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Abstract Climate deterioration, water shortages, and abiotic stress are the main threats worldwide that seriously affect cotton growth, yield, and fiber quality. Therefore, research on improving cotton yield and tolerance to biotic and abiotic stresses is of great importance. The NAC proteins are crucial and plant-specific transcription factors (TFs) that are involved in cotton growth, development, and stress responses. The comprehensive utilization of cotton NAC TFs in the improvement of cotton varieties through novel biotechnological methods is feasible. Based on cotton genomic data, genome-wide identification and analyses have revealed potential functions of cotton NAC genes. Here, we comprehensively summarize the recent progress in understanding cotton NAC TFs roles in regulating responses to drought, salt, and Verticillium wilt-related stresses, as well as leaf senescence and the development of fibers, xylem, and glands. The detailed regulatory network of NAC proteins in cotton is also elucidated. Cotton NAC TFs directly bind to the promoters of genes associated with ABA biosynthesis and secondary cell-wall formation, participate in several biological processes by interacting with related proteins, and regulate the expression of downstream genes. Studies have shown that the overexpression of NAC TF genes in cotton and other model plants improve their drought or salt tolerance. This review elucidates the latest findings on the functions and regulation of cotton NAC proteins, broadens our understanding of cotton NAC TFs, and lays a fundamental foundation for further molecular breeding research in cotton.

AbstractContext The mechanisms of Traditional Chinese Medicine (TCM) Guizhi-Gancao Decoction (GGD) remain unknown.Objective This study explores the mechanisms of GGD against cardiac hypertrophy.Materials and methods Network pharmacology analysis was carried out to identify the potential targets of GGD. In vivo experiments, C57BL/6J mice were divided into Con, phenylephrine (PE, 10 mg/kg/d), 2-chloroadenosine (CADO, the stable analogue of adenosine, 2 mg/kg/d), GGD (5.4 g/kg/d) and GGD (5.4 g/kg/d) + CGS15943 (a nonselective adenosine receptor antagonist, 4 mg/kg/d). In vitro experiments, primary neonatal rat cardiomyocytes (NRCM) were divided into Con, PE (100 µM), CADO (5 µM), GGD (10−5 g/mL) and GGD (10−5 g/mL) + CGS15943 (5 µM). Ultrasound, H&E and Masson staining, hypertrophic genes expression and cell surface area were conducted to verify the GGD efficacy. Adenosine receptors (ADORs) expression were tested via real-time polymerase chain reaction (PCR), western blotting and immunofluorescence analysis.Results Network pharmacology identified ADORs among those of the core targets of GGD. In vitro experiments demonstrated that GGD attenuated PE-induced increased surface area (with an EC50 of 5.484 × 10−6 g/mL). In vivo data shown that GGD attenuated PE-induced ventricular wall thickening. In vitro and in vivo data indicated that GGD alleviated PE-induced hypertrophic gene expression (e.g., ANP, BNP and MYH7/MYH6), A1AR over-expression and A2aAR down-expression. Moreover, CADO exerts effects similar to GGD, whereas CGS15943 eliminated most effects of GGD.Discussion and conclusions Our findings suggest the mechanism by which GGD inhibits cardiac hypertrophy, highlighting regulation of ADORs as a potential therapeutic strategy for HF.

Abstract Chemical etching of nano-sized metal clusters at the atomic level has a high potential for creating metal number-specific structures and functions that are difficult to achieve with bottom-up synthesis methods. In particular, precisely etching metal atoms one by one from nonmetallic element-centred metal clusters and elucidating the relationship between their well-defined structures, and chemical and physical properties will facilitate future materials design for metal clusters. Here we report the single-gold etching at a hypercarbon centre in gold(I) clusters. Specifically, C-centred hexagold(I) clusters protected by chiral N-heterocyclic carbenes are etched with bisphosphine to yield C-centred pentagold(I) (CAu I 5 ) clusters. The CAu I 5 clusters exhibit an unusually large bathochromic shift in luminescence, which is reproduced theoretically. The etching mechanism is experimentally and theoretically suggested to be a tandem dissociation-association-elimination pathway. Furthermore, the vacant site of the central carbon of the CAu I 5 cluster can accommodate AuCl, allowing for post-functionalisation of the C-centred gold(I) clusters.

Abstract Background Acute gouty is caused by the excessive accumulation of Monosodium Urate (MSU) crystals within various parts of the body, which leads to a deterioration of the local microenvironment. This degradation is marked by elevated levels of uric acid (UA), increased reactive oxygen species (ROS) production, hypoxic conditions, an upsurge in pro-inflammatory mediators, and mitochondrial dysfunction. Results In this study, we developed a multifunctional nanoparticle of polydopamine-platinum (PDA@Pt) to combat acute gout by leveraging mild hyperthermia to synergistically enhance UA degradation and anti-inflammatory effect. Herein, PDA acts as a foundational template that facilitates the growth of a Pt shell on the surface of its nanospheres, leading to the formation of the PDA@Pt nanomedicine. Within this therapeutic agent, the Pt nanoparticle catalyzes the decomposition of UA and actively breaks down endogenous hydrogen peroxide (H2O2) to produce O2, which helps to alleviate hypoxic conditions. Concurrently, the PDA component possesses exceptional capacity for ROS scavenging. Most significantly, Both PDA and Pt shell exhibit absorption in the Near-Infrared-II (NIR-II) region, which not only endow PDA@Pt with superior photothermal conversion efficiency for effective photothermal therapy (PTT) but also substantially enhances the nanomedicine’s capacity for UA degradation, O2 production and ROS scavenging enzymatic activities. This photothermally-enhanced approach effectively facilitates the repair of mitochondrial damage and downregulates the NF-κB signaling pathway to inhibit the expression of pro-inflammatory cytokines. Conclusions The multifunctional nanomedicine PDA@Pt exhibits exceptional efficacy in UA reduction and anti-inflammatory effects, presenting a promising potential therapeutic strategy for the management of acute gout. Graphical Abstract

Abstract Genetic variation in human populations can result in the misfolding and aggregation of proteins, giving rise to systemic and neurodegenerative diseases that require management by proteostasis. Here, we define the role of GRP94, the endoplasmic reticulum Hsp90 chaperone paralog, in managing alpha-1-antitrypsin deficiency on a residue-by-residue basis using Gaussian process regression-based machine learning to profile the spatial covariance relationships that dictate protein folding arising from sequence variants in the population. Covariance analysis suggests a role for the ATPase activity of GRP94 in controlling the N- to C-terminal cooperative folding of alpha-1-antitrypsin responsible for the correction of liver aggregation and lung-disease phenotypes of alpha-1-antitrypsin deficiency. Gaussian process-based spatial covariance profiling provides a standard model built on covariant principles to evaluate the role of proteostasis components in guiding information flow from genome to proteome in response to genetic variation, potentially allowing us to intervene in the onset and progression of complex multi-system human diseases.

BackgroundMyelofibrosis (MF) is a myeloproliferative neoplasm characterized by bone marrow fibrosis associated with substantial morbidity and mortality. The therapeutic landscape for MF has advanced with the development of Janus kinase inhibitors (JAKis) like ruxolitinib (RUX), fedratinib (FED), pacritinib (PAC), and momelotinib (MMB), aiming to alleviate symptoms and enhance patient comfort.MethodsA network meta-analysis was conducted to assess the efficacy and safety of eleven JAKi treatment regimens across nine randomized controlled trials (RCTs) with a total of 2340 participants. Outcomes were evaluated in terms of spleen volume reduction (SVR), total symptom score reduction (TSSR), hematological safety profiles, and overall survival (OS).ResultsRUX and MMB were superior in achieving SVR and TSSR, with significant dose-response relationships observed. PAC and MMB were associated with a decreased risk of grade 3/4 anemia and thrombocytopenia compared to other JAKis. However, no substantial benefits in OS were observed with newer JAKis compared to RUX. The poorer OS outcomes with certain PAC dosages were likely influenced by baseline patient characteristics, particularly severe cytopenias.ConclusionThe introduction of JAKis significantly changed the treatment of MF. This meta-analysis reaffirms the core role of RUX and positions MMB as a potentially powerful alternative for treating symptoms and reducing spleen size. Meanwhile, MMB and PAC have a positive effect on anemia in MF while FED is more tolerable for patients with thrombocytopenia. However, it should be noted that these results are influenced by baseline patient characteristics, particularly cytopenias, which affects both management and overall survival. Therefore, there is an urgent need for personalized dosing strategies to optimize the balance between efficacy and safety, with careful consideration of patient-specific factors.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023424179.

This study used ultrasound-enzyme-assisted deep eutectic solvents to establish a green and highly efficient total flavonoids extraction process from mulberry leaves. On the basis of the results of single-factor experiments, the extraction amount of total flavonoids was used as the response value, and the Box-Behnken response surface method was used to optimize, and the antioxidative ability of total flavonoids from mulberry leaves on DPPH radicals and ABTS+ radicals was studied. The results showed that when the choline chloride/fructose/alcohol molar ratio was 1:1:3, water content 30%, liquid-solid ratio 40 mL/g, ultrasonic power 360 W, ultrasonic temperature 40 ℃, ultrasonic time 40 min, dosage of enzyme 4%, the extraction amount of total flavonoids from mulberry leaves reached 46.58 mg/g. When the mass concentration of total flavonoids from mulberry leaves was 0.08 mg/mL, the scavenging rate of DPPH radicals was 98.36%. And when the mass concentration of total flavonoids from mulberry leaves was 0.2 mg/mL, the scavenging rate of ABTS+ radicals was 72.12%. Therefore, the ultrasonic-enzyme-assisted deep eutectic solvents method was green and simple to operate, and could effectively improve the extraction yield of total flavonoids from mulberry leaves. This method provided a scientific basis for the development and utilization of mulberry leaf resources.

The purpose of this study is to further investigate the strength size effect and failure mechanism of asphalt mixtures and clarify the strength parameter conversion relationship between standard and non-standard size samples. The article established an improved microscopic model for uniaxial compression and indirect tensile testing of asphalt mixtures based on laboratory and discrete element simulation tests. The effects of thickness and gradation on the uniaxial compressive strength (UCS) and indirect tensile strength (ITS) of asphalt mixtures were studied. The loading rates of the UCS and ITS tests were set at 2 mm/min and 50 mm/min, respectively. Additionally, the tensile-compressive stress distribution, crack propagation, and strength contribution rates of different contact types within the sample were investigated during the virtual model loading process. The reliability of the model was validated through laboratory test results. Finally, the strength parameter conversion relationship between standard and non-standard size samples was investigated. The study found that the UCS of asphalt mixtures decreases with increasing thickness, while the ITS increases with increasing thickness, with average reduction and increase rates of 70.69 % and 24.18 %, respectively. The contact fracture ratio and the strength contribution rate of the aggregate-asphalt mortar contacts both exceed 50 %, indicating that the fracture of these contacts is the primary cause of asphalt mixture failure. The use of small-sized samples instead of standard samples in practical applications is promising. These research work outcomes can serve as a theoretical basis for designing asphalt pavement materials and acquiring existing asphalt pavement material parameters.

Summary: The model of M2-like tumor-associated macrophages (TAMs) is an increasingly attractive model for the study of TAMs. However, the detailed process of M2-like TAMs polarization induced by lactic acid or conditioned medium from Lewis cells (LCM) and the identification of M2-like TAMs is not yet available. In this protocol, we present the detailed methods to induce M2-like TAMs polarization and verify its functionality in order to better carry out related research.For complete details on the use and execution of this protocol, please refer to Fang et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract The increasing demand for high‐performance devices on heat dissipation makes it approach the bottleneck even for metals with high thermal conductivities. The coating of only one layer of graphene, the heat dissipation performances of Cu, Ag, and Al can be further enhanced, e.g., with a maximum temperature reduction by ≈9% for a Cu foil is demonstrated. Molecular dynamics (MD) analysis of spectral phonon transmission reveals that low‐frequency phonons play a significant role in the thermal transport within the Cu/single‐layer graphene (SLG) system, and the high‐frequency phonons exhibit substantial mismatch. It suggests that the thermal anisotropy of graphene enables a rapid heat dispersion in the in‐plane direction and provides an effective thermal insulation in the out‐of‐plane direction. The thermal conductivity calculations demonstrate an enhanced participation of phonons in heat conduction by the graphene layer, indicating a novel heat conduction mechanism in the Cu/single‐layer graphene system. These findings highlight the positive impact of graphene on the heat conduction of metals, and they will hold crucial implications for the design and application of graphene‐based thermal devices is believed.

Cotton is one of the world’s most important economic crops. Verticillium wilt is a devastating cotton disease caused by Verticillium dahliae, significantly impacting cotton yield and quality. E3 ubiquitin ligases are essential components of the ubiquitin-mediated 26S proteasome system, responsible for recognizing ubiquitinated target proteins and promoting their degradation, which play a crucial regulatory role in plant immune responses. In this study, on the basis of the confirmation of differential expression of GhDIRP1, a RING-type E3 ubiquitin ligase encoding gene, in two cotton varieties resistant (Zhongzhimian 2) or susceptible (Jimian 11) to V. dahliae, we demonstrated that GhDIRP1 is a negative regulator of V. dahliae resistance because silencing GhDIRP1 in cotton and heterogeneously overexpressing the gene in Arabidopsis enhanced and compromised resistance to V. dahliae, respectively. The GhDIRP1-mediated immune response seemed to be realized through multiple physiological pathways, including hormone signaling, reactive oxygen species, and lignin biosynthesis. Based on the sequences of GhDIRP1 isolated from Zhongzhimian 2 and Jimian 11, we found that GhDIRP1 had identical coding but different promoter sequences in the two varieties, with the promoter of Zhongzhimian 2 being more active than that of Jimian 11 because the former drove a stronger expression of GUS and LUC reporter genes. The results link the ubiquitination pathway to multiple physiological pathways acting in the cotton immune response and provide a candidate gene for breeding cotton varieties resistant to V. dahliae.

Forecasting energy demand is critical to ensure the steady operation of the power system. However, present approaches to estimating power load are still unsatisfactory in terms of accuracy, precision, and efficiency. In this paper, we propose a novel method, named ELFNet, for estimating short-term electricity consumption, based on the deep convolutional neural network model with a double-attention mechanism. The Gramian Angular Field method is utilized to convert electrical load time series into 2D image data for input into the proposed model. The prediction accuracy is greatly improved through the use of a convolutional neural network to extract the intrinsic characteristics from the input data, along with channel attention and spatial attention modules, to enhance the crucial features and suppress the irrelevant ones. The present ELFNet method is compared to several classic deep learning networks across different prediction horizons using publicly available data on real power demands from the Belgian grid firm Elia. The results show that the suggested approach is competitive and effective for short-term power load forecasting.

Abstract Background Cotton is extremely affected by severe natural stresses. Drought is one of the most serious abiotic stress that adversely influences cotton growth, productivity, and fiber quality. Previous studies indicate that basic leucine-zipper (bZIP) transcription factors are involved in the response of plants to various stresses. However, the molecular function and regulatory mechanism of GhVIP1 in response to drought stress are still unknown. Results In this research, GhVIP1 was cloned from a drought-tolerant variety. Expression of GhVIP1 was up-regulated in response to multiple abiotic stresses, especially under drought stress. And GhVIP1 was highly expressed in the root, stem, and 10 days post-anthesis ovule. Inhibiting the expression of GhVIP1 in cotton using the virus-induced gene silencing method resulted in higher electrical conductivity in leaves, but lower water content under drought stress compared with the WT plant. Overexpression of GhVIP1 in Arabidopsis enhanced plant drought tolerance through increasing the seed germination rate and improving the development of root. The exogenous expression of GhVIP1 up-regulated the transcription of genes associated with drought response and proline biosynthesis during drought stress in Arabidopsis. Conclusion In summary, these results indicated that GhVIP1 played a positive role in plants' response to drought stress. The use of GhVIP1 via modern biotechnology might facilitate the improvement of drought tolerance in cotton cultivars.

Abstract Chemical functionalisation of semiconducting single-walled carbon nanotubes (SWNTs) can tune their local band gaps to induce near-infrared (NIR) photoluminescence (PL). However, tuning the PL to telecommunication wavelengths (>1300 nm) remains challenging. The selective emergence of NIR PL at the longest emission wavelength of 1320 nm was successfully achieved in (6,5) SWNTs via cyclic perfluoroalkylation. Chiral separation of the functionalised SWNTs showed that this functionalisation was also effective in SWNTs with five different chiral angles. The local band gap modulation mechanism was also studied using density functional theory calculations, which suggested the effects of the addenda and addition positions on the emergence of the longest-wavelength PL. These findings increase our understanding of the functionalised SWNT structure and methods for controlling the local band gap, which will contribute to the development and application of NIR light-emitting materials with widely extended emission and excitation wavelengths.

Introduction: Female-specific cancers seriously affect physical and psychological health of women worldwide. Objectives: We aimed to elucidate trends in the age-standardized mortality rates (ASMRs) of breast cancer, cervical cancer, uterine cancer, and ovarian cancer in female populations with different socioeconomic statuses in China and in countries with different Human Development Index (HDI). Methods: A longitudinal study was performed using the data of cancer death in China and other 39 countries. The mortality rates were standardized with the Segi’s world population. Trends in the mortalities were exhibited by estimated annual percentage change (EAPC). Pearson correlation was used to assess the association between EAPC and HDI. Results: In mainland China, female breast cancer, cervical cancer, uterine cancer, and ovarian cancer accounted for 6.60 %, 4.21 %, 2.50 %, and 2.02 % of cancer death (n = 1,314,040) in women with 1,220,251,032 person-years, respectively. The ASMRs of cervical cancer (EAPC = 3.87 %, P

A reliable strategy for improving the stability and shelf life of protein-stabilized systems is by covalently attaching the protein onto a polysaccharide. In this study, ovalbumin (OVA) was modified with dextran (DEX) of different molecular weights by the Maillard reaction, and was used to enhance the stability of emulsions loaded with resveratrol. The surface hydrophobicity, thermal stability, and FT-IR spectroscopy of the OVA–DEX conjugates were evaluated. The results showed that the surface hydrophobicity of OVA decreased, while the thermal stability of OVA was significantly improved after DEX covalent modification. The OVA–DEX1k-stabilized emulsion exhibited high encapsulation efficiency of resveratrol, with the value of 89.0%. In addition, OVA–DEX was considerably more effective in droplet stabilization against different environmental stresses (heat, pH, and ionic strength). After 28 days of storage at 25 °C, the OVA-stabilized emulsion showed faster decomposition of resveratrol, whereas the OVA–DEX-conjugate-stabilized emulsion had approximately 73% retention of resveratrol. Moreover, the antioxidant activity of resveratrol-loaded emulsions stabilized by OVA–DEX was higher during storage under different temperatures. These results proved that the OVA–DEX conjugates had the potential to form stable, food-grade emulsion-based delivery systems against environmental stresses, which strongly supports their potential in the field of food and biomedical applications.

Abstract Composite structures consisting of two-dimensional (2D) materials deposited on elastic substrates have a wide range of potential applications in flexible electronics. For such devices, robust 2D film/substrate interfacial adhesion is essential for their reliable performance when subjected to external thermal and mechanical loads. To better understand the strength and failure behavior of the 2D film/substrate interfaces, two types of graphene/polymer samples with distinct interfacial adhesion properties are fabricated and tested by uniaxially stretching the substrates. Depending on the interfacial adhesion, two drastically different debonding rates are observed, i.e., rapid snap-through debonding and more progressive crack propagation. Motivated by the experimental observation, we propose an improved shear-lag model with a trapezoidal-shaped cohesive zone to derive an analytical solution for the decohesion behavior. The theoretical model reveals that the decohesion behavior of the frictional adhesive interface is governed by three dimensionless parameters. Particularly, the dimensionless length of the film essentially determines the decohesion rate; while the other two parameters affect the critical substrate strain to initiate debonding. By fitting the experimental data with the theoretical model, the intrinsic adhesion properties of the two samples are obtained with physically meaningful values. This work offers an analytical solution to describing the decohesion behavior of general thin film/substrate systems with a frictional adhesive interface, which is beneficial for characterizing and optimizing the mechanical properties of various thin film/polymer devices.

Abstract Background Menopausal women are regarded as “abnormal people” in China and are often discriminated against and ostracized, especially in the privacy of their homes. However, research on the stigmatization of menopausal women in China is limited. The aim of this study is to explore and describe the stigmatization experiences of Chinese menopausal women in the family and their feelings about these experiences. Methods A phenomenological qualitative research design involving in-depth semi-structured interviews was selected. Our data analysis adopted Colaizzi's methodology. Results Fourteen menopausal women participated in this study. Four themes and 12 subthemes emerged: (1) violent treatment (verbal and physical violence); (2) lack of attention and companionship (lack of understanding of physical and psychological suffering, neglect of the value of labour and difficulty finding someone to talk to and accompany them); (3) coping struggles (keeping quiet, fighting back, changing inappropriate perceptions and developing a menopausal transition management plan); and (4) despair (deep-rooted perceptions, restrictions on travel and consumption, and unknown "healing" times). Conclusion Our results suggest that Chinese menopausal women suffer physically and mentally within their families. The stigma of menopause is both a symptom of the broad societal lack of knowledge regarding menopause and a reflection of the patriarchal oppression of women in a specific cultural context. Accordingly, this study can help menopausal women and society in general better understand the former’s stigmatization experiences and amplify their inner voices. Moreover, it can serve as a reference for the formulation of menopause-related health policies in China and for advocating and promoting humanistic care for menopausal women.

While urbanization’s strong effect on local precipitation has been widely documented, knowledge of how urbanization affects isotopic composition in precipitation is still lacking. In the present study, deuterium-excess (d-excess) served to quantify the contribution of recycled vapor to precipitation in Chengdu city (China) and a nearby rural area. Precipitation from the urban and rural areas showed no significant difference in δ18O values (p > 0.05). The rural area had significantly higher d-excess (24.29 ± 7.39‰) than the urban (12.71 ± 4.88‰) through the seasons due to higher evapotranspiration flux in the rural area. In summer, however, urban precipitation amount was higher than that of the rural area. Based on d-excess model, the average ratio of recycled vapor was 8.2% in Chengdu, which was lower than in the rural area (36.1%). This highlights the effect of urbanization in decreasing the proportion of vapor from local evapotranspiration contributing to precipitation but blocked much advected moisture. This also implied that precipitation taken in cities were used to represent upwind advected vapor or used as referenced isotopic records for paleoclimate reconstruction based on tree rings or stalagmites sampled in rural area may be erroneous as the effect of urbanization on precipitation vapor. Further studies are needed to explore the effect of urbanization on vapor source of precipitation under different climatic zones.

Plant-derived natural compounds are desired for their anti-inflammatory properties. We investigated the chemical composition and the anti-inflammatory effects of the essential oil obtained from leaves of the Chinese medicinal plant Artemisia annua L. Artemisia annua L. essential oil (AO) was obtained by hydrodistillation; the extraction yield was approximately 1.2%. Gas chromatography–mass spectrometry (GC–MS) revealed the presence of 13 compounds in AO; the major compounds were caryophyllene (32.16%), eucalyptol (28.62%), α-pinene (19.08%), and β-pinene (14.72%). Cell counting kit-8 (CCK8) assay revealed that AO did not show in vitro cytotoxicity toward RAW264.7 cells and suppressed the expression of nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-induced RAW264.7 cells. Pretreatment with AO significantly reduced xylene-induced inflammation in the ears of Kunming mice. AO inhibited inflammatory cell infiltration, decreased epidermis thickness in the ear, and suppressed expression of TNF-α in the serum. The in vivo anti-inflammatory activity of AO was similar to that of the positive control compound Di Song Zhang Bo Cream. Overall, AO was observed to be an effective anti-inflammatory agent. These results provide an experimental basis for commercializing AO-derived external preparations for pharmacological and cosmetic industries.

Rubberized asphalt has excellent environmental protection and road property, but its storage stability needs improvement. Existing studies have found that the compound modification of bone glue (BG) and crumb rubber (CR) can effectively raise the separation of CR in asphalt, along with outstanding comprehensive properties. Therefore, this paper explores the micro mechanism, aging performance, and engineering characteristics of bone glue and crumb rubber compound modified asphalt (BCCMA). First, the adhesion of BCCMA was evaluated by a static drop test, and a scanning electron microscope test revealed its microscopic surface morphology. Second, three aging indices using rheological tests were developed to evaluate the aging resistance ability of the BCCMA. Lastly, the road performance of the bone glue and crumb rubber compound modified asphalt mixture (BCCMAM) was investigated. The results indicate that the surface energy of BCCMA (15% BG and 20% CR) increased by 52.39% compared to the neat asphalt. BG can improve asphalt's aging resistance, and the BCCMA with a BG content of 10% has the lowest aging sensitivity. BG promotes the dispersion uniformity of CR in neat asphalt, making the low-temperature crack resistance, high-temperature stability, and water stability of BCCMAM better than rubberized asphalt mixture.

Sika deer are known to prefer oak leaves, which are rich in tannins and toxic to most mammals; however, the genetic mechanisms underlying their unique ability to adapt to living in the jungle are still unclear. In identifying the mechanism responsible for the tolerance of a highly toxic diet, we have made a major advancement by explaining the genome of sika deer. We generated the first high-quality, chromosome-level genome assembly of sika deer and measured the correlation between tannin intake and RNA expression in 15 tissues through 180 experiments. Comparative genome analyses showed that the UGT and CYP gene families are functionally involved in the adaptation of sika deer to high-tannin food, especially the expansion of the UGT family 2 subfamily B of UGT genes. The first chromosome-level assembly and genetic characterization of the tolerance to a highly toxic diet suggest that the sika deer genome may serve as an essential resource for understanding evolutionary events and tannin adaptation. Our study provides a paradigm of comparative expressive genomics that can be applied to the study of unique biological features in non-model animals.

The oral delivery strategy of natural anti-oxidant and anti-inflammatory agents has attracted great attention to improve the effectiveness of ulcerative colitis (UC) treatment. Herein, we developed a novel orally deliverable nanoparticle, carboxymethyl chitosan (CMC)-modified astaxanthin (AXT)-loaded nanoparticles (CMC-AXT-NPs), for UC treatment. The CMC-AXT-NPs were evaluated by appearance, morphology, particle size, ζ-potential, and encapsulation efficiency (EE). The results showed that CMC-AXT-NPs were nearly spherical in shape with a particle size of 34.5 nm and ζ-potential of −30.8 mV, and the EE of CMC-AXT-NPs was as high as 95.03%. The CMC-AXT-NPs exhibited preferable storage stability over time and well-controlled drug-release properties in simulated intestinal fluid. Additionally, in vitro studies revealed that CMC-AXT-NPs remarkably inhibited cytotoxicity induced by LPS and demonstrated superior antioxidant and anti-inflammatory abilities in Raw264.7 cells. Furthermore, CMC-AXT-NPs effectively alleviated clinical symptoms of colitis induced by dextran sulfate sodium salt (DSS), including maintaining body weight, inhibiting colon shortening, and reducing fecal bleeding. Importantly, CMC-AXT-NPs suppressed the expression of pro-inflammatory cytokines like TNF-α, IL-6, and IL-1β and ameliorated DSS-induced oxidative damage. Our results demonstrated the potential of CMC-modified nanoparticles as an oral delivery system and suggested these novel AXT nanoparticles could be a promising strategy for UC treatment.

Abstract Background Postoperative pulmonary embolism (PE) is a severe complication leading to death and poor prognosis. The present study investigated the risk factors and potential predictors of PE in cancer patients undergoing thoracic and abdominopelvic surgery. Methods A retrospective study was conducted on the patients with cancer who underwent thoracic and abdominopelvic surgery in Sichuan Cancer Hospital from December 2016 to January 2022. A total of 189 patients were included, in which 63 patients diagnosed PE after operation were collected as PE group, and 126 patients matched by age, type of cancer and cancer location were enrolled as control group. Conditional logistic regression was conducted to analyze the association between PE and risk factors. Predictive values of key factors were compared by the area under the curve (AUC) in receiver operating characteristic curve (ROC) curve. Results Conditional multivariate logistic regression showed that BMI (odds ratio [OR] 4.065, 95% confidence interval [CI] 1.138–14.527; p = 0.031), intraoperative hypotension time (OR 4.095, 95% CI 1.367–12.266; p = 0.009), same day fluid balance (OR 0.245, 95% CI 0.061–0.684; p = 0.048), and postoperative D-Dimer (OR 1.693, 95% CI 1.098–2.611; p = 0.017) were significantly related to the occurrence of postoperative PE. Postoperative D-Dimer had the maximal AUC value 0.8014 (95% CI: 0.7260–0.8770) for predicting PE, with a cutoff value of 1.505 μg/ml. Conclusions BMI, intraoperative hypotension time, lower same day fluid balance and postoperative D-dimer are independent risk factors associated with PE in cancer patients undergoing thoracic and abdominopelvic surgery. Postoperative D-Dimer seems to be a good indicator to predict postoperative PE for cancer patients.

Photoluminescent gold clusters have unique chemical and physical properties based on their perturbed electronic structures. Here, the authors report the synthesis of carbon-centered Au(I)-Ag(I) clusters with high phosphorescence quantum yields using N-heterocyclic carbene ligands.

Abstract Objectives To research whether medial PTS, lateral PTS and MTD were different between the PCL injury group and the PCL intact group. Design Retrospective case–control study, level of evidence III. Methods Fifty patients with PCL rupture from 2015 to 2020 in our hospital, and 50 patients matched by age and sex with intact PCL were enrolled in our study. The intraclass correlation coefficient (ICC) was used to assess the reliability of each parameter. The independent t-test was conducted to identify the differences in tibial morphometric characteristics between the PCL-injured and PCL-intact individuals, including the posterior tibial slope (PTS), meniscal slope (MS), medial tibial depth (MTD). A binary logistic regression model was established to evaluate the roles of those anatomic parameters of interest play in PCL injuries. Results The interobserver reliability of each parameter showed excellent agreement. Significant differences in the medial (P = .023) and lateral (P = .009) PTS were found between the PCL-injured group (3.68 ± 2.70 and 4.55 ± 3.19, respectively) and the controls (5.00 ± 2.73 and 6.39 ± 3.29, respectively). And the MTD was 1.98 ± 0.64 mm in the PCL-injured group and 2.37 ± 0.55 mm in the control group (P = 0.007). Binary logistic regression analysis showed that smaller lateral PTS and MTD were directly associated with PCL injury, with an OR of 1.17 and OR of 3.14, respectively. The medial PTS was independent to PCL injures. Conclusion Decreased lateral PTS and MTD were underlying anatomic risk factors for PCL injury.

Thrombotic events are the most frequent manifestations of essential thrombocythemia (ET). The objective of this study is to determine the incidence of thrombosis at different sites on follow-up in patients with ET. We searched PubMed, Web of Science, and The Cochrane Library databases and calculated the incidence of thrombosis by pooling and analyzing the extracted data using a random-effects model. A total of 70 studies (N = 25,805) were included in the analysis. The total and annual incidences of arterial thrombosis on follow-up were 13.4% and 2.0%, respectively. The total and annual incidences of the different manifestations of arterial thrombosis were as follows: stroke (5.3% and 0.8%), transient ischemic attack (5.1% and 1.2%), myocardial infarction (2.4% and 0.5%), unstable angina (0.9% and 0.2%), and peripheral arterial thrombosis (2.0% and 0.2%), respectively. In contrast, the total and annual incidences of arterial thrombosis in JAK2-positive patients were 18.4% and 2.7%, respectively. The total and annual incidences of arterial thrombosis in JAK2-negative patients were 5.9% and 0.8%, respectively. The total and annual incidences of venous thrombosis were 5.5% and 0.7%, respectively, and the incidences of the different manifestations of venous thrombosis at different sites were as follows: peripheral venous thrombosis (2.9% and 0.5%), superficial venous thrombosis (1.8% and 0.7%), deep venous thrombosis (1.6% and 0.3%), abdominal venous thrombosis (0.8% and 0.1%), pulmonary embolism (0.3% and 0.1%), and cerebral venous thrombosis (0.2% and 0%), respectively. The total and annual incidences of venous thrombosis in JAK2-positive patients were 7.4% and 1.2%, respectively. The total and annual incidences of venous thrombosis in JAK2-negative patients were 1.6% and 0.4%, respectively. The incidence of arterial thrombosis was higher than that of venous thrombosis in patients with ET. Arterial thrombosis manifested with cerebral arterial thrombosis, followed by cardiac thrombosis. Venous thrombosis events were mainly peripheral and superficial venous thrombosis. JAK2-positive patients have a higher incidence of arterial and venous thromboses than JAK2-negative patients, the sequence of thrombsis sites was similar to that of the overall patients.

Abstract The interfacial shear coupling (ISC) governs the relative in-plane deformations of layered two-dimensional (2D) van der Waals (vdW) materials, which is significant for both the fundamental theory of solid mechanics and the stability design of 2D devices. Here we study the representative ISC of 2D vdW stacks using bilayer graphene (BLG) and isotope-labeled Raman spectroscopy. The results show that under uniaxial tensile strain, the ISC between two graphene layers evolves sequentially with bonding, sliding and debonding process, and the corresponding interfacial shear strength is inversely proportional to the sample size. Molecular dynamics (MD) simulations demonstrate the origin of this inverse proportionality as stronger interlayer vdW interaction induced by the edge lattices and atoms of BLG that have more degrees of freedom. These results not only provide new fundamental insights into the multiscale interpretation of macroscopic interfacial shear properties of 2D vdW stacks but also have great potential in guiding the design of graphene-based composite materials and flexible 2D electronics.

In recent years, various methods for detecting exogenous and endogenous hypochlorite have been studied, considering its essential role as a biomolecule. However, the existing technologies still pose obstacles such as their invasiveness, high costs, and complicated operation. In the current study, we developed a glow-type chemiluminescent probe, hypochlorite chemiluminescence probe (HCCL)-1, based on the scaffold of Schaap's 1,2-dioxetane luminophores. To better explore the physiological and pathological functions of hypochlorite, we modified the luminophore scaffold of HCCL-1 to develop several probes, including HCCL-2, HCCL-3, and HCCL-4, which amplify the response signal of hypochlorite. By comparing the luminescent intensities of the four probes using the IVIS® system, we determined that HCCL-2 with a limit of detection of 0.166 μM has enhanced sensitivity and selectivity for tracking hypochlorite both in vitro and in vivo.

Abstract Background Trans-cinnamaldehyde (TCA) is one of the main pharmaceutical ingredients of Cinnamomum cassia Presl, which has been shown to have therapeutic effects on a variety of cardiovascular diseases. This study was carried out to characterize and reveal the underlying mechanisms of the protective effects of TCA against cardiac hypertrophy. Methods We used phenylephrine (PE) to induce cardiac hypertrophy and treated with TCA in vivo and in vitro. In neonatal rat cardiomyocytes (NRCMs), RNA sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were carried out to identify potential pathways of TCA. Then, the phosphorylation and nuclear localization of calcium/calmodulin-dependent protein kinase II (CaMKII) and extracellular signal-related kinase (ERK) were detected. In adult mouse cardiomyocytes (AMCMs), calcium transients, calcium sparks, sarcomere shortening and the phosphorylation of several key proteins for calcium handling were evaluated. For mouse in vivo experiments, cardiac hypertrophy was evaluated by assessing morphological changes, echocardiographic parameters, and the expression of hypertrophic genes and proteins. Results TCA suppressed PE-induced cardiac hypertrophy and the phosphorylation and nuclear localization of CaMKII and ERK in NRCMs. Our data also demonstrate that TCA blocked the hyperphosphorylation of ryanodine receptor type 2 (RyR2) and phospholamban (PLN) and restored Ca2+ handling and sarcomere shortening in AMCMs. Moreover, our data revealed that TCA alleviated PE-induced cardiac hypertrophy in adult mice and downregulated the phosphorylation of CaMKII and ERK. Conclusion TCA has a protective effect against PE-induced cardiac hypertrophy that may be associated with the inhibition of the CaMKII/ERK pathway.

Objectives. Bronchopleural fistula (BPF) is a serious and life-threatening complication. Following the advent of interventional radiology, subsequent treatment methods for BPF have gradually diversified. Therefore, this article provides an overview of the present scenario of interventional treatment and research advancements pertaining to BPF. Methods. Relevant published studies on the interventional treatment of BPF were identified from the PubMed, Sci-Hub, Google Scholar, CNKI, VIP, and Wanfang databases. The included studies better reflect the current status of and progress in interventional treatments for BPF with representativeness, reliability, and timeliness. Studies with similar and repetitive conclusions were excluded. Results. There are many different interventional treatments for BPF that can be applied in cases of BPF with different fistula diameters. Conclusion. The application of interventional procedures for bronchopleural fistula has proven to be safe, efficacious, and minimally invasive. However, the establishment of comprehensive, standardized treatment guidelines necessitates further pertinent research to attain consensus within the medical community. The evolution of novel technologies, tools, techniques, and materials specifically tailored to the interventional management of bronchopleural fistula is anticipated to be the focal point of forthcoming investigations. These advancements present promising prospects for seamless translation into clinical practice and application, thereby potentially revolutionizing patient care in this field.

Valley, as a new degree of freedom for electrons, has drawn considerable attention due to its significant potential for encoding and storing information. Lifting the energy degeneracy to achieve valley polarization is necessary for realizing valleytronic devices. Here, on the basis of first-principles calculations, we show that single-layer FeCl2 exhibits a large spontaneous valley polarization (∼101 meV) arising from the broken time-reversal symmetry and spin-orbital coupling, which can be continuously tuned by varying the direction of magnetic crystalline. By employing the perturbation theory, the underlying physical mechanism is unveiled. Moreover, the coupling between valley degree of freedom and ferromagnetic order could generate a spin- and valley-polarized anomalous Hall current in the presence of the in-plane electric field, facilitating its experimental exploration and practical applications.

Our previous studies revealed the protection of stachydrine hydrochloride (STA) against cardiopathological remodeling. One of the underlying mechanisms involves the calcium/calmodulin-dependent protein kinase Ⅱ (CaMKII). However, the way STA influences CaMKII needs to be further investigated. The nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2)-coupled reactive oxygen species (ROS) overproduction putatively induces the oxidative activation of CaMKII, resulting in the occurrence of pathological cardiac remodeling and dysfunction in experimental models of mice. Thus, in this study, we assessed the role of the NOX2-ROS signal axis in STA cardioprotection. The transverse aortic constriction (TAC)-induced heart failure model of mice, the phenylephrine-induced hypertrophic model of neonatal rat primary cardiomyocytes, and the H2O2-induced oxidative stress models of adult mouse primary cardiomyocytes and H9c2 cells were employed. The echocardiography and histological staining were applied to assess the cardiac effect of STA (6 mg/kg/d or 12 mg/kg/d), which was given by gavage. NOX2, ROS, and excitation-contraction (EC) coupling were detected by Western blotting, immunofluorescence, and calcium transient-contraction synchronous recordings. ROS and ROS-dependent cardiac fibrosis were alleviated in STA-treated TAC mice, demonstrating improved left ventricular ejection fraction and hypertrophy. In the heart failure model of mice and the hypertrophic model of cardiomyocytes, STA depressed NOX2 protein expression and activation, as shown by inhibited translocation of its phosphorylation, p67phox and p47phox, from the cytoplasm to the cell membrane. Furthermore, in cardiomyocytes under oxidative stress, STA suppressed NOX2-related cytosolic Ca2+ overload, enhanced cell contractility, and decreased Ca2+-dependent regulatory protein expression, including CaMKⅡ and Ryanodine receptor calcium release channels. Cardioprotection of STA against pressure overload-induced pathological cardiac remodeling correlates with the NOX2-coupled ROS signaling cascade.

Quantitative detection of veterinary drug residues in animal-derived food is of great significance. In this work, a simple and label-free electrochemical aptasensor for the highly sensitive detection of chloramphenicol (CAP) in milk was successfully developed based on a new biosensing method, where the single- or few-layer Ti3C2 MXene nanosheets functionalized via the specific aptamer by self-assembly were used as electrode modifiers for a glassy carbon electrode (aptamer/Ti3C2 MXene/GCE). Differential pulse voltammetry (DPV), electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), scanning electron microscopy (SEM), atomic force microscope (AFM), and so on were utilized for electrochemical and morphological characterization. Under the optimized conditions, the constructed aptasensor exhibited excellent performance with a wider linearity to CAP in the range from 10 fM to 1 μM and a low detection limit of 1 fM. Aptamer/Ti3C2 MXene/GCE demonstrated remarkable selectivity over other potentially interfering antibiotics, as well as exceptional reproducibility and stability. In addition, the aptasensor was successfully applied to determine CAP in milk with acceptable recovery values of 96.13% to 108.15% and relative standard deviations below 9%. Therefore, the proposed electrochemical aptasensor is an excellent alternative for determining CAP in food samples.

Anodes equipped with limited lithium offer a way to deal with the increasing market requirement for high-energy-density rechargeable batteries and inadequate global lithium reserves. Anode-free lithium-ion batteries (AFLBs) with zero excess metal could provide high gravimetric energy density and high volumetric energy density. Moreover, the elimination of lithium with a bare current collector on the anode side can reduce metal consumption, simplify the cell technological procedure, and improve manufacturing safety. However, some great challenges, such as insufficient cycling stability, significant lithium dendrite growth, as well as unstable solid electrolyte interface, impede the commercial application of AFLBs. Fortunately, significant progress has been made for AFLBs with enhanced electrode stability and improved cycling performance. This review highlights research on the design of anode-free lithium-ion batteries over the past two decades, presents an overview of the main advantages and limitations of these designs, and provides improvement strategies including the modification of the current collectors, improvement of the liquid electrolytes, and optimization of the cycling protocols. Prospects are also given to broaden the understanding of the electrochemical process, and it is expected that the further development of these designs can be accelerated in both scientific research and practical applications.

Background: Iron deficiency anemia (IDA) is a public health problem worldwide. Shengxuening Tablet (SXN) has been used for the treatment of various types of anemia, attaining high efficacy.Objective: To evaluate the safety of SXN as well as its preventive and therapeutic efficacy against IDA across different population groups.Methods: PubMed, Embase, Web of Science, the Cochrane Library, the China Knowledge Network, the China Biomedical Literature Database, the Wanfang Data Knowledge Service Platform, and the China Science and Technology Journal Database was searched for relevant clinical trials through June 2022 and a systematic review and meta-analysis of the identified studies was undertaken.Results: A total of 39 trials involving 4,562 cases were included in the meta-analysis. The total efficiency of SXN was superior than the control group in improving red blood cell (RBC) count [SMD = 1.31, 95% CI (0.7, 1.91), p < 0.0001], hemoglobin (Hb) [SMD = 1.11, 95% CI (0.75, 1.46), p < 0.00001], mean corpuscular volume (MCV) [SMD = 0.5, 95% CI (0.33, 0.68), p < 0.00001], total serum iron (SI) levels [SMD = 1.87, 95% CI (1.3, 2.44), p < 0.00001], and transferrin saturation (TSAT) levels [SMD = 2.07, 95% CI (1.86, 2.27), p < 0.00001]. Besides, the total effects of SXN to improve mean corpuscular hemoglobin (MCH) [SMD = 0.12, 95% CI (−0.16, 0.4), p = 0.41], mean corpuscular hemoglobin concentration (MCHC) [SMD = 0.03, 95% CI (−0.18, 0.24), p = 0.77], hematocrit (HCT) [SMD = 0.65, 95% CI (−0.25, 1.55), p = 0.16], and serum ferritin (SF) levels [SMD = 0.59, 95% CI (−0.67, 1.85), p = 0.36] and reduce the total iron binding capacity (TIBC) [SMD = 0.34, 95% CI (−0.07, 0.74), p = 0.1] was comparable to that of iron supplementation. SXN significantly raised the total effective rates of IDA [risk ratio (RR) = 1.06, 95% CI (1.02, 1.09), p = 0.0005] and was associated with fewer adverse events [RR = 0.24, 95% CI (0.18, 0.31), p < 0.00001], fewer adverse pregnancy outcomes [RR = 0.34, 95% CI (0.2, 0.57), p < 0.0001], and lower anemia recurrence rates during pregnancy [RR = 0.29, 95% CI (0.1, 0.84), p = 0.02]. Regarding prevention, the effects of SXN to maintain the RBC count, Hb level and other IDA-related parameters were comparable to that of control group and SXN reduced the risk of IDA incidence during pregnancy.Conclusion: SXN demonstrated promising efficacy in the treatment and prevention of IDA and outperformed routine iron formulations in terms of safety, thus rendering SXN a reliable treatment option for IDA.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier: CRD42022353247.

Abstract Background A functionally deficient anterior cruciate ligament (ACL) is considered one of the contraindications in unicompartmental knee arthroplasty (UKA). But there is still a lack of standardized and reproducible methods to assess ACL functional integrity in patients with advanced anteromedial osteoarthritis of the knee (AMOA). This study explores the value of passive anterior tibial subluxation (PATS) on axial MRI in evaluating ACL status in this population. Methods Patients who met UKA indications between November 2017 and September 2020 were included and grouped into “intact” (ACLI) or “deficient” (ACLD) group according to their ACL status during surgery. All participants underwent MRI with a standardized protocol. The measurements of medial and lateral PATS were conducted on axial MRI, and the mean of them was calculated as global PATS. Then the reliability and diagnostic ability of PATS were determined. Results A total of 85 patients (45 for ACLI group, 40 for ACLD group) were included after selection. The measurements of PATS showed excellent intra- and inter-observer reliabilities (with an intraclass correlation coefficient of at least 0.986). The global PATS of the ACLI group was significantly lower than that of the ACLD group (− 2.30 ± 1.96 vs. 1.03 ± 1.96 mm, P

Abstract Lateral superlattices in 2D materials provide a powerful platform for exploring intriguing quantum phenomena, which can be realized through the proximity coupling in forming moiré pattern with another layer. This approach, however, is invasive, material-specific, and requires small lattice mismatch and suitable band alignment, largely limited to graphene and transition metal dichalcogenides (TMDs). Hexagonal boron nitride (h-BN) of antiparallel (AA′) stacking has been an indispensable building block, as dielectric substrates and capping layers for realizing high-quality van der Waals devices. There is also emerging interest on parallelly aligned h-BN of Bernal (AB) stacking, where the broken inversion and mirror symmetries lead to out-of-plane electrical polarization. Here we show the that laterally patterned electrical polarization at a nearly parallel interface within the h-BN substrate can be exploited to create noninvasively a universal superlattice potential in general 2D materials. The feasibility is demonstrated by first principle calculations for monolayer MoSe2, black phosphorus, and antiferromagnetic MnPSe3 on such h-BN. The potential strength can reach 200 meV, customizable in this range through choice of distance of target material from the interface in h-BN. We also find sizable out-of-plane electric field at the h-BN surface, which can realize superlattice potential for interlayer excitons in TMD bilayers as well as dipolar molecules. The idea is further generalized to AB-stacked h-BN subject to torsion with adjacent layers all twisted with an angle, which allows the potential and field strength to be scaled up with film thickness, saturating to a quasi-periodic one with chiral structure.

BackgroundThe contribution of hepatitis B virus (HBV) and hepatitis C virus (HCV) to primary liver cancer (PLC) and their association with cancer aggressiveness remains uncertain in China, a country with half of global PLC. We aimed to characterize this using data from four representative medical centers.MethodsIn total, 15,801 PLC patients were enrolled from the centers distributed in Easter5n, Southern, Northern, and Western China from 2003 to 2020. Of those, 7585 with curative surgery were involved in survival analysis. A nomogram was constructed using preoperative parameters to predict postoperative survival.ResultsHepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma accounted for 93.0%, 4.3%, and 1.6% in PLC, respectively. The seropositivities of HBV and HCV were 84.4% and 3.2% in HCC, respectively. The seropositivity of anti-HCV antibody was significantly higher in HBV-negative than in HBV-positive HCC patients (13.2% vs. 1.1%). Compared to HCV-positive HCC (HCV-HCC), HBV-positive HCC (HBV-HCC) was associated with 12-year earlier onset, higher proportions of males, high α-fetoprotein, large tumor size, advanced Barcelona Clinic Liver Cancer (BCLC) stage, and vascular tumor thrombus. The proportions of HCC and HBV seropositivity increased, whereas that of anti-HCV decreased, from 2003 to 2020. Postoperative five-year survival rate was 73.5%, 64.1%, 34.9%, and 19.7% in HCC at BCLC stage 0, A, B, and C, respectively. The multivariate Cox regression analysis showed that HBV seropositivity, incomplete tumor capsule, vascular tumor thrombus, tumor diameter (≥3 cm), advanced BCLC stage (B+C), α-fetoprotein (≥20ng/ml), and direct bilirubin (>8µmol/L) contributed independently to shorter overall survival (OS); whereas post-operative radiofrequency ablation and second resection independently improved OS in HCC. HCV-HCC had a more favorable prognosis than did HBV-HCC (Log-rank test, P

Ultra-high-pressure jet processing (UHPJ) is a new non-thermal processing technique that can be employed for the homogenization and the sterilization of dairy products. However, the effects on dairy products are unknown when using UHPJ for homogenization and sterilization. Thus, this study aimed to investigate the effects of UHPJ on the sensory and curdling properties of skimmed milk and the casein structure in skimmed milk. Skimmed bovine milk was treated with UHPJ using different pressures (100, 150, 200, 250, 300 MPa) and casein was extracted by isoelectric precipitation. Subsequently, the average particle size, Zeta potential, contents of free sulfhydryl and disulfide bonds, secondary structure, and surface micromorphology were all used as evaluation indicators to explore the effects of UHPJ on the structure of casein. The results showed that with an increase of pressure, the free sulfhydryl group content changed irregularly, while the disulfide bond content increased from 1.085 to 3.0944 μmol/g. The content of α-helix and random coil in the casein decreased, while the β-sheet content increased at 100, 150, 200 MPa pressure. However, treatment with higher pressures of 250 and 300 MPa had the opposite effect. The average particle size of the casein micelles first decreased to 167.47 nm and then increased up to 174.63 nm; the absolute value of Zeta potential decreased from 28.33 to 23.77 mV. Scanning electron microscopy analysis revealed that the casein micelles had fractured into flat, loose, porous structures under pressure instead of into large clusters. After being ultra-high-pressure jet-processed, the sensory properties of skimmed milk and its fermented curd were analyzed concurrently. The results demonstrated that UHPJ could alter the viscosity and color of skimmed milk, shortening curdling time from 4.5 h to 2.67 h, and that the texture of the curd fermented with this skimmed milk could be improved to varying degrees by changing the structure of casein. Thus, UHPJ has a promising application in the manufacture of fermented milk due to its ability to enhance the curdling efficiency of skimmed milk and improve the texture of fermented milk.

Abnormal platelet activation can lead to thrombosis in essential thrombocythemia (ET) and thus impact patient prognosis. Platelet activation-associated proteins are key molecules for platelet activation. However, it is unclear which proteins are most closely associated with the disease’s prognosis. To determine which platelet activation-related proteins can be employed as ET patient prognosis predictors, we used label-free quantification (LFQ) and parallel reaction monitoring (PRM) technology and first determined the serum proteomic expression levels and the differential proteins of ET patients. Then, based on the IPSET (International Prognostic Score for ET), the differential protein associated with the prognostic score was found. To investigate potential processes affecting prognosis, the connection of this protein with prognostic markers, such as thrombotic history, age, white blood cell count, coagulation factors, and inflammatory factors, were further examined. The levels of platelet activation-related proteins GPIbα, SELP, PF4, MMP1, and FLNA were significantly higher in ET patients, according to LFQ and PRM analyses (p < 0.01). Based on regression analysis of the IPSET prognostic score, it is suggested that the SELP level was positively correlated with the prognostic score and prognostic risk factor analysis (p < 0.05). Further regression analysis of SELP with coagulation factors showed that antithrombin (AT-III) was negatively correlated with SELP levels (p < 0.05). Further regression analysis of the inflammatory factors with AT-III and SELP revealed that IL-10, IL-12P70, and IL-31 were negatively correlated with AT-III and SELP (p < 0.01). Platelet activation pathway-related proteins are expressed more frequently in ET patients, and serum SELP may be a prognostic marker for these individuals by encouraging leukocyte increase and inflammatory factor expression and causing aberrant coagulation.

Objective: The aim of this review was to identify the possible mechanisms behind cupping therapy by employing an evidence-based approach, and to explore its possible regional and systemic effects in the human body. Methods: We searched six electronic databases and four online trial registries for articles published up to January 1, 2020. Clinical studies on the mechanisms of retained cupping, flashing cupping, moving cupping, and vacuum cupping were considered for this review. The methodological qualities of controlled studies were assessed using the National Institute for Clinical Excellence methodology checklist, the Newcastle-Ottawa Scale, and the Cochrane risk of bias tool. Characteristic statistical description and qualitative summary of results were used for data analysis. Results: Thirty-eight studies (37 full texts and one abstract) were included in this study. Due to the clinical heterogeneity among the studies, we could not conduct a meta-analysis. The results showed that the key factors that contribute to the efficacy of cupping therapy are negative pressure and temperature. Cupping therapy mainly causes local and systemic changes in hemodynamics, immune regulation, metabolism, and pain relief. Conclusion: We identified negative pressure as the key element behind cupping therapy. Cupping therapy may cause redistribution of oxygen at the cupping site and in neighboring tissues, thereby inducing a therapeutic effect by increasing regional blood flow. It may also induce metabolic change, immunomodulation, and neuromodulation. However, additional rigorous clinical research needs to be conducted to further clarify the mechanism behind cupping therapy.

BackgroundPrevious studies have revealed ethnic disparities in the prevalence of metabolic syndrome (MetS); however, the literature regarding aging-related patterns of disparities in MetS and its components remains limited.MethodsThis cross-sectional study recruited 28,049 subjects, consisting of one Chinese race and three American races, 18–85 years of age, from the National Health and Nutrition Examination Survey (NHANES, 1999–2018) of the United States, and the Guangdong Gut Microbiome Project (GGMP, 2018) of China. MetS was defined in accordance with the National Cholesterol Education Program Adult Treatment Panel III. A modified sliding-window-based algorithm was used to depict the trajectories of the prevalence of MetS with increased age. Logistic regression analysis was performed to investigate associations between MetS and its components.ResultsThe prevalence of MetS increased non-linearly with age, with growth speed reaching its maximum at approximately 40–50 years. Chinese subjects exhibited a lower prevalence of MetS than non-Hispanic whites, non-Hispanic blacks, and Mexican Americans in all age groups. The two most prevalent components in Chinese subjects were reduced high-density lipoprotein cholesterol levels (42.0%) and elevated blood pressure (49.5%), and elevated triglyceride levels (36.3–49.5%) and abdominal obesity (55.8–55.9%) in Americans. Before 40 years of age, the top two MetS-associated components were abdominal obesity and elevated triglyceride levels in all races, while after 40 years, the prominent associations between MetS and its components varied among the different races and age groups.ConclusionsAlthough racial disparities in the epidemic of MetS varied with increased age, abdominal obesity and elevated triglyceride levels were the top two MetS-associated components in all younger adults of different races.

Background: Cardiovascular diseases have become a major public health problem that seriously threatens human health. The cumulative effects of various cardiovascular events will eventually develop into chronic heart insufficiency and even heart failure, and the β1 adrenergic receptor signal pathway plays an important role in this process. Stachytine hydrochloride is the main active ingredient of Yimucao, which is a traditional Chinese medicine used to treat gynecological diseases. Modern studies have found that stachytine hydrochloride has a good cardioprotective effect, but it is still unclear whether stachytine hydrochloride has an effect on the β1 adrenergic receptor signal pathway. The purpose of this study is to explore the effect of stachytine hydrochloride on the β1 adrenergic receptor signal pathway.Method: In this study, a continuous infusion of isoproterenol (40 mg/kg/day) was administered to mice and ventricular myocytes explored the potential mechanism of stachytine hydrochloride (12 mg/kg/day) on the β1 adrenergic receptor signal pathway in the heart. Evaluate changes in cardiac morphology and function by echocardiography, cardiac hemodynamics, and histological methods, and detect molecular changes by Western blot and immunofluorescence. Treat primary cultured adult mouse or neonatal rat ventricular myocytes with or without isoproterenol (0.1 μMol), PNGase F (10–2 units/ml), and stachytine hydrochloride (10 μMol) at different time points. Detect α-1,6-fucosylation on N-glycosylation, calcium transient, contraction, and relaxation function and related signals.Results: Stachytine hydrochloride reduces cardiac remodeling and modulates hemodynamic parameters during chronic β1 adrenergic receptor activation in vivo. The N-glycosylation of β1 adrenergic receptors decreased after continuous isoproterenol stimulation, while stachytine hydrochloride can increase the N-glycosylation of β1AR in the heart of mice with isoproterenol-induced heart failure. Decreased N-glycosylation of β1 adrenergic receptors will downregulate the cAMP/PKA signal pathway and inhibit myocardial excitation and contraction coupling. Stachytine hydrochloride significantly reduced isoproterenol-induced cardiac N-linked glycoproteins with α-1,6-fucosylation.Conclusion: Our results show that stachytine hydrochloride inhibits the synthesis of α-1,6-fucosylation on the N-terminal sugar chain by reducing α-1,6-fucosyltransferase (FUT8) and α-1,3-mannosyl-glycoprotein 4-β-N-acetylglucosaminyltransferase A (MGAT4a), upregulating the N-glycosylation level on β1 adrenergic receptors, and maintaining cAMP/PKA signal pathway activation.

Abstract Background Radix Paeoniae Alba (RPA) and other natural medicines have remarkable curative effects and are widely used in traditional Chinese Medicine (TCM). However, due to their multi-component and multi-target characteristics, it is difficult to study the detailed pharmacological mechanisms for those natural medicines in vivo. Therefore, their real effects on organisms is still uncertain. Methods RPA was selected as research object, the present study was designed to study the complex mechanisms of RPA in vivo by integrating and interpreting the transcriptomic based RNA-seq and metabolomic based NMR spectrum after RPA administration in mice. A variety of dimension-reduction algorithms and classifier models were applied to the processing of high-throughput data. Results Among serum metabolites, the contents of PC and glucose were significantly increased, while the contents of various amino acids, lipids and their metabolites were significantly decreased in mice after RPA administration. Based on the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, differential analysis showed that the liver was the site where RPA exerted a significant effect, which confirmed the rationality of “meridian tropism” in the theory in TCM. In addition, RPA played a role in lipid metabolism by regulating genes encoding enzymes of the glycerolipid metabolism pathway, such as 1-acyl-sn-glycerol-3-phosphate acyltransferase (Agpat), phosphatidate phosphatase (Lpin), phospholipid phosphatase (Plpp) and endothelial lipase (Lipg). We also found that RPA regulates several substance addiction pathways in the brain, such as the cocaine addiction pathway, and the related targets were predicted based on the sequencing data from pathological model in the GEO database. The overall effective pattern of RPA was intuitively presented with a multidimensional radar map through a self-designed model which found that liver and brain were mainly regulated by RPA compared with the traditional meridian tropism theory. Conclusions Overall this study expanded the potential application of RPA and provided possible targets and directions for further mechanism study, meanwhile, it also established a multi-dimensional evaluation model to represent the overall effective pattern of TCM for the first time. In the future, such study based on the high-throughput data sets can be used to interpret the theory of TCM and to provide a valuable research model and clinical medication reference for the TCM researchers and doctors.

How epigenetics coordinate with genetics to impact protein fitness is unknown. Here, using a Variation Spatial Profiling strategy and machine learning, the authors map HDAC impact on a full set of Niemann pick C1 disease variants to quantitate an unanticipated plasticity in central dogma.