2 position of the bicyclic ring. These compounds, alone and in combination with meropenem, were tested against ten bacterial strains for their antibacterial activity in vitro. All compounds did not show antibacterial activity when tested alone (MIC >64 mg/L), however, they exhibited a moderate inhibition activity in the presence of meropenem by lowering its MIC values. The compound A12 proved most potent among the other counterparts against all bacterial species with MIC from

In this paper, an attempt to exploit the benefits of data-driven methods in solving joint relay selection and beamforming for non-regenerative relay networks has been made. The common relay selection and beamforming optimization problem aiming to maximize the receiver’s achievable rate under the constraint of relay transmit power is intrinsically hard since the mixed discrete and continuous variables. The direct map from channel state information to select a relay with optimized beamforming weights via data-driven methods often fails to yield good results. To overcome this difficulty, we propose a two-stage algorithm based on data-driven method. Firstly, we convert relay selection to a multi-class classification problem, and a support vector machine (SVM) based data-driven scheme is proposed to determine the best relay. After the relay is selected, we utilize a closed-form solution to obtain the corresponding relay beamforming weights. Since the number of relays is often more than two, the sample imbalance problem exists in the classification problem, considered in our proposed data-driven scheme. The core idea of SVM based classification method is to train the optimal parameters of the SVM classifier through a large number of offline sample data. In this way, the computation of relay selection can be transferred to offline SVM training. Simulation results demonstrate that the performance of the proposed method is close to that of the global optimal relay selection scheme. Moreover, our proposed scheme has much lower complexities than the global optimal relay selection scheme, especially when the number of relays is large.

Drilling has demonstrated that oil can be produced from the lacustrine shale in the upper part of the fourth member of the Shahejie Formation (Es4s) in Dongying Depression. These wells are often drilled in multiple lithofacies combinations, rather than a single lithofacies. Thus, it is necessary to classify the shale lithofacies combinations to optimize favorable exploration targets. The basic characteristics of carbonate mineral-rich shales in the Es4s were determined by core description, optical microscopy of thin sections, mineral analysis by X-ray diffraction, and scanning electron microscope analysis of argon ion-polished samples, combined with organic geochemical analysis and reservoir property analysis. The depositional setting was determined, and the lithofacies combinations of the shale were divided based on the depositional setting and vertical changes in lithofacies combination. Lithofacies combinations include 1) laminated argillaceous limestone interbedded with the calcareous mudstone (LLM); 2) laminated argillaceous limestone interbedded with dolomite (LLD); and 3) calcareous mudstone intercalated with argillaceous limestone (BML). LLM formed in a semi-humid climate, with limited detrital provenance, while LLD was mainly the product of an arid climate, little detrital input, semi-deep water, and a strongly reducing saltwater environment. In addition to the basal strata in the center of the depression, the LLD lithofacies combination was also widely developed on the gentle slope and the slope area transitional to deep depression in the south of the basin. BML was mainly formed in a semi-humid climate, brackish, deep water, and a reducing environment with many detrital provenances. The porosity in LLM and LLD consists of various types. Intercrystalline pores in clay minerals, intercrystalline pores and dissolution pores in carbonate minerals, interbedded fractures, and ultra-pressure fractures are well developed. The pore width distribution range of both LLM and LLD is large. The porosity of LLM is slightly higher than that of LLD. Interlayers with higher dolomite content have higher permeability. The types of pores in BML with no significant laminae characteristics are less abundant, and it is difficult to form an effective reservoir porosity network from the pores and microfractures, and hence, the reservoir physical properties are relatively poor. Oil saturation index indicates that both LLD and LLM of medium–low degree of evolution have good oil content.

Although a dysfunctional gut microbiome is strongly linked to colorectal cancer (CRC), our knowledge of the mediators between CRC and the microbiome is limited. MicroRNAs (miRNAs) affect critical cellular processes, such as apoptosis, proliferation, and differentiation, and contribute to the regulation of CRC progression. Increasingly, studies found that miRNAs can significantly mediate bidirectional interactions between the host and the microbiome. Notably, miRNA expression is regulated by the gut microbiome, which subsequently affects the host transcriptome, thereby influencing the development of CRC. This study typically focuses on the specific functions of the microbiome in CRC and their effect on CRC-related miRNA production and reviews the role of several bacteria on miRNA, including Fusobacterium nucleatum, Escherichia coli, enterotoxigenic Bacteroides fragilis, and Faecalibacterium prausnitzii. Based on the important roles of miRNAs and the gut microbiome in CRC, strategies for modulating miRNA expression and regulating the gut microbiome composition need to be applied, such as bioactive dietary components and fecal microorganism transplantation.

Background: Long noncoding RNAs (LncRNA) lead a vital role in colorectal cancer (CRC) development. The infiltrating CD8+ T cell is the main target of immunotherapy. Our study aimed to figure out the potential mechanism of lncRNAs regulating the function of CD8+ T cells in CRC. Methods: We collected bulk RNA-seq, miRNA-seq, and single-cell RNA-seq (scRNA-seq) data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The cibersort algorithm and correlation analysis were used to estimate the abundance of CD8+ T cells and screened out the most relevant lncRNAs. We used scRNA-seq data to identify the main cell lncRNA expressed. Furthermore, one competing endogenous RNA (ceRNA) network focusing on the potential mechanism of lncRNA-derived CD8+ T cell infiltration was constructed. We established a co-culture system to assess the immunosuppressive function of the lncRNA. And we evaluated the effects of the lncRNA on CD8+ T cell cytotoxicity by flow cytometry, qPCR, and clone formation assay. Results: Three CD8+ T cell infiltration-related lncRNAs were identified, and LINC00657 was expressed mainly in tumor cells, negatively associated with CD8+ T cell infiltration. Hsa-miRNA-1224-3p and hsa-miRNA-338-5p and SCD, ETS2, UBE2H, and YY1 were identified to construct the ceRNA network. Immunosuppression-related tumor marker CD155 was proved to be positively correlated with LINC00657 and mRNAs in the ceRNA network. In addition, we proved that LINC00657 could impair the cytotoxicity of CD8+ T cells, and its expression was positively associated with CD155 in vitro. Conclusions: We successfully constructed an lncRNA-derived CD8+ T cell infiltration ceRNA network in CRC. LINC00657 may play a leading role in the CRC immune escape and could be a novel immunotherapy target.

Abstract Cancer displays high levels of heterogeneity and mutation potential, and curing cancer remains a challenge that clinicians and researchers are eager to overcome. In recent years, the emergence of cancer immunotherapy has brought hope to many patients with cancer. Cancer immunotherapy reactivates the immune function of immune cells by blocking immune checkpoints, thereby restoring the anti-tumor activity of immune cells. However, immune-related adverse events are a common complication of checkpoint blockade, which might be caused by the physiological role of checkpoint pathways in regulating adaptive immunity and preventing autoimmunity. In this context, the intestinal microbiota has shown great potential in the immunotherapy of cancer. The intestinal microbiota not only regulates the immune function of the body, but also optimizes the therapeutic effect of immune checkpoint inhibitors, thus reducing the occurrence of complications. Therefore, manipulating the intestinal microbiota is expected to enhance the effectiveness of immune checkpoint inhibitors and reduce adverse reactions, which will lead to new breakthroughs in immunotherapy and cancer management. Video abstract

Ovarian cancer (OC) is one of the most common gynecological malignant tumors. Understanding the molecular mechanisms involved in the development of ovarian cancer is helpful for the diagnosis and treatment of OC. In this study, we found that lncRNA XIST was significantly overexpressed in normal ovarian tissues and down-regulated in OC. Moreover, we showed XIST was associated with the development of OC and down-regulated in advanced stage OC compared to early-stage OC samples. Overexpression of XIST was significantly associated with longer survival in patients with OC. Also, our analysis also showed that lncRNA XIST was closely related to biological processes such as transcription, protein phosphorylation, transport, protein ubiquitination, and DNA repair. To further reveal the function and role of XIST in OC, we constructed a protein-protein interaction network and an endogenous competitive RNA network. The present study provided a theoretical basis for the diagnosis and treatment of OC.

The robotic grinding system for a thin-walled workpiece is a multi-dimensional coupling system composed of a robot, a grinding spindle and the thin-walled workpiece. In the grinding process, a dynamic coupling effect is generated, while the thin-walled workpiece stimulates elastic vibration; the grinding spindle, as an electromechanical coupling actuator, is sensitive to the elastic vibration in the form of load fluctuations. It is necessary to investigate the electromechanical coupling dynamic characteristics under the vibration coupling of the thin-walled workpiece as well as the vibration control of the robotic grinding system. Firstly, considering the dynamic coupling effect between the grinding spindle and thin-walled workpiece, a dynamic model of the grinding spindle and thin-walled workpiece coupling system is established. Secondly, based on this established coupling dynamic model, the vibration characteristics of the thin-walled workpiece and the electromechanical coupling dynamic characteristics of the grinding spindle are investigated. Finally, a speed adaptive control system for the grinding spindle is designed based on a fuzzy PI controller, which can achieve a stable speed for the grinding spindle under vibration coupling and has a certain suppression effect on the elastic vibration of the thin-walled workpiece at the same time.

Pancreatic cancer is associated with highly malignant tumors and poor prognosis due to strong therapeutic resistance. Accumulating evidence shows that activated pancreatic stellate cells (PSC) play an important role in the malignant progression of pancreatic cancer. In recent years, the rapid development of single-cell sequencing technology has facilitated the analysis of PSC population heterogeneity, allowing for the elucidation of the relationship between different subsets of cells with tumor development and therapeutic resistance. Researchers have identified two spatially separated, functionally complementary, and reversible subtypes, namely myofibroblastic and inflammatory PSC. Myofibroblastic PSC produce large amounts of pro-fibroproliferative collagen fibers, whereas inflammatory PSC express large amounts of inflammatory cytokines. These distinct cell subtypes cooperate to create a microenvironment suitable for cancer cell survival. Therefore, further understanding of the differentiation of PSC and their distinct functions will provide insight into more effective treatment options for pancreatic cancer patients.

To solve the time-consuming, laborious, and inefficient problems of traditional methods using classical optimization algorithms combined with electromagnetic simulation software to design antennas, an efficient design method of the multi-objective antenna is proposed based on the multi-strategy improved sparrow search algorithm (MISSA) to optimize a BP neural network. Three strategies, namely Bernoulli chaotic mapping, inertial weights, and t-distribution, are introduced into the sparrow search algorithm to improve its convergent speed and accuracy. Using the Bernoulli chaotic map to process the population of sparrows to enhance its population richness, the weight is introduced into the updated position of the sparrow to improve its search ability. The adaptive t-distribution is used to interfere and mutate some individual sparrows to make the algorithm reach the optimal solution more quickly. The initial parameters of the BP neural network were optimized using the improved sparrow search algorithm to obtain the optimized MISSA-BP antenna surrogate model. This model is combined with multi-objective particle swarm optimization (MOPSO) to solve the design problem of the multi-objective antenna and verified by a triple-frequency antenna. The simulated results show that this method can predict the performance of the antennas more accurately and can also design the multi-objective antenna that meets the requirements. The practicality of the method is further verified by producing a real antenna.

Objective: This exploration aims to explore the effect of Helicobacter pylori infection on blood glucose mechanism and gastric function in patients with type 2 diabetes under the background of electronic medicine, and the effect of community information management platform on health management efficiency of patients with Helicobacter pylori, so as to lay the foundation for clinical research on Helicobacter pylori participation in the mechanism of type 2 diabetes. Methods: In this paper, 300 patients who were treated in our hospital from June 2016 to June 2019 were selected as the research object. Among them, 228 patients with type 2 diabetes were recorded as the experimental group, and 72 patients with non-type 2 diabetes were recorded as the control group. 13C breath test and serum IgG antibody test were performed on each research object. Patients infected with Helicobacter pylori in the experimental group were divided into groups according to the degree of urine albumin excretion. Urinary albumin excretion rate was

Abstract Background As a novel class of non-coding RNAs, circular RNAs (circRNAs) are key regulators of the development and progression of different cancers. However, little is known about the function and biological mechanism of circLMTK2, also named hsa_circ_0001725, in gastric cancer (GC) tumourigenesis. Methods circLMTK2 was identified in ten paired cancer specimens and adjacent normal tissues by RNA sequencing and genome-wide bioinformatic analysis and verified by quantitative real-time PCR (qRT-PCR). Knockdown or exogenous expression of circLMTK2 combined with in vitro and in vivo assays were performed to prove the functional significance of circLMTK2. The molecular mechanism of circLMTK2 was demonstrated by searching the CircNet database and confirmed by RNA in vivo precipitation assays, western blotting, luciferase assays and rescue experiments. Results circLMTK2 was frequently upregulated in GC tissues, and high circLMTK2 expression was associated with poor prognosis, lymph node metastasis and poor TNM stage in GC patients. Functionally, circLMTK2 overexpression promoted GC cell proliferation and tumourigenicity in vitro and in vivo. Furthermore, ectopic circLMTK2 expression enhanced GC cell migration and invasion in vitro and tumour metastasis in vivo. In addition, we demonstrated that circLMTK2 could sponge miR-150-5p, thus indirectly regulating the c-Myc expression and contributing to GC tumourigenesis. Conclusion Our findings demonstrate that circLMTK2 functions as a tumour promoter in GC through the miR-150-5p/c-Myc axis and could thus be a prognostic predictor and therapeutic target for GC.

Antibacterial resistance towards the β-lactam (BL) drugs is now ubiquitous, and there is a major global health concern associated with the emergence of new β-lactamases (BLAs) as the primary cause of resistance. In addition to the development of new antibacterial drugs, β-lactamase inhibition is an alternative modality that can be implemented to tackle this resistance channel. This strategy has successfully revitalized the efficacy of a number of otherwise obsolete BLs since the discovery of the first β-lactamase inhibitor (BLI), clavulanic acid. Over the years, β-lactamase inhibition research has grown, leading to the introduction of new synthetic inhibitors, and a few are currently in clinical trials. Of note, the 1, 6-diazabicyclo [3,2,1]octan-7-one (DBO) scaffold gained the attention of researchers around the world, which finally culminated in the approval of two BLIs, avibactam and relebactam, which can successfully inhibit Ambler class A, C, and D β-lactamases. Boronic acids have shown promise in coping with Ambler class B β-lactamases in recent research, in addition to classes A, C, and D with the clinical use of vaborbactam. This review focuses on the further developments in the synthetic strategies using DBO as well as boronic acid derivatives. In addition, various other potential serine- and metallo- β-lactamases inhibitors that have been developed in last few years are discussed briefly as well. Furthermore, binding interactions of the representative inhibitors have been discussed based on the crystal structure data of inhibitor-enzyme complex, published in the literature.

Background. Owing to the intrinsic stability against common β-lactamases and metallo-lactamases, monobactams gathered special attention in antibiotic drug development. However, so far, aztreonam is the only monobactam approved by FDA for clinical use. We designed new derivatives of aztreonam to enhance its antibacterial efficacy. Methods. We synthesized a series of monocyclic β-lactams by modifying mainly at the C3 position of azetidinone ring. NH2 group at C3 of azetidinone was attached to thiazole and thiadiazole which in turn was linked to nitrogenous heterocyclic rings via amidine moieties. We then investigated the in vitro antibacterial activities of synthesized compounds against ten bacterial strains of clinical interest in comparison to aztreonam and ceftazidime. Results. All compounds showed improved antibacterial activities against tested strains compared to reference drugs. Compounds 14d and 14e were most potent and showed the highest potency against all bacterial strains, with MIC values ranging from 0.25 µg/mL to 8 µg/mL, as compared to aztreonam (MIC 16 µg/mL to >64 µg/mL) and ceftazidime (MIC >64 µg/mL). These compounds (14d and 14e) may be valuable lead targets against multidrug-resistant Gram-negative bacteria.

The development of next generation sequencing (NGS) platform-based single-cell RNA sequencing (scRNA-seq) techniques has tremendously changed biological researches, while there are still many questions that cannot be addressed by them due to their short read lengths. We developed a novel scRNA-seq technology based on third-generation sequencing (TGS) platform (single-cell amplification and sequencing of full-length RNAs by Nanopore platform, SCAN-seq). SCAN-seq exhibited high sensitivity and accuracy comparable to NGS platform-based scRNA-seq methods. Moreover, we captured thousands of unannotated transcripts of diverse types, with high verification rate by reverse transcription PCR (RT-PCR)-coupled Sanger sequencing in mouse embryonic stem cells (mESCs). Then, we used SCAN-seq to analyze the mouse preimplantation embryos. We could clearly distinguish cells at different developmental stages, and a total of 27,250 unannotated transcripts from 9,338 genes were identified, with many of which showed developmental stage-specific expression patterns. Finally, we showed that SCAN-seq exhibited high accuracy on determining allele-specific gene expression patterns within an individual cell. SCAN-seq makes a major breakthrough for single-cell transcriptome analysis field.

Background/Aims: Increased expression of galectin-1 (Gal-1) in gastric cancer (GC) promotes metastasis and correlates with poor prognosis. The mechanisms by which Gal-1 promotes GC metastasis remain unknown. Methods: Gal-1and Sphingosine-1-phosphate receptor 1 (S1PR1) were determined by immunohistochemistry(IHC) and quantitative real time polymerase chain reaction (qRT-PCR) in GC specimens. Stably transfected Gal-1 or S1PR1 into SGC7901 and MGC-803 cells, western blot and invasion assays in vitro and nude mice tumorigenicity in vivo were also employed. Results: Overexpression of Gal-1 enhanced expression of S1PR1 in SGC-7901 cells, and increased cell invasion, while knockdown Gal-1 in MGC-803 cells reduced S1PR1 expression and diminished invasion. Simultaneous knockdown of Gal-1 and overexpression of S1PR1 in MGC803 cells rescued invasive ability of MGC803 cells. S1PR1 was associated with expression of epithelial-to-mesenchymal transition (EMT) markers in vitro and in clinical samples. EMT induced in MGC-803 cells by TGF-β1 was accompanied by S1PR1 activation, while knockdown of S1PR1 reduced response to TGF-β1, suggest that Gal-1 promotes GC invasion by activating EMT through a S1PR1-dependent mechanism. Overexpression of S1PR1 promoted subcutaneous xenograft growth and pulmonary metastases, and enhanced expression of EMT markers. Conclusion: Galectin-1 promotes metastasis in gastric cancer through a S1PR1- dependent mechanism, our results indicate that targeting S1PR1 may be a novel strategy to treat GC metastasis.

Abstract Background We previously reported the development of a set of Gossypium hirsutum-G. australe alien chromosome addition lines. Naturally, however, G. hirsutum-G. australe chromosome exchanges were very limited, impeding the stable transference of useful genes from G. australe (G2G2 genome) into the most cultivated cotton, G. hirsutum (AADD). Results In the present report, the pollen from a pentaploid (2n = AADDG2) of G. hirsutum-G. australe was irradiated with seven different doses ranging from 10 to 40 Grays and used to pollinate emasculated flowers of G. hirsutum over three consecutive years. Irradiation greatly increased the genetic recombination rates of the G. hirsutum and G. australe chromosomes and a total of 107 chromosome introgression individuals in 192 GISH-negative (with no GISH signal on chromosome) survived individuals, 11 chromosome translocation individuals (containing 12 chromosome translocation events) and 67 chromosome addition individuals were obtained in 70 GISH-positive (with GISH signal(s) on chromosome(s)) survived individuals, which are invaluable for mining desirable genes from G. australe. Multicolor genomic in situ hybridization results showed that there were three types of translocation, whole arm translocation, large alien segment translocation and small alien segment translocation, and that all translocations occurred between the G2-genome and the A-subgenome chromosomes in G. hirsutum. We also found that higher doses induced much higher rates of chromosome variation but also greatly lowered the seed viability and seedling survivability. Conclusions Irradiation has been successfully employed to induce chromosome introgressions and chromosome translocations and promote chromosome exchanges between cultivated and wild species. In addition, by balancing the rates of chromosome introgression and translocation to those of seed set, seed germination, and seedling rates in the M1 generation, we conclude that the dosage of 20 Grays is the most suitable. The established methodology may guide the utilization of the tertiary gene pool of Gossypium species such as G. australe in cotton breeding in the future.

Abstract The Chinese concave‐eared frog (Odorrana tormota) is a rare and threatened species with remarkable sexual dimorphism. Intestinal microbes are understood to play important roles in animal physiology, growth, ecology, and evolution. However, little is known about the intestinal microbes in female and male frogs, as well as the contributing effect by gut infesting nematodes to the co‐habiting bacteria and their function in degradation food rich in chitin. Here, this study analyzed the microbiota of the intestinal tract of both female and male, healthy as well as nematode‐infested concave‐eared frogs using high throughput 16S rRNA sequencing and metagenomic techniques. The results showed that the bacterial composition of the microbiota at the phylum level was dominated by Firmicutes, Verrucomicrobia, Bacteroidetes, and Proteobacteria. The study also revealed that the community composition below the class level could be represent sex differences, particularly with regard to Enterobacteriales, Enterobacteriaceae, Peptostreptococcaceae, and Rikenellaceae, among others. Carbohydrate‐active enzyme‐encoding genes and modules were identified in related gut bacteria by metagenomic analysis, with Bacteroidia, Clostridia, and gammaproteobacteria predicted to be the main classes of chitin‐decomposing bacteria in the frog intestine. In addition, the abundance of some bacteria significantly increased or decreased in nematode‐infected hosts compared with healthy individuals, including Verrucomicrobia, Verrucomicrobiae, Negativicutes, Actinobacteria, and Bacilli, among others. This indicates that nematode infection may affect the richness and composition of some gut bacteria.