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Abstract The emulation of tactile sensory nerves to achieve advanced sensory functions in robotics with artificial intelligence is of great interest. However, such devices remain bulky and lack reliable competence to functionalize further synaptic devices with proprioceptive feedback. Here, we report an artificial organic afferent nerve with low operating bias (−0.6 V) achieved by integrating a pressure-activated organic electrochemical synaptic transistor and artificial mechanoreceptors. The dendritic integration function for neurorobotics is achieved to perceive directional movement of object, further reducing the control complexity by exploiting the distributed and parallel networks. An intelligent robot assembled with artificial afferent nerve, coupled with a closed-loop feedback program is demonstrated to rapidly implement slip recognition and prevention actions upon occurrence of object slippage. The spatiotemporal features of tactile patterns are well differentiated with a high recognition accuracy after processing spike-encoded signals with deep learning model. This work represents a breakthrough in mimicking synaptic behaviors, which is essential for next-generation intelligent neurorobotics and low-power biomimetic electronics.

Abstract The increasing prevalence of myopia worldwide presents a significant public health challenge. A key strategy to combat myopia is with early detection and prediction in children as such examination allows for effective intervention using readily accessible imaging technique. To this end, we introduced DeepMyopia, an artificial intelligence (AI)-enabled decision support system to detect and predict myopia onset and facilitate targeted interventions for children at risk using routine retinal fundus images. Based on deep learning architecture, DeepMyopia had been trained and internally validated on a large cohort of retinal fundus images (n = 1,638,315) and then externally tested on datasets from seven sites in China (n = 22,060). Our results demonstrated robustness of DeepMyopia, with AUCs of 0.908, 0.813, and 0.810 for 1-, 2-, and 3-year myopia onset prediction with the internal test set, and AUCs of 0.796, 0.808, and 0.767 with the external test set. DeepMyopia also effectively stratified children into low- and high-risk groups (p

Abstract Background Astragaloside IV is a main medicinal active ingredient in Astragalus membranaceus Bge. var. mongholicus (Bge.) Hsiao, which is also the key biomarker of A. membranaceus quality. Ethylene has been well-documented to involve in secondary metabolites biosynthesis in plants. Nevertheless, how ethylene regulates astragaloside IV biosynthesis in A. membranaceus is still unclear. Therefore, in the present study different dosages and time-dependent exogenous application of ethephon (Eth) were employed to analyze astragaloside IV accumulation and its biosynthesis genes expression level in hydroponically A. membranaceus. Results Exogenous 200 µmol·L− 1Eth supply is most significantly increased astragaloside IV contents in A. membranaceus when compared with non-Eth supply. After 12 h 200 µmol·L− 1 Eth treatment, the astragaloside IV contents reaching the highest content at 3 d Eth treatment(P ≤ 0.05). Moreover, After Eth treatment, all detected key genes involved in astragaloside IV synthesis were significant decrease at 3rd day(P ≤ 0.05). However, SE displayed a significant increase at the 3rd day under Eth treatment(P ≤ 0.05). Under Eth treatment, the expression level of FPS, HMGR, IDI, SS, and CYP93E3 exhibited significant negative correlations with astragaloside IV content, while expression level of SE displayed a significant positive correlation. Conclusions These findings suggest that exogenous Eth treatment can influence the synthesis of astragaloside IV by regulating the expression of FPS, HMGR, IDI, SS, CYP93E3 and SE. This study provides a theoretical basis for utilizing molecular strategies to enhance the quality of A. membranaceus.

Abstract Invasive candidiasis (IC) is a notable healthcare-associated fungal infection, characterized by high morbidity, mortality, and substantial treatment costs. Candida albicans emerges as a principal pathogen in this context. Recent academic advancements have shed light on the critical role of exosomes in key biological processes, such as immune responses and antigen presentation. This burgeoning body of research underscores the potential of exosomes in the realm of medical diagnostics and therapeutics, particularly in relation to fungal infections like IC. The exploration of exosomal functions in the pathophysiology of IC not only enhances our understanding of the disease but also opens new avenues for innovative therapeutic interventions. In this investigation, we focus on exosomes (Exos) secreted by macrophages, both uninfected and those infected with C. albicans. Our objective is to extract and analyze these exosomes, delving into the nuances of their protein compositions and subgroups. To achieve this, we employ an innovative technique known as Proximity Barcoding Assay (PBA). This methodology is pivotal in our quest to identify novel biological targets, which could significantly enhance the diagnostic and therapeutic approaches for C. albicans infection. The comparative analysis of exosomal contents from these two distinct cellular states promises to yield insightful data, potentially leading to breakthroughs in understanding and treating this invasive fungal infection. In our study, we analyzed differentially expressed proteins in exosomes from macrophages and C. albicans -infected macrophages, focusing on proteins such as ACE2, CD36, CAV1, LAMP2, CD27, and MPO. We also examined exosome subpopulations, finding a dominant expression of MPO in the most prevalent subgroup, and a distinct expression of CD36 in cluster14. These findings are crucial for understanding the host response to C. albicans and may inform targeted diagnostic and therapeutic approaches. Our study leads us to infer that MPO and CD36 proteins may play roles in the immune escape mechanisms of C. albicans. Additionally, the CD36 exosome subpopulations, identified through our analysis, could serve as potential biomarkers and therapeutic targets for C. albicans infection. This insight opens new avenues for understanding the infection's pathology and developing targeted treatments.

Abstract Background Premature infants commonly encounter difficulties with oral feeding, a complication that extends hospital stays, affects infants’ quality of life, and imposes substantial burdens on families and society. Enhancing preterm infants’ oral feeding skills and facilitating their transition from parenteral or nasal feeding to full oral feeding pose challenges for neonatal intensive care unit (NICU) healthcare professionals. Research indicates that oral motor interventions (OMIs) can enhance preterm infants’ oral feeding capabilities and expedite the transition from feeding initiation to full oral feeding. Nonetheless, the most suitable timing for commencing these interventions remains uncertain. Methods This is a single-blind, randomized controlled trial. Preterm with a gestational age between 29+0 to 34+6 weeks will be eligible for the study. These infants will be randomized and allocated to one of two groups, both of which will receive the OMIs. The intervention commences once the infant begins milk intake during the early OMIs. Additionally, in the late OMIs group, the intervention will initiate 48 h after discontinuing nasal continuous positive airway pressure. Discussion OMIs encompass non-nutritive sucking and artificial oral stimulation techniques. These techniques target the lips, jaw, muscles, or tongue of premature infants, aiming to facilitate the shift from tube feeding to oral feeding. The primary objective is to determine the ideal intervention timing that fosters the development of oral feeding skills and ensures a seamless transition from parenteral or nasal feeding to full oral feeding among preterm infants. Furthermore, this study might yield insights into the long-term effects of OMIs on the growth and neurodevelopmental outcomes of preterm infants. Such insights could bear substantial significance for the quality of survival among preterm infants and the societal burden imposed by preterm birth. Trial registration chictr.org.cn ChiCTR2300076721. Registered on October 17, 2023.

BackgroundBreast cancer recurrence and lymph node metastasis significantly impact patient outcomes. Understanding the molecular mechanisms behind these processes is crucial for developing effective treatments. CCN5 and E-cadherin are proteins involved in cell adhesion and epithelial-mesenchymal transition (EMT), playing roles in breast cancer progression.ObjectiveThis study aimed to analyze the expression levels and clinical significance of CCN5 and E-cadherin in primary and recurrent breast cancer lesions.MethodsImmunohistochemical staining using the SP method was performed to detect CCN5 and E-cadherin expression levels in 28 normal breast tissue samples, 52 primary breast cancer lesions, and paired recurrent chest wall lesions. The expression levels of these proteins were compared across different tissue types and correlated with lymph node metastasis.ResultsCCN5 and E-cadherin expression levels significantly differed among normal breast tissues, primary breast cancer lesions, and recurrent lesions (Χ2 = 18.934 and Χ2 = 14.516, p < 0.05). Primary breast cancer lesions exhibited higher CCN5 and E-cadherin expression levels compared with recurrent lesions and normal tissues, although these differences were not statistically significant. Patients without lymph node metastases exhibited significantly higher expression levels of CCN5 and E-cadherin compared with those with lymph node metastases (Χ2 = 9.775, Χ2 = 9.1479, p < 0.05). A positive correlation between CCN5 and E-cadherin expression levels was found in breast cancer tissues (r = 0.398, p < 0.001).ConclusionCCN5 and E-cadherin were expressed at lower levels in recurrent breast cancer tissues and those with lymph node metastases, indicating their potential roles in breast cancer recurrence and metastasis. These findings suggest that CCN5 and E-cadherin might work synergistically to influence breast cancer progression.

Theoretical studies have unequivocally determined the exceptional electron transport properties of the fluorinated tetracyanoquinodimethane (Fx‐TCNQ) family, presenting a promising avenue for the realization of high‐performance n‐channel organic thin‐film transistors (OTFTs). However, owing to the intrinsic low crystallinity of this class of materials, Fx‐TCNQ‐based n‐channel OTFTs have not been experimentally achieved so far. Herein, a molecular step template (MST)‐assisted method that dramatically improves the crystallinity of F4‐TCNQ thin films is reported. The MST not only lowers the nucleation barrier of F4‐TCNQ molecules along the in‐plane direction but also reduces the nucleation density. This approach facilitates the realization of compact, oriented, and highly crystalline F4‐TCNQ thin films, resulting in impressive electron mobility of up to 2.58 cm2 V−1 s−1. Notably, this achievement surpasses the electron mobility of F4‐TCNQ thin films fabricated without the MST by a factor of 107. Furthermore, the incorporation of the p‐type MST provides a novel pathway for constructing complementary inverters, showcasing a high voltage gain of 112.6 V V−1 and a substantial noise margin of 89.3% with exceptional uniformity. In this work, a general and efficient route is paved to produce high‐performance n‐channel OTFTs toward organic complementary circuits.

Although accumulating evidence indicates that endangered animals suffer from plastic pollution, this has been largely overlooked. Here, we explored the bacteria and eukaryotes living in the plastics gathered from the natural habitat of the highly endangered crocodile lizard. The results demonstrated that the bacterial and eukaryotic communities on plastics formed a unique ecosystem that exhibited lower diversity than those in the surrounding water and soil. However, microbes displayed a more complex and stable network on plastic than that in water or soil, implying unique mechanisms of stabilization. These mechanisms enhanced their resilience and contributed to the provision of stable ecological services. Eukaryotes formed a simpler and smaller network than bacteria, indicating different survival strategies. The bacteria residing on the plastics played a significant role in carbon transformation and sequestration, which likely impacted carbon cycling in the habitat. Furthermore, microbial exchange between plastics and the crocodile lizard was observed, suggesting that plastisphere serves as a mobile gene bank for the exchange of information, including potentially harmful substances. Overall, microbes on plastic appear to significantly impact the crocodile lizard and its natural habitat via various pathways. These results provided novel insights into risks evaluation of plastic pollution and valuable guidance for government efforts in plastic pollutant control in nature reserves.

The rapidly developed Unmanned Aerial Vehicles (UAV) and artificial intelligence technology has prompted the real-time and accurate observation measurements of tidal bore, the basis of which is tidal bore propagation velocity. In this article, we construct a tidal observation system framework based on UAV and computer vision in order to obtain the tidal bore propagating velocity datasets. Firstly, we focus on the identification of tidal headlines based on the Sobel edge detection, the improved Otsu image segmentation algorithm and the edge connection algorithm with an accuracy of 91%. And then, the detected tidal headlines could be used to control the flight parameters of UAV in order to stably track tidal bore on the specified route with the deviation range below 0.5, and finally to acquire the tidal bore propagation velocity datasets. Comparing with the propagation velocity of the tidal line measured on site, the error of the results is maintained within 0.1 m/s, which demonstrates the effectiveness of our proposed observation method.

Context: It is very necessary to delay ovarian aging and prevent age-related health problems. The active ingredient in Honghua Xiaoyao tablet (HHXYT) has the effects of anti-oxidation, anti-inflammation, immune regulation and so on.Objective: To explore the effect and mechanism of Honghua Xiaoyao tablet on aging model mice.Materials and methods: The aging model was established by intraperitoneal injection of D-galactose in model mice. The mice in the HHXYT-L,M,H group were given 0.3 g/kg, 0.6 g/kg and 1.2 g/kg Honghua Xiaoyao tablet suspension respectively, and the HHXYT-M + E2 group was given 0.6 g/kg HHXYT +0.13 mg/kg estradiol valerate for 30 days. In this study, ELISA, HE, Western blot, IH and TUNEL were used.Results: HHXYT + E2 can improve the gonadal index, estrous cycle of aging mice. In HHXYT-M + E2 group, the level of FSH and LH decreased, while E2 and AMH increased significantly. The number of growing follicles in HHXYT-M + E2 group increased, which was better than that of HHXYT alone. Western blot results showed that HHXYT-M + E2 group decreased the expression of Bax, cleaved-Parp, cleaved-Casp-3 and CytC molecules and increased the expression of Bcl-2 in ovarian tissue. FSHR expression decreased in model group and increased in HHXYT group. TUNEL staining showed that the number of apoptotic cells in HHXYT group was reduced, and the HHXYT-M + E2 group was the most significantly.Discussion and conclusion: HHXYT can improve the level of sex hormones and increase the number of growing follicles in aging mice. HHXYT-M + E2 group has the best effect, and its mechanism may be related to reducing ovarian granulosa cell apoptosis.

Background: The accurate preoperative localization of pulmonary nodules is essential for a successful video-assisted thoracic surgery (VATS). The aim of this research was to clarify the efficacy and safety of CT-guided localization of pulmonary nodules by mixture of methylene blue and medical adhesive. Methods: Between January 2020 and January 2021, 103 subjects who have received the CT-guidance pulmonary nodules localization operation were included and retrospectively analyzed. The data on efficiency and complications of preoperative localization using medical adhesives mixed with methylene blue mixture were collected and analyzed. Results: 103 patients with 111 localized pulmonary nodules were included, 95 of whom had one nodule and 8 of whom had two nodules. The nodule localization success rate reaches as high as 100 %. The mean diameter of pulmonary nodules was 9.50 ± 3.67 mm. The mean distance of pulmonary nodule and pleural surface was 19.95 ± 14.92 mm. The mean depth of localized adhesive in the lung parenchyma was 18.99 ± 11.62 mm, and the mean time required for localization was 16.98 ± 5.72 min. The average time from the nodule localization to VATS surgery was 16.97 ± 7.34 h. The common complications of localization were minor pulmonary hemorrhage (9.74 %) and mild pneumothorax (15.53 %). Besides, pulmonary hemorrhage was related with depths of medical adhesives and nodules in lung parenchyma (p = 0.018 and 0.002, respectively). Conclusion: Medical adhesive mixed with methylene blue is safe and effective in pulmonary nodules localization for VATS, and surgeons have flexibility in scheduling the procedure.

In recent decades, alpine meadows have experienced severe degradation owing to external disturbances. Although soil microorganisms are critical for ecosystem services, little is known about their responses to soil degradation and the potential patterns in alpine meadows. To solve this question, we collected and analyzed soil samples from three degraded alpine meadows situated on the Qinghai-Tibet Plateau. We aimed to examine the effects of degradation on soil microbial diversity and identify the ecological predictors for the diversity of bacteria and fungi. Our results showed that alpine meadow degradation significantly changed soil bacterial and fungal diversity and community composition. Specifically, the relationship between bacterial and fungal diversity and degradation intensity was a hump-shaped, with the highest diversity observed at a moderate degradation level. Additionally, alpine meadow degradation-induced changes in microbial diversity were strongly correlated with decreased plant production, with fungal diversity showing a closer link with below-ground biomass (BGB) than with bacterial diversity. Our findings offer empirical evidence that intermediate disturbance (i.e., moderate degradation) may be beneficial for supporting soil biodiversity. This has important implications for informing policy and management strategies meant to conserve soil biodiversity and ecosystem services when facing anthropogenic change.

The blood-brain Barrier (BBB), combined with immune clearance, contributes to the low efficacy of drug delivery and suboptimal treatment outcomes in glioma. Here, we propose a novel approach that combines the self-assembly of mouse bone marrow-derived macrophage membrane with a targeted positive charge polymer (An-PEI), along with low-frequency ultrasound (LFU) irradiation, to achieve efficient and safe therapy for glioma. Our findings demonstrate the efficacy of a charge-induced self-assembly strategy, resulting in a stable co-delivery nanosystem with a high drug loading efficiency of 44.2 %. Moreover, this structure triggers a significant release of temozolomide in the acidic environment of the tumor microenvironment. Additionally, the macrophage membrane coating expresses Spyproteins, which increase the amount of An-BMP-TMZ that can evade the immune system by 40 %, while LFU irradiation treatment facilitates the opening of the BBB, allowing for enormously increased entry of An-BMP-TMZ (approximately 400 %) into the brain. Furthermore, after crossing the BBB, the Angiopep-2 peptide-modified An-BMP-TMZ exhibits the ability to selectively target glioma cells. These advantages result in an obvious tumor inhibition effect in animal experiments and significantly improve the survival of glioma-bearing mice. These results suggest that combining the macrophage membrane-coated drug delivery system with LFU irradiation offers a feasible approach for the accurate, efficient and safe treatment of brain disease.

Unmanned Aerial Vehicle (UAV) can be used as wireless aerial mobile base station for collecting data from sensors in UAV-based Wireless Sensor Networks (WSNs), which is crucial for providing seamless services and improving the performance in the next generation wireless networks. However, since the UAV are powered by batteries with limited energy capacity, the UAV cannot complete data collection tasks of all sensors without energy replenishment when a large number of sensors are deployed over large monitoring areas. To overcome this problem, we study the Real-time Data Collection with Laser-charging UAV (RDCL) problem, where the UAV is utilized to collect data from a specified WSN and is recharged using Laser Beam Directors (LBDs). This problem aims to collect all sensory data from the WSN and transport it to the base station by optimizing the flight trajectory of UAV such that real-time data performance is ensured It has been proven that the RDCL problem is NP-hard. To address this, we initially focus on studying two sub-problems, the Trajectory Optimization of UAV for Data Collection (TODC) problem and the Charging Trajectory Optimization of UAV (CTO) problem, whose objectives are to find the optimal flight plans of UAV in the data collection areas and charging areas, respectively. Then we propose an approximation algorithm to solve each of them with the constant factor. Subsequently, we present an approximation algorithm that utilizes the solutions obtained from TODC and CTO problems to address the RDCL problem. Finally, the proposed algorithm is verified by extensive simulations.

Abstract Structurally colored composite films, composed of orderly arranged colloids in polymeric matrix, are emerging flexible optical materials, but their production is bottlenecked by time-consuming procedures and limited material choices. Here, we present a mild approach to producing large-scale structurally colored composite films by shearing supramolecular composites composed of polymers and colloids with supramolecular interactions. Leveraging dynamic connection and dissociation of supramolecular interactions, shearing force stretches the polymer chains and drags colloids to migrate directionally within the polymeric matrix with reduced viscous resistance. We show that meter-scale structurally colored composite films with iridescence color can be produced within several minutes at room temperature. Significantly, the tunability and diversity of supramolecular interactions allow this shearing approach extendable to various commonly-used polymers. This study overcomes the traditional material limitations of manufacturing structurally colored composite films by shearing method and opens an avenue for mildly producing ordered composites with commonly-available materials via supramolecular strategies.

The introduction of alleles into commercial crop breeding pipelines is both time consuming and costly. Two technologies that are disrupting traditional breeding processes are doubled haploid (DH) breeding and genome editing (GE). Recently, these techniques were combined into a GE trait delivery system called HI-Edit (Haploid Inducer-Edit) [1]. In HI-Edit, the pollen of a haploid inducer line is reprogrammed to deliver GE traits to any variety, obviating recurrent selection. For HI-Edit to operate at scale, an efficient transformable HI line is needed, but most maize varieties are recalcitrant to transformation, and haploid inducers are especially difficult to transform given their aberrant reproductive behaviors. Leveraging marker assisted selection and a three-tiered testing scheme, we report the development of new Iodent and Stiff Stalk maize germplasm that are transformable, have high haploid induction rates, and exhibit a robust, genetically-dominant anthocyanin native trait that may be used for rapid haploid identification. We show that transformation of these elite “HI-Edit” lines is enhanced using the BABYBOOM and WUSCHEL morphogenetic factors. Finally, we evaluate the HI-Edit performance of one of the lines against both Stiff Stalk and non-Stiff Stalk testers. The strategy and results of this study should facilitate the development of commercially scalable HI-Edit systems in diverse crops.

This paper establishes a location-routing optimization model of the distribution center for emergency supplies with the goals of system reaction time, total cost of consumption, psychological fear of the populace in disaster-affected locations, and material usage rate. Where the excess time, demand, and penalty coefficient are the components of the penalty cost in the total consumption cost, and where the psychological panic of those in the affected area is represented by the psychological perception function of panic developed in accordance with the prospect theory. An improved hybrid multi-objective cuckoo-large-neighborhood search algorithm was then designed to introduce tent mapping, nonlinear inertia weights, elite strategies, congestion operators, and dynamically adjusted discovery probabilities into the standard multi-objective cuckoo optimization algorithm, which generates a new solution using a large-neighborhood search algorithm after discarding part of the solution with the discovery probability, and then accepts the current nondominated solution with dynamic probabilities. The paper uses the improved algorithm to solve Christofides69, an arithmetic example from the standard dataset of the LRP problem, and the results show that the solution provided by the improved algorithm outperforms the solutions provided by the standard multi-objective cuckoo search algorithm and the NSGA-II algorithm in terms of the total cost of dissipation, the level of psychological panic of the people in the affected area, the rate of utilization of the supplies, and the number of distribution centers open. Finally, the improved algorithm was used to analyze cases of different sizes separately, and it was found that the algorithm yielded better results and was therefore able to demonstrate its effectiveness.

Abstract Some ancient Chinese paper artifacts dyed with amur cork tree bark extracts are currently preserved to different extents in museums and libraries worldwide. As traditional natural plant dyes, the long-term performance of the amur cork tree bark extract-dyed handmade paper has been questioned under a preserved environment. The photodegradation process of the extract-dyed papers was examined under accelerating artificial UVA irradiation conditions according to China national standard-paper and board- accelerated aging (exposure to light). Changes during aging were analyzed by optical observation and scanning electron microscopy (SEM), X-ray diffraction (XRD), thermogravimetric analysis (TGA), Fourier transform infrared spectrometry (FTIR), pH, and tensile strength and folding endurance tests. The results showed that the main components from extracted dyes played an important role in affecting the photodegradation properties of dyed paper. The changes in surface color, pH, morphology and mechanical properties after the artificial UVA accelerated degradation tests revealed that a suitable concentration of the extract dyes for maintaining the long-term irradiation stability of the paper is important.

Abstract Background Overweight/obesity in children and adolescents has become a global health problem, and family function may be associated with its occurrence. Studies exploring the association between family function and overweight/obesity in children and adolescents were performed in Western and Taiwan, China. To date, related studies haven’t been conducted in Mainland China. Objectives To investigate the current status of overweight, obesity, and family function among children and adolescents in Chengdu, China, and to explore their associations. Methods Children and adolescents in five primary and middle schools were chosen by cluster sampling. Body Mass Index was used to measure the status of overweight and obesity, and the Chinese family assessment instrument was adopted to assess family function. Latent profile analysis and stepwise logistic regression were applied to identify family classification and explore the relationships between family function and overweight/obesity. Results A total of 7616 (84.92%) children and adolescents out of 8968 completed the study with qualified-filled questionnaires. Nine hundred and sixty-six (12.68%)participants were overweight and 656 (8.61%) were obese. The family function was categorized into three profiles: mild (63.93%), moderate (12.32%), and severe (23.75%) dysfunction. The prevalence of overweight was 12.16%, 14.71%, and 13.05% for mild, moderate, and severe family dysfunction, respectively. And the prevalence of obesity was 8.19%, 10.77%, and 8.62% respectively. Participants in moderate and severe dysfunction families were more likely to be overweight (moderate: OR = 1.27, 95% CI:1.01 ~ 1.59, P = 0.04; severe: OR = 1.38, 95% CI:1.15 ~ 1.66, P = 0.001) and obese (moderate: OR = 1.35, 95% CI:1.02 ~ 1.79, P = 0.03; severe: OR = 1.55, 95% CI:1.23 ~ 1.96, P

ABSTRACT: Objectives: Treating patients with diabetic foot infection (DFI) is challenging because of high rates of antibiotic resistance. Therefore, to administer a suitable antibiotic treatment, it is necessary to know the antibiotic resistance patterns in DFIs. Methods: To explore this question, we selected metagenomic data of 36 tissue samples from patients with DFI in the National Center for Biotechnology Information Sequence Read Archive database. Results: A total of 229 antibiotic-resistant gene (ARG) subtypes belonging to 20 ARG types were detected. The antibiotic resistome of 229 different genes in the tissue samples of patients with DFI comprised 24 core and 205 accessory resistance genes. Among the core antibiotic resistome, multidrug, tetracycline, macrolide-lincosamide-streptogramin, and beta-lactam resistance genes were the dominant categories. Procrustes analysis indicated that both the microbial community composition and mobile genetic elements (MGEs) were determinants of the ARGs. In the network analysis, 29 species were speculated to be potential hosts of 28 ARGs based on the co-occurrence results. Plasmids and transposons were the most common elements that co-occurred with ARGs. Conclusions: Our study provided detailed information about antibiotic resistance patterns in DFI, which has practical implications for suggesting a more specific antibiotic choice.

Background: The combined effect of hepatitis B virus infection and metabolic dysfunction-associated steatotic liver disease (MASLD) on hepatocellular carcinoma (HCC) risk remains unclear. The current study sought to elucidate the impact of MASLD on HCC progression in chronic hepatitis B (CHB) patients.Method: This retrospective cohort study included CHB patients who had undergone liver biopsy and abdominal imaging at the Guangdong Provincial Hospital of Chinese Medicine between 2013 and 2019. We investigated the correlation between MASLD and HCC risk, and inverse probability treatment weighting (IPTW) was used to adjust for patient characteristics.Results: A total of 1,613 patients were included, and 483 (29.9%) were diagnosed with MASLD. Over a median follow-up period of 5.02 years, 36 (2.2%) developed HCC, comprising 4.8% (23/483) of those with MASLD and 1.2% (13/1,130) of those without. Those with MASLD had a significantly higher cumulative incidence of HCC than those without (p < 0.001). The presence of MASLD was associated with a higher risk of HCC (adjusted hazard ratio [HR], 3.996; 95% confidence interval [CI], 2.007–7.959; p < 0.001). After adjustment using IPTW, the patients with MASLD retained a higher cumulative incidence of HCC (p < 0.001). Moreover, MASLD was found to be an independent risk factor for the development of HCC (adjusted HR, 10.191; 95% CI, 4.327–24.002; p < 0.001). However, among patients with MASLD, there were no significant differences in the cumulative risk of HCC between patients with and without overweight, between those with

The toxicity factor (TF), a critical parameter within the potential ecological risk index (RI), is determined without accounting for microbial factors. It is considerable uncertainty exists concerning its validity for quantitatively assessing the influence of metal(loid)s on microorganisms. To evaluate the suitability of TF, we constructed microcosm experiments with varying RI levels (RI = 100, 200, 300, 500, and 700) by externally adding zinc (Zn), chromium (Cr), copper (Cu), lead (Pb), nickel (Ni), cadmium (Cd), and mercury (Hg) to uncontaminated soil (CK). Quantitative real-time PCR (qPCR) and high-throughput sequencing techniques were employed to measure the abundance and community of bacteria and fungi, and high-throughput qPCR was utilised to quantify functional genes associated with CNPS cycles. The results demonstrated that microbial diversity and function exhibited significant alterations (p

This study aimed to investigate the inhibitory effects of three major flavonoids from the Hippophae rhamnoides subsp. yunnanensis berries on four pathogenic microorganisms. The antimicrobial activity of total flavonoids from Hippophae rhamnoides subsp. yunnanensis berries on Staphylococcus aureus, Escherichia coli, Bacillus subtilis and Candida albicans was firstly measured by filter paper method. Then, the total flavonoids compositions were identified by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and the main components were quantified by high performance liquid chromatography (HPLC). Finally, the Bradford method and the double dilution method were used to assess the antimicrobial effect of the three flavonoids. The results showed that the major flavonoid components of the Hippophae rhamnoides subsp. yunnanensis berries were isorhamnetin-3-O-glucoside-7-O-rhamnoside (Is-3-G-7-Rh), quercetin-3-O-rutinoside (Qu-3-R) and isorhamnetin-3-O-glucoside (Is-3-G), which with the contents of 38.43±0.85, 29.44±0.42 and 21.11±0.55 mg/g, respectively. The extract and its three main flavonoids had inhibitory effect on the four microorganisms. The inhibitory effects of Is-3-G-7-Rh and Is-3-G on the microorganisms were better than Qu-3-R and extract, and the results of protein detection showed that flavonoids induced antimicrobial death through intracellular protein efflux. This study can provide a scientific basis for the application of flavonoids in the berries of Hippophae rhamnoides for antimicrobial purposes.

Abstract Introduction Conventional etiological detection and pathogenic antibody methods make it challenging to identify the atypical pathogens among the community‐acquired pneumonia (CAP). Metagenomic next‐generation sequencing (mNGS) could rapidly detect all potentially infectious diseases and identifies novel or potential pathogens. Methods Eighteen patients diagnosed with atypical CAP were enrolled in this retrospective study, including nine Chlamydia psittaci pneumonia (C. p), four Legionella pneumonia (L. p) and five Mycoplasma pneumonia (M. p). We simultaneously tested bronchoalveolar lavage fluid (BALF) samples for conventional microbiological methods and mNGS, and blood specimens were analysed. We also collected and compared baseline and clinical characteristics and treatment responses. Results Patients with C. p and L. p had similar symptoms, including fever, cough, headache, dyspnoea, asthenia, shivering and headache, compared with M. p, whose symptoms were slight. C. p and L. p usually showed multiple lobar distributions with pleural effusion. Serologic testing indicated that L. p had higher levels of white blood cells (WBCs), neutrophils, C‐reactive protein (CRP), procalcitonin (PCT), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and creatinine compared with M. p and L. p (p

Abstract Hexokinase 2 (HK2), a critical rate-limiting enzyme in the glycolytic pathway catalyzing hexose phosphorylation, is overexpressed in multiple human cancers and associated with poor clinicopathological features. Drugs targeting aerobic glycolysis regulators, including HK2, are in development. However, the physiological significance of HK2 inhibitors and mechanisms of HK2 inhibition in cancer cells remain largely unclear. Herein, we show that microRNA-let-7b-5p (let-7b-5p) represses HK2 expression by targeting its 3′-untranslated region. By suppressing HK2-mediated aerobic glycolysis, let-7b-5p restrains breast tumor growth and metastasis both in vitro and in vivo. In patients with breast cancer, let-7b-5p expression is significantly downregulated and is negatively correlated with HK2 expression. Our findings indicate that the let-7b-5p/HK2 axis plays a key role in aerobic glycolysis as well as breast tumor proliferation and metastasis, and targeting this axis is a potential therapeutic strategy for breast cancer.

Abstract The last 20 years have witnessed growing impacts of the topological concept on the branches of physics, including materials, electronics, photonics, and acoustics. Topology describes objects with some global invariant property under continuous deformation, which in mathematics could date back to the 17th century and mature in the 20th century. In physics, it successfully underpinned the physics of the Quantum Hall effect in 1984. To date, topology has been extensively applied to describe topological phases in acoustic metamaterials. As artificial structures, acoustic metamaterials could be well theoretically analyzed, on‐demand designed, and easily fabricated by modern techniques, such as three‐dimensional printing. Some new theoretical topological models were first discovered in acoustic metamaterials analogous to electronic counterparts, associated with novel effects for acoustics closer to applications. In this review, we focused on the concept of topology and its realization in airborne acoustic crystals, solid elastic phononic crystals, and surface acoustic wave systems. We also introduced emerging concepts of non‐Hermitian, higher‐order, and Floquet topological insulators in acoustics. It has been shown that the topology theory has such a powerful generality that among the disciplines from electron to photon and phonon, from electronic to photonics and acoustics, from acoustic topological theory to acoustic devices, could interact and be analogous to fertilize fantastic new ideas and prototype devices, which might find applications in acoustic engineering and noise‐vibration control engineering in the near future.

Abstract Background Ulcerative colitis, a typical subtype of inflammatory bowel disease, can cause many serious complications. Burdock fructooligosaccharide (BFO), a linear inulin with a purity of 99.439% and a molecular weight of 2345 Da, demonstrates anti‐inflammatory and immunomodulatory properties. Methods The Kunming mice were divided into two experimental models: a normal pretreatment model and a colitis experimental model. During the experimental treatment period, we assessed changes in weight and disease activity index (DAI), quantified the intestinal index, and determined myeloperoxidase (MPO) activity and reactive oxide species (ROS) levels in colitis mice. We also photographed colon morphology to investigate alterations in the integrity of the intestinal barrier function. Finally, we performed ELISA and qRT‐PCR to evaluate the anti‐inflammatory effect of BFO treatment on colitis mice. Result The long‐term oral administration of BFO alone exhibited protective effects by preventing disruption of the intestinal functional structure and increasing the colon index in mice. However, in a dextran sodium sulfate (DSS)‐induced colitis mouse model, BFO administration facilitated quick recovery of body weight and effectively reduced the DAI, especially in the BFO‐H group (500 mg/kg/day). BFO treatment maintained the integrity of the intestinal barrier by attenuating the crypt distortion and increasing the goblet cells count It restored the DSS‐induced colon shortening and reduced the symptoms of colitis. These effects may be attributed to the appropriate concentrations of BFO effectively inhibiting MPO activity, clearing excessive ROS, and relieving spleen abnormalitie. BFO also attenuated the overexpression and excessive secretion of inflammatory cytokines (TNF‐α, IL‐1β, IL‐6, and MCP‐1) induced by DSS, reduced intestinal inflammation, and consequently protected the intestinal barrier function. Conclusion BFO effectively alleviated the symptoms of DSS‐induced colitis by mediating anti‐inflammatory effects and protecting the intestinal barrier integrity, thereby potentially facilitating the utilization of safer and more efficacious polysaccharides for managing chronic inflammatory diseases.

The diagnosis of invasive pulmonary aspergillosis (IPA) diseases in non-neutropenic patients remains challenging. It is essential to develop optimal non-invasive or minimally invasive detection methods for the rapid and reliable diagnosis of IPA. Metagenomic next-generation sequencing (mNGS) in bronchoalveolar lavage fluid (BALF) can be a valuable tool for identifying the microorganism. Our study aims to evaluate the performance of mNGS in BALF in suspected IPA patients and compare it with other detection tests, including serum/BALF galactomannan antigen (GM) and traditional microbiological tests (BALF fungal culture and smear and lung biopsy histopathology). Ninety-four patients with suspicion of IPA were finally enrolled in our study. Thirty-nine patients were diagnosed with IPA, and 55 patients were non-IPA. There was significance between the IPA and non-IPA groups, such as BALF GM (P < 0.001), history of glucocorticoid use (P = 0.004), and pulmonary comorbidities (P = 0.002), as well as no significance of the other demographic data including age, sex, BMI, history of cigarette, blood GM assay, T-SPOT.TB, and NEUT#/LYMPH#. The sensitivity of the BALF mNGS was 92.31%, which was higher than that of the traditional tests or the GM assays. The specificity of BALF mNGS was 92.73%, which was relatively similar to that of the traditional tests. The AUC of BALF mNGS was 0.925, which presented an excellent performance compared with other traditional tests or GM assays. Our study demonstrated the important role of BALF detection by the mNGS platform for pathogen identification in IPA patients with non-neutropenic states, which may provide an optimal way to diagnose suspected IPA disease.

The alpine grasslands of the Qinghai-Tibetan Plateau play an important role in multiple ecosystem functions, all of which are key in regulating regional climate influences and providing pristine headwaters for millions of people downstream from this basin. Alpine grasslands act as a carbon sink, storing carbon dioxide and keeping heat-trapping greenhouse gases out of the atmosphere, but it is not clear how this will change in a warming climate in the future. In this paper, the net ecosystem productivity (NEP) of alpine grasslands in Qinghai province, on the Qinghai-Tibetan Plateau, was predicted for the period from 2010 to 2099. Trends and stability were analyzed under two climate scenarios, Representative Concentration Pathway 4.5 (RCP4.5) and 8.5 (RCP8.5) representing the lower and higher emission scenarios for greenhouse gases. The results suggest that grasslands will continue to contribute as a carbon sink, with a positive NEP through this century. Almost the same magnitude (38 Tg C a-1, 1 T g = 1012 g) of contribution was projected under both scenarios. Grasslands are projected to be the major contributor to NEP in Qinghai province, with more than 89% of NEP in the future. The carbon sink function will increase over more than 69% of the grasslands and peak around 2069 (RCP4.5) or 2066 (RCP8.5). Then the carbon sink function will begin to decrease and it will decrease more quickly and become more variable under the RCP8.5 than the RCP4.5. The impacts of temperature and precipitation changes were analyzed and NEP was found to be more sensitive to temperature than precipitation change. The trend of increasing contribution to NEP is driven by a warming climate, while the stability of NEP is mainly influenced by the precipitation, which results in an upward trend before the peak and a decline due to stresses from limits in available water in a continued warming climate.

Vegetation response to climate change can be characterized as long-term trends, but with periodic oscillations. Revealing vegetation response trends, with oscillations, is essential for formulating climate change mitigation and adaptation planning, as well as adopting ecological protection and restoration measures. Here, the long-term trend and periodic oscillations in vegetation changes were explored through a measure of gross primary production (GPP), an indicator of vegetation photosynthesis, using data of both high spatial resolution (1 km2) and a long-term of nearly 4 decades, from 1980 to 2018. The GPP data were estimated for China’s terrestrial ecosystem and validated against the eddy covariance-based observations of 70 site-year in China and compared to other GPP data products. The results showed the estimated GPP can explain 76% of spatial–temporal variance with the same data accuracy as other products, but with the advantage of both high spatial resolution and long time periods that other products do not have. From the estimated GPP data, Chinese terrestrial vegetation growth was found to have a periodic oscillation of close to 2.79 years and a long-term increasing trend of 59.8 Mt C per year over 92% of all vegetated land in China from 1980 to 2018. Moreover, it was found that vegetation growth accelerated significantly in the two recent decades over the previous two decades. The growth rate was 83.5 Mt C a−1 from 2000 to 2018, which was 2.31 times faster than the rate from 1980 to 2000. The underlying mechanism of the vegetation responses was analyzed by ridge regression, a method to decrease the effects of multicollinearity. Long-term variability and trends in vegetation could be attributed to a warming minimum air temperature when examined with precipitation, maximum air temperature, and solar shortwave radiation. Though more influences, such as those from freezing and thawing and human activities, should be explored in the future, this study offers insight that warming, with increasing daily minimum temperatures, is likely to be a vital contributor to ecosystem changes, and will be essential knowledge for mitigation of effects and adaptation to future climate.

Middle East respiratory syndrome coronavirus (MERS-CoV), a highly pathogenic coronavirus in the same Betacoronavirus genus and Coronaviridae family as SARS-CoV-2, continues to post a threat to human health. Mortality remains high; therefore, there is a need to develop effective vaccines to prevent MERS-CoV infection. The receptor-binding domain (RBD) within the MERS-CoV spike (S) protein is a critical vaccine target. The latest mRNA technology has enabled rapid development of much-needed vaccines with high efficiency and scalable manufacturing capacity. Here, we designed a mRNA vaccine encoding the RBD of MERS-CoV S protein (RBD-mRNA) and evaluated its immunogenicity and protective efficacy in a mouse model. The data showed that nucleoside-modified RBD-mRNA, but not RBD-mRNA lacking the nucleoside modification, was stable and elicited broadly and durable neutralizing antibody and cellular immune responses, which neutralized the original strain and multiple MERS-CoV variants. Among all immunization routes tested, the intradermal route was appropriate for this RBD-mRNA to induce strong B-cell responses and the highest neutralizing antibody titers. Importantly, injection of nucleoside-modified RBD-mRNA through the intradermal route protected immunized mice against challenge with MERS-CoV. This protection correlated with serum neutralizing antibody titers. Overall, we have developed an effective MERS-CoV RBD-based mRNA vaccine (with potential for further development) that prevents infection by divergent strains of MERS-CoV.

Background: Nontuberculous mycobacterial (NTM) pulmonary disease (PD) has rapidly increased globally. The characteristics and comparison of rapidly growing mycobacteria PD (RGM-PD) and slowly growing mycobacteria PD (SGM-PD) are still unclear. Methods: Our study enrolled 31 NTM-PD patients. Clinical data, including baseline, symptoms, underlying disease, laboratory tests, metagenomic next-generation sequencing (mNGS) results, radiological images, treatment, and outcome were recorded and analyzed. Results: Of the 31 patients with NTM-PD, 22 patients were female and 9 were male. It included 11 RGM-PD and 20 SGM-PD. There was no difference in age (P = 0.425) and body mass index (P = 0.152) between the two groups. The common respiratory diseases in prevalence included bronchiectasis and chronic obstructive pulmonary disease. Three patients had positive results of T-SPOT tuberculosis (TB), and none had positive Xpert-Mycobacterium tuberculosis/rifampin results. On admission, patients were symptomatic and included cough/sputum production, fever, weight loss, fatigue, and hemoptysis. In comparison to RGM-PD, patients with SGM-PD had a greater chance of experiencing fatigue (P = 0.012). No significance was found in serum biomarkers between RGM and SGM-PD, including CD4/CD8 ratio, white blood cells, neutrophils, lymphocytes, procalcitonin, ferritin, C-reactive protein, and erythrocyte sedimentation rate. No liver or kidney impairment was found. Patients with RGM-PD were more likely to have right lower lobe (RLL) impairment (P = 0.021) and a cavity characteristic (P = 0.012). All 31 cases had positive mNGS results. The duration of mNGS was shorter than conventional methods (3.4 ± 0.7 vs. 26.4 ± 20.9, P < 0.001). Conclusions: Patients with SGM-PD were more likely to experience fatigue. The cavity and RLL involvement were more frequent in the RGM-PD. mNGS increases the identification of NTM specimens and complements the capabilities of conventional methods.

Abstract Background As a member of the Ephrin protein family that elicits short distance cell‐cell signaling, EphrinA3 has been shown to promote or inhibit tumorigenesis depending on tumor types, but its roles and the underlying mechanisms in lung adenocarcinoma (LUAD) have not been reported. Materials and Methods The TCGA database and Kaplan‐Meier Plotter database were used to analyze the differential expression of EphrinA3 between LUAD and para‐carcinoma tissues, and its effect on overall survival of LUAD patients. CCK‐8 assay, Edu assay, and flow cytometry were used to probe the effect of EphrinA3 on the proliferation of LUAD cells, and transwell assay was employed to examine its effect on migration and invasion. In addition, the effect of EphrinA3 on the growth of LUAD was further evaluated using a xenograft tumor model. Results EphrinA3 was expressed highly in LUAD, and its expression level was negatively correlated with the prognosis of LUAD patients. In addition, EphrinA3 promoted proliferation, migration, and invasion of LUAD cells, and accelerated tumor growth in a xenograft LUAD model. The reported EphrinA3 receptors, EphA1 and EphA10, were expressed in clinical LUAD tissues and co‐localized with EphrinA3 in LUAD cells. Mechanistically, EphrinA3/Eph signaling activated AKT, ERK, and p38MAPK, induced epithelial‐mesenchymal transition (EMT), and upregulated matrix metalloproteases‐2 and ‐9 (MMP‐2/−9). Conclusion EphrinA3 expression was negatively correlated with prognosis of patients with LUAD. EphrinA3 promoted proliferation, migration, and invasion of LUAD cells. EphrinA3 enhanced the phosphorylation of ERK and AKT, and potentiates EMT and MMP expression in LUAD cells.

Climate change plays a pivotal role in shaping the shifting patterns of plant distribution, and gaining insights into how medicinal plants in the plateau region adapt to climate change will be instrumental in safeguarding the rich biodiversity of the highlands. Gymnosia orchidis Lindl. (G. orchidis) is a valuable Tibetan medicinal resource with significant medicinal, ecological, and economic value. However, the growth of G. orchidis is severely constrained by stringent natural conditions, leading to a drastic decline in its resources. Therefore, it is crucial to study the suitable habitat areas of G. orchidis to facilitate future artificial cultivation and maintain ecological balance. In this study, we investigated the suitable zones of G. orchidis based on 79 occurrence points in the Qinghai–Tibet Plateau (QTP) and 23 major environmental variables, including climate, topography, and soil type. We employed the Maximum Entropy model (MaxEnt) to simulate and predict the spatial distribution and configuration changes in G. orchidis during different time periods, including the last interglacial (LIG), the Last Glacial Maximum (LGM), the Mid-Holocene (MH), the present, and future scenarios (2041–2060 and 2061–2080) under three different climate scenarios (SSP126, SSP370, and SSP585). Our results indicated that annual precipitation (Bio12, 613–2466 mm) and mean temperature of the coldest quarter (Bio11, −5.8–8.5 °C) were the primary factors influencing the suitable habitat of G. orchidis, with a cumulative contribution of 78.5%. The precipitation and temperature during the driest season had the most significant overall impact. Under current climate conditions, the suitable areas of G. orchidis covered approximately 63.72 × 104/km2, encompassing Yunnan, Gansu, Sichuan, and parts of Xizang provinces, with the highest suitability observed in the Hengduan, Yunlin, and Himalayan mountain regions. In the past, the suitable area of G. orchidis experienced significant changes during the Mid-Holocene, including variations in the total area and centroid migration direction. In future scenarios, the suitable habitat of G. orchidis is projected to expand significantly under SSP370 (30.33–46.19%), followed by SSP585 (1.41–22.3%), while contraction is expected under SSP126. Moreover, the centroids of suitable areas exhibited multidirectional movement, with the most extensive displacement observed under SSP585 (100.38 km2). This study provides a theoretical foundation for the conservation of biodiversity and endangered medicinal plants in the QTP.

The development of acquired resistance to small molecule tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) signaling has hindered their efficacy in treating non-small cell lung cancer (NSCLC) patients. Our previous study showed that constitutive activation of the 70 kDa ribosomal protein S6 kinase 1 (S6K1) contributes to the acquired resistance to EGFR-TKIs in NSCLC cell lines and xenograft tumors in nude mice. However, the regulatory mechanisms underlying S6K1 constitutive activation in TKI-resistant cancer cells have not yet been explored. In this study, we recapitulated this finding by taking advantage of a gefitinib-resistant patient-derived xenograft (PDX) model established through a number of passages in mice treated with increasing doses of gefitinib. The dissociated primary cells from the resistant PDX tumors (PDX-R) displayed higher levels of phosphor-S6K1 expression and were resistant to gefitinib compared to cells from passage-matched parental PDX tumors (PDX-P). Both genetic and pharmacological inhibition of S6K1 increased sensitivity to gefitinib in PDX-R cells. In addition, both total and phosphorylated mechanistic target of rapamycin kinase (MTOR) levels were upregulated in PDX-R and gefitinib-resistant PC9G cells. Knockdown of MTOR by siRNA decreased the expression levels of total and phosphor-S6K1 and increased sensitivity to gefitinib in PDX-R and PC9G cells. Moreover, a transcription factor ELK1, which has multiple predicted binding sites on the MTOR promoter, was also upregulated in PDX-R and PC9G cells, while the knockdown of ELK1 led to decreased expression of MTOR and S6K1. The chromatin immunoprecipitation (ChIP)-PCR assay showed the direct binding between ELK1 and the MTOR promoter, and the luciferase reporter assay further indicated that ELK1 could upregulate MTOR expression through tuning up its transcription. Silencing ELK1 via siRNA transfection improved the efficacy of gefitinib in PDX-R and PC9G cells. These results support the notion that activation of ELK1/MTOR/S6K1 signaling contributes to acquired resistance to gefitinib in NSCLC. The findings in this study shed new light on the mechanism for acquired EGFR-TKI resistance and provide potential novel strategies by targeting the ELK1/MTOR/S6K1 pathway.

Astragalus membranaceus (A. membranaceus) is a homologous plant with high medicinal and edible value. Therefore, the extraction methods of Astragalus polysaccharide (APS) have attracted the attention of many research groups, but the yield of the active components is still not high. The aim of this study was to extract APS by a semi-bionic extraction method, optimize the extraction process, and evaluate the anti-aging activities of APS in vivo. The results showed that the APS yield was 18.23% when extracted by the semi-bionic extraction method. Anti-aging evaluation in rats showed that APS extracted by this method significantly decreased the malondialdehyde (MDA) content and increased superoxide dismutase (SOD) activity to cope with D-galactose-induced aging. Serum metabolomic analysis indicated that a total of 48 potential biomarkers showed significant differences, mainly involving 5 metabolic pathways. These altered metabolic pathways were mainly related to energy metabolism, amino acid metabolism, and lipid metabolism. These results indicated that the semi-bionic extraction method can effectively improve the yield of APS, and the extracted APS exhibited anti-aging activity in rats. Our study provided a novel and effective method to extract APS and indicated that APS can be used as functional food and natural medicine to delay aging and prevent its complications.

Hibiscus manihot L. seed oil is an emerging high-value edible vegetable oil that also has a variety of important health functions, and concerns about its pressing method have great significance for commercial and consumer health. This study compared triacylglycerols (TAGs), diacylglycerol (DAG), free fatty acids (FFAs), and volatile flavor compounds for discriminating cold-pressed oil from hot-pressed oil. The profiles of TAGs, DAGs, FFAs, and flavor compounds were established by a lipidomic approach and electronic-nose (E-nose). Our results demonstrated that a slight decrease in TAG content and a significant increase in FFA and DAG contents were observed after roasting. The E-nose results showed that sulfides, terpenes, methane, compounds containing oxygen and nitrogen, alcohol and aromatic compounds greatly influenced the oil flavor. The PCA result of the E-nose data indicated that flavor compounds showed great promise for distinguishing the two samples. The quality indices and the oxidative stability of oil samples were detected to identify their nutritional value and edible quality. This study revealed that roasting greatly influenced the lipid and flavor substances of the Hibiscus manihot L. seed oil. Our findings could provide useful information on the impact of the pressing method for Hibiscus manihot L. seed oil.

Coenzyme Q10 nanoemulsion (CoQ10-NE) was improved and made utilizing Pinus koraiensis nuts oil as the oil phase, soybean lecithin as the surfactant, and ethanol as the cosurfactant in this study. The effects of different factors on the mean particle size and polydispersity index (PDI) of CoQ10-NE were studied, and the quality was evaluated by DLS, TEM, FT-IR, stability, in vitro release behavior and in vivo pharmacokinetic experiments in rats.The results showed that when the mass ratio of CoQ10 to mixed surfactant was 3:40, the mass ratio of CoQ10 to Pinus koraiensis nuts oil was 1:4, the homogenizing pressure was 800 bar, and the number of cycles was 6 times, the CoQ10-NE of mean particle size of 150.30±1.43 nm and PDI of 0.234±0.012 was obtained. The morphology and microstructure showed that the CoQ10-NE was round and non-adhesive at the size of 500 nm and 1 µm. FT-IR results showed that CoQ10 was completely encapsulated in nanoemulsion. The stability experiment showed that there was no significant difference in the mean particle size and PDI (P>0.05). CoQ10-NE had good stability. In vitro release experiments showed that the cumulative dissolution rate of CoQ10-NE was 4.7-fold that of the CoQ10 suspension at 120 min. The dissolution rate was significantly improved. According to the results of pharmacokinetic investigations in rats, the maximum plasma concentration Cmax of CoQ10-NE was 2.80-fold that of CoQ10 suspension, the drug concentration of CoQ10-NE in rats was greatly enhanced. The area \begin{document}${\rm{AUC}}_{0{\text -}\infty} $\end{document} was 3.25-fold that of the CoQ10 suspension, demonstrating that CoQ10-NE bioavailability and absorption were greatly increased. The CoQ10-NE developed in this study provides a theoretical foundation for investigating the creation of new CoQ10 formulations and their potential application as a functional ingredient in food.

Abstract Background To reveal the function of protein tyrosine phosphatase‐L1 (PTPL1) in lung adenocarcinoma. Methods Lung cancer cell lines were transfected with short hairpin RNA against PTPL1 (shPTPL1 group) or negative control (shmock group). Quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blotting were used to verify the transfection efficacy. Cell proliferation was analyzed by ethynyldeoxyuridine (EdU), Cell counting kit 8 (CCK8), and colony formation assay after PTPL1 or PTPL1 and yes‐associated protein (YAP1) knockdown. The effect of PTPL1 on tumor growth was examined in a xenograft lung cancer model. Results PTPL1 was downregulated in various types of lung cancer cell lines. The EdU, CCK8, colony formation assays and investigation using a xenograft lung cancer model indicated that PTPL1 knockdown increased the proliferation of lung cancer cells. Mechanistically, PTPL1 knockdown induced the activation of the Proto‐oncogene tyrosine‐protein kinase SRC (Src)/Extracellular regulated MAP kinase (ERK) pathway and thereby promoted yes‐associated protein (YAP1) nuclear translocation and activation. Conclusions In our study, PTPL1 played a crucial suppressive role in the pathogenesis of lung cancer potentially through counteracting the Src/ERK/YAP1 pathway.

The direct linear dichroism photodetection without external optics is crucial for applications. Here, Jie et al. exploit the anisotropic charge trapping in organic phototransistors to achieve the dichroic ratio of 104 and to demonstrate a polarizer-free celestial compass for bio-inspired navigation.

Acoustic metamaterials (AMMs) are a type of artificial materials that make use of appropriate structural designs and exhibit exotic properties not found in natural materials, such as negative effective material parameters (e.g., bulk modulus, mass density, and refractive index). These interesting properties offer novel means for sound manipulation and thus have drawn a great deal of attention. Over the past two decades, tremendous progress has been made in the fundamental research of AMMs, which has not only promoted the development of modern acoustics but also shown the potential of AMMs for engineering applications. Here, we review recent developments in AMMs with a focus on their future engineering, especially in the most promising fields of sound absorption/isolation, acoustic imaging, cloaking, and so on, furthermore, we outline the opportunities and challenges they are encountering.

Abstract Background Sex differentiation can be viewed as a controlled regulatory balance between sex differentiation-related mRNAs and post-transcriptional mechanisms mediated by non-coding RNAs. In mammals, increasing evidence has been reported regarding the importance of gonad-specific microRNAs (miRNAs) in sex differentiation. Although many fishes express a large number of gonadal miRNAs, the effects of these sex-biased miRNAs on sex differentiation in teleost fish remain unknown. Previous studies have shown the exclusive and sexually dimorphic expression of miR-34b/c in the gonads of the Amur sturgeon (Acipenser schrenckii), suggesting its potential role in the sex differentiation process. Results Using quantitative real-time PCR (qPCR), we observed that miR-34b/c showed consistent spatiotemporal expression patterns; the expression levels significantly increased during early sex differentiation. Using in situ hybridization, miR-34c was found to be located in the germ cells. In primary germ cells in vitro, the group subjected to overexpression and inhibition of miR-34c showed significantly higher proliferation ability and lower apoptosis, respectively, compared to the corresponding control group. Luciferase reporter assays using the ar-3′UTR-psiCHECK-2 luciferase vector suggested a targeted regulatory interaction between miR-34b/c and the 3′UTR of the androgen receptor (ar) mRNA. Furthermore, miR-34b/c and ar showed negative expression patterns during early sex differentiation. Additionally, a negative feedback regulation pattern was observed between foxl2 expression in the ovaries and amh and sox9 expression in the testes during early sex differentiation. Conclusions This study sheds new light on the roles of miR-34b/c in gonad development of Amur sturgeon, and provides the first comprehensive evidence that the gonad-predominant microRNAs may have a major role in sex differentiation in teleost fish.

Abstract Background This study aimed to examine the association between oral health behaviors and tooth retention among Chinese older adults. Methods Data were used from the 4th Chinese National Oral Health Survey, a nationally representative sample. The sample included 9054 older adults aged 55 to 74. Control variables and oral health behaviors were measured through a questionnaire interview, and the number of remaining teeth and periodontal health were obtained from an oral health examination. A chi-square test was used for univariate analysis. Multivariate Logistic regression was used to explore the association between health behaviors and the number of remaining teeth. Results The average number of remaining teeth in the sample was 24.4 ± 7.7. There was a higher proportion of older adults living in urban areas with 20 or more teeth than those living in rural areas (83.2% vs. 79.4%, P

Abstract This study is to explore the therapeutic effect and potential mechanisms of exosomal microRNAs (miRNAs) derived from the ovaries with primary ovarian insufficiency (POI). The POI mouse model was established by intraperitoneal injection of cyclophosphamide (CTX) and busulfan. The apoptosis of granulosa cells (GCs) incubated with exosomes extracted from ovarian tissues of control and POI groups was analyzed by flow cytometry. Then, high‐throughput sequencing was performed to detect the difference of miRNAs profile in ovarian tissue‐derived exosomes between the control and POI mice. The effect of differential miRNA on the apoptosis of CTX‐induced ovarian GCs was analyzed by flow cytometry. The results showed that POI mouse model was successfully established. Exosomes extracted from ovarian of normal and POI group have different effects on apoptosis of GCs induced by CTX. miRNA‐seq found that exosomal miR‐122‐5p in POI group increased significantly. miR‐122‐5p as the dominant miRNA targeting BCL9 was significantly upregulated in ovarian tissues of chemotherapy‐induced POI group. Exosomes derived from the ovaries in the control group and miR‐122‐5p inhibitor group attenuated the apoptosis of primary cultured ovarian GCs. In conclusion, exosomal miR‐122‐5p promoted the apoptosis of ovarian GCs by targeting BCL9, suggested that miR‐122‐5p may function as a potential target to restore ovarian function.

Abstract Autophagy has been demonstrated to play important roles in the infection and pathogenesis of many viruses. We previously found that porcine parvovirus (PPV) infection can induce autophagy in porcine placental trophoblast cells (PTCs), but its underlying mechanism has not yet been fully revealed. In this study, we showed that PPV infection inhibited the activation of mTORC1 and promoted the expression of Beclin 1 and LC3II in PTCs. Treatment with a mTOR activator inhibited the expression of Beclin 1 and LC3II, as well as autophagy formation, and reduced viral replication in PPV-infected PTCs. Furthermore, we found that inhibition of AMPK expression, but not the inhibition of PI3K/Akt, p53, or MAPK/ERK1/2 pathway activation, can significantly increase mTOR phosphorylation in PPV-infected PTCs. Then, we found that the regulation of mTOR phosphorylation by AMPK was mediated by Raptor. AMPK expression knockout inhibited the activation of Raptor, decreased the expression of Beclin 1 and LC3II, suppressed the formation of autophagosomes, and reduced viral replication during PPV infection. Together, our results showed that PPV infection induces autophagy to promote viral replication by inhibiting the activation of mTORC1 through activation of the AMPK/Raptor pathway. These findings provide information to understand the molecular mechanisms of PPV-induced autophagy.

The global livestock system is one of the largest sources of ammonia emissions and there is an urgent need for ammonia mitigation. Here, we designed and constructed a novel strategy to abate ammonia emissions via livestock manure acidification based on a synthetic lactic acid bacteria community (LAB SynCom). The LAB SynCom possessed a wide carbon source spectrum and pH profile, high adaptability to the manure environment, and a high capability of generating lactic acid. The mitigation strategy was optimized based on the test and performance by adjusting the LAB SynCom inoculation ratio and the adding frequency of carbon source, which contributed to a total ammonia reduction efficiency of 95.5 %. Furthermore, 16S rDNA amplicon sequencing analysis revealed that the LAB SynCom treatment reshaped the manure microbial community structure. Importantly, 22 manure ureolytic microbial genera and urea hydrolysis were notably inhibited by the LAB SynCom treatment during the treatment process. These findings provide new insight into manure acidification that the conversion from ammonia to ammonium ions and the inhibition of ureolytic bacteria exerted a synergistic effect on ammonia mitigation. This work systematically developed a novel strategy to mitigate ammonia emissions from livestock waste, which is a crucial step forward from traditional manure acidification to novel and environmental-friendly acidification.

ObjectivePolyethylene glycol loxenatide (PEG-Loxe) is a novel, once-weekly glucagon-like peptide 1 receptor agonist that is approved in doses of 0.1 mg and 0.2 mg for the treatment of type 2 diabetes mellitus (T2DM). However, no clinical trials have been designed to determine the effect of 0.3 mg PEG-Loxe on weight loss in overweight or obese patients with T2DM. This trial aimed to evaluate the short-term effect of 0.3 mg PEG-Loxe, injected subcutaneously once weekly, for weight management in overweight or obese patients with T2DM.MethodsThis 16-week, open-label, parallel-arm, randomized, metformin-controlled trial was conducted at Shandong Provincial Hospital in Shandong, China. Patients with T2DM, who were overweight or obese (body mass index ≥ 25.0 kg/m2) and had been treated with lifestyle interventions or a combination with oral antidiabetic drug monotherapy were randomized (2:1) to receive 0.3 mg PEG-Loxe or 1500 mg metformin. The primary endpoint was a change in body weight from baseline to week 16.ResultsOverall, 156 patients were randomized and exposed to treatment. Weight loss was 7.52 kg (8.37%) with PEG-Loxe and 2.96 kg (3.00%) with metformin, with a between-group difference of 4.55 kg (95% CI, 3.43 to 5.67) (P < 0.001). A significantly higher proportion of patients lost ≥5% (61.5% vs. 25.0%) or 10% (26.9% vs. 5.8%) body weight in the PEG-Loxe group than in the metformin group (P < 0.01). Additionally, PEG-Loxe resulted in marked improvements in several cardiovascular risk factors compared to metformin, including body mass index, waist circumference, visceral fat area, blood pressure, and lipid profile. PEG-Loxe and metformin displayed almost equal potency for glycemic control. The incidence of adverse events was 46.2% (48/104) and 44.2% (23/52) in the PEG-Loxe and metformin groups, respectively.ConclusionIn overweight or obese patients with T2DM, a once-weekly subcutaneous administration of PEG-Loxe for 16 weeks, in addition to lifestyle interventions or oral antidiabetic drug therapy, resulted in significantly greater weight loss compared to metformin. Additional trials are necessary to establish whether these effects can be maintained in the long term.Clinical trial registrationwww.chictr.org.cn, identifier ChiCTR2200057800.

ObjectiveThe potential ecological risk index (RI) is the most commonly used method to assess heavy metals (HMs) contamination in soils. However, studies have focused on the response of soil microorganisms to different concentrations, whereas little is known about the responses of the microbial community structures and functions to HMs at different RI levels.MethodsHere, we conducted soil microcosms with low (L), medium (M) and high (H) RI levels, depending on the Pb and Cd concentrations, were conducted. The original soil was used as the control (CK). High-throughput sequencing, qPCR, and Biolog plate approaches were applied to investigate the microbial community structures, abundance, diversity, metabolic capacity, functional genes, and community assembly processes.ResultThe abundance and alpha diversity indices for the bacteria at different RI levels were significantly lower than those of the CK. Meanwhile, the abundance and ACE index for the fungi increased significantly with RI levels. Acidobacteria, Basidiomycota and Planctomycetes were enriched as the RI level increased. Keystone taxa and co-occurrence pattern analysis showed that rare taxa play a vital role in the stability and function of the microbial community at different RI levels. Network analysis indicates that not only did the complexity and vulnerability of microbial community decrease as risk levels increased, but that the lowest number of keystone taxa was found at the H level. However, the microbial community showed enhanced intraspecific cooperation to adapt to the HMs stress. The Biolog plate data suggested that the average well color development (AWCD) reduced significantly with RI levels in bacteria, whereas the fungal AWCD was dramatically reduced only at the H level. The functional diversity indices and gene abundance for the microorganisms at the H level were significantly lower than those the CK. In addition, microbial community assembly tended to be more stochastic with an increase in RI levels.ConclusionOur results provide new insight into the ecological impacts of HMs on the soil microbiome at different risk levels, and will aid in future risk assessments for Pb and Cd contamination.

The past decades have witnessed the flourishing of non-Hermitian physics in non-conservative systems, leading to unprecedented phenomena of unidirectional invisibility, enhanced sensitivity and more recently the novel topological features such as bulk Fermi arcs. Among them, growing efforts have been invested to an intriguing phenomenon, known as the non-Hermitian skin effect (NHSE). Here, we review the recent progress in this emerging field. By starting from the one-dimensional (1D) case, the fundamental concepts of NHSE, its minimal model, the physical meanings and consequences are elaborated in details. In particular, we discuss the NHSE enriched by lattice symmetries, which gives rise to unique non-Hermitian topological properties with revised bulk-boundary correspondence (BBC) and new definitions of topological invariants. Then we extend the discussions to two and higher dimensions, where dimensional surprises enable even more versatile NH.SE phenomena. Extensions of NHSE assisted with extra degrees of freedom such as long-range coupling, pseudospins, magnetism, non-linearity and crystal defects are also reviewed. This is followed by the contemporary experimental progress for NHSE. Finally, we provide the outlooks to possible future directions and developments.

Abstract Background Birth defects are responsible for approximately 7% of neonatal deaths worldwide by World Health Organization in 2004. Many methods have been utilized for examining the congenital anomalies in fetuses. This study aims to investigate the efficiency of simultaneous CNV-seq and whole-exome sequencing (WES) in the diagnosis of fetal anomaly based on a large Chinese cohort. Methods In this cohort study, 1800 pregnant women with singleton fetus in Hubei Province were recruited from 2018 to 2020 for prenatal ultrasonic screening. Those with fetal structural anomalies were transferred to the Maternal and Child Health Hospital of Hubei Province through a referral network in Hubei, China. After multidisciplinary consultation and decision on fetal outcome, products of conception (POC) samples were obtained. Simultaneous CNV-seq and WES was conducted to identify the fetal anomalies that can compress initial DNA and turnaround time of reports. Results In total, 959 couples were finally eligible for the enrollment. A total of 227 trios were identified with a causative alteration (CNV or variant), among which 191 (84.14%) were de novo. Double diagnosis of pathogenic CNVs and variants have been identified in 10 fetuses. The diagnostic yield of multisystem anomalies was significantly higher than single system anomalies (32.28% vs. 22.36%, P = 0.0183). The diagnostic rate of fetuses with consistent intra- and extra-uterine phenotypes (172/684) was significantly higher than the rate of these with inconsistent phenotypes (17/116, P = 0.0130). Conclusions Simultaneous CNV-seq and WES analysis contributed to fetal anomaly diagnosis and played a vital role in elucidating complex anomalies with compound causes.