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Objective: Accumulating evidences indicate that long non-coding RNAs (lncRNAs) play key roles in cancer. This study aims to clarify role of the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in non-small cell lung cancer (NSCLC) and uncover the underlying mechanisms. Materials and Methods: In this experimental study, MALAT1 and miR-202 expression in tissues and cell lines were detected using quantitative real time polymerase chain reaction (qRT-PCR) assay. Cell transfection was conducted using Lipofectamine 3000. Cell proliferation was determined with CCK-8 assay. MMP2 and MMP9 expressions were measured with Western blot. Cell invasive ability was evaluated by Transwell assay. Starbase 2.0 tool was used to predict targets of MALAT1. Dual luciferase reporter assay, RNA-binding protein immunoprecipitation assay and RNA pull-down assay were conducted to confirm the potential direct interaction between MALAT1 and miR-202. Results: MALAT1 was overexpressed in NSCLC samples and cell lines. High expression of MALAT1 was related to large tumor size (>3 cm), poor histological grade, advanced cancer and tumor metastasis in NSCLC. In vitro assays exhibited that knockdown of MALAT1 remarkably decreased A549 cell growth and invasion capacity, while overexpression of MALAT1 significantly enhanced NCI-H292 cell proliferation and invasion ability. Next, we verified that MALAT1 could act as a competing endogenous RNA (ceRNA) by sponging miR-202 in NSCLC and there is a negative correlation between MALAT1 and miR-202. Besides, overexpression of miR-202 inhibited cell proliferation and invasive ability in MALAT1-overexpressed cells. Conclusion: This study demonstrated that lncRNA-MALAT1 gets involved in NSCLC progression by targeting miR- 202, indicating that MALAT1 may serve as a novel therapeutic target for NSCLC treatment.

Pancreatic ductal adenocarcinoma rapidly acquires resistance to chemotherapy, remaining a fatal disease. Immunotherapy is one of the breakthroughs in cancer treatment, which includes immune checkpoint inhibitors, chimeric antigen receptor T‐cell immunotherapy, and neoantigen vaccines. However, immunotherapy has not achieved satisfactory results in the treatment of pancreatic cancer. Immunogenic death comprises proinflammatory cell death, which provides a way to enhance tumor immunogenicity and promote an immune response in solid tumors. Herein, an ionic liquid ablation agent (LAA), synthesized from choline and geranic acid, which triggers necrosis‐induced immunotherapy by remodeling an immunosuppressive "cold" tumor to an immune activated "hot" tumor is described. The results indicate that LAA‐treated tumor cells can enhance immunogenicity, inducing dendritic cell maturation, macrophage M1 polarization, and cytotoxic T lymphocyte infiltration. The results of the present study provide a novel strategy for solid tumor immunotherapy. [ABSTRACT FROM AUTHOR]

The longitudinal distance between the vehicle and the forward vehicle, as well as the longitudinal distance between the vehicle and the opposite vehicle, is the main risk factor of overtaking behavior on two-way two-lane roads. Accurate measurement of these distances is the basis and key to automatic driving technology of two-way two-lane roads. In order to measure these longitudinal distances and improve the ranging accuracy, a vehicle distance measurement method of two-way two-lane roads based on monocular vision was proposed. Firstly, the vehicle detection model suitable for two-way two-lane roads was trained using YOLOv5s neural network. Secondly, aiming at the problem that the camera roll angle is not considered in the traditional geometric ranging method, the influence of the roll angle of the camera on ranging results using the traditional geometric ranging method was analyzed. In addition, the improved geometric ranging method considering the roll angle of the camera was proposed. Then, tests were conducted on a two-way two-lane road, and the results showed that the proposed method was effective. Compared with other methods, the improved geometric ranging method has higher ranging accuracy in this scene and can provide a reference for vision-based vehicle distance measurement in multi-lane scenes. [ABSTRACT FROM AUTHOR]

Migration of fine materials such as soil from the roadbed and the ground will gradually pollute the aggregate in the arrester bed of truck escape ramps. However, there are few studies on the impact of aggregate pollution of the arrester bed on the stopping distance of runaway vehicles. This paper uses the discrete element method to study the influence of aggregates with different degrees of pollution on stopping distance by taking silty cohesive soil as a typical pollutant. In this paper, the stopping process of the uncontrolled vehicle on the arrester bed with different pollution levels was numerically simulated. The simulation results show that the uncontrolled vehicle's stopping distance increases with the contaminated aggregate's soil content. The simulation results show that when the soil content in the contaminated aggregate is less than 15%, the increase in the stopping distance of the uncontrol vehicle is less than 5%; when the soil content is 20–25%, the stopping distance of the uncontrolled vehicle increases by more than 20%; and when the soil content is 30–35%, the stopping distance of uncontrol vehicle increases by more than 50%. Different maintenance measures should be taken according to the increase in stopping distance. [ABSTRACT FROM AUTHOR]

Introduction: Although the fall protection net installed at the end of the truck escape ramp has a protective effect on trucks and drivers, but lacks sufficient theoretical basis and verification method. Objectives: The primary objective of this paper was to design a fall protection net that meets the regulations and research its protection performance. Methods: The finite-element method was used to design the overall size, material, mesh length, mesh type, shape, and supporting structure of the fall protection net installed at the end of truck escape ramp, then dummy and truck models were used to impact the fall protection net to verify the rationality of the design. After the design completed, the truck model was used to impact the fall protection net twice to research the cumulative protection performance. Results: A fall protection net with a width of 6000 mm, a span of 6000 mm, a depth of 5196 mm, a mesh length of 150 mm, a mesh type of diamond mesh, a shape of 60-degree V-shaped, a supporting structure of steel pipe supporting has a better effect on energy absorption and protection. Within the two consecutive impacts, the residual plastic deformation and stress of the fall protection net generated in the first impact severely affect the protection performance in the second impact. Conclusion: It is feasible to use the finite-element method to design and research the fall prevention net installed at the end of the truck escape ramp, and the fall protection net can indeed protect the trucks and drivers, and it should be inspected and maintained after impact to ensure the protective performance in subsequent use. [ABSTRACT FROM AUTHOR]

Southern China is considered an important source of influenza virus pandemics because of the large, diverse viral reservoirs in poultry and swine. To examine the trend in influenza A virus of swine (IAV-S), an active surveillance program has been conducted from 2013 to 2015 in Guangdong, China. The phylogenetic analyses showed that the external genes of the isolates were assigned to the Eurasian avian-like swine (EA) H1N1 and/or human-like H3N2 lineages with multiple substitutions, indicating a notable genetic shift. Moreover, the internal genes derived from different origins (PB2, PB1, PA, NP: pdm/09 (pandemic influenza virus 2009)-origin, M: pdm/09- or EA-origin, NS: North American Triple Reassortant (TR)-origin have become the dominant backbone of IAV-S in southern China. According to the origins of the eight gene segments, the isolates can be categorized into five genotypes. The results of mice experiment showed that the YJ4 (genotype 1) and DG2 (genotype 4) are the most pathogenic to mice, and the viruses are observed in kidneys and brains, indicating the systemic infection. The alterations of the IAV-S gene composition supported the continued implementation of the intensive surveillance of IAV-S and the greater attention focused on potential shifts toward transmission to humans. [ABSTRACT FROM AUTHOR]

Micro-blogging systems have become one of the most important ways for information sharing. Network structure and users’ interactions such as forwarding behaviors have aroused considerable research attention, while mention, as a key feature in micro-blogging platforms which can improve the visibility of a message and direct it to a particular user beyond the underlying social structure, is seldom studied in previous works. In this paper, we empirically study the mention effect in information diffusion, using the dataset from a population-scale social media website. We find that users with high number of followers would receive much more mentions than others. We further investigate the effect of mention in information diffusion by examining the response probability with respect to the number of mentions in a message and observe a saturation at around 5 mentions. Furthermore, we find that the response probability is the highest when a reciprocal followship exists between users, and one is more likely to receive a target user’s response if they have similar social status. To illustrate these findings, we propose the response prediction task and formulate it as a binary classification problem. Extensive evaluation demonstrates the effectiveness of discovered factors. Our results have consequences for the understanding of human dynamics on the social network, and potential implications for viral marketing and public opinion monitoring. [ABSTRACT FROM AUTHOR]

Food occupies a central position in every culture and it is therefore of great interest to understand the evolution of food culture. The advent of the World Wide Web and online recipe repositories have begun to provide unprecedented opportunities for data-driven, quantitative study of food culture. Here we harness an online database documenting recipes from various Chinese regional cuisines and investigate the similarity of regional cuisines in terms of geography and climate. We find that geographical proximity, rather than climate proximity, is a crucial factor that determines the similarity of regional cuisines. We develop a model of regional cuisine evolution that provides helpful clues for understanding the evolution of cuisines and cultures. [ABSTRACT FROM AUTHOR]

The present study was designed to evaluate the effects of Prunella Vulgaris (P. vulgaris) on the immune function in mice. The mice were randomly divided into one control group and three treatment groups of 10 mice each. The control group received pure water and the treatment groups received P. vulgaris extract at concentrations of 0.15, 0.30 and 0.90 g/kg BW orally for 30 days, respectively. Changes in cell immune function, non-specific immunity and humoral immunity function were evaluated. Active lymphocytes and T lymphocyte subsets were determined by fluorescence-activated cell sorting (FACS). Certain Serum concentrations of cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that, for cell immune function, compared with the control group, foot pad thickness in high dose group increased significantly (p<0.01), whereas no significant difference in the proliferative ability of splenic lymphocytes was observed among all groups (p>0.05). For non-specific immunity, NK cell activity increased significantly in a dose-dependent manner in P. vulgaris treated mice (p<0.01), mononuclear-macrophage function in medium and high dose P. vulgaris treated mice were significantly higher than that of the control group (p<0.05). For humoral immunity, no significant differences were observed in terms of the half value of hemolysis (HC50), number of hemolytic plaques and serum IgG level (p>0.05). The percentage of active T and Th lymphocytes of mice peripheral blood in high dose group were significantly higher than that of the control group (p<0.01). There was no significant difference in serum levels of IL-1β, IL-4, IL-10 and IFN-γ among all of the four groups (p>0.05). The data indicated that 0.90 g/kg BW P. vulgaris extract (equivalent to 7.5 g/kg BW crude drug) had some effect on cellular immune function and non-specific immune function in mice. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To investigate the associations of genetic polymorphisms in GSTs genes of the Hakka population of south China with family histories of certain chronic diseases. Methods: Five hundred and thirty-nine healthy Hakka natives of Meizhou city of Guangdong province in south China were involved. The genotypes of GSTM1, GSTT1, GSTP1, GSTM3, and GSTA1 were determined using PCR and restriction fragment length polymorphism analysis. The observed polymorphisms were analyzed by Chi-square and Hardy-Weinberg equilibrium tests. Logistic regression analysis was used to determine the associations of the distributions of GST genotypes with family history of certain chronic diseases. Results: The distributions of polymorphisms in GSTP1, GSTM3, and GSTA1 conformed to the Hardy-Weinberg equilibrium. Compared to the Cantonese, the Hakka had a lower distribution of the GSTM3 deletion genotype (3.15% vs. 11.9%). A weak association was observed between the GSTM1 genetic polymorphism and family history of hypertension. Alcohol drinkers had a higher frequency of the null-GSTM1 genotype, while smokers had a higher frequency of a variant GSTP1 genotype. Conclusion: The results suggest that the Hakka is a special and distinctive Han Chinese ethnic group with different GSTs genetic polymorphisms. Smoking and drinking might be related to the distribution of GST genotypes. [Copyright &y& Elsevier]

The global prevalence of osteoporosis is being exacerbated by the increasing number of aging societies and longer life expectancies. In response, numerous drugs have been developed in recent years to mitigate bone resorption and enhance bone density. Nonetheless, the efficacy and safety of these pharmaceutical interventions remain constrained. Corylin (CL), a naturally occurring compound derived from the anti-osteoporosis plant Psoralea corylifolia L., has exhibited promising potential in impeding osteoclast differentiation. This study aims to evaluate the effect and molecular mechanisms of CL regulating osteoclast differentiation in vitro and its potential as a therapeutic agent for osteoporosis treatment in vivo . Our investigation revealed that CL effectively inhibits osteoclast formation and their bone resorption capacity by downregulating the transcription factors NFATc1 and c-fos, consequently resulting in the downregulation of genes associated with bone resorption. Furthermore, it has been observed that CL can effectively mitigate the migration and fusion of pre-osteoclast, while also attenuating the activation of mitochondrial mass and function. The results obtained from an in vivo study have demonstrated that CL is capable of attenuating the bone loss induced by ovariectomy (OVX). Based on these significant findings, it is proposed that CL exhibits considerable potential as a novel drug strategy for inhibiting osteoclast differentiation, thereby offering a promising approach for the treatment of osteoporosis.

Introduction: Pediatric sepsis (PS) is a life-threatening infection associated with high mortality rates, necessitating a deeper understanding of its underlying pathological mechanisms. Recently discovered programmed cell death induced by copper has been implicated in various medical conditions, but its potential involvement in PS remains largely unexplored. Methods: We first analyzed the expression patterns of cuproptosis-related genes (CRGs) and assessed the immune landscape of PS using the GSE66099 dataset. Subsequently, PS samples were isolated from the same dataset, and consensus clustering was performed based on differentially expressed CRGs. We applied weighted gene co-expression network analysis to identify hub genes associated with PS and cuproptosis. Results: We observed aberrant expression of 27 CRGs and a specific immune landscape in PS samples. Our findings revealed that patients in the GSE66099 dataset could be categorized into two cuproptosis clusters, each characterized by unique immune landscapes and varying functional classifications or enriched pathways. Among the machine learning approaches, Extreme Gradient Boosting demonstrated optimal performance as a diagnostic model for PS. Discussion: Our study provides valuable insights into the molecular mechanisms underlying PS, highlighting the involvement of cuproptosis-related genes and immune cell infiltration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Huang, Chen, Wang, Lai, Mi and Chen.)

Osteoporosis is one of the major health problems characterized by decreased bone density and increased risk of fractures. Nowadays, the treating strategies against osteoporosis are efficient, but still have some drawbacks. Micheliolide, a guaianolide sesquiterpene lactone isolated from Michelia compressa and Michelia champac, has been reported to have anti-inflammatory effects. Here, our data suggest that Micheliolide could protect mice from ovariectomy induced bone loss. According to the Micro-CT scan and histomorphometry quantification data, Micheliolide treatment inhibits excessive osteoclast bone resorption without affecting bone formation in estrogen deficiency mice. Consistently, our data suggest that Micheliolide could inhibit osteoclastogenesis in vitro. Additionally, we confirmed that Micheliolide inhibits osteoclasts formation via inhibiting P38 MAPK signaling pathway, and P79350 (a P38 agonist) could rescue this effect. In summary, our data suggest that Micheliolide could ameliorate estrogen deficiency-induced bone loss via attenuating osteoclastogenesis. Hence, Micheliolide could be used as a novel anti-resorptive agent against osteoporosis.

The US global leadership in science and technology has greatly benefitted from immigrants from other countries, most notably from China in the recent decades. However, feeling the pressure of potential federal investigations since the 2018 launch of the China Initiative, scientists of Chinese descent in the United States now face higher incentives to leave the United States and lower incentives to apply for federal grants. Analyzing data pertaining to institutional affiliations of more than 200 million scientific papers, we find a steady increase in the return migration of scientists of Chinese descent from the United States to China. We also conducted a survey of scientists of Chinese descent employed by US universities in tenured or tenure-track positions (n = 1,304), with results revealing general feelings of fear and anxiety that lead them to consider leaving the United States and/or stop applying for federal grants. If the situation is not corrected, American science will likely suffer the loss of scientific talent to China and other countries.

Frequency-sensitive super-collimation (FSSC) is a novel dispersion phenomenon of photonic crystals (PhCs) that can realize the beam collimating propagation with very high frequency sensitivity. In order to deeply investigate the origin and the stability of FSSC phenomenon in a wide parameter space, we study the geometry of dispersion surface in detail. Four features for the special geometry of dispersion surface with FSSC are found for rectangular PhCs. The special geometry supports the stability of FSSC in a wide range of parameter space. Two-parameter modulation (TPM) method, in which the aspect ratio β and the dielectric constant of rods ɛ r of rectangular lattice are chosen as the key parameters, is used to analyze the geometry of dispersion surface from the frequency changes at the high-symmetry points. Step by step, the origin of such geometry is revealed and the evolving process can be explained by the field distribution changes of Bloch modes at the high-symmetry points. Furthermore, we show that the geometry not only can be used to explain the origin and the stability of FSSC, but also can help us to find other FSSC phenomenons. Theoretically, we believe the geometry of dispersion surface and the TPM can be widely used on the studies of complex dispersion properties of PhCs. The FSSCs found in this work with higher sensitivity or higher stability can help us to design new on-chip PhC devices.

Background: LTX-315 is an oncolytic peptide deriving from bovine lactoferrin, with the ability to induce cancer immunogenic cell death. However, the mechanism used by LTX-315 to trigger the antitumor immune response is still poorly understood. The expression of programmed cell death ligand 1 (PD-L1) largely determines the efficacy and effectiveness of cancer immunotherapies targeting this specific immune checkpoint. This study aimed to demonstrate the potential effect and mechanism of LTX-315 in PD-L1 inhibition-induced anti-pancreatic cancer immunity., Methods: Both immunodeficient and immunocompetent mouse models were used to evaluate the therapeutic efficacy of monotherapy and combination therapy. Flow cytometry and immunohistochemistry were used to assess the immune microenvironment. Multiomic analysis was used to identify the potential target and down-streaming signaling pathway. Both in-house tissue microarray and open accessed The Cancer Genome Atlas data sets were used to evaluate the clinical relevance in pancreatic cancer prognosis., Results: LTX-315 treatment inhibited PD-L1 expression and enhanced lymphocyte infiltration in pancreatic tumors. ATP11B was identified as a potential target of LTX-315 and a critical regulator in maintaining PD-L1 expression in pancreatic cancer cells. As regards the mechanism, ATP11B interacted with PD-L1 in a CKLF-like MARVEL transmembrane domain containing 6 (CMTM6)-dependent manner. The depletion of ATP11B promoted CMTM6-mediated lysosomal degradation of PD-L1, thus reactivating the immune microenvironment and inducing an antitumor immune response. The significant correlation among ATP11B, CMTM6, and PD-L1 was confirmed in clinical samples of pancreatic cancer., Conclusions: LTX-315 was first identified as a peptide drug inducing PD-L1 downregulation via ATP11B. Therefore, LTX-315, or the development of ATP11B-targeting drugs, might improve the efficacy of cancer immunotherapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Classical swine fever (CSF) is one of the most important viral diseases in swine, causing severe economic losses in the swine industry. In China, CSF is one of the key diseases that needs to be controlled; the government has implemented control measures, and vaccination with C-strain vaccines (C-vacs) has been compulsory since the 1950s. C-vacs do not allow the differentiation of field virus-infected and vaccinated animals (DIVA). In 2012, China proposed a goal of eradicating CSF. Additionally, a baculovirus-expressed E2 subunit vaccine (E2-vac) was licensed in 2018. However, the C-vac and E2-vac characteristics have not been compared. Here, we demonstrate that both the C-vac and E2-vac provide complete protection against CSF in pigs. The E2-vac allows DIVA, and the E2 antibody responses of stimulated pigs are developed earlier and are stronger than the C-vac antibody responses. Therefore, the E2-vac is a new candidate licensed vaccine to completely eradicate CSF on pig farms.

Pregnane X receptor (PXR) which belongs to the nuclear hormone receptor superfamily plays vital roles in several biological functions, especially in the inflammatory procedure. Besides that, PXR is revealed by recent studies to have essential effects on bone tissue. As an agonist of PXR, meclizine is a piperazine-derived histamine H1 antagonist, and has been frequently used for prevention and treatment of vomiting and nausea. Because osteoclastogenesis is characterized by the activation of inflammation-related signaling pathways, we speculated that meclizine may affect formation and function of osteoclast. In the present study, we explored the effect of meclizine on RANKL-induced osteoclastogenesis both in vivo and in vitro . In primary bone marrow-derived macrophages (BMMs), meclizine reduced osteoclast formation and bone resorption in a dose-dependent manner, while knockdown of PXR with siRNA partially abrogated the osteoclastogenesis inhibition of meclizine. On the one hand, at the molecular level, meclizine attenuated RANKL-induced activation of c-Fos, NFATc1, nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPKs), including ERK and p38, but not JNK. Meanwhile, meclizine reduced the expression of osteoclast-specific genes, including TRAP, MMP9, Cathepsin K and NFATc1 . On the other hand, meclizine decreased OVX-induced bone loss by repressing osteoclast activity. In conclusion, our results indicated that meclizine inhibits osteoclastogenesis via regulation of several RANKL signaling pathways and PXR was involved in the processes. Therefore, meclizine may be considered as a novel therapeutic candidate for osteoclast-related diseases.

Human behaviors exhibit ubiquitous correlations in many aspects, such as individual and collective levels, temporal and spatial dimensions, content, social and geographical layers. With rich Internet data of online behaviors becoming available, it attracts academic interests to explore human mobility similarity from the perspective of social network proximity. Existent analysis shows a strong correlation between online social proximity and offline mobility similarity, namely, mobile records between friends are significantly more similar than between strangers, and those between friends with common neighbors are even more similar. We argue the importance of the number and diversity of common friends, with a counter intuitive finding that the number of common friends has no positive impact on mobility similarity while the diversity plays a key role, disagreeing with previous studies. Our analysis provides a novel view for better understanding the coupling between human online and offline behaviors, and will help model and predict human behaviors based on social proximity.

For the study of information propagation, one fundamental problem is uncovering universal laws governing the dynamics of information propagation. This problem, from the microscopic perspective, is formulated as estimating the propagation probability that a piece of information propagates from one individual to another. Such a propagation probability generally depends on two major classes of factors: the intrinsic attractiveness of information and the interactions between individuals. Despite the fact that the temporal effect of attractiveness is widely studied, temporal laws underlying individual interactions remain unclear, causing inaccurate prediction of information propagation on evolving social networks. In this report, we empirically study the dynamics of information propagation, using the dataset from a population-scale social media website. We discover a temporal scaling in information propagation: the probability a message propagates between two individuals decays with the length of time latency since their latest interaction, obeying a power-law rule. Leveraging the scaling law, we further propose a temporal model to estimate future propagation probabilities between individuals, reducing the error rate of information propagation prediction from 6.7% to 2.6% and improving viral marketing with 9.7% incremental customers.

The present study was designed to evaluate the effects of Prunella Vulgaris (P. vulgaris) on the immune function in mice. The mice were randomly divided into one control group and three treatment groups of 10 mice each. The control group received pure water and the treatment groups received P. vulgaris extract at concentrations of 0.15, 0.30 and 0.90 g/kg BW orally for 30 days, respectively. Changes in cell immune function, non-specific immunity and humoral immunity function were evaluated. Active lymphocytes and T lymphocyte subsets were determined by fluorescence-activated cell sorting (FACS). Certain Serum concentrations of cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that, for cell immune function, compared with the control group, foot pad thickness in high dose group increased significantly (p<0.01), whereas no significant difference in the proliferative ability of splenic lymphocytes was observed among all groups (p>0.05). For non-specific immunity, NK cell activity increased significantly in a dose-dependent manner in P. vulgaris treated mice (p<0.01), mononuclear-macrophage function in medium and high dose P. vulgaris treated mice were significantly higher than that of the control group (p<0.05). For humoral immunity, no significant differences were observed in terms of the half value of hemolysis (HC50), number of hemolytic plaques and serum IgG level (p>0.05). The percentage of active T and Th lymphocytes of mice peripheral blood in high dose group were significantly higher than that of the control group (p<0.01). There was no significant difference in serum levels of IL-1β, IL-4, IL-10 and IFN-γ among all of the four groups (p>0.05). The data indicated that 0.90 g/kg BW P. vulgaris extract (equivalent to 7.5 g/kg BW crude drug) had some effect on cellular immune function and non-specific immune function in mice.