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Abstract Organs-on-chips are microphysiological systems that allow to replicate the key functions of human organs and accelerate the innovation in life sciences including disease modeling, drug development, and precision medicine. However, due to the lack of standards in their definition, structural design, cell source, model construction, and functional validation, a wide range of translational application of organs-on-chips remains a challenging. “Organs-on-chips: Intestine” is the first group standard on human intestine-on-a-chip in China, jointly agreed and released by the experts from the Chinese Society of Biotechnology on 29th April 2024. This standard specifies the scope, terminology, definitions, technical requirements, detection methods, and quality control in building the human intestinal model on a chip. The publication of this group standard will guide the institutional establishment, acceptance and execution of proper practical protocols and accelerate the international standardization of intestine-on-a-chip for translational applications.

The imaging of aerial targets using Inverse Synthetic Aperture Radar (ISAR) is affected by micro-Doppler effects resulting from localized micromotions, such as rotation and vibration. These effects introduce additional Doppler frequency modulation into the echo, leading to spectral broadening. Under ultrahigh-resolution conditions, these micromotions interfere with the focusing process of subject scatterers, resulting in images with poor focus showing significantly reduced quality. Furthermore, micro-Doppler signals exhibit temporal variability and nonstationary characteristics, posing difficulties in their estimation and differentiation from the echo. To address these challenges, this paper proposes a nonparametric method based on Variational Mode Decomposition (VMD) and mode optimization to separate the echo of the subject from micro-Doppler components. This separation is achieved by utilizing differences in their respective time-frequency distributions. This methodology mitigates the effect of micro-Doppler signals on the echo and obtains imaging results of a drone with ultrahigh-resolution. The VMD algorithm is introduced and subsequently extended to the complex domain. The method entails the decomposition of the ISAR echo along the azimuth direction into several mode functions distributed uniformly across the Doppler sampling bandwidth. Subsequently, image entropy indices are employed to optimize the decomposition parameters and select the imaging modes. This ensures the effective suppression of micro-Doppler signals and preservation of the subject echo. Compared to existing methods based on Empirical Mode Decomposition (EMD) and Local Mean Decomposition (LMD), the proposed method exhibits superior performance in suppressing image blurring caused by micro-Doppler effects while ensuring complete retention of fuselage details. Furthermore, the effectiveness and advantages of the proposed method are validated through simulations and processing of ultrawideband microwave photonic data obtained from drone measurements.

Abstract Background Liver ischemia–reperfusion injury (LIRI) is closely associated with immune infiltration, which commonly occurs after liver surgery, especially liver transplantation. Therefore, it is crucial to identify the genes responsible for LIRI and develop effective therapeutic strategies that target immune response. Methylation modifications in mRNA play various crucial roles in different diseases. This study aimed to identify potential methylation-related markers in patients with LIRI and evaluate the corresponding immune infiltration. Methods Two Gene Expression Omnibus datasets containing human liver transplantation data (GSE12720 and GSE151648) were downloaded for integrated analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted to investigate the functional enrichment of differentially expressed genes (DEGs). Differentially expressed methylation-related genes (DEMRGs) were identified by overlapping DEG sets and 65 genes related to N6-methyladenosine (m6A), 7-methylguanine (m7G), 5-methylcytosine (m5C), and N1-methyladenosine (m1A). To evaluate the relationship between DEMRGs, a protein–protein interaction (PPI) network was utilized. The core DEMRGs were screened using three machine learning algorithms: least absolute shrinkage and selection operator, random forest, and support vector machine-recursive feature elimination. After verifying the diagnostic efficacy using the receiver operating characteristic curve, we validated the expression of the core DEMRGs in clinical samples and performed relative cell biology experiments. Additionally, the immune status of LIRI was comprehensively assessed using the single sample gene set enrichment analysis algorithm. The upstream microRNA and transcription factors of the core DEMRGs were also predicted. Results In total, 2165 upregulated and 3191 downregulated DEGs were identified, mainly enriched in LIRI-related pathways. The intersection of DEGs and methylation-related genes yielded 28 DEMRGs, showing high interaction in the PPI network. Additionally, the core DEMRGs YTHDC1, METTL3, WTAP, and NUDT3 demonstrated satisfactory diagnostic efficacy and significant differential expression and corresponding function based on cell biology experiments. Furthermore, immune infiltration analyses indicated that several immune cells correlated with all core DEMRGs in the LIRI process to varying extents. Conclusions We identified core DEMRGs (YTHDC1, METTL3, WTAP, and NUDT3) associated with immune infiltration in LIRI through bioinformatics and validated them experimentally. This study may provide potential methylation-related gene targets for LIRI immunotherapy.

Abstract The Global Navigation Satellite Systems (GNSS), including the US’s GPS, China’s BDS, the European Union’s Galileo, and Russia’s GLONASS, offer real-time, all-weather, any-time, anywhere and high precision observations by transmitting L band signals continuously, which have been widely used for positioning, navigation and timing. With the development of GNSS technology, it has been found that GNSS-reflected signals can be used to detect Earth’s surface characteristics together with other signals of opportunity. In this paper, the current status and latest advances are presented on Global Navigation Satellite System-Reflectometry (GNSS-R) in theory, methods, techniques and observations. New developments and progresses in GNSS-R instruments, theoretical modeling, and signal processing, ground and space-/air-borne experiments, parameters retrieval (e.g. wind speed, sea surface height, soil moisture, ice thickness), sea surface altimetry and applications in the atmosphere, oceans, land, vegetation, and cryosphere are given and reviewed in details. Meanwhile, the challenges in the GNSS-R development of each field are also given. Finally, the future applications and prospects of GNSS-R are discussed, including multi-GNSS reflectometry, new GNSS-R receivers, GNSS-R missions, and emerging applications, such as mesoscale ocean eddies, ocean phytoplankton blooms, microplastics detection, target recognition, river flow, desert studies, natural hazards and landslides monitoring.

Microwave Photonic (MWP) radars have remarkably improved traditional microwave radar hardware architectures using photonics devices. With the exceptional physical properties of photonic devices, MWP radars can emit ultra-wideband, high-linearity, high-quality linear frequency modulation signals, allowing ultra-high-resolution target imaging and detection. Different target regions exhibit distinct responses to different frequency signals during target imaging and detection due to their diverse structures and characteristics. Therefore, MWP radars have the potential to generate pseudo-color images based on scattering differences, further enhancing the information retrieval capability of MWP Synthetic Aperture Radar (MWP-SAR). Pseudo-color images generated using traditional remote sensing techniques cannot achieve centimeter-level resolution. Therefore, we propose a method for generating pseudo-color images while maintaining the resolution of MWP-SAR. The algorithm first determines an optimal sub-band echo search model and subsequently employs the optimal sub-band search algorithm to process the ultra-wideband echoes to obtain sub-band echo channels with the largest scattering characteristic differences. The multi-sub-band images are then color-composited to generate pseudo-color images that best describe the target scattering characteristics. However, to ensure the high resolution of MWP-SAR, a fusion model is established to combine the full-resolution SAR image with the multi-sub-band image. Finally, full-resolution pseudo-color images are successfully synthesized using the measured airborne MWP-SAR data, validating the effectiveness of the algorithm. This algorithm enables MWP-SAR to obtain more target information during imaging, offering assistance in implementing imaging radar and microwave vision.

Abstract Exosomes are a subtype of extracellular vesicles composed of bioactive molecules, including nucleic acids, proteins, and lipids. Exosomes are generated by the fusion of intracellular multivesicular bodies (MVBs) with the cell membrane and subsequently released into the extracellular space to participate in intercellular communication and diverse biological processes within target cells. As a crucial mediator, exosomes have been implicated in regulating ferroptosis—an iron-dependent programmed cell death characterized by lipid peroxide accumulation induced by reactive oxygen species. The involvement of exosomes in iron, lipid, and amino acid metabolism contributes to their regulatory role in specific mechanisms underlying how exosomes modulate ferroptosis, which remains incompletely understood, and some related studies are still preliminary. Therefore, targeting the regulation of ferroptosis by exosomes holds promise for future clinical treatment strategies across various diseases. This review aims to provide insights into the pathophysiology and mechanisms governing the interaction between exosomes and ferroptosis and their implications in disease development and treatment to serve as a reference for further research.

Abstract Background Cold stress has negative effects on the growth and health of mammals, and has become a factor restricting livestock development at high latitudes and on plateaus. The gut-liver axis is central to energy metabolism, and the mechanisms by which it regulates host energy metabolism at cold temperatures have rarely been illustrated. In this study, we evaluated the status of glycolipid metabolism and oxidative stress in pigs based on the gut-liver axis and propose that AMP-activated protein kinase (AMPK) is a key target for alleviating energy stress at cold temperatures by dietary fat supplementation. Results Dietary fat supplementation alleviated the negative effects of cold temperatures on growth performance and digestive enzymes, while hormonal homeostasis was also restored. Moreover, cold temperature exposure increased glucose transport in the jejunum. In contrast, we observed abnormalities in lipid metabolism, which was characterized by the accumulation of bile acids in the ileum and plasma. In addition, the results of the ileal metabolomic analysis were consistent with the energy metabolism measurements in the jejunum, and dietary fat supplementation increased the activity of the mitochondrial respiratory chain and lipid metabolism. As the central nexus of energy metabolism, the state of glycolipid metabolism and oxidative stress in the liver are inconsistent with that in the small intestine. Specifically, we found that cold temperature exposure increased glucose transport in the liver, which fully validates the idea that hormones can act on the liver to regulate glucose output. Additionally, dietary fat supplementation inhibited glucose transport and glycolysis, but increased gluconeogenesis, bile acid cycling, and lipid metabolism. Sustained activation of AMPK, which an energy receptor and regulator, leads to oxidative stress and apoptosis in the liver; dietary fat supplementation alleviates energy stress by reducing AMPK phosphorylation. Conclusions Cold stress reduced the growth performance and aggravated glycolipid metabolism disorders and oxidative stress damage in pigs. Dietary fat supplementation improved growth performance and alleviated cold temperature-induced energy stress through AMPK-mediated mitochondrial homeostasis. In this study, we highlight the importance of AMPK in dietary fat supplementation-mediated alleviation of host energy stress in response to environmental changes.

LncRNA is a type of transcript with a length exceeding 200 nucleotides, which was once considered junk transcript with no biological function during the transcription process. In recent years, lncRNA has been shown to act as an important regulatory factor at multiple levels of gene expression, affecting various programmed cell death modes including ferroptosis. Ferroptosis, as a new form of programmed cell death, is characterized by a deficiency of cysteine or inactivation of glutathione peroxidase, leading to depletion of glutathione, aggregation of iron ions, and lipid peroxidation. These processes are influenced by many physiological processes, such as the Nrf2 pathway, autophagy, p53 pathway and so on. An increasing number of studies have shown that lncRNA can block the expression of specific molecules through decoy effect, guide specific proteins to function, or promote interactions between molecules as scaffolds. These modes of action regulate the expression of key factors in iron metabolism, lipid metabolism, and antioxidant metabolism through epigenetic or genetic regulation, thereby regulating the process of ferroptosis. In this review, we snapshotted the regulatory mechanism of ferroptosis as an example, emphasizing the regulation of lncRNA on these pathways, thereby helping to fully understand the evolution of ferroptosis in cell fate.

Introduction: The Maximum Entropy models (MaxEnt) is commonly employed for early detection of disease transmission, particularly effective in assessing the risk zones and intensity of tick-borne disease transmission based on climatic factors.Methods: Utilizing the diversity data of common ticks in Qinghai, along with surveillance statistics tick-borne pathogens of ticks and epidemiological information, we have charted and predicted the prevalence of tick and tick-borne pathogens across Qinghai province.Results and Discussion: The findings indicate that the pivotal environmental factors influencing the distribution of ticks and tick-borne pathogens include land use and land cover (Lucc), elevation (Elev), annual precipitation (Bio12) and annual mean temperature (Bio1). Notably, for Dermacentor nuttalli, the significant environmental factors accounted for 35.2% for Lucc, 24.7% for Elev and 18.6% for Bio12. In the case of Dermacentor silvaru, the pivotal factors contributed 33.2% for Lucc, 23.7% for Elev and 22.6% for Bio1. For Haemaphysalis qinghaiensis, the key environmental variables were 45% for Elev, 30.9% for Lucc and 18.4% for Bio12. Regarding the pathogens, the environmental factors influencing Borrelia burgdorferi contributed 61.5% for Lucc, 13.3% for Elev and 11.9% for Bio1. For Piroplasmida, the contribution was 62.1% for Lucc, 16.7% for Bio1 and 9.9% for Bio12. Rickettsia was influenced by factors accounting for 34.2% for Lucc, 29.7% for Elev and 17.3% for Bio12, while Anaplasma variables contributed 38.2% for Bio1, 26.6% for Lucc and 18.9% for Bio12. The finding indicated that the three predominantly ticks species (D. nuttalli, D. silvaru, and H. qinghaiensis) and the primary tick-borne pathogens (B. burgdorferi, Piroplasmida, Rickettsia, and Anaplasma) are predominantly concentrated in the source regions of the Yellow River, the Yangtze River, the Lancang River, and the eastern part of the Haixi Autonomous Prefecture. Projected under the ssp245 scenario, there is a notable expansion trend in the risk areas for ticks and tick-borne pathogens These findings are consistent with previous epidemiological studies on major ticks and tick-borne diseases in Qinghai conducted by our laboratory, this suggests the feasibility of using the MaxEnt model to predict the distribution of tick-borne disease transmission and compensates for the paucity of research on the Maxent model in the Qinghai Province.

Background: Ticks are ectoparasites that feed on blood and pose a threat to both the livestock industry and public health due to their ability to transmit pathogens through biting. However, the impact of factors such as bloodmeal and geographic regions on the bacterial microbiota of Haemaphysalis qinghaiensis remains poorly understood. Methods: In this study, we used the v3-v4 region of the 16S rRNA gene to sequence the microbiota of Haemaphysalis qinghaiensis from eight groups (HY_M, YS_M, XH_M, LD_M, BM_M, LD_F_F, LD_F, and BM_F_F) in Qinghai Province. Results: Significant differences in bacterial richness were observed between LD_F_F, BM_F_F, and LD_F (P

Increasing the synthetic aperture radar (SAR) imaging frame rate is vital for obtaining continuous SAR images and dynamic scene monitoring, which multistatic SAR can achieve. Multiple source synchronization errors in multistatic SAR enable the image to produce positional offset and target defocus, which deteriorate the image quality. In order to obtain highly precise multistatic SAR images, synchronization errors must be compensated for. However, geometry errors are unavoidable during platform movement, which introduce Doppler frequency errors and range cell migration just like synchronization errors. Therefore, these two errors will jointly affect the imaging quality when coupled together, which will increase the difficulty of compensation. Aiming to resolve the issue of obtaining imaging results when the two errors exist simultaneously, this article proposes a decoupled estimation and compensation method for geometry and synchronization error. At first, the coupling relationship between geometry error and synchronization error on echo delay and Doppler frequency is analyzed. Next, the decoupled estimation problem with geometry and synchronization error is transformed into a constrained optimization problem. Then, the differential evolutionary algorithm is employed to address the optimization problem. Finally, the estimated values are utilized to compensate for the echoes to obtain high-resolution imaging results, which are verified by the simulation results. The experimental results convincingly demonstrate the improvement of the proposed method in imaging frame rate and error decoupling ability.

Raw data simulation is very important for system parameter design, performance evaluation, and route planning of bistatic synthetic aperture radar (SAR). However, most conventional simulation methods focus on improving the efficiency of echo simulation, without considering the impact of terrain fluctuations, resulting in insufficient fidelity of simulated echoes. In this article, a raw data simulation framework under undulating terrain for bistatic SAR with arbitrary configuration is proposed. In the framework, based on the prior information of digital elevation model of undulating terrain and the small facet theory, the time-variant scattering coefficient is computed first with the empirical formula related with the angle variation of transmitter and receiver for bistatic SAR. Then the shadow is judged from the perspectives of transmitter and receiver, respectively, and the formation of double shadow is discussed. At last, the above process was embedded into the time domain pulse by the pulse echo simulation algorithm, forming a framework for simulating bistatic SAR raw data under undulating terrain with arbitrary configuration, and the simulated and measured data experiments are illustrated to verify the effectiveness of the proposed framework.

Cisplatin, a frequently prescribed chemotherapeutic agent, serves as a clinically therapeutic strategy for a broad range of malignancies. Its primary mode of action centers around interference with DNA replication and RNA transcription, thereby inducing apoptosis in cancer cells. Nevertheless, the clinical utility of cisplatin is constrained by its severe adverse effects and the burgeoning problem of drug resistance. Ginsenosides, potent bioactive constituents derived from ginseng, possess an array of biological activities. Recent scientific investigations underscore the substantial amplification of cisplatin's anticancer potency and the mitigation of its harmful side effects when administered concomitantly with ginsenosides. This review aims to explore the underlying mechanisms at play in this combination therapy. Initially, we provide a concise introduction to the cisplatin. Then, we pivot towards illuminating how ginsenosides bolster the anticancer efficacy of cisplatin and counteract cisplatin resistance, culminating in enhanced therapeutic outcomes. Furthermore, we provide an extensive discussion on the reduction of cisplatin-induced toxicity in the kidneys, liver, gastrointestinal tract, nervous system, and ear, accompanied by immune-fortification with ginsenosides. The existing clinical combined use of cisplatin and ginsenosides is also discussed. We propose several recommendations to propel additional research into the mechanisms governing the synergistic use of ginsenosides and cisplatin, thereby furnishing invaluable insights and fostering advancement in combined modality therapy.

Abstract Polymeric ultralong organic phosphorescence (UOP) with persistent emission is of great importance in practical applications. However, achieving good water‐resistance for long‐term environmental stability is a formidable challenge. In this contribution, through tailoring the alkyl‐chain length of the hardeners and emitters, polymeric UOPs with varying crosslinking density and hydrophobic effect were obtained. Notably, all the polymers show no obvious decrease in UOP emission after high temperature‐humidity test (85°C/85% relative humidity for 7 days). Detailed investigations demonstrate that the rigid covalent crosslinking networks suppress the quenching of triplet excitons while the hydrophobic microenvironment affords good water/moisture‐resistance ability. Moreover, the polymers with superior processability are successfully applied as optical coatings, prepreg, and afterglow displays. With this work, we provide a new strategy to promote the long‐term stability of polymeric UOP materials in high‐temperature‐humidity conditions.

In recent years, millimeter-wave radar has been widely used in safety detection, nondestructive detection of parts, and medical diagnosis because of its strong penetration ability, small size, and high detection accuracy. However, due to the limitation of hardware transmission bandwidth, achieving ultra-high two-dimensional resolution using millimeter-wave radar is challenging. Two-dimensional high-resolution imaging of altitude and azimuth can be realized using radar platform scanning to form a two-dimensional aperture. However, during the scanning process, the millimeter-wave radar produces sparse tracks in the height dimension, resulting in a sparse sampling of the altitude echo, thus reducing the imaging quality. In this paper, a high-resolution three-dimensional imaging algorithm for millimeter-wave radar based on Hankel transformation matrix filling is proposed to solve this problem. The matrix filling algorithm restores the sparse sampling echo, which guarantees the imaging accuracy of the millimeter-wave radar in the scanning plane. First, the low-rank prior characteristics of the millimeter-wave radar's elevation-range section were analyzed. To solve the problem of missing whole rows and columns of data during sparse trajectory sampling, the echo data matrix was reconstructed using the Hankel transform, and the sparse low-rank prior characteristics of the constructed matrix were analyzed. Furthermore, a matrix filling algorithm based on truncated Schatten-p norm combining low-rank and sparse priors was proposed to fill and reconstruct the echoes to ensure the three-dimensional resolution of the sparse trajectory millimeter-wave radar. Finally, using simulation and several sets of measured data, the proposed method was proved to achieve high-resolution three-dimensional imaging even when only 20%–30% of the height echo was used.

Fufang Muji granules (FMGs) are a prominent modern prescription Chinese patent formulation derived from the Muji decoction. Utilized in clinical practice for nearly four decades, FMGs have demonstrated efficacy in treating liver diseases. However, the precise mechanism of action remains unclear. This study investigates the hepatoprotective effects of FMGs against liver fibrosis in rats based on untargeted metabolomics and elucidates their underlying mechanisms. A comprehensive model of liver fibrosis was established with 30% CCl4 (2 mL/kg) injected intraperitoneally, and a fat and sugar diet combined with high temperatures and humidity. Rats were orally administered FMGs (3.12 g/kg/d) once daily for six weeks. FMG administration resulted in improved liver fibrosis and attenuated hepatic oxidative stress and apoptosis. Furthermore, FMGs inhibited hepatic stellate cell activation and modulated transforming growth factor β1/Smad signaling. Additionally, FMG treatment influenced the expression levels of interleukin-6, interleukin-1β, and tumour necrosis factor alpha in the injured liver. Metabolic pathways involving taurine and hypotaurine metabolism, as well as primary bile acid biosynthesis, were identified as mechanisms of action for FMGs. Immunohistochemistry, quantitative reverse transcription polymerase chain reaction (RT-qPCR), and quantitative analysis also revealed that FMGs regulated taurine and hypotaurine metabolism and bile acid metabolism. These findings provide a valuable understanding of the role of FMGs in liver fibrosis management.

IntroductionProduce prescription programs are rapidly expanding as a type of Food is Medicine intervention with prospects for mitigating food insecurity and reducing diet-related health disparities. Gaining insight into participant perspectives on program logistics and perceived impacts is crucial to program success and improvements.MethodsBetween May and June 2021, we conducted individual and small group interviews with 23 caregivers with children aged 1–5 years who participated in a produce prescription program from 2020 to 2021 in Texas, U.S. They were provided with a gift card to a major national grocery retailer to purchase fresh produce. The card was reloaded $60 monthly for 8 months with automatic roll-over of unused funds to the next month. Participants also received nutrition education in the form of two videos. A deductive analysis approach was employed, and NVivo qualitative data analysis software was used to perform coding and to assist with subsequent analyses.ResultsAll 23 participants were female, with an average age of 37.5 years, and the majority identified as Hispanic/Latino (83%). About 43% of the families had three or more children. Six themes were generated from interviews. Three of these themes were related to program logistics: (1) ease of program use; (2) participant satisfaction with the incentive; and (3) desire for additional store options. The remaining main themes pertained to program impact: (1) the enhanced ability to purchase produce; (2) the usefulness of the nutrition education; and (3) persistent challenges encountered when preparing the produce for picky eaters and young children.ConclusionA pediatric produce prescription program was perceived as logistically easy and a helpful source of financial support for accessing fresh produce. Program features such as card-based incentive system and partnership with major grocery retailer were favored by participants. For future program design, it may be beneficial to consider collaborating with multiple grocery outlets and enhancing the intensity and targeting of nutrition education.

The relationship between anxiety and sleep disorders is a key research topic in the academic community. However, evidence on the mechanism through which anxiety influences sleep disorders remains limited. The purpose of this study was to investigate the roles of flourishing and neuroticism in the mechanism through which anxiety influences sleep disorders in medical students. We constructed a moderated mediation model and tested the mediating role of flourishing and the moderating role of neuroticism in medical college students. The results showed that: (1) anxiety was significantly and positively related to sleep disorders and significantly and negatively related to flourishing; flourishing was significantly and negatively related to sleep disorders; neuroticism was significantly and positively related to sleep disorders; (2) flourishing had a mediation effect on the relationship between anxiety and sleep disorders; (3) neuroticism moderated the process through which flourishing mediated the effect of anxiety on sleep disorders. Our research expands the literature on the mechanism underlying the effects of anxiety on sleep disorders and provides insights into the potential prevention and intervention of sleep and emotional problems in medical students.

Bacterial cellulose (BC) has been recognized as an ideal supporter owning to its abundant hydroxyl groups on the surface. In this work, Keggin-type phosphotungstic acid (H3PW12O40, PWA) is self-anchored on the three-dimensional network of BC by a simple diffusion method at room-temperature. BC fibers can protect the well-dispersed PWA with high transparency, high mechanical strength, and high stability. When PWA/BC serves as a photochromic material, the coloration time and bleaching time are only 3 min and 30 min respectively. After 6 cycles, the photochromic ability of the PWA/BC composite film almost unchanged. At the same time, we convert the coloration and bleaching degree into quantitative data including a color difference calculation of ΔE2000 and the remaining degree of color (RC%). Within the BC system, PWA exhibits a special linear relationship between RC% and bleaching time (0–30 min). The processes of PWA/BC reduction (W6+→W5+) and oxidation (W5+→W6+) are analysed by photo-electrochromic, XPS and ESR characterizations. The revealed excellent photochromic properties of soft PWA/BC films highlight their potential as the photoresponsive materials.

BackgroundThe association between natural products and dietary interventions on liver enzymes is unclear; therefore, this study aimed to examine their effects on liver enzymes in adults.MethodsPubMed, Embase, and Cochrane Library of Systematic Reviews databases were searched from inception until March 2023. The Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) systems were used to assess the methodological and evidence quality, and the therapeutic effects were summarized in a narrative form.ResultsA total of 40 meta-analyses on natural products (n = 25), dietary supplements (n = 10), and dietary patterns (n = 5) were evaluated, and results were presented in a narrative form. The overall methodological quality of the included studies was relatively poor. The results indicated that positive effects were observed for nigella sativa, garlic, artichoke, curcumin, silymarin, vitamin E, vitamin D, L-carnitine, propolis, and polyunsaturated fatty acids on certain liver enzymes. The dietary patterns, including high-protein, Mediterranean, and calorie-restriction diets and evening snacks, may reduce liver enzymes; however, other supplements and herbs did not reduce liver enzyme levels or have minimal effects. The evidence quality was generally weak given the risk of bias, heterogeneity, and imprecision.ConclusionThis umbrella review suggests that natural products and dietary interventions have beneficial therapeutic effects on liver enzymes levels. Further clinical trials are necessary to establish the effectiveness of supplements that reduce liver enzymes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), characterized by its high fatality rate and contagious nature, has led to significant morbidity and mortality worldwide, significantly impacting both our daily lives and public health. The respiratory pathway serves as the primary route for SARS-CoV2 propagation within the human body, with the lung acting as the initial target organ. Simultaneously, the lung functions as a protective barrier, preventing the entry of viruses into the bloodstream through the alveolar-capillary barrier. Bioengineered microfluidic lung chips, utilizing advanced near-to-native technologies, offer a novel perspective for comprehending the intricate workings of human lungs and facilitating the discovery of anti-coronavirus drugs to combat the challenges posed by coronavirus disease 2019 (COVID-19). This review aims to introduce the key elements and design types of artificial lung chips that closely resemble in vivo-like niches in terms of both structure and function. Furthermore, quantitative and qualitative techniques for evaluating the functionality of the alveolar-capillary barrier are summarized, confirming the successful construction of lung chip systems through engineering approaches. The prospects and persistent challenges associated with establishing next-generation artificial lung models to meet the demands of virology studies are also discussed.

Chlamydia trachomatis, is a kind of obligate intracellular pathogen. The removal of C. trachomatis relies primarily on specific cellular immunity. It is currently considered that CD4+ Th1 cytokine responses are the major protective immunity against C. trachomatis infection and reinfection rather than CD8+ T cells. The non-specific immunity (innate immunity) also plays an important role in the infection process. To survive inside the cells, the first process that C. trachomatis faces is the innate immune response. As the “sentry” of the body, mast cells attempt to engulf and remove C. trachomatis. Dendritic cells present antigen of C. trachomatis to the “commanders” (T cells) through MHC-I and MHC-II. IFN-γ produced by activated T cells and natural killer cells (NK) further activates macrophages. They form the body’s “combat troops” and produce immunity against C. trachomatis in the tissues and blood. In addition, the role of eosinophils, basophils, innate lymphoid cells (ILCs), natural killer T (NKT) cells, γδT cells and B-1 cells should not be underestimated in the infection of C. trachomatis. The protective role of innate immunity is insufficient, and sexually transmitted diseases (STDs) caused by C. trachomatis infections tend to be insidious and recalcitrant. As a consequence, C. trachomatis has developed a unique evasion mechanism that triggers inflammatory immunopathology and acts as a bridge to protective to pathological adaptive immunity. This review focuses on the recent advances in how C. trachomatis evades various innate immune cells, which contributes to vaccine development and our understanding of the pathophysiologic consequences of C. trachomatis infection.

Abstract Synergistically improving T-cell responsiveness is promising for favorable therapeutic outcomes in immunologically cold tumors, yet current treatments often fail to induce a cascade of cancer-immunity cycle for effective antitumor immunity. Gasdermin-mediated pyroptosis is a newly discovered mechanism in cancer immunotherapy; however, cleavage in the N terminus is required to activate pyroptosis. Here, we report a single-agent mRNA nanomedicine-based strategy that utilizes mRNA lipid nanoparticles (LNPs) encoding only the N-terminus of gasdermin to trigger pyroptosis, eliciting robust antitumor immunity. In multiple female mouse models, we show that pyroptosis-triggering mRNA/LNPs turn cold tumors into hot ones and create a positive feedback loop to promote antitumor immunity. Additionally, mRNA/LNP-induced pyroptosis sensitizes tumors to anti-PD-1 immunotherapy, facilitating tumor growth inhibition. Antitumor activity extends beyond the treated lesions and suppresses the growth of distant tumors. We implement a strategy for inducing potent antitumor immunity, enhancing immunotherapy responses in immunologically cold tumors.

Ni and carbon materials exhibit remarkable catalysis for the hydriding reaction of Mg. But the underlying mechanism of Ni/C hybrid catalysis is still unclear. In this work, density functional theory (DFT) calculation is applied to investigate the effect of Ni/C co-incorporation on the hydriding reaction of Mg crystal. The morphology and crystal structure of the Ni/C co-incorporated Mg sample show that the co-incorporated structure is credible. The transition state searching calculation suggests that both the incorporations of Ni and C are beneficial for the H2 dissociation. But Ni atom has a dramatic improvement for H2 dissociation and makes the H diffusion become limiting step of the hyriding reaction. The Ni dz2 orbit and H s orbit accept the electrons and combine together compactly, while the Ni dxy orbit is half-occupied. The catalytic effect of Ni on H2 dissociation can be ascribed to the bridging effect of Ni dxy orbit. The incorporation of C can weaken the over-strong interaction between Ni and H which hindered the H diffusion on Mg(0001). The Ni/C co-incorporated Mg(0001) shows the best performance during hyriding reaction compared with the clean and single incorporated Mg(0001).

Abstract Several studies have shown that males suffer more severe damage than females in the process of ischemia and reperfusion of the brain, heart and kidney. Accordingly, our study will reveal the correlation between the severity of hepatic ischemia‒reperfusion injury (HIRI) and sex, and preliminarily analyze the underlying mechanism. A total of 75 patients who were considered to have "benign liver tumors" at the initial admission and underwent partial hepatectomy were enrolled. We identified potential differences between different groups and discussed the correlation between the severity of HIRI and sex through a comparative analysis. Results showed that HIRI was more severe in males than in females, especially in younger patients. To explore whether estrogen level differences are the main reason for the sex differences in HIRI, we further revealed that HIRI in premenopausal females was more severe than that in postmenopausal females. By comparing the levels of gonadal hormones, we speculated that multiple gonadal hormones, including follicle-stimulating hormone, luteinizing hormone and testosterone, may jointly participate in the regulation of sex differences in HIRI together with estrogen.

Magnolol shows promise as an effective anti-tumor therapeutic agent. Nevertheless, the clinical application of this agent is constrained by its inherent water insolubility and diminished stability. In the present investigation, we have developed a new approach to address these limitations by creating an acid-responsive amphiphilic polymeric prodrug (PMag) that contains acetal bonds and magnolol, and can self-assemble into polymeric micelles (PMag-Ms) in aqueous solutions. We conducted in vitro release studies and observed that the micelles rapidly released magnolol at an acidic pH of 5.0, but only released minimal amounts of magnolol at a neutral pH of 7.4. In vitro investigations performed on gastric cancer cells elucidated that PMag-Ms selectively induced cell apoptosis and G1 phase cell cycle arrest, exhibiting higher efficacy than magnolol alone. Furthermore, in vivo studies confirmed that PMag-Ms exhibited superior inhibition of tumor growth, favorable biocompatibility with organs, increased accumulation in tumor tissues, and enhanced targeting efficiency compared to magnolol. Pharmacokinetic analysis also revealed that PMag-Ms had a longer half-life and extended duration of action in vivo. These results highlight the potential of the synthesized acid-degradable PMag-Ms as a promising therapeutic option for gastric cancer.

BackgroundProduce prescription programs represent a promising intervention strategy in the healthcare setting to address disparities in diet quality and diet-related chronic disease. The objective of this study was to understand adoption and implementation factors related to these programs that are common across contexts and those that are context-specific.MethodsIn this qualitative case comparison study, we conducted qualitative interviews with eight clinic staff from five primary care “safety net” clinics, identified by a partnering non-profit organization that operated the programs, in April–July 2021.ResultsAcross clinics, the ability to provide a tangible benefit to patients was a key factor in adoption. Flexibility in integrating into clinic workflows was a facilitator of implementation. Fit with usual operations varied across clinics. Common challenges were the need for changes to the workflow and extra staff time. Clinic staff were skeptical about the sustainability of both the benefits to patients and the ability to continue the program at their clinics.DiscussionThis study adds to a growing body of knowledge on the adoption and implementation of produce prescription programs. Future research will further this understanding, providing the evidence necessary to guide adopting clinics and to make informed policy decisions to best promote the growth and financial sustainability of these programs.

To evaluate the thermal stability of composite polymer-modified asphalt, thermoplastic elastomer styrene-butadiene rubber (SBR)/polypropylene (PP) pellets were prepared using a hot-melt blending technique, with butyl rubber powder and waste polypropylene pellets as raw materials. The effects of different evaluation indexes on the thermal stability of SBR/PP-modified asphalt were investigated using a frequency scan test and a multi-stress creep recovery (MSCR) test, and the compatibility of SBR/PP particles with asphalt was studied using the Cole–Cole diagram and microstructure images. The tests show that, firstly, the performance grade (PG) classification of asphalt can be improved by adding an SBR/PP thermoplastic elastomer to enhance the adaptability of asphalt in high- and low-temperature environments, and the evaluation separation index can reflect the high-temperature storage stability of composite-modified asphalt more reasonably. Additionally, the larger the rubber-to-plastic ratio the worse the high-temperature thermal stability of composite-modified asphalt. Moreover, the addition of additives to the composite particles can promote the SBR/PP particles in the asphalt to be more uniformly dispersed, forming a more desirable microstructure and improving the thermal stability of composite-modified asphalt. Ultimately, the semicircular curve of the Cole–Cole diagram can reflect the compatibility characteristics of the two-phase structure of SBR/PP-modified asphalt, which can be used as an auxiliary index to evaluate the compatibility of polymer-modified asphalt.

Background: Ginseng consumption has been associated with various health outcomes. However, there are no review articles summarizing these reports.Methods: PubMed, Embase, the Cochrane Library of Systematic Reviews, Scopus, CNKI and Wanfang databases were searched from inception to 31 July 2022. The Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) and Grading of Recommendations Assessment, Development and Evaluation (GRADE) systems were used to assess the methodological quality and quality of evidence in each meta-analysis, and the results were summarized in a narrative form.Results: Nineteen meta-analyses that met the eligibility criteria were identified from among 1,233 papers. The overall methodological quality was relatively poor, with only five studies being low-quality, and 14 critically low-quality. When compared with control treatments (mainly placebo), ginseng was beneficial for improving fatigue and physical function, sexual function, menopausal symptoms, metabolic indicators, inflammatory markers, unstable angina and respiratory diseases. Adverse events included gastrointestinal symptoms and potential bleeding; however, no serious adverse events were reported.Conclusion: This umbrella review suggests that ginseng intake has beneficial therapeutic effects for diverse diseases. However, the methodological quality of studies needs to be improved considerably. In addition, it is imperative to establish the clinical efficacy of ginseng through high-quality randomized controlled trials.

Persistent infection of Chlamydia trachomatis is thought to be responsible for the debilitating sequelae of blinding trachoma and infertility. Inhibition of host cell apoptosis is a persistent C. trachomatis infection mechanism. ZEB1-AS1 is a long non-coding RNA (lncRNA), which was up-regulated in persistent C. trachomatis infection in our previous work. In this study, we investigated the role of ZEB1-AS1 in persistent infection and the potential mechanisms. The results showed that ZEB1-AS1 was involved in the regulation of apoptosis, and targeted silencing of ZEB1-AS1 could increase the apoptosis rate of persistently infected cells. Mechanically, interference ZEB1-AS1 caused an apparent down-regulation of the Bcl-2/Bax ratio and the repression of the mitochondrial membrane potential with the remarkable release of cytochrome c, resulting in the significant elevation level of caspase-3 activation. Meanwhile, the luciferase reporter assay confirmed that ZEB1-AS1 acted as a sponge for miR-1224-5p to target MAP4K4. The regulatory effect of miR-1224-5p/MAP4K4 on persistent infection-induced antiapoptosis was regulated by ZEB1-AS1. In addition, ZEB1-AS1 inhibited the apoptosis of Chlamydia-infected cells by activating the MAPK/ERK pathway. In conclusion, we found a new molecular mechanism that the ZEB1-AS1/miR-1224-5p/MAP4K4 axis contributes to apoptosis resistance in persistent C. trachomatis infection. This work may help understand the pathogenic mechanisms of persistent C. trachomatis infection and reveal a potential therapeutic strategy for its treatment.

To study the effect of drilling rig working parameters and rock type on the temperature of the polycrystalline diamond composite (PDC) bit, an analytical temperature calculation model was established, and the correctness of the analytical model was verified by numerical simulation analysis. Combined with an infrared thermal imager, the temperature of PDC cutting teeth under different parameter combinations was qualitatively analyzed, and the sensitivity of cutting teeth temperature to different parameters was discussed through an orthogonal test. The research results show that increasing the rotational speed and rate of penetration (ROP) value causes more severe shearing and friction of the bit, thereby increasing the temperature of the cutting teeth. The experimental results are consistent with the simulation results. Under the same working parameters, the maximum temperature of the bit when drilling granite is about 1.5 times that of curbs and 2 times that of artificial rocks. Finally, the orthogonal test analysis found that the cutting teeth temperature has a high sensitivity to rock type and ROP value, with a weight of 48% and 32.9%, respectively; also, the index has a general sensitivity to the rotation speed, with a weight of 19.1%. The research results provide a certain reference value for the reasonable selection of the working parameters of the drilling rig.

Immunotherapy is emerging as a powerful tool for combating many human diseases. However, the application of this life-saving treatment in serious brain diseases, including glioma, is greatly restricted. The major obstacle is the lack of effective technologies for transporting therapeutic agents across the blood-brain barrier (BBB) and achieving targeted delivery to specific cells once across the BBB. Ferritin, an iron storage protein, traverses the BBB via receptor-mediated transcytosis by binding to transferrin receptor 1 (TfR1) overexpressed on BBB endothelial cells. Here, we developed bioengineered ferritin nanoparticles as drug delivery carriers that enable the targeted delivery of a small-molecule immunomodulator to achieve enhanced immunotherapeutic efficacy in an orthotopic glioma-bearing mouse model. We fused different glioma-targeting moieties on self-assembled ferritin nanoparticles via genetic engineering, and RGE fusion protein nanoparticles (RGE-HFn NPs) were identified as the best candidate. Furthermore, RGE-HFn NPs encapsulating a stimulator of interferon genes (STING) agonist (SR717@RGE-HFn NPs) maintained stable self-assembled structure and targeting properties even after traversing the BBB. In the glioma-bearing mouse model, SR717@RGE-HFn NPs elicited a potent local innate immune response in the tumor microenvironment, resulting in significant tumor growth inhibition and prolonged survival. Overall, this biomimetic brain delivery platform offers new opportunities to overcome the BBB and provides a promising approach for brain drug delivery and immunotherapy in patients with glioma.

Limited evidence suggests that elderly patients with advanced colorectal cancer (ACRC) may benefit from traditional Chinese medicine (TCM). This study investigated the efficacy and safety of TCM in old ACRC patients treated in the Oncology Department of Xiyuan Hospital between January 2012 and December 2021. The clinical characteristics of these patients were retrospectively reviewed. Their progression-free survival (PFS) and total duration of TCM therapy (TTCM) were analyzed using the Kaplan-Meier curve. Forty-eight patients (F:M 13:35) with a mean age of 78.75 ± 2.99 years (range, 75–87) met the inclusion criteria. There were 18 cases of rectal cancer and 30 of colon cancer. The median PFS was 4 months (range, 1–26; 95% CI 3.26–4.73). The median TTCM was 5.5 months (range, 1–50; 95% CI 1.76–8.24). Subgroup analysis revealed that PFS and TTCM were shorter in patients with bone metastases and an ECOG performance status score of 2–3 (p < 0.05). No hematological toxicity or serious adverse reactions occurred during the study period. This real-world study demonstrates that TCM may be a potentially beneficial therapy for old ACRC patients, including when the ECOG performance status score is 2–3.

BackgroundTraditional emulsion adjuvants are limited in clinical application because of their surfactant dependence. Graphene oxide (GO) has unique amphiphilic properties and therefore has potential to be used as a surfactant substitute to stabilize Pickering emulsions.MethodsIn this study, GO–stabilized Pickering emulsion (GPE) was prepared and used as an adjuvant to facilitate an enhanced immune response to the Chlamydia trachomatis (Ct) Pgp3 recombinant vaccine. Firstly, GPE was prepared by optimizing the sonication conditions, pH, salinity, GO concentration, and water/oil ratio. GPE with small-size droplets was characterized and chosen as the candidate. Subsequently, controlled-release antigen delivery by GPE was explored. Cellular uptake behaviors, M1 polarization, and cytokine stimulation by GPE + Pgp3 was considered in terms of the production of macrophages. Finally, GPE’s adjuvant effect was evaluated by vaccination with Pgp3 recombinant in BALB/c mouse models.ResultsGPE with the smallest droplet sizes was prepared by sonication under 163 W for 2 min at 1 mg/mL GO in natural salinity with a pH of 2 when the water/oil ratio was 10:1 (w/w). The optimized average GPE droplet size was 1.8 μm and the zeta potential was –25.0 ± 1.3 mv. GPE delivered antigens by adsorption onto the droplet surface, demonstrating the controlled release of antigens both in vitro and in vivo. In addition, GPE promoted antigen uptake, which stimulated proinflammatory tumor necrosis factor alpha (TNF-α), enhancing the M1 polarization of macrophages in vitro. Macrophage recruitment was also significantly promoted by GPE at the injection site. In the GPE + Pgp3 treatment group, higher levels of immunoglobin (IgG), immunoglobin G1 (IgG1), immunoglobin G2a (IgG2a) sera, and immunoglobin A (IgA) were detected in vaginal fluid, and higher levels of IFN-γ and IL-2 secretion were stimulated, than in the Pgp3 group, showing a significant type 1 T helper (Th1)-type cellular immune response. Chlamydia muridarum challenging showed that GPE enhanced Pgp3’s immunoprotection through its advanced clearance of bacterial burden and alleviation of chronic pathological damage in the genital tract.ConclusionThis study enabled the rational design of small-size GPE, shedding light on antigen adsorption and control release, macrophage uptake, polarization and recruitment, which enhanced augmented humoral and cellular immunity and ameliorated chlamydial-induced tissue damage in the genital tract.

Arginyl-fructosyl-glucose (AFG) is one of the typical active non-saponins in red ginseng. This study investigates the hepatoprotective effects of AFG against acute liver injury (ALI) induced by D-galactosamine (D-GalN) and lipopolysaccharide (LPS) in mice. A metabolomics study was performed to clarify the hepatoprotective effect mechanisms of AFG on ALI. Eight metabolites were identified in the liver samples as potential biomarkers responsible for the hepatoprotective effect of AFG. The pathway analysis showed that the hepatoprotective effects of AFG were associated with amino acid metabolism and oxidative stress. Amino acid quantitative results revealed that Hyp, Harg, Aad, β-Ala, and Abu significantly changed after the pretreatment with AFG. In addition, AFG pre-treatment attenuated the upregulated Nrf2 and HO-1, and enhanced the expression level of Mrp2 in liver. These results has demonstrated a promising hepatoprotective of AFG for ALI, and AFG is expected to become a functional food with hepatoprotective effect.

Microbial degradation is a cost-effective and environmentally friendly method for removing microcystin-LR (MC-LR). However, the application of free bacteria has limitations due to low operational stability and difficulties in recovery. In a previous study, our group successfully isolated a highly efficient MC-LR-degrading bacterium, Sphingopyxis sp. YF1, from Taihu. To enhance its practical potential in addressing MC-LR-contaminated water pollution, a novel biological material named polyacrylonitrile-based carbon fiber @Sphingopyxis sp. YF1 (PAN-CF@YF1) was synthesized. The immobilization conditions of strain Sphingopyxis sp. YF1 on PAN-CF surfaces were optimized using Box–Behnken design and response surface methodology (RSM), which turned out to be an optimal pH of 7.6 for the culture medium, a ratio of 0.038 g of supporting materials per 100 mL of culture media, and an incubation time of 53.4 h. The resultant PAN-CF@YF1 showed a great degradation effect both for low and high concentrations of MC-LR and exhibited satisfactory cyclic stability (85.75% after six cycles). Moreover, the application of PAN-CF@YF1 in the bioreactors demonstrated effective and sustainable MC-LR removal, with a removal efficiency of 78.83% after three consecutive treatments. Therefore, PAN-CF@YF1 with high degradation activity, environmental compatibility, straightforward preparation, and recyclability shows significant application potential for the bioremediation of MC-LR-contaminated water bodies.

The effects of maternal dietary energy and arginine level on embryonic development and serum lipid metabolism were investigated in this study. A 2 × 3 factorial experiment was conducted with six treatments represented by 10 replicates of eight Arbor Acre broiler breeder hens each. Diets fed from 40 to 50 weeks of age were formulated to contain two digestible arginine levels (9.6 g/kg and 14.5 g/kg) and three metabolic energy levels (10.08 MJ ME/kg, 11.88 MJ ME/kg, and 13.68 MJ ME/kg). Artificial insemination was used, and eggs collected from 50 weeks of hens’ age were hatched. Embryonic growth, biochemical and endocrine indexes of embryonic serum and allantoic fluid were measured on different embryonic days (E). The results were as follows: Egg weight (E0, E11, E13) and embryonic weight (E12, E15) in the high-energy group (13.68 MJ ME/kg) were significantly decreased (p < 0.01), as were embryonic breast rate (E13, E15, E21), thigh rate (E13–E21) and liver rate (E15–E21). The reciprocal effects of arginine and energy were significant on breast rate (E11, E13, E17), thigh rate (E19, E21) and liver rate (E11, E19) of the embryo (p < 0.05). CHO (E13–E19), high-density lipoprotein (E13, E15, E21), low-density lipoprotein (E15, E19, E21), and blood glucose (E13) levels in embryonic serum decreased with the increase in maternal dietary energy level (p < 0.05), but triglyceride levels (E19, E21) showed the opposite result (p < 0.05). The levels of cholesterol and blood glucose in embryonic serum at E11 and urea nitrogen in allantoic fluid at E11–E15 were significantly decreased in the 14.5 g/kg arginine group (p < 0.01). With the increase in maternal dietary energy and arginine levels, embryonic serum nitric oxide synthases levels (E11, E15, E19) increased significantly (p < 0.01). The reciprocal effect of arginine and energy in maternal diets was significant on the embryonic serum high-density lipoprotein level at E21 (p < 0.05). Embryonic serum insulin levels at E13 were significantly elevated in the high-energy group (13.68 MJ ME/kg). The reciprocal effect of arginine and energy was significant on the embryonic serum growth hormone level (p < 0.01). Embryonic serum growth hormone levels were significantly reduced in the 14.5 g/kg arginine and 13.68 MJ/kg metabolic energy group (p < 0.01). In conclusion, maternal restricted feeding improved embryonic development and regulated lipid metabolism-related indices in embryonic serum. Maternal dietary addition of digestible arginine had a significant effect on lipid metabolism indices in embryos. There was a maternal effect of maternal dietary energy and arginine levels on embryo growth and development. The deposition of maternal nutrients affects the development of embryos.

BackgroundNigella sativa (N. sativa) consumption has been associated with various health outcomes; however, the results are not completely consistent.ObjectivesThis overview of systematic reviews and meta-analyses aimed to evaluate the reporting and methodological quality, and to grade the available evidence of associations between N. sativa and health outcomes.MethodsPubMed, Cochrane Library, Embase, and Scopus databases were searched from their inception to September 30, 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 statement, Assessment of Multiple Systematic Reviews (AMSTAR) 2 checklist, and Grades of Recommendations, Assessment, Development and Evaluations (GRADE) systems were used to assess the reporting, methodological, and evidence quality for each meta-analysis, respectively. The results were synthesized in a narrative form.ResultsThis overview included 20 eligible meta-analyses published in peer-reviewed journals between 2013 and 2021. The overall methodological quality was relatively poor, with only one moderate quality, four low quality, and 15 critically low quality studies. For reporting quality, items two, five, eight, nine, 15, and 24 need to improve. Among the 110 outcome indicators of the quality of evidence, five were graded as moderate, 17 as low, and 88 as very low. Risk of bias, inconsistency, and imprecision were the main downgrading factors.ConclusionThis overview suggests that N. sativa is beneficial for various clinical outcomes. However, there are certain limitations to reporting and methodological quality. The clinical efficacy of N. sativa requires confirmation in high-quality, large-sample, randomized controlled trials.

Traumatic brain injury (TBI) is the main cause of driver death in electric two-wheeler accidents in China. Traumatic brain injury not only brings great threat to people's life safety, but also causes great economic losses in the process of national economic and social development. In this study, a head fluid–structure coupling finite element model was combined with a multi-rigid dummy body to form a finite element and multi-rigid body coupling model of an electric two-wheeler driver. Moreover, a human–vehicle-to-road combined system model was established that included a multi-rigid body two-wheeler model, a multi-rigid body vehicle model, and a road model, which is verified by an actual accident information. According to some simulation tests, moderate and severe nerve injuries may have happened to the driver although the HIC(Head Injury Criteria, common used in vehcile collision injury) is less than 1000. The result shows that the maximum pressure of the simulation result is 455.27 kPa, which exceeds the critical value of brain contusion. The overall relative error between simulation results and actual accident results is less than 10%. The driver model, especially the head model, can accurately simulate the bicyclist head injury and thereby provide a theoretical basis for the traffic injury assessment.

Atmospheric pollutants, including particulate matters, nanoparticles, bioaerosols, and some chemicals, have posed serious threats to the environment and the human’s health. The lungs are the responsible organs for providing the interface between the circulatory system and the external environment, where pollutant particles can deposit or penetrate into bloodstream circulation. Conventional studies to decipher the mechanism underlying air pollution and human health are quite limited, due to the lack of reliable models that can reproduce in vivo features of lung tissues after pollutants exposure. In the past decade, advanced near-to-native lung chips, combining cell biology with bioengineered technology, present a new strategy for atmospheric pollutants assessment and narrow the gap between 2D cell culture and in vivo animal models. In this review, the key features of artificial lung chips and the cutting-edge technologies of the lung chip manufacture are introduced. The recent progresses of lung chip technologies for atmospheric pollutants exposure assessment are summarized and highlighted. We further discuss the current challenges and the future opportunities of the development of advanced lung chips and their potential utilities in atmospheric pollutants associated toxicity testing and drug screening.

In vivo, the complex process of drugs metabolism alters the change in drug composition and determines the final pharmacological properties of oral drugs. Ginsenosides are primary constituents of ginseng, whose pharmacological activities are greatly affected by liver metabolism. However, the predictive power of existing in vitro models is poor due to their inability to mimic the complexity of drug metabolism in vivo. The advance of organs-on-chip-based microfluidics system could provide a new in vitro drug screening platform by recapitulating the metabolic process and pharmacological activity of natural product. In this study, an improved microfluidic device was employed to establish an in vitro co-culture model by culturing multiple cell types in compartmentalized microchambers. Different cell lines were seeded on the device to examine the metabolites of ginsenosides from the hepatocytes in top layer and its resulting efficacy on the tumors in bottom layer. Metabolism dependent drug efficacy of Capecitabine in this system demonstrated the model is validated and controllable. High concentrations of CK, Rh2 (S), and Rg3 (S) ginsenosides showed significant inhibitory effects on two types of tumor cells. In addition, apoptosis detection showed that Rg3 (S) through liver metabolism promoted early apoptosis of tumor cells and displayed better anticancer activity than prodrug. The detected ginsenoside metabolites indicated that some protopanaxadiol saponins were converted into other anticancer aglycones in varying degrees due to orderly de-sugar and oxidation. Ginsenosides exhibited different efficacy on target cells by impacting their viabilities, indicating hepatic metabolism plays an important role in determining ginsenosides efficacy. In conclusion, this microfluidic co-culture system is simple, scalable, and possibly widely applicable in evaluating anticancer activity and metabolism of drug during the early developmental phases of natural product.

Scientific and practical calculations on the thermal stability of typical automobile road surface (semi-limited objects) with fluctuations in air temperatures, transitions from positive to negative, with actual heat transfer coefficients, thermal conductivity of components, specific mass isobaric heat capacities, material densities, periods of regular fluctuations are presented. The study shows that temperature fluctuations occur in road surfaces, therefore deformations are brought about in them, generating thermal cracks. Thermal deformations include free, proportional to temperature gradients, stressed deformations due to temperature stresses, characterized by linear thermal expansion coefficients. In road materials, physical and mechanical properties change over time: strength, moduli of elastic longitudinal deformations, shear, transverse deformation coefficients. Thus, the temperature of pavement materials depends on the coordinates, time, and thermophysical characteristics of the materials. Thermal engineering calculations have shown that many road surfaces have limited thermal stability; under the influence of relatively small external influences, they are more stable (supercooled water vapor exists for a short time, turning into a liquid, saturated, supersaturated steam into a superheated liquid, this depends on the radiation characteristics of the surfaces, the presence of external disturbances, etc.). Thus, a complex non-stationary thermal regime takes place, when the temperature fields of the coatings, their gradients of temperature potentials, and masses depend on the boundary conditions of the 1st–4th kind. A citation analysis of the data of the Journal Citation Reports of world scientific serial publications has been developed to carry out research on heat and mass transfer in road surface. The analysis shows that in order to improve the reliability and durability of pavements, fundamental studies of both the physical and technical and thermal properties of all components of road construction mixtures are of great importance.

In terms of the global coverage provided by global navigation satellite system (GNSS) signals, radar images of a large field-of-view can be obtained via passive synthetic aperture radar (SAR) using these signals of opportunity. Usually, large field-of-view imaging is challenging using conventional SAR methods owing to the space-variant resolution. In addition, only a moderate range resolution can be provided by the GNSS transmitters in the passive SAR system. In this article, an optimal imaging method for a large field-of-view using GNSS-based passive SAR is proposed, which exploits the inherent multistatic nature of GNSS. At first, the spatial resolution of each scatterer in the observation area relative to each GNSS transmitter is calculated according to the geometry. Then, the selection of the transmitter set is modeled as an optimization problem, where the minimal resolution cell is used as the optimal criterion. After that, an evolutionary algorithm is applied to solve the optimization problem. Finally, the space-time combination of the echoes over a long dwell time concerning selected GNSS transmitters is performed to form the radar image with a minimal spatial resolution. The proposed method is extensively validated using two experimental datasets, where the passive radar consists of BeiDou satellites and a fixed receiver. The spatial resolution improvement and the large field-of-view imaging capability of the proposed method are forcefully demonstrated according to the experimental results.

The combinatorial complexity of the protein sequence space presents a significant challenge for recombination experiments targeting beneficial positions. To overcome these difficulties, a machine learning (ML) approach was employed, which was trained on a limited literature dataset and combined with iterative generation and experimental data implementation. The PyPEF method was utilized to identify existing variants and predict recombinant variants targeting the substrate channel of P450 CYP116B3. Through molecular dynamics simulations, eight multiple-substituted improved variants were successfully validated. Specifically, the RMSF of variant A86T/T91H/M108S/A109M/T111P was decreased from 3.06 Å (wild type) to 1.07 Å. Additionally, the average RMSF of the variant A86T/T91P/M108V/A109M/T111P decreased to 1.41 Å, compared to the wild type’s 1.53 Å. Of particular significance was the prediction that the variant A86T/T91H/M108G/A109M/T111P exhibited an activity approximately 15 times higher than that of the wild type. Furthermore, during the selection of the regression model, PLS and MLP regressions were compared. The effect of data size and data relevance on the two regression approaches has been summarized. The aforementioned conclusions provide evidence for the feasibility of the strategy that combines ML with experimental approaches. This integrated strategy proves effective in exploring potential variations within the protein sequence space. Furthermore, this method facilitates a deeper understanding of the substrate channel in P450 CYP116B3.

Considering the shortcomings in current chlamydia infection control strategies, a major challenge in curtailing infection is the implementation of an effective vaccine. The immune response induced by C. trachomatis plasmid encoded Pgp3 was insufficient against C. trachomatis infection, which requires adjuvant applications to achieve the robust immune response induced by Pgp3. There is increasing promising in developing adjuvant systems relying on the delivery potential of Pickering emulsions and the immunomodulatory effects of interleukin (IL)-12. Here, owing to the polycationic nature, chitosan particles tended to absorb on the oil/water interphase to prepare the optimized chitosan particle-stabilized Pickering emulsion (CSPE), which was designed as a delivery system for Pgp3 protein and IL-12. Our results showed that the average droplets size of CSPE was 789.47 ± 44.26 nm after a series of optimizations and about 90% antigens may be absorbed by CSPE owing to the positively charged surface (33.2 ± 3mV), and CSPE promoted FITC-BSA proteins uptake by macrophages. Furthermore, as demonstrated by Pgp3-specific antibody production and cytokine secretion, CSPE/IL-12 system enhanced significantly higher levels of Pgp3-specific IgG, IgG1, IgG2a, sIgA and significant cytokines secretion of IFN-γ, IL-2, TNF-α, IL-4. Similarly, vaginal chlamydial shedding and hydrosalpinx pathologies were markedly reduced in mice immunized with Pgp3/CSPE/IL-12. Collectively, vaccination with Pgp3/CSPE/IL-12 regimen elicited robust cellular and humoral immune response in mice resulting in an obvious reduction of live chlamydia load in the vaginal and inflammatory pathologies in the oviduct, which further propells the development of vaccines against C. trachomatis infection.

Urogenital tract infections with Chlamydia trachomatis have frequently been detected among patients diagnosed with sexually transmitted infections, and such infections lead to inflammatory complications. Currently, no licensed chlamydial vaccine is available in clinical practice. We previously reported that immunization with recombinant C. trachomatis plasmid-encoded virulence factor Pgp3 provided cross-serovar protection against C. muridarum genital tract infection. Because Pgp3 is a homotrimer and human antisera only recognize the trimeric form of Pgp3, we compared the effects of the native conformation of Pgp3 (trimer) and heat-denatured Pgp3 (monomer) to determine whether the native conformation is dispensable for the induction of protective immunity against chlamydial vaginal challenge. Both Pgp3 trimer and monomer immunization induced corresponding specific antibody production, but only trimer-induced antibody recognized endogenous Pgp3, and trimer-immunized mouse splenocytes showed the highest IFN-γ production upon restimulation with the chlamydial elementary body or native Pgp3 in vitro. Importantly, only Pgp3 trimer-immunized mice showed shortened lower genital tract chlamydial shedding and decreased upper genital tract pathology. Thus, Pgp3-induced protective immunity against Chlamydia urogenital tract infection is highly dependent on the native conformation, which will guide the design of Pgp3-based polypeptides and multi-subunit chlamydial vaccines.

LncRNAs are involved in the pathophysiologic processes of multiple diseases, but little is known about their functions in hepatic ischemia/reperfusion injury (HIRI). As a novel lncRNA, the pathogenetic significance of hepatic nuclear factor 4 alpha, opposite strand (Hnf4αos) in hepatic I/R injury remains unclear. Here, differentially expressed Hnf4αos and Hnf4α antisense RNA 1 (Hnf4α-as1) were identified in liver tissues from mouse ischemia/reperfusion models and patients who underwent liver resection surgery. Hnf4αos deficiency in Hnf4αos-KO mice led to improved liver function, alleviated the inflammatory response and reduced cell death. Mechanistically, we found a regulatory role of Hnf4αos-KO in ROS metabolism through PGC1α upregulation. Hnf4αos also promoted the stability of Hnf4α mRNA through an RNA/RNA duplex, leading to the transcriptional activation of miR-23a and miR-23a depletion was required for PGC1α function in hepatoprotective effects on HIRI. Together, our findings reveal that Hnf4αos elevation in HIRI leads to severe liver damage via Hnf4αos/Hnf4α/miR-23a axis-mediated PGC1α inhibition.

The outbreak of the coronavirus (COVID-19) has heightened awareness of the importance of quick and easy testing. The convenience, speed, and timely results from point-of-care testing (POCT) in all vitro diagnostic devices has drawn the strong interest of researchers. However, there are still many challenges in the development of POCT devices, such as the pretreatment of samples, detection sensitivity, specificity, and so on. It is anticipated that the unique properties of nanomaterials, e.g., their magnetic, optical, thermal, and electrically conductive features, will address the deficiencies that currently exist in POCT devices. In this review, we mainly analyze the work processes of POCT devices, especially in nucleic acid detection, and summarize how novel nanomaterials used in various aspects of POCT products can improve performance, with the ultimate aims of offering new ideas for the application of nanomaterials and the overall development of POCT devices.

Study objective: To demonstrate a case for the successful use of the robotic-assisted laparoscopic hepatic hilar cholangiocarcinoma (Bismuth-Corlette Ⅲb) radical resection. Design: Stepwise demonstration with narrated video footage, including left hemi hepatectomy, total caudate lobectomy, extrahepatic biliary tract resection and reconstruction, hepaticojejunostomy, cholecystectomy, and hepatic hilar lymph node dissection. Setting: The First Affiliated Hospital of Harbin Medical University. Case presentation: A 34-year-old female patient developed icteric skin and sclera without obvious triggers, accompanied by dark urine, and light-colored loose stools. She had a dull pain in the upper abdomen and lost 2.5 ​kg weight in this period. Before admission, she had accepted percutaneous transhepatic cholangial drainage (PTCD) in other hospital, with two drainage tubes collecting 500 ml of bile per day in total. Due to the liver-enhanced CT scan suggesting proximal bile duct obstruction, space-occupying lesions of the hilar bile duct are considered, with no exclusion of cholangiocarcinoma. Routine preoperative laboratory examinations were performed after admission. The total bilirubin level was 75.5 μmol/L (normal range, 3.4–21 μmol/L) and the direct bilirubin level was 40.8 μmol/L (normal range, 0.01–3.4 μmol/L); alanine aminotransferase level was 282.6 U/L (normal range, 5–40 U/L); aspartate aminotransferase level was 124.2 U/L (normal range, 8–40 U/L); γ-glutamyl transpeptidase level was 79.8 U/L (normal range, 10–60 U/L); CA19-9 level was 62.68 U/mL (normal range, 0–37 U/mL). Intervention: Since the first robot-assisted hepatectomy was reported in 2002, the use of robot-assisted surgery in the hepatobiliary department has grown rapidly.1,2 However, robot-assisted surgery for hepatic hilar cholangiocarcinoma radical resection is rarely reported. Although the tumor volume is not large, hepatic hilar cholangiocarcinoma radical resection is regarded as one of the most challenging operations because it includes major hepatectomy, hepatic hilar lymph node dissection, and bile duct reconstruction.3,4. The operative area is located at the core of the first porta hepatis, possessing a close anatomic relationship with the hepatic artery and portal vein, which greatly increases the difficulty and risk of the operation. In addition, for such tumors located at such a unique place, operating space for surgeons is objectively limited, and the radical resection of tumors can only be achieved by ensuring the absolute negative margin of the bile duct and the precise dissection of the hepatic hilar lymph node. The emergence of the robotic-assisted system has solved this problem5. With the three core technologies: naked eye 3D high-definition vision, turnable surgical instruments, and intuitive movement, the robotic-assisted system helps surgeons operate in the limited and narrow space under the best vision through the flexible conversion of robotic arms from multiple angles. During the operation, the patient was placed in a supine position, and our conventional trocar layout used in liver resection was adopted (Fig. 1). The liver was suspended by pulling round ligaments during the operation, and Pringle maneuver was used for first hepatic portal occlusion. We completely removed the left hemi liver, caudate lobe, diseased biliary tract and hepatic hilar lymph node. The hepaticojejunostomy was completed after biliary duct reconstruction. Through the application of the robot-assisted system, we can identify the anatomical structure more clearly, avoid collateral damage, shorten the intraoperative time, and improve the prognosis of patients. The results were as follows: The procedure was successfully performed with one 5 cm and five 0.8 cm incisions. The patient had a good recovery, getting rid of the drainage tube on the left on postoperative day 7, and another drainage tube on the right on day 9. Suffering with no complications, the patient was discharged on day 10. The pathology report showed moderately or poorly differentiated adenocarcinoma in the hepatic hilar bile duct, which invaded surrounding liver tissue and nerve. None of the nine lymph nodes we harvested presented metastasis at the final pathology report. All the incisional edges we sent for examination during the operation were reported negative. Conclusion: Robotic-assisted laparoscopic hepatic hilar cholangiocarcinoma (Bismuth-Corlette Ⅲb) radical resection gives full play to the advantages of the robotic-assisted system, providing better vision and more delicate operations, which makes the tissue dissection safer and less damage, so as to accelerate the postoperative recovery of patients and bring better therapeutic effects to them.

This paper proposes colaGAE, a self-supervised learning framework for graph-structured data. While graph autoencoders (GAEs) commonly use graph reconstruction as a pretext task, this simple approach often yields poor model performance. To address this issue, colaGAE employs mutual isomorphism as a pretext task for a continuous latent space sampling GAE (colaGAE). The central idea of mutual isomorphism is to sample from multiple views in the latent space and reconstruct the graph structure, with significant improvements in terms of the model’s training difficulty. To investigate whether continuous latent space sampling can enhance GAEs’ learning of graph representations, we provide both theoretical and empirical evidence for the benefits of this pretext task. Theoretically, we prove that mutual isomorphism can offer improvements with respect to the difficulty of model training, leading to better performance. Empirically, we conduct extensive experiments on eight benchmark datasets and achieve four state-of-the-art (SOTA) results; the average accuracy rate experiences a notable enhancement of 0.3%, demonstrating the superiority of colaGAE in node classification tasks.