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In this work, Cr2O3/TiO2 composite coatings were prepared on α-Al2O3 insulating ceramic matrix surface by screen printing and solid phase sintering methods to yield an average film thickness of about 14.10 μm. Scanning electron microscopy (SEM) revealed changes in the pore structures of the coatings at different TiO2 contents. The atomic force microscopy (AFM) analysis of the coating surface roughness suggested a TiO2 content of 0.025 mol to yield the best surface roughness and pore structure of the coating. The calculation showed an increase in the energy level of the deep trap center on the surface from 1.506 eV to 1.547 eV, reaching a maximum. The surface resistivity of insulating ceramics decreased from 1016 Ω to 1012 Ω. The formation of deep surface traps and the decrease in surface resistivity promoted charge dispersion and suppressed the formation of flashover channels, effectively improving the surface flashover voltage of the ceramics.

Abstract Background Predicting an individual’s risk of death from COVID-19 is essential for planning and optimising resources. However, since the real-world mortality rate is relatively low, particularly in places like Hong Kong, this makes building an accurate prediction model difficult due to the imbalanced nature of the dataset. This study introduces an innovative application of graph convolutional networks (GCNs) to predict COVID-19 patient survival using a highly imbalanced dataset. Unlike traditional models, GCNs leverage structural relationships within the data, enhancing predictive accuracy and robustness. By integrating demographic and laboratory data into a GCN framework, our approach addresses class imbalance and demonstrates significant improvements in prediction accuracy. Methods The cohort included all consecutive positive COVID-19 patients fulfilling study criteria admitted to 42 public hospitals in Hong Kong between January 23 and December 31, 2020 (n = 7,606). We proposed the population-based graph convolutional neural network (GCN) model which took blood test results, age and sex as inputs to predict the survival outcomes. Furthermore, we compared our proposed model to the Cox Proportional Hazard (CPH) model, conventional machine learning models, and oversampling machine learning models. Additionally, a subgroup analysis was performed on the test set in order to acquire a deeper understanding of the relationship between each patient node and its neighbours, revealing possible underlying causes of the inaccurate predictions. Results The GCN model was the top-performing model, with an AUC of 0.944, considerably outperforming all other models (p

The thermal hazards generated during the tunnel boring machine construction process significantly impact the physical and mental health of personnel. A field test was conducted on the tunnel of Metro Line 1 in Changsha, China, where the average temperature in the work zone reached up to 33.16 °C, and the air velocity was generally below 0.2 m/s. These conditions were unfavorable for ventilation and heat dissipation. In this paper, a full-scale CFD simulation model was established to simulate the construction environment and analyze the cooling demand. The results indicated that increasing the fresh air velocity could lower the temperature in the work zone; however, this effect was limited. When the fresh air temperature exceeded a certain threshold, it actually raised the average temperature of the work zone. Consequently, there is a need for supplementary cooling of the fresh air during the hot summer months. At a fresh air velocity of 15 m/s, the maximum temperature in the work zone was recorded at 27.8 °C when the fresh air was cooled down to 22.5 °C through auxiliary cooling measures. This approach effectively controlled the temperature in the work zone, reduced flow dead zones, and significantly improved air distribution and heat dissipation. Additionally, it ensured the physical and mental well-being of the construction workers and the safe operation of the equipment. This study provides valuable guidance for managing thermal environments in underground tunnel construction.

Abstract Objective This study aims to screen the differentially expressed long non-coding RNAs (DELncRNAs) related to the regulation of epithelial-mesenchymal transition (EMT) in hypospadias in mesenchymal stem cell-derived exosomes (MSC-Exons) and explore the potential mechanism of these lncRNAs for the EMT in hypospadias. Methods In this study, the microarray data related to MSC-Exos and hypospadias were downloaded from Gene Expression Omnibus (GEO). Besides, the lncRNAs highly expressed in MSC-Exos and the differentially expressed mRNAs and lncRNAs in children with hypospadias were screened, respectively. In addition, the lncRNAs enriched in MSC-Exos and differentially expressed lncRNAs in hypospadias were intersected to obtain the final DElncRNAs. Moreover, the co-expression interaction pairs of differentially expressed lncRNAs and mRNAs were analyzed to construct a Competing Endogenous RNA (ceRNA) network. Finally, the candidate lncRNAs in exosomes were subjected to in vitro cell function verification. Results In this study, a total of 4 lncRNAs were obtained from the microarray data analysis. Further, a ceRNA regulatory network of MSC-Exo-derived lncRNAs related to the regulation of EMT in hypospadias was constructed, including 4 lncRNAs, 2 mRNAs, and 6 miRNAs. The cell function verification results indicated that the exosomes secreted by MSCs may transport HLA complex group 18 (HCG18) into target cells, which promoted the proliferation, migration, and EMT of these cells. Conclusion MSC-Exo-derived lncRNA HCG18 can enter target cells, and it may be involved in the regulation of EMT in hypospadias through the ceRNA network.

Abstract Oxidative stress-induced lipid accumulation is mediated by lipid droplets (LDs) homeostasis, which sequester vulnerable unsaturated triglycerides into LDs to prevent further peroxidation. Here we identify the upregulation of lipopolysaccharide-binding protein (LBP) and its trafficking through LDs as a mechanism for modulating LD homeostasis in response to oxidative stress. Our results suggest that LBP induces lipid accumulation by controlling lipid-redox homeostasis through its lipid-capture activity, sorting unsaturated triglycerides into LDs. N-acetyl-L-cysteine treatment reduces LBP-mediated triglycerides accumulation by phospholipid/triglycerides competition and Peroxiredoxin 4, a redox state sensor of LBP that regulates the shuttle of LBP from LDs. Furthermore, chronic stress upregulates LBP expression, leading to insulin resistance and obesity. Our findings contribute to the understanding of the role of LBP in regulating LD homeostasis and against cellular peroxidative injury. These insights could inform the development of redox-based therapies for alleviating oxidative stress-induced metabolic dysfunction.

Abstract Background The tumour microenvironment (TME) consists of tumour-supportive immune cells, endothelial cells, and fibroblasts. PhenoCycler, a high-plex single cell spatial biology imaging platform, is used to characterize the complexity of the TME. Researchers worldwide harvest and bank tissues from mouse models which are employed to model a plethora of human disease. With the explosion of interest in spatial biology, these panoplies of archival tissues provide a valuable resource to answer new questions. Here, we describe our protocols for developing tunable PhenoCycler multiplexed imaging panels and describe our open-source data analysis pipeline. Using these protocols, we used PhenoCycler to spatially resolve the TME of 8 routinely employed pre-clinical models of lymphoma, breast cancer, and melanoma preserved as FFPE. Results Our data reveal distinct TMEs in the different cancer models that were imaged and show that cell-cell contacts differ depending on the tumour type examined. For instance, we found that the immune infiltration in a murine model of melanoma is altered in cellular organization in melanomas that become resistant to αPD-1 therapy, with depletions in a number of cell-cell interactions. Conclusions This work presents a valuable resource study seamlessly adaptable to any field of research involving murine models. The methodology described allows researchers to address newly formed hypotheses using archival materials, bypassing the new to perform new mouse studies.

Background: Central nervous system (CNS) injury is the most prominent feature of heatstroke and the hippocampus is prone to damage. However, the mechanisms underlying the heatstroke-induced hippocampal injury remain unclear. Hyperbaric oxygen (HBO) therapy prevents CNS injury in heatstroke mice. However, the underlying mechanisms of HBO in heatstroke-induced hippocampal injury remain unclear. This study aimed to elucidate the protective effects of HBO against hippocampal injury and its potential role in microglial pyroptosis in heatstroke rats.Methods: A rat heatstroke model and a heat stress model with a mouse microglial cell line (BV2) were, respectively, used to illustrate the effect of HBO on heat-induced microglial pyroptosis in vivo and in vitro. We used a combination of molecular and histological methods to assess microglial pyroptosis and neuroinflammation both in vivo and in vitro.Results: The results revealed that HBO improved heatstroke-induced survival outcomes, hippocampal injury, and neurological dysfunction in rats. In addition, HBO mitigates microglial pyroptosis and reduces the expression of pro-inflammatory cytokines in the hippocampus of heatstroke rats. In vitro experiments showed that HBO attenuated BV2 cell injury under heat stress. Furthermore, HBO prevented heat-induced pyroptosis of BV2 cells, and the expression of pro-inflammatory cytokines IL-18 and IL-1β was reduced. Mechanistically, HBO alleviates heatstroke-induced neuroinflammation and hippocampal injury by preventing microglial pyroptosis. Conclusions: In conclusion, HBO attenuates heatstroke-induced neuroinflammation and hippocampal injury by inhibiting microglial pyroptosis.

Protein products perform important roles in the biochemistry field, but the thermal inactivation of proteins will increase the difficulty of their transport, storage and application. Therefore, improving the thermal stability of proteins has become a thorny challenge. Natural molecular chaperones can efficiently improve the resistance of proteins to environmental stimuli by reversible supramolecular assembly with proteins. Inspired by this machine, herein we designed a nanochaperone (nChap) with thermo-responsive amphiphilic surfaces that can prevent thermal denaturation and facilitate refolding of green fluorescent proteins (GFPs). By mimicking the hydrophobic microregion of natural chaperones, this nChap can effectively capture free GFPs and hide them into surface confined spaces, thereby shielding exposed hydrophobic sites of GFPs and preventing their irreversible thermal aggregation. When the heat stimulation disappeared, the thermosensitive segments of the nChaps underwent the hydrophilic transition, which provided suitable microenvironments for GFPs refolding. More importantly, nChaps could also actively adsorb to the surface of immobilized GFPs at high temperatures and realize the satisfactory dissociation of the nChap-protein complex upon cooling, which exhibited excellent chaperone-like activity. This work provides significant insights for understanding and developing strategies to improve protein stability.

Background Psychological distress has been a growing challenge to healthy living worldwide. Special attention has been concentrated on examining the cost of psychological distress on the life satisfaction of college students who are vulnerable groups coping with the challenge. The purpose of this study is to explore the roles of physical literacy (PL) and mindfulness in mediating the impact of psychological distress on life satisfaction among college students in China. Methods A sample of 653 students from six universities across three cities in China participated in an online survey, which included measures of PL, mindfulness, life satisfaction, as well as stress, anxiety, and depression levels. Structural equation modeling (SEM) was implemented to analyze the survey data. Results The findings of the SEM analysis demonstrated an acceptable model fit (X2/df = 3.63, CFI = 0.951, TLI = 0.940, RMSEA = 0.068, 90% CI = [0.060, 0.075], SRMR = 0.051) with a large effect size (R2 = 0.36) for life satisfaction, indicating that 36% of the variation in life satisfaction could be explained by the model. In addition, significant partial-mediation effects of PL and mindfulness were observed in the relationship between psychological distress and life satisfaction. These findings provide empirical support for the notion that interventions targeting PL and mindfulness practices may effectively enhance well-being and alleviate psychological distress among college students. Furthermore, this study suggests that integrating PL and mindfulness components into physical education and activity programs could be beneficial in meeting individuals’ holistic health needs.

Abstract Background Paranasal sinus angiosarcoma is an uncommon malignancy, with only a few reported cases worldwide. Although it exhibits multiple symptoms, facial paralysis has not been previously documented as a noticeable presentation. Case Presentation In this case, we report a 40-year-old male who presented with facial numbness and pain for one month, weakness of his facial muscles for 15 days, and recurrent right epistaxis for 1 year. He had a history of nasal inflammatory polyps with chronic sinusitis. Computed tomography and magnetic resonance imaging showed space-occupying lesions in the right nasal cavity and maxillary sinus, with bone destruction occurring in the sinus wall and turbinate. This patient then underwent endoscopic surgery. According to the histopathological and immunohistochemical results, he was eventually diagnosed with paranasal sinus angiosarcoma in April 2021. To date, this patient has not initiated any radiotherapy or chemotherapy and has survived with lymphatic metastasis for at least 3 years. Conclusions This manuscript suggests that paranasal sinus angiosarcoma can present with facial paralysis. Moreover, pathological and immunohistochemical tests are still vital for diagnosing paranasal sinus angiosarcoma and differential diagnosis. Additionally, regular follow-up is crucial for patients with paranasal sinus angiosarcoma, enabling monitoring of recurrence, metastasis, and recovery while contributing valuable clinical data to understanding this rare disease and associated research endeavours.

Traditional drilling methods often face difficulty meeting the demand for efficient and accurate coring under complex geological conditions. Cordless coring is an advanced technology that uses hydraulic lifting to carry out coring, which can achieve automation and automated and intelligent drilling operations. In this research, a new type of hydraulic lifting cordless coring drilling tool is designed. Moreover, a numerical simulation model of the fluid flow in the annulus between the spearhead and spool of the cordless coring drilling tool was established. Orthogonal simulation tests are carried out, and according to the orthogonal test data, a numerical prediction model of the spool annulus fluid field based on the Backpropagation Neural Network (BP neural network) is established. The prediction of the flow rate of the drilling fluid and the spool back-pressure ratio was obtained when the structural parameters of the spearhead and the spool annulus were different. A multi-objective optimization of the annulus flow structure of the cordless core drilling tool has been carried out. The optimization objectives include deciding the back pressure ratio of the spool overcoming the spring and the flow rate of the drilling fluid. According to the established nonlinear optimization model and based on the improved Non-dominated Sorting Genetic Algorithm II (NSGA-II) multi-objective optimization algorithm, it is verified that the convergence speed and diversity of the improved algorithm are better than those before the improvement. The simulation and experimental validation are carried out. It is verified that the flow rate of drilling fluid increased by 33.56% after optimization, and the force ratio was lowered by 5.825%. Finally, based on the simulation and optimization results, the φ96 cordless core drilling tool was manufactured on a trial basis, and on-site concrete drilling, coring, and hydraulic lifting operations were conducted for smooth coring and lifting. This study could provide an important scientific basis and technical support for the application and development of hydraulic lifting cordless coring technology.

Previous studies on the Ke’eryin pegmatite-type lithium ore field in the Songpan–Ganzi Orogenic Belt have explored the characteristics of the parent rock but have not precisely determined its magma source area. This uncertainty limits our understanding of the regularity of lithium ore formation in this region. In this study, to address the issue of the precise source area of the parent rock of lithium mineralization, a detailed analysis of the Li isotope composition of the ore-forming parent rock (Ke’eryin two-mica monzogranite) and its potential source rocks (Triassic Xikang Group metamorphic rocks) was conducted. The δ7Li values of the Ke’eryin two-mica monzogranite, Xikang Group metasandstone, and Xikang Group mica schist are −3.3–−0.7‰ (average: −1.43‰), +0.1–+6.9‰ (average: +3.83‰), and −9.1–0‰ (average: −5.00‰), respectively. The Li isotopic composition of the Ke’eryin two-mica monzogranite is notably different from the metasandstone and aligns more closely with the mica schist, suggesting that the mica schist is its primary source rock. The heavy Li isotopic composition of the two-mica monzogranite compared to the mica schist may have resulted from the separation of the peritectic garnet into the residual phase during the biotite dehydration melting process. Moreover, the low-temperature weathering of the source rocks may have been the main factor leading to the lighter lithium isotope composition of the Xikang Group mica schist compared to the metasandstone. Further analysis suggests that continental crust weathering and crustal folding and thickening play crucial roles in the enrichment of lithium during multi-cycle orogenies.

The morphological architecture of inflorescence influences seed production. The regulatory mechanisms underlying alfalfa (Medicago sativa) inflorescence elongation remain unclear. Therefore, in this study, we conducted a comparative analysis of the transcriptome, proteome, and metabolome of two extreme materials at three developmental stages to explore the mechanisms underlying inflorescence elongation in alfalfa. We observed the developmental processes of long and short inflorescences and found that the elongation capacity of alfalfa with long inflorescence was stronger than that of alfalfa with short inflorescences. Furthermore, integrative analysis of the transcriptome and proteome indicated that the phenylpropanoid biosynthesis pathway was closely correlated with the structural formation of the inflorescence. Additionally, we identified key genes and proteins associated with lignin biosynthesis based on the differential expressed genes and proteins (DEGs and DEPs) involved in phenylpropanoid biosynthesis. Moreover, targeted hormone metabolome analysis revealed that IAA, GA, and CK play an important role in the peduncle elongation of alfalfa inflorescences. Based on omics analysis, we detected key genes and proteins related to plant hormone biosynthesis and signal transduction. From the WGCNA and WPCNA results, we furthermore screened 28 candidate genes and six key proteins that were correlated with lignin biosynthesis, plant hormone biosynthesis, and signaling pathways. In addition, 19 crucial transcription factors were discovered using correlation analysis that might play a role in regulating candidate genes. This study provides insight into the molecular mechanism of inflorescence elongation in alfalfa and establishes a theoretical foundation for improving alfalfa seed production.

The volatile aroma compounds of 15 representative dark tea products in Sichuan Province were analyzed by sensory evaluation and headspace solid phase micro-extraction (HS-SPME) combined with gas chromato graphy-mass spectrometry (GC-MS) in this study. The results showed that ''stale flavor'' were the main aromatic aroma type of Sichuan dark tea, other tea samples had glutinous rice aroma, sweet , sour gas and smoky, which were typical of dark tea. A total of 121 aroma components were detected in the dark teas,and the major aroma compounds were alkenes (5.41%~42.38%), aldehydes (7.26%~19.97%), ketones (6.68%~39.26%) and alcohols (14.03%~27.06%). 7 principal components were extracted from the 32 common aroma components byprincipal component analysis（principal component analysis, PCA） and the total contribution attained 84.27%. Characteristic aroma components included β-ionone, 1-octen-3-ol, 2,3-dihydro-2,2,6-trimethyl,5,6-epoxy-β-ionone, geranylacetone, 3,5-octadienone (E,E), trans-2-octenal, 2-n-pentylfuran, which played important roles in the aromatic characteristics of strong and pure ''stale flavor'' of Sichuan dark tea. Relative odor activity value (ROAV) was used to evaluate the contribution of aroma components to flavor characteristics of Sichuan dark tea. It was found that the ROAV values of (E,E)-2, 4-heptadienal, linalool, geraniyl acetone, α-ionone and 1-octene-3-ol were greater than 1. The above components made great contributions to the formation of aroma characteristics of Sichuan dark tea. This study could provide a theoretical reference for research on characteristic aroma formation and quality evaluation of Sichuan dark tea.

Cholangiocarcinoma (CCA) is a highly aggressive malignant tumor that originates from the biliary system. With restricted treatment options at hand, the challenging aspect of early CCA diagnosis leads to a bleak prognosis. Besides the intrinsic characteristics of tumor cells, the generation and progression of CCA are profoundly influenced by the tumor microenvironment, which engages in intricate interactions with cholangiocarcinoma cells. Of notable significance is the role of extracellular vesicles as key carriers in enabling communication between cancer cells and the tumor microenvironment. This review aims to provide a comprehensive overview of current research examining the interplay between extracellular vesicles and the tumor microenvironment in the context of CCA. Specifically, we will emphasize the significant contributions of extracellular vesicles in molding the CCA microenvironment and explore their potential applications in the diagnosis, prognosis assessment, and therapeutic strategies for this aggressive malignancy.

Toad skin (TS) and toad venom (TV) are two different traditional Chinese medicine (TCM) prepared from Bufo bufo gargarizans Cantor and Bufo melanostictus Schneider. Both of them were used in the treatment of ulcers, and now they are regarded as animal drugs with anti-tumor activity. However, the comparison analysis between their compositions and anti-tumor active ingredients has not been elucidated clearly. In this study, technology of ultra-performance liquid chromatography coupled with tandem quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) and bioactivity-based molecular networking were applied to investigate the anti-tumor active ingredients of TS and TV. A method of collision energies-relied mass spectrometry combined with molecular networking was initially developed for identifying their chemical components. A combination of Cytoscape and molecular networking was then employed to analyze the prototype constitutes of TS absorbed in rat serum. In addition, cytotoxicity test was applied to evaluate their anti-proliferative activities against human gastric cancer (GC) cells. As a result, a total of 162 compounds were tentatively characterized, and four structural types existed in both TS and TV, including bufogenins, bufotoxins, indolealkylamines (IAAs), and acyl-arginine. Cyclic dipeptides could only be detected in TS, and the total number of bufogenins and bufotoxins in TV was higher than that of TS. Both of them significantly inhibited the viability of SGC7901 cells, and 70% methanol eluate of TS was the most potential active fraction. 44 prototype compounds in TS were identified, from which three types of potential tumor cytotoxic components, including bufogenins, IAAs, and cyclic dipeptides, were predicted. In human GC cells SGC7901, a mixture of nine bufogenins, including bufotalin, cinobufotalin, gamabufotalin, telocinobufagin, cinobufagin, bufarenogin, arenobufagin, hellebrigenin, and desacetylcinobufotalin, was conducted as bioactive components, which exerted a significant inhibitory effect on the cell viability of SGC7901 cells with a half maximal inhibitory concentration (IC50) value of 0.23 (0.19–0.27, 95%CI) μg/mL. Comparison of their chemical composition and anti-tumor activity reveals that TS might be able to partially replace TV, whilst bufogenins are the potential active ingredients.

Floral bud growth influences seed yield and quality; however, the molecular mechanism underlying the development of floral buds in alfalfa (Medicago sativa) is still unclear. Here, we comprehensively analyzed the transcriptome and targeted metabolome across the early, mid, and late bud developmental stages (D1, D2, and D3) in alfalfa. The metabolomic results revealed that gibberellin (GA), auxin (IAA), cytokinin (CK), and jasmonic acid (JA) might play an essential role in the developmental stages of floral bud in alfalfa. Moreover, we identified some key genes associated with GA, IAA, CK, and JA biosynthesis, including CPS, KS, GA20ox, GA3ox, GA2ox, YUCCA6, amid, ALDH, IPT, CYP735A, LOX, AOC, OPR, MFP2, and JMT. Additionally, many candidate genes were detected in the GA, IAA, CK, and JA signaling pathways, including GID1, DELLA, TF, AUX1, AUX/IAA, ARF, GH3, SAUR, AHP, B-ARR, A-ARR, JAR1, JAZ, and MYC2. Furthermore, some TFs related to flower growth were screened in three groups, such as AP2/ERF-ERF, MYB, MADS-M-type, bHLH, NAC, WRKY, HSF, and LFY. The findings of this study revealed the potential mechanism of floral bud differentiation and development in alfalfa and established a theoretical foundation for improving the seed yield of alfalfa.

The petals of Medicago sativa ssp. sativa and M. sativa ssp. falcata are purple and yellow, respectively. Free hybridization between M. sativa ssp. sativa and M. sativa ssp. falcata has created hybrids with various flower colors in nature. Moreover, the flower colors of alfalfa are closely correlated with yield, nutritional quality, stress tolerance and other agronomic characteristics. To elucidate the underlying mechanisms of flower color formation in M. sativa ssp. sativa and M. sativa ssp. falcata, we conducted an integrative analysis of the transcriptome and metabolome of alfalfa with three different petal colors (purple, yellow and cream). The metabolic profiles suggested that anthocyanins and carotenoids are the crucial pigments in purple and yellow flowers, respectively. A quantitative exploration of the anthocyanin and carotenoid components indicated that the accumulations of cyanidin, delphinidin, peonidin, malvidin, pelargonidin and petunidin derivatives are significantly higher in purple flowers than in cream flowers. In addition, the content of carotenes (phytoene, α-carotene and β-carotene) and xanthophylls (α-cryptoxanthin, lutein, β-cryptoxanthin, zeaxanthin, antheraxanthin and violaxanthin derivatives) was markedly higher in yellow flowers than in cream flowers. Furthermore, we found that delphinidin-3,5-O-diglucoside and lutein were the predominant pigments accumulated in purple and yellow flowers, respectively. The transcriptomic results revealed that twenty-five upregulated structural genes (one C4H, three 4CL, twelve CHS, two CHI, one F3H, one F3′H, one F3′5′H and four DFR) are involved in the accumulation of anthocyanins in purple flowers, and nine structural genes (two PSY, one ZDS, two CRTISO, two BCH, one ZEP and one ECH) exert an effect on the carotenoid biosynthesis pathway in yellow flowers. The findings of this study reveal the underlying mechanisms of anthocyanin and carotenoid biosynthesis in alfalfa with three classic flower colors.

Melanomas reprogram their metabolism to rapidly adapt to therapy-induced stress conditions, allowing them to persist and ultimately develop resistance. We report that a subpopulation of melanoma cells tolerate MAPK pathway inhibitors (MAPKis) through a concerted metabolic reprogramming mediated by peroxisomes and UDP-glucose ceramide glycosyltransferase (UGCG). Compromising peroxisome biogenesis, by repressing PEX3 expression, potentiated the proapoptotic effects of MAPKis via an induction of ceramides, an effect limited by UGCG-mediated ceramide metabolism. Cotargeting PEX3 and UGCG selectively eliminated a subset of metabolically active, drug-tolerant CD36+ melanoma persister cells, thereby sensitizing melanoma to MAPKis and delaying resistance. Increased levels of peroxisomal genes and UGCG were found in patient-derived MAPKi-relapsed melanomas, and simultaneously inhibiting PEX3 and UGCG restored MAPKi sensitivity in multiple models of therapy resistance. Finally, combination therapy consisting of a newly identified inhibitor of the PEX3-PEX19 interaction, a UGCG inhibitor, and MAPKis demonstrated potent antitumor activity in preclinical melanoma models, thus representing a promising approach for melanoma treatment.

Background: The significance of hepatitis B virus (HBV) in cerebrospinal fluid (CSF) is unclear. Methods: Synchronous serum and CSF samples were collected from 13 patients. HBV DNA, full-length genome, quasispecies, phylogenetic tree, compartmentalization and mutation of the reverse transcriptase (RT) region were performed based on PCR and sequencing methods. Results: HBV DNA was detected in the CSF of 3 antiviral-naïve individuals and 1 individual after successful antiviral therapy. Complete full-length HBV genomes were isolated from the CSF of 5 individuals, including 2 with undetectable serum HBV DNA. Ten individuals exhibited distinct CSF-serum quasispecies, 8 harbored independent CSF-serum genetic compartmentalization and phylogenetic trees, and 5 lamivudine/entecavir-associated resistance mutations only in the CSF. The frequencies of rtL180M and rtM204I/V mutations in both serum and CSF were higher in HIV-HBV-coinfected individuals than in the HBV-monoinfected ones (serum: rtL180M: 3.9% vs. 0, P = 0.004; rtM204I/V: 21.3% vs. 0, P

Abstract A comprehensive comparison of the trends and drivers of global surface and canopy urban heat islands (termed Is and Ic trends, respectively) is critical for better designing urban heat mitigation strategies. However, such a global comparison remains largely absent. Using spatially continuous land surface temperatures and surface air temperatures (2003–2020), here we find that the magnitude of the global mean Is trend (0.19 ± 0.006°C/decade, mean ± SE) for 5,643 cities worldwide is nearly six‐times the corresponding Ic trend (0.03 ± 0.002°C/decade) during the day, while the former (0.06 ± 0.004°C/decade) is double the latter (0.03 ± 0.002°C/decade) at night. Variable importance scores indicate that global daytime Is trend is slightly more controlled by surface property, while background climate plays a more dominant role in regulating global daytime Ic trend. At night, both global Is and Ic trends are mainly controlled by background climate.

Although the relationship between anesthesia and consciousness has been investigated for decades, our understanding of the underlying neural mechanisms of anesthesia and consciousness remains rudimentary, which limits the development of systems for anesthesia monitoring and consciousness evaluation. Moreover, the current practices for anesthesia monitoring are mainly based on methods that do not provide adequate information and may present obstacles to the precise application of anesthesia. Most recently, there has been a growing trend to utilize brain network analysis to reveal the mechanisms of anesthesia, with the aim of providing novel insights to promote practical application. This review summarizes recent research on brain network studies of anesthesia, and compares the underlying neural mechanisms of consciousness and anesthesia along with the neural signs and measures of the distinct aspects of neural activity. Using the theory of cortical fragmentation as a starting point, we introduce important methods and research involving connectivity and network analysis. We demonstrate that whole-brain multimodal network data can provide important supplementary clinical information. More importantly, this review posits that brain network methods, if simplified, will likely play an important role in improving the current clinical anesthesia monitoring systems.

Abstract Background IQ motif-containing GTPase-activating proteins (IQGAPs) are a group of scaffold proteins which have been identified to be involved in tumor initiation and progression in diverse types of cancer. Clinical studies and experimental evidence suggest that IQGAPs play an essential role in hepatocellular carcinoma (HCC) progression and alterations in their expression are closely related to patient prognosis. However, the different expression patterns and prognostic values of all three IQGAP isoforms in HCC have not yet been analyzed simultaneously. Methods We analyzed the transcriptional and survival data of IQGAPs in HCC patients using Oncomine, UALCAN, Kaplan–Meier Plotter, cBioPortal, and GeneMANIA. We further examined tumor and adjacent normal tissues from 250 HCC patients using immunohistochemistry to assess the relationship between IQGAPs expression and clinicopathological features and validate the prognostic value of IQGAPs. In addition, we analyzed transcriptional changes of IQGAPs with regards to survival data in HCC patients from the TCGA-LIHC (liver hepatocellular carcinoma) cohort to validate our results. Results We found that the expression levels of IQGAP1 and 3 were significantly elevated in HCC tissues than in normal liver tissues, whereas the expression level of IQGAP2 was decreased in the former than in the latter. The clinical data showed that positive IQGAP1 expression was associated with larger tumor size, advanced tumor-node-metastasis (TNM) stage, poor relapse-free survival (RFS), and overall survival (OS), and positive IQGAP3 expression was associated with poorer tumor differentiation, RFS, and OS. Conversely, positive IQGAP2 expression predicted less tumor numbers and microvascular invasion, as well as higher RFS and OS in these patients. Conclusions IQGAPs may serve as new prognostic biomarkers and potential targets for precision therapy in HCC.

Nuclear energy is a clean and reliable alternative to traditional fuels such as gasoline and coal. However, the treatment of wastewater from nuclear plants is an issue that needs wildly exploration. In this study, novel cerium (Ce) modified aminated MOF UiO-66 was synthesized through solvothermal reactions. Using ZrCl 4 as a sacrificial template, the target product Ce-UiO-66-NH2 had been prepared by hydrothermal process. The microscopic surface morphology and characterized structure were investigated by BET, SEM, and FTIR characteristic protocols. The results revealed that Ce and amino groups have been successfully introduced on the surface of UiO-66. The absorbent Ce-UiO-66-NH2 showed its maximum specific surface area, with 823 m2/g. And the average pore size was 0.52 and 0.47 cm 3/g for Ce-UiO-66 and Ce-UiO-66-NH2, respectively. For the SEM results, both absorbents showed spherical structure, with the particles presenting 0.2–0.5μmsize core–shell structures. Considering the FTIR spectra, the characteristic peaks were located at 1656, 1569, 1385, 963, 894 cm −1 wavenumbers, indicating the incorporation of Ce and -NH2. The absorbance effect was highly enhanced by suitable functionalization of the material by introducing addition metal element Ce and amino group and thus more binding storage can be used in nuclear wastewater treatment.

The rate of surface warming in cities exceeds that in rural areas, but urban greening can partly offset enhanced urban warming that is driven by climate change and urban expansion, according to an analysis of satellite land surface temperature data in 2000 city clusters between 2002 and 2021.

Cascade-reaction chemistry can generate reactive-oxygen-species that can be used for the eradication of infectious biofilms. However, suitable and sufficient oxygen sources are not always available near an infection site, while the reactive-oxygen-species generated are short-lived. Therefore, we developed a magnetic cascade-reaction container composed of mesoporous Fe3O4@SiO2 nanoparticles containing glucose-oxidase and l-arginine for generation of reactive-oxygen-species. Glucose-oxidase was conjugated with APTES facilitating coupling to Fe3O4@SiO2 nanoparticles and generation of H2O2 from glucose. l-arginine was loaded into the nanoparticles to generate NO from the H2O2 generated. Using an externally-applied magnetic field, cascade-reaction containers could be homogeneously distributed across the depth of an infectious biofilm. Cascade-reaction containers with coupled glucose-oxidase were effective in killing planktonic, Gram-positive and Gram-negative bacteria. Additional efficacy of the l-arginine based second cascade-reaction was only observed when H2O2 as well as NO were generated in-biofilm. In vivo accumulation of cascade-reaction containers inside abdominal Staphylococcus aureus biofilms upon magnetic targeting was observed real-time in living mice through an implanted, intra-vital window. Moreover, vancomycin-resistant, abdominal S. aureus biofilms could be eradicated consuming solely endogenous glucose, without any glucose addition. Herewith, a new, non-antibiotic-based infection-control strategy has been provided, constituting a welcome addendum to the shrinking clinical armamentarium to control antibiotic-resistant bacterial infections.

BackgroundIn terms of assessing obesity-associated risk, quantification of visceral adipose tissue (VAT) has become increasingly important in risk assessment for cardiovascular and metabolic diseases. However, differences exist in the accuracy of various modalities, with a lack of up-to-date comparison with three-dimensional whole volume assessment.AimsUsing CT or MRI three-dimensional whole volume VAT as a reference, we evaluated the correlation of various commonly used modalities and techniques namely body impedance analysis (BIA), dual-energy x-ray absorptiometry (DXA) as well as single slice CT to establish how these methods compare.MethodsWe designed the study in two parts. First, we performed an intra-individual comparison of the 4558 participants from the UK Biobank cohorts with matching data of MRI abdominal body composition, DXA with VAT estimation, and BIA. Second, we evaluated 174 CT scans from the publicly available dataset to assess the correlation of the commonly used single-slice technique compared to three-dimensional VAT volume.ResultsAcross the UK Biobank cohort, the DXA-derived VAT measurement correlated better (R2 0.94, p

With increasing concerns for energy conservation and environmental protection, research on glazed hollow bead thermal insulation mortar is of utmost importance. This type of mortar offers superior thermal insulation, leading to reduced energy consumption and emissions, in line with the current green building trends. This article aims to investigate the impact of varying component proportions on the parameters of thermal insulation mortar through an orthogonal experiment with four factors and three levels: glazed hollow bead, sepiolite, air-entraining agent, and cellulose ether. Additionally, a single-factor experiment is conducted to analyze the influence degree of water-solid ratio and these four factors. The experimental results are then verified through SEM (Scanning Electron Microscope) observation. The research findings indicate that glazed hollow beads have the most significant impact on thermal conductivity and compressive strength, while the air-entraining agent exerts the greatest influence on flexural strength. Specifically, when the content of glazed hollow bead is 2%, sepiolite 1%, air-entraining agent 0.6%, and cellulose ether 0.6%, the thermal conductivity can reach a minimum value of 0.0533W/(m·K). On the other hand, when the content of glazed hollow bead is 1%, sepiolite 2%, air-entraining agent 0.4%, and cellulose ether 0.6%, the compressive strength can achieve a maximum value of 2.4 MPa. These findings provide a solid foundation for further exploration into improving the performance of thermal insulation mortar.

The proper dispatching of hydraulic structures in water diversion projects is a desirable way to maximize project benefits. This study aims to provide a reliable, optimal scheduling model for hydraulic engineering to improve the regional water environment. We proposed an improved gravitational search algorithm (IPSOGSA) based on multi-strategy hybrid technology to solve this practical problem. The opposition-based learning strategy, elite mutation strategy, local search strategy, and co-evolution strategies were employed to balance the exploration and exploitation of the algorithm through the adaptive evolution of the elite group. Compared with several other algorithms, the preponderance of the proposed algorithm in single-objective optimization problems was demonstrated. We combined the water quality mechanism model, an artificial neural network (ANN), and the proposed algorithm to establish the optimal scheduling model for hydraulic structures. The backpropagation neural network (IGSA-BPNN) trained by the improved algorithm has a high accuracy, with a coefficient of determination (R2) over 0.95. Compared to the two traditional algorithms, the IGSA-BPNN model was, respectively, improved by 1.5% and 0.9% on R2 in the train dataset, and 1.1% and 1.5% in the test dataset. The optimal scheduling model for hydraulic structures led to a reduction of 46~69% in total power consumption while achieving the water quality objectives. With the lowest cost scheme in practice, the proposed intelligent scheduling model is recommended for water diversion projects in plain river networks.

Lacustrine strata-bound magnesite deposits associated with Alpine-type ultramafic rocks are hydrothermal in origin. The magnesite ores of the Kamado deposit are unconformably underlain by mid-Jurassic marine carbonate and ultramafic rocks of the Bangong-Nujiang ophiolite suite and are in fault contact with hanging wall rocks composed of siliceous sinter. Three types of cryptocrystalline magnesite ores can be identified in Kamado: (1) strata-bound massive magnesites, representing the main ore type in the upper part; (2) banded ores in the lower part; and (3) some vein and stockwork ore in the ultramafic wall rocks. Integrated scanning electron microscopy, C–O isotope analysis, and geochemical analyses were carried out on the Kamado deposit. The results indicate that: (1) the orebody is composed of magnesite, with accessory minerals of aragonite, opal, and chromite; (2) the siliceous sinter and relatively high B (32.0–68.1 ppm) and Li (14.7–23.4 ppm) contents of the magnesite ores reflect long-term spring activity in Kamado; (3) the light carbon (δ13CV-PDB: −4.7 ± 0.3‰ to −4.1 ± 0.6‰) and oxygen isotopic compositions (δ18OV-SMOW: +12.3 ± 0.3 to +16.3 ± 0.1‰) of the stockwork ores in the foot wall rocks indicated that the carbon in fractures in the ultramafic rocks is from a mixture of marine carbonate and oxidized organic-rich sedimentary rocks, reflecting a typical “Kraubath-type” magnesite deposit; and (4) the relatively heavy carbon isotopic (δ13CV-PDB: +8.7 ± 0.4‰ to +8.8 ± 0.3‰) composition of the banded magnesite ores in the lower segment may have formed from heavy CO2 generated by anaerobic fermentation in the lakebed. Additionally, the carbon isotopic (δ13CV-PDB: +7.3 ± 0.3‰ to +7.7 ± 0.7‰) composition of the massive magnesite ores in the upper segment indicates a decline in the participation of anaerobic fermentation. As this economically valuable deposit is of the strata-bound massive ore type, Kamado can be classified as a lacustrine hydrothermal-sedimentary magnesite deposit, formed by continuous spring activities under salt lakes on the Tibetan Plateau, with the Mg mainly being contributed by nearby ultramafic rocks and the carbon mainly being sourced from atmosphere-lake water exchange, with minor amounts from marine carbonate strata.

This study evaluates the effects of a combined rice-crayfish farming model and compares this model with traditional paddy fields. The focus is on soil aggregate characteristics, organic matter content, and also the distribution of soil aggregates. This research was conducted in Qianjiang, Hubei Province. The surface soil samples were collected from two types of arable land: paddy fields (WR) and rice-crayfish fields (CR). We performed an analysis of soil aggregate distribution and organic matter content. Results reveal that the majority of soil aggregates exceed 2 mm in size (≥74.94%). The integrated rice-crayfish farming model significantly enhances the presence of large soil aggregates. And these parameters such as the average weight diameter (MWD), average geometric diameter (GWD), and agglomerate stability (PAD) also increase. Moreover, it mitigates agglomerate fragmentation (WASR). However, the net increase in total soil organic matter due to the integrated farming model remains modest. Organic matter content within the agglomerates follows an initial increase followed by a decrease. The highest content occurs in the 0.25–0.5 mm grain size (D4). When examining the distribution of soil aggregates and organic matter, it becomes evident that organic matter primarily originates from grain sizes larger than 2 mm (≥71.92%). Notably, the rice-crayfish paddy field (CR) exhibits a substantially higher contribution compared to the traditional rice paddy field (WR). This study demonstrates several positive outcomes of the integrated rice-crayfish farming model compared to traditional paddy farming. It promotes the development of larger soil aggregates, enhances the structural integrity of soil aggregates, and improves their mechanical and hydrological stability. Additionally, it marginally increases the organic matter content within each component of soil aggregates. Furthermore, integrated modelling increases the impact of larger soil aggregates on soil organic matter. This improves the quality of the soil and as a result, crop yields are increased. The health of the soil is also improved and this contributes positively to food security.

The Yongfeng composite granitic pluton, located in the southern section of the Nanling area, is composed of the Yongfeng and Longshi biotite monzonitic granites. In order to reveal the genesis of this composite granitic pluton and its relationship with mineralization, this study conducted zircon U-Pb dating, whole-rock major and trace element analysis, and biotite electron probe analysis. The results show that the Yongfeng composite granitic pluton is rich in silicon and alkali, weakly peraluminous, and poor in calcium and iron. It shows the enrichment of light rare earth elements and a significant fractionation of light and heavy rare earth elements. It also shows the enrichment of large ion lithophile elements and depletion of Ba, K, P, Eu, and Ti relative to the primitive mantle. The contents of TFe2O3, MgO, CaO, TiO2, and P2O5 are low and decrease with increasing SiO2 content. The Yongfeng composite granitic pluton does not contain alkaline dark minerals. Its average zircon saturation temperature is 776 °C, average TFe2O3/MgO is 4.81, and average Zr + Nb + Ce + Y is 280.6 ppm, which correspond to a highly fractionated I-type granite. The Yongfeng and Longshi granites were respectively formed at 152.0 ± 1.0 Ma–151.3 ± 1.1 Ma and 148.9 ± 1.2 Ma. They were formed in the extensional tectonic setting during the post-orogenic stage, under the control of the breakup or retreat of the backplate after the subduction of the Pacific Plate into the Nanling hinterland. The magmatic system of the Yongfeng composite granitic pluton is characterized by high fractionation, high content of F, high temperature, and low oxygen fugacity, which is conducive to mineralization of Sn, Mo, and fluorite.

Since the second industrial revolution, the widespread use of various fossil fuels, such as coal, oil and natural gas, has boosted the rapid development of society and economy. However, the greenhouse gases emitted by the extensive use of energy have caused more and more serious environmental problems. In this context, optimization of the energy structure and accomplishment of the carbon-reduction targets are not just the focus and difficulty faced by China but even by the world. As a center in southwest China and a big province in energy consumption, Sichuan province’s energy consumption structure in the future will deeply influence its development under the background of accelerating industrialization and urbanization. And furthermore, the study on the relationship between energy consumption structure and carbon emissions in Sichuan province also provides a theoretical basis for the establishment of development planning in Southwest China. This paper is composed of the following parts: firstly, the characteristics of energy structure in Sichuan Province are analyzed by collecting the data of energy production and consumption over the years. Then, using the calculation method provided by IPCC, this paper calculates the carbon emissions generated by fossil energy consumption in Sichuan Province from 2005 to 2019, and analyzes its characteristics and trends. Finally, by analyzing the characteristics of the energy endowment and fossil energy consumption structure of Sichuan Province, this paper puts forward the “coal-gas transition balance theory” to discuss the impact of fossil energy consumption transition on carbon emissions, and provides guidance and ideas for the realization of emission reduction.

ObjectiveThe objective of this study is to evaluate the methodological quality of Tuina clinical practice guidelines (CPGs).MethodsComputer searches of China National Knowledge Infrastructure (CNKI), Chinese Technical Periodicals (VIP), Wanfang Data Knowledge Service Platform, PubMed, Cochrane Library, Embase, and other databases were conducted to search for published guidelines on Tuina, with a search time frame from database creation to March 2021. Four evaluators independently used the Appraisal of Guidelines for Research and Evaluation II instrument to evaluate the quality of the included guidelines.ResultsA total of eight guidelines related to Tuina were included in this study. The quality of reporting was low in all included guidelines. The highest quality report had a total score of 404 and was rated as “highly recommended.” The worst guideline had a final score of 241 and was rated as “not recommended.” Overall, 25% of the included guidelines were recommended for clinical use, 37.5% were recommended after revision, and 37.5% were not recommended.ConclusionThe number of existing Tuina clinical practice guidelines is limited. The methodological quality is low, far from the internationally accepted clinical practice guideline development and reporting norms. In the future, reporting specifications of guidelines and the methodology of guideline development, including the rigor of the guideline development process, the clarity, application, and independence of reporting, should be emphasized in the development of the Tuina guidelines. These initiatives could improve the quality and applicability of clinical practice guidelines to guide and standardize the clinical practice of Tuina.

The study aims to examine the mediation effects of physical literacy and physical activity behavior in a relationship between psychological distress and life satisfaction among Chinese college students during the real-life Coronavirus disease pandemic (COVID-19) circumstance. This study implemented a cross-sectional design, and 1,516 participants from 12 universities participated in this study. Structural equation modeling was used to examine a hypothesized model. The findings indicated an acceptable model fit ( X 2 [61] = 508.2, Comparative Fit Index [CFI] = 0.958, Tucker Lewis Index [TLI] = 0.946, Root Mean Square Error of Approximation [RMSEA] = 0.076, 90% CI [0.070, 0.082], Standardized Root Mean Square Residual [SRMR] = 0.047). The results indicated that college students with low participation in physical activity could experience less than healthy living conditions. The findings offered empirical support to the theory that physical literacy could advance individuals’ healthy living by promoting physical activity participation. The study suggested that educational institutions and physical activity programs should cultivate individuals’ physical literacy in order to promote lifelong healthy living.

Retinal images have been proven significant in diagnosing multiple diseases such as diabetes, glaucoma, and hypertension. Retinal vessel segmentation is crucial for the quantitative analysis of retinal images. However, current methods mainly concentrate on the segmentation performance of overall retinal vessel structures. The small vessels do not receive enough attention due to their small percentage in the full retinal images. Small retinal vessels are much more sensitive to the blood circulation system and have great significance in the early diagnosis and warning of various diseases. This paper combined two unsupervised methods, local phase congruency (LPC) and orientation scores (OS), with a deep learning network based on the U-Net as attention. And we proposed the U-Net using local phase congruency and orientation scores (UN-LPCOS), which showed a remarkable ability to identify and segment small retinal vessels. A new metric called sensitivity on a small ship (Sesv) was also proposed to evaluate the methods’ performance on the small vessel segmentation. Our strategy was validated on both the DRIVE dataset and the data from Maastricht Study and achieved outstanding segmentation performance on both the overall vessel structure and small vessels.

IntroductionPhysical fitness is a health indicator contributing to the prevention of non-communicable diseases that threaten public health. Studies across a number of global populations indicate that physical fitness is generally declining. This study investigated the trend in physical fitness of Chinese male first-year college students from 2013 to 2019 to offer critical information for fostering individual and public health.MethodsThis study used archival data and a natural experiment design capturing 4 years of data prior to implementation of the Healthy China 2030 initiative and 3 years following. Physical fitness tests were based on the Chinese national student physical fitness standards for males including body mass index, vital capacity, standing-long-jump, sit-and-reach, pull-ups, 50 m sprint, and 1,000 m run. Because the physical fitness tests set different standards for males and females, female data will be reported separately. Data from a total of 3,185 Chinese male first-year college students from a private university in Hebei Province of China were included in the study. A one-way multivariate analysis of variance was used for analyzing the research data.ResultsThe results indicated an overall significant difference in health-related physical fitness of Chinese male first-year college students, with scores on health indicators generally declining from 2013 to 2019. Despite improvement on some fitness variables in some years, performance on virtually all indicators was diminished compared to baseline years.DiscussionThese findings can contribute to the existing global literature in the field of public health showing general declines in physical fitness. Chinese universities have the opportunity to support Healthy China 2030 goals and cultivate individuals' physical fitness by offering physical education course that encourage college students to participate in moderate-to-vigorous-intensity physical activities in order to support physical fitness development.

Bisphenol A (BPA), one of the typical environmental endocrine disruptors (EEDs), can promote the proliferation and migration of cancer cells, but the mechanism of which remains largely unclear. Exosome secretion plays an important role in the stress response of cells to environmental stimuli. This study was designed to explore whether exosome secretion was involved in the toxic effect of BPA on the proliferation and migration of MCF-7 cells, and the related mechanism. Our data shows that the IC50 value of MCF-7 exposure to BPA was about 65.82 µM. The exposure of MCF‐7 to 10 µM BPA resulted in a decreased miR-26b expression and the activation of miR-26b/Rab-31 pathway, consequently, the number and activity of lysosomes decreased, the secretion of exosomes increased, cell proliferation and migration were enhanced obviously. Interestingly, miR-26b mimic up-regulated the number and activity of lysosomes via miR-26b/miR-31 pathway, exosome secretion was down-regulated, cell proliferation and migration decreased. Further, when GW4869 was used to directly inhibit the exosome secretion of MCF-7 treated with BPA, their proliferation and migration were down-regulated. Herein, we concluded that the stimulating effect of BPA on the proliferation and migration of MCF-7 cells was associated with the lysosome - related exosome secretion via miR-26b / Rab31 pathway.

Abstract The collection capacity of common nasopharyngeal swabs and irregularities of medical personnel limit the accuracy of PCR testing. This study describes a newly designed 3D-printed swab that is combined with a 3D-printed cover to prevent the extraction of undesired nasal secretions. This swab improved the accuracy of PCR test results. The results of a series of experiments showed that, because of the mucus extraction effect, 3D-printed swabs can replace ordinary cotton swabs. The crisis of the worldwide medical supply shortage can be ameliorated to a certain extent by applying 3D printing technology.

Climate and human activities change spatial and temporal distribution of water and land use. The Tarim River, the largest inland river in China, faced a long-term exploitation of land and water over a rapid economic development. We analyzed land and water use from 1997 to 2019 in Tarim River Basin by Landsat images, and data on hydrology, climate, population, economy and PM2.5 (air particulate matter ≤2.5 μm). Agricultural land expanded the fastest (4–11%), followed by natural vegetation (15–16%) and water area (4–5%) with population and economic increase. Air quality (PM2.5 μg m−3) improved in upper (62–27) and middle (48–17) reaches. The water area in lower increase 5% because of ecological water delivery since 2000. Land use in the lower reach was dominated by agriculture, where the downstream runoff consumption increased by 6.8 times. The average annual air temperature and precipitation gradually increased by 0.5 °C and 51 mm in source and 0.9 °C and 30 mm in main reaches. The average annual water consumption in upper and middle reaches was 4 × 109 m3, accounting for 87% of input runoff in the main reach. Water consumption in middle reach increased by 33 times in 2009–2017. The industry structure was changing from primary to secondary and tertiary industry. To sum up, implementation of water saving strategies and ecological water delivery restored local ecology. Sustainable strategies should be applied facing industrialization. Furthermore, changing the industry structure and restoring the degraded farmlands to grasslands or forests would keep sustainability of Tarim River Basin.

Abstract Light is a complex vectorial field characterized by its amplitude, phase, and polarization properties, which can be further represented by four basic parameters, that is, amplitudes and phases of two orthogonally polarized components. Controlling these parameters simultaneously and independently at will using metasurfaces are essential in arbitrarily manipulating the light propagation. However, most of the studies so far commonly require a great number of different meta‐atoms or rely on diffraction under oblique incidence, which lack convenience and flexibility in design and implementation. Here, a new metasurface paradigm is proposed that can completely manipulate the amplitudes and phases of two spin components based on the interference effect, where only two different meta‐atoms are applied. For proof‐of‐concept demonstration, two five‐channel meta‐holograms for imaging and information encryption are designed and experimentally characterized. The interference method provides a simple route toward compact complex and multifunctional meta‐devices.

Background: Septic shock has increasingly become a cause of death threatening human survival. Shenfu Injection (SFI), a patented Chinese medicine, has been widely used in the treatment of patients with sepsis and cardiovascular diseases domestically. We sought to examine whether combination therapy with SFI can improve clinical outcomes in critically ill patients undergoing mechanical ventilation (MV).Methods: This real-world, multicenter retrospective trial enrolled consecutive adult patients with sepsis requiring MV from four medical/surgical intensive care units (ICUs) in China between August 2016 and September 2021. Patients were identified from the medical information department database of each center and assigned to either of two groups (SFI or control) on the basis of the initial treatment received. The primary outcome was 28-day all-cause mortality, and the durations of vasopressor therapy and MV, the ICU length of stay, and costs were assessed as secondary outcomes. Subsequently, we performed a meta-analysis of randomized controlled trials (RCTs) on SFI published before July 2021 to verify our conclusions.Results: 2311 mechanically ventilated patients with septic shock (1128 patients in the SFI group and 1183 in the control group) were analyzed. The survival probability during the first 28 days after admission in the SFI group was greater than that in the control group [p < 0.01 by log-rank test; hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.39–0.72]. Patients in the SFI group also experienced a significantly reduced duration of vasopressor therapy [7.28 (95% CI, 6.14–8.42) vs. 12.06 (95% CI, 10.71–13.41) days, p < 0.001], more ventilator-free days [6.49 (95% CI, 5.42–7.55) vs. 10.84 (95% CI, 9.59–12.09) days, p < 0.001], a shorter ICU length of stay [18.48 (95% CI, 17.59–19.38) vs. 23.77 (95% CI, 22.47–25.07) days, p < 0.001], and more time free from organ failure [14.23 (95% CI, 12.94–15.52) vs. 19.07 (95% CI, 16.09–22.05) days, p < 0.001]. No major adverse effects were reported in either group.Conclusion: Among critically ill patients requiring MV, combination therapy with SFI can improve the survival probability without any obvious adverse reactions.

Plant root growth is inhibited markedly by aluminium (Al) even at micromolar concentration and Al is mainly accumulated in plant roots outer layer cell walls. But the underlying reason for this asymmetric transverse distribution is unknown. In this study, two wheat (Triticum aestivum L.) genotypes ET8 and ES8 differing in Al resistance were investigated by hydroculture. The Al-tolerant ET8 expressed a higher root elongation rate (RER) than Al-sensitive ES8 under Al stress. Morphological examination showed symptoms such as root surface ruptures were observed in ET8 and ES8, with ES8 being more obvious. The cation exchange capacity (CEC) values of root tips of ES8 under different Al concentrations are higher than those of ET8. The sensitive genotype ES8 accumulated more Al than ET8 in plant apical root tips as well as cell walls. Under 48 h Al exposure, the root cell wall pectin concentration was increased with a higher magnitude in ES8 than in ET8. The functional groups on ET8 and ES8 roots outer layer and inner cells were investigated by Fourier transform infrared spectrometry (FTIR) under Al stress. The FTIR spectra of selected examined areas showed that the characteristic absorption peaks were located at 1692, 2920, and 3380 cm−1. The outer layer cells had stronger peaks than inner cells at wavenumber 1680–1740 cm−1, indicating root outer layer cells contain more carboxyls in both ET8 and ES8. The results demonstrate that Al transverse distribution on plants apical root cross section is likely influenced by functional groups such as negatively charged carboxylic acid.

Abstract Discrete fracture network (DFN) is an effective means of describing the coupling of heat flow in an underground fractured rock mass. In this paper, an improved DFN is proposed by introducing the correlation function of fracture trace length and aperture, which is more consistent with the real fracture data. Next, based on the improved model, the influence of fracture roughness on the fluid flow and heat transmission was evaluated, and the relationship between the fracture aperture and the joint roughness coefficient (JRC) is established. Finally, based on the exponential function between confining pressure and aperture, the influence of confining pressure on the heat‐flow coupling process is considered in the improved model. Besides, the reliability of the model was verified by comparing with the analytical solution of the two‐dimensional single‐fracture heat‐flow coupling problem. The results show that under the same conditions, considering the correlation between the geometric parameters of the fracture, the seepage and heat transfer rates of the model increased, the outlet boundary flow reached the maximum value, and the average outlet temperature dropped rapidly. However, the fracture roughness reduces the outlet flow rate and the decline rate of average temperature. The confining pressure will lead to a decrease of about 3.5% in the outlet flow of the model, which is consistent with the seepage law in practical engineering. The model presented in this paper is an effective supplement to the two‐dimensional fracture network heat‐flow coupling model and can provide a theoretical basis and a numerical calculation tool for related underground rock mass engineering.

Abstract Increasing bacterial drug resistance to antibiotics has posed a major threat to contemporary public health, which resulted in a large number of people suffering from serious infections and ending up dying without any effective therapies every year. Here, a dynamic covalent polymeric antimicrobial, based on phenylboronic acid (PBA)‐installed micellar nanocarriers incorporating clinical vancomycin and curcumin, is developed to overcome drug‐resistant bacterial infections. The formation of this antimicrobial is facilitated by reversible dynamic covalent interactions between PBA moieties in polymeric micelles and diols in vancomycin, which impart favorable stability in blood circulation and excellent acid‐responsiveness in the infection microenvironment. Moreover, the structurally similar aromatic vancomycin and curcumin molecules can afford π–π stacking interaction to realize simultaneous delivery and release of payloads. In comparison with monotherapy, this dynamic covalent polymeric antimicrobial demonstrated more significant eradication of drug‐resistant bacteria in vitro and in vivo due to the synergism of the two drugs. Furthermore, the achieved combination therapy shows satisfied biocompatibility without unwanted toxicity. Considering various antibiotics contain diol and aromatic structures, this simple and robust strategy can become a universal platform to combat the ever‐threatening drug‐resistant infectious diseases.

Recurrent aphthous ulcer (RAU), one of the most common diseases in humans, has an unknown etiology and is difficult to treat. Thalidomide is an important immunomodulatory and antitumor drug and its effects on the gut microbiota still remain unclear. We conducted a metagenomic sequencing study of fecal samples from a cohort of individuals with RAU, performed biochemical assays of cytokines, immunoglobulins and antimicrobial peptides in serum and saliva, and investigated the regulation effects of thalidomide administration and withdrawal. Meanwhile we constructed the corresponding prediction models. Our metagenome-wide association results indicated that gut dysbacteriosis, microbial dysfunction and immune imbalance occurred in RAU patients. Thalidomide regulated gut dysbacteriosis in a species-specific manner and had different sustainable effects on various probiotics and pathogens. A previously unknown association between gut microbiota alterations and RAU was found, and the specific roles of thalidomide in modulating the gut microbiota and immunity were determined, suggesting that RAU may be affected by targeting gut dysbacteriosis and modifying immune imbalance. In-depth insights into sophisticated networks consisting of the gut microbiota and host cells may lead to the development of emerging treatments, including prebiotics, probiotics, synbiotics, and postbiotics.

Background: Colon cancer is the fifth most common cause of cancer-related death worldwide, and despite significant advances in related treatment, the prognosis of colon cancer patients remains poor.Objective: This study performs systematic bioinformatics analysis of prognostic-associated RNA processing factor genes in colon cancer using the Cancer Related Genome Atlas database to explore their role in colon carcinogenesis and prognosis and excavate potential therapeutic targets.Methods: Data sets of colon cancer patients were obtained from GEO and TCGA databases. Univariate cox analysis was performed on the GSE39582 training set to identify prognosis-associated RNA processing factor genes and constructed a muticox model. The predictive performance of the model was validated by Correlation curve analysis. Similar results were obtained for the test dataset. Functional analyses were performed to explore the underlying mechanisms of colon carcinogenesis and prognosis.Results: A constructed muticox model consisting of βi and prognosis-related RNA processing factor gene expression levels (Expi) was established to evaluate the risk score of each patient. The subgroup with a higher risk score had lower overall survival (OS), higher risk factor, and mortality. We found that the risk score, age, gender, and TNM Stage were strongly associated with OS, and the 13-gene signature as an independent prognostic factor for colon cancer. The model has good accuracy in predicting patient survival and is superior to traditional pathological staging.Conclusion: This study proposes 13 RNA processing factor genes as a prognostic factor for colon cancer patients, which can independently predict the clinical outcome by risk score. The gene expression profile in this model is closely related to the immune status and prognosis of colon cancer patients. The interaction of the 13 RNA processing factor genes with the immune system during colon carcinogenesis provides new ideas for the molecular mechanisms and targeted therapies for colon cancer.

South China is a well-known grand felsic igneous rocks province. However, it is still controversial and not well understood whether the Mesozoic tectono-magmatic pattern is dominated by the subduction of the paleo-Pacific oceanic plate. In this study, we address this question by concentrating on the long-term evolutionary Guandimiao batholith, which has complex lithofacies with different formation ages and can be a superb record of the Mesozoic tectonic evolution in South China. Geochronologically, four stages of magmatism can be identified combined with previous reports: granodiorite (G1, 239 Ma), biotite monzogranite (G2-1) and two-mica monzogranite (G2-2) (230–203 Ma), granite porphyry (G3, 211–190 Ma), and lamprophyre (L4, 121 Ma). G1 and G2-1 have an affinity with I-type granite and were derived from metabasaltic to metatonalitic sources, whereas G2 and G3 show S-type granite characteristics and were derived from the para-metamorphic basement of the Cathaysia block. The L4 was derived from partial melting of garnet and spinel lherzolite and underwent mixing between Mesoproterozoic pelagic and/or terrigenous sediments and the subcontinental lithosphere mantle (SCLM) of South China. The granitoids of the Guandimiao batholith underwent intensely fractional crystallization of feldspar, Ti-bearing minerals, allanite and monazite. The zircon U–Pb dating of L4 in the Guandimiao batholith completely records the six stages of pre-Mesozoic tectonic events in the SCB. During the Mesozoic, the main body of the Guandimiao batholith (G1, G2-1 and G2-2) recorded the closure of the paleo-Tethys Ocean in the Triassic and the subsequent regional extension of the postcollision. G-3 and L4 of the Guandimiao batholith documented the transition of tectonic and dynamic regimes in the early Yanshanian and the rollback and steep subduction of the paleo-Pacific Ocean in the late Yanshanian.

The Sijiaying iron deposit is located in the Eastern Hebei area of the southern section of the northern margin of the North China Craton (NCC) and is the largest single iron deposit in China. The deposit contains many banded iron formations (BIFs) and was proven to have more than 3 million tons of high-grade iron ore resources. This study carried out geochemistry and zircon U–Pb analysis of normal-grade iron ore, high-grade iron ore, and wall rock (biotite–leptynite, chlorite–sericite schist) in the Sijiaying deposit and discussed the genesis and metallogenic age of high-grade iron ore. BIFs have low concentrations of Al2O3 and TiO2 and high field strength element (HFSE) depletion, indicating almost no contamination via terrestrial debris. The standardized post-Archean Australian shale (PAAS) rare earth element (REE) distribution pattern indicates that the iron formation exhibits positive Eu, Y, and heavy rare earth element (HREE) anomalies and lacks negative Ce anomalies, indicating that the Sijiaying BIF was enriched with iron sources via high-temperature hydrothermal fluids from the seabed and deposited in an anoxic ancient marine environment. In addition, geological field work identified two types of high-grade iron ore in the mining area: primitive sedimentary and hydrothermally altered high-grade iron ore. Further ore geochemical research showed that the primitive sedimentary-type iron ore is similar in geochemistry to the BIF. In addition to low Eu/Eu* values, the hydrothermally altered high-grade iron ore shows geochemical characteristics similar to those of the BIF, suggesting that they share the same iron source but did not form at the same time. The total large ion lithophile element (LILE) (Sr, Ba, Pb) contents in primitive sedimentary-type high-grade iron ore are higher than those in hydrothermally altered high-grade iron ore, indicating that LILEs are carried away via fluids during the hydrothermal alteration process in normal-grade iron ore. The geochemical characteristics of biotite–leptynite and chlorite–sericite schist include high contents of SiO2 and Al2O3, light rare earth elements (LREEs), LILE enrichment (Rb, Ba, Sr, Zr), and HFSE depletion (Nb, Ta, P, Ti), characteristics that are similar to island arc volcanic rocks. The reconstruction of the original rock indicates that the wall rock is a product of volcanic sedimentary cycles in an island arc setting. Zircon cathodoluminescence images and LA–ICP–MS zircon U–Pb dating can be divided into four age groups (3283 Ma, 2547 Ma, 2500 Ma, and 2407 Ma), which correspond to the earliest volcanic activity in eastern Hebei, the main mineralization age of the Sijiaying BIF (the mineralization age of primitive sedimentary high-grade iron ore), a regional tectonic–metamorphic event, and the occurrence of migmatization (the mineralization age of hydrothermally altered high-grade iron ore), respectively. Therefore, the Sijiaying BIF and primitive sedimentary high-grade iron ores were deposited and mineralized at 2547 Ma, and the iron orebody was later altered via the hydrothermal solution at 2407 Ma, forming large-scale high-grade iron ores.