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Cold milling is a widely used method for rehabilitating asphalt pavement, generating reclaimed asphalt pavement (RAP) chunks. Within this process, aggregates within the asphalt pavement will be crushed, forming RAP agglomerates and aggregate breakdown. However, the mechanism of these phenomena has remained unclear, and a unified evaluation method has yet to be established. In this study, RAP agglomeration and aggregate fragmentation were characterized, five distinct methods were systematically assessed, and the mechanism of RAP agglomeration and breakdown was analyzed by discrete element method (DEM) simulation based on setting different particle contact parameters, then followed by a mechanical analysis, and demonstrated in engineering. The results revealed that both agglomeration and aggregate breakdown occur within RAP particles of various sizes, with the five methods showing similar trends in quantifying these effects. Through DEM simulations and mechanical analyses, the aggregate breakdown predominantly occurs at the cutter's motion trajectory of the cutter and during crack propagation, while agglomeration was mainly related to the sliding surface's area. The milling speed and depth positively impact RAP agglomeration, while negatively affecting aggregate breakdown, and milling drum speed exerts minimal influence on these phenomena. RAP agglomeration varies considerably in different engineering projects, and cold milling parameters should be determined based on the material composition of the asphalt pavement and design requirements to control agglomeration and breakdown rates of RAP.

Abstract Sterile neutrinos with masses at the keV scale and mixing to the active neutrinos offer an elegant explanation of the observed dark matter (DM) density. However, the very same mixing inevitably leads to radiative photon emission and the non-observation of such peaked X-ray lines rules out this minimal sterile neutrino DM hypothesis. We show that in the context of the Standard Model effective field theory with sterile neutrinos (νSMEFT), higher dimensional operators can produce sterile neutrino DM in a broad range of parameter space. In particular, νSMEFT interactions can open the large mixing parameter space due to their destructive interference, through operator mixing or matching, in the X-ray emission. We also find that, even in the zero mixing limit, the DM density can always be explained by νSMEFT operators. The testability of the studied νSMEFT operators in searches for electric dipole moments, neutrinoless double beta decay, and pion decay measurements is discussed.

Abstract Maize rough dwarf disease (MRDD) threatens maize production globally. The P7-1 effector of the rice black-streaked dwarf virus (RBSDV) targets maize Rab GDP dissociation inhibitor alpha (ZmGDIα) to cause MRDD. However, P7-1 has difficulty recruiting a ZmGDIα variant with an alternative helitron-derived exon 10 (ZmGDIα-hel), resulting in recessive resistance. Here, we demonstrate that P7-1 can recruit another maize protein, gibberellin 2-oxidase 13 (ZmGA2ox7.3), which also exhibits tighter binding affinity for ZmGDIα than ZmGDIα-hel. The oligomerization of ZmGA2ox7.3 is vital for its function in converting bioactive gibberellins into inactive forms. Moreover, the enzymatic activity of ZmGA2ox7.3 oligomers increases when forming hetero-oligomers with P7-1/ZmGDIα, but decreases when ZmGDIα-hel replaces ZmGDIα. Viral infection significantly promotes ZmGA2ox7.3 expression and oligomerization in ZmGDIα-containing susceptible maize, resulting in reduced bioactive GA1/GA4 levels. This causes an auxin/cytokinin imbalance and ultimately manifests as MRDD syndrome. Conversely, in resistant maize, ZmGDIα-hel counters these virus-induced changes, thereby mitigating MRDD severity.

Abstract The insufficient availability and activity of interfacial water remain a major challenge for alkaline hydrogen evolution reaction (HER). Here, we propose an “on-site disruption and near-site compensation” strategy to reform the interfacial water hydrogen bonding network via deliberate cation penetration and catalyst support engineering. This concept is validated using tip-like bimetallic RuNi nanoalloys planted on super-hydrophilic and high-curvature carbon nanocages (RuNi/NC). Theoretical simulations suggest that tip-induced localized concentration of hydrated K+ facilitates optimization of interfacial water dynamics and intermediate adsorption. In situ synchrotron X-ray spectroscopy endorses an H* spillover-bridged Volmer‒Tafel mechanism synergistically relayed between Ru and Ni. Consequently, RuNi/NC exhibits low overpotential of 12 mV and high durability of 1600 h at 10 mA cm‒2 for alkaline HER, and demonstrates high performance in both water electrolysis and chlor-alkali electrolysis. This strategy offers a microscopic perspective on catalyst design for manipulation of the local interfacial water structure toward enhanced HER kinetics.

Abstract To reduce system complexity and bridge the interface between electronic and photonic circuits, there is a high demand for a non-volatile memory that can be accessed both electrically and optically. However, practical solutions are still lacking when considering the potential for large-scale complementary metal-oxide semiconductor compatible integration. Here, we present an experimental demonstration of a non-volatile photonic-electronic memory based on a 3-dimensional monolithic integrated ferroelectric-silicon ring resonator. We successfully demonstrate programming and erasing the memory using both electrical and optical methods, assisted by optical-to-electrical-to-optical conversion. The memory cell exhibits a high optical extinction ratio of 6.6 dB at a low working voltage of 5 V and an endurance of 4 × 104 cycles. Furthermore, the multi-level storage capability is analyzed in detail, revealing stable performance with a raw bit-error-rate smaller than 5.9 × 10−2. This ground-breaking work could be a key technology enabler for future hybrid electronic-photonic systems, targeting a wide range of applications such as photonic interconnect, high-speed data communication, and neuromorphic computing.

Abstract Targeted delivery and precise release of toxins is a prospective strategy for the treatment of triple-negative breast cancer (TNBC), yet the flexibility to incorporate both properties simultaneously remains tremendously challenging in the X-drug conjugate fields. As critical components in conjugates, linkers could flourish in achieving optimal functionalities. Here, we pioneered a pH-hypersensitive tumor-targeting aptamer AS1411-triptolide conjugate (AS-TP) to achieve smart release of the toxin and targeted therapy against TNBC. The multifunctional acetal ester linker in the AS-TP site-specifically blocked triptolide toxicity, quantitatively sustained aptamer targeting, and ensured the circulating stability. Furthermore, the aptamer modification endowed triptolide with favorable water solubility and bioavailability and facilitated endocytosis of conjugated triptolide by TNBC cells in a nucleolin-dependent manner. The integrated superiorities of AS-TP promoted the preferential intra-tumor triptolide accumulation in xenografted TNBC mice and triggered the in-situ triptolide release in the weakly acidic tumor microenvironment, manifesting striking anti-TNBC efficacy and virtually eliminated toxic effects beyond clinical drugs. This study illustrated the therapeutic potential of AS-TP against TNBC and proposed a promising concept for the development of nucleic acid-based targeted anticancer drugs.

Residual δ-ferrite is ubiquitous in M50NiL bearing steel and seriously deteriorates impact toughness. In the present work, the formation mechanism of δ-ferrite in M50NiL steel and the influence of element segregation on its formation process were investigated. The residual δ-ferrite was proved to form directly from the final liquid phase at the end of solidification due to serious segregation of Mo and V elements. Calculation results indicate that the segregation of Mo and V elements expanded the “L + δ'' two-phase region and stabilized δ-ferrite. Due to the high concentration of Mo and V, large-sized V-rich MC and Mo-rich M2C carbides would precipitate in δ-ferrite at 900–1200 °C if the cooling rate is slow. When kept at 1200 °C for no more than 30 min, Mo and V elements derived from the decomposition of large-sized carbides are preferentially diffused into δ-ferrite, enhancing the stability of δ-ferrite. To achieve the effective elimination of δ-ferrite in M50NiL steel, it is necessary to keep the ingot at 1200 °C for at least 20 h.

Abstract Background Achilles tendon is vital in maintaining the stability and function of ankle joint. It is quite difficult to achieve the structural and functional repair of Achilles tendon in tissue engineering. Methods A tissue-engineered tendon micro-tissue was prepared using rat tail tendon extracellular matrix (TECM) combined with rat adipose stem cells (ADSCs) to repair Achilles tendon injuries. The TECM was prepared by repeated freezing and thawing. The in vitro characteristics of TECM and its effect on ADSCs proliferation were detected. This tissue-engineered tendon micro-tissue for Achilles tendon repair in vivo was evaluated based on general characteristics, gait analysis, ultrasound findings, histological analysis, and biomechanical testing. Results The results showed that the TECM scaffold had good biocompatibility for ADSCs. At 2 weeks post-surgery, collagen types I and III and tenomodulin expression were higher, and vascular endothelial growth factor expression was lower in the micro-tissue group than other groups. At 4 and 8 weeks post-surgery, the results of histological analysis and ultrasound findings showed that the repaired tendon tissue was smooth and lustrous, and was arranged regularly and evenly in the micro-tissue group. Gait analysis confirmed that better motor function recovery was noted in micro-tissue group than other groups. In addition, the mechanical properties of the repaired tendon tissue in micro-tissue group were better than other groups. Conclusion Tissue-engineered tendon micro-tissue fabricated by TECM and ADSCs has good biocompatibility and can promote structural and functional repair of tendon in vivo. This composite biomaterial has broad application prospects in tissue engineering.

Abstract Exosomes, a specific subset of extracellular vesicles, have diverse functions in various biological processes. In the field of cancer research, there has been a growing interest in the potential of exosomes to act as versatile vehicles for targeted tumor imaging and therapy. In this study, we constructed a targeted delivery platform using hypoimmunogenic exosomes by genetically modifying β2‐microglobulin knocking‐out HEK‐293F cells to express a fusion protein, referred to as αMUC1‐Exo, which comprises the exosomal membrane‐enriched platelet‐derived growth factor receptor, intracellular nanoluciferase, and extracellular anti‐MUC1 single‐chain variable fragment. The findings of this study indicate that αMUC1‐Exos exhibited notable drug delivery properties toward MUC1‐positive pancreatic cancer cells, resulting in a substantial inhibition of tumor growth. Moreover, these exosomes demonstrated a high level of biosafety and the absence of any adverse effects. The application of engineered exosomes as a vehicle for drug delivery holds promise for enhancing the immunogenicity of neoplastic cells following treatment, thereby inducing antitumor immune memory in mice with intact immune systems, and also improving the response to anti‐PD1 therapy. This approach utilizing engineered exosomes for Gemcitabine administration holds promise as a potential strategy for overcoming drug resistance in pancreatic carcinoma thereby improving the overall treatment efficacy.

Abstract Continuous and quantitative monitoring of knee joint function has clinical value in rehabilitation assessment and the timing of return to play for anterior cruciate ligament injury patients. However, the existing approaches, including clinical examination, arthrometry and inertial solutions, can only be used for qualitative, off‐line and low‐quality evaluations, respectively. Burgeoning Kirigami stretchable sensors could be a disruptive candidate solution, but they usually suffer from structural buckling issues when used for large strain applications, such as knee joint motion capture where the buckling degrades sensor reliability and repeatability. Here, we propose a buckling‐resistant stretchable and wearable sensor for knee joint motion capture. It enables continuous and precise motion signal capture of the knee joint and provides high wearing comfort and reliability. Clinical tests were conducted on 30 patients in the field, tracking data provided by the sensor from their initial hospitalization to later surgery. And the full rehabilitation of one subject was recorded and analyzed. The test results show that our sensor can dynamically assess knee function in real time and recommend the best timing for return to play, which paves the way for personalized and telerehabilitation.

Abstract As 5G and early‐stage network technologies mature, a wealth of data and experience is accumulated. The ubiquitous sensing and communication network (USCN) can leverage these existing communication infrastructures to maximize resource utilization and reduce the costs of redeployment through integration with modern 6G and beyond 6G networks. However, implementing future integrated sensing and communication (ISAC) functions in USCN may possess different hardware capabilities and communication protocols, presenting significant challenges. This is due to the lack of a unified framework for managing and optimizing these heterogeneous resources, as well as the absence of reasonable performance metrics. This letter proposes a dynamic pricing coordinated resource allocation (DPCRA) mechanism to realize the emerging ISAC in legacy USCNs. The DPCRA is designed to optimize the spectrum efficiency (SE) of USCN and manages resource interactions between heterogeneous devices through price variables, thereby resolving resource conflicts and deadlocks. The novelties include: (1) employing a price mechanism to foster resource cooperation in non‐cooperative networks; (2) introducing an SE metric incorporating an information similarity factor for optimization; (3) dynamically selecting resources to enhance SE. Simulations demonstrate that the DPCRA effectively resolves device deadlock while maintaining high SE levels, promoting device collaboration.

Cisplatin is widely used to treat various solid tumors. However, its toxicity to normal tissues limits its clinical application, particularly due to its ototoxic effects, which can result in hearing loss in patients undergoing chemotherapy. While significant progress has been made in preclinical studies to elucidate the cellular and molecular mechanisms underlying cisplatin-induced ototoxicity (CIO), the precise mechanisms remain unclear. Moreover, the optimal protective agent for preventing or mitigating cisplatin-induced ototoxicity has yet to be identified. This review summarizes the current understanding of the roles of apoptosis, autophagy, ferroptosis, pyroptosis, and protective agents in cisplatin-induced ototoxicity. A deeper understanding of these cell death mechanisms in the inner ear, along with the protective agents, could facilitate the translation of these agents into clinical therapeutics, help identify new therapeutic targets, and provide novel strategies for cisplatin-based cancer treatment.

Mariculture ponds are essential components of the coastal wetland, which are often criticized by eutrophication risk for the dissolved inorganic nitrogen (DIN) input to the coastal zone by the culture tailwater. However, the reduce of this DIN pollution was difficult because the tailwater is hard to collect and the treatment is inefficient and expensive. Sesuvium Portulacastrum is a coastal vegetation which has high efficiency in DIN absorption from the seawater and sediment. In this study, we use Sesuvium Portulacastrum as a tool species to study the control behavior of the DIN in mariculture ponds wetland. The change trend of DIN in pond water and benthic species in pond sediment was investigated. The results showed that Sesuvium Portulacastrum reduced NH4+, NO3-, and NO2- in the pond water by 83.21%, 95.22%, and 91.32%, respectively. The species number of benthic organisms was enhanced from 2 to 5 and the species structure was more optimized in Sesuvium Portulacastrum pond than control pond. At the end of the experiment, eutrophication indicator species (Capitella capitata) was disappeared in the Sesuvium Portulacastrum pond. Those suggest that the coastal vegetation (Sesuvium Portulacastrum) have great potential to eliminate DIN pollutants in mariculture pond wetland.

BackgroundConstitution is a valuable part of traditional Chinese medicine theory; it is defined as the internal foundation for the occurrence, development, transformation and outcome of diseases, and has its characteristic gut microbiota. Previous study showed that deficiency constitution was related to lower Hb counts. However, no research has examined how alterations in the gut microbiome induced by deficiency constitution may increase the tendency for anemia.MethodsWe used a multiomics strategy to identify and quantify taxonomies and compounds found under deficient constitution individuals and further explore the possible pathological factors that affect red blood cell indices.Results① People with deficient constitution showed lower hemoglobin (Hb), more Firmicutes, less Bacteroidetes, and higher α diversity. ② We identified Escherichia coli, Clostridium bolteae, Ruminococcus gnavus, Streptococcus parasanguinis and Flavonifractor plautii as potential biomarkers of deficient constitution. ③ Slackia piriformis, Clostridium_sp_L2_50 and Bacteroides plebeius were enriched in balanced-constitution individuals, and Parabacteroides goldsteinii was the key bacterial marker of balanced constitution. ④ Flavonifractor plautii may be a protective factor against the tendency for anemia among deficient individuals. ⑤ Ruminococcus gnavus may be the shared microbe base of deficiency constitution-related the tendency for anemia. ⑥ The microorganism abundance of the anaerobic phenotype was lower in deficient constitution group. ⑦ Alterations in the microbiome of deficient-constitution individuals were associated with worse health status and a greater risk of anemia, involving intestinal barrier function, metabolism and immune responses, regulated by short-chain fatty acids and bile acid production.ConclusionThe composition of the gut microbiome was altered in people with deficient constitution, which may explain their poor health status and tendency toward anemia.

A new type of lightweight high aluminum bearing steel had been developed based on the widely used high carbon chromium bearing steel. Via multi-scale experimental characterizations and theoretical calculations, here we mainly focused on the evolution of microstructure including precipitates under different quenching temperatures. Accordingly, the mechanical properties, mechanisms and fracture features of the new high-Al steel after tempering were characterized in detail. As austenitizing temperature rose, matrix of steel varied from multiphase structure of martensite, retained austenite (RA) and ferrite to the full martensite and RA. RA was found in all four samples with the austenitizing temperature from 850 °C to 1000 °C. In terms of precipitates, a transformation from M3C to M7C3 were observed. As a phase newly introduced by Al, AlFe3C (κ carbides) would dissolve into matrix at 900 °C. Eventually, the yield strength of the researched steel could reach 1430 MPa with an unnotched impact energy of 35 J. Theoretical results showed that high strength of researched steel was mainly caused by solid solution effect of carbon and high density of dislocation. In terms of toughness and fracture observation, high impact energy was attributed to the highest density of grain boundary, and also, κ carbides were found at the origin of secondary crack. This study highlighted the significant effect of Al addition and quenching process based on the traditional bearing steel, which showed a novel method and idea to reduce significantly the weight of bearings.

Abstract When somatic cells acquire complex karyotypes, they often are removed by the immune system. Mutant somatic cells that evade immune surveillance can lead to cancer. Neurons with complex karyotypes arise during neurotypical brain development, but neurons are almost never the origin of brain cancers. Instead, somatic mutations in neurons can bring about neurodevelopmental disorders, and contribute to the polygenic landscape of neuropsychiatric and neurodegenerative disease. A subset of human neurons harbors idiosyncratic copy number variants (CNVs, “CNV neurons”), but previous analyses of CNV neurons are limited by relatively small sample sizes. Here, we develop an allele-based validation approach, SCOVAL, to corroborate or reject read-depth based CNV calls in single human neurons. We apply this approach to 2,125 frontal cortical neurons from a neurotypical human brain. SCOVAL identifies 226 CNV neurons, which include a subclass of 65 CNV neurons with highly aberrant karyotypes containing whole or substantial losses on multiple chromosomes. Moreover, we find that CNV location appears to be nonrandom. Recurrent regions of neuronal genome rearrangement contain fewer, but longer, genes.

Abstract Background Circular RNAs (circRNAs) play critical roles in the tumorigenesis and radiosensitivity of multiple cancers. Nevertheless, the biological functions of circRNA periostin (circ‐POSTN) in esophageal cancer (EC) progression and radiosensitivity have not been well elucidated. Methods The expression of circ‐POSTN, microRNA‐876‐5p (miR‐876‐5p), and proto‐oncogene tyrosine‐protein kinase (FYN) was analyzed by quantitative reverse transcription PCR (RT‐qPCR). Cell proliferation was assessed by MTT, colony formation, and 5‐ethynyl‐2′‐deoxyuridine (EDU) assays. All protein levels were detected by western blot assay. Cell apoptosis and invasion were assessed by flow cytometry analysis and transwell assay, respectively. Dual‐luciferase reporter and RNA immunoprecipitation (RIP) assays were used to validate the interaction between miR‐876‐5p and circ‐POSTN or FYN. The role of circ‐POSTN in vivo was explored by establishing mice xenograft model. Results Circ‐POSTN was overexpressed in EC tissues and cells. Knockdown of circ‐POSTN inhibited cell proliferation and invasion and elevated apoptosis and radiosensitivity in EC cells. MiR‐876‐5p was a direct target of circ‐POSTN, and its knockdown reversed the role of sh‐circ‐POSTN in EC cells. FYN was a direct target of miR‐876‐5p, and FYN elevation weakened the effects of miR‐876‐5p overexpression on the progression and radiosensitivity of EC cells. Moreover, circ‐POSTN acted as a miR‐876‐5p sponge to regulate FYN expression. Circ‐POSTN interference also suppressed tumor growth and enhanced radiosensitivity in vivo. Conclusion Circ‐POSTN knockdown inhibited proliferation and invasion, but increased apoptosis and enhanced radiosensitivity in EC cells via modulating miR‐876‐5p/FYN axis, which might be a potential diagnostic and therapeutic target for EC.

This study aims to investigate the impact of metacognitive strategy on students’ Chinese speaking skills development by using students’ self-assessments and teacher comments to cultivate students’ capacity in metacognition. Stratified sampling was adopted in this research; a total of 36 junior school sample students (17 students from Grade 8, 19 students from Grade 9) from Sacred Heart College Chiangmai who were learning Chinese as a foreign language (CFL) participated in this study. In order to explore the application and impact of metacognitive strategy, teaching intervention was conducted during the research process including pre-test, oral Chinese activities implementation with metacognitive training strategies, building up students’ metacognitive learning ability by students’ self-assessments and teacher comments, post-test. Content analysis was applied to analyze the students’ self-assessments to recognize their metacognitive learning ability and explore their distribution of the metacognitive learning acts. The results revealed that students could apply the MLC (Metacognitive Learning Cycle) model to conduct metacognitive learning, however, a stronger emphasis was placed on the monitoring strategy. Paired Samples T-Test was adopted to analyze data in the pre-test and post-test score and the result showed that the post-test mean scores (M=13.25) of students’ oral Chinese activities significantly improved compared to the pre-test mean scores (M=11.58), and is statistically significant difference (t=7.77, p

Abstract Background To investigate the potential of Native T1-mapping in predicting the prognosis of patients with chronic kidney disease (CKD). Methods We enrolled 119 CKD patients as the study subjects and included 20 healthy volunteers as the control group, with follow-up extending until October 2022. Out of these patients, 63 underwent kidney biopsy measurements, and these patients were categorized into high (25–50%), low (

Abstract Background Blood stasis constitution in traditional Chinese medicine (TCM) is believed to render individuals more susceptible to metabolic diseases. However, the biological underpinnings of this constitutional imbalance remain unclear. Methods This study explored the association between blood stasis constitution, serum metabolic markers including uric acid (UA), high-density lipoprotein cholesterol (HDLC), their ratio (UHR), serum metabolites, and gut microbiota. Clinical data, fecal and serum samples were acquired from 24 individuals with a blood stasis constitution and 80 individuals with a balanced constitution among healthy individuals from Guangdong. Gut microbiota composition analysis and serum metabolomics analysis were performed. Results Females with a blood stasis constitution had higher UA levels, lower HDLC levels, and higher UHR in serum, suggesting a higher risk of metabolic abnormalities. Analysis of the gut microbiome revealed two distinct enterotypes dominated by Bacteroides or Prevotella. Intriguingly, blood stasis subjects were disproportionately clustered within the Bacteroides-rich enterotype. Metabolomic analysis identified subtle differences between the groups, including lower phenylalanine and higher trimethylaminoacetone levels in the blood stasis. Several differential metabolites displayed correlations with HDLC, UA, or UHR, unveiling potential new markers of metabolic dysregulation. Conclusions These findings elucidate the intricate interplay between host constitution, gut microbiota, and serum metabolites. The concept of blood stasis offers a unique perspective to identify subtle alterations in microbiome composition and metabolic pathways, potentially signaling underlying metabolic vulnerability, even in the presence of ostensibly healthy profiles. Continued investigation of this TCM principle may reveal critical insights into the early biological processes that foreshadow metabolic deterioration.

Abstract Patients with lymphangioleiomyomatosis (LAM) are considered high risk for most surgeries and require specific anesthetic considerations mainly because of the common spontaneous pneumothorax (PTX). To explore whether intraoperative mechanical ventilation could increase the risk of PTX in those patients, we included 12 surgical patients with LAM in this study, of whom four (33.3%) experienced postoperative PTX. According to our results, patients with higher CT grade, poorer pulmonary function, and a history of preoperative PTX might be more likely to develop postoperative PTX. However, intraoperative mechanical ventilation did not show obvious influence, which might help clinicians reconsider the perioperative management of LAM patients.

Antibiotic resistance in soil introduced by organic fertilizer application pose a globally recognized threat to human health. Insect organic fertilizer may be a promising alternative due to its low antibiotic resistance. However, it is not yet clear how to regulate soil microbes to reduce antibiotic resistance in organic fertilizer agricultural application. In this study, we investigated soil microbes and antibiotic resistome under black soldier fly organic fertilizer (BOF) application in pot and field systems. Our study shows that BOF could stimulate ARB (antibiotic resistant − bacteria) − suppressive Bacillaceae in the soil microbiome and reduce antibiotic resistome. The carbohydrate transport and metabolism pathway of soil Bacillaceae was strengthened, which accelerated the synthesis and transport of polysaccharides to form biofilm to antagonistic soil ARB, and thus reduced the antibiotic resistance. We further tested the ARB − suppressive Bacillus spp. in a microcosm assay, which resulted in a significant decrease in the presence of ARGs and ARB together with higher abundance in key biofilm formation gene (epsA). This knowledge might help to the development of more efficient bio-fertilizers aimed at mitigating soil antibiotic resistance and enhancing soil health, in particular, under the requirements of global “One Health”.

Leonurine is an alkaloid unique to the Leonurus genus, which has many biological activities, such as uterine contraction, anti-inflammation, anti-oxidation, regulation of cell apoptosis, anti-tumor, angiogenesis, anti-platelet aggregation, and inhibition of vasoconstriction. This paper summarizes the extraction methods, synthetic pathways, biosynthetic mechanisms, pharmacokinetic properties, pharmacological effects in various diseases, toxicology, and clinical trials of leonurine. To facilitate a successful transition into clinical application, intensified efforts are required in several key areas: structural modifications of leonurine to optimize its properties, comprehensive pharmacokinetic assessments to understand its behavior within the body, thorough mechanistic studies to elucidate how it works at the molecular level, rigorous safety evaluations and toxicological investigations to ensure patient wellbeing, and meticulously conducted clinical trials to validate its efficacy and safety profile.

Abstract Water evaporation–induced electricity generators (WEGs) are regarded as one of the most promising solutions for addressing the increasingly severe environmental pollution and energy crisis. Owing to the potential carbon emission in the preparation process of WEGs, whether WEG represents a clean electricity generation technology is open to question. Here, a brand‐new strategy is proposed for manufacturing negative carbon emission WEG (CWEG). In this strategy, the microalgae film is used as the electricity generation interface of WEG, which achieves a stable open‐circuit voltage (Voc) of 0.25 V and a short‐circuit current (Isc) of 3.3 µA. Since microalgae can capture carbon dioxide during its growing process, CWEG holds great promise to generate electricity without carbon emissions in the full life cycle compared with other WEGs. To the best of the author's knowledge, this is the first work using microalgae films to fabricate WEG. Therefore, it is believed that this work not only provides a new direction for designing high‐efficiency and eco‐friendly WEG but also offers an innovative approach to the resource utilization of microalgae.

The leakage from submarine gas pipelines presents a significant threat to marine ecological environments. Bubble plumes can be formed when gas escapes, which can give rise to the distinctive fountain phenomenon by interacting with the water surface. It is imperative to understand the factors that influence the physical dimensions and temporal characteristics of the resulting fountain to elucidate the formation mechanism of this phenomenon. Gas leakage experiments under various conditions are conducted to investigate the dynamic characteristics of the fountain in the study. The findings reveal the following: The initial kinetic energy of the escaping gas varies significantly under different leakage scenarios, resulting in the positive correlation between the maximum fountain height and width, as well as the leakage pressure and diameter of the leakage hole. Then, the analysis of dimensional indicates that the dynamic equilibrium of the bubbles is intricately tied to both the Froude number (Fr) and Reynolds number (Re). Notably, the effect of leakage pressure on Fr and Re follows similar patterns. However, the trends of Fr and Re values across varying leak hole diameters are opposite. At last, the frequency analysis of the time series data related to the fountain height demonstrates that higher leakage pressure and larger leak hole diameters result in an increase in both the main frequency and bandwidth. The research results offer valuable insights for evaluating the impact of gas leakage intensity on the marine environment by analyzing the size parameters of fountain.

Abstract Transmembrane transport analysis is essential for understanding cell physiological processes. Based on an artificial simulation of internal and external cellular environment, this paper introduces an innovative approach to investigate the microscopic behavior of small molecules through porin protein under mechanical curvature of lipid membrane. A flexible device system is developed, enabling quantitative electronic transmembrane analysis. The key transistor comprises a flexible, microporous electrode covered with the support lipid bilayers (SLBs) to mimic artificial cellular membrane, serving as an extended gate of the field‐effect transistor (FET). The transmembrane behaviors of charged ions and small molecules can be effectively monitored in real time by this FET‐based flexible device system. The flexibility of the electrode allows analyzing the transmembrane behavior under different mechanical bends. In this study, the developed flexible device is employed for the first time to simulate the mechanical bending of cellular membrane embedded with channel proteins and to monitor the transmembrane behavior of small molecules, thus providing a more authentic representation of membrane protein at a curved state. This approach holds the potential to contribute as a platform‐based technological advancement, supporting research into toxicological mechanisms and facilitating drug screening endeavors.

Species diversity and functional diversity indices reflect the variations of community structure and their responses to environmental stress. This study clarifies the biodiversity of macroinvertebrates in the Jingui River of Shenzhen and their response to the aquatic environment across different seasons. Utilizing ten functional traits, we conducted a seasonal survey at ten sampling points to examine changes in macroinvertebrate species and functional diversity, along with their relationships with environmental variables in the JGR. The results of the study demonstrated that the species and functional diversity of macroinvertebrates were significantly affected by season. Redundancy analysis indicated that water velocity, hydrogen ion concentration, turbidity, water depth, and total nitrogen were the most important factors for macroinvertebrate functional diversity. Moreover, structural equation modeling demonstrated that seasonal variations in total nitrogen, ammonia nitrogen, nitrate nitrogen, conductivity, water velocity, and hydrogen ion concentration directly or indirectly impacted the species diversity and functional diversity of macroinvertebrates. This study provides valuable information into the seasonal variation characteristics of macroinvertebrate communities, contributing to a more comprehensive understanding of biodiversity crucial for maintaining river ecosystem functioning and stability.

As the complexity of autonomous vehicles (AVs) continues to increase and artificial intelligence algorithms are becoming increasingly ubiquitous, a novel safety concern known as the safety of the intended functionality (SOTIF) has emerged, presenting significant challenges to the widespread deployment of AVs. SOTIF focuses on issues arising from the functional insufficiencies of the AVs’ intended functionality or its implementation, apart from conventional safety considerations. From the systems engineering standpoint, this study offers a comprehensive exploration of the SOTIF landscape by reviewing academic research, practical activities, challenges, and perspectives across the development, verification, validation, and operation phases. Academic research encompasses system-level SOTIF studies and algorithm-related SOTIF issues and solutions. Moreover, it encapsulates practical SOTIF activities undertaken by corporations, government entities, and academic institutions spanning international and Chinese contexts, focusing on the overarching methodologies and practices in different phases. Finally, the paper presents future challenges and outlook pertaining to the development, verification, validation, and operation phases, motivating stakeholders to address the remaining obstacles and challenges.

Spectral efficiency (SE) and energy efficiency (EE) are two main metrics for the transmit design in Visible Light Communications (VLC). However, the SE-optimal and EE-optimal strategies may be in conflict with each other to some extent. In this paper, we investigate the the tradeoff between EE and SE in rate splitting multiple access (RSMA)-aided VLC systems to maximize the system resource efficiency (RE) taking both perfect and imperfect channel state information (CSI) into consideration. For the scenarios with perfect CSI, we explore the joint precoding design and common rate allocation to maximize the RE of RSMA-aided VLC systems under the constraints of quality of service (QoS) and linear operation region (LoR) of LED, and propose a primal-dual-gradient-based precoding strategy. Furthermore, in the presence of CSI estimation errors, we propose a worst-case robust precoding design by exploiting quadratic transform and $\mathcal {S}$-Procedure. Numerical results indicate that the proposed resource efficient RSMA algorithm achieves the tradeoff between EE and SE.

Solar-driven CO2-to-fuel conversion assisted by another major greenhouse gas CH4 is promising to concurrently tackle energy shortage and global warming problems. However, current techniques still suffer from drawbacks of low efficiency, poor stability, and low selectivity. Here, a novel nanocomposite composed of interconnected Ni/MgAlOx nanoflakes grown on SiO2 particles with excellent spatial confinement of active sites is proposed for direct solar-driven CO2-to-fuel conversion. An ultrahigh light-to-fuel efficiency up to 35.7%, high production rates of H2 (136.6 mmol min−1g−1) and CO (148.2 mmol min−1g−1), excellent selectivity (H2/CO ratio of 0.92), and good stability are reported simultaneously. These outstanding performances are attributed to strong metal-support interactions, improved CO2 absorption and activation, and decreased apparent activation energy under direct light illumination. MgAlOx@SiO2 support helps to lower the activation energy of CH* oxidation to CHO* and improve the dissociation of CH4 to CH3* as confirmed by DFT calculations. Moreover, the lattice oxygen of MgAlOx participates in the reaction and contributes to the removal of carbon deposition. This work provides promising routes for the conversion of greenhouse gasses into industrially valuable syngas with high efficiency, high selectivity, and benign sustainability.

Abstract Background Although non-invasive radiological techniques are widely applied in kidney renal clear cell carcinoma (KIRC) diagnosis, more than 50% of KIRCs are detected incidentally during the diagnostic procedures to identify renal cell carcinoma (RCC). Thus, sensitive and accurate KIRC diagnostic methods are required. Therefore, in this study, we aimed to identify KIRC-associated microRNAs (miRNAs). Methods This three-phase study included 224 participants (112 each of patients with KIRC and healthy controls (NCs)). RT-qPCR was used to evaluate miRNA expression in KIRC and NC samples. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used to predict the usefulness of serum miRNAs in KIRC diagnosis. In addition, we performed survival and bioinformatics analyses. Results We found that miR-1-3p, miR-129-5p, miR-146b-5p, miR-187-3p, and miR-200a-3p were significantly differentially expressed in patients with KIRC. A panel consisting of three miRNAs (miR-1-3p, miR-129-5p, and miR-146b-5p) had an AUC of 0.895, ranging from 0.848 to 0.942. In addition, using the GEPIA database, we found that the miRNAs were associated with CREB5. According to the survival analysis, miR-146b-5p overexpression was indicative of a poorer prognosis in patients with KIRC. Conclusions The identified three-miRNA panel could serve as a non-invasive indicator for KIRC and CREB5 as a potential target gene for KIRC treatment.

Artificial Intelligence (AI) has gained significant attention and extensive research across various fields in recent years. In the realm of wireless communication, researchers are exploring the use of AI to facilitate various physical layer (PHY) procedures. Within the standardization efforts of the Third Generation Partnership Project (3GPP), one prominent direction being explored is AI-based beam management (BM). The primary objective is to harness AI techniques for predicting optimal beams, thereby reducing measurement overhead and latency. This paper aims to discuss the progress made in AI-based beam management within the Release 18 standardization. Furthermore, through our research, we have identified the mobile speed of user equipment (UE) as a crucial factor that impacts the optimal time window size for collecting input data in AI models. We have observed an inverse correlation between UE speed and the time window size. Accordingly, to mitigate unnecessary measurement overhead and latency, we propose that the determination of the time window size for input data collection should be based on the UE speed. Additionally, we will present our simulation results and provide a comprehensive analysis of this relationship.

This paper investigates the application of artificial intelligence (AI) to wireless technology, specifically in the context of beam management (BM) in the advanced 5th-generation (5G) communication system. Our focus lies in aligning our study with the ongoing discussions within the Third Generation Partnership Project (3GPP) as of December 2022. Instead of evaluating the performance of specific AI models, we take user equipment (UE) receiver (Rx) beam prediction as an illustrative example of AI-based BM. We explore various aspects of AI model management, including model selection, monitoring, and activation/deactivation operations, from a 3GPP perspective. For model selection, we propose deploying distinct AI models for different propagation environments, categorized based on base station (BS) transmitter (Tx) beam measurement results. Reference Signal Received Power (RSRP) serves as a pivotal key performance index (KPI) for model performance monitoring. Our simulation results indicate that, instead of training one all-encompassing AI model with numerous layers for universal application, transitioning between domain-specific AI models with fewer layers yields superior performance. Model activation/deactivation procedures determine whether AI-based BM or traditional BM should be employed in a given scenario. We also introduce the use of AI for predicting the performance of both AI-based BM and traditional BM. By comparing the performance of these strategies, we can ascertain whether link performance degradation results from AI output errors or UE movement into challenging propagation environments. This approach enables the effective management of model switching between AI-based BM and traditional BM. The simulation shows that we can reduce the number of unnecessary switches by 10%.

The solid-state metal battery with solid-state electrolytes has been considered the next generation of energy storage technology owing to its superior safety and high energy density. But, unfavorable ionic conductivity and interfacial problems make it difficult to widely use in practice. In this work, Si3N4 was rationally introduced into the NASICON matrix as a sintering aid, and the influence of Si3N4 on the crystal phase, microstructure, electrochemical and electrical performance of Na3Zr2Si2PO12 (NZSP) ceramic was systematically studied. The results demonstrate that the introduction of Si3N4 can effectively lower the densification sintering temperature of Na3Zr2Si2PO12 electrolyte and enhance the room temperature ionic conductivity of the NZSP to 3.82 × 10−4 S cm−1. In addition, since Si3N4 has a high thermal conductivity and can inhibit the transmission of electrons between the grains of the electrolyte matrix, it will effectively hinder the generation of sodium metal dendrites and relieve the concentration of the heat source. Moreover, owing to the desirable interface compatibility of the Na and NZSP-Si3N4 electrolyte, the Na/NZSP-1150-1%Si3N4/Na symmetric battery exhibits excellent stability, and the electrode/electrolyte interface still maintains good integrity even after long-term cycling. The assembled Na/NZSP-1150-1%Si3N4/Na3.5V0.5Mn0.5Fe0.5Ti0.5(PO4)3 cell manifests an initial specific capacity of 152.5 mA h g−1, together with an initial Coulombic efficiency of 99.8%. Furthermore, after 200 cycles, the battery displays a capacity retention rate of 82%.

Existing antithrombotic drugs have side effects such as bleeding, and there is an urgent need to discover antithrombotic drugs with better efficacy and fewer side effects. In this study, a zebrafish thrombosis model was used to evaluate the antithrombotic activity and mechanism of Brevianamide F, a deep-sea natural product, with transcriptome sequencing analysis, RT-qPCR analysis, and molecular docking. The results revealed that Brevianamide F significantly attenuated the degree of platelet aggregation in the thrombus model zebrafish, leading to an increase in the number of circulating platelets, an augmentation in the return of blood to the heart, an elevated heart rate, and a significant restoration of caudal blood flow velocity. Transcriptome sequencing and RT-qPCR validation revealed that Brevianamide F may exert antithrombotic effects through the modulation of the MAPK signaling pathway and the coagulation cascade reaction. Molecular docking analysis further confirmed this result. This study provides a reference for the development of therapeutic drugs for thrombosis.

Background: Prostate cancer (PCa) is one of the most prevalent malignancies affecting the male life cycle. The incidence and mortality of prostate cancer are also increasing every year. Detection of MicroRNA expression in serum to diagnose prostate cancer and determine prognosis is a very promising non-invasive modality.Materials and method: A total of 224 study participants were included in our study, including 112 prostate cancer patients and 112 healthy adults. The experiment consisted of three main phases, namely, the screening phase, the testing phase, and the validation phase. The expression levels of serum miRNAs in patients and healthy adults were detected using quantitative reverse transcription-polymerase chain reaction. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to evaluate the diagnostic ability, specificity, and sensitivity of the candidate miRNAs.Result: Eventually, three miRNAs most relevant to prostate cancer diagnosis were selected, namely, miR-106b-5p, miR-129-1-3p and miR-381-3p. We used these three miRNAs to construct a diagnostic panel with very high diagnostic potential for prostate cancer, which had an AUC of 0.912 [95% confidence interval (CI): 0.858 to 0.950; p < 0.001; sensitivity = 91.67%; specificity = 79.76%]. In addition, the three target genes (DTNA, GJB1, and TRPC4) we searched for are also expected to be used for prostate cancer diagnosis and treatment in the future.

Development of a micromodel that recapitulates multiple mechanical properties to mimic the complex mechanical microenvironment is crucial for cell‐based research. Herein, a microsystem combining structure of hydrogel matrix and acoustic streaming (AS) to mimic the cellular microenvironment is proposed, which can realize multiplex cellular mechanical cues, including matrix stiffness, fluid shear stress (FSS) generated by AS, and matrix roughness. The results demonstrate that the cell spreading area enlarges with the increase of matrix stiffness, and cell spreading is encouraged by integrin β1 cluster to polymerize actin when combines the hydrogel matrix with FSS. In addition, FSS has the influence on the roughness of the hydrogel, which further affects the cell morphology and mechanical properties, inducing mesenchymal stem cells (MSCs) differentiation into astrocytes rapidly. Meanwhile, cell migration is also enhanced by FSS stimulation, particularly, undifferentiated cells at 22 kPa hydrogel have the fastest migration speed, and change the movement model from contact inhibition to contact stimulation migration. Especially, matrix roughness and stiffness dominantly control of cell spreading and differentiation, whereas FSS affects cell migration. In conclusion, the microsystem in this work shows superior performance in regulating the spreading, differentiation, and migration of MSCs, which provides a new tool for cell‐microenvironment study.

Methamphetamine is a potent and highly addictive neurotoxic psychostimulant that triggers a spectrum of adverse emotional responses during withdrawal. G-protein coupled receptor 55 (GPR55), a novel endocannabinoid receptor, is closely associated with mood regulation. Herein, we developed a murine model of methamphetamine-induced anxiety- and depressive-like behavior during abstinence which showed a decreased GPR55 expression in the hippocampus. Activation of GPR55 mitigated these behavioral symptoms, concomitantly ameliorating impairments in hippocampal neurogenesis and reducing neuroinflammation. These findings underscore the pivotal role of GPR55 in mediating the neuropsychological consequences of methamphetamine withdrawal, potentially via mechanisms involving the modulation of hippocampal neurogenesis and inflammation.

Antimicrobial resistance (AMR) is commonly associated with the inappropriate use of antibiotics during meat-rabbit production, posing unpredictable risks to rabbit welfare and public health. However, there is limited research on the epidemiological dynamics of antibiotic resistance among bacteria indicators derived from local healthy meat-rabbits. To bridge the knowledge gap between antibiotic use and AMR distribution, a total of 75 Escherichia coli (E. coli) and 210 Enterococcus spp. strains were successfully recovered from fecal samples of healthy meat-rabbits. The results revealed that diverse AMR phenotypes against seven commonly used antimicrobials, including ampicillin (AMP), amoxicillin-clavulanic acid (A/C), doxycycline (DOX), enrofloxacin (ENR), florfenicol (FFC), gentamicin (GEN), and polymycin B (PMB), were observed among most strains of E. coli and Enterococcus spp. in two rabbit farms, although the distribution pattern of antibiotic resistance between young and adult rabbits was similar. Among them, 66 E. coli strains showed resistance against 6 antimicrobials except for PMB. However, 164 Enterococcus spp. strains only exhibited acquired resistance against DOX and GEN. Notably, the DOX-based AMR phenotypes for E. coli and Enterococcus spp. strains were predominant, indicating the existing environmental stress conferred by DOX exposure. The MICs tests suggested elevated level of antibiotic resistance for resistant bacteria. Unexpectedly, all GEN-resistant Enterococcus spp. strains resistant high-level gentamicin (HLGR). By comparison, the blaTEM, tetA, qnrS and floR were highly detected among 35 multi-resistant E. coli strains, and aac[6']-Ie-aph[2']-Ia genes widely spread among the 40 double-resistant Enterococcus spp. strains. Nevertheless, the presence of ARGs were not concordant with the resistant phenotypes for a portion of resistant bacteria. In conclusion, the distribution of AMR and ARGs are prevalent in healthy meat-rabbits, and the therapeutic antimicrobials use in farming practice may promote the antibiotic resistance transmission among indicator bacteria. Therefore, periodic surveillance of antibiotic resistance in geographic locations and supervisory measures for rational antibiotic use are imperative strategies for combating the rising threats posed by antibiotic resistance, as well as maintaining rabbit welfare and public health.

Water-saving irrigation is becoming more important in the upper Yellow River basin (YRB) due to reduced water allocation and growing water scarcity. However, drip irrigation as an efficient irrigation method, has not gained as much acceptance as one might expect. In this study, integrated approaches involving field experiments, agro-ecosystem modeling, and financial analysis were proposed to evaluate the multiple benefits of two irrigation methods. Field experiments on maize irrigated with border irrigation and drip irrigation under plastic mulching (i.e., BI-M and DI-M) were conducted in the Hetao Irrigation District (Hetao) of the upper YRB during 2021 and 2022. The AHC model was calibrated and validated using two-year experimental data, performing well in simulations of soil water-salt-nitrogen (N) dynamics and crop growth. An irrigation scheduling module was newly incorporated into AHC. Then the model was applied to analyze scenarios consisting of three classes of groundwater depth (GWD) and five N application levels. Optimal irrigation and N-fertilization strategies were suggested; and DI-M showed significant advantages over BI-M in terms of water-saving (56–66 mm), labor-saving, environmental benefits (50 kg ha−1 less N fertilizer and 19–25 kg ha−1 less N loss), and crop yields (

The outbreak of the COVID-10 variant Omicron epidemic in Shanghai in 2022 had a huge impact on residents' food security. This study examines the roles, challenges, and sustainability of online community group food purchasing by analyzing survey data collected from 1168 households in Shanghai between March and May 2022, in the aftermath of COVID-19. This study demonstrates that online community group food purchasing played a crucial role in ensuring residents' food access and food security during the pandemic. However, this study also reveals that residents expressed concerns about the risk of epidemic transmission, food safety, increased prices, and difficulty in safeguarding rights. Only 21.5 % of residents are willing to continue using online community group purchasing. Based on the above conclusions, this study offers some suggestions.

LA, one of important phenolic acids of health food Salvia miltiorrhiza Bge. and Crocus sativus L. (Saffron) has defined proangiogenic effect. However, the mechanisms of its proangiogenic effect are unknow. The present study aimed to further evaluate the proangiogenic effect of LA and to explore the potential mechanisms. The results showed that LA restored the length of PTK787-damaged intersegmental vessels (ISVs) and promoted the germination of subintestinal vessels (SIVs) in zebrafish. LA promoted the proliferation and migration of HUVECs under VRI-inhibited and normal conditions. The results of network pharmacology, transcriptomics, and molecular docking showed that ALB, AKT1, EGFR, SRC, and MMP9 were key targets for LA to promote angiogenesis. KEGG enrichment analysis and qPCR analysis showed that LA promoted angiogenesis by regulating the VEGF, PI3K-Akt and MAPK pathways. These results indicated that LA has proangiogenic effects both in vitro and in vivo by regulating the VEGF, PI3K-Akt and MAPK pathways.

This paper presents the design, fabrication, and characterization of cantilever-type resonators with a novel stacked structure. Aluminum nitride is adopted as the material for both the structural layer and the piezoelectric layer; this simplifies the fabrication process and improves the quality factor of the resonator. Both in-plane and out-of-plane flexural modes were investigated. The effect of the structural dimensions and electrode patterns on the resonator’s performance were also studied. Finite-element simulations and experiments examining anchor loss and thermoelastic damping, which are the main loss mechanisms affecting the quality factor of these resonators, were carried out. The optimal structural dimensions and electrode patterns of the cantilever-type resonators are presented. A quality factor of 7922 with a motional impedance of 88.52 kΩ and a quality factor of 8851 with a motional impedance of 67.03 kΩ were achieved for the in-plane and out-of-plane flexural-mode resonators, respectively. The proposed resonator design will contribute to the development of high-performance devices such as accelerometers, gyroscopes, and pressure sensors.

Background: Myoprotein degradation accelerates in obese individuals, resulting in a decline in muscular mass. Atg7 plays a crucial role in regulating protein stability and function through both autophagy-dependent and independent pathways. As obesity progresses, the expression of Atg7 gradually rises in muscle tissue. Nonetheless, the precise impact and mechanism of Atg7 in promoting muscle mass decline in obesity remain uncertain. The study aimed to elucidate the role and underly mechanism of Atg7 action in the context of obesity-induced muscle mass decline. Methods: In this study, we established a murine model of high-fat diet-induced obesity (DIO) and introduced adeno-associated virus delivery of short hairpin RNA to knock down Atg7 (shAtg7) into the gastrocnemius muscle. We then examined the expressions of Atg7 and myoprotein degradation markers in the gastrocnemius tissues of obese patients and mice using immunofluorescence and western blotting techniques. To further investigate the effects of Atg7, we assessed skeletal muscle cell diameter and the myoprotein degradation pathway in C2C12 and HSkMC cells in the presence or absence of Atg7. Immunofluorescence staining for MyHC and western blotting were utilized for this purpose. To understand the transcriptional regulation of Atg7 in response to myoprotein degradation, we conducted luciferase reporter assays and chromatin immunoprecipitation experiments to examine whether FoxO3a enhances the transcription of Atg7. Moreover, we explored the role of Akt in Atg7-mediated regulation and its relevance to obesity-induced muscle mass decline. This was accomplished by Akt knockdown, treatment with MK2206, and GST pulldown assays to assess the interaction between Atg7 and Akt. Results: After 20 weeks of being on a high-fat diet, obesity was induced, leading to a significant decrease in the gastrocnemius muscle area and a decline in muscle performance. This was accompanied by a notable increase in Atg7 protein expression (p

Objective: Setting tetrahydropalmatine as an internal reference, to establish a quantitative analysis of multi-components by single marker (QAMS) method for the determination of five alkaloids contents in vinegar Corydalis yanhusuo. Method: HPLC was employed using gradient elution with a mobile phase consisting of acetonitrile-water (containing 0.1% phosphoric acid, pH6.0). The methodological investigation was conduct to estalish a proper method. According to the relationship between the content and the chromatographic peak area of each component, calculated the relative correction factors (RCF) of protopine, palmatine hydrochloride, berberine hydrochloride and corydaline to tetrahydropalmatine. And then, the contents of five alkaloid components were determined in the various samples. Meanwhile, external standard method (ESM) was used to determine the contents. The variation in the results obtained from QAMS and RCF was statistically analyzed to confirm the precision and practicability of QAMS. Results: The linear relationship between the five alkaloids was good in a certain linear range, and the precision, stability, and repeatability met the required standards. The average recovery ranged from 98.38% to 101.28%. The RCF values of protopine, palmatine hydrochloride, berberine hydrochloride, and corydaline to tetrahydropalmatine were 0.405, 1.868, 1.571, and 1.049, respectively. There was no significant difference in the content of the five alkaloids measured by QAMS and ESM in 10 batches of processed Corydalis yanhusuo from different regions after vinegar processing. Conclusion: The developed QAMS method in this study could be effectively used for the quantitative analysis of five alkaloid components in vinegar Corydalis yanhusuo. The results were highly accurate and the method was considered feasible. This method could be served as a valuable reference for the quality evaluation of raw and processed products of TCM, containing alkaloids or multi-indicator components.

Abstract Current diagnosis of glioma types requires combining both histological features and molecular characteristics, which is an expensive and time-consuming procedure. Determining the tumor types directly from whole-slide images (WSIs) is of great value for glioma diagnosis. This study presents an integrated diagnosis model for automatic classification of diffuse gliomas from annotation-free standard WSIs. Our model is developed on a training cohort (n = 1362) and a validation cohort (n = 340), and tested on an internal testing cohort (n = 289) and two external cohorts (n = 305 and 328, respectively). The model can learn imaging features containing both pathological morphology and underlying biological clues to achieve the integrated diagnosis. Our model achieves high performance with area under receiver operator curve all above 0.90 in classifying major tumor types, in identifying tumor grades within type, and especially in distinguishing tumor genotypes with shared histological features. This integrated diagnosis model has the potential to be used in clinical scenarios for automated and unbiased classification of adult-type diffuse gliomas.

Abstract Background The presence of Staphylococcus aureus in the bloodstream can lead to the development of sepsis; however, the severity and risk factors of the systemic inflammatory response to Staphylococcus aureus bloodstream infections were unclear. This study is aimed to build a model to predict the risk of sepsis in children with Staphylococcus aureus bloodstream infections. Methods A retrospective analysis of hospitalized pediatric patients diagnosed with Staphylococcus aureus bloodstream infections was performed between January 2013 and December 2019. Each patient was assessed using the pediatric version of the Sequential Organ Failure Assessment score (pSOFA) within 24 h of blood culture collection. A nomogram based on logistic regression models was constructed to predict the risk factors for sepsis in children with Staphylococcus aureus bloodstream infections. It was validated using the area under the receiver-operating characteristic curve (AUC). Results Of the 94 patients included in the study, 35 cases (37.2%) developed sepsis. The pSOFA scores ranged from 0 to 8, with 35 patients having a pSOFA score of ≥ 2. Six children (6.4%) died within 30 days, who were all from the sepsis group and had different pSOFA scores. The most common organs involved in sepsis in children with staphylococcal bloodstream infections were the neurologic system (68.6%), respiratory system (48.6%), and coagulation system (45.7%). Hospital-acquired infections (adjusted odds ratio [aOR], 3.0; 95% confidence interval [CI], 1.3–7.2), implanted catheters (aOR, 10.4; 95% CI, 3.8–28.4), procalcitonin level ≥ 1.7 ng/mL (aOR, 15.4; 95% CI, 2.7–87.1), and underlying diseases, especially gastrointestinal malformations (aOR, 14.0; 95% CI, 2.9–66.7) were associated with Staphylococcus aureus sepsis. However, methicillin-resistant Staphylococcus aureus infection was not a risk factor for sepsis. The nomogram had high predictive accuracy for the estimation of sepsis risk, with an AUC of 0.85. Conclusions We developed a predictive model for sepsis in children with Staphylococcus aureus infection.

Abstract Straw returning has been demonstrated as a beneficial approach for the utilization of renewable biomass source, which contributes to reducing environmental pollution and strengthening the sustainability of agriculture. However, information on how microorganisms respond to different straw return modes (SRMs) at varying nitrogen fertilizer levels (NFLs) in the black soil is still limited. The community composition, network pattern, and modular function of bacteria and fungi are investigated under three SRMs, including straw removal (CK), crushed straw incorporation (SD), and biochar incorporation (BC) at three NFLs (0, 144, and 240 kg N ha−1, respectively) mainly using Illumina MiSeq technique based on a long‐term maize field experiment. Results showed that bacterial richness, diversity, and fungal richness decreased with NFL reduction. However, these decreases can be compensated by SD and BC, demonstrating superiority for BC at reduced NFLs. SD and BC differed in their effects on the bacterial and fungal abundances (showing increments only in SD) and fungal Shannon diversity (remaining stable only in BC irrespective of NFLs). Microbial communities were substantially affected by SRMs and interacted with NFLs, which were driven by soil NH4+‐N, available potassium, total nitrogen, and pH. In addition, SD induced a network characterized by its highly complex (average degree 10.259 vs. 3.364) and stable structure (average clustering coefficient 0.503 vs. 0.239), Ascomycota as predominating keystone taxa, and abundant N‐cycling related bacteria, while BC formed a network comprising a superior modular structure (modularity 2.599 vs. 0.912), dominant symbiotic fungi, and soil bulk density as specific shaping factor, indicating that network pattern, keystone taxa, modular function, and determining factors shifted between SD and BC co‐occurrence networks. These results deepen insights into the response divergence of bacteria and fungi to SRMs and NFLs, providing a scientific basis for selecting the suitable strategy for sustainable straw utilization in the black soil area.

Abstract Background We aimed to develop machine learning models for prediction of molecular subgroups (low-risk group and intermediate/high-risk group) and molecular marker (KIAA1549-BRAF fusion) of pediatric low-grade gliomas (PLGGs) based on radiomic features extracted from multiparametric MRI. Methods 61 patients with PLGGs were included in this retrospective study, which were divided into a training set and an internal validation set at a ratio of 2:1 based on the molecular subgroups or the molecular marker. The patients were classified into low-risk and intermediate/high-risk groups, BRAF fusion positive and negative groups, respectively. We extracted 5929 radiomic features from multiparametric MRI. Thereafter, we removed redundant features, trained random forest models on the training set for predicting the molecular subgroups or the molecular marker, and validated their performance on the internal validation set. The performance of the prediction model was verified by 3-fold cross-validation. Results We constructed the classification model differentiating low-risk PLGGs from intermediate/high-risk PLGGs using 4 relevant features, with an AUC of 0.833 and an accuracy of 76.2% in the internal validation set. In the prediction model for predicting KIAA1549-BRAF fusion using 4 relevant features, an AUC of 0.818 and an accuracy of 81.0% were achieved in the internal validation set. Conclusions The current study demonstrates that MRI radiomics is able to predict molecular subgroups of PLGGs and KIAA1549-BRAF fusion with satisfying sensitivity. Trial registration This study was retrospectively registered at clinicaltrials.gov (NCT04217018).

Abstract Background The development of periodontal disease is closely linked to individual oral healthcare behaviors. This study aimed to investigate the knowledge, attitude, and practice (KAP) toward the self-control of dental plaque among patients with periodontal diseases. Methods This cross-sectional study was conducted at Jinan Stomatological Hospital between July 2022 and September 2022 through a self-administrated questionnaire for patients with periodontal diseases. Results A total of 563 participants were included. Among them, 147 (26.11%) had gingivitis and 416 (73.89%) had periodontitis. Participants' knowledge, attitude, and practice scores were 8.71 ± 2.81 (range 0–12), 39.82 ± 3.69 (range 10–50), 33.13 ± 5.91 (range 11–55), respectively. The multivariate logistic regression analysis showed that the knowledge [odds ratio (OR) = 1.212, 95% confidence interval (CI): 1.097–1.339, P