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The quality detection of alfalfa hay is crucial for the development of animal husbandry. In this study, a method for quality detection of alfalfa hay based on the fusion of multisource information including near-infrared spectroscopy, image processing techniques, and electronic nose is proposed. After SG convolution smoothing, feature wavelengths were extracted using Competitive Adaptive Re-weighting Scheme and Successive Projections Algorithm from the spectral data. The image data were denoised using adaptive wavelet thresholding, and color and texture features were extracted using color histograms and random forest algorithms, respectively. Electronic nose data using principal component analysis was used for data dimensionality reduction. Support Vector Machine, Extreme Learning Machine, and Multi-Layer Perceptron were employed to establish quality detection models of alfalfa hay based on spectroscopy, image, gas information, and their combination, respectively. Experimental results demonstrate that the fusion of near-infrared spectroscopy, image data, and gas information effectively enhances the classification accuracy of the model. The accuracy of the test set reaches 100%, with root mean square error and determination coefficient values of 0.1728 and 0.9239, respectively, surpassing prediction models established solely on individual information. This study provides new insights into alfalfa hay quality detection.

Abstract Epigenetic mechanisms bridge genetic and environmental factors that contribute to the pathogenesis of major depression disorder (MDD). However, the cellular specificity and sensitivity of environmental stress on brain epitranscriptomics and its impact on depression remain unclear. Here, we found that ALKBH5, an RNA demethylase of N6-methyladenosine (m6A), was increased in MDD patients’ blood and depression models. ALKBH5 in astrocytes was more sensitive to stress than that in neurons and endothelial cells. Selective deletion of ALKBH5 in astrocytes, but not in neurons and endothelial cells, produced antidepressant-like behaviors. Astrocytic ALKBH5 in the mPFC regulated depression-related behaviors bidirectionally. Meanwhile, ALKBH5 modulated glutamate transporter-1 (GLT-1) m6A modification and increased the expression of GLT-1 in astrocytes. ALKBH5 astrocyte-specific knockout preserved stress-induced disruption of glutamatergic synaptic transmission, neuronal atrophy and defective Ca2+ activity. Moreover, enhanced m6A modification with S-adenosylmethionine (SAMe) produced antidepressant-like effects. Our findings indicate that astrocytic epitranscriptomics contribute to depressive-like behaviors and that astrocytic ALKBH5 may be a therapeutic target for depression.

Abstract Oncolytic viruses (OVs) offer a novel approach to treat solid tumors; however, their efficacy is frequently suboptimal due to various limiting factors. To address this challenge, we engineered an OV containing targets for neuron-specific microRNA-124 and Granulocyte-macrophage colony-stimulating factor (GM-CSF), significantly enhancing its neuronal safety while minimally compromising its replication capacity. Moreover, we identified PARP1 as an HSV-1 replication restriction factor using genome-wide CRISPR screening. In models of glioblastoma (GBM) and triple-negative breast cancer (TNBC), we showed that the combination of OV and a PARP inhibitor (PARPi) exhibited superior efficacy compared to either monotherapy. Additionally, single-cell RNA sequencing (scRNA-seq) revealed that this combination therapy sensitized TNBC to immune checkpoint blockade, and the incorporation of an immune checkpoint inhibitor (ICI) further increased the survival rate of tumor-bearing mice. The combination of PARPi and ICI synergistically enhanced the ability of OV to establish durable tumor-specific immune responses. Our study effectively overcomes the inherent limitations of OV therapy, providing valuable insights for the clinical treatment of TNBC, GBM, and other malignancies.

Abstract Background Family-centered empowerment programs have been widely used in the pediatric field. Therefore, the current study investigated the effectiveness of family empowerment programs on caregiving ability and adverse mood among caregivers of children with acute leukemia. Objective To evaluate the effect of a family empowerment program on the caregiving ability and adverse mood of caregivers of children with acute leukemia. Methods Sixty-eight children with acute leukemia and their family caregivers admitted to our hospital were selected for the study. The control group received routine care during hospitalization, and the family empowerment program was implemented in the intervention group to compare the changes in caregiving capacity (FCTI), illness uncertainty (PPUS) and anxiety(SAS)of the caregivers of the two groups. Results After 8 weeks of intervention, the FCTI score of the intervention group was significantly lower than that of the control group (P

Abstract Under long-standing threat of seasonal influenza outbreaks, it remains imperative to understand the drivers of influenza dynamics which can guide mitigation measures. While the role of absolute humidity and temperature is extensively studied, the possibility of ambient ozone (O3) as an environmental driver of influenza has received scant attention. Here, using state-level data in the USA during 2010–2015, we examined such research hypothesis. For rigorous causal inference by evidence triangulation, we applied 3 distinct methods for data analysis: Convergent Cross Mapping from state-space reconstruction theory, Peter-Clark-momentary-conditional-independence plus as graphical modeling algorithms, and regression-based Generalised Linear Model. The negative impact of ambient O3 on influenza activity at 1-week lag is consistently demonstrated by those 3 methods. With O3 commonly known as air pollutant, the novel findings here on the inhibition effect of O3 on influenza activity warrant further investigations to inform environmental management and public health protection.

Abstract The circadian clock regulates animal physiological activities. How temperature reorganizes circadian-dependent physiological activities remains elusive. Here, using in-vivo two-photon imaging with the temperature control device, we investigated the response of the Drosophila central circadian circuit to temperature variation and identified that DN1as serves as the most sensitive temperature-sensing neurons. The circadian clock gate DN1a’s diurnal temperature response. Trans-synaptic tracing, connectome analysis, and functional imaging data reveal that DN1as bidirectionally targets two circadian neuronal subsets: activity-related E cells and sleep-promoting DN3s. Specifically, behavioral data demonstrate that the DN1a-E cell circuit modulates the evening locomotion peak in response to cold temperature, while the DN1a-DN3 circuit controls the warm temperature-induced nocturnal sleep reduction. Our findings systematically and comprehensively illustrate how the central circadian circuit dynamically integrates temperature and light signals to effectively coordinate wakefulness and sleep at different times of the day, shedding light on the conserved neural mechanisms underlying temperature-regulated circadian physiology in animals.

Abstract Background Traditional biochemical screening for neonatal inherited metabolic diseases has high false-positive rates and low positive predictive values, which are not conducive to early diagnosis and increase parents’ anxiety. This study analysed the relationship between gene variant carriers and their biochemical indicators in traditional biochemical screening, aiming to find explanations for false positives in newborns. Results This retrospective study included 962 newborns. Newborns underwent traditional biochemical screening at birth using blood staining and genomic sequencing of their stored blood staining using the NeoSeq Pro panel, which was able to detect 154 pathogenic genes and 86 diseases. A total of 632 newborns were carriers of gene variants. 56% of congenital hypothyroidism carriers had higher thyroid-stimulating hormone levels than normal newborns. Abnormal biochemical indices were detected in 71% of carriers of organic acid metabolic diseases, 69% of carriers of amino acid metabolic diseases, and 85% of carriers of fatty acid β oxidation disorders. In carriers associated with organic acid metabolic diseases, the propionylcarnitine (C3), C3/acetylcarnitine (C2), and methylmalonylcarnitine (C4DC) + 3-hydroxyisovalerylcarnitine (C5OH) levels were higher than those in non-carriers (C3: 4.12 vs. 1.66 µmol/L; C3/C2: 0.15 vs. 0.09; C4DC + C5OH: 0.22 vs. 0.19 µmol/L). In carriers associated with amino acid metabolic diseases, phenylalanine levels were higher than those in non-carriers (68.00 vs. 52.05 µmol/L). For carriers of fatty acid β oxidation disorders, butyrylcarnitine levels were higher than those in non-carriers (0.31 vs. 0.21 µmol/L), while the free carnitine levels were lower than those in non-carriers (14.65 vs. 21.87 µmol/L). There was a higher occurrence of carriers among newborns who received false-positive results for amino acid metabolic diseases compared to those who received negative results (15.52% vs. 6.71%). Similarly, there was a higher occurrence of carriers among newborns who received false-positive results for fatty acid β oxidation disorders compared to those who received negative results (28.30% vs. 7.29%). Conclusions This study showed that the carriers comprised a large number of newborns. Carriers had abnormal biochemical indicators compared with non-carriers, which could explain the false-positive rate for newborns using traditional newborn biochemical screening, especially in amino acid metabolic and fatty acid β oxidation disorders.

Investigating the role of surface-modified 3D printed titanium implants in modulating oral soft tissue closure and antimicrobial properties. Eighteen 6-month-old healthy adult New Zealand White rabbits were selected as experimental animals, the left and right mandibular teeth of each experimental animal were randomly divided into two groups, and the bilateral first premolar teeth were extracted after general anesthesia, and one implant was implanted into each of the magnesium/zinc ionized surface-treated group (experimental group) and the surface-untreated group (control group), with a total of 36 implants, i.e., 18 implants for the experimental group and 18 implants for the control group. Bilateral mandibular samples from both groups were removed after 2 and 4 weeks of implantation to investigate the attachment and spreading of human gingival fibroblasts (HGFs) on the surface of the samples, their proliferative and migratory behaviors as well as the expression levels of related gene proteins (CoL-1 and TGF-β), and HE staining of the soft tissues of the samples and inflammatory cell counts. After 2 and 4 weeks of implantation, the experimental group’s HGFs adhesion and spreading were significantly better than that of the control group, the migration and proliferation of HGFs were significantly greater than that of the control group ( p < .05), and the expression of CoL-1 and TGF-β genes was significantly higher than that of the control group ( p < .05), and the inflammatory cell count was significantly smaller than that of the control group ( p < .05). Surface modification by magnesium and zinc ions enhances the sealing performance and antimicrobial performance of 3D printed titanium implants in oral soft tissues, with significant effects.

Although modern meteorological service and prediction systems have achieved good applications in numerical models, these models are often influenced by multiple random factors and cannot adapt well to the meteorological service and prediction needs of complex climate regions. Therefore, this article aims to designing an AI intelligent meteorological service platform to simulate what happens when people use it. Based on commonly used AI technologies in meteorological research, the temporal data algorithm mentioned in this article is used for prediction. This article selected the actual daily average water vapor pressure and daily average relative humidity data of three meteorological stations over the past 10 days for analysis. The maximum and minimum values of the actual daily average water vapor pressure in the 10 days of San Jose are 30.2 and 28.1 Pa, respectively, the maximum and minimum values of the actual daily average vapor pressure over 10 days of Cupertino are 30.4 and 28.4 Pa, respectively, and the maximum and minimum values of the actual daily average vapor pressure over 10 days of Santa Clara are 30.5 and 28.4 Pa, respectively, which can prove the effectiveness of AI-based intelligent virtual imaging meteorological services. HIGHLIGHTS Modern meteorological services and forecasting systems are susceptible to the influence of a variety of random factors and cannot well cope with the meteorological service and forecasting needs in complex climate areas.; With the continuous development and maturity of artificial intelligence (AI) algorithms represented by neural networks, meteorological departments are trying to use statistical methods to replace or compensate for traditional numerical models. This article also designs an AI weather service platform based on this to simulate what will happen when people use it.; This article selected the actual daily average water vapor pressure and daily average relative humidity data of three weather stations in the past 10 days for research and analysis, and found that the virtual imaging weather service system based on AI was more effective.;

[Introduction] Accurate estimation of the Li-ion batteries' State of Health (SoH) is essential for future intelligent battery management systems. To solve the problems of poor quality of data features and difficulties in adjusting model parameters, this study proposes a method for estimating the SoH of lithium batteries based on singular value fixed-order noise reduction and the sparrow search algorithm which can optimize the gated recurrent unit (GRU) neural network.[Method] Firstly, three indicators highly correlated with SoH decay were extracted from the battery charge and discharge data. Noise reduction was applied to the features using singular value decomposition techniques to improve their correlation with SoH. Next, using the sparrow search algorithm to optimize the model structure and parameters of the GRU neural network improve the accuracy of estimation of SoH. Finally, the battery data sets from Centre for Advanced Life Cycle Engineering (CALCE) were used to verify the validity of the proposed model. [Result] The experimental results show that the model proposed in this study applies to the battery SoH estimation, with a maximum root mean square error (RMSE) of only 0.018 4. After data noise reduction and algorithm optimization, the RMSE of the GRU model is reduced by 55.41% compared to the initial model. [Conclusion] The method proposed in this paper accurately estimates SoH and can be used as a reference for practical engineering applications.

[Introduction] With the rapid development of AC/DC distribution networks and distributed generation technology, the role of DC microgrids in distribution networks is becoming increasingly important and will become an important component of future distribution networks. Due to the small coverage area and low line impedance of the DC microgrid, when an inter pole short circuit fault occurs, the fault current increases rapidly and has a large amplitude, which can reach more than 10 times the rated working current. This makes it difficult to set the protection of DC microgrids and requires high equipment selection, which restricts the rapid development of DC microgrids. [Method] In response to the above issues, taking the DC microgrid as the research object, starting from the working principle of inter pole faults in the DC microgrid, the fault characteristics on the DC side of the DC microgrid were analyzed. In response to the shortcomings of existing main current limiting methods, a voltage controllable fault current controller was proposed to achieve precise control of fault current. The simulation model of DC microgrid and fault current controller was built for simulation verification. [Result] The simulation results show that the fault current controller can significantly reduce the fault current and achieve precise control of the fault current, making the system controllable before and after the fault without locking the protection. During steady-state operation, the fault current controller can also assist the VSC (Voltage Source Converter) in further stabilizing the DC bus voltage. [Conclusion] To cooperate with the normal operation of the relay protection device and avoid VSC triggering overcurrent protection blocking, it is recommended to set the fault current control range between 1~2 pu.

[Introduction] With the development of new loads, such as distributed power sources and electric vehicles, DC(Direct Current) microgrids have the advantages of fewer commutation links and lower system losses than AC(Alternating Current) microgrids, and have become the current research hotspot. Due to the small coverage of the DC microgrid and access to a large amount of distributed power sources, the fault current rises quickly with a large amplitude when inter-pole short-circuit fault occurs, making it difficult to achieve differential coordination with traditional overcurrent protection used in AC distribution networks and posing a great challenge to fault localization. [Method] Therefore, in response to the characteristics of fault current in DC microgrids, the method for designing overcurrent protection setting value based on the precise control value of fault current through the integration of current limiting and protection was proposed. Combined with the reasonable capacity design of each branch, it can easily achieve differential coordination and accurately locate faults. [Result] A corresponding DC microgrid model is built on the PSCAD/EMTDC simulation platform. The proposed protection scheme is simulated and verified, and the result shows that the scheme can correctly locate the fault point and quickly remove the fault. [Conclusion] The proposed protection scheme can ensure the selectivity of overcurrent, which verifies the rationality of the scheme.

The challenge of mixing high-viscosity materials is a common issue encountered in the manufacturing process of food materials. The advantages of the internal meshing screw mixer have led to its adoption in various manufacturing processes, but it has yet to be implemented in the food industry. The paper presents a design method for an internal meshing screw mixer based on kinematic principles. The mixer features a helical chamber created by alternating volumes formed by the stator and rotor, establishing an extension-dominated environment for mixing high-viscosity fluids. A kinematic model based on the internal cycloid principle was established, providing trajectories and equations for key points on the rotor, simulating both its rotation and revolution processes, and revealing the velocity variations at different points on the rotor. Based on the kinematic analysis results, a stator and rotor design method was developed according to relevant functional divisions. To achieve the desired motion effects, transmission and support devices were designed, and the relationship between the transmission device and the internal cycloid surface of the fixed rotor was established. The mixer’s application and mixing effectiveness in the food industry were validated using corn syrup and flour. Experimental results showed that the extensional mixer described in the paper effectively mixed high-viscosity fluids while also efficiently blending fine powders. Slurry viscosity was tested with a rheometer at different speeds with an eccentric rotor mixer. Results showed that viscosity decreased with increasing shear rate, with a more pronounced decrease at higher shear rates. The apparent viscosity trend remained consistent at different speeds, although variations were observed at lower shear rates, especially concerning speed. The non-Newtonian fluid index exhibited minimal variations at different speeds, while the consistency coefficient showed significant fluctuations. The mixing uniformity index of the slurry was used to evaluate the mixing uniformity and dispersion uniformity of this extensional mixer. At different rotational speeds, the density of the slurry changes little. The uniformity index of mixing decreases gradually with the increase of rotational speed, reaching its maximum at 15 r/min. The overall trend of the uniformity index decreases with increasing rotational speed, indicating a decrease in density uniformity. A peak appears at 45 r/min, possibly due to the maximum values of elongation rate and shear rate at this speed. As the rotational speed increases, the residence time of the material in the mixer decreases, which may be the main reason for the decrease in mixing uniformity. These findings provide valuable insights into the design and utilization of extension-dominated screw mixers within the food industry, laying a solid foundation for future research and practical applications in this field.

Renewable, green, and safe natural biopolymer-derived materials are highly desired for the purification of pollutants, but significantly improving their performance without the introduction of additional harmful chemicals remains a huge challenge. Based on the concept of “structure optimization design”, environment-friendly composite beads (named SA/PASP/RE) with excellent adsorption performance and recyclability were rationally constructed through a green ionic crosslinking route, using the completely green biopolymer sodium alginate (SA), sodium salt of polyaspartic acid (PASP), and the natural nanoclay rectorite (RE) as starting materials. The nano-layered RE was embedded in the polymer matrix to prevent the polymer chain from becoming over-entangled so that more adsorption sites inside the polymer network were exposed, which effectively improved the mass transfer efficiency of the adsorbent and the removal rate of contaminants. The composite beads embedded with 0.6% RE showed high adsorption capacities of 211.78, 197.13, and 195.69 mg/g for Pb(II) and 643.00, 577.80, and 567.10 mg/g for methylene blue (MB) in Yellow River water, Yangtze River water, and tap water, respectively. And the beads embedded with 43% RE could efficiently adsorb Pb(II) and MB with high capacities of 187.78 mg/g and 586.46 mg/g, respectively. This study provides a new route to design and develop a green, cost-effective, and efficient adsorbent for the decontamination of wastewater.

Background: Short-term exposure to fine particulate matter (PM2.5) and its specific constituents might exacerbate allergic rhinitis (AR) conditions. However, the evidence is still inconclusive. Method: We conducted a panel study of 49 patients diagnosed with AR > 1 year prior to the study in Taiyuan, China, to investigate associations of individual exposure to PM2.5 and its constituents with oxidative parameters, symptoms, and quality of life among AR patients. All participants underwent repeated assessments of health and PM exposure at 4 time points in both the heating and nonheating seasons from June 2017 to January 2018. AR patients’ oxidative parameters were assessed using nasal lavage, and their subjective symptoms and quality of life were determined through in-person interviews using a structured questionnaire. Short-term personal exposure to PM2.5 and its constituents was estimated using the time-microenvironment-activity pattern and data from the nearest air sampler, respectively. We applied mixed-effects regression models to estimate the short-term effects of PM2.5 and its constituents. Results: The results showed that exposure to PM2.5 and its constituents, including BaP, PAHs, SO42−, NH4+, V, Cr, Cu, As, Se, Cd, and Pb, was significantly associated with increased oxidative stress, as indicated by an increase in the malondialdehyde (MDA) index. Exposure to PM2.5 and its components (V, Mn, Fe, Zn, As, and Se) was associated with decreased antioxidant activity, as indicated by a decrease in the superoxide dismutase (SOD) index. Additionally, increased visual analog scale (VAS) and rhinoconjunctivitis quality of life questionnaire (RQLQ) scores indicated that exposure to PM2.5 and its constituents exacerbated inflammatory symptoms and affected quality of life in AR patients. Conclusion: Exposure to PM2.5 and specific constituents, could exacerbate AR patients' inflammatory symptoms and adversely affect their quality of life in the heavily industrialized city of Taiyuan, China. These findings may have potential biological and policy implications.

Examining medical supply–demand imbalances, as revealed through patients’ cross-boundary treatment behaviors, is vital for reducing a metropolitan area’s medical supply–demand gap and furthering sustainable development goals. This study, leveraging medical supply–demand and commuting data, scrutinizes medical imbalances in the Wuhan metropolitan area core. It includes a ‘People-centered’ theory for elucidating patients’ treatment behaviors, proposes a method for constructing a regional medical supply–demand network, and explores the problem of supply–demand imbalance. The key findings include: (1) Wuhan’s central area, despite its abundance of quality medical resources, fails to adequately cover the entire metropolitan area, indicating a need for broader resource distribution. (2) The Ezhou–Huangshi–Huanggang junction shows a stark contrast to Wuhan with its limited medical services and extensive hinterland connections. Future initiatives should aim to integrate resources dispersed from Wuhan, reducing regional disparities. (3) The city’s periphery, influenced by resource distribution models and geographic distance, exhibits significant variance from central urban areas in medical supply–demand connectivity, particularly around Wuhan’s eastern administrative boundaries. Future urban planning is needed to reinforce this area’s role as a vital medical services conduit. (4) The distinguishing differences among the nine medical service communities in terms of resource recognition, service sharing, and patient mobility provide policy guidance for the allocation of medical resources.

To adapt to the development trend of intelligent air combat, it is necessary to research the autonomous generation of maneuvering decisions for unmanned combat aerial vehicles (UCAV). This paper presents a maneuver decision-making method for UCAV based on a hybridization of deep Q-network (DQN) and extended Kalman filtering (EKF). Firstly, a three-dimensional air combat simulation environment is constructed, and a flight motion model of UCAV is designed to meet the requirements of the simulation environment. Secondly, we evaluate the current situation of UCAV based on their state variables in air combat, for further network learning and training to obtain the optimal maneuver strategy. Finally, based on the DQN, the system state equation is constructed using the uncertain parameter values of the current network, and the observation equation of the system is constructed using the parameters of the target network. The optimal parameter estimation value of the DQN is obtained by iteratively updating the solution through EKF. Simulation experiments have shown that this autonomous maneuver decision-making method hybridizing DQN with EKF is effective and reliable, as it can eliminate the opponent and preserve its side.

A novel fluorescent “off” probe R-β-D-1 containing a 1,2,3-triazole moiety was obtained by the Click reaction with azidoglucose using H8-BINOL as a substrate, and the structure was characterized by 1H NMR and 13C NMR and ESI-MS analysis. The fluorescence properties of R-β-D-1 in methanol were investigated, and it was found that R-β-D-1 could be selectively fluorescently quenched by Bi3+ in the recognition of 19 metal ions and basic cations. The recognition process of Bi3+ by R-β-D-1 was also investigated by fluorescence spectroscopy, SEM, AFM, etc. The complex pattern of R-β-D-1 with Bi3+ was determined by Job’s curve as 1 + 1, and the binding constant Ka of R-β-D-1 and Bi3+ was valued by the Benesi–Hildebrand equation as 1.01 × 104 M−1, indicating that the binding force of R-β-D-1 and Bi3+ was medium. The lowest detection limit (LOD) of the self-assembled H8-BINOL derivative for Bi3+ was up to 0.065 µM. The mechanism for the recognition of Bi3+ by the sensor R-β-D-1 may be the intramolecular charge transfer effect (ICT), which was attributed to the fact that the N-3 of the triazole readily serves as an electron acceptor while the incorporation of Bi3+ serves as an electron donor, and the two readily undergo coordination leading to the quenching of fluorescence. The recognition mechanism and recognition site could be verified by DFT calculation and CDD (Charge Density Difference).

In this study, tracking control and saturation nonlinearities problems of a flexible mobile vehicle-manipulator with disturbance uncertainty are investigated. Based on differential equations model, a novel iterative learning control (ILC) algorithm is designed, where two saturation functions and two hyperbolic tangent functions are developed to deal with actuator saturation constraint and an adaptive law is developed to reduce the impact of disturbance uncertainty. With the ILC algorithm, the target of tracking control and vibration attenuation of mobile manipulator can come true. Simulations are executed to verify the effectiveness of designed algorithm.

Long-term drug treatment for Restless Legs Syndrome (RLS) patients can frequently result in augmentation, which is the deterioration of symptoms with an increased drug dose. The cause of augmentation, especially derived from dopamine therapy, remains elusive. Here, we review recent research and clinical progress on the possible mechanism underlying RLS augmentation. Dysfunction of the dopamine system highly possibly plays a role in the development of RLS augmentation, as dopamine agonists improve desensitization of dopamine receptors, disturb receptor interactions within or outside the dopamine receptor family, and interfere with the natural regulation of dopamine synthesis and release in the neural system. Iron deficiency is also indicated to contribute to RLS augmentation, as low iron levels can affect the function of the dopamine system. Furthermore, genetic risk factors, such as variations in the BTBD9 and MEIS1 genes, have been linked to an increased risk of RLS initiation and augmentation. Additionally, circadian rhythm, which controls the sleep–wake cycle, may also contribute to the worsening of RLS symptoms and the development of augmentation. Recently, Vitamin D deficiency has been suggested to be involved in RLS augmentation. Based on these findings, we propose that the progressive reduction of selective receptors, influenced by various pathological factors, reverses the overcompensation of the dopamine intensity promoted by short-term, low-dose dopaminergic therapy in the development of augmentation. More research is needed to uncover a deeper understanding of the mechanisms underlying the RLS symptom and to develop effective RLS augmentation treatments.

As a thin fibrous layer covering the bone surface, the periosteum plays a significant role in bone physiology during growth, development and remodeling. Over the past several decades, the periosteum has received considerable scientific attention as a source of mesenchymal stem cells (MSCs). Periosteum-derived cells (PDCs) have emerged as a promising strategy for tissue engineering due to their chondrogenic, osteogenic and adipogenic differentiation capacities. Starting from the history of PDCs, the present review provides an overview of their characterization and the procedures used for their isolation. This study also summarizes the chondrogenic, osteogenic, and adipogenic abilities of PDCs, serving as a reference about their potential therapeutic applications in various clinical scenarios, with particular emphasis on the comparison with other common sources of MSCs. As techniques continue to develop, a comprehensive analysis of the characterization and regulation of PDCs can be conducted, further demonstrating their role in tissue engineering. PDCs present promising potentials in terms of their osteogenic, chondrogenic, and adipogenic capacities. Further studies should focus on exploring their utility under multiple clinical scenarios to confirm their comparative benefit over other commonly used sources of MSCs.

Introduction: Reliable biomarkers are in need to predict the prognosis of hepatocellular carcinoma (HCC). Whilst recent evidence has established the critical role of copper homeostasis in tumor growth and progression, no previous studies have dealt with the copper-related genes (CRGs) signature with prognostic potential in HCC.Methods: To develop and validate a CRGs prognostic signature for HCC, we retrospectively included 353 and 142 patients as the development and validation cohort, respectively. Copper-related Prognostic Signature (Copper-PSHC) was developed using differentially expressed CRGs with prognostic value. The hazard ratio (HR) and the area under the time-dependent receiver operating characteristic curve (AUC) during 3-year follow-up were utilized to evaluate the performance. Additionally, the Copper-PSHC was combined with age, sex, and cancer stage to construct a Copper-clinical-related Prognostic Signature (Copper-CPSHC), by multivariate Cox regression. We further explored the underlying mechanism of Copper-PSHC by analyzing the somatic mutation, functional enrichment, and tumor microenvironment. Potential drugs for the high-risk group were screened.Results: The Copper-PSHC was constructed with nine CRGs. Patients in the high-risk group demonstrated a significantly reduced overall survival (OS) (adjusted HR, 2.65 [95% CI, 1.83–3.84] and 3.30, [95% CI, 1.27–8.60] in the development and validation cohort, respectively). The Copper-PSHC achieved a 3-year AUC of 0.74 [95% CI, 0.67–0.82] and 0.71 [95% CI, 0.56–0.86] for OS in the development and validation cohort, respectively. Copper-CPSHC yield a 3-year AUC of 0.73 [95% CI, 0.66–0.80] and 0.72 [95% CI, 0.56–0.87] for OS in the development and validation cohort, respectively. Higher tumor mutation burden, downregulated metabolic processes, hypoxia status and infiltrated stroma cells were found for the high-risk group. Six small molecular drugs were screened for the treatment of the high-risk group.Conclusion: Copper-PSHC services as a promising tool to identify HCC with poor prognosis and to improve disease outcomes by providing potential clinical decision support in treatment.

Abstract Background Icariin (ICA), a main active ingredient of Herba Epimedium, could promote bone formation, inhibit bone resorption and alleviate inflammatory responses. The aim of this study was to investigate the effect of ICA on the inhibition of bacteria associated with peri-implantitis, and fabricate a calcium phosphate cement (CPC) with ICA-loaded gelatin microspheres (GMs) as a local drug delivery system efficiently promoting bone formation and alleviating inflammation. Results In this study, ICA exhibited antibacterial activity against P. gingivalis with a MIC value of 1 × 10–4 mol/L. When the concentration of ICA was 0.5 mM, the encapsulation efficiency of GMs reached the maximum value of 76.26 ± 3.97%. GMs with ICA revealed a controlled release profile, 0.5 mM ICA exhibited a higher ICA release profile than the other groups during a 21 d monitoring span. The results of SEM and XRD demonstrated successful fabrication of a calcium phosphate cement with ICA-loaded GMs. ICA released from CPC/GMs (ICA) was slower than ICA released from GMs within 10 days. CPC/GMs (ICA) exhibited antibacterial activity against P. gingivalis, but the antibacterial rate of CPC/GMs (ICA) was only 17.15 ± 6.06%. In addition, CPC/GMs (ICA) promoted the proliferation of BMSCs and significantly stimulated the differentiation and maturation of BMSCs. In vivo, H&E and Masson staining experiments demonstrated that CPC/GMs (ICA) exhibited better capacity for bone regeneration than CPC/GMs and CPC, and the expression of TNF-α and IL-1β in the tissue around CPC/GMs (ICA) was significantly lower than CPC/GMs and CPC in IHC staining (P

Abstract Background Given malignant ascites with a terrible prognosis and a unique immune microenvironment, our purpose is to evaluate whether oncolytic herpes simplex virus type 2(OH2) is able to safely eliminate ascites of colon cancer and through which specific mechanism it exerts antitumor immunity. Methods We established an ascites mice model through intraperitoneal injection of CT26 cells and obtained an appropriate dose range for in vivo tests. Efficacy and safety of OH2 were detected by weight of ascites, blood routine analysis, histopathological examination, and the survival time of mice. The specific mechanism underlying antitumor immunity was analyzed by cytometric bead array, flow cytometry, and single‐cell RNA sequencing. Furthermore, anti‐interleukin (IL)‐6R antibody tocilizumab was synchronously or sequentially delivered with OH2 to explore the role of the regional cytokine storm, mainly IL‐6 hypersecretion. Results OH2 was able to eliminate ascites and significantly prolong the survival of mice‐bearing CT26 tumor cells by intraperitoneal injection, without obvious systemic damage to the main organs even though a regional cytokine storm. Hypersecretion of pro‐inflammatory cytokines, mainly IL‐6, and increased infiltration of CD4+ and CD8+ T cells were observed in ascites mice treated by OH2, compared with those treated by 5‐fluorouracil or nonresponders. Furthermore, the initial‐stage blocking of the IL‐6 pathway was able to considerably suppress antitumor immune responses driven by OH2. Surprisingly, we discovered upregulations of the immune checkpoint genes such as Cd274 and Pdcd1 by single‐cell RNA sequencing. Conclusions OH2 could safely eliminate malignant ascites of colon cancer and convert the cold immune microenvironment by inducing a remarkably regional cytokine storm in ascites, mainly IL‐6, in the early stage of antitumor immune responses beyond directed oncolytic virotherapy.

Abstract Background Drug-target interactions (DTIs) prediction becomes more and more important for accelerating drug research and drug repositioning. Drug-target interaction network is a typical model for DTIs prediction. As many different types of relationships exist between drug and target, drug-target interaction network can be used for modeling drug-target interaction relationship. Recent works on drug-target interaction network are mostly concentrate on drug node or target node and neglecting the relationships between drug-target. Results We propose a novel prediction method for modeling the relationship between drug and target independently. Firstly, we use different level relationships of drugs and targets to construct feature of drug-target interaction. Then, we use line graph to model drug-target interaction. After that, we introduce graph transformer network to predict drug-target interaction. Conclusions This method introduces a line graph to model the relationship between drug and target. After transforming drug-target interactions from links to nodes, a graph transformer network is used to accomplish the task of predicting drug-target interactions.

Background Immune checkpoint molecules, especially programmed death 1 (PD-1) and its ligand, programmed death ligand 1 (PD-L1), protect tumor cells from T cell-mediated killing. Immune checkpoint inhibitors, designed to restore the antitumor immunosurveillance, have exhibited significant clinical benefits for patients with certain cancer types. Nevertheless, the relatively low response rate and acquisition of resistance greatly limit their clinical applications. A deeper understanding of the regulatory mechanisms of PD-L1 protein expression and activity will help to develop more effective therapeutic strategies.Methods The effects of AR-A014418 and THZ531 on PD-L1 expression were detected by western blot, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and flow cytometry. In vitro kinase assays with recombinant proteins were performed to confirm that AR-A014418 functioned as a CDK12 and CDK13 dual inhibitor. The roles of CDK12 and CDK13 in intronic polyadenylation (IPA) and transcription of PD-L1 were determined via RNA interference or protein overexpression. T-cell cytotoxicity assays were used to validate the activation of antitumor immunity by AR-A014418 and THZ531.Results AR-A014418 inhibits CDK12 to enhance the IPA, and inhibits CDK13 to repress the transcription of PD-L1. IPA generates a secreted PD-L1 isoform (PD-L1-v4). The extent of IPA was not enough to reduce full-length PD-L1 expression obviously. Only the superposition of enhancing IPA and repressing transcription (dual inhibition of CDK12 and CDK13) dramatically suppresses full-length PD-L1 induction by interferon-γ. AR-A014418 and THZ531 could potentiate T-cell cytotoxicity against tumor cells.Conclusions Our work identifies a new regulatory pathway for PD-L1 expression and discovers CDK12 and CDK13 as promising drug targets for immune modulation and combined therapeutic strategies.

Abstract Background This study aimed to identify genes related to the degree of immune cell infiltration in head and neck squamous cell carcinoma (HNSCC), explore their new biological functions, and evaluate their diagnostic and prognostic value in HNSCC. Methods Transcriptomic data from The Cancer Genome Atlas (TCGA) HNSCC dataset was used to screen differentially expressed genes between tumors and normal tissues, followed by weighted correlation network analysis (WGCNA) to identify immune‐related modules. Differential gene expression, immune cell infiltration, and survival analyses were performed to screen key genes. The expression of these key genes was validated in Oncomine and gene expression omnibus (GEO) datasets and by immunohistochemistry (IHC). Results 1869 and 1578 genes were significantly upregulated and downregulated in HNSCC. WGCNA showed that the brown module was associated with the most significant number of immune‐related genes. PPI network analysis demonstrated that PPL, SCEL, KRT4, KRT24, KRT78, KRT13, SPRR3, TGM3, CRCT1, and CRNN were key components in the brown module. Furthermore, the expression levels of KRT4, KRT78, KRT13, and SPRR3 in HNSCC correlated with infiltration levels of CD8+ T cells and macrophages. Survival analyses revealed that the expression of KRT78, KRT13, and SPRR3 in HNSCC correlated with overall survival (OS). The IHC assay indicated that KRT13 (p = .042), KRT78 (p

Major depressive disorder is a common and devastating psychiatric disease, and the prevalence and burden are substantially increasing worldwide. Multiple studies of depression patients have implicated glucose metabolic dysfunction in the pathophysiology of depression. However, the molecular mechanisms by which glucose and related metabolic pathways modulate depressive-like behaviors are largely uncharacterized. Uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) is a glucose metabolite with pivotal functions as a donor molecule for O-GlcNAcylation. O-GlcNAc transferase (OGT), a key enzyme in protein O-GlcNAcylation, catalyzes protein posttranslational modification by O-GlcNAc and acts as a stress sensor. Here, we show that Ogt mRNA was increased in depression patients and that astroglial OGT expression was specifically upregulated in the medial prefrontal cortex (mPFC) of susceptible mice after chronic social-defeat stress. The selective deletion of astrocytic OGT resulted in antidepressant-like effects, and moreover, astrocytic OGT in the mPFC bidirectionally regulated vulnerability to social stress. Furthermore, OGT modulated glutamatergic synaptic transmission through O-GlcNAcylation of glutamate transporter-1 (GLT-1) in astrocytes. OGT astrocyte–specific knockout preserved the neuronal morphology atrophy and Ca2+ activity deficits caused by chronic stress and resulted in antidepressant effects. Our study reveals that astrocytic OGT in the mPFC regulates depressive-like behaviors through the O-GlcNAcylation of GLT-1 and could be a potential target for antidepressants.

Abstract Background Whether neuroinflammation causes comorbid mood disorders in neuropathic pain remains elusive. Here we investigated the role of high mobility group box 1 protein (HMGB1), a proinflammatory cytokine, in the medial prefrontal cortex (mPFC) in anxiety comorbidity of neuropathic pain. Methods Neuropathic pain was induced by partial transection of the infraorbital nerve (p-IONX) or partial sciatic nerve ligation (PSL) in mice and evaluated by measuring nociceptive thresholds to mechanical and heat stimulation. Anxiety-like behaviors were assessed by elevated plus maze, light dark box and open field tests. Aversive or anti-aversive effect was detected by conditioned place preference test. Neuronal activity was evaluated by single-unit and patch clamp recordings. The contribution of mPFC pyramidal neurons to anxiety was further examined by selectively inhibiting them by optogenetics. HMGB1 expression was measured by immunohistochemistry and western blotting. Antagonism of HMGB1 was achieved by injecting anti-HMGB1 monoclonal antibody (mAb) intracerebrally or intraperitoneally. Results Anxiety-like behaviors were presented earlier after p-IONX than after PSL. HMGB1 expression was upregulated in the mPFC temporally in parallel to anxiety onset, rather than in other regions associated with anxiety. The upregulation of HMGB1 expression and its translocation from the nucleus to cytoplasm in the mPFC occurred predominantly in neurons and were accompanied with activation of microglia and astrocytes. Infusion of anti-HMGB1 mAb into the mPFC during the early and late phases after either p-IONX or PSL alleviated anxiety-like behaviors and aversion without changing pain sensitization, while local infusion of exogenous ds-HMGB1, the proinflammatory form of HMGB1, into the mPFC induced anxiety and aversion but not pain sensitization in naïve mice. In addition to reversing established pain sensitization and anxiety simultaneously, intraperitoneal injection of anti-HMGB1 mAb reduced HMGB1 upregulation and suppressed the hyperexcitability of layer 2/3 pyramidal neurons in the mPFC after p-IONX. Moreover, optogenetic inhibition of mPFC pyramidal neurons alleviated anxiety in p-IONX mice. Conclusion These results demonstrate that HMGB1 in the mPFC drives and maintains anxiety comorbidity in neuropathic pain by increasing the excitability of layer 2/3 pyramidal neurons, and justify antagonism of HMGB1, e.g., neutralization by mAb, as a promising therapeutic strategy for neuropathic pain with anxiety comorbidity.

Abstract Background According to the validation literature on items of Young’s Internet Addiction Test (IAT), this study rephrased disputable items to improve the psychometric properties of this Chinese version of IAT and identify the presence of differential item function (DIF) among demographic and Internet use factors; detect the effect of demographic and Internet use factors on IAT after adjusting for DIF. Methods An online questionnaire was distributed to college students in Zhe Jiang province in two stage. The 1st phase study collected 384 valid responses to examine the quality of IAT items by using Rasch Model analysis and exploring factor analysis (EFA). The online questionnaire was modified according to the 1st phase study and distributed online for the 2nd phase study which collected a total of 1131 valid responses. The 2nd phase study applied confirmatory factor analysis (CFA) and a multiple indicator multiple causes (MIMIC) model to verify the construct of IAT, potential effect of covariates on IAT latent factors, as well as the effect of differential item functioning (DIF). Results Rasch model analysis in the 1st phase study indicated a 5-point rating scale was performed better, no sever misfit was found on item. The overall property of Chinese version IAT with the 5-point scale was good to excellent person and item separation (2.66 and 6.86). A three-factor model was identified by EFA. In the 2nd phase study, IAT 13 were detected with DIF for gender in MIMIC model. After correcting DIF effect, the significant demographic and Internet use factors on IAT were time spent online per day, year 3, year 2, general users. Conclusion Item improvement was efficient that the problematic items found in literature was performed good in this study. The overall psychometric property of this Chinese version IAT was good with limited DIF effect in one item. Item improvement on IAT13 was encouraged in the future study to avoid gender bias and benefit for epidemiology on PIU.

During the production process of high temperature and high pressure gas well, high temperature fluids are produced from the formation. The change of wellbore temperature and pressure, due to the change of production, has an important impact on the production tubular column, which threatens the safety of the completion tubular column and the integrity of the wellbore. A single-phase gas transient flow temperature–pressure​ coupling mathematical model is developed for the fluid in the tubular column during gas well production, and the pressure and temperature distribution patterns of the gas in the tubular column during gas well production are obtained, and the influence of production rate on the temperature–pressure distribution in the tubular column during gas well production is analyzed. The coupled temperature–pressure model takes into account the mutual influence of temperature and pressure during the transient flow of gas in the column, and the comparison with the measured data in the field and the calculation results of the analytical model shows that the coupled model has higher accuracy. The model will provide theoretical support for the selection and optimal design of completion production tubular tools.

Manufacturing errors are one of the main causes of vibration and noise of gear transmission system，and the combination of multiple errors seriously affects the meshing performance of gear pairs. The influence degree and law of various manufacturing errors on meshing performance of herringbone gear pairs are mainly studied. Firstly，the manufacturing error model is established，and the actual tooth surface is constructed based on the theory of spatial coordinate transformation. Secondly，the influence law of different errors on the meshing performance of the gear pair is explored through the load distribution on the tooth surface，and the influence degree of different errors is explored based on the orthogonal experiment. Finally，the relationship between the influence of typical error types on the meshing performance of gear pairs and the system load is analyzed. The results show that the influence law of various errors on the meshing performance of gear pair is different，and the positive tilt deviation of helix direction has the most prominent influence on the meshing performance of gear pairs under heavy load.

Epithelial ovarian cancer (EOC) is the leading cause of gynecological cancer-related death. The high mortality and morbidity associated with EOC are mostly due to late diagnosis and chemotherapy drug resistance. Currently, the standard first-line chemotherapy regimen is systemic administration of platinum-based chemotherapy combined with a taxane. A major problem besides cisplatin resistance (occurring in nearly one-third of patients) is the greater toxicity of the drug combinations. A synergistic treatment with drug supporting activity could maximize the cytotoxic effects of chemotherapeutic agents on tumor cells while decreasing the dosage of each drug to potentially reduce toxicity. The ALDH-blocking agent Disulfiram (DSF), a clinically approved drug used for alcoholism treatment, has displayed promising anti-cancer activity. We previously described that blocking ALDH activity enhances the induction of apoptosis, especially in ovarian cancer stem cells treated with chemotherapeutic agents. In this study, we further investigated the synergistic effect of DSF in combination with cytotoxic chemotherapeutic drugs. The concentration of each chemotherapeutic agent could be significantly reduced with sustained efficacy on tumor cell apoptosis in cell lines in vitro (Dose-Reduction Index at IC50 from 1 to 50). Moreover, the potential chemo-sensitizing effects of DSF on ALDH-associated cisplatin-resistant ovarian cancer stem cells were also investigated and shown that in contrast to its high resistance to cisplatin, the cisplatin-resistant cells remain very sensitive to DSF-induced cytotoxicity (apoptosis and necrosis: cisplatin-resistant cells vs. parental cells: 60.4% vs. 20.5%). In combination with DSF and cisplatin, relatively more apoptosis and necrosis were induced in cisplatin-resistant cells than in their parental cells (apoptosis and necrosis: cisplatin-resistant cells vs. parental cells: 81.5% vs. 50.1%). A transcriptome analysis identified that ALDH was mainly enriched in the cancer-associated fibroblasts and showed that ALDH plays roles in responding to oxidative stress, metabolisms, and energy transition in the ALDH-associated cisplatin-resistant ovarian cancer stem cells. In conclusion, our data demonstrate a key role of ALDH-associated cisplatin-resistant cancer stem cells and identifies DSF as a potential adjuvant for a rational protocol design by computational quantitative assessment in vitro on ovarian cancer cell lines. Our work contributes to resolving the ALDH-associated cisplatin resistance and provides a resource for the development of novel chemotherapeutic regimens.

High overpotential and poor long‐term operation stability of electrocatalysts are two major barriers for the hydrogen evolution reaction (HER). Herein, 2D ultrathin PdAgAu nanorings are synthesized and further self‐assembled on Ti2CTx–graphene oxide (GO) heterostructure for efficiently boosting HER. The best candidate, Pd50Ag31Au19/Ti2CTx–GO electrocatalyst, can initiate hydrogen evolution at an overpotential of 90 mV at 10 mA cm−2 and exhibits the lowest Tafel slope of 75 mV dec−1 as well as the highest mass activity of 284.4 mA mg−1Pd at −100 mV, in comparison with those of Pd50Ag31Au19/Ti2CTx, Pd50Ag31Au19/GO, and commercial Pd/C. Most remarkably, impressive long‐term stability is achieved even after a 112 h chronoamperometric test. The great performance of Pd50Ag31Au19/Ti2CTx–GO electrocatalyst can be attributed to the advantageous synergistic effect among the morphological modulation, composition optimization, and strong metal–support interaction effect between the Pd50Ag31Au19 nanorings and Ti2CTx–GO support.

Phytoplankton is an important primary producer of the estuarine ecosystem, which is essential for the biogeochemical cycle of water elements and nutrient transfer. The Pearl River estuary (PRE) is a dynamically complex estuary, and the environment of PRE is significantly impacted by anthropogenic activities, variation of phytoplankton community structure in the PRE are complex. This review aims to compare phytoplankton species, species diversity, and abundance variation characteristics from the 1980s and 2020s, evaluate the overall trend of phytoplankton in the PRE, and discuss the main environmental factors affecting phytoplankton growth in the PRE. The data from the past 40 years in PRE showed that the number of phytoplankton species significantly decreased (p < 0.05). There was no significant difference in the abundance of phytoplankton at the 10-year scale, however, the fluctuation range of the abundance has increased. Under the conditions of a decreasing species number and no significant difference in abundance, the species diversity of phytoplankton showed a downward trend. In addition, the dominant phytoplankton species in the nearshore waters were relatively homogenous, and the abundance of phytoplankton in the nearshore waters was higher than that in the open waters, which suggested that human activities have a great influence. This review can form the basis for facilitating health management in the PRE ecosystem. Further, relevant guidelines can be developed and implemented for promoting the ecological health of the Guangdong-Hong Kong-Macao Greater Bay Area and ensuring its sustainable development.

The complete removal of low concentration organic pollutants from wastewater to obtain clean water has always been a highly desired but challenging issue. In response to this, we proposed a new strategy to fabricate a carbon-in-silicate nanohybrid composite by recycling dye-loaded layered clay adsorbent and converting them to new heterogeneous carbon-in-silicate nanocomposite through an associated calcination-hydrothermal activation process. It has been confirmed that most of the dye molecules were present in waste rectorite adsorbent using an intercalation mode, which can be in situ converted to carbon in the confined interlayer spacing of rectorite. The further hydrothermal activation process may further improve the pore structure and increase surface active sites. As expected, the optimal composite shows extremely high removal rates of 99.6% and 99.5% for Methylene blue (MB) and Basic Red 14 (BR) at low concentrations (25 mg/L), respectively. In addition, the composite adsorbent also shows high removal capacity for single-component and two-component dyes in deionized water and actual water (i.e., Yellow River water, Yangtze River water, and seawater) with a removal rate higher than 99%. The adsorbent has good reusability, and the adsorption efficiency is still above 93% after five regeneration cycles. The waste clay adsorbent-derived composite adsorbent can be used as an inexpensive material for the decontamination of dyed wastewater.

This paper involves a novel adaptive control approach of a flexible wing system with hysteresis nonlinearity. The usual control design strategies based on the ordinary differential equations (ODEs) are inapplicable due to the flexible wing system described in the partial differential equations (PDEs), and the design of the control algorithm becomes highly intricate. Firstly, the inverse dynamic model of hysteresis is introduced to compensate for the hysteresis nonlinearity. Considering the unknown external disturbances, an adaptive technique is utilized for compensation. Then, the direct Lyapunov approach is employed to prove the bounded stability of the system. Lastly, the effectiveness of the proposed approach is validated via simulation results.

Red meat and animal-sourced protein are often disparaged as risk factors for developing metabolic syndrome, while emerging research has shown the beneficial effects of dietary taurine, creatine, carnosine, and anserine which are all exclusively abundant in red meat. Thus, it is imperative to highlight the available evidence to help promote red meat as part of a well-balanced diet to optimize human health. In this study, a bibliometric analysis was conducted to investigate the current research status of dietary taurine, creatine, carnosine, and anserine with metabolic syndrome, identify research hotspots, and delineate developmental trends by utilizing the visualization software CiteSpace. A total of 1094 publications were retrieved via the Web of Science Core Collection from 1992 to 2022. There exists a gradual increase in the number of publications on this topic, but there is still much room for research papers to rise. The United States has participated in the most studies, followed by China and Japan. The University of Sao Paulo was the research institute contributing the most; Kyung Ja Chang and Sanya Roysommuti have been identified as the most prolific authors. The analysis of keywords reveals that obesity, lipid profiles, blood pressure, and glucose metabolism, as well as ergogenic aid and growth promoter have been the research hotspots. Inflammation and diabetic nephropathy will likely be frontiers of future research related to dietary taurine, creatine, carnosine, and anserine. Overall, this paper may provide insights for researchers to further delve into this field and enlist the greater community to re-evaluate the health effects of red meat.

Due to the limitation of machining accuracy, the transmission performance uncertainty of mass gears must be evaluated quantitatively to provide the basis for its application in the whole machine. Based on the polynomial chaotic expansion (PCE) method, a dynamic uncertainty analysis method for gear systems with a specified precision was proposed in this paper. Combined with tooth surface contact analysis and load-bearing contact analysis, a dynamic model of the gear system was established to fully reflect the influence of typical manufacturing errors. Based on this, a PCE model was established to approximate the system dynamics model. The dynamic uncertainty of the gear system was quantified based on the PCE approximation model and the Monte Carlo method, respectively, and the computational accuracy and efficiency of the PCE model with different orders and numbers of sample points were compared and analyzed. Finally, Sobol′ sensitivity indices from the PCE model of the gear system to random errors were computed, and the primary and secondary relationships of influence on the dynamic performance of the gear system were determined. The results showed that the PCE method had good applicability to the quantification of dynamic uncertainty and error sensitivity analysis of gear systems, and it had both accuracy and high efficiency.

Objective: To investigate the application value of metagenomic next-generation sequencing (mNGS) in children with hematological diseases presenting with Febrile Neutropenia (FN). Methods: We retrospectively analyzed the clinical data of 49 hematological children with FN, and compared the results of mNGS with those of traditional pathogen detection (TPD) and the prognoses of mNGS positive group and negative group. Results: A total of 77 pathogenic strains were identified, of which 70 strains were detected by mNGS, 19 strains by TPD, and Aspergillus and G- bacterias were the predominant strains in FN children who developed bloodstream infections. 42 cases were in the mNGS-positive group, of which 17 were simple infections, 25 were mixed infections, and 7 were in the negative group; the TPD-positive group contained 19 cases, all of which were simple infections. The detection rate of total and mixed pathogens was higher than that of TPD, and the difference was statistically significant (P

Aim: EBV encodes at least 44 miRNAs involved in immune regulation and disease progression. Exosomes can be used as carriers of EBV-miRNA-BART intercellular transmission and affect the biological behavior of cells. We characterized exosomes and established a co-culture experiment of exosomes to explore the mechanism of miR-BART1-3p transmission through the exosome pathway and its influence on tumor cell proliferation and invasion. Materials and methods: Exosomes of EBV-positive and EBV-negative gastric cancer cells were characterized by transmission electron microscopy. NanoSight and Western blotting, and miRNA expression profiles in exosomes were sequenced with high throughput. Exosomes with high or low expression of miR-BART1-3p were co-cultured with AGS cells to study the effects on proliferation, invasion, and migration of gastric cancer cells. The target genes of EBV-miR-BART1-3p were screened and predicted by PITA, miRanda, RNAhybrid, virBase, and DIANA-TarBase v.8 databases, and the expression of the target genes after co-culture was detected by qPCR. Results: The exosomes secreted by EBV-positive and negative gastric cancer cells range in diameter from 30 nm to 150 nm and express the exosomal signature proteins CD9 and CD63. Small RNA sequencing showed that exosomes expressed some human miRNAs, among which hsa-miR-23b-3p, hsa-miR-320a-3p, and hsa-miR-4521 were highly expressed in AGS-exo; hsa-miR-21-5p, hsa-miR-148a-3p, and hsa-miR-7-5p were highly expressed in SNU-719-exo. All EBV miRNAs were expressed in SNU-719 cells and their exosomes, among which EBV-miR-BART1-5p, EBV-miR-BART22, and EBV-miR-BART16 were the highest in SNU-719 cells; EBV-miR-BART1-5p, EBV-miR-BART10-3p, and EBV-miR-BART16 were the highest in SNU-719-exo. After miR-BART1-3p silencing in gastric cancer cells, the proliferation, healing, migration, and invasion of tumor cells were significantly improved. Laser confocal microscopy showed that exosomes could carry miRNA into recipient cells. After co-culture with miR-BART1-3p silenced exosomes, the proliferation, healing, migration, and invasion of gastric cancer cells were significantly improved. The target gene of miR-BART1-3p was FAM168A, MACC1, CPEB3, ANKRD28, and USP37 after screening by a targeted database. CPEB3 was not expressed in all exosome co-cultured cells, while ANKRD28, USP37, MACC1, and FAM168A were all expressed to varying degrees. USP37 and MACC1 were down-regulated after up-regulation of miR-BART1-3p, which may be the key target genes for miR-BART1-3p to regulate the proliferation of gastric cancer cells through exosomes. Conclusions: miR-BART1-3p can affect the growth of tumor cells through the exosome pathway. The proliferation, healing, migration, and invasion of gastric cancer cells were significantly improved after co-culture with exosomes of miR-BART1-3p silenced expression. USP37 and MACC1 may be potential target genes of miR-BART1-3p in regulating cell proliferation.

Background: 5-Hydroxymethylcytosine (5hmC) with dynamic existence possesses multiple regulatory functions. Whereas, 5hmC’s impact on small hepatocellular carcinoma (SHCC) remains unclear. The present work focused on characterizing 5hmC content within SHCC and assessing the possibility of using global genomic 5hmC level as the predicative factor of clinical outcome. Methods: This study applied ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) in measuring 5mC, 5fC and 5hmC contents. In addition, immunohistochemistry (IHC) was adopted to measure CK19 and 5hmC contents. Results: Research showed 5mC, 5hmC, and 5fC contents from global genomics of SHCC reduced extensively compared with healthy samples (p < 0.001). Moreover, SHCC was associated with lymph node metastasis (LNM). Greater 5mC and 5hmC levels were observed in non-metastasis group compared with the metastasis group (p < 0.001). Correlation analysis between the HBV DNA level and 5mC, 5fC and 5hmC levels exhibited that HBV DNA was associated with 5mC, 5hmC, and 5fC content reduction, which was verified in the cytological experiments. Moreover, 5hmC content had a negative correlation with the expression level of CK19 in SHCC. The decrease in 5hmC and CK19 containing 5hmC positive cell (called CK195hmC+) should be ascribed to the bad prognosis among SHCC patients. Conclusions: The contents of 5hmC and CK195hmC+ of genomic DNA might be adopted for predicting SHCC survival as an important biomarker.

The sliding mode observer (SMO)–based sensorless control is essentially a discontinuous switching control algorithm. Therefore, there is large speed or torque chattering in the permanent magnet synchronous motor (PMSM) with existing sliding mode observer–based control methods. In order to solve this problem well, an algorithm based on an improved sliding mode observer is proposed. In detail, the piecewise power function approach is used to replace the traditional ones, that is, the sgn function or the sigmoid function approach. Simulation verifications are conducted to validate the effectiveness of the proposed observer. It shows that the piecewise power function–based sliding mode observer algorithm has obvious advantages in the stability of the three-phase current, namely, it improves the estimation accuracy of the rotor position, rotor speed, and dynamic response to various loads. For further verification, the proposed sliding mode observer algorithm is implemented and verified in a marine electric propulsion motor with a DSP chip of TMS320F28377D. Experimental results validate that the piecewise power function–based sliding mode observer algorithm has high control accuracy and fewer fluctuations, which are all vital in marine engineering.

In subtropical karst area, small wetlands are widely distributed owing to the well-developed karst and the high degree of groundwater-surface water interaction. However, detailed plankton community composition, spatial-temporal dynamics, and its assembly mechanism were rarely discussed. To address these, plankton distribution patterns and its relationship with hydrological conditions and environment gradients were analyzed to discover the biological characteristics of wetlands in a typical karst basin in South China. The results showed that the wetlands were diverse in types due to the hydrogeological background. Water quality evaluation according to major ions analyses showed good results, with significant differences among samples and a poor status when measured by biotic indicator such as Escherichia coli. During high and low-flow condition, a total of 163 and 162 species of phytoplankton, and a total of 62 and 36 species of zooplankton, respectively were observed. The dominant species of phytoplankton communities in low-flow condition metamorphosed from Cyclotella sp. to Navicula sp. and Cocconeis placentula; and Pediastrum simplex to Ankistrodesmus spiralis. The metamorphosis in zooplankton community was from Difflugia globulosa to Strobilidium sp. Comparing with other karst water in different climate regimes, the number of plankton species in the subtropical karst wetland was the highest, which is related to the high and stable water temperature, large karst underground spaces, and frequent interaction between groundwater and surface water. The abundance, biomass and community semblance of plankton were increased with an increase in nutrients, precipitating improvement in hydrodynamics and light intensity. This study also suggested that the plankton in karst cave wetlands in subtropical area were characterized by low diversity, attributable to the calcium-rich and weakly alkaline, but poor nutrient status of the water environment, as well as drew attention to the possible functions of wetlands in relation to the quality of connected river.

Abstract Controversial results have been reported about the association of calcium, magnesium, and phosphorus and stroke risk, but none in China. To investigate the association between dietary calcium, magnesium, phosphorus, and stroke incidence in Chinese adults, we collected data from the China Health and Nutrition Survey (CHNS) from 2004 to 2011, including 6411 participants aged 45–79 years and free of stroke at baseline. Diet was assessed by interviews combining 3-d 24-h food recalls and household food inventory weighing at each survey round. The stroke incident was identified based on the validated self-report. Multivariate Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). For 32,024 person-years of follow-up, 179 stroke cases were documented. After adjustment for major lifestyle and dietary risk factors, calcium intake was positively associated with reduced stroke risk, and the HR of stroke comparing extreme quartiles was 0.53 (95% CI 0.29–0.96, P trend = 0.03). In further stratified analyses, significant heterogeneity across sex strata was found (P interaction = 0.03). Dietary calcium intake among men was more inversely related to stroke, with HRs being 0.33 (95% CI 0.15–0.76, P trend = 0.02), compared to 1.24 (95% CI 0.46–3.35, P trend = 0.89) among women. However, no significant association between stroke and magnesium or phosphorus was revealed. Our findings suggest that higher dietary calcium intake was associated with a lower risk of stroke in Chinese adults, particularly in men.

Direct cloning of biosynthetic gene clusters is difficult due to their size and repetitive nature. Here, the authors present CAPTURE, which uses Cas12a and in vivo Cre-lox recombination for efficient cloning of gene clusters up to 113 kb, and demonstrate how this method can be used for large-scale discovery of novel natural products.

Abstract Background In recent years, first-trimester intrauterine hematoma (IUH) has become increasingly common in twin pregnancy. The majority of studies on IUH have excluded twin pregnancies, and others did not differentiate between singleton and twin pregnancies. The impact of IUH on twin pregnancy is unclear. Therefore, the primary objective of our study was to examine associations between first-trimester IUH and pregnancy outcomes in twin pregnancies. Methods The data of 1020 twin pregnancies in women who received a routine examination from January 2014 to December 2018 were reviewed. We compared baseline data and pregnancy outcomes between those with and without IUH. Multivariable logistic regression analysis was used to adjust for possible confounding factors. Results A total of 209 patients (21.3%) developed IUH in the first trimester. First-trimester IUH was significantly associated with increased odds of miscarriage (adjusted odds ratio 14.27, 95% CI 8.25–24.70) and vanishing twin syndrome (adjusted odds ratio 3.26, 95% CI 1.11–4.61). However, there were no differences in the rates of stillbirth, preeclampsia, preterm labor ( 0.05). Conclusion In women with twin pregnancy, the presence of IUH in the first trimester was associated with the loss of one or both fetuses before 20 weeks of gestation. However, previous miscarriage, the conception method, the IUH size and the presence of vaginal bleeding were not independently associated with miscarriage or vanishing twin syndrome.

Background: Fever-range hyperthermia or fever-range temperature (hereafter FRT) improves survival and shortens disease duration in microbial infections. However, the mechanisms of these beneficial effects still remain elusive. We hypothesized that FRT might enhance cell responsiveness to infections by promoting cGAS-STING signaling to cause enhanced production of IFN-β. Objective: To investigate the effect fever-range hyperthermia on cGAS-STING pathway. Methods: RAW 264.7 and cGAS-/- RAW 264.7 cells, stimulated with 5μg/ml herring testis DNA (htDNA), were heated to 39.5°C and analyzed for the expression of cGAS, STING, IFN-β, and the synthesis of cGAMP and IRF3 phosphorylation. In vivo, wild type C57BL/6J mice were subjected to whole body hyperthermia (WBH) at 39.5°C. The mice were then challenged with influenza virus and analyzed for antiviral response in term of IFN-β expression, body weight and survival. Results: We found that 39.5°C FRT upregulated the expression of cGAS and STING, and induced the synthesis of cGAMP and production of IFN-β in htDNA-transfected RAW 264.7 cells more potently as compared to 37°C. Moreover, FRT+DMXAA-treated cells were better protected from vesicular stomatitis virus (VSV)-induced cytotoxicity in vitro in contrast to the nonprotected control (no FRT and DMXAA) or DMXAA treatment alone. In vivo, FRT at 39.5°C, co-administered with DMXAA, significantly induced the expression of IFN-β, showed reduced weight loss mice and exhibited 25% more survival over the course of 14 days as compared to DMXAA treated mice 37°C. Conclusion: We conclude that fever-range hyperthermia promotes cGAS-STING pathway to cause increased expression of IFN-β and mediate its antiviral effects.

Exercise training has profound effects on the renin-angiotensin system, inflammatory cytokines and oxidative stress, all of which affect autonomic nervous system activity and regulate blood pressure (BP) in both physiological and pathophysiological states. Using the Induction-Delay-Expression paradigm, our previous studies demonstrated that various challenges (stressors) during Induction resulted in hypertensive response sensitization (HTRS) during Expression. The present study tested whether voluntary exercise would protect against subpressor angiotensin (ANG) II-induced HTRS in rats. Adult male rats were given access to either “blocked” (sedentary rats) or functional running (exercise rats) wheels for 12 weeks, and the Induction-Delay-Expression paradigm was applied for the rats during the last 4 weeks. A subpressor dose of ANG II given during Induction produced an enhanced hypertensive response to a pressor dose of ANG II given during Expression in sedentary rats in comparison to sedentary animals that received saline (vehicle control) during Induction. Voluntary exercise did not attenuate the pressor dose of ANG II-induced hypertension but prevented the expression of HTRS seen in sedentary animals. Moreover, voluntary exercise reduced body weight gain and feed efficiency, abolished the augmented BP reduction after ganglionic blockade, reversed the increased mRNA expression of pro-hypertensive components, and upregulated mRNA expression of antihypertensive components in the lamina terminalis and hypothalamic paraventricular nucleus, two key brain nuclei involved in the control of sympathetic activity and BP regulation. These results indicate that exercise training plays a beneficial role in preventing HTRS and that this is associated with shifting the balance of the brain prohypertensive and antihypertensive pathways in favor of attenuated central activity driving sympathetic outflow and reduced BP.

ObjectivesTo discover the profiles of different steroid hormones at the maternal-fetal interface and reveal the change characteristics in pregnant women at advanced maternal age (AMA).MethodsForty pregnant women were recruited in the study, including 20 AMA women (age ≥ 35) and 20 normal controls (age < 35 and without pregnancy complications). Among AMA women, 6 (AMA2) had pregnancy complications, and 14 (AMA1) had no complications. Their maternal blood (MB), placental tissue (P), and fetal cord blood (CB) were collected, and 18 different steroid hormone metabolites were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS).ResultsThe estradiol (E2) levels in MB were higher than those in P and CB. In contrast, the estrone (E1) and estriol (E3) levels were higher in P and CB. Compared with the progesterone levels (P4) in MB, those in P and CB were higher; however, cortisol (F) levels were deficient. In contrast, F in MB was maintained at an elevated level. Further, cortisone (E) levels in CB were higher than those in MB and P. Except for the decline of testosterone (T), androstenedione (A2) and Dihydrotestosterone (DHT), there were no significant differences in the other 15 steroid hormones in MB between the AMA1 and the control group (p>0.05). Compared with the AMA1 group, androgen levels were significantly higher in AMA2, especially in T (1.55 vs. 0.68 ng/ml, p=0.023), A2 (2.27 vs. 0.92 ng/ml, p=0.011) and Dehydroepiandrosterone (DHEA) (2.39 vs. 1.50 ng/ml, p=0.028). However, there were no significant changes in P and CB between two groups.ConclusionThere are distribution rules and cascade changes of steroid profiles in maternal-fetal compartments. Significantly high androgen levels in AMA women have a positive relationship with adverse pregnancy complications.