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The influences of aging temperatures (160–200 °C) and 8% pre-rolling on the mechanical properties, and microstructures of the creep-aged AA2050 alloys were investigated. The results show that for the solid-solutioned alloys after the creep aging, the strength increased with an increase of aging temperatures. The ultimate tensile strength (UTS) and yield strength (YS) reached the highest value of 527 and 484 MPa at 200 °C, respectively, although the elongation (EL) reduced to 10.8%. At expense of σ phases, the temperature increase promoted the dislocation accumulation and the dense precipitation of θ′ and T1 phases, which increased the strength. It is noted that the strong oriented precipitation at 200 °C lost some strengthening effect. After the 8% pre-rolling, the strength of creep-aged alloys increased firstly and then decreased with the increase of temperature. The high strength (UTS = 574 MPa, YS = 535 MPa) at 180 °C was attributed to the dense precipitation of T1 phases under the action of diffusion kinetic and thermodynamic driving force. When the temperature reached 200 °C, the activated ledge mechanism significantly thickened T1 phases, thus decreasing the strength. The work revealed the critical roles of aging temperature and pre-rolling in tailoring precipitation behaviors and mechanical performance of Al–Li alloys, paving a way in designing creep-aged Al–Li alloys with the superb mechanical properties.

Aflatoxin B1 (AFB1) is a potent toxin in food, necessitating rapid, instant, and sensitive detection. We have engineered an electrochemical sensor to monitor AFB1 using a system composed of Fe3O4-NH4/AuNPs/apt-S1. The aptamer specifically recognizes AFB1, while ‘S1’ is functionalized with methylene blue to enhance the current. The RecJf exonuclease promotes the formation of the electrochemical strategy. The Fe3O4 component, with its magnet properties, enables a rapid separation of solids and liquids without the need for instrumentation. The sensor exhibits a linear range for AFB1 ranging from 1 ng to 10 μg. The regression equation is I(nA) = 446.8 × logc+2085 (where I and c represent the peak current and AFB1 concentration, respectively). The correlation coefficient is 0.9508, and the detection limit is 3.447 nM. The relative standard deviation of AFB1 in peanut oil ranges from 4.80% to 6.80%. These results demonstrate that the sensor has high sensitivity, stability, repeatability, and specificity for AFB1 detection.

Porous asphalt concrete (PAC) is typically used as a paving material for porous asphalt pavement in rainy areas due to its abundant interconnected pores structure. Not all interconnected pores in PAC are valid for permeability, mainly influenced by the composition of aggregate gradation. The main purpose of this paper is to investigate the effect of aggregate gradation on pores structure distribution in PAC by X-ray computed tomography (CT) system and digital image processing (DIP) techniques. The distributions of porosity, number and average equivalent diameter of air voids in middle part are much more evenly compared to the both ends in PAC specimens, accounting for about 70 % of the total of specimen height. The average equivalent diameter of interconnected air voids mainly ranges from 0.5 mm to 5 mm in PAC, accounting for about 80 % of the total numbers. For PAC with similar porosity, the larger the normal maximum aggregate size (NMAS), the less the number and the larger the average equivalent diameter of air voids (interconnected air voids), the smaller the difference between the interconnected porosity and porosity. For PAC with same NMAS, as the porosity increase, the number and average equivalent diameter of air voids (interconnected air voids) are respectively decreased and increased gradually, the difference between the interconnected porosity and porosity is also showed a decreasing trend. And then, the correlated equation is established among porosity, interconnected porosity and the composition of aggregate gradation. The distribution of air voids (interconnected air voids) size could be well described by the two-parameter Weibull model, and the relationships are explored and developed between Weibull model parameters and the composition of aggregate gradation.

Summary: Adjustments in foliar photoprotective pigments are crucial for plant adaptation to harsh environments, serving as indicators of environmental stress. However, understanding when and where these adjustments occur across diverse biomes remains unclear due to challenges in large-scale observation. Here, we propose a novel approach to assess dynamics in photoprotective pigments at the canopy level using a new index derived from space-borne optical sensors. This approach generates a global map depicting the daily mean shortwave radiation threshold at which adjustments typically occur under prevailing climatic conditions. The global average of this threshold is 262 ± 50 W m⁻2, with lower values at high latitudes and peaks near 40° in both hemispheres. Temperature exerts a stronger influence on this latitudinal pattern than humidity. Future projections suggest a decrease in this threshold over northern high latitudes, implying exacerbated vulnerability under identical radiation levels due to negative warming responses. Based on this threshold, a high-stress zone around 60°N is identified and is predicted to shift southward in the future. These findings bridge critical gaps in photoprotection research and offer a new perspective on understanding the biogeochemical cycles of global ecosystems. This framework can also enhance our ability to predict the fate of diverse ecosystems under future climate.

In this study, a six-month pot experiment was conducted to explore the effects of nanoparticles (NPs), including CeO2, TiO2 and SiO2 NPs at 200 and 800 mg/kg, on the growth and quality of model medicinal plant Salvia miltiorrhiza. A control group was implemented without the application of NPs. Results showed that NPs had no significant effect on root biomass. Treatment with 200 mg/kg of SiO2 NPs significantly increased the total tanshinone content by 44.07 %, while 200 mg/kg of CeO2 NPs were conducive to a 22.34 % increase in salvianolic acid B content. Exposure to CeO2 NPs induced a substantial rise in the MDA content in leaves (176.25 % and 329.15 % under low and high concentration exposure, respectively), resulting in pronounced oxidative stress. However, TiO2 and SiO2 NPs did not evoke a robust response from the antioxidant system. Besides, high doses of CeO2 NP-amended soil led to reduced nitrogen, phosphorus and potassium contents. Furthermore, the NP amendment disturbed the carbon and nitrogen metabolism in the plant rhizosphere and reshaped the rhizosphere microbial community structure. The application of CeO2 and TiO2 NPs promoted the accumulation of metabolites with antioxidant functions, such as D-altrose, trehalose, arachidonic acid and ergosterol. NPs displayed a notable suppressive effect on pathogenic fungi (Fusarium and Gibberella) in the rhizosphere, while enriching beneficial taxa with disease resistance, heavy metal antagonism and plant growth promotion ability (Lysobacter, Streptomycetaceae, Bacillaceae and Hannaella). Correlation analysis indicated the involvement of rhizosphere microorganisms in plant adaptation to NP amendments. NPs regulate plant growth and quality by altering soil properties, rhizosphere microbial community structure, and influencing plant and rhizosphere microbe metabolism. These findings were beneficial to deepening the understanding of the mechanism by which NPs affect medicinal plants.

Salinity is an important abiotic factor in aquaculture because of its significance in the multiple physiological progress of marine fish. The liver is the main organ involved in energy metabolism, supplying energy to other body tissues and organs. Greater amberjack (Seriola dumerili) is characterized by fast growth and is an important aquatic export product in China. In this study, the greater amberjack was cultured in varying salinity levels, i.e., from 5 to 40 ppt, for 72 h. Notably, all fish under 5 ppt salinity died within 24 h because of limited tolerance ability. A comparative transcriptome analysis was performed to explore the molecular response mechanism of the liver, a non-osmoregulatory organ, when fish was subjected to hypo- (10 ppt) and hyper-salinity (40 ppt) stress. A total of 100 and 5 DEGs were identified under hypo- (10 ppt) and hyper-salinity (40 ppt) stress, respectively. The DEGs were involved in lipid metabolism, glycine, serine, and threonine metabolism, and in various signaling pathways, including Calcium, PPAR and adipocytokine, and adrenergic signaling in cardiomyocytes. The mRNA expression levels of acsl5, lipin1, and apoeb in the liver were down-regulated under 10 ppt salinity, suggesting an elevation of fatty acids oxidation and energy requirement in response to the hypo-salinity stress. Similarly, there was a decrease in the expression levels of atp1b1b and cftr, responsible for the reduced Na+, K+ movement and Cl- ion secretion, under hypo-salinity stress. This study provides important basic data for the optimal artificial breeding of greater amberjack, and reveals the osmotic regulation mechanism of the liver in response to salinity stress.

Background: Ras association domain family member 1 (RASSF1) encodes the RASSF1A protein, serving as a scaffold protein situated at the intersection of a complex signalling network. Aims: To evaluate the immunological and prognostic significance of RASSF1 expression in various types of human cancers, with a specific focus on lung cancer. Methods: Differential expression analysis of RASSF1 was conducted based on data from The Cancer Genome Atlas, Genotype-Tissue Expression, and Cancer Cell Line Encyclopaedia databases. Prognostic analysis was performed using the Cox regression test and Kaplan-Meier test. Spearman's test was utilized for correlation analysis. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) gene sets were employed to enrich the associated signaling pathways. Immunohistochemical staining and quantitative real-time PCR were employed to detect protein and mRNA expression levels, respectively. Results: RASSF1 expression was significantly lower in tumour tissues than in normal tissues in most cancers, and Cox regression analysis demonstrated a significant correlation between RASSF1 expression and the prognosis of over 12 types of cancer. Specifically, high RASSF1 expression was associated with poor OS in nine cancer types, including GBMLGG (HR = 4.98, P = 1.2e-31), LGG (HR = 3.72, P = 2.5e-10), and LAML (HR = 1.48, P = 2.4e-3). Further analysis showed that RASSF1 expression was significantly correlated with immune checkpoint- and immune-related genes. Moreover, RASSF1 expression is involved in tumour microenvironment (TME), RNA modification, genomic heterogeneity, and tumour stemness. GO and KEGG analyses showed that RASSF1 was closely related to tumour immune-related pathways. Finally, RASSF1A was moderately correlated with PD-L1 (R = 0.556), and RASSF1A overexpression significantly affected the expression of several genes involved in the Th17 cell differentiation signalling pathway in lung cancer. Conclusions: RASSF1 was differentially expressed in 29 human cancers and played a critical role in tumour immunity. Thus, RASSF1 has the potential to be used as a prognostic marker and reference for achieving more precise immunotherapy, particularly in lung cancer.

Summary: Chemical warfare agents (CWAs), epitomized by the notoriously used mustard gas (HD), represent a class of exceptionally toxic chemicals whose airborne removal is paramount for battlefield safety. This study integrates high-throughput computational screening (HTCS) with advanced machine learning (ML) techniques to investigate the efficacy of metal-organic frameworks (MOFs) in adsorbing and capturing trace amounts of HD present in the air. Our approach commenced with a comprehensive univariate analysis, scrutinizing the impact of six distinct descriptors on the adsorption efficiency of MOFs. This analysis elucidated a pronounced correlation between MOF density and the Henry coefficient in the effective capture of HD. Then, four ML algorithms were employed to train and predict the performance of MOFs. The Random Forest (RF) algorithm demonstrates strong model learning and good generalization, achieving the best prediction result of 98.3%. In a novel exploratory stride, we incorporated a 166-bit MACCS molecular fingerprinting (MF) to identify critical functional groups within adsorbents. From the top 100 MOFs analyzed, 22 optimal functional groups were identified. Leveraging these insights, we designed three innovative substructures, grounded in these key functional groups, to enhance HD adsorption efficiency. In this work, the combination of MF and ML could provide a new direction for efficient screening of MOFs for the capture of HD in the air. The outcomes of this study offer substantial potential to revolutionize the domain of CWA capture. This represents a significant stride toward developing practical solutions that enhance both environmental protection and battlefield security.

Hereditary hemochromatosis (HH) is a disease characterized by disordered iron metabolism. It often involves mutations of the HFE gene, which encodes the homeostatic iron regulator protein (HFE), as well as mutations affecting hepcidin antimicrobial peptide, hemojuvelin, or transferrin receptor 2. Historically, HH has been observed primarily in European and European diaspora populations, while classical HH is rare in Asian populations, including in China. In this article, we report a rare case of HH in a Chinese man that could be attributed to a heterozygous C282Y/H63D HFE mutation. Based on clinical examination, liver biopsy, and genetic testing results, the patient was diagnosed with HH. Clinical signs and symptoms and serum iron-related test results were recorded for a period of two years after the patient began treatment. Over this observation period, the patient was subjected to 25 phlebotomies (accounting for a total blood loss of 10.2 L). His serum ferritin levels decreased from 1550 μg/L to 454 μg/L, his serum iron concentration decreased from 40 μmol/L to 24.6 μmol/L, and his transferrin saturation decreased from 97.5% to 55.1%. Early diagnosis is essential for patients with HH to obtain good outcomes. Regular phlebotomy after diagnosis can improve HH symptoms and delay HH disease progression.

Purpose: This study aimed to screen biomarkers to predict the efficacy of programmed cell death 1 (PD-1) blockade immunotherapy combined with chemotherapy as neoadjuvant therapy for esophageal squamous cell carcinoma (ESCC). Methods: In the first stage of the study, the baseline concentrations of 40 tumor-related chemokines in the serum samples of 50 patients were measured to screen for possible biomarkers. We investigated whether the baseline concentration of the selected chemokine was related to the therapeutic outcomes and tumor microenvironment states of patients treated with the therapy. In the second stage, the reliability of the selected biomarkers was retested in 34 patients. Results: The baseline concentration of macrophage migration inhibitory factor (MIF) was negatively correlated with disease-free survival (DFS) and overall survival (OS) in patients treated with the therapy. In addition, a low baseline expression level of MIF is related to a better tumor microenvironment for the treatment of ESCC. A secondary finding was that effective treatment decreased the serum concentration of MIF. Conclusion: Baseline MIF levels were negatively correlated with neoadjuvant therapy efficacy. Thus, MIF may serve as a predictive biomarker for this therapy. The accuracy of the prediction could be improved if the serum concentration of MIF is measured again after the patient received several weeks of treatment.

Background: The association between breast cancer patients with a TP53 pathogenic variant and risk of local recurrence and contralateral breast cancer remains largely unknown. Methods: The study population of 11093 patients was derived from two cohorts at the Breast Center of Peking University Cancer Hospital in China from November 2003, to March 2018. TP53 germline variants were determined for all patients. Results: In the study, forty-one (0.37%) carried a TP53 germline pathogenic variant, and 11052 were non-carriers (99.63%). Nineteen TP53 carriers (46.3%) and 4173 non-carriers (37.8%) were treated with breast-conserving therapy (BCT), while the remaining were treated with mastectomy. After a median follow-up of 6.7 years, the rate of ipsilateral breast tumor recurrence (IBTR) in TP53 carriers was significantly higher than that in non-carriers when treated with BCT (21.1% vs 3.8%, P = 0.006). No difference in the rate of IBTR was found between TP53 carriers and non-carriers when treated with mastectomy (0.0% vs 2.6%, P = 1.0). Furthermore, the rate of IBTR in TP53 carriers treated with BCT was significantly higher than that in those treated with mastectomy (21.1% vs 0.0%, P = 0.038). The 10-year cumulative risk of contralateral breast cancer in TP53 carriers was significantly higher than that in non-carriers (17.9% vs 3.6%, hazard ratio (HR) = 7.0, 95% CI: 3.3–14.9, P

Cats are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and risk transmitting viruses to naive cats or humans. Here, based on our novel adenovirus-vectored COVID-19 vaccine, the immunogenicity of Sad23L-nCoV-S vaccine was evaluated in cats by prime-boost vaccinations. Five cats were primed with a dose of 108 plaque-forming units (PFUs) Sad23L-nCoV-S vaccine and then boosted with an equal dose of same vaccine at a 4-week interval. Cat serum neutralizing antibody (NAb) titers (the sample dilution at which 50% inhibitory concentration [IC50]) were measured as IC50 15,849 to wild-type strain, IC50 6,591 to Alpha, IC50 2,315 to Beta, IC50 2,744 to Gamma, IC50 1,848 to Delta, and IC50 318 to Omicron variants of pseudotyped SARS-CoV-2 viruses at week 6 post-prime vaccination. All NAb levels to these five variants were ≥IC50 49 from vaccinated cats at week 10, while 48.8% to Delta and 100% to Omicron variants were

ABSTRACT: Background: As several vaccines for SARS-CoV-2 have been developed, a large proportion of individuals have been vaccinated worldwide so far. The rapid and accurate immunoassays are urgently needed for detecting the specific virus-neutralizing antibody (NAb), which reflect the protective effect of the vaccines among different populations. Methods: In this study, we designed a quantum dot lateral flow immunoassay strip (QD-LFIA) for smartphones for the detection of specific IgG or neutralizing antibodies in SARS-CoV-2 in human serum or whole blood samples. The recombinant receptor binding domain of the SARS-CoV-2 spike protein was used as the antigen to combine with NAb or angiotensin-converting enzyme 2. Results: Among 81 patients who recovered from COVID-19 who were diagnosed using the nucleic acid test initially, 98.8% (80/81) were positive for IgG and 88.9% (72/81) were positive for NAb by QD-LFIA. Among 64 individuals inoculated with inactivated vaccines and six subunit vaccines, 90% (63/70) were positive for IgG and 82.9% (58/70) were positive for NAb by QD-LFIA, whereas no cross-reaction was found in 150 healthy blood donors, two patients with influenza B, and three patients with common cold. Conclusion: The established platform could achieve a rapid and accurate detection of NAb specific to SARS-CoV-2, which could be used for detecting the protective effect of the vaccines in areas of world that currently affected by the pandemic.

Considering rapid climate change and its effects, an increasing number of enterprises are paying more attention to environmental protection behavior in order to realize their green innovation activities. However, environmental leadership is critical for delivering green innovation in business and industry. As such, can environmental leadership promote the green innovation performance of enterprises? If so, what is the influence mechanism? In the previous research on environmental leadership, the impact of environmental leadership on the green innovation performance of enterprises had not yet been effectively explored. Therefore, drawing on a resource-based view, this study explored the mechanism through which environmental leadership influences a firm's green innovation performance. In this study, with the help of the mature scale at home and abroad, variables were measured, and the relationship between variables was verified by multiple regression analysis using samples collected from 224 heavy-polluting enterprises in western China at multiple time points. It was found that (1) environmental leadership has significant positive effects on green product innovation performance and green process innovation performance; (2) proactive environmental strategies partly mediate the relationships between environmental leadership and green product, as well as green process innovation performance; and (3) a firm's organizational structure positively moderates the relationship between environmental leadership and proactive environmental strategies. Therefore, the results of our study provide theoretical and practical contributions for research on environmental leadership and proactive environmental strategies.

In this work, we propose a capillarity-promoted laser re-sintering method of printed semisolid Cu nanoparticles for facile fabrication of conductive patterns with voidless structure and improved conductivity. Conductive circuits with a thickness of 5 μm are fabricated. By using a semisolid Cu particle paste instead of a dry paste, a more compact sintered structure is obtained, and the resistivity is reduced from 18 to 9.2 μΩ cm. Thermal diffusion tests reveal that the semisolid paste exhibits a much higher thermal diffusion coefficient (∼7 × 10−6 m2/s) than the dry paste (∼3 × 10−6 m2/s). Through four repeated laser scannings, the fully sintered layer on the upper surface of the circuits thickens and transits into a solid structure without internal voids. The resistivity is further reduced to 3.8 μΩ cm, which is only two times that of bulk copper. The capillary phenomena of the semisolid paste also promotes the closure of large-scale voids. These effects drive the improvement of the properties and formable thickness of the sintered circuits. These findings could provide new experimental basis for structure and property modifications of printed circuits by similar techniques.

Background/aims: This study aims to determine which cell death modes contribute most in the progression of cirrhosis and acute-on-chronic liver failure (ACLF), and to investigate whether Yes associated protein (YAP) affects the disease process by regulating cell death. Materials and methods: 30C57BL/6 male mice were divided into five groups: control, carbon tetrachloride (CCl4)-induced liver fibrosis model, CCl4+verteporfin, CCl4+lipopolysaccharides (LPS) combined with the D-(+)-Galactosamine (LPS/D-GalN)-induced ACLF model, and ACLF + verteporfin. Patients with chronic hepatitis B (CHB), hepatitis B virus (HBV) related liver cirrhosis or ACLF were enrolled. Histology, immunohistochemistry, transmission electron microscopy, Western blot and ELISA were conducted to assess the roles of YAP and cell death in liver cirrhosis and ACLF, and to explore the effect of YAP inhibition on cell deaths. Results: YAP was markedly increased in mice with liver fibrosis and ACLF, along with ferroptosis and necroptosis. Furthermore, YAP inhibition significantly suppressed fibrosis in CCl4-mediated liver fibrosis and ACLF-associated liver injury. Notably, CCl4 induced up-regulation of ACSL4 and RIPK3 and down-regulation of SLC7A11, key factors in ferroptosis and necroptosis. This was significantly abrogated by verteporfin treatment. Similar changes in ferroptosis and necroptosis were found in ACLF and ACLF + verteporfin groups. Consistent with the above findings in mice, we found that plasma YAP levels were gradually increased with the development of HBV-related liver fibrosis and ACLF. Conclusion: Ferroptosis and necroptosis are involved in the development of liver cirrhosis and ACLF. Inhibition of YAP improved liver fibrosis and liver damage in ACLF through a reduction in ferroptosis and necroptosis. Our findings may help better understanding the role of YAP in liver fibrosis and ACLF.

The effects of increasing levels of pre-deformation on the mechanical properties and microstructure evolution (dominantly T1 phase) of an extensively used aerospace Al-Cu-Li alloy have been systematically investigated during the non-isothermal aging. Quantitative descriptions extracted from the microstructure parameters further revealed the separated strengthening contributions and mechanism. Pre-deformation prior to the NIA significantly accelerated the aging kinetics and improved the strength, and yet showed a limited benefit due to the generally decreased precipitation strengthening. Elevated pre-deformation in conjunction with the NIA process reduced the T1 diameter and interprecipitate spacing, the interprecipitate diffusion was gradually activated, responsible for the undulatory mean thickness. The experimental yield strength was successfully described by invoking the shearing mechanism in the pre-deformed samples (4–20 %). However, the strengthening transition from shearing to by-passing occurred in the 0 % sample, the by-passing model should be considered simultaneously owing to the larger diameter T1 precipitates. The critical diameter of the T1 precipitate for this transition ranged from 84 to 117 nm and was approximately 100 nm.

Objective: To investigate the gross α and β radioactivity levels of drinking water source in the city, the largest oil field production base in northeast China, in order to ensure the safety of drinking water and public health. Methods: The water samples from three drinking water sources were collected and tested in the dry and wet season, respectively. The gross α radioactivity was measured by standard curve method, gross β was measured by thin sample method. Results: Totally 184 samples were collected from the three sampling areas in dry and wet season respectively. The average values of gross α and β radioactivity levels in the drinking water source area were (0.24±0.09) and (0.30±0.17) Bq/L respectively. The average activity concentration of gross α and gross β in the dry season was (0.23±0.09) and (0.29±0.18) Bq/L, respectively. The gross α and β radioactivity levels gradually decreased from the intake to the end of the reservoir of drinking water source areas. Conclusions: The gross α and β radioactivity levels and distribution of drinking water source areas in this city were all lower than the drinking water limit issued by China and the reference level recommended by the World Health Organization. The radioactivity of water body of the drinking water source was within the normal background level.

Thioester-containing proteins (TEPs) superfamily is known to play important innate immune functions in vertebrates and invertebrates, and involved in recognition, and killing of invading pathogens. Here, a TEP gene (designated as Pf-TEP) was obtained from the pearl oyster Pinctada fucata by RT-PCR and rapid amplification of cDNA ends (RACE). The Pf-TEP cDNA consists of 4335 bp with an open reading frame (ORF) of 3639 bp encoding a protein of 1212 amino acids. The deduced TEP protein possessed the characteristic structure features present in its homologs and contained the A2M_N_2, A2M, A2M_comp, A2M_recep, and thioester domain, as well as the conserved Cys, His, and Glu residues. Phylogenetic analysis revealed that Pf-TEP is closely related to the TEPs from other invertebrates. Pf-TEP mRNA was expressed in all examined tissues including gill, digestive gland, adductor muscle, mantle and hemocyte, while the highest expression was found in gill. Following challenge with Vibrio alginolyticus, Pf-TEP expression was significantly induced in hemocytes. Further knockdown of Pf‐TEP by specific siRNA could significantly reduce the phagocytosis of V. alginolyticus by hemocytes in vitro. These results would help increase understanding of TEP existed as an ancient complement-like molecular and therefore provide new insights into the roles of TEP in the invertebrate immune system.

The exposure of polycyclic aromatic hydrocarbons (PAHs) can cause wheat leaf chlorosis. Thus, we hypothesize that chloroplast inner structure damage is the reason for leaf chlorosis. This study was conducted with the wheat seedlings exposed to Hoagland nutrient solution containing 1.0 mg L−1 phenanthrene for 9 days. Subcellular observation showed that chloroplast turns round and loses its structural integrity. Herein, iTRAQ (isobaric tag for relative and absolute quantification) was applied to analyze the changes of protein profile in chloroplast exposed to phenanthrene. A total of 517 proteins are identified, 261 of which are up-regulated. Eight proteins related with thylakoid (the structural component of chloroplast) are down-regulated and the expression of related genes further confirms the proteomic results through real-time PCR under phenanthrene treatment, suggesting that the thylakoid destruction is the reason for chloroplast deformation. Four proteins related with envelope and stroma are up-regulated, and this is the reason why chloroplast remains round. This study is useful in discussing the carcinogenic and teratogenic effects of PAHs in plant cells in the environment, and provides necessary knowledge for improving crop resistance to PAH pollution. Keywords: Polycyclic aromatic hydrocarbons, Leaf cell, Proteomics, Chloroplast deformation, Toxicity, iTRAQ

Swine wastewater (SW) treatment by Myriophyllum aquaticum is an important biotechnology for its resource utilization. However, some knowledge gaps remain in compound-pollutant removal in SW, especially in practical applications. To clarify the responses of M. aquaticum to the compound pollutants as well as the related operational parameters in SW treatment, three initial doses (0.5, 1.0, and 1.5 kg per pond in 150 L simulated SW) of M. aquaticum and a control (no plant; CK) were allocated to 12 ponds under a plastic roof in Nanjing city of Eastern China during 75 days in the summer of 2019. Results showed that M. aquaticum could be used as a pioneer plant to efficiently remove compounded pollutants of nitrogen (N), phosphorus (P), and especially for heavy metals in simulated SW. Compared with CK, M. aquaticum assisted in improving the total N, NH4+–N, NO3-–N, NO2-–N, and dissolved organic N by 30.1%, 100%, 100%, 97.6%, 20.2%, 39.8% whereas Cu, Zn, and Cd by 50.4%, 36.4% and 47.9% on average during the 75-day experiment in summer, respectively. Moreover, concentrations of Cu and Cd at day 75 were in the ranges of 1.92–2.82 and 0.64–1.47 g kg−1 DW, respectively, exceeding the corresponding limits of the heavy-metal hyperaccumulator. For the operational parameters, the optimized initial dose was 1.0 kg per pond with M. aquaticum harvested after 45 summer days, respectively. Given that M. aquaticum has been widely used as animal feed in recent years and limit values for Cu and Zn in animal feed are not set in China, the toxicities of Cu and Zn should be assessed and the guideline of their limit values needs to be established for safe feed production. Interestingly, NH4+–N could dominate the removal of heavy metals especially Cd in the simulated SW, however, related mechanisms are needed for further study.

A laser metal deposition (LMD) process has been applied to the fabrications of the (CrMnFeCoNi)1-xFex (x = 0.1, 0.2, 0.3, 0.4, 0.5 and 0.6) Multi-principal elements alloys (MPEAs). It is found that the LMD-fabricated (CrMnFeCoNi)50Fe50 alloy keeps a single-phase solid solution microstructure. Compared with the CrMnFeCoNi MPEA, the (CrMnFeCoNi)50Fe50 alloy obtains remarkably improved plasticity from 45% to 77%, while maintaining tensile strength (415 MPa to 470 MPa), due to the strain-induced FCC to BCC phase transformation. Furthermore, the (CrMnFeCoNi)50Fe50 alloy shows excellent mechanical properties at cryogenic temperatures. This alloy has lower cost and better mechanical property than the well-known CrMnFeCoNi MPEA by the addition of inexpensive Fe elements. The present work provides important pathways in the development of low-cost LMD-fabricated MPEA for cryogenic engineering applications.

The objective of this study is to investigate the feasibility of using chitosan–sodium alginate (CS–SA) based matrix tablets for extended-release of highly water-soluble drugs by changing formulation variables. Using trimetazidine hydrochloride (TH) as a water-soluble model drug, influence of dissolution medium, the amount of CS–SA, the CS:SA ratio, the type of SA, the type and amount of diluents, on in vitro drug release from CS–SA based matrix tablets were studied. Drug release kinetics and release mechanisms were elucidated. In vitro release experiments were conducted in simulated gastric fluid (SGF) followed by simulated intestinal fluid (SIF). Drug release rate decreased with the increase of CS–SA amount. CS:SA ratio had only slight effect on drug release and no influence of SA type on drug release was found. On the other hand, a large amount of water-soluble diluents could modify drug release profiles. It was found that drug release kinetics showed the best fit to Higuchi equation with Fickian diffusion as the main release mechanism. In conclusion, this study demonstrated that it is possible to design extended-release tablets of water-soluble drugs using CS–SA as the matrix by optimizing formulation components, and provide better understanding about drug release from CS–SA matrix tablets.

The objective of this paper is to prepare vinpocetine (VIN) inclusion complex and evaluate its brain targeting effect after intranasal administration. In the present study, VIN inclusion complex was prepared in order to increase its solubility. Stability constant (Kc) was used for host selection. Factors influencing properties of the inclusion complex was investigated. Formation of the inclusion complex was identified by solubility study and DSC analysis. The brain targeting effect of the complex after intranasal administration was studied in rats. It was demonstrated that properties of the inclusion complex was mainly influenced by cyclodextrin type, organic acids type, system pH and host/guest molar ratio. Multiple component complexes can be formed by the addition of citric acid, with solubility improved for more than 23 times. Furthermore, In vivo study revealed that after intranasal administration, the absolute bioavailability of vinpocetine inclusion complex was 88%. Compared with intravenous injection, significant brain targeting effect was achieved after intranasal delivery, with brain targeting index 1.67. In conclusion, by intranasal administration of VIN inclusion complex, a fast onset of action and good brain targeting effect can be achieved. Intranasal route is a promising approach for the treatment of CNS diseases.

In the context of Industry 4.0, the most important trend in the shipbuilding industry is to efficiently manufacture intelligent and more environmentally friendly ships. This requires the shipbuilding industry to achieve technological innovations in all aspects of the ship's life cycle and accelerate the digital transformation of the industry. Thanks to the development of new-generation information technology, digital twins have received widespread attention and application in the manufacturing industry. The excellent performance of digital twins in monitoring, diagnosis and decision support also provides strong support for the digital transformation of the manufacturing industry. However, the application and development of digital twin technology are constrained when faced with the complex and discrete manufacturing processes in the shipbuilding industry. To address the constraints in the shipbuilding industry, promote the application of digital twin technology, and support the digital transformation of the shipbuilding industry, a statistical analysis of publications linked to the shipbuilding industry and digital twin using the Web of Science and the Scopus are done in this paper. The application and development of digital twin in the shipbuilding industry was systematically analyzed, the problems restricting the development of digital twin in the shipbuilding industry was summarized. Finally, the development trend of digital twin in shipbuilding industry prospects.

To study the multilevel coupled vibration of a naval gun under the foundation motion excitation of the ship, a mechanical-electrical-hydraulic coupled dynamic model of the naval gun including the follow-up systems’ influence was established. The subprogram for calculating the ship foundation motion was written by the harmonic superposition method, and the motion in the 3 and 5-scale sea waves was reconstructed, respectively. Based on the multidisciplinary simulation, the transmission characteristics of the ship’s foundation motion excitation along the naval gun and the influence of the tooth arc arrangement on the stabilization accuracy of the naval gun are analyzed. The results show that: the foundation motion excitation of the ship will aggravate the imbalance of the contact forces at the left and right trunnions of the cradle. A bilateral symmetrical arrangement scheme of the tooth arcs can reduce the contact forces’ imbalance at the trunnions and reduce the adverse influence on the stabilization accuracy of the naval gun. The relevant research provides theoretical support and technical guidance for the structural design or verification of the naval gun.

Background & Aims: The function of cholinergic anti-inflammatory pathway (CAP) in acute liver failure (ALF) with inflammatory storm remains indefinite. The liver-gut axis has been proved to be crucial for liver homeostasis. Investigation about CAP regulation on liver-gut axis would enrich our understanding over cholinergic anti-inflammatory mechanism. Methods: Co-injection of lipopolysaccharide and D-galactosamine was used to establish the model of ALF. PNU-282987 was used to activate the CAP. Histological staining, real-time polymerase chain reaction, Western blotting, RNA sequencing, and flow cytometry were conducted. Liver biopsy specimens and patients’ serum from patients with liver failure were also analyzed. Results: We confirmed that activating the CAP alleviated hepatocyte destruction, accompanied by a significant decrease in hepatocyte apoptosis, pro-inflammatory cytokines, and NLRP3 inflammasome activation. Moreover, hepatic MAdCAM1 and serum MAdCAM1 levels were induced in ALF, and MAdCAM1 levels were positively correlated with the extent of liver damage and the expression of pro-inflammatory markers. Furthermore, activating the CAP mainly downregulated ectopic expression of MAdCAM1 on endothelial cells, and inhibition of NF-κB p65 nuclear translocation was partly attributed to the decreased MAdCAM1. Notably, in ALF, the aberrant hepatic expression of MAdCAM1 subsequently recruited gut-derived α4β7+ CD4+T cells to the liver, which exhibited an augmented IFN-γ-secreting and IL-17-producing phenotype. Finally, we revealed that the levels of serum and hepatic MAdCAM1 were elevated in patients with liver failure and closely correlated with clinical course. Increasing hepatic infiltration of β7+ cells were also confirmed in patients. Conclusions: Activating the CAP attenuated liver injury by inhibiting MAdCAM1/α4β7 -mediated gut-derived proinflammatory lymphocytes infiltration, which provides a potential therapeutic target for ALF.

Oral diseases include oral cancer, periodontitis, endodontium infection, and caries. The oral cavity is prone to the proliferation of pathogenic bacteria and infectious diseases owing to its unique environment. During the drug-based treatment of oral diseases, saliva can dilute the drug formulation, reduce the interaction between the drug and site of action, and weaken drug efficacy. Therefore, searching an effective drug delivery approach is extremely critical and urgent. Stimuli responsive hydrogels respond to altered environmental conditions under disease states, allowing specific drug delivery. Accordingly, smart drug delivery systems can prolong the duration of drug action, reduce adverse reactions, decrease the frequency of administration, and improve patient compliance, thereby accelerating recovery. In this review, we discuss the different types of stimuli responsive hydrogels for smart drug delivery, focusing on their application in oral disease management. Further, we present current challenges and provide suggestions for future research on stimuli responsive hydrogels for oral disease treatment.

The FASER experiment at the LHC is designed to search for light, weakly-interacting particles produced in proton-proton collisions at the ATLAS interaction point that travel in the far-forward direction. The first results from a search for dark photons decaying to an electron-positron pair, using a dataset corresponding to an integrated luminosity of 27.0 fb−1 collected at centre-of-mass energy s=13.6 TeV in 2022 in LHC Run 3, are presented. No events are seen in an almost background-free analysis, yielding world-leading constraints on dark photons with couplings ϵ∼2×10−5−1×10−4 and masses ∼17 MeV−70 MeV. The analysis is also used to probe the parameter space of a massive gauge boson from a U(1)B−L model, with couplings gB−L∼5×10−6−2×10−5 and masses ∼15 MeV−40 MeV excluded for the first time.

Summary: Background: Severe eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) remains the most relapsed subtype of uncontrolled CRSwNP. CM310, a humanised anti-interleukin (IL)-4 receptor alpha monoclonal antibody, inhibits IL-4 and IL-13 signaling which underlying eosinophilic inflammation. This study aims to evaluate the efficacy and safety of CM310 in patients with severe ECRSwNP. Methods: A multicentre, randomised, double-blind, and placebo-controlled phase 2 clinical trial was conducted. 56 eligible adult patients with severe ECRSwNP were randomised 1:1 to receive subcutaneously either CM310 (300 mg) or placebo every 2 weeks under the background therapy of mometasone furoate nasal spray (MFNS) for 16 weeks, with 8 weeks of follow-up. Coprimary endpoints included the changes from baseline in nasal polyp score (NPS) and nasal congestion score (NCS) at week 16. Key secondary endpoints included sinus Lund-Mackay CT score, change in sinus volume occupied by disease, University of Pennsylvania Smell Identification Test score, 22-item Sino-nasal Outcome Test score, and total symptom score. Safety, pharmacodynamics, and changes in type 2 inflammation biomarkers were assessed. This study is registered with ClinicalTrials.gov, NCT04805398. Findings: Between April 6, 2021, and March 18, 2022, 27 patients respectively in both the CM310 and placebo groups completed the study. Findings suggested that CM310 improved the coprimary efficacy endpoints of decreasing nasal polyp size and alleviating nasal congestion compared with the placebo. Least squares (LS) mean differences (CM310 vs placebo) of change from baseline in NPS and NCS at week 16 were −2.1 (95% CI −2.9, −1.4; p

Multidrug resistance (MDR) promotes tumor recurrence and metastasis and heavily reduces anticancer efficiency, which has become a primary reason for the failure of clinical chemotherapy. The mechanisms of MDR are so complex that conventional chemotherapy usually fails to achieve an ideal therapeutic effect and even accelerates the occurrence of MDR. In contrast, the combination of chemotherapy with dual-drug has significant advantages in tumor therapy. A novel dual-drug codelivery nanosystem, which combines dual-drug administration with nanotechnology, can overcome the application limitation of free drugs. Both the characteristics of nanoparticles and the synergistic effect of dual drugs contribute to circumventing various drug-resistant mechanisms in tumor cells. Therefore, developing dual-drug codelivery nanosystems with different multidrug-resistant mechanisms has an important reference value for reversing MDR and enhancing the clinical antitumor effect. In this review, the advantages, principles, and common codelivery nanocarriers in the application of dual-drug codelivery systems are summarized. The molecular mechanisms of MDR and the dual-drug codelivery nanosystems designed based on different mechanisms are mainly introduced. Meanwhile, the development prospects and challenges of codelivery nanosystems are also discussed, which provide guidelines to exploit optimized combined chemotherapy strategies in the future.

Isoniazid (INH) is a highly effective single and/or combined first-line anti-tuberculosis (anti-TB) therapy drug, and the hepatotoxicity greatly limits its clinical application. INH-induced liver injury (INH-DILI) is a typical immune-mediated idiosyncratic drug-induced liver injury. Existing mechanisms including genetic variations in drug metabolism and immune responses cannot fully explain the differences in susceptibility and sensitivity to INH-DILI, suggesting that other factors may be involved. Accumulating evidence indicates that the development and severity of immune-mediated liver injury is related to gut microbiota. In this study, INH exposure caused liver damage, immune disregulation and microbiota profile alteration. Depletion of gut microbiota ameliorated INH-DILI, and improved INH-DILI-associated immune disorder and inflammatory response. Moreover, hepatotoxicity of INH was ameliorated by fecal microbiota transplantation (FMT) from INH-treated mice. Notably, Bifidobacterium abundance was significantly associated with transaminase levels. In conclusion, our results suggested that the effect of gut microbiota on INH-DILI was related to immunity, and the difference in INH-DILI sensitivity was related to the structure of gut microbiota. Changes in the structure of gut microbiota by continuous exposure of INH resulted in the tolerance to liver injury, and probiotics such as Bifidobacterium might play an important role in INH-DILI and its ''adaptation'' phenomenon. This work provides novel evidence for elucidating the underlying mechanism of difference in individual’s response to INH-DILI and potential approach for intervening anti-TB drug liver injury by modulating gut microbiota.

Mitochondrial dysfunction is the main cause of damage to the pathological mechanism of ischemic cardiomyopathy. In addition, mitochondrial dysfunction can also affect the homeostasis of cardiomyocytes or endothelial cell dysfunction, leading to a vicious cycle of mitochondrial oxidative stress. And mitochondrial dysfunction is also an important pathological basis for ischemic cardiomyopathy and reperfusion injury after myocardial infarction or end-stage coronary heart disease. Therefore, mitochondria can be used as therapeutic targets against myocardial ischemia injury, and the regulation of mitochondrial morphology, function and structure is a key and important way of targeting mitochondrial quality control therapeutic mechanisms. Mitochondrial quality control includes mechanisms such as mitophagy, mitochondrial dynamics (mitochondrial fusion/fission), mitochondrial biosynthesis, and mitochondrial unfolded protein responses. Among them, the increase of mitochondrial fragmentation caused by mitochondrial pathological fission is the initial factor. The protective mitochondrial fusion can strengthen the interaction and synthesis of paired mitochondria and promote mitochondrial biosynthesis. In ischemia or hypoxia, pathological mitochondrial fission can promote the formation of mitochondrial fragments, fragmented mitochondria can lead to damaged mitochondrial DNA production, which can lead to mitochondrial biosynthesis dysfunction, insufficient mitochondrial ATP production, and mitochondrial ROS. Burst growth or loss of mitochondrial membrane potential. This eventually leads to the accumulation of damaged mitochondria. Then, under the leadership of mitophagy, damaged mitochondria can complete the mitochondrial degradation process through mitophagy, and transport the morphologically and structurally damaged mitochondria to lysosomes for degradation. But once the pathological mitochondrial fission increases, the damaged mitochondria increases, which may activate the pathway of cardiomyocyte death. Although laboratory studies have found that a variety of mitochondrial-targeted drugs can reduce myocardial ischemia and protect cardiomyocytes, there are still few drugs that have successfully passed clinical trials. In this review, we describe the role of MQS in ischemia/hypoxia-induced cardiomyocyte physiopathology and elucidate the relevant mechanisms of mitochondrial dysfunction in ischemic cardiomyopathy. In addition, we also further explained the advantages of natural products in improving mitochondrial dysfunction and protecting myocardial cells from the perspective of pharmacological mechanism, and explained its related mechanisms. Potential targeted therapies that can be used to improve MQS under ischemia/hypoxia are discussed, aiming to accelerate the development of cardioprotective drugs targeting mitochondrial dysfunction.

Background: In the last two decades, electrical stimulation (ES) has been tested in patients with various eye diseases and shows great treatment potential in retinitis pigmentosa and optic neuropathy. However, the clinical application of ES in ophthalmology is currently limited. On the one hand, optimization and standardization of ES protocols is still an unmet need. On the other hand, poor understanding of the underlying mechanisms has hindered clinical exploitation. Main Text: Numerous experimental studies have been conducted to identify the treatment potential of ES in eye diseases and to explore the related cellular and molecular mechanisms. In this review, we summarized the in vitro and in vivo evidence related to cellular and tissue response to ES in eye diseases. We highlighted several pathways that may be utilized by ES to impose its effects on the diseased retina. Conclusions: Therapeutic effect of ES in retinal degenerative diseases might through preventing neuronal apoptosis, promoting neuronal regeneration, increasing neurotrophic factors production in Müller cells, inhibiting microglial activation, enhancing retinal blood flow, and modulating brain plasticity. Future studies are suggested to analyse changes in specific retinal cells for optimizing the treatment parameters and choosing the best fit ES delivery method in target diseases.

Immune checkpoint blockade (ICB) therapy has revolutionized the treatment of various types of cancer. However, even promising systemically administered ICB agents can cause immune-related adverse events (irAEs). The management of irAEs has been a significant concern. In addition to the risk of compromised immune function with corticosteroids and other immunomodulatory regimens used to treat irAEs, the complex mechanisms of irAEs make management of the “off-target” effects extremely challenging. Various materials with high biocompatibility, controllable degradability, and the ability for local and targeted delivery and controlled and sustained release of drugs have been explored to limit irAEs. Herein, we briefly review the fundamental mechanisms and clinical applications of immune checkpoint inhibitors and the potential mechanisms and clinical treatment of irAEs. We also highlight the application of emerging materials in the management of irAEs through “prevention” and “treatment”.

Recently the STAR Collaboration reported measurement of the “subatomic swirls”, that is, the most vortical fluid flow structures in the quark–gluon plasma produced via the AuAu collisions at the Relativistic Heavy Ion Collider (RHIC). This result has attracted significant interest and generated wide enthusiasm. For such an important finding, it is crucial to look for additional evidences of confirmation and to critically test the current interpretation of the global polarization measurement. We suggest that the CuCu and CuAu colliding systems at RHIC provide such opportunity. Interestingly, our calculations reveal that the fluid vorticity in the CuCu or CuAu collision is comparable to that in the AuAu collision. We find the computed Λ hyperon polarization effect is stronger in the CuCu and CuAu systems than the AuAu system at the same collisional beam energy and centrality class, with an interesting hierarchy CuCu > CuAu > AuAu due to interplay between Λ production timing and the time evolution of the vorticity. These predictions can be readily tested by experimental data.

A strong magnetic field influences significantly the masses of the charged light mesons. For example, the mass of charged pion increases with the magnetic field increasing. We propose this mechanism as a possible way to extract the magnitude of magnetic field at freeze-out in heavy ion collisions and thus help constrain its lifetime which is currently a major open question to resolve. Specifically we show that the ratio between the yield of charged pions and that of charged rhos is very sensitive to the magnetic field value at freeze-out. By using a viscous-hydrodynamic framework (iEBE-VISHNU) to simulate heavy ion collisions and implementing magnetic-field-dependent meson masses, we compute their yields and predict the dependence of such ratio on the magnetic field. We suggest to use this ratio of charged rho yield over charged pion yield as an experimental observable to extract the possible magnetic field at freeze-out in heavy ion collisions.

Recent STAR measurements suggest a difference in the global spin polarization between hyperons and anti-hyperons, especially at relatively low collision beam energy. One possible cause of this difference is the potential presence of in-medium magnetic field. In this study, we investigate the phenomenological viability of this interpretation. Using the AMPT model framework, we quantify the influence of different magnetic field evolution scenarios on the size of the polarization difference in a wide span of collision beam energies. We find that such difference is very sensitive to the lifetime of the magnetic field. For the same lifetime, the computed polarization difference only mildly depends on the detailed form of its evolution. Assuming magnetic polarization as the mechanism to enhance anti-hyperon signal while suppress hyperon signal, we phenomenologically extract an upper limit on the needed magnetic field lifetime in order to account for the experimental data. The so-obtained lifetime values are in a quite plausible ballpark and follow approximately the scaling relation of being inversely proportional to the beam energy. Possible implications on other magnetic field related effects are also discussed. Keywords: Heavy ion collision, Vorticity, Global polarization, Magnetic field