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Many researchers have reported that obesity is a major risk factor for diabetes, cardiovascular diseases, several forms of cancer (such as breast, colon and prostate), pulmonary, osteoarticular and metabolic diseases in the past decades. Recently, the hypolipidemic and anti-obesity effects of green tea in animals and humans have slowly become a hot topic in nutritional and food science research. This review will up-date the information of the anti-obesity effects of green tea in human intervention and animal studies. During recent years, an increasing number of clinical trials have confirmed the beneficial effects of green tea on obesity. However, the optimal dose has not yet been established owing to the very different results from studies with a similar design, which may be caused by differences in the extent of obesity, dietary intake, physical activity intensity, the strength of subjects' compliance to test instruction, the genetic background of populations, body composition and dietary habits. Therefore, further investigations on a larger scale and with longer periods of observation and tighter controls are needed to define optimal doses in subjects with varying degrees of metabolic risk factors and to determine differences in beneficial effects among diverse populations. Moreover, data from laboratory studies have shown that green tea has important roles in fat metabolism by reducing food intake, interrupting lipid emulsification and absorption, suppressing adipogenesis and lipid synthesis and increasing energy expenditure via thermogenesis, fat oxidation and fecal lipid excretion. However, the exact molecular mechanisms remain elusive. European Journal of Clinical Nutrition (2014) 68, 1075-1087; doi: 10.1038/ejcn.2014.143; published online 30 July 2014, INTRODUCTION Obesity, defined as a body mass index (BMI) of [greater than or equal to]30 kg/[m.sup.2] in western countries, (1) is a nutritional and metabolic disorder, which has the clinical [...]

Phosphorus (P) and potassium (K) affect seedling growth, root configuration, and nutrient uptake in hydroponic rice, but there are few studies on all growth stages of rice. The purpose of this experiment was to determine the response characteristics of root morphology, plant physiology, and P and K uptake and utilization efficiency to different supplies of P and K. Two local conventional rice varieties (Shennong 265 and Liaojing 294) were used as experimental materials across four treatments, including HPHK (sufficient P and K supply), HPLK (sufficient P supply under low K levels), LPHK (sufficient K supply under low P levels) and LPLK (low P and K levels) in a hydroponic setting. The results showed that HPHK and HPLK significantly decreased the acid phosphatase activity of leaves and roots from full heading to filling stages when compared to LPHK and LPLK. Sufficient supply of P or K significantly increased the accumulation of P and K (aboveground, leaves, stem sheath, and whole plant) and root morphological parameters (root length, root surface area, total root volume, and tips) during major growth stages when compared to LP or LK levels. HPHK was significantly higher than other treatments in terms of dry weight and the root activity at the main growth stage, P and K uptake rates in nutrient solutions at various stages, related P and K efficiency at the maturity stage, yield, effective panicle number, and grain number per panicle. In addition, the effect of HPHK on the above indexes were significantly greater than those of single sufficient supply of P or K. In conclusion, HPHK can improve plant configuration, increase plant P and K absorption and root activity, and increase rice yield and related P and K utilization efficiency., (© 2024. The Author(s).)

Hepatocellular Carcinoma (HCC), the most common primary liver cancer, ranks as the third most common cause of cancer-related deaths globally. A deeper understanding of the cell death mechanisms in HCC is essential for developing more effective treatment strategies. This review explores programmed cell death (PCD) pathways involved in HCC, including apoptosis, necroptosis, pyroptosis, ferroptosis, and immunogenic cell death (ICD). These mechanisms trigger specific cell death cascades that influence the development and progression of HCC. Although multiple PCD pathways are involved in HCC, shared cellular factors suggest a possible interplay between the different forms of cell death. However, the exact roles of different cell death pathways in HCC and which cell death pathway plays a major role remain unclear. This review also highlights how disruptions in cell death pathways are related to drug resistance in cancer therapy, promoting a combined approach of cell death induction and anti-tumor treatment to enhance therapeutic efficacy. Further research is required to unravel the complex interplay between cell death modalities in HCC, which may lead to innovative therapeutic breakthroughs., (© 2024. The Author(s).)

Camellia oleifera, a significant woody edible oil species, was examined using 48 germplasm resources from high-altitude regions in East Guizhou Province, China, to analyze fruit quality. The analysis aimed to identify high-performance germplasm, providing theoretical and research foundations for selecting and cross-breeding superior C. oleifera varieties in these regions. Fifteen primary traits of mature fruits were measured and analyzed, including four phenotypic traits (single fruit weight, transverse diameter, longitudinal diameter, peel thickness) and eleven quality traits (fresh seed yield rate, dry seed yield rate, dry kernel yield rate, seed kernel oil content, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, α-linolenic acid, cis-11-eicosenoic acid). A comprehensive evaluation employing cluster and principal component analyses (PCA) was conducted. The cluster analysis categorized the germplasms into five groups at a squared Euclidean distance of 14, with the first category comprising 17 germplasms, the second 28, and the third, fourth, and fifth each containing one. PCA reduced the 15 traits to five principal components (PCs), with PC1 having the highest eigenvalue of 3.57 and a contribution rate of 23.8%, mainly representing phenotypic traits. PC2, contributing 20.44%, represented linoleic acid, while PC3, PC4, and PC5, with contribution rates of 12.99%, 9.13%, and 7.45% respectively, predominantly represented seed kernel oil content, fresh seed yield, and palmitoleic acid. Employing a weighted sum method, a comprehensive evaluation function was developed to calculate total scores for each superior individual, forming the basis for rankings and selections. Notable variability was detected in single fruit weight, peel thickness, and fresh and dry seed yields, while oleic acid exhibited the lowest coefficient of variation. Dry seed yield showed a robust positive correlation with seed kernel oil content and the concentrations of palmitic and linoleic acids, whereas seed kernel oil content was inversely correlated with cis-11-eicosenoic acid levels. Five PCs with eigenvalues > 1 were identified, highlighting the top ten superior individuals: QD (Qian Dong: the code of eastern Guizhou Province)-33 > QD-34 > QD-48 > QD-38 > QD-27 > QD-15 > QD-35 > QD-5 > QD-14 > QD-36. Thus, the 48 C. oleifera germplasms from East Guizhou's high-altitude areas demonstrate significant potential for enhancing traits such as single fruit weight, peel thickness, and fresh and dry seed yields. Specifically, QD-33, QD-34, and QD-48 exhibited superior comprehensive performance, designating them as prime candidates for variety selection and breeding., (© 2024. The Author(s).)

Fructus hippophae (Hippophae rhamnoides spp. mongolica×Hippophae rhamnoides sinensis), a hybrid variety of sea buckthorn that Hippophae rhamnoides spp. mongolica serves as the female parent and Hippophae rhamnoides sinensis serves as the male parent, is a traditional plant with great potentials of economic and medical values. Herein, we gained a chromosome-level genome of Fructus hippophae about 918.59 Mb, with the scaffolds N50 reaching 83.65 Mb. Then, we anchored 440 contigs with 97.17% of the total genome sequences onto 12 pseudochromosomes. Next, de-novo, homology and transcriptome assembly strategies were adopted for gene structure prediction. This predicted 36475 protein-coding genes, of which 36226 genes could be functionally annotated. Simultaneously, various strategies were used for quality assessment, both the complete BUSCO value (98.80%) and the mapping rate indicated the high assembly quality. Repetitive elements, which occupied 63.68% of the genome, and 1483600 bp of non-coding RNA were annotated. Here, we provide genomic information on female plants of a popular variety, which can provide data for pan-genomic construction of sea buckthorn and for the resolution of the mechanism of sex differentiation., (© 2024. The Author(s).)

The resolution of traffic congestion and personal safety issues holds paramount importance for human's life. The ability of an autonomous driving system to navigate complex road conditions is crucial. Deep learning has greatly facilitated machine vision perception in autonomous driving. Aiming at the problem of small target detection in traditional YOLOv5s, this paper proposes an optimized target detection algorithm. The C3 module on the algorithm's backbone is upgraded to the CBAMC3 module, introducing a novel GELU activation function and EfficiCIoU loss function, which accelerate convergence on position loss l box , confidence loss l obj , and classification loss l cls , enhance image learning capabilities and address the issue of inaccurate detection of small targets by improving the algorithm. Testing with a vehicle-mounted camera on a predefined route effectively identifies road vehicles and analyzes depth position information. The avoidance model, combined with Pure Pursuit and MPC control algorithms, exhibits more stable variations in vehicle speed, front-wheel steering angle, lateral acceleration, etc., compared to the non-optimized version. The robustness of the driving system's visual avoidance functionality is enhanced, further ameliorating congestion issues and ensuring personal safety., (© 2024. The Author(s).)

Stag beetles (Coleoptera: Lucanidae) represent a significant saproxylic assemblage in forest ecosystems and are noted for their enlarged mandibles and male polymorphism. Despite their relevance as ideal models for the study of exaggerated mandibles that aid in attracting mates, the regulatory mechanisms associated with these traits remain understudied, and restricted by the lack of high-quality reference genomes for stag beetles. To address this limitation, we successfully assembled the first chromosome-level genome of a representative species Dorcus hopei. The genome was 496.58 Mb in length, with a scaffold N50 size of 54.61 Mb, BUSCO values of 99.8%, and 96.8% of scaffolds anchored to nine pairs of chromosomes. We identified 285.27 Mb (57.45%) of repeat sequences and annotated 11,231 protein-coding genes. This genome will be a valuable resource for further understanding the evolution and ecology of stag beetles, and provides a basis for studying the mechanisms of exaggerated mandibles through comparative analysis., (© 2024. The Author(s).)

Cumulative studies have established the significance of transfer RNA-derived small RNA (tsRNA) in tumorigenesis and progression. Nevertheless, its function and mechanism in pancreatic cancer metastasis remain largely unclear. Here, we screened and identified tiRNA-Val-CAC-2 as highly expressed in pancreatic cancer metastasis samples by tsRNA sequencing. We also observed elevated levels of tiRNA-Val-CAC-2 in the serum of pancreatic cancer patients who developed metastasis, and patients with high levels of tiRNA-Val-CAC-2 exhibited a worse prognosis. Additionally, knockdown of tiRNA-Val-CAC-2 inhibited the metastasis of pancreatic cancer in vivo and in vitro, while overexpression of tiRNA-Val-CAC-2 promoted the metastasis of pancreatic cancer. Mechanically, we discovered that tiRNA-Val-CAC-2 interacts with FUBP1, leading to enhanced stability of FUBP1 protein and increased FUBP1 enrichment in the c-MYC promoter region, thereby boosting the transcription of c-MYC. Of note, rescue experiments confirmed that tiRNA-Val-CAC-2 could influence pancreatic cancer metastasis via FUBP1-mediated c-MYC transcription. These findings highlight a potential novel mechanism underlying pancreatic cancer metastasis, and suggest that both tiRNA-Val-CAC-2 and FUBP1 could serve as promising prognostic biomarkers and potential therapeutic targets for pancreatic cancer., (© 2024. The Author(s).)

Dynamically organized chromatin complexes often involve multiplex chromatin interactions and sometimes chromatin-associated RNA 1-3 . Chromatin complex compositions change during cellular differentiation and ageing, and are expected to be highly heterogeneous among terminally differentiated single cells 4-7 . Here we introduce the multinucleic acid interaction mapping in single cells (MUSIC) technique for concurrent profiling of multiplex chromatin interactions, gene expression and RNA-chromatin associations within individual nuclei. When applied to 14 human frontal cortex samples from older donors, MUSIC delineated diverse cortical cell types and states. We observed that nuclei exhibiting fewer short-range chromatin interactions were correlated with both an 'older' transcriptomic signature and Alzheimer's disease pathology. Furthermore, the cell type exhibiting chromatin contacts between cis expression quantitative trait loci and a promoter tends to be that in which these cis expression quantitative trait loci specifically affect the expression of their target gene. In addition, female cortical cells exhibit highly heterogeneous interactions between XIST non-coding RNA and chromosome X, along with diverse spatial organizations of the X chromosomes. MUSIC presents a potent tool for exploration of chromatin architecture and transcription at cellular resolution in complex tissues., (© 2024. The Author(s).)

Although Chaenomeles is widely used in horticulture, traditional Chinese medicine and landscape greening, insufficient research has hindered its breeding and seed selection. This study investigated the floral phenology, floral organ characteristics, palynology, and breeding systems of Chaenomeles speciosa (Sweet) Nakai. The floral characteristics of C. speciosa were observed both visually and stereoscopically. The microstructures of the flower organs were observed using scanning electron microscopy. Pollen stainability was determined using triphenyl tetrazolium chloride staining. Stigma receptivity was determined using the benzidine-H 2 O 2 method and the post-artificial pollination pollen germination method. The breeding system was assessed based on the outcrossing index and pollen-ovule ratio. The flowers of C. speciosa were bisexual with a flowering period from March to April. The flowering periods of single flowers ranged from 8 to 19 d, and those of single plants lasted 18-20 d. The anthers were cylindrical, with the base attached to the filament, and were split longitudinally to release pollen. The flower had five styles, with a connate base. The ovaries had five carpels and five compartments. The inverted ovules were arranged in two rows on the placental axis. The stigma of C. speciosa was dry and had many papillary protrusions. In the early flowering stage (1-2 d of flowering), the pollen exhibited high stainability (up to 84.24%), but all stainability was lost at 7 d of flowering. Storage at - 20 °C effectively delayed pollen inactivation. The stigma receptivity of C. speciosa lasted for approximately 7 days, and the breeding system was classified as outcrossing with partial self-compatibility., (© 2024. The Author(s).)

The disruption of circadian rhythms caused by long-term shift work can cause metabolic diseases such as obesity. Early growth response 3 (EGR3) is a member of early growth response (EGR) family, which is involved in several cellular responses, had been reported as a circadian rhythm gene in suprachiasmatic nucleus. In this research, EGR3 was found to be widely expressed in the different tissue of human and mice, and downregulated in adipose tissue of obese subjects and high-fat diet mice. Moreover, EGR3 was found negatively regulated by cortisol. In addition, EGR3 is a key negative modulator of hADSCs and 3T3-L1 adipogenesis via regulating HDAC6, which is a downstream target gene of EGR3 and a negative regulator of adipogenesis and lipogenesis. These findings may explain how circadian rhythm disorder induced by shift works can cause obesity. Our study revealed a potential therapeutic target to alleviate metabolic disorders in shift workers and may provide better health guidance to shift workers., (© 2024. The Author(s).)

Ammonia-oxidizing microorganisms (AOM) contribute to one of the largest nitrogen fluxes in the global nitrogen budget. Four distinct lineages of AOM: ammonia-oxidizing archaea (AOA), beta- and gamma-proteobacterial ammonia-oxidizing bacteria (β-AOB and γ-AOB) and complete ammonia oxidizers (comammox), are thought to compete for ammonia as their primary nitrogen substrate. In addition, many AOM species can utilize urea as an alternative energy and nitrogen source through hydrolysis to ammonia. How the coordination of ammonia and urea metabolism in AOM influences their ecology remains poorly understood. Here we use stable isotope tracing, kinetics and transcriptomics experiments to show that representatives of the AOM lineages employ distinct regulatory strategies for ammonia or urea utilization, thereby minimizing direct substrate competition. The tested AOA and comammox species preferentially used ammonia over urea, while β-AOB favoured urea utilization, repressed ammonia transport in the presence of urea and showed higher affinity for urea than for ammonia. Characterized γ-AOB co-utilized both substrates. These results reveal contrasting niche adaptation and coexistence patterns among the major AOM lineages., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The molecular mechanism of glioblastoma (GBM) radiation resistance remains poorly understood. The aim of this study was to elucidate the potential role of Melanophilin (MLPH) O-GlcNAcylation and the specific mechanism through which it regulates GBM radiotherapy resistance. We found that MLPH was significantly upregulated in recurrent GBM tumor tissues after ionizing radiation (IR). MLPH induced radiotherapy resistance in GBM cells and xenotransplanted human tumors through regulating the NF-κB pathway. MLPH was O-GlcNAcylated at the conserved serine 510, and radiation-resistant GBM cells showed higher levels of O-GlcNAcylation of MLPH. O-GlcNAcylation of MLPH protected its protein stability and tripartite motif containing 21(TRIM21) was identified as an E3 ubiquitin ligase promoting MLPH degradation whose interaction with MLPH was affected by O-GlcNAcylation. Our data demonstrate that MLPH exerts regulatory functions in GBM radiation resistance by promoting the NF-κB signaling pathway and that O-GlcNAcylation of MLPH both stabilizes and protects it from TRIM21-mediated ubiquitination. These results identify a potential mechanism of GBM radiation resistance and suggest a potential therapeutic strategy for GBM treatment., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Increasing income for grain farmers is crucial to mobilise farmers' incentive for grain cultivation. This article, based on the survey data of 2032 wheat growers in Anhui Province, China, employs the Logit model, multinomial Logit model, and entropy balance-OLS regression method to empirically analyze the factors influencing wheat growers' participation in agricultural industrial organization models and the impact of their participation decisions on planting returns. The research found that: (1) Wheat growers with richer resource endowments are more likely to participate in agricultural industrial organization models. Factors such as household head's education level, training experience, quality of arable land, scale of operation, and labor endowment are crucial determinants of wheat growers' decisions to participate in industrial organization models. (2) Participation in agricultural industrial organizations significantly enhances the net income of wheat growers. Comparatively, the income-boosting effect is more pronounced for those participating in the "household + farmer cooperatives/agricultural enterprises" model. (3) The mechanisms through which wheat growers' participation in different agricultural industrial organization models affects their crop yields vary. The income-enhancing effects of wheat growers' participation in the "household + farmer cooperatives/agricultural enterprises" model of industrial organization primarily stem from the improvement in land productivity and market bargaining power. On the other hand, the income-enhancing effects of participation in the "household + village collective + farmer cooperatives/agricultural enterprises" model are mainly attributed to the improvement in market bargaining power. The policy implication is that priority should be given to cultivating and developing industrial organisations based on the model of "household + farmers' co-operatives/agribusinesses" in regions where farmers are richly endowed with resources, and at the same time, the development of industrial organisations based on the model of "household + village collectives + farmers' co-operatives/agribusinesses" should be supplemented in accordance with local conditions. At the same time, the development of "household + village collectives + farmers' cooperatives/agribusinesses" mode is supplemented according to local conditions., (© 2023. Springer Nature Limited.)

Surgery is one of the most frequent and effective intervention strategies for lumbar spinal stenosis, however, one-third of patients are not satisfied with postoperative outcomes. It is not clear whether perioperative systemic lidocaine could accelerate the early postoperative quality of recovery in patients undergoing lumbar spinal stenosis surgery. 66 patients were enrolled in this trial. Lidocaine or placebo was administered at a loading dose of 1.5 mg/kg for 10 min and then infused at 2.0 mg/kg/hour till the end of surgery. Continued infusion by postoperative patient-controlled intravenous analgesia with a dose of 40 mg/hour. The primary outcome was the quality of recovery. Secondary outcomes included the time of the patient's first flatus, catheter removal time, underground time from the end of the surgery, pain score, levels of inflammatory factors (IL-6, IL-10, TNF-α), postoperative nausea and vomiting (PONV), sufentanil rescues, patients' satisfaction scores, and complications of lidocaine. Eventually, 56 patients were in the final analysis with similar age, Body Mass Index (BMI), duration of surgery and anesthesia, and median QoR-15 score (a development and Psychometric Evaluation of a Postoperative Quality of Recovery Score). The difference in median QoR-15 score in placebo versus lidocaine patients was statistically significant (IQR, 106 (104-108) versus 114 (108.25-119.25), P < 0.001). The Numeric Rating Scale (NRS) score at the 12th hour, median sufentanil rescue consumption, IL-6, tumor necrosis factor-alpha (TNF-α) of patients treatment with lidocaine were lower. Nevertheless, patients given lidocaine had high satisfaction scores. Suggesting that lidocaine enhanced the postoperative quality of recovery, met early postoperative gastrointestinal function recovery, provided superior pain relief, lessened inflammatory cytokines, etc., indicating it may be a useful intervention to aid recovery following lumbar spinal stenosis surgery., (© 2023. Springer Nature Limited.)

In terrestrial ecosystems, leaf litter is the main source of nutrients returning to the soil. Understanding how litter decomposition responds to stand age is critical for improving predictions of the effects of forest age structure on nutrient availability and cycling in ecosystems. However, the changes in this critical process with stand age remain poorly understood due to the complexity and diversity of litter decomposition patterns and drivers among different stand ages. In this study, we examined the effects of stand age on litter decomposition with two well-replicated age sequences of naturally occurring secondary forests and Chinese fir (Cunninghamia lanceolata) plantations in southern China. Our results showed that the litter decomposition rates in the secondary forests were significantly higher than those in the Chinese fir plantations of the same age, except for 40-year-old forests. The litter decomposition rate of the Chinese fir initially increased and then decreased with stand age, while that of secondary forests gradually decreased. The results of a structural equation model indicated that stand age, litter quality and microbial community were the primary factors driving nutrient litter loss. Overall, these findings are helpful for understanding the effects of stand age on the litter decomposition process and nutrient cycling in plantation and secondary forest ecosystems., (© 2023. Springer Nature Limited.)

The patterns of communication among different chondrocyte subtypes in human cartilage degeneration and regeneration help us understand the microenvironment of osteoarthritis and optimize cell-targeted therapies. Here, a single-cell transcriptome dataset of chondrocytes is used to explore the synergistic and communicative patterns of different chondrocyte subtypes. We collected 1600 chondrocytes from 10 patients with osteoarthritis and analyzed the active communication patterns for the first time based on network analysis and pattern recognition at the single-cell level. Manifold learning and quantitative contrasts were performed to analyze conserved and specific communication pathways. We found that ProCs (Proliferative chondrocytes), ECs (Effector chondrocytes), preHTCs (Prehypertrophic chondrocytes), HTCs (Hypertrophic chondrocytes), and FCs (Fibrocartilage chondrocytes) are more active in incoming and outgoing signaling patterns, which is consistent with studies on their close functional cooperation. Among them, preHTCs play multiple roles in chondrocyte communication, and ProCs and preHTCs have many overlapping pathways. These two subtypes are the most active among all chondrocyte subtypes. Interestingly, ECs and FCs are a pair of "mutually exclusive" subtypes, of which ECs are predominant in incoming patterns and FCs in outgoing patterns. The active signaling pathways of ECs and FCs largely do not overlap. COLLAGEN and LAMININ are the main pivotal pathways, which means they are very important in the repair and expansion of joint homeostasis. Notably, only preHTCs assume multiple roles (including sender, receiver, mediator, and influencer) and are involved in multiple communication pathways. We have examined their communication patterns from the perspective of cellular interactions, revealed the relationships among different chondrocyte subtypes, and, in particular, identified a number of active subtypes and pathways that are important for targeted therapy in the osteoarthritic microenvironment. Our findings provide a new research paradigm and new insights into understanding chondrocyte activity patterns in the osteoarthritic microenvironment., (© 2023. Springer Nature Limited.)

Living in high expressed emotion (EE) environments tends to increase the relapse rate in schizophrenia (SZ). At present, the neural substrates responsible for high EE in SZ remain poorly understood. Functional near-infrared spectroscopy (fNIRS) may be of great use to quantitatively assess cortical hemodynamics and elucidate the pathophysiology of psychiatric disorders. In this study, we designed novel low- (positivity and warmth) and high-EE (criticism, negative emotion, and hostility) stimulations, in the form of audio, to investigate cortical hemodynamics. We used fNIRS to measure hemodynamic signals while participants listened to the recorded audio. Healthy controls (HCs, [Formula: see text]) showed increased hemodynamic activation in the major language centers across EE stimulations, with stronger activation in Wernicke's area during the processing of negative emotional language. Compared to HCs, people with SZ ([Formula: see text]) exhibited smaller hemodynamic activation in the major language centers across EE stimulations. In addition, people with SZ showed weaker or insignificant hemodynamic deactivation in the medial prefrontal cortex. Notably, hemodynamic activation in SZ was found to be negatively correlated with the negative syndrome scale score at high EE. Our findings suggest that the neural mechanisms in SZ are altered and disrupted, especially during negative emotional language processing. This supports the feasibility of using the designed EE stimulations to assess people who are vulnerable to high-EE environments, such as SZ. Furthermore, our findings provide preliminary evidence for future research on functional neuroimaging biomarkers for people with psychiatric disorders., (© 2023. The Author(s).)

High-entropy alloy nanoparticles (HEA-NPs) show great potential as functional materials 1-3 . However, thus far, the realized high-entropy alloys have been restricted to palettes of similar elements, which greatly hinders the material design, property optimization and mechanistic exploration for different applications 4,5 . Herein, we discovered that liquid metal endowing negative mixing enthalpy with other elements could provide a stable thermodynamic condition and act as a desirable dynamic mixing reservoir, thus realizing the synthesis of HEA-NPs with a diverse range of metal elements in mild reaction conditions. The involved elements have a wide range of atomic radii (1.24-1.97 Å) and melting points (303-3,683 K). We also realized the precisely fabricated structures of nanoparticles via mixing enthalpy tuning. Moreover, the real-time conversion process (that is, from liquid metal to crystalline HEA-NPs) is captured in situ, which confirmed a dynamic fission-fusion behaviour during the alloying process., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

In view of the current debate about the relationship between lipids and deep venous thrombosis (DVT) in clinical studies, a two-sample Mendelian randomization (MR) study was conducted to clarify the effects of five circulating lipids (apolipoprotein A1, apolipoprotein B, low-density lipoprotein, high-density lipoprotein and triglycerides) on DVT from the perspective of genetic inheritance. Five lipids (exposure) were analysed by MR with DVT (outcome) from two different data sources. For the analysis, we used inverse variance weighting and a weighted mode, weighted median, simple mode and MR-Egger regression to analyse the effect of circulating lipids on DVT. In addition, we used the MR-Egger intercept test, Cochran's Q test and "leave-one-out" sensitivity analysis to evaluate horizontal multiplicity, heterogeneity and stability, respectively, in the analysis. In the analysis, the two-sample Mendelian randomization analysis of five common circulating lipids and DVT showed that common circulating lipids had no causal effect on DVT, which is somewhat inconsistent with the findings of many published observational studies. Based on our results, our two-sample MR analysis failed to detect a statistically significant causal relationship between five common circulating lipids and DVT., (© 2023. The Author(s).)

Poly(ADP-ribose) polymerase 1 (PARP1) is essential for the progression of several types of cancers. However, whether and how PARP1 is stabilized to promote genomic stability in triple-negative breast cancer (TNBC) remains unknown. Here, we demonstrated that the deubiquitinase USP15 interacts with and deubiquitinates PARP1 to promote its stability, thereby stimulating DNA repair, genomic stability and TNBC cell proliferation. Two PARP1 mutations found in individuals with breast cancer (E90K and S104R) enhanced the PARP1-USP15 interaction and suppressed PARP1 ubiquitination, thereby elevating the protein level of PARP1. Importantly, we found that estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) inhibited USP15-mediated PARP1 stabilization through different mechanisms. ER bound to the USP15 promoter to suppress its expression, PR suppressed the deubiquitinase activity of USP15, and HER2 abrogated the PARP1-USP15 interaction. The specific absence of these three receptors in TNBC results in high PARP1 levels, leading to increases in base excision repair and female TNBC cell survival., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

In this paper, production system (PS) of shale oil is optimized according to production data and indoor experiments, including core and fluid tests. Results showed that: ① Pressure drop rate at wellhead is a reasonable reference for the determination of post-fracture shut-in duration (PFSID). When pressure at a wellhead of horizontal well is relatively stable and the pressure drop less than 0.1 MPa per day for three consecutive days, PFSID ends; ② Flowback intensity of fracturing fluid affects the effectiveness of proppant underground, thus flowback intensity can be determined by the critical flow rate and safety factor of each proppant; ③ Flowback intensity should be varied during different development stages, which could be divided into four according to production gas and oil ratio(GOR) of a shale oil horizontal well: low, medium-high, high and high-low production GOR. During the stage of low production GOR, ratio of flow pressure and saturation pressure should be maintained greater than 1.0, and the initial daily liquid productivity for a hundred-meter oil-bearing lateral length in a horizontal well is 2.4 ~ 2.9 m 3 /d; and during the medium-high production GOR, high production GOR and high-low production GOR stages, the responding initial daily liquid productivity should be maintained between 0.8 ~ 1.0 or less than 0.8 respectively., (© 2023. The Author(s).)

Blockade of programmed cell death 1 (PD-1)/programmed cell death 1 ligand (PD-L1) has evolved into one of the most promising immunotherapy strategies for cancer patients. Tumor cells frequently overexpress PD-L1 to evade T cell-mediated immune surveillance. However, the specific genetic alterations that drive aberrant overexpression of PD-L1 in cancer cells remain poorly understood. The gene encoding the E3 ubiquitin ligase substrate-binding adaptor SPOP is frequently mutated in endometrial cancer (EC). Here, we report that SPOP negatively regulates PD-L1 expression at the transcriptional level. Wild-type SPOP binds to IRF1, a primary transcription factor responsible for the inducible expression of PD-L1, and subsequently triggers its ubiquitin- proteasomal degradation to suppress IRF1-mediated transcriptional upregulation of PD-L1. In contrast, EC-associated SPOP mutants lose their capacity to degrade IRF1 but stabilize IRF1, and upregulate PD-L1 expression. EC-associated SPOP mutations accelerate xenograft tumor growth partially by increasing IRF1 and PD-L1 expression. Together, we identify SPOP as a negative regulator of the IRF1-PD-L1 axis and characterize the critical roles of IRF1 and PD-L1 in SPOP mutation-driven tumor immune evasion in EC., (© 2022. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

Aberrant hyperactivation of the Hippo pathway effector YAP/TEAD complex causes tissue overgrowth and tumorigenesis in various cancers, including endometrial cancer (EC). The transcription factor SOX17 (SRY [sex-determining region Y]-box 17) is frequently mutated in EC; however, SOX17 mutations are rare in other cancer types. The molecular mechanisms underlying SOX17 mutation-induced EC tumorigenesis remain poorly understood. Here, we demonstrate that SOX17 serves as a tumor suppressor to restrict the proliferation, migration, invasion, and anchorage-independent growth of EC cells, partly by suppressing the transcriptional outputs of the Hippo-YAP/TEAD pathway. SOX17 binds to TEAD transcription factors through its HMG domain and attenuates the DNA-binding ability of TEAD. SOX17 loss by inactivating mutations leads to the malignant transformation of EC cells, which can be reversed by small-molecule inhibitors of YAP/TEAD or cabozantinib, an FDA-approved drug targeting the YAP/TEAD transcriptional target AXL. Our findings reveal novel molecular mechanisms underlying Hippo-YAP/TEAD pathway-driven EC tumorigenesis, and suggest potential therapeutic strategies targeting the Hippo-YAP/TEAD pathway in SOX17-mutated EC., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Chemoresistance has long been the bottleneck of ovarian cancer (OC) prognosis. It has been shown that mitochondria play a crucial role in cell response to chemotherapy and that dysregulated mitochondrial dynamics is intricately linked with diseases like OC, but the underlying mechanisms remain equivocal. Here, we demonstrate a new mechanism where CRL4 CUL4A/DDB1 manipulates OC cell chemoresistance by regulating mitochondrial dynamics and mitophagy. CRL4 CUL4A/DDB1 depletion enhanced mitochondrial fission by upregulating AMPKα Thr172 and MFF Ser172/Ser146 phosphorylation, which in turn recruited DRP1 to mitochondria. CRL4 CUL4A/DDB1 loss stimulated mitophagy through the Parkin-PINK1 pathway to degrade the dysfunctional and fragmented mitochondria. Importantly, CRL4 CUL4A/DDB1 loss inhibited OC cell proliferation, whereas inhibiting autophagy partially reversed this disruption. Our findings provide novel insight into the multifaceted function of the CRL4 E3 ubiquitin ligase complex in regulating mitochondrial fission, mitophagy, and OC chemoresistance. Disruption of CRL4 CUL4A/DDB1 and mitophagy may be a promising therapeutic strategy to overcome chemoresistance in OC., (© 2022. The Author(s).)

Polymyxins are a class of antibiotics that were discovered in 1947 from programs searching for compounds effective in the treatment of Gram-negative infections. Produced by the Gram-positive bacterium Paenibacillus polymyxa and composed of a cyclic peptide chain with a peptide-fatty acyl tail, polymyxins exert bactericidal effects through membrane disruption. Currently, polymyxin B and colistin (polymyxin E) have been developed for clinical use, where they are reserved as "last-line" therapies for multidrug-resistant (MDR) infections. Unfortunately, the incidences of strains resistant to polymyxins have been increasing globally, and polymyxin heteroresistance has been gaining appreciation as an important clinical challenge. These phenomena, along with bacterial tolerance to this antibiotic class, constitute important contributors to polymyxin treatment failure. Here, we review polymyxins and their mechanism of action, summarize the current understanding of how polymyxin treatment fails, and discuss how the next generation of polymyxins holds promise to invigorate this antibiotic class., (© 2022. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Non-suicidal self-injury (NSSI) has attracted increasing attention due to its high detection rate, high risk and high repeatability. There is a need for the early identification of preventable occurrence factors, which is necessary to facilitate screening and intervention, especially to facilitate the early detection of high-risk individuals. This research aims to investigate the relationship between bullying behaviour and non-suicidal self-injury among children and adolescents by means of meta-analysis. The PubMed, Embase, Web of Science, SCOPUS, PsycINFO, CKNI and WAN FANG databases were searched from inception to 14 December 2021 for studies that explored the relationship between bullying behaviour and NSSI among children and adolescents. A total of 29 articles met the inclusion criteria of the meta-analysis, and 54 independent effect sizes were obtained, including 53,501 subjects. Victims [OR 2.46 (95% CI 2.14-2.83); p < 0.001], bullies [OR 2.12 (95% CI 1.37-3.27); p < 0.001], and bully-victims [OR: 2.98 (95% CI 1.85-4.82); p < 0.001] were more likely to have NSSI than uninvolved children or adolescents. In addition, analyses showed the absence of publication bias. In the victim group, the older the age was, the lower the risk of NSSI (z = - 3.74, p = 0.00). Gender does not play a moderating effect on the association between bullying behaviour and non-suicidal self-injury. The relationship between involvement in bullying and NSSI was demonstrated. By taking measures to prevent bullying, the incidence of NSSI in children and adolescents can be potentially reduced., (© 2022. The Author(s).)

Imiquimod (IMQ) is widely used as animal model of psoriasis, a chronic inflammatory skin disorder. Although topical application of IMQ to back skin causes splenomegaly in mice, how the spleen affects the psoriasis-like phenotype of IMQ-treated mice remains unclear. In this study, we analyzed the cellular composition of spleen and measured metabolites in blood of IMQ-treated mice. We also investigated whether splenectomy influences the degree of skin inflammation and pathology in IMQ-treated mice. Flow cytometry showed that the numbers of CD11b + Ly6c + neutrophils, Ter119 + proerythroblasts, B220 + B cells, F4/80 + macrophages, and CD11c + dendritic cells in the spleen were significantly higher in IMQ-treated mice compared to control mice. An untargeted metabolomics analysis of blood identified 14 metabolites, including taurine and 2,6-dihydroxybenzoic acid, whose levels distinguished the two groups. The composition of cells in the spleen and blood metabolites positively correlated with the weight of the spleen. However, splenectomy did not affect IMQ-induced psoriasis-like phenotypes compared with sham-operated mice, although splenectomy increased the expression of interleukin-17A mRNA in the skin of IMQ-treated mice. These data suggest that the spleen does not play a direct role in the development of psoriasis-like phenotype on skin of IMQ-treated mice, though IMQ causes splenomegaly., (© 2022. The Author(s).)

Changes in the online car-hailing industry have brought new challenges to government governance. Effectively enhancing governance efficiency has become the focus of academic research. Based on the technical governance perspective, this paper introduces the consortium blockchain to construct an evolutionary game model between the online car-hailing platform and the government under blockchain technology. By solving the replicated dynamic equations and the Jacobian matrix, the influences of the change in initial conditions and decision parameters on the evolutionary stability results are revealed, and numerical experiments are carried out by using the Python programming language. This paper claims that the system presents three evolutionary stable results and a periodic stochastic state when the key parameters are located in different thresholds. The additional cost of the platform's negative regulation and the government's punishment intensity have a positive effect on the evolution of the system to the ideal state (active regulation, active governance). Platform technology R&D cost and government innovation input have a negative effect on the evolution of the system to the ideal state. Therefore, using blockchain to increase the additional cost of the platform's negative regulation, appropriately increasing the government's punishment intensity, reasonably controlling the government's innovation input to the platform, and reducing the technology R&D cost of the platform will help the system evolve into an ideal state. This paper provides useful references to implement effective governance and the innovative and healthy development of the online car-hailing industry., (© 2022. The Author(s).)

Activating RAS mutations are found in a subset of fusion-negative rhabdomyosarcoma (RMS), and therapeutic strategies to directly target RAS in these tumors have been investigated, without clinical success to date. A potential strategy to inhibit oncogenic RAS activity is the disruption of RAS prenylation, an obligate step for RAS membrane localization and effector pathway signaling, through inhibition of farnesyltransferase (FTase). Of the major RAS family members, HRAS is uniquely dependent on FTase for prenylation, whereas NRAS and KRAS can utilize geranylgeranyl transferase as a bypass prenylation mechanism. Tumors driven by oncogenic HRAS may therefore be uniquely sensitive to FTase inhibition. To investigate the mutation-specific effects of FTase inhibition in RMS we utilized tipifarnib, a potent and selective FTase inhibitor, in in vitro and in vivo models of RMS genomically characterized for RAS mutation status. Tipifarnib reduced HRAS processing, and plasma membrane localization leading to decreased GTP-bound HRAS and decreased signaling through RAS effector pathways. In HRAS-mutant cell lines, tipifarnib reduced two-dimensional and three-dimensional cell growth, and in vivo treatment with tipifarnib resulted in tumor growth inhibition exclusively in HRAS-mutant RMS xenografts. Our data suggest that small molecule inhibition of FTase is active in HRAS-driven RMS and may represent an effective therapeutic strategy for a genomically-defined subset of patients with RMS., (© 2022. The Author(s).)

The cell identity of malignant cells and how they acquire it are fundamental for our understanding of cancer. Here, we report that esophageal squamous cell carcinoma (ESCC) cells display molecular features equally similar but distinct to all three types of normal esophageal epithelial cells, which we term as confused cell identity (CCI). CCI is an independent prognostic marker associated with poor prognosis in ESCC. Further, we identify tropomyosin 4 (TPM4) as a critical CCI gene that promotes the aggressiveness of ESCC in vitro and in vivo. And TPM4 creates CCI through activating the Jak/STAT-SOX2 pathway. Thus, our study suggests an unrecognized feature of ESCC cells, which might be of value for clinic prognosis and potential interference., (© 2022. The Author(s).)

Despite advances in clinical diagnosis and treatment, the prognosis of patients with osteosarcoma (OS) remains poor, and the treatment efficacy has plateaued. Therefore, it is important to identify new therapeutic targets for OS. N 6 -methyladenosine (m 6 A) modification has been reported to participate in tumor malignancy. In this study, functional screening showed that the m 6 A demethylase FTO could be a candidate therapeutic target for OS. Upregulated FTO in OS could predict a poorer prognosis. FTO promoted the growth and metastasis of OS in vitro and in vivo. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were performed to identify DACT1 as a potential target of FTO. In vitro assays demonstrated that FTO could reduce the mRNA stability of DACT1 via m 6 A demethylation, which decreased DACT1 expression and further activated the Wnt signaling pathway. The oncogenic effect of FTO on OS was dependent on DACT1. In addition, the m 6 A reader IGF2BP1 was validated to participate in the regulation of DACT1. Entacapone, a conventional drug for Parkinson's disease, was confirmed to suppress OS via m 6 A-mediated regulation through the FTO/DACT1 axis. Our findings demonstrate that FTO may be a novel therapeutic target and that entacapone has preclinical value to be repurposed for OS., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

We recently reported that genetic or pharmacological inhibition of insulin-like growth factor receptor (IGF-1R) slows DNA replication and induces replication stress by downregulating the regulatory subunit RRM2 of ribonucleotide reductase, perturbing deoxynucleotide triphosphate (dNTP) supply. Aiming to exploit this effect in therapy we performed a compound screen in five breast cancer cell lines with IGF neutralising antibody xentuzumab. Inhibitor of checkpoint kinase CHK1 was identified as a top screen hit. Co-inhibition of IGF and CHK1 caused synergistic suppression of cell viability, cell survival and tumour growth in 2D cell culture, 3D spheroid cultures and in vivo. Investigating the mechanism of synthetic lethality, we reveal that CHK1 inhibition in IGF-1R depleted or inhibited cells further downregulated RRM2, reduced dNTP supply and profoundly delayed replication fork progression. These effects resulted in significant accumulation of unreplicated single-stranded DNA and increased cell death, indicative of replication catastrophe. Similar phenotypes were induced by IGF:WEE1 co-inhibition, also via exacerbation of RRM2 downregulation. Exogenous RRM2 expression rescued hallmarks of replication stress induced by co-inhibiting IGF with CHK1 or WEE1, identifying RRM2 as a critical target of the functional IGF:CHK1 and IGF:WEE1 interactions. These data identify novel therapeutic vulnerabilities and may inform future trials of IGF inhibitory drugs., (© 2021. The Author(s).)

Rifamycins are a class of antibiotics that were first discovered in 1957 and are known for their use in treating tuberculosis (TB). Rifamycins exhibit bactericidal activity against many Gram-positive and Gram-negative bacteria by inhibiting RNA polymerase (RNAP); however, resistance is prevalent and the mechanisms range from primary target modification and antibiotic inactivation to cytoplasmic exclusion. Further, phenotypic resistance, in which only a subpopulation of bacteria grow in concentrations exceeding their minimum inhibitory concentration, and tolerance, which is characterized by reduced rates of bacterial cell death, have been identified as additional causes of rifamycin failure. Here we summarize current understanding and recent developments regarding this critical antibiotic class., (© 2021. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Application of differentiation therapy targeting cellular plasticity for the treatment of solid malignancies has been lagging. Nasopharyngeal carcinoma (NPC) is a distinctive cancer with poor differentiation and high prevalence of Epstein-Barr virus (EBV) infection. Here, we show that the expression of EBV latent protein LMP1 induces dedifferentiated and stem-like status with high plasticity through the transcriptional inhibition of CEBPA. Mechanistically, LMP1 upregulates STAT5A and recruits HDAC1/2 to the CEBPA locus to reduce its histone acetylation. HDAC inhibition restored CEBPA expression, reversing cellular dedifferentiation and stem-like status in mouse xenograft models. These findings provide a novel mechanistic epigenetic-based insight into virus-induced cellular plasticity and propose a promising concept of differentiation therapy in solid tumor by using HDAC inhibitors to target cellular plasticity., (© 2021. The Author(s).)

The aberrant classical miRNAs are considered to play significant roles in tumor progression. However, it remains unclear for nonclassical miRNAs, a set of Drosha-independent miRNAs in the process of various biology. Here, we reveal that a nonclassical miR-4646-5p plays a pivotal role in gastric cancer (GC) metastasis. MiR-4646-5p, one of Drosha-independent mirtronic miRNA, is aberrant up-regulated in Drosha-low expressed GC and Drosha-knockdown gastric cancer cells. Mirtronic miR-4646-5p is a specific transcription splicing product of intron 3 of the host gene Abhd16a with the aid of SRSF2. The enhanced miR-4646-5p can stabilize HIF1A by targeting PHD3 to positive feedback regulate Abhd16a and miR-4646-5p itself expressions. ABHD16A, as an emerging phosphatidylserine-specific lipase, involves in lipid metabolism leading to lysophosphatidylserines (lyso-PSs) accumulation, which stimulates RhoA and downstream LIMK/cofilin cascade activity through GPR34/Gi subunit, thus causes metastasis of gastric cancer. In addition, miR-4646-5p/PHD3/HIF1A signaling can also up-regulate RhoA expression and synergistically promote gastric cancer cell invasion and metastasis. Our study provides new insights of nonclassical mirtronic miRNA on tumor progress and may serve as a new diagnostic biomarker for gastric cancer. MiR-4646-5p and its host gene Abhd16a mediated abnormal lipid metabolism may be a new target for clinical treatment of gastric cancer., (© 2021. The Author(s).)

Invasion and metastasis are the leading causes of death in patients with breast cancer (BC), and epithelial-mesenchymal transformation (EMT) plays an essential role in this process. Here, we found that Lnc-408, a novel long noncoding RNA (lncRNA), is significantly upregulated in BC cells undergoing EMT and in BC tumor with lymphatic metastases compared with those without lymphatic metastases. Lnc-408 can enhance BC invasion and metastasis by regulating the expression of LIMK1. Mechanistically, Lnc-408 serves as a sponge for miR-654-5p to relieve the suppression of miR-654-5p on its target LIMK1. Knockdown or knockout of Lnc-408 in invasive BC cells clearly decreased LIMK1 levels, and ectopic Lnc-408 in MCF-7 cells increased LIMK1 expression to promote cell invasion. Lnc-408-mediated enhancement of LIMK1 plays a key role in cytoskeletal stability and promotes invadopodium formation in BC cells via p-cofilin/F-actin. In addition, the increased LIMK1 also facilitates the expression of MMP2, ITGB1, and COL1A1 by phosphorylating CREB. In conclusion, our findings reveal that Lnc-408 promotes BC invasion and metastasis via the Lnc-408/miR-654-5p/LIMK1 axis, highlighting a novel promising target for the diagnosis and treatment of BC.

The stability properties of dark solitons in quasi-one-dimensional Bose-Einstein condensate (BEC) loaded in a Jacobian elliptic sine potential with three-body interactions are investigated theoretically. The solitons are obtained by the Newton-Conjugate Gradient method. A stationary cubic-quintic nonlinear Schrödinger equation is derived to describe the profiles of solitons via the multi-scale technique. It is found that the three-body interaction has distinct effect on the stability properties of solitons. Especially, such a nonlinear system supports the so-called dark solitons (kink or bubble), which can be excited not only in the gap, but also in the band. The bubbles are always linearly and dynamically unstable, and they cannot be excited if the three-body interaction is absent. Both stable and unstable kinks, depending on the physical parameters, can be excited in the BEC system.

The hostile hypoxic microenvironment takes primary responsibility for the rapid expansion of breast cancer tumors. However, the underlying mechanism is not fully understood. Here, using RNA sequencing (RNA-seq) analysis, we identified a hypoxia-induced long noncoding RNA (lncRNA) KB-1980E6.3, which is aberrantly upregulated in clinical breast cancer tissues and closely correlated with poor prognosis of breast cancer patients. The enhanced lncRNA KB-1980E6.3 facilitates breast cancer stem cells (BCSCs) self-renewal and tumorigenesis under hypoxic microenvironment both in vitro and in vivo. Mechanistically, lncRNA KB-1980E6.3 recruited insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) to form a lncRNA KB-1980E6.3/IGF2BP1/c-Myc signaling axis that retained the stability of c-Myc mRNA through increasing binding of IGF2BP1 with m6A-modified c-Myc coding region instability determinant (CRD) mRNA. In conclusion, we confirm that lncRNA KB-1980E6.3 maintains the stemness of BCSCs through lncRNA KB-1980E6.3/IGF2BP1/c-Myc axis and suggest that disrupting this axis might provide a new therapeutic target for refractory hypoxic tumors.

The change in gut microbiota is an important mechanism of the amelioration of type 2 diabetes mellitus (T2DM) after bariatric surgery. Here, we observe that the modified jejunoileal bypass effectively decreases body weight gain, fasting blood glucose, and lipids level in serum; additionally, islet β-cell function, glucose tolerance, and insulin resistance were markedly ameliorated. The hypoglycemic effect and the improvement in islet β-cell function depend on the changes in gut microbiota structure. modified jejunoileal bypass increases the abundance of gut Escherichia coli and Ruminococcus gnavus and the levels of serum glycine, histidine, and glutamine in T2DM rats; and decreases the abundance of Prevotella copri and the levels of serum branched chain amino acids, which are significantly related to the improvement of islet β-cell function in T2DM rats. Our results suggest that amino acid metabolism may contribute to the islet β-cell function in T2DM rats after modified jejunoileal bypass and that improving gut microbiota composition is a potential therapeutic strategy for T2DM.

Due to the independence of the gradiometer instrument's orientation in space, the second invariant [Formula: see text] of gravity gradients in combination with individual gravity gradients are demonstrated to be valid for gravity field determination. In this contribution, we develop a novel gravity field model named I3GG, which is built mainly based on three novel elements: (1) proposing to utilize the third invariant [Formula: see text] of the gravity field and steady-state ocean circulation explorer (GOCE) gravity gradient tensor, instead of using the [Formula: see text], similar to the previous studies; (2) applying an alternative two-dimensional fast fourier transform (2D FFT) method; (3) showing the advantages of [Formula: see text] over [Formula: see text] in the effect of measurement noise from the theoretical and practical computations. For the purpose of implementing the linearization of the third invariant, this study employs the theory of boundary value problems with sphere approximation at an accuracy level of [Formula: see text]. In order to efficiently solve the boundary value problems, we proposed an alternative method of 2D FFT, which uses the coherent sampling theory to obtain the relationship between the 2D FFT and the third invariant measurements and uses the pseudo-inverse via QR factorization to transform the 2D Fourier coefficients to spherical harmonic ones. Based on the GOCE gravity gradient data of the nominal mission phase, a novel global gravity field model (I3GG) is derived up to maximum degree/order 240, corresponding to a spatial resolution of 83 km at the equator. Moreover, in order to investigate the differences of gravity field determination between [Formula: see text] with [Formula: see text], we applied the same processing strategy on the second invariant measurements of the GOCE mission and we obtained another gravity field model (I2GG) with a maximum degree of 220, which is 20 degrees lower than that of I3GG. The root-mean-square (RMS) values of geoid differences indicates that the effects of measurement noise of I3GG is about 20% lower than that on I2GG when compared to the gravity field model EGM2008 (Earth Gravitational Model 2008) or EIGEN-5C (EIGEN: European Improved Gravity model of the Earth by New techniques). Then the accuracy of I3GG is evaluated independently by comparison the RMS differences between Global Navigation Satellite System (GNSS)/leveling data and the model-derived geoid heights. Meanwhile, the re-calibrated GOCE data released in 2018 is also dealt with and the corresponding result also shows the similar characteristics.

In an increasingly connected global market, news sentiment towards one company may not only indicate its own market performance, but can also be associated with a broader movement on the sentiment and performance of other companies from the same or even different sectors. In this paper, we apply NLP techniques to understand news sentiment of 87 companies among the most reported on Reuters for a period of 7 years. We investigate the propagation of such sentiment in company networks and evaluate the associated market movements in terms of stock price and volatility. Our results suggest that, in certain sectors, strong media sentiment towards one company may indicate a significant change in media sentiment towards related companies measured as neighbours in a financial network constructed from news co-occurrence. Furthermore, there exists a weak but statistically significant association between strong media sentiment and abnormal market return as well as volatility. Such an association is more significant at the level of individual companies, but nevertheless remains visible at the level of sectors or groups of companies.

Endometrial cancer (EC) is a common gynaecological cancer worldwide. Exosomes, secreted by living cells and detected in various body fluids, can exchange information between organs and compartments to affect cellular functions, such as proliferation, apoptosis, migration and angiogenesis. We hypothesise that plasma exosomal contents are altered during cancer progression and promote cancer growth and angiogenesis by delivering biomolecules to cancer and vascular endothelial cells. In this study, circulating exosomes derived from EC patients and age-matched healthy people were acquired by commercial kits. Cell counting kit-8, Transwell and Matrigel tube formation assays showed that circulating exosomes from EC patients promote EC cell growth and human umbilical vein endothelial cell (HUVEC) angiogenesis. Next, proteomic analysis and ELISA revealed that plasma exosomal lectin galactoside-binding soluble 3 binding protein (LGALS3BP) increased during EC progression. Moreover, to explore the function of exosomal LGALS3BP, we acquired exosomes containing high levels of LGALS3BP by overexpressing LGALS3BP in human embryonic kidney 293 cells, and we demonstrated that highly contained exosomal LGALS3BP contributed to EC cell proliferation and migration and HUVEC functions via the activation of the PI3K/AKT/VEGFA signalling pathway both in vitro and in vivo. Finally, high LGALS3BP expression was observed in human EC tissue, which indicated a poor prognosis. In addition, immunohistochemical analysis of human EC tissues revealed that LGALS3BP expression was correlated with VEGFA expression and blood vessel density. Hence, we proposed that plasma exosomes containing LGALS3BP contributed to EC growth and angiogenesis during EC progression, which also provided a novel perspective on EC diagnosis and prognosis.

Protein structure can provide insights that help biologists to predict and understand protein functions and interactions. However, the number of known protein structures has not kept pace with the number of protein sequences determined by high-throughput sequencing. Current techniques used to determine the structure of proteins are complex and require a lot of time to analyze the experimental results, especially for large protein molecules. The limitations of these methods have motivated us to create a new approach for protein structure prediction. Here we describe a new approach to predict of protein structures and structure classes from amino acid sequences. Our prediction model performs well in comparison with previous methods when applied to the structural classification of two CATH datasets with more than 5000 protein domains. The average accuracy is 92.5% for structure classification, which is higher than that of previous research. We also used our model to predict four known protein structures with a single amino acid sequence, while many other existing methods could only obtain one possible structure for a given sequence. The results show that our method provides a new effective and reliable tool for protein structure prediction research.

Brain tumors are dynamic complex ecosystems with multiple cell types. To model the brain tumor microenvironment in a reproducible and scalable system, we developed a rapid three-dimensional (3D) bioprinting method to construct clinically relevant biomimetic tissue models. In recurrent glioblastoma, macrophages/microglia prominently contribute to the tumor mass. To parse the function of macrophages in 3D, we compared the growth of glioblastoma stem cells (GSCs) alone or with astrocytes and neural precursor cells in a hyaluronic acid-rich hydrogel, with or without macrophage. Bioprinted constructs integrating macrophage recapitulate patient-derived transcriptional profiles predictive of patient survival, maintenance of stemness, invasion, and drug resistance. Whole-genome CRISPR screening with bioprinted complex systems identified unique molecular dependencies in GSCs, relative to sphere culture. Multicellular bioprinted models serve as a scalable and physiologic platform to interrogate drug sensitivity, cellular crosstalk, invasion, context-specific functional dependencies, as well as immunologic interactions in a species-matched neural environment.

The recent novel coronavirus disease (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is seeing a rapid increase in infected patients worldwide. The host immune response to SARS-CoV-2 appears to play a critical role in disease pathogenesis and clinical manifestations. SARS-CoV-2 not only activates antiviral immune responses, but can also cause uncontrolled inflammatory responses characterized by marked pro-inflammatory cytokine release in patients with severe COVID-19, leading to lymphopenia, lymphocyte dysfunction, and granulocyte and monocyte abnormalities. These SARS-CoV-2-induced immune abnormalities may lead to infections by microorganisms, septic shock, and severe multiple organ dysfunction. Therefore, mechanisms underlying immune abnormalities in patients with COVID-19 must be elucidated to guide clinical management of the disease. Moreover, rational management of the immune responses to SARS-CoV-2, which includes enhancing anti-viral immunity while inhibiting systemic inflammation, may be key to successful treatment. In this review, we discuss the immunopathology of COVID-19, its potential mechanisms, and clinical implications to aid the development of new therapeutic strategies against COVID-19.