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Abstract Cervical cancer is the second leading cause of morbidity and mortality in women worldwide. Traditional treatment methods have become limited. Naringenin, a flavonoid abundant in various fruits and herbal medicines, has demonstrated anti-tumor properties among other effects. This research undertook to elucidate the mechanism of naringenin in the context of cervical cancer treatment by leveraging network pharmacology and performing experimental validation. Initial steps involved predicting potential naringenin targets and subsequently screening for overlaps between these targets and those related to cervical cancer, followed by analysis of their interrelationships. Molecular docking was subsequently utilized to verify the binding effect of the central target. Within the framework of network pharmacology, it was discovered that naringenin might possess anti-cancer properties specific to cervical cancer. Following this, the anti-tumor effects of naringenin on Hela cell viability, migration, and invasion were assessed employing CCK-8, transwell, wound healing assays, and western blotting. Experimental data indicated that naringenin attenuates the migration and invasion of Hela cells via downregulation EGFR/PI3K/AKT signaling pathway. Thus, our findings suggest that naringenin has therapeutic impacts on cervical cancer via multiple mechanisms, primarily by inhibiting the migration and invasion through the EGFR/PI3K/AKT/mTOR pathway. This study offers fresh insights for future clinical studies.

Abstract Background Immune checkpoint inhibitor therapy has revolutionized the clinical management of a diverse range of cancer types, including advanced cutaneous melanoma. While immunotherapy targeting the PD-1/PD-L1 system has become standard of care, overall response rates remain unsatisfactory for most patients and there are no approved small molecule inhibitors of the PD-1/PD-L1 system. Flubendazole (FLU) is an anthelmintic that has been used to treat worm infections in humans and animals for decades. Methods Here we tested the anti-cancer activity of systemically delivered FLU with suppression of PD-1 in immunocompetent mice. Results In C57BL/6J mice bearing subcutaneous B16F10 melanoma, FLU reduced both tumor growth and PD-1 protein levels without affecting levels of PD-L1. FLU’s suppression of PD-1 was accompanied by increased CD3+ T cell infiltration. Western blotting with extracts from human Jurkat T cells showed that FLU inhibited PD-1 protein expression, findings confirmed by flow cytometry. To gain mechanistic insights on FLU’s ability to suppress PD-1 protein levels, we performed bulk RNA sequencing on extracts of Jurkat T cells exposed to the benzimidazole for 4 h. From a pool of 14,475 genes there were 1218 differentially-expressed genes; 687 with increased expression and 531 with decreased expression. Among the genes induced by FLU was the AP-1 family member, JUN and surprisingly, pdcd1. KEGG pathway analysis showed FLU up-regulated genes over-represented in multiple pathways (p

Adapters and Low-Rank Adaptation (LoRA) are parameter-efficient fine-tuning techniques designed to make the training of language models more efficient. Previous results demonstrated that these methods can even improve performance on some classification tasks. This paper complements existing research by investigating how these techniques influence classification performance and computation costs compared to full fine-tuning. We focus specifically on multilingual text classification tasks (genre, framing, and persuasion techniques detection; with different input lengths, number of predicted classes and classification difficulty), some of which have limited training data. In addition, we conduct in-depth analyses of their efficacy across different training scenarios (training on the original multilingual data; on the translations into English; and on a subset of English-only data) and different languages. Our findings provide valuable insights into the applicability of parameter-efficient fine-tuning techniques, particularly for multilabel classification and non-parallel multilingual tasks which are aimed at analysing input texts of varying length.

As the relevance between left and right brain neurons when transmitting electrical signals of umami taste is unknown, the aim of this work was to investigate responsive regions of the brain to the umami tastant monosodium glutamate (MSG) by using scalp-electroencephalogram (EEG) to identify the most responsive brain regions to MSG. Three concentrations of MSG (0.05, 0.12, 0.26 g/100 mL) were provided to participants for tasting while recoding their responsive reaction times and brain activities. The results indicated that the most responsive frequency to MSG was at 2 Hz, while the most responsive brain regions were T4CzA2, F8CzA2, and Fp2CzA2. Moreover, the sensitivity of the brain to MSG was significantly higher in the right brain region. This study shows the potential of using EEG to investigate the relevance between different brains response to umami taste, which contributes to better understanding the mechanism of umami perception.

Abstract Carbon dots (CDs) with excellent cytocompatibility, tunable optical properties, and simple synthesis routes are highly desirable for use in optical bioimaging. However, the majority of existing CDs are triggered by ultraviolet/blue light, presenting emissions in the visible/first near‐infrared (NIR‐I) regions, which do not allow deep tissue penetration. Emerging research into CDs with NIR‐II emission in the red region has generated limited designs with poor quantum yield, restricting their in vivo imaging applications due to low penetration depth. Developing novel CDs with NIR‐II emissions and high quantum yield has significant and far‐reaching applications in bioimaging and photodynamic therapy. Here, it is developed for the first time Fe‐doped CDs (Fe‐CDs) exhibiting the excellent linear relationship between 900–1200 nm fluorescence‐emission and pH values, and high quantum yield (QY‐1.27%), which can be used as effective probes for in vivo NIR‐II bioimaging. These findings demonstrate reliable imaging accuracy in tissue as deep as 4 mm, reflecting real‐time pH changes comparable to a standard pH electrode. As an important example application, the Fe‐CDs probe can non‐invasively monitor in vivo gastric pH changes during the digestion process in mice, illustrating its potential applications in aiding imaging‐guided diagnosis of gastric diseases or therapeutic delivery.

Abstract This paper proposes an enhanced three‐layer predictive hierarchical power management framework for secure and economic operation of islanded microgrids. The tertiary control, guaranteeing the microgrid economic operation, is built upon the semi‐definite programming‐based AC optimal power flow model, which periodically sends power references to secondary control. To mitigate uncertainties arising from renewable generations and loads, a centralized linear model predictive control (MPC) controller is proposed and implemented for secondary control. The MPC controller can effectively regulate the microgrid system frequency by closely tracking reference signals from the tertiary controller with low computational complexity. Droop‐based primary controllers are implemented to coordinate with the secondary MPC controller to balance the system in real time. Both synchronous generators (SGs) and solar photovoltaics (PVs) are simulated in the microgrid power management framework. A unified linear input‐state estimator (ULISE) is proposed for SG state variable estimation and control anomaly detection due to compromised cyber‐physical system components, etc. Simulation results demonstrated that SG states can be accurately estimated, while inconsistency in control signals can be effectively detected for an enhanced MPC. Furthermore, comparing with conventional proportional‐integral (PI) control, the proposed hierarchical power management scheme exhibits superior frequency regulation capability whilst maintaining lower system operating costs.

Shield thrust is a critical operational parameter during shield driving, which is of vital significance for adjusting operational parameters and ensuring efficient and safe propulsion of shield tunneling machine. In this paper, a novel hybrid prediction model (CLM) combining attention mechanism, convolutional neural networks (CNN) and Bi-directional long short-term memory (BiLSTM) network is proposed for shield thrust prediction. Correlation analysis based on Maximal Information Coefficient (MIC) between the thrust and other parameters is first conducted to select optimal parameters and reduce input dimension. An attention mechanism is introduced into CNN to distinguish the importance of different features, with the convolution layer and pooling layer further extracting dimension features of the data. Then, a BiLSTM neural network integrating first attention layer is employed to extract time-varying characteristics of the data, with a second attention layer added to capture important time information. Field data during shield cutting bridge piles are investigated to support and validate the effectiveness and superiority of the proposed method. Results show that the proposed CLM model are general enough to avoid overfitting problems and have good performance at prediction. The predicted value match reasonably well the monitoring data, with coefficient of determination ( $\text{R}^{2}$ ) equaling to 0.85, root mean square error (RMSE) equaling to 0.05, mean absolute error (MAE) equaling to 0.02. The CLM model in this paper can accurately predict the thrust even under complicated construction conditions, which provides reference for similar industrial application.

The growing needs for high-speed and secure communications create an increasing challenge to the contemporary framework of signal processing. The coexistence of multiple high-speed wireless communication systems generates wideband interference. To protect the security and especially the privacy of users’ communications requires stealth communication that hides and recovers private information against eavesdropping attacks. The major problem in interference management and stealth information recovery is to separate the signal of interest from wideband interference/noise. However, the increasing signal bandwidth presents a real challenge to existing capabilities in separating the mixed signal and results in unacceptable latency. The photonic circuit processes a signal in an analog way with a unanimous frequency response over GHz bandwidth. The digital processor measures the statistical patterns of the signals with sampling rate orders of magnitude smaller than the Nyquist frequency. Under-sampling the signals significantly reduces the workload of the digital processor while providing accurate control of the photonic circuit to perform the real-time signal separations. The wideband mixed signal separation, based on photonic signal processing is scalable to multiple stages with the performance of each stage accrued.

Background: The Midfacial Skeletal Expander (MSE) produces a greater skeletal effect than its dentoalveolar side effects. The aim of this study was to quantify the stability of the different components of MSE expansion post-orthodontic treatment. Methods: Fourteen subjects (mean age of 20.4 ± 3.5 years) were treated with the MSE. The pre-expansion (T0), post-expansion (T1), and post-treatment (T2) CBCT records were superimposed and compared. The rotational fulcrum of the zygomaticomaxillary complex was identified, and angular measurements were generated to assess changes in the zygomaticomaxillary complex (skeletal expansion), dentoalveolar bone (alveolar bone bending), and maxillary first molars (dental tipping). The stability of all three components after orthodontic treatment was also assessed by comparing changes between T0–T1 and T0–T2. Results: Post-expansion, angular measurements showed that skeletal expansion accounted for 87.50% and 88.56% of total expansion, alveolar bone bending for 7.09% and 5.23%, and dental tipping for 5.41% and 6.21% on the right and left sides, respectively. Post-treatment skeletal expansion relapsed by 11.20% and 13.28% on the right and left sides, respectively. Conclusions: The MSE mainly produces skeletal changes with insignificant and negligible dentoalveolar changes immediately after expansion. In the long term, the majority of skeletal expansion was maintained.

Abstract Background This study is aimed to (1) investigate the influence of sagittal and vertical patterns on mandibular cross-sectional morphology and to (2) provide visualized mandibular cross-sectional morphology in different groups with General Procrustes Analysis (GPA), canonical variance analysis (CVA) and discriminant function analysis (DFA). Methods 324 cone-beam computed tomography (CBCT) images were collected to analyze mandibular cross-sectional morphology and were categorized into 12 groups according to sagittal and vertical pattern and gender. One-way analysis of variance (ANOVA) was used to compare the difference among the groups. Thirty equidistant points were marked along the contour of mandibular cross-section and GPA, CVA and DFA were applied. Results (1) Mandibular height in hyperdivergent groups was significantly higher than that in normodivergent and hypodivergent groups (P 0.05). (3) Class II hyperdivergent group showed narrowest lower third width in the molar region, with the mean value of 12.03 mm in females and 11.98 mm in males. (4) For males and females, the ratio between height and lower third width at symphysis was significantly higher in Class II hyperdivergent group than that in Class I hyperdivergent group (P

Due to the continuous expansion of congested urban areas, many new tunnels are inevitable to over-cross the existing subway lines and may even affect the operation of existing lines. It is vital to investigate the response of existing tunnel caused by over-crossing tunneling. In this study, a case history of closely spaced twin tunnels excavated above the existing tunnels in soft soil stratum was presented. The deformation of the existing tunnels induced by the excavation of the new tunnels was automatically monitored. In-situ monitoring results showed that the vertical displacement of the existing tunnels was mainly uplift and its development showed obvious phase characteristics. The increase rate of the vertical displacement in Phase I and II induced by the second over-crossing was smaller than that of the first over-crossing. A superposition method was employed to describe the uplift section characteristics of the existing tunnels. The influence ranges of tunnel excavation on the left and right lines of the existing tunnels were approximately 5.5D and 4.5D, respectively. The torsional deformation of the rail bed and the convergence of the existing tunnels are explored, and the reasons for the changes of the over-crossing sections are analyzed at the same time.

Abstract A differentiation switch of bone marrow mesenchymal stem/stromal cells (BMSCs) from osteoblasts to adipocytes contributes to age‐ and menopause‐associated bone loss and marrow adiposity. Here it is found that osteocytes, the most abundant bone cells, promote adipogenesis and inhibit osteogenesis of BMSCs by secreting neuropeptide Y (NPY), whose expression increases with aging and osteoporosis. Deletion of NPY in osteocytes generates a high bone mass phenotype, and attenuates aging‐ and ovariectomy (OVX)‐induced bone‐fat imbalance in mice. Osteocyte NPY production is under the control of autonomic nervous system (ANS) and osteocyte NPY deletion blocks the ANS‐induced regulation of BMSC fate and bone‐fat balance. γ‐Oryzanol, a clinically used ANS regulator, significantly increases bone formation and reverses aging‐ and OVX‐induced osteocyte NPY overproduction and marrow adiposity in control mice, but not in mice lacking osteocyte NPY. The study suggests a new mode of neuronal control of bone metabolism through the ANS‐induced regulation of osteocyte NPY.

This paper proposes a theoretical model for the stability analysis of a box tunnel face in non-cohesive soils considering the uneven distribution of support pressure caused by multiple cutter heads and screw conveyors. The support pressure distribution on the tunnel face is concave. Accordingly, the failure mechanism is composed of a prism and a wedge, both including three blocks. The relatively smaller support pressure acting on the middle blocks lead to the tendency of slide. Assuming that the support pressure acting on the side blocks is obtained using the active earth pressure coefficient, the support pressure acting on block II can be achieved by limit equilibrium analysis considering the interactions between the blocks. The influences of strength parameters and geometric parameters on the tunnel face stability are discussed in the parametric analysis. For comparison, numerical analysis is conducted in the commercial software OptumG3. It is found that the results given by the proposed model agree well with those from the numerical model. Therefore, the rationality of the proposed model in predicting the collapse geometry is verified.

BackgroundLinc00312 is dysregulated in nasopharyngeal carcinoma (NPC) and participates in the initiation and progression of NPC. Our previous studies suggested that linc00312 was able to enhance the sensitivity of NPC cells to irradiation and NPC patients with higher expression of linc00312 was associated with better short-term curative effect and overall survival. The single nucleotide polymorphisms (SNPs) of lncRNAs may influence the disease course and outcome by affecting the expression, secondary structure or function of lncRNAs. However, the role of SNPs in linc00312 on the occurrence and survival of NPC remains unknown.MethodsWe recruited 684 NPC patients and 823 healthy controls to evaluate the association between linc00312 SNPs and NPC susceptibility by using multivariate logistic regression analysis. Kaplan-Meier analysis and Cox proportional hazards regression were applied to assess the effect of linc00312 SNPs on the survival of NPC patients. The relative expression of linc00312 in NPC tissues was determined by real-time PCR. The interaction between linc00312 and mir-411-3p was explored by luciferase reporter assay. In silico prediction of the changes on linc00312 folding structure was conducted by RNAfold WebServer.ResultWe demonstrated that rs12497104 (G > A) GA genotype carriers had a higher risk than others for suffering from NPC (GA vs GG, OR = 1.437, P = 0.003). Besides, patients with rs12497104 AA genotype showed a poorer overall survival in contrast to GG genotype (AA vs GG, HR = 2.117, P = 0.011). In addition, the heterozygous carriers of rs15734 (G > A) and rs164966 (A > G) were correlated with decreased risk of NPC (GA vs GG, OR = 0.778, P = 0.031; GA vs AA, OR = 0.781, P = 0.033, respectively). We found that the three SNPs might influence the expression of linc00312 in a genotype specific feature. The local centroid secondary structure as well as the minimum free energy of linc00312 were changed following the candidate SNPs alterations. Besides, we revealed that the G to A alteration at rs12497104 disrupted the binding between mir-411-3p and linc00312.ConclusionOur results indicated genetic polymorphisms of linc00312 might serve as potential biomarkers for NPC carcinogenesis and prognosis.

Abstract Recently, the gut microbiota (GM) has been shown to be a regulator of bone homeostasis and the mechanisms by which GM modulates bone mass are still being investigated. Here, it is found that colonization with GM from children (CGM) but not from the elderly (EGM) prevents decreases in bone mass and bone strength in conventionally raised, ovariectomy (OVX)‐induced osteoporotic mice. 16S rRNA gene sequencing reveals that CGM reverses the OVX‐induced reduction of Akkermansia muciniphila (Akk). Direct replenishment of Akk is sufficient to correct the OVX‐induced imbalanced bone metabolism and protect against osteoporosis. Mechanistic studies show that the secretion of extracellular vesicles (EVs) is required for the CGM‐ and Akk‐induced bone protective effects and these nanovesicles can enter and accumulate into bone tissues to attenuate the OVX‐induced osteoporotic phenotypes by augmenting osteogenic activity and inhibiting osteoclast formation. The study identifies that gut bacterium Akk mediates the CGM‐induced anti‐osteoporotic effects and presents a novel mechanism underlying the exchange of signals between GM and host bone.

In this paper, we propose and experimentally demonstrate a three-dimensional (3D) microscopic system that reconstructs a 3D image based on structured light illumination. The spatial pattern of the structured light changes according to the profile of the object, and by measuring the change, a 3D image of the object is reconstructed. The structured light is generated with a digital micro-mirror device (DMD), which controls the structured light pattern to change in a kHz rate and enables the system to record the 3D information in real time. The working distance of the imaging system is 9 cm at a resolution of 20 μm. The resolution, working distance, and real-time 3D imaging enable the system to be applied in bridge and road crack examinations, and structure fault detection of transportation infrastructures.

Following successful abatement of external nutrient sources, one must shift the focus to the role of phosphorus (P) release from sediment. This enables us to better assess the causes for sustained eutrophication in freshwater ecosystem and how to deal with this challenge. In this study, five sediment cores from the shallow YuQiao Reservoir in northern China were investigated. The reservoir serves as the main raw water source for tap water services of Tianjin megacity, with a population of 15.6 million. Sediment characteristics and P fractions were determined in order to assess the role of the sediments as the P source to the water body. The total P content (TP) in sediments was similar to what was found in catchment soils, although the P sorption capacity of sediments was 7–10 times greater than for the catchment soils. Isotherm adsorption experiments documented that when P concentration in overlying water drops below 0.032–0.070 mg L−1, depending on the site, the sediment contributes with a positive flux of P to the overlying water. Adsorbed P at different depths in the sediments is found to be released with a similarly rapid release rate during the first 20 h, though chronic release was observed mainly from the top 30 cm of the sediment core. Dredging the top 30 cm layer of the sediments will decrease the level of soluble reactive phosphate in the water being sustained by the sediment flux of P.

We propose and demonstrate an anti-jamming system to defend against wideband jamming attack. Free space optical communication is deployed to provide a reference for jamming cancellation. The mixed signal is processed and separated with photonic signal processing method to achieve large bandwidth. As an analog signal processing method, the cancellation system introduces zero latency. The radio frequency signals are modulated on optical carriers to achieve wideband and unanimous frequency response. With wideband and zero latency, the system meets the key requirements of high speed and real-time communications in transportation systems.

We proposed and experimentally demonstrated a secure key generation and distribution system that is compatible with optical amplifiers and standard wavelength-division multiplexing (WDM) transmission systems. The key is generated from the phase fluctuations induced by environmental instabilities. The key generation system is tested in a 240 km bidirectional fiber-pair link with multiple optical amplifiers. To demonstrate the compatibility with WDM systems, 38 WDM channels are transmitted together with the key distribution channel. The secret key is protected against eavesdropping and coherence detection attack by the wide-band property of the signal carrier and the fast-changing rate of the phase fluctuations.

Finding unique peptides to target specific biological surfaces is crucial to basic research and technology development, though methods based on biological arrays or large libraries limit the speed and ease with which these necessary compounds can be found. We reasoned that because biological surfaces, such as cell surfaces, mineralized tissues, and various extracellular matrices have unique molecular compositions, they present unique physicochemical signatures to the surrounding medium which could be probed by peptides with appropriately corresponding physicochemical properties. To test this hypothesis, a naïve pilot library of 36 peptides, varying in their hydrophobicity and charge, was arranged in a two-dimensional matrix and screened against various biological surfaces. While the number of peptides in the matrix library was very small, we obtained "hits" against all biological surfaces probed. Sequence refinement of the "hits" led to peptides with markedly higher specificity and binding activity against screened biological surfaces. Genetic studies revealed that peptide binding to bacteria was mediated, at least in some cases, by specific cell-surface molecules, while examination of human tooth sections showed that this method can be used to derive peptides with highly specific binding to human tissue.