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Dengue fever as a mosquito-borne disease caused by dengue virus is responsible for a substantial disease burden to the world. Wolbachia as an innovative technique has been approved to inhibit the replication of dengue viruses in mosquitoes or reduce the number of wild mosquitoes. We firstly establish a birth-pulse model with sex structures to depict the nonlinear dynamics of mosquito population and then to investigate how Wolbachia can suppress or replace wild mosquitoes. The existence and stability of periodic solutions of the system are proved by analyzing its stroboscopic map. Theoretical results show that under complete maternal transmission, Wolbachia will successfully establish and completely replace wild mosquitoes. Under incomplete maternal transmission, there may be two pairs of bistable periodic solutions, including the coexistence of replacement failure and partial replacement periodic solutions, or the coexistence of replacement failure and mosquito eradication periodic solutions. For these bistable situations, if the initial proportion of Wolbachia-carrying mosquitoes is greater than the critical threshold, then the strategy of partial replacement or mosquito eradication can be succeeded. Since the initial proportion of Wolbachia mosquitoes is not always greater enough in the field, we introduce mosquito releases into the birth-pulse model, and obtain the condition for the stability of complete replacement periodic solution. Finally, we give rich numerical simulations to show the multiple attractors of the systems, the comparison of three common release strategies and the effects of Wolbachia-induced parameters on control strategies. At last section, we summarize some key suggestions on the control of mosquitoes and dengue fever in practice. This work will be helpful for public health authorities in designing proper release strategies to control the spread of dengue fever. • Birth-pulse mosquito population models with sex structures are established. • Dynamics of the systems are investigated by analyzing their stroboscopic map. • Existence for two pairs of bistable periodic solutions are proved and simulated. • Effects of three release methods and control parameters on control strategies are discussed. [ABSTRACT FROM AUTHOR]

Electrocardiograph signals reflect the current state of the heart and have great significance to the clinical diagnosis of the heart. Convolutional neural networks perform excellently in electrocardiograph pattern recognition. However, CNNs processing ECG signals need to convert them from 1D to 2D, leading to additional circuit and time costs in hardware. Here, a convolution organic transistor (COT) is proposed for monitoring the ECG with CNNs. Based on the surface electric field effect and trap effect, COT can directly process 1D ECG data without complex preprocessing. It can complete the convolution calculation of ECG signals ≈20 000 times per second in theory and reduce the number of devices by 83% compared to conventional arrays. Further, actual ECG signals are measured and input into the COT, which can initially recognize the type of ECG abnormality. Finally, a point calculation detection system is established with 96.2% recognition accuracy in the five‐heartbeat classification task by combining the 1D CNN. [ABSTRACT FROM AUTHOR]

Sarcoma is a malignant tumor that originates from mesenchymal tissue. The common treatment for sarcoma is surgery supplemented with radiotherapy and chemotherapy. However, patients have a 5-year survival rate of only approximately 60%, and sarcoma cells are highly resistant to chemotherapy. Ferroptosis is an iron-dependent nonapoptotic type of regulated programmed cell death that is closely related to the pathophysiological processes underlying tumorigenesis, neurological diseases and other conditions. Moreover, ferroptosis is mediated via multiple regulatory pathways that may be targets for disease therapy. Recent studies have shown that the induction of ferroptosis is an effective way to kill sarcoma cells and reduce their resistance to chemotherapeutic drugs. Moreover, ferroptosis-related genes are related to the immune system, and their expression can be used to predict sarcoma prognosis. In this review, we describe the molecular mechanism underlying ferroptosis in detail, systematically summarize recent research progress with respect to ferroptosis application as a sarcoma treatment in various contexts, and point out gaps in the theoretical research on ferroptosis, challenges to its clinical application, potential resolutions of these challenges to promote ferroptosis as an efficient, reliable and novel method of clinical sarcoma treatment. [ABSTRACT FROM AUTHOR]

Rapid economic development has led to increasingly serious air quality problems. Accurate air quality prediction can provide technical support for air pollution prevention and treatment. In this paper, we proposed a novel encoder-decoder model named as Enhanced Autoformer (EnAutoformer) to improve the air quality index (AQI) prediction. In this model, (a) The enhanced cross-correlation (ECC) is proposed for extracting the temporal dependencies in AQI time series; (b) Combining the ECC with the cross-stage feature fusion mechanism of CSPDenseNet, the core module CSP_ECC is proposed for improving the computational efficiency of the EnAutoformer. (c) The time series decomposition and dilated causal convolution added in the decoder module are exploited to extract the finer-grained features from the original AQI data and improve the performance of the proposed model for long-term prediction. The real-world air quality datasets collected from Lanzhou are used to validate the performance of our prediction model. The experimental results show that our EnAutoformer model can greatly improve the prediction accuracy compared to the baselines and can be used as a promising alternative for complex air quality prediction. [ABSTRACT FROM AUTHOR]

Specific localization of photosensitizers (PSs) to a certain organelle could result in targeted attack to cause greater trauma to cancer cells, eventually maximizing photodynamic therapy (PDT). However, currently, efficient and precise transportation of PSs via drug delivery to tumor cells and subcellular organelles is still challenging, due to a so‐called step‐reduction delivery dilemma (SRDD) which also threatens anticancer drug delivery to exert their efficacy. Herein, a cascade targeting near infrared II (NIR II) fluorescent nanoparticles (NPER/BO‐PDT) is designed that can target bone tumor first and then target the subcellular organelle of endoplasmic reticulum (ER). It is found that NPER/BO‐PDT achieves the targeted accumulation of the bone tumor and then ER. NPER/BO‐PDT generates reactive oxygen species (ROS) in the subcellular organelles of ER under near infrared light irradiation. The continuous ER stress by ROS promotes the release of more damage‐associated molecular patterns, induces immunogenic cell death, stimulates the adaptive immune response, and further synergistically inhibits tumor growth, achieving the so‐called photodynamic‐immunotherapy. Overall, this study exemplifies a safe and efficient nano‐drug delivery system for a bone and ER cascade targeting via delivery of PSs to break the SRDD and highlights potential clinical translation. [ABSTRACT FROM AUTHOR]

There are no studies assessing the epidemiology and burden of decubitus ulcers at global, regional, and national levels. We aim to report this issue from 1990 to 2019 by extracting data from the Global Burden of Disease Study (GBD) 2019 and stratifying it by age, gender, and socio-demographic index (SDI). Globally, the number of prevalent cases of decubitus ulcers in 2019 is 0.85 (95% UI 0.78 to 0.94) million. The age-standardized rates of prevalence, incidence, and years lived with disability (YLDs) in 2019 are 11.3 (95% UI 10.2 to 12.5), 41.8 (37.8 to 46.2), and 1.7 (1.2 to 2.2) per 100,000 population, and compared with 1990, it has decreased by 10.6% (95% UI 8.7% to 12.3%), 10.2% (8.2 to 11.9%), and 10.4% (8.1 to 12.5%), respectively. In addition, the global prevalence rate of decubitus ulcers increases with age, peaking at the > 95 age group among men and women. At the regional and national levels, we observe a positive correlation between age-standardized YLDs and SDI. Malaysia, Saudi Arabia, and Thailand experienced the most significant increases in age-standardized prevalence rates at the national level. Finally, we concluded that the age-standardized prevalence, incidence, and YLDs rates of decubitus ulcer declined from 1990 to 2019, with significant regional differences. In order to monitor the dynamic changes of decubitus ulcers burden, it is recommended to improve the quality of decubitus ulcer health data in all regions and countries. [ABSTRACT FROM AUTHOR]

Introduction: It has been proposed that the copy number (CN) variation (CNV) in β-defensin genes (DEFB) on human chromosome 8p23 determines phenotypic differences in inflammatory diseases. However, no method for accurate and easy DEFB CN quantification is yet available. Objective: Droplet digital polymerase chain reaction (ddPCR) is a novel method for CNV quantification and has been used for genes such as CCL4L, CCL3L1, AMY1, and HER2. However, to date, no ddPCR assay has been available for DEFB CN determination. In the present study, we aimed to develop and evaluate such a ddPCR assay. Methods: The assay was designed using DEFB4 and RPP30 as the target and the reference gene, respectively. To evaluate the assay, 283 DNA samples with known CNs previously determined using the multiple ligation-dependent probe amplification (MLPA) method, the current gold standard, were used as standards. To discover the optimal DNA template amount, we tested 80 to 2.5 ng DNA by a serial of one to two dilutions of eight samples. To evaluate the reproducibility of the assay, 31 samples were repeated to calculate the intra- and inter-assay variations. To further validate the reliability of the assay, the CNs of all 283 samples were determined using ddPCR. To compare results with those using quantitative PCR (qPCR), DEFB CNs for 48 samples were determined using qPCR with the same primers and probes. Results: In a one-dimensional plot, the positive and negative droplets were clearly separated in both DEFB4 and RPP30 detection channels. In a two-dimensional plot, four populations of droplets were observed. The 20 ng template DNA proved optimal, with either high (80 ng) or low (10, 5, 2.5 ng) template input leading to ambiguous or inaccurate results. For the 31 standard samples, DEFB CNs were accurately determined with small intra- and inter-assay variations (coefficient of variation < 0.04 for both). In the validation cohort, ddPCR provided the correct CN for all 283 samples with high confidence. qPCR measurements for the 48 samples produced noisy data with high uncertainty and low accuracy. Conclusions: ddPCR is an accurate, reproducible, easy-to-use, cheap, high-throughput method for DEFB CN determination. ddPCR could be applied to DEFB CN quantification in large-scale case–control studies. [ABSTRACT FROM AUTHOR]

Background: Revision surgery for complex acetabular defects is still technically challenging. In this study, we discussed and compared the clinical and radiological outcomes of revision surgery between two methods using double-trabecular metal (TM) cups alone or combined with impacting bone grafting (IBG). Methods: The records of 18 patients (18 hips) who underwent revision surgery using double-trabecular metal (double-TM) cups between 2008 and 2016 were retrospectively reviewed. All the patients were diagnosed with Paprosky III acetabular defects. The acetabular defects were reconstructed by double-TM cups alone or in combination with IBG. We used the modified Harris Hip Score (mHHS), University of California, Los Angeles (UCLA), and Short Form 36 (SF-36) to evaluate the clinical outcomes. Pelvis plain X-ray was used to assess hip center of rotation (COR), abduction angle and anteversion angle of acetabular cup, and incorporation of the bone graft to host bone. Results: The median follow-up time was 61.0 (IQR 56.0 to 65.8) months. No patients underwent re-revision for loosening or any other reasons. Complications included 3 patients (16.7%) with early dislocation and 3 patients (16.7%) with delayed wound healing. The average mHHS and UCLA preoperatively were 44.1 ± 4.0 (range 35 to 50) and 2.6 ± 0.7 (range 2 to 4), respectively and at the last follow-up were 73.7 ± 4.2 (range 68 to 85) and 7.3 ± 0.5 (range 7 to 8), respectively. The mean SF-36 scores at the last follow-up were improved significantly than preoperative scores, especially in bodily pain category (P < 0.05). The average limb-length discrepancy (LLD) decreased significantly from 24.2 ± 2.6 (range 20 to 32) mm preoperatively to 5.8 ± 1.8 (range 3 to 9) mm at the last follow-up, respectively. However, there was no significant difference between two methods at the last follow-up in terms of mHHS, UCLA, SF-36, LLD, and hip COR (P > 0.05). Radiographic evaluation demonstrated bone graft incorporation in all hips in the follow-up. Conclusions: Defect reconstruction using double-TM cups alone or combined with IBG are practical and reliable treatment options for Paprosky III acetabular defects without pelvic discontinuity. Nevertheless, high postoperative complication rate, especially in terms of dislocation, remains a challenge. [ABSTRACT FROM AUTHOR]

Despite centuries of continuous efforts, mosquito-borne diseases (MBDs) remain enormous health threat of human life worldwide. Lately, the USA government has approved an innovative technology of releasing Wolbachia-infected male mosquitoes to suppress the wild mosquito population. In this paper we first introduce a stage-structured model for natural mosquitos, then we establish a new model considering the releasing of Wolbachia-infected male mosquitoes and the mating competition between the natural male mosquitoes and infected males on the suppression of natural mosquitoes. Dynamical analysis of the two models, including the existence and local stability of the equilibria and bifurcation analysis, reveals the existence of a forward bifurcation or a backward bifurcation with multiple attractors. Moreover, globally dynamical properties are further explored by using Lyapunov function and theory of monotone operators, respectively. Our findings suggest that infected male augmentation itself cannot always guarantee the success of population eradication, but leads to three possible levels of population suppression, so we define the corresponding suppression rate and estimate the minimum release ratio for population eradication. Furthermore, we study how the release ratio of infected males and natural ones, mating competition, the rate of cytoplasmic incompatibility and the basic offspring number affect the suppression rate of natural mosquitoes. Our results show that the successful eradication relies on assessing the reproductive capacity of natural mosquitoes, a selection of suitable Wolbachia strains and an appropriate release amount of infected males. This study will be helpful for public health authorities in designing proper strategies to control vector mosquitoes and prevent the epidemics of MBDs. [ABSTRACT FROM AUTHOR]

Background: We evaluated our results of lengthening of free vascularized fibular grafts using a unilateral external fixator in patients with residual leg length discrepancy after free vascularized fibular graft for lower limb reconstruction.Cases Presentation: Two patients were administrated to our hospital with residual tibial length discrepancy after vascularized free fibular graft surgery. Lengthening of the free vascularized fibular graft with a unilateral external fixator was performed to correct the leg length discrepancy. Both patients recovered well with no difficult in activities of daily living at the last follow-up.Conclusions: This study shows that lengthening of free vascularized fibular grafts with an external fixator is an effective treatment for massive residual leg shortening after vascularized free fibular graft surgery. [ABSTRACT FROM AUTHOR]

Dengue fever is the most common arboviral infection of humans, responsible for a substantial disease burden to the world. Lately, an innovative technology has been approved to suppress natural mosquitoes by releasing Wolbachia-carrying male mosquitoes. To depict the transmission of dengue virus among mosquito and human populations, we respectively couple a stage-structure mosquito population model with and without male augmentation and mating competition into a dengue epidemic model. Dynamical properties of the two high dimensional systems are investigated, including the invariance and boundedness, the existence and local stability of their equilibria and bifurcation analysis. It reveals that there may be a forward or backward bifurcation, or a combination of a saddle-node bifurcation and a forward or backward bifurcation. Moreover, global dynamical properties are explored by comprehensively using the properties of limit system, Lyapunov function and geometric approach. Our results suggest that male augmentation cannot always ensure the eradication of mosquitoes or dengue cases, but it can suppress dengue epidemic to a certain extent. Thus we define the five possible suppression levels of dengue fever and obtain their suppression rates. Also, we investigate how release ratio, mating competition, the rate of cytoplasmic incompatibility and the basic offspring number affect the suppression rates. Finally, under different environment situations, we discuss how to combine male releases, traditional mosquito control methods and human control measures to suppress dengue cases. This study will be helpful for public health authorities in designing proper strategies to control and prevent the epidemics of dengue fever. [ABSTRACT FROM AUTHOR]

Objectives: The physiology of nearly all mammalian organisms are entrained by light and exhibit circadian rhythm. The data derived from animal studies show that light influences immunity, and these neurophysiologic pathways are maximally entrained by the blue spectrum. Here, we hypothesize that bright blue light reduces acute kidney injury by comparison with either bright red or standard, white fluorescent light in mice subjected to sepsis. To further translational relevance, we performed a pilot clinical trial of blue light therapy in human subjects with appendicitis.Design: Laboratory animal research, pilot human feasibility trial.Setting: University basic science laboratory and tertiary care hospital.Subjects: Male C57BL/6J mice, adult (> 17 yr) patients with acute appendicitis.Interventions: Mice underwent cecal ligation and puncture and were randomly assigned to a 24-hour photoperiod of bright blue, bright red, or ambient white fluorescent light. Subjects with appendicitis were randomized to receive postoperatively standard care or standard care plus high-illuminance blue light.Measurements and Main Results: Exposure to bright blue light enhanced bacterial clearance from the peritoneum, reduced bacteremia and systemic inflammation, and attenuated the degree of acute kidney injury. The mechanism involved an elevation in cholinergic tone that augmented tissue expression of the nuclear orphan receptor REV-ERBα and occurred independent of alterations in melatonin or corticosterone concentrations. Clinically, exposure to blue light after appendectomy was feasible and reduced serum interleukin-6 and interleukin-10 concentrations.Conclusions: Modifying the spectrum of light may offer therapeutic utility in sepsis. [ABSTRACT FROM AUTHOR]

Dengue fever has rapidly become the world's most common vector-borne viral disease. Use of endosymbiotic Wolbachia is an innovative technology to prevent vector mosquitoes from reproducing and so break the cycle of dengue transmission. However, strategies such as population eradication and replacement will only succeed if appropriate augmentations with Wolbachia-infected mosquitoes that take account of a variety of factors are carried out. Here, we describe the spread of Wolbachia in mosquito populations using an impulsive differential system with four state variables, incorporating the effects of cytoplasmic incompatibility and the augmentation of Wolbachia-infected mosquitoes with different sex ratios. We then evaluated (a) how each parameter value contributes to the success of population replacement; (b) how different release quantities of infected mosquitoes with different sex ratios affect the success of population suppression or replacement; and (c) how the success of these two strategies can be realized to block the transmission of dengue fever. Analysis of the system's stability, bifurcations and sensitivity reveals the existence of forward and backward bifurcations, multiple attractors and the contribution of each parameter to the success of the strategies. The results indicate that the initial density of mosquitoes, the quantities of mosquitoes released in augmentations and their sex ratios have impacts on whether or not the strategies of population suppression or replacement can be achieved. Therefore, successful strategies rely on selecting suitable strains of Wolbachia and carefully designing the mosquito augmentation program. [ABSTRACT FROM AUTHOR]

Abstract: In a prey–predator model, an effective management strategy called the threshold policy control (TPC) is proposed, resulting in Filippov system. Considering the limitation of environmental resources, Filippov system with the weighted sum as the index is put forward in the prey–predator model with Ivlev’s function response. Firstly, the existences of sliding segments in four cases have been discussed completely. Further, the sliding mode dynamics, the existences of different types of equilibria and tangent point, regular/virtual equilibrium and sliding mode bifurcations have been addressed. Moreover, the results obtained in present work indicate that the local sliding bifurcations such as boundary focus, boundary node and tangent bifurcations occur sequentially with the threshold value varying. Finally, some global sliding bifurcations including touching and buckling bifurcations are investigated by employing numerical techniques. [Copyright &y& Elsevier]

Abstract: Pure zeolite Rho has been synthesized by the hydrothermal method using CsOH and 18-crown-6 ether as the template agent and methylcellulose (MC) as the space-confinement additive. XRD, SEM, FT-IR and TGA-DTA techniques were applied to characterize the obtained zeolite Rho powders. The results indicate that the addition of MC is able to promote the overall crystallization rate of zeolite Rho and simultaneously to control the particles to a size smaller than 1μm and a uniform size distribution. However, a higher calcination temperature, i.e. around 600°C is also required to remove the water and organic species occluded in the zeolite precursor. [Copyright &y& Elsevier]

Oxidization of diamond in the sintering process of diamond/glass composites results in uncontrolled expansion with many irregular pores and low bending strength of the tools. In this paper, Al powder was used as oxygen getter due to its excellent affinity with oxygen. Its oxidization product, Al2O3, entered into glass network. Consequently, oxidization of the grits was inhibited, and the wettability of diamond grits by the matrix improved. As a result, the expansion phenomenon was inhibited and the bending strength improved for all the composites. The minimum volume expansion rate and maximum bending strength were obtained for the composite with 4 wt% Al powder. This Al content resulted in a decrease of volume expansion rate from 175.2% to −10.9%, and an increase in bending strength from 11.3 to 75.1 MPa compared with the composite without Al powder. [ABSTRACT FROM AUTHOR]

Abstract: The wettability and interfacial reactivity between diamond and matrix are of great importance to their bonding strength and the applications, but the relating investigations are scarce. In this paper the wettability and interfacial reactivity in diamond–borosilicate glass system were studied by wettability measurements, thermogravimetry, scanning electron microscope, X-ray diffraction and Raman spectra. Results show an excellent wettability of the diamond by the borosilicate glass melt at temperatures above 700°C. A distinct expansion with many irregular pores can be found in the diamond–borosilicate glass composites sintered above 800°C, which caused by the oxidation of the diamonds. The start oxidation temperature of the diamond in the composites is 817.7°C. So the quite compact bulk composites can be obtained below this temperature. [Copyright &y& Elsevier]

• We proposed a switching patch model to capture ASFV spread from one initial epidemic pig house consecutively to the whole farm. • Spreading process and innocent culling rates of three large-scale pig farms are assessed by model fitting with their data groups, which indicates unnecessarily slaughter all pigs in the farms. • We explore how the disinfection and fixation of employees impact ASFV spread in the farms. • Some essential requirements for large-scale pig farms are summarized to reduce ASFV spreading risk. African swine fever virus (ASFV) leads to a highly contagious, lethal and economically devastating disease among pigs. Since no effective treatment for the disease, it is crucial to investigate its transmission mechanism and control strategies in large-scale pig farms. We first established a toy model to explore ASFV spread in one pig unit. Then a switching patch model was developed to capture its spread from one initial epidemic pig house consecutively to others, even the whole farm. Assessing innocent culling rates of three large-scale epidemic pig farms in Jiangsu Province showed that it is unnecessary to slaughter all pigs in the farms compulsively. Then we explored how the disinfection and fixation of employees impact ASFV spread in the farms. To control ASFV, we can block or slow down its spreading by improving the efficiency of disinfection and decreasing employee population to some extend. We can also shrink potential areas to be infected by properly improving the matching refinement degree among employees and houses. Some essential requirements for large-scale pig farms are presented to reduce their ASFV spreading risk, which can be helpful for animal health authorities in establishing regulation to standardize large-scale pig farms. [ABSTRACT FROM AUTHOR]

Ochratoxin A (OTA), as one of the most important and harmful mycotoxins, is classed as possible human carcinogen (group 2B). As we all know, DNA damage may cause genomic instability, cell cycle disorder, activation of DNA damage pathway, and stimulation of DNA repair system. To explore the roles of DNA damage repair protein (hMLH1) on OTA-induced G 2 arrest, the DNA damage, chromosome aberration, cell cycle distribution and p53-p21 signaling pathway were evaluatd after different time OTA exposure (6, 12, 24, 48 h) in immortalized human gastric epithelial cells (GES-1). Our results demonstrated that OTA exposure could trigger genomic instability, DNA damage and G 2 phase arrest of GES-1 cells. At the same time, OTA treatment could increase the expression of hMLH1, and induce phosphorylation of the p53 protein, as well as p21, in response to DNA damage. Finally, inhibition of hMLH1 by siRNA effectively prevented the activation of p53-p21 signaling pathway and rescued the G 2 arrest elicited by OTA. This study demonstrated that hMLH1-p53-p21 signaling pathway played an important role in DNA damage and G 2 cell cycle arrest the mediated by OTA in GES-1 cells. • OTA treatment for different amounts of time in GES-1 cells could induce chromosomal aberrations, DNA damage and G 2 /M phase arrest. • OTA treatment for different amounts of time induced GES-1 cells to arrest at G 2 /M phase by regulating the expression of Cdc2, p-Cdc2 and CyclinB1. • The hMLH1-p53-p21 signaling pathway play an important role in OTA-caused G 2 phase arrest in GES-1 cells. [ABSTRACT FROM AUTHOR]

Backgroud: Type II congenital pulmonary airway malformation (CPAM) is a rare pulmonary microcystic developmental malformation. Surgical excision is the primary treatment for CPAM, although maternal steroids and betamethasone have proven effective in reducing microcystic CPAM. Disturbed intercellular communication may contribute to the development of CPAM. This study aims to investigate the expression profile and analyze intercellular communication networks to identify genes potentially associated with type II CPAM pathogenesis and therapeutic targets. Methods: RNA sequencing (RNA-seq) was performed on samples extracted from both the cystic area and the adjacent normal tissue post-surgery in CPAM patients. Iterative weighted gene correlation network analysis (iWGCNA) was used to identify genes specifically expressed in type II CPAM. Single-cell RNA-seq (scRNA-seq) was integrated to unveil the heterogeneity in cell populations and analyze the communication and interaction within epithelial cell sub-populations. Results: A total of 2,618 differentially expressed genes were identified, primarily enriched in cilium-related biological process and inflammatory response process. Key genes such as EDN1, GPR17, FPR2, and CHRM1, involved in the G protein-coupled receptor (GPCR) signaling pathway and playing roles in cell differentiation, apoptosis, calcium homeostasis, and the immune response, were highlighted based on the protein-protein interaction network. Type II CPAM-associated modules, including ciliary function-related genes, were identified using iWGCNA. By integrating scRNA-seq data, AGR3 (related to calcium homeostasis) and SLC11A1 (immune related) were identified as the only two differently expressed genes in epithelial cells of CPAM. Cell communication analysis revealed that alveolar type 1 (AT1) and alveolar type 2 (AT2) cells were the predominant communication cells for outgoing and incoming signals in epithelial cells. The ligands and receptors between epithelial cell subtypes included COLLAGEN genes enriched in PI3K-AKT singaling and involved in epithelial to mesenchymal transition. Conclusions: In summary, by integrating bulk RNA-seq data of type II CPAM with scRNA-seq data, the gene expression profile and critical signaling pathways such as GPCR signaling and PI3K-AKT signaling pathways were revealed. Abnormally expressed genes in these pathways may disrupt epithelial-mesenchymal transition and contribute to the development of CPAM. Given the effectiveness of prenatal treatments of microcystic CPAM using maternal steroids and maternal betamethasone administration, targeting the genes and signaling pathways involved in the development of CPAM presents a promising therapeutic strategy. [ABSTRACT FROM AUTHOR]

Empowering displays with intelligent functions enables their application in intelligent image processing and intelligent interactive displays, which is the combination of future display and artificial intelligence technologies. However, existing display technologies face significant processing and transmission burdens due to their conventional hardware separation architecture, which separates memory from the processor and display module from the processing module. To address these challenges, a highly integrated memory‐ processing‐display intelligent light‐emitting hardware (MPDIH) capable of information generation, memory, processing, and visualization is proposed. The MPDIH, based on an organic light‐sensitive layer and activated by ultraviolet light irradiation, exhibits unique photoinhibition behavior attributed to the reverse light‐induced electric field formed by the directional arrangement of photo‐generated excitons. This behavior enables dynamic regulation and autonomous learning during the device training process. Leveraging this phenomenon, intelligent image processing is successfully demonstrated, achieving a significant contrast improvement with a maximum enhancement of 261% compared to unprocessed raw signals. Furthermore, the memory‐processing‐display intelligent image processing scheme enables fashion MNIST image recognition using an artificial neural network, and achieves noticeably higher recognition accuracy (>89%) compared to the original fuzzy images (<59%). Consequently, the proposed memory‐processing‐display intelligent light‐emitting hardware holds promise for future applications in integrated photonic systems and interactive artificial intelligence displays. [ABSTRACT FROM AUTHOR]

Organic photoelectric neuromorphic devices that mimic the brain are widely explored for advanced perceptual computing. However, current individual neuromorphic synaptic devices mainly focus on utilizing linear models to process optoelectronic signals, which means that there is a lack of effective response to nonlinear structural information from the real world, severely limiting the computational efficiency and adaptability of networks to static and dynamic information. Here, a feedforward photoadaptive organic neuromorphic transistor with mixed‐weight plasticity is reported. By introducing the potential of the space charge to couple gate potential, photoexcitation, and photoinhibition occur successively in the channel under the interference of constant light intensity, which enables the device to transform from a linear model to a nonlinear model. As a result, the device exhibits a dynamic range of over 100 dB, exceeding the currently reported similar neuromorphic synaptic devices. Further, the device achieves adaptive tone mapping within 5 s for static information and achieves over 90% robustness recognition accuracy for dynamic information. Therefore, this work provides a new strategy for developing advanced neuromorphic devices and has great potential in the fields of intelligent driving and brain‐like computing. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to gather temporal trends on bacteria epidemiology and resistance of intraoperative bone culture from chronic ostemyelitis at an affiliated hospital in South China.Method: Records of patients with chronic osteomyelitis from 2003 to 2014 were retrospectively reviewed. The medical data were extracted using a unified protocol. Antimicrobial susceptibility testing was carried out by means of a unified protocol using the Kirby-Bauer method, results were analyzed according to Clinical and Laboratory Standards Institute definitions.Result: Four hundred eighteen cases met our inclusion criteria. For pathogen distribution, the top five strains were Staphylococcus aureus (27.9%); Pseudomonas aeruginosa (12.1%); Enterobacter cloacae (9.5%); Acinetobacter baumanii (9.0%) and Escherichia coli (7.8%). Bacterial culture positive rate was decreased significantly among different year-groups. Mutiple bacterial infection rate was 28.1%. One strain of Staphylococcus aureus was resistant to linezolid and vancomycin. Resistance of Pseudomonas aeruginosa stains to Cefazolin, Cefuroxime, Cefotaxime, and Cefoxitin were 100% nearly. Resistance of Acinetobacter baumanii stains against Cefazolin, Cefuroxime were 100%. Ciprofloxacin resistance among Escherichia coli isolates increased from 25 to 44.4%. On the contrary, resistance of Enterobacter cloacae stains to Cefotaxime and Ceftazidime were decreased from 83.3 to 36.4%.Conclusions: From 2003 to 2014, positive rate of intraoperative bone culture of chronic osteomyelitis was decreased; the proportion of Staphylococcus aureus was decreased gradually, and our results indicate the importance of bacterial surveilance studies about chronic osteomyelitis. [ABSTRACT FROM AUTHOR]

Background: Circular ribose nucleic acids (circRNAs), an abundant type of noncoding RNAs, are widely expressed in eukaryotic cells and exert a significant impact on the initiation and progression of various disorders, including different types of cancer. However, the specific role of various circRNAs in colorectal cancer (CRC) pathology is still not fully understood. Methods: The initial step involved the use of quantitative reverse transcription polymerase chain reaction (RT-qPCR) to assess the expression levels of circRNAs and messenger RNA (mRNA) in CRC cell lines and tissues. Subsequently, functional analyses of circCOL1A1 knockdown were conducted in vitro and in vivo through cell counting kit (CCK)-8, colony formation and transwell assays, as well as xenograft mouse model of tumor formation. Molecular expression and interactions were investigated using luciferase reporter assays, Western blot analysis, RNA immunoprecipitation (RIP), and immunohistochemical staining. Results: The RT-qPCR results revealed elevated levels of circCOL1A1 expressions in CRC tissues and cell lines as compared to the normal counterparts. In addition, circCOL1A1 expression level was found to be correlated with TNM stage, lymph node metastases, distant metastases, and invasion. Knockdown of circCOL1A1 resulted in impaired invasion, migration, and proliferation of CRC cells, and suppressed tumor generation in the animal model. We further demonstrated that circCOL1A1 could act as a sponge for miR-214-3p, suppressing miR-214-3p activity and leading to the upregulation of GLS1 protein to promote glutamine metabolism. Conclusion: These findings suggest that circCOL1A1 functions as an oncogenic molecule to promote CRC progression via miR-214-3p/GLS1 axis, hinting on the potential of circCOL1A1 as a therapeutic target for CRC. [ABSTRACT FROM AUTHOR]

The article discusses a study that compares the use of patellar tendon and hamstring autograft in anterior cruciate ligament (ACL) reconstruction in knee amomg female patients. Topics discussed include high occurrence of osteoarthritis in patients with ACL injury, recording of sports activity in athletes after ACL reconstruction using both methods and variations in the ranges of motion among patients.

Anoikis is a specific form of programmed cell death induced by the loss of cell contact with the extracellular matrix and other cells, and plays an important role in organism development, tissue homeostasis, disease development and tumor metastasis. We comprehensively investigated the expression patterns of anoikis-related genes (ARGs) in kidney renal clear cell carcinoma (KIRC) from public databases. Anoikis-related prognostic signatures were established based on four ARGs expression, in which KIRC patients were assigned different risk scores and divided into two different risk groups. In addition, four ARGs expression was validated by qRT-PCR. A better prognosis was observed in the low-risk group, but with lower immune activity (including immune cells and immune-related functions) in the tumor microenvironment. Combined with the relevant clinical characteristics, a nomogram for clinical application was established. Receiver operating characteristics (ROC) and calibration curves were constructed to demonstrate the predictive power of this risk signature. In addition, higher risk scores were significantly and positively correlated with higher gene expression of tumor mutation load (TMB), immune checkpoints (ICPs) and mismatch repair (MMR)-related proteins in general. The results also suggested that the high-risk group was more sensitive to immunotherapy and certain chemotherapeutic agents. Anoikis-related prognostic signatures may provide a better understanding of the roles of ARGs and offer new perspectives for clinical prognosis and individualized treatment. [ABSTRACT FROM AUTHOR]

Background: Wnt signaling contributes to carcinogenesis and tumor progression but the detailed mechanism of constitutive activation or silencing of Wnt signaling is not well-established. We have shown that human iNOS (hiNOS) gene is a target of Wnt/β-catenin signaling pathway, and Wnt/β-catenin signaling regulates hiNOS by inhibiting NF-κB activity in cancer cells. DKK1 is a potent secreted Wnt antagonist that plays a key role in the negative regulation of the canonical Wnt system, by interacting with Wnt co-receptor proteins in the LRP family to inhibit Wnt signaling. However, the relationship between induced NO synthesis and DKK1-mediated inhibition of Wnt signaling has not been examined. The purpose of this study was to determine if iNOS expression and NO influence Wnt/β-catenin activity, and if so whether this was mediated by an effect on DKK1 expression. Methods: Stable cell lines transfected with human iNOS (hiNOS) or DKK-1genes were established in the SW480 colon cancer cell line. Stable cell lines transfected with shRNA-iNOS were established in SW480 colon and MCF7 breast cancer cell lines. A Wnt signaling pathway microarray analysis (SuperArray) was employed to study the global transcriptional response to hiNOS gene expression. The Greiss reaction was used for the detection of NO production. RT-PCR and Western blotting were used for gene expression analysis. Banked cancer tissues were examined for hiNOS and DKK1 expression. Results: Human iNOS (hiNOS) gene expression was inversely correlated with DKK1 expression in human colon and breast cancer tumor samples and intestinal adenoma tumors from Min (APC min/+) mice. HiNOS gene expression promoted canonical Wnt signaling in cancer cells. HiNOS expression transcriptionally downregulated DKK1 gene expression in the Wnt-related gene superarray, and in cancer cell lines stably expressing hiNOS. Cytokines that induced iNOS expression in cancer cells and primary human hepatocytes decreased constitutive DKK1 protein levels. Knocking down hiNOS gene by shRNA restored DKK1 expression and inhibitory effect on Wnt signaling. These findings demonstrate that iNOS/NO down-regulate DKK1 gene expression at the transcriptional level in vitro, and are consistent with the in vivo findings in cancer tissues where iNOS and DKK1 expression are inversely correlated. Conclusion: These data identify a previously unrecognized mechanism by which the iNOS/NO pathway promotes cancer by inhibiting DKK1 which unleashes Wnt/β-catenin signaling leading to enhanced β-catenin target gene activation. The findings provide new insight into the complex control mechanisms of iNOS/NO, DKK1, and Wnt/β-catenin during carcinogenesis. Disclosure: Nothing to disclose. [ABSTRACT FROM AUTHOR]

Chronic inflammation, which is dominated by macrophage‐involved inflammatory responses, is an instigator of cancer initiation. Macrophages are the most abundant immune cells in healthy lungs, and associated with lung tumor development and promotion. PD‐L1 is a negative molecule in macrophages and correlated with an immunosuppressive function in tumor environment. Macrophages expressing PD‐L1, rather than tumor cells, exhibits a critical role in tumor growth and progression. However, whether and how PD‐L1 in macrophages contributes to inflammation‐induced lung tumorigenesis requires further elucidation. Here, we found that higher expression of PD‐L1 in CD11b+CD206+ macrophages was positively correlated with tumor progression and PD‐1+CD8+ T cells population in human adenocarcinoma patients. In the urethane‐induced inflammation‐driven lung adenocarcinoma (IDLA) mouse model, the infiltration of circulating CD11bhighF4/80+ monocyte‐derived macrophages (MoMs) was increased in pro‐tumor inflamed lung tissues and lung adenocarcinoma. PD‐L1 was mainly upregulated in MoMs associated with enhanced T cells exhaustion in lung tissues. Anti‐PD‐L1 treatment can reduce T cells exhaustion at pro‐tumor inflammatory stage, and then inhibit tumorigenesis in IDLA. The pro‐tumor lung inflammation depended on TNF‐α to upregulate PD‐L1 and CSN6 expression in MoMs, and induced cytokines production by alveolar type‐II cells (AT‐II). Furthermore, inflammatory AT‐II cells could secret TNF‐α to upregulate PD‐L1 expression in bone‐marrow driven macrophages (BM‐M0). Inhibition of CSN6 decreased PD‐L1 expression in TNF‐α‐activated macrophage in vitro, suggesting a critical role of CSN6 in PD‐L1 upregulation. Thus, pro‐tumor inflammation can depend on TNF‐α to upregulate PD‐L1 in recruited MoMs, which may be essential for lung tumorigenesis. [ABSTRACT FROM AUTHOR]

The epithelial–mesenchymal transition (EMT) is a critical stage during the development of silicosis fibrosis. In the current study, we hypothesized that the anti-fibrotic tetrapeptide, N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) may exert its anti-fibrotic effects via activation of the TGF-β1/ROCK1 pathway, leading to inhibition of EMT. To address this hypothesis, we first examined the effect of Ac-SDKP upon EMT using an in vivo rat silicosis model, as well as in an in vitro model of TGF-β1-induced EMT. Confocal laser scanning microscopy was used to examine colocalization of surfactant protein A (SP-A), fibroblast specific protein-1 (FSP-1) and α-smooth muscle actin (α-SMA) in vivo. Western blot analysis was used to examine for changes in the protein levels of E-cadherin (E-cad) and SP-A (epithelial cell markers), vimentin (mesenchymal cell marker), α-SMA (active myofibroblast marker), and collagen I and III in both in vivo and in vitro experiments. Secondly, we utilized Western blot analysis and confocal laser scanning microscopy to examine the protein expression of TGF-β1 and ROCK1 in in vivo and in vitro studies. The results revealed that Ac-SDKP treatment prevented increases in the expression of mesenchymal markers as well as TGF-β1, ROCK1, collagen I and III. Furthermore, Ac-SDKP treatment prevented decreases in the expression of epithelial cell markers in both in vivo and in vitro experiments. Based on the results, we conclude that Ac-SDKP inhibits the transition of epithelial cell-myofibroblast in silicosis via activation of the TGF-β1/ROCK1 signaling pathway, which may serve as a novel mechanism by which it exerts its anti-fibrosis properties. [ABSTRACT FROM AUTHOR]

Highlights: [•] The expression of Sox11 is increased in the injured spinal cord after SCI. [•] Sox11 expression is located in NSCs and newly-generated neurons after SCI. [•] Over-expression of Sox11 promoted neuronal regeneration after SCI. [•] Over-expression of Sox11 increased expression of BDNF after SCI. [•] Sox11 over-expression promoted locomotor recovery after SCI. [Copyright &y& Elsevier]

Indoor cases of Tetranychus cinnabarinus displaying resistance have been documented, but the resistance level in field populations remains unexplored in China. This study delves into the resistance dynamics of T. cinnabarinus to fenpropathrin in various field populations across China, a pressing concern in contemporary agricultural pest control. The conventional bioassay and amplicon sequencing reveal a notable absence of significant fenpropathrin resistance in field populations, contrasting with known resistance in indoor cases. Current study highlights the limitations of traditional bioassays in detecting early-stage resistance and underscores the nuanced capabilities and constraints of amplicon sequencing in resistance gene frequency analysis. By employing an integrated approach, we combined dose-response bioassays, amplicon sequencing, and statistical modeling to assess resistance levels and investigate underlying genetic factors. The model with empirical data indicates that a 5% mutation frequency represents the threshold before resistance emerges. However, the detection of the kdr mutation in certain populations ranging from 0 to 1.2%, signals an early looming threat of future resistance emergence. Additionally, we further assessed a specific dsRNA targeting VGSC genes at two concentrations (10 ng/μL and 100 ng/μL), both inducing substantial mortality by silencing target genes effectively. The exploration of RNA interference (RNAi) as a novel, more environmentally friendly pest control measure opens new avenues, despite the ongoing challenge of resistance evolution. Overall, this study underscores the necessity for evolving pest management strategies, integrating advanced biotechnological approaches with traditional methods, to effectively counter pesticide resistance and ensure sustainable agricultural productivity. [Display omitted] • Current work identified a crucial 5% mutation threshold for resistance. • Novel RNAi method targeting on VGSC shows high pest mortality. • Urges combining biotech with traditional pesticide resistance monitoring. [ABSTRACT FROM AUTHOR]

[Display omitted] • The combined weight model clarifies that economics affect MSW separation vitally. • The prediction model solves the problem of missing urban sanitation data sets. • An artificial neural network were established to evaluate MSW separation ability. • An MSW separation evaluation system has been designed for model application. With the increase in municipal solid waste (MSW), most cities face solid waste management issues. In this study, the analytic hierarchy process (AHP) and artificial neural network (ANN) models were improved to assess the MSW separation capability based on 18 selected indicators of solid waste separation in 15 cities in China. The entropy weight method (EWM) was used in AHP to optimize and determine the indicators and then evaluate their weights, which showed that the general public budget expenditure had the highest weight (0.5239). This implied that the MSW separation capability could be mainly influenced by government financial support. ANN based on scan optimization and machine learning methods were established (R2 = 0.9992) to predict the missing indicators. The mapping relationship between MSW separation indicators and capabilities was also significantly improved from R2 = 0.5317 to R2 = 0.9993, thereby increasing the prediction accuracy of MSW separation capabilities to 95.15%. Thus, this research provides a new avenue for MSW separation and establishes a combined model to predict the separation capability in practical applications. [ABSTRACT FROM AUTHOR]

Abstract: Current study we purified a polysaccharide (BRP) from Boschniakia rossica and the antitumor effects of BRP alone or combined with 5-Fluorouracil (5-FU) was examined in S180 tumor bearing mice by intragastric administration. The high performance size-exclusion chromatography (HPGEC) analysis showed that BRP was a homogeneous polysaccharide and had a molecular weight of 2.2×104 Da. Total carbohydrate content in BRP was determined to be 96.9%, without the presence of protein and nucleic acid. BRP alone or combined with 5-FU could significantly inhibit Sarcoma-180 (S180) tumor growth and increase the spleen index in a dose-dependent manner. Meanwhile a synergistic effect was observed in boosting various immunity functions when the tumor bearing mice receiving BRP plus 5-FU administration, such as stimulating lymphocytes proliferation, increasing NK cell cytotoxicity, enhancing serum interleukin-2 (IL-2) and interferon-gamma (TNF-γ) secretion, as well as augmenting CD4+ and CD8+ spleen T lymphocytes subsets. The results showed that BRP combined with 5-FU presented synergistic effects on antitumor activity in tumor bearing mice. In conclusion, the combination of BRP may boost the suppressed immunity in tumor bearing mice subject to 5-FU chemotherapy, and could serve as a new, promising approach for cancer treatment. [Copyright &y& Elsevier]

Abstract: Aflatoxins (AF) are the mycotoxin with the carcinogenic effect produced by the fungi like Aspergillus flavus, including AFB1, B2, G1, G2, M1, and so on. The detection rate of Aflatoxin G1 (AFG1) is very high in the diet of residents in the high incidence area of the gastric carcinoma and esophageal carcinoma in China, which is the main polluting mycotoxin of the local grain. However, there were no available data regarding the gastric toxicity of AFG1 up to now. In the present study, The toxicity of AFG1 in vitro-cultured human primary adult esophageal epithelial cells was explored by employing the methods of Western blot, semi-quantitative RT-PCR and observing the effect of AFG1 on the expression of the HLA-I molecules of the human esophageal epithelial cells and the antigen processing relative genes TAP-1 and LMP-2. The results showed that AFG1 treatment could decrease both the protein expression of HLA-ABC of the cell surface and the mRNA expression of HLA-A and HLA-B. Moreover, In the AFG1 treatment groups of different densities, both the TAP-1 mRNA and protein expression level of the human esophageal epithelial cells decreased. Furthermore, the LMP-2 protein expression level of the human esophageal epithelial cells decreased, while the mRNA expression level was not obviously changed by AFG1 treatment. It is indicated that the decrease of the HLA-I expression of the cell surface was probably dependent on the decrease of the TAP-1 and LMP-2 expression to a great extent. The decrease of LMP-2 expression resulted in the decrease of HLA-I expression and stability in the cell membrane and finally led to the defect in the antigen presentation, which hindered its identification by the T lymphocytes, made it escape the immune surveillance, and then caused the tumor genesis. [Copyright &y& Elsevier]

Ochratoxin A (OTA) is a widespread mycotoxin worldwide that causes major health risks. The esophageal epithelium is unavoidably exposed to food contaminated OTA after ingestion. Yet, few studies have involved in the putative effects of OTA on the cytotoxicity and glucose metabolism responses on esophageal epithelial cells. In this in vitro study, we aimed to investigate the effects of OTA on esophageal epithelial cell intracellular apoptosis, oxidative stress, DNA damage, mitochondrial function and glucose metabolism. Human esophageal epithelial Het-1A cells were exposed to 2.5, 5 or 10 μM OTA for 24 h. The results showed that OTA decreased cell viability and concomitantly increased apoptosis-related indices, reactive oxygen species generation, oxidative DNA damage, mitochondrial dysfunction and mitochondrial apoptotic pathway activation. In addition, OTA switched the glucose metabolism of Het-1A cells from oxidative phosphorylation towards glycolysis by decreasing the expression of tricarboxylic acid cycle-associated enzymes such as α-ketoglutarate dehydrogenase and isocitrate dehydrogenase 1 and by increasing pyruvate dehydrogenase kinase 1 expression. The data indicated that cell apoptosis, oxidative damage, mitochondrial dysfunction and glucose metabolism perturbation might play pivotal roles in the mechanism of OTA-induced esophageal toxicity. [Display omitted] • Ochratoxin A(OTA) induces oxidative stress of esophageal epithelium cells. • OTA triggers DNA damage and apoptosis. • Oxidative-stress mediated mitochondrial damage involved in OTA-induced apoptosis. • OTA switchs glucose metabolism from oxidative phosphorylation to glycolysis. [ABSTRACT FROM AUTHOR]

Purpose: Long noncoding RNAs (lncRNAs) are emerging as key regulators in cancer initiation and progression. LINC01137 is a recently identified lncRNA of which the functional role in the development of oral squamous cell carcinoma (OSCC) has not been determined yet. Methods: We analyzed the expression of LINC01137 using a microarray-based OSCC gene expression dataset (GSE31056), and validated the results obtained using RT-qPCR in 26 pairs of primary OSCC tumor tissues and adjacent non-tumor tissues. The proliferative and invasive effects of LINC01137 on OSCC cells were determined using CCK-8, colony formation and transwell assays, respectively. Targeted binding between miR-22-3p and LINC01137 was verified using a dual luciferase reporter assay. Results: We found that LINC01137 was significantly upregulated in primary OSCCs. LINC01137 knockdown inhibited OSCC cell proliferation, migration and invasion, whereas LINC01137 overexpression induced opposite effects. LINC01137 upregulation along with p53 inhibition enhanced the malignant transformation of oral cells. In addition, we found that miR-22-3p can directly target LINC01137 through interaction with a putative miR-22-3p-binding site present within the LINC01137 sequence. A significant negative correlation was observed between LINC01137 and miR-22-3p expression in primary OSCC specimens. Exogenous overexpression of miR-22-3p markedly reduced the endogenous expression level of LINC01137 in OSCC cells. Additional functional assays showed that miR-22-3p overexpression enhanced the inhibitory effect of siRNA-mediated LINC01137 silencing on OSCC cell proliferation, migration and invasion, whereas miR-22-3p inhibition had the opposite effect. Conclusions: Our results indicate that LINC01137 functions as an oncogenic lncRNA in OSCC. miR-22-3p can directly target LINC01137 and negatively regulate its expression and function. [ABSTRACT FROM AUTHOR]

Purpose: Gefitinib is a first-line treatment option for epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma. However, most patients inevitably develop gefitinib resistance. The mechanism underlying this resistance is not fully understood. Y-box binding protein 1 (YB-1) has been reported to play a role in modulating drug sensitivity, but its role in gefitinib resistance is currently unknown. Here, we investigated the role of YB-1 in gefitinib resistance of lung adenocarcinoma. Methods: We determined the expression of YB-1, epithelial–mesenchymal transition (EMT) and AKT signaling markers, as well as the viability of lung adenocarcinoma cell lines bearing mutant (HCC827, PC-9) or wild-type (H1299) EGFR. We also evaluated PC-9 cell migration and invasion using transwell assays. The clinical importance of YB-1 and major vault protein (MVP) was evaluated using primary lung adenocarcinoma patient samples. Results: We found that YB-1 was significantly upregulated in gefitinib-resistant lung adenocarcinoma cells compared to gefitinib-sensitive cells. YB-1 augmented gefitinib resistance by activating the AKT pathway and promoting EMT. Decreased migration and invasion was observed upon MVP silencing in YB-1-overexpressing PC-9 cells, as well as restored gefitinib sensitivity. A retrospective analysis of 85 patients with lung adenocarcinoma revealed that YB-1 levels were significantly increased in tyrosine kinase inhibitor (TKI)-resistant patients compared to those in TKI-sensitive patients, indicating that YB-1 may serve as a biomarker to clinically predict acquired gefitinib resistance. Conclusion: YB-1 activates AKT signaling and promotes EMT at least in part by directly activating MVP. Hence, targeting the YB-1/MVP axis may help to overcome gefitinib resistance in lung adenocarcinoma patients. [ABSTRACT FROM AUTHOR]

Sarcomas, originating from mesenchymal progenitor stem cells, are a group of rare malignant tumors with poor prognosis. Wide surgical resection, chemotherapy, and radiotherapy are the most common sarcoma treatments. However, sarcomas' response rates to chemotherapy are quite low and sarcoma cells can have intrinsic or acquired resistance after treatment with chemotherapeutics drugs, leading to the development of multi-drug resistance (MDR). Cancer cellular plasticity plays pivotal roles in cancer initiation, progression, therapy resistance and cancer relapse. Moreover, cancer cellular plasticity can be regulated by a multitude of factors, such as genetic and epigenetic alterations, tumor microenvironment (TME) or selective pressure imposed by treatment. Recent studies have demonstrated that cellular plasticity is involved in sarcoma progression and chemoresistance. It's essential to understand the molecular mechanisms of cellular plasticity as well as its roles in sarcoma progression and drug resistance. Therefore, this review focuses on the regulatory mechanisms and pathological roles of these diverse cellular plasticity programs in sarcoma. Additionally, we propose cellular plasticity as novel therapeutic targets to reduce sarcoma drug resistance. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

• Ochratoxin A(OTA) induces aerobic glycolysis of GES-1 cells. • OTA increases the glycolytic-associated enzymes (HK2, PFK1, LDHA) in GES-1 cells. • OTA promotes the phosphorylation and nuclear translocation of PKM2. • OTA reduces the TCA-cycle-associated enzymes (IDH1 and ODGH) in GES-1 cells. Ochratoxin A (OTA) is a ubiquitous mycotoxin with potential nephrotoxic, hepatotoxic and immunotoxic effects. We previously demonstrated that OTA could cause mitochondrial function disturbance in GES-1 cells in vitro , which lead to the presumption that the glucose metabolism of GES-1 cells will be altered by OTA. Therefore in the present study, we explored the toxicity of OTA on glucose metabolism of GES-1 cells and the molecular mechanism. We found that OTA could induce aerobic glycolysis, evidenced shown by increase of glucose consumption, lactate production and cellular ATP concentration. We further detected expressions of GLUT1 and glycolytic enzymes including HK2, PFK1, PKM2 and LDHA as well as tricarboxylic acid (TCA) cycle-associated enzymes including IDH1, OGDH and CS. The results showed that expression of GLUT1 as well as the activities and expressions of HK2, PFK1 and LDHA were significantly increased while IDH1 and OGDH were reduced by OTA. As to PKM2, western blot showed that OTA could elevated the phospho-PKM2 Ser37 protein level and induce the nuclear accumulation of PKM2, which was further supported by immunofluorescence analyses, in addition, pyruvate kinase activity was reduced by OTA. In conclusion, these findings suggest that OTA exposure induces the metabolic shift from oxidative phosphorylation to aerobic glycolysis via regulating the activities and expressions of glycolysis and TCA-cycle associated molecules in GES-1 cells. [ABSTRACT FROM AUTHOR]

• Upregulation of HMGB1 was observed in AFG 1 -induced lung inflamed tissues. • AFG 1 -induced TNF-α-dependent inflammation regulates HMGB1 upregulation in vivo. • AFG 1 enhanced cytosolic translocation and secretion of HMGB1 in Beas-2b cells. • The addition of extracellular soluble HMGB1 protected AFG 1 -induced DNA damage. • Blockade endogenous HMGB1 by siRNA significantly enhanced AFG 1 -induced damage. Aflatoxin G 1 (AFG 1) is a member of the carcinogenic aflatoxin family. Our previous studies indicated that oral administration of AFG 1 caused tumor necrosis factor (TNF)-α-dependent inflammation that enhanced oxidative DNA damage in alveolar epithelial cells, which may be related to AFG 1 -induced lung carcinogenesis. High mobility group box-1 (HMGB1) is a nuclear DNA-binding protein; the intracellular and extracellular roles of HMGB1 have been shown to contribute to DNA repair and sterile inflammation. The role of HMGB1 in DNA damage in an aflatoxin-induced lung inflammatory environment was investigated in this study. Upregulation of HMGB1, TLR2, and RAGE was observed in AFG 1 -induced lung inflamed tissues and adenocarcinoma. Blocking AFG 1 -induced inflammation by neutralization of TNF-α inhibited the upregulation of HMGB1 in mouse lung tissues, suggesting that AFG 1 -induced TNF-α-dependent inflammation regulated HMGB1 expression. In the in vitro human pulmonary epithelial cell line model, Beas-2b, AFG 1 directly enhanced the cytosolic translocation of HMGB1 and its extracellular secretion. The addition of extracellular soluble HMGB1 protected AFG 1 -induced DNA damage through the TLR2/NF-κB pathway in Beas-2b cells. In addition, blockade of endogenous HMGB1 by siRNA significantly enhanced AFG 1 -induced damage. Thus, our findings showed that both extracellularly-released and nuclear and cytosolic HMGB1 could protect the cell from AFG 1 -induced cell damage in a TNF-α-dependent lung inflammatory environment. [ABSTRACT FROM AUTHOR]

Background: Our recent studies have indicated that miR‐153‐3p is downregulated in the esophageal squamous cell carcinoma (ESCC) cell lines and tissues. Upregulation of miR‐153‐3p was found to inhibit migration and invasion of ESCC cells. However, whether miR‐153‐3p regulates the cisplatin sensitivity in ESCC cells remains unclear. In this study, we explored whether and how miR‐153‐3p regulates the proliferation and confers cisplatin resistance in ESCC by targeting the Nrf‐2 protein. Methods: Eca109 cell line was transfected with microRNA‐153‐3p mimics or Nrf‐2siRNA and cell proliferation and cisplatin resistance were studied. A dual‐luciferase reporter assay was performed on Eca109 cells cotransfected with the wild‐type/mutant 3′UTR sequences of Nrf‐2 and control or microRNA‐153‐3p mimics. We determined the correlation between microRNA‐153‐3p and Nrf‐2 expression in human ESCC samples and explored the effect of Nrf‐2 in the overall survival rate of ESCC patients. Results: MiR‐153‐3p significantly suppressed cell proliferation and increased the sensitivity of Eca‐109 cells to cisplatin. MiR‐153‐3p showed a negative correlation with Nrf‐2 in human esophageal carcinoma tissues. MiR‐153‐3p suppressed the expression of Nrf‐2 via binding to its 3′‐UTR region. Furthermore, inhibition of Nrf‐2 also decreased cell proliferation and increased the sensitivity of Eca109 cells to cisplatin. High expression of Nrf‐2 in human ESCC samples was associated with poor overall survival of ESCC patients. Conclusion: MiR‐153‐3p inhibits cell proliferation and confers cisplatin resistance by downregulating Nrf‐2 expression in Eca‐109 cells. Thus, miR‐153‐3p/Nrf‐2 may play an important role in conferring cisplatin resistance in ESCC. Nrf‐2 appears to be a promising therapeutic target for ESCC. [ABSTRACT FROM AUTHOR]

• The protein identification analysis identified five differentially expressed proteins in the OTA-GES-1 T cells group. • The expressions of Annexin A3 both at protein and mRNA levels increased in OTA-GES-1 T cells group. • Annexin A3 siRNA transfection could inhibit the proliferation of OTA-GES-1 T cells. • Annexin A3 siRNA transfection could lead cells to be arrested at G0/G 1 phase in OTA-GES-1 T cells group. • Inhibition Annexin A3 by siRNA effectively prevented the migration and invasion abilities of OTA-GES-1 T cells. Ochratoxin A (OTA), one of the most abundant food-contaminating mycotoxins, is a possible carcinogen to humans. We previously demonstrated that long-term (40 weeks) OTA exposure induces the malignant transformation of human gastric epithelium cells (GES-1) in vitro. However, the specific mechanism underlying OTA-induced gastric carcinogenesis is complex. In the present study, we used 2-DE and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI/TOF MS) combined with bioinformatics and immunoblotting to investigate the differentially expressed proteins between GES-1 and OTA-malignant transformed GES-1 cells (OTA-GES-1 T cells) in vitro. We found that four differentially expressed proteins were identified after malignant transformation, including actin, cytoplasmic 1 (ACTB), F-actin-capping protein subunit alpha-1 (CAPZA1), Annexin A3 (ANXA3), thioredoxin peroxidase B from red blood cells (TPx-B) and Fibrinogen beta B (Fibrinogen β). Among the differentially expressed proteins, the effect of Annexin A3 was analyzed by MTT assay, western blot, cell cycle analysis, wound healing assay, Transwell assay, and colony formation assay in OTA-GES-1 T cells. The results showed that inhibition of Annexin A3 by siRNA effectively prevented the proliferation, migration, and invasion abilities of OTA-GES-1 T cells. Collectively, the results of this study will guide future research on OTA carcinogenicity. [ABSTRACT FROM AUTHOR]

Aflatoxin G1 (AFG1), a member of the AF family with cytotoxic and carcinogenic properties, could cause DNA damage in alveolar type II (AT‐II) cells and induce lung adenocarcinoma. Recently, we found AFG1 could induce chronic lung inflammation associated with oxidative stress in the protumor stage. Chronic inflammation plays a critical role in cigarette smoke or benzo[a]pyrene‐induced lung tissues damage. However, it is unclear whether and how AFG1‐induced lung inflammation affects DNA damage in AT‐II cells. In this study, we found increased DNA damage and cytochrome P450 (CYP2A13) expression in AFG1‐induced inflamed lung tissues. Furthermore, we treated the mice with a soluble tumor necrosis factor (TNF)‐α receptor and AFG1 and found that TNF‐α neutralization inhibited the AFG1‐induced chronic lung inflammation in vivo, and then reversed the CYP2A13 expression and DNA damage in AT‐II cells. The results suggest that AFG1 induces TNF‐α‐dependent lung inflammation to regulate 2A13 expression and enhance DNA damage in AT‐II cells. Then, we treated the primary mice AT‐II cells and human AT‐II like cells (A549) with AFG1 and TNF‐α and found that TNF‐α enhanced the AFG1‐induced DNA damage in mice AT‐II cells as well as A549 cells in vitro. In AFG1‐exposed A549 cells, TNF‐α‐enhanced DNA damage and apoptosis were reversed by CYP2A13 small interfering RNA. Blocking NF‐κB pathway inhibited the TNF‐α‐enhanced CYP2A13 upregulation and DNA damage confirming that the CYP2A13 upregulation by TNF‐α plays an essential role in the activation of AFG1 under inflammatory conditions. Taken together, our findings suggest that AFG1 induces TNF‐α‐dependent lung inflammation, which upregulates CYP2A13 to promote the metabolic activation of AFG1 and enhance oxidative DNA damage in AT‐II cells. [ABSTRACT FROM AUTHOR]

Ochratoxin A (OTA) is a common natural contaminant found in human and animal food worldwide. Our previous work has shown that OTA can cause oxidative DNA damage, G2 arrest and malignant transformation of human gastric epithelium (GES-1) cells. Mitochondria are considered to be target for the action of many cytotoxic agents. However, the role of mitochondria in the cytotoxicity of OTA remains unknown. The aim of this study is to explore the putative role of mitochondria on OTA cytotoxicity by analyzing mitochondrial changes in GES-1 cells. The results showed that OTA treatment (5, 10, 20 µM) for different times caused increases in the production of reactive oxygen species, and induced mitochondrial damage, shown by loss of mitochondrial membrane potential (ΔΨM), and decrease in cellular ATP concentration. Subsequently, the mitochondrial apoptotic pathway was activated, presented by increase of apoptotic rate and activation of apoptotic proteins. Autophagic cell death was also triggered, demonstrated by the conversion of light chain 3B (LC3B)-I to LC3B-II and elevated levels of green fluorescent protein-LC3 (GFP-LC3) puncta. Moreover, Parkin-dependent mitophagy was also activated presented by the colocalization of MitoTracker with LysoTracker or GFP-LC3 puncta. The inhibition of autophagy and mitophagy by inhibitors or siRNA attenuated the toxic effect of OTA on cell growth. Interestingly, OTA treatment also enhanced mitochondrial biogenesis confirmed by activation of AMPK/PGC-1α/TFAM pathway and promoted cell survival. Collectively, the effects of OTA on mitochondria of GES-1 cells are complex. OTA could cause mitochondrial function disturbance, apoptotic and autophagic cell death and also induce mitochondrial biogenesis. [ABSTRACT FROM AUTHOR]

Schwann cell apoptosis is one of the characteristics of diabetic peripheral neuropathy (DPN). The mammalian target of rapamycin (mTOR) is a multifunctional signaling pathway that regulates cell apoptosis in various types of tissues and cells. To investigate whether the mTOR pathway is involved in cell apoptosis in the Schwann cells of DPN, diabetic mice and rat Schwann cells (RSC96) were chosen to detect phospho-mTOR (Ser 2448), phospho-S6K1 (Thr 389), phospho-4EBP1 (Thr 37/46), Bcl-2, Bax and cleaved caspase-3 by diverse pathological and biological techniques. The results showed that phospho-mTOR (Ser 2448) was decreased in the sciatic nerves of diabetic mice, concomitant with decreased Bcl-2, increased Bax, cleaved caspase-3 and cell apoptosis. In addition, high glucose treatment for 72 h caused a 35.95% decrease in the phospho-mTOR (Ser 2448)/mTOR ratio, a 65.50% decrease in the phospho-S6K1 (Thr 389)/S6K1 ratio, a 3.67-fold increase in the Bax/Bcl-2 ratio and a 1.47-fold increase in the cleaved caspase-3/caspase-3 ratio. Furthermore, mTORC1 inhibition, rather than mTORC2 inhibition, resulted in mitochondrial controlled apoptosis in RSC96 cells by silencing RAPTOR or RICTOR. Again, suppression of the mTORC1 pathway by a chemical inhibitor led to mitochondrial controlled apoptosis in cultured RSC96 cells in vitro . By contrast, activation of the mTORC1 pathway with MHY1485 prevented decreased phospho-S6K1 (Thr 389) levels caused by high glucose and cell apoptosis. Additionally, constitutive activation of S6K1 avoided high glucose-induced cell apoptosis in RSC96 cells. In summary, our findings suggest that activating mTORC1/S6K1 signaling in Schwann cells may be a promising strategy for the prevention and treatment of DPN. [ABSTRACT FROM AUTHOR]

Conclusion: An intralesional bleomycin A5 (BLE) injection might be used as an alternative therapy for eosinophilic-type nasal polyps (NPs). BLE-induced apoptosis might play an important role in shrinkage of NPs. Objectives: The aim of this study is to determine the effect and explore the possible role of apoptosis in shrinkage of NPs. Methods: Twenty-nine patients with eosinophilic-type NPs experienced repeated local injection of BLE. The recurrence rate of this group was obtained. The mechanism of BLE treatment was investigated through an in vitro experiment. Nasal polyp tissues were treated with BLE. The apoptotic activity was detected by the presence of DNA smear and test of terminal deoxynucleotidyl transferase dUTP nick end labeling. The caspase-8 and PARP were examined through immunohistochemistry and Western blotting. Results: After several local injections of BLE, the nasal polyp tissues decreased and then disappeared. During follow-up of 3 years the recurrence rate of this group was significantly lower than another one treated with operation plus medicine treatment. Apoptosis in BLE-treated tissue was prominently detected in the infiltrating inflammatory cells. The expression of PARP and casp-8 were increased in BLE-treated nasal polyp tissue compared with PBS-treated tissue. [ABSTRACT FROM AUTHOR]