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Physical properties, such as electrochemical and electromagnetic properties, of two-dimensional MXenes can be improved by enhancing their stability. However, MXenes fabricated via acid etching contain defects, which affect their physical properties. In this study, a method to effectively remove Al residues using only water during MXene fabrication while maintaining structural stability is proposed. The fabrication and intercalation of MXenes are controlled via epitaxial self-intercalation of H2O-etched Cr2(AlLi)C. On the basis of this mechanism, the room-temperature ferromagnetism of two-dimensional few-layered Cr2CTx MXenes, which has a specific saturation magnetization of ~0.26 emu/g and a Curie temperature of > 353 K, is experimentally verified. The calculated electronic band structure implies that the semimetal Cr2CTx MXene has a band gap of 0.75 eV. This study opens new possibilities for the research and applications of industrial-scale manufacturing of MXenes and 2D semiconductors.

Abstract Background Emerging evidence suggested the association between gut dysbiosis and Alzheimer’s disease (AD) progression. However, it remained unclear how the gut microbiome and neuroinflammation in the brain mutually interact or how these interactions affect brain functioning and cognition. Here we hypothesized that “gut-brain” axis mediated by microbial derived metabolites was expected to novel breakthroughs in the fields of AD research and development. Methods Multiple technologies, such as immunofluorescence, 16s rDNA sequencing, mass spectrometry-based metabolomics (LC-QQQ-MS and GC-MS), were used to reveal potential link between gut microbiota and the metabolism and cognition of the host. Results Microbial depletion induced by the antibiotics mix (ABX) verified that “gut-brain” can transmit information bidirectionally. Short-chain fatty acid-producing (SCFAs-producing) bacteria and amino acid-producing bacteria fluctuated greatly in 5×FAD mice, especially the reduction sharply of the Bifidobacteriaceae and the increase of the Lachnospiraceae family. Concentrations of several Tryptophan-kynurenine intermediates, lactic acid, CD4+ cell, and CD8+ cells were higher in serum of 5×FAD mice, whilst TCA cycle intermediates and Th1/Th2 were lower. In addition, the levels of iso-butyric acid (IBA) in feces, serum, and brain of 5×FAD mice were increased compared with WT-M mice, especially in serum. And IBA in the brain was positively correlated with Aβ and proinflammatory factors. Conclusion Together, our finding highlighted that the alternation in gut microbiota affected the effective communication between the “gut-brain” axis in 5×FAD mice by regulating the immune system, carbohydrate, and energy metabolism.

The Pacific white shrimp or white leg shrimp, Penaeus vannamei, is native to the tropical coastal regions of Central and South America. It is one of the three major shrimp species with high production worldwide. It was brought from Hawaii, USA, in 1988 and introduced into China. It has been widely promoted and cultivated due to its adaptability to the environment, fast growth rate, and suitability for high-density industrial farming. As of 2022, China's total production of P. vannamei reached 2.09 million tons, accounting for > 90% of the country's total shrimp farming production. It has become one of the pillar industries in China's aquaculture sector.With the continuous expansion of aquaculture, diseases are becoming increasingly severe. Among them, acute hepatopancreatic necrosis disease (AHPND) hinders the development of the global shrimp farming industry and causes catastrophic economic losses. After infection, most shrimp show hepatopancreatic enlargement, which appears pale white or light yellow. In the later stages of infection, some diseased shrimp may exhibit atrophy of the hepatopancreas, appearing reddish-brown and blackened, with a hardened texture. Within 20–30 d after infection, death can occur, with a mortality rate of up to 90%. As of 2021, the economic losses caused by this disease to the major P. vannamei farming areas (China, Malaysia, Thailand, Vietnam, and Mexico) have exceeded 43 billion US dollars. Cultivating novel P. vannamei germplasm with AHPND resistance is an effective way to solve AHPND.Recently, domestic researchers have established independent shrimp breeding systems and cultivated 12 novel P. vannamei strains, such as "Hai Xing Nong No.2", "Ren Hai No.1", and "Zheng Jin Yang No.1". These varieties mainly target traits such as growth, resistance to white spot syndrome virus, farming survival rate, and temperature, salinity, and ammonia nitrogen tolerance. However, no reports of novel varieties specifically targeting AHPND resistance are available. Growth traits are essential economic traits in the genetic breeding of aquatic animals. Among the 12 novel P. vannamei varieties in China, 11 have excellent traits related to growth. Evaluating the genetic relationship between growth and AHPND resistance in the core breeding population of P. vannamei is important for fully utilizing existing high-quality germplasm and breeding novel varieties with composite traits and AHPND resistance.Genetic parameters reflect the genetic variation of target traits in a breeding population and are important references for breeding decisions. Due to the complex genetic background of existing P. vannamei germplasm resources in China, genetic parameters are influenced considerably by the tested population, infection methods, and other factors. Before breeding, stable infection tests must be conducted on the base population and obtain accurate parameters.This study used two independently bred P. vannamei strains as research objects to test their growth and AHPND resistance. Among them, 40 families were selected for high resistance (20 individuals per family, total 800 experimental individuals), and 30 families were selected for fast growth (32 individuals per family, total 960 experimental individuals). The test was conducted at P70–P90 by feeding with VpAHPND quantitative oral infection. Feeding with toxic bait was stopped after 50% of the experimental individuals died. The genetic heritability and correlation of the weight, individual survival time after VpAHPND infection, and half-lethal survival rate of the two strains were evaluated using individual animal and male and female threshold models. The results showed that the weight heritability estimate of the highly resistant strain was 0.599±0.120, indicating a high level of genetic heritability. The heritability estimates of survival time and half-lethal survival rate were 0.240±0.072 and 0.173±0.051, respectively, indicating a moderate to low level of genetic heritability, and all significantly different from 0 (P < 0.01). The weight heritability estimate of the fast-growth strain was 0.266±0.082, indicating a low level of genetic heritability. The heritability estimates of survival time and half-lethal survival rate were 0.374± 0.096 and 0.257±0.048, respectively, indicating a moderate level of genetic heritability, and all significantly different from 0 (P < 0.01). The genetic correlation between weight and AHPND resistance traits (survival time and half-lethal survival rate) in both strains showed a low positive correlation (0.061–0.235), and no significant difference was observed from 0 (P > 0.05). The genetic correlation between survival time and half-lethal survival rate in both strains was highly positively correlated, with estimates of 0.997±0.129 and 0.967±0.044, respectively. The results indicate that growth and AHPND resistance can be included as selection indicators in the comprehensive selection index for breeding and seed production in the actual breeding process. Under limited conditions, the infection program can be simplified, and the half-lethal survival rate can be used as the AHPND resistance indicator for the breeding population. This study provides a primary reference for utilizing existing germplasm resources to develop high-quality P. vannamei strains for growth and AHPND resistance breeding.

Timely and effective blood resuscitation is very important for patients with severe blood loss. The resuscitation fluids for hemorrhagic shock have evolved from whole blood to crystalloid/colloid solutions, crystalloid combined with red blood cells, to balanced blood components. In the past 20 years, it is a growing trend that low titer antibody group O whole blood (LTOWB) is used as the preferred universal bridging resuscitation fluid for emergent blood resuscitation. Herein we provide a review of the history and current status of whole blood for patients with severe bleeding and make a suggestion to launch a national implementation research program of LTOWB in China.

Abstract In the railway system, fasteners have the functions of damping, maintaining the track distance, and adjusting the track level. Therefore, routine maintenance and inspection of fasteners are important to ensure the safe operation of track lines. Currently, assessment methods for fastener tightness include manual observation, acoustic wave detection, and image detection. There are limitations such as low accuracy and efficiency, easy interference and misjudgment, and a lack of accurate, stable, and fast detection methods. Aiming at the small deformation characteristics and large elastic change of fasteners from full loosening to full tightening, this study proposes high-precision surface-structured light technology for fastener detection and fastener deformation feature extraction based on the center-line projection distance and a fastener tightness regression method based on neural networks. First, the method uses a 3D camera to obtain a fastener point cloud and then segments the elastic rod area based on the iterative closest point algorithm registration. Principal component analysis is used to calculate the normal vector of the segmented elastic rod surface and extract the point on the centerline of the elastic rod. The point is projected onto the upper surface of the bolt to calculate the projection distance. Subsequently, the mapping relationship between the projection distance sequence and fastener tightness is established, and the influence of each parameter on the fastener tightness prediction is analyzed. Finally, by setting up a fastener detection scene in the track experimental base, collecting data, and completing the algorithm verification, the results showed that the deviation between the fastener tightness regression value obtained after the algorithm processing and the actual measured value RMSE was 0.2196 mm, which significantly improved the effect compared with other tightness detection methods, and realized an effective fastener tightness regression.

ABSTRACTMultiple myeloma (MM) is an incurable malignancy of the B-cell lineage. Remarkable progress has been made in the treatment of MM with anti-CD38 monoclonal antibodies such as daratumumab and isatuximab, which can kill MM cells by inducing complement-dependent cytotoxicity (CDC). We showed that the CDC efficacy of daratumumab and isatuximab is limited by membrane complement inhibitors, including CD46 and CD59, which are upregulated in MM cells. We recently developed a small recombinant protein, Ad35K++, which is capable of transiently removing CD46 from the cell surface. We also produced a peptide inhibitor of CD59 (rILYd4). In this study, we tested Ad35K++ and rILYd4 in combination with daratumumab and isatuximab in MM cells as well as in cells from two other B-cell malignancies. We showed that Ad35K++ and rILYd4 increased CDC triggered by daratumumab and isatuximab. The combination of both inhibitors had an additive effect in vitro in primary MM cells as well as in vivo in a mouse xenograft model of MM. Daratumumab and isatuximab treatment of MM lines (without Ad35K++ or rILYd4) resulted in the upregulation of CD46/CD59 and/or survival of CD46high/CD59high MM cells that escaped the second round of daratumumab and isatuximab treatment. The escape in the second treatment cycle was prevented by the pretreatment of cells with Ad35K++. Overall, our data demonstrate that Ad35K++ and rILYd4 are efficient co-therapeutics of daratumumab and isatuximab, specifically in multi-cycle treatment regimens, and could be used to improve treatment of multiple myeloma.

Postherpetic neuralgia (PHN) is a common, severe, and hard-to-treat chronic pain condition in clinics. Although PHN is developed from herpes zoster (HZ), the developing mechanism is unknown. A previous study investigated blood metabolomic and proteomic profiling in patients with PHN and HZ. The current study aims to explore the blood transcriptomic signature of PHN compared to HZ patients. Whole blood from eight PHN and 15 HZ patients was used for RNA-Seq analysis. There were 82 and 1,788 genes detected specifically in the PHN and HZ groups, respectively. PHN-specific genes are involved in viral infection, lipid and carbohydrate metabolism, and immune response. For genes coexpressed in PHN and HZ patients, there were 407 differential expression genes (DEGs), including 205 upregulated (UP DEGs) and 202 downregulated (DOWN DEGs) in PHN compared to HZ groups. DEGs are involved in viral infection, type I interferon (IFN), and hemoglobin and oxygen carrier activity. UP DEGs are associated with regulatory T cells (Tregs), activated NK cells, and neutrophils, while DOWN DEGs are associated with Tregs, resting NK cells, and monocytes. The results suggest that the metabolism of lipid, glycan, and nucleotides, type I IFN signaling, and altered neutrophil activation are associated with and might contribute to the development of PHN in HZ. It is also suggested that persistent or altered activation of nonspecific immunity may contribute to the development of PHN from HZ.

IntroductionCross-sectional evidence suggests that sleep problems increased the risk of suicide during the 2019 coronavirus disease (COVID-19) pandemic. However, a lack of longitudinal studies examined the relationship between pre-COVID-19 sleep duration, chronotype and incident suicide during the COVID-19 pandemic. Thus, we examined these associations in a longitudinal study of medical students.MethodsFrom the Shantou College Student Sleep Cohort, a total of 333 first and second grade medical students (age 19.41 ± 0.82 years, female 61.26%), without suicidal ideation (SI) at pre-COVID-19 period, were followed up during the COVID-19 pandemic. Incident SI was defined by their response to the 9th question from the Beck Depression Inventory. Short sleep duration was defined as less than 7 h/night. The Morningness-Eveningness Questionnaire was used to evaluate the participants’ chronotype. Logistic regression with adjusted odds ratios (AOR) and 95% confidence intervals (95% CI) was used to examine the association between sleep and SI.ResultsThe incidence of SI during the COVID-19 pandemic was 5.71%. Logistic regressions with confounding factors adjustment showed that both short sleep duration (AOR = 4.91, 95% CI = 1.16–20.74) and eveningness (AOR = 3.80, 95% CI = 1.08–13.30) in the pre-COVID-19 period were associated with increased risk of incident SI during the COVID-19 pandemic.ConclusionPre-COVID-19 short sleep duration and eveningness predict incident SI during the COVID-19 pandemic in medical students. Prolonging sleep duration may help to decrease SI during major public health crises.

BackgroundPrevalent urological cancers, including kidney, prostate, bladder, and testicular cancers, contribute significantly to global cancer incidence and mortality. Metabolomics, focusing on small-molecule intermediates, has emerged as a tool to understand cancer etiology. Given the knowledge gap in this field, we employ a two-sample Mendelian randomization (MR) analysis to investigate the causal relationships between genetically determined metabolites (GDMs) and the susceptibility to four common urological cancers.MethodsThe study employs genome-wide association studies (GWAS) data from European populations, featuring the most extensive case count available for both blood metabolites and four prevalent urological cancers. Preliminary and secondary MR analyses were separately conducted, employing inverse variance weighted (IVW) as the primary method. Multiple statistical analyses, including the MR-Steiger test, Cochran’s Q test, leave-one-out analysis, MR-Egger intercept analysis, and MR-PRESSO analysis, were executed to ensure robustness. Additionally, a meta-analysis was carried out to consolidate findings. The weighted median (WM) method was utilized for a relatively lenient correction (PWM < 0.05).ResultsAfter rigorous genetic variation filtering, 645 out of 1,400 metabolites were included in both preliminary and secondary MR analyses. Preliminary MR analysis identified 96 potential causal associations between 94 distinct metabolites and four urological cancers. Secondary analysis based on Finnish outcome data revealed 93 potential causal associations. Cross-database meta-analysis identified 68 blood metabolites associated with four urological cancers. Notably, 31 metabolites remained significant after using WM for correction, with additional 37 suggestive causal relationships. Reverse MR analysis revealed a significant causal association between genetically predicted prostate cancer and elevated 4-hydroxychlorothalonil levels (IVW, combined OR: 1.039, 95% CI 1.014–1.064, p = 0.002; WM, combined OR: 1.052, 95% CI 1.010–1.095, p = 0.014).ConclusionThis comprehensive MR study provides insights into the causal relationships between blood metabolites and urological cancers, revealing potential biomarkers and therapeutic targets, thereby addressing gaps in understanding and laying the foundation for targeted interventions in urological cancer research and treatment.

Litopenaeus vannamei, also known as the Pacific white shrimp or white foot shrimp, is a member of the Crustacea, Decapoda, Palaemonidae, and Litopenaeus families. This species is mainly distributed on the Mexican and Pacific coasts of South America. Owing to its excellent immune characteristics, L. vannamei is currently one of the most important economic shrimp species in China.In the aquaculture process and under natural environmental conditions, low dissolved oxygen (DO) condition or even hypoxia frequently occurs. Under high-density culture operations, acute hypoxia is one of the major factors affecting the survival rate of shrimp and the quality of aquaculture water, causing not only a large number of shrimp deaths in the short term but also water decay and fermentation, increased turbidity, and other phenomena. The genetic improvement of L. vannamei, as well as the screening and breeding of exceptionally tolerant species under low DO conditions, are crucial to the sustainable development of the shrimp industry. Global selective breeding efforts based on quantitative genetics to improve genetic progress in L. vannamei have been extensive, and the main targeted traits were growth, survival, disease resistance, and stress tolerance. Few studies have been conducted on the evaluation of genetic parameters and screening of strains for hypoxic tolerance traits in L. vannamei; in particular, the genetic parameters and cytological characteristics of key tissues of L. vannamei under short-term highly lethal DO levels (0.3–0.5 mg/L) have not been reported.In this study, we used two strains of L. vannamei, GK (a strain with high disease resistance) and K (a strain with fast growth characteristics), each with a total of 6 560 shrimp from 41 families, to count survival traits at highly lethal DO levels, analyze differences in hypoxia tolerance traits between strains and within families of the same strain, and evaluate genetic parameters. Individual gill, muscle, and hepatopancreas tissues from families with significantly different tolerance levels were histologically investigated and compared at the cellular level. The results showed that there was a significant difference (P < 0.05) in semi-lethal survival (SS50) between families within both the GK and K strains when overall semi-lethality was reached under hypoxic environmental conditions of 0.3 mg/L, with SS50 values of 49.30% for GK and 42.52% for K. The coefficients of variation for survival times of families within each strain were 60% and 45% for GK and K, respectively. Using the threshold trait animal model, the genetic parameters were estimated to be between 0.345±0.031 and 0.378±0.029 using the survival status of the individual at semi-lethal levels as the observed value (1 for survival and 0 for death), and the heritability was between 0.219±0.031 and 0.237±0.029 following transformation on a continuously varying scale of observed values, indicating a moderate level of heritability. Moreover, the gill, muscle, and hepatopancreas tissues of the hypoxia-tolerant and hypoxia-sensitive families in the GK strain exhibited varying degrees of damage and different degrees of variations in the physiological characteristics of resistance among different families. This may be related to the resistance tolerance strength of different GK families. In contrast to the gill, muscle, and hepatopancreas tissues of the control shrimp, the equivalent tissues of shrimp from tolerant and sensitive families showed different degrees of changes following stress. The gill lumen of the filaments of the experimental group from sensitive families increased, the number of blood cells increased, the structure of the epithelial layer was gradually destroyed or even disintegrated, the vacuolation of the hepatopancreas was severe, the lumen of the ducts became irregularly deformed, and the muscle tissue muscle bundle interval widened with a certain degree of deformation. These results suggested that there was abundant genetic variation in the tolerance traits of L. vannamei at highly lethal DO levels and that this species was amendable to selective breeding practices. This study provides a reference and basis for the selection and breeding of hypoxia-tolerant traits in L. vannamei.

Abstract Background The chloroplast genome (cp genome) is directly related to the study and analysis of molecular phylogeny and evolution of plants in the phylogenomics era. The cp genome, whereas, is highly plastic and exists as a heterogeneous mixture of sizes and physical conformations. It is advantageous to purify/enrich the circular chloroplast DNA (cpDNA) to reduce sequence complexity in cp genome research. Large-insert, ordered DNA libraries are more practical for genomics research than conventional, unordered ones. From this, a technique of constructing the ordered BAC library with the goal-insert cpDNA fragment is developed in this paper. Results This novel in-situ-process technique will efficiently extract circular cpDNA from crops and construct a high-quality cpDNA library. The protocol combines the in-situ chloroplast lysis for the high-purity circular cpDNA with the in-situ substitute/ligation for the high-quality cpDNA library. Individually, a series of original buffers/solutions and optimized procedures for chloroplast lysis in-situ is different than bacterial lysis in-situ; the in-situ substitute/ligation that reacts on the MCE membrane is suitable for constructing the goal-insert, ordered cpDNA library while preventing the large-insert cpDNA fragment breakage. The goal-insert, ordered cpDNA library is arrayed on the microtiter plate by three colonies with the definite cpDNA fragment that are homologous-corresponds to the whole circular cpDNA of the chloroplast. Conclusion The novel in-situ-process technique amply furtherance of research in genome-wide functional analysis and characterization of chloroplasts, such as genome sequencing, bioinformatics analysis, cloning, physical mapping, molecular phylogeny and evolution.

Unfolding-based single-stage ac-dc converters offer benefits in terms of efficiency and power density due to the low-frequency operation of the Unfolder, resulting in negligible switching losses. However, the operation of the Unfolder results in time-varying dc voltages at the input of the subsequent dc-dc converter, complicating its soft-switching analysis. The complication is further enhanced due to the nonlinear nature of the output capacitance ($C_\text{oss}$) of MOSFETs employed in the dc-dc converter. Furthermore, unlike two-stage topologies with a constant dc-link voltage, as seen in high-frequency grid-tied converters, grid voltage fluctuations also impact the dc input voltages of the dc-dc converter in unfolding-based systems. This work comprehensively analyzes the soft-switching phenomenon in the T-type primary bridge-based dc-dc converter used in unfolding-based topologies, considering all the aforementioned challenges. An energy-based methodology is proposed to determine the minimum zero-voltage switching (ZVS) current and ZVS time during various switching transitions of the T-type bridge. It is shown that the existing literature on the ZVS analysis of the T-type bridge-based resonant dc-dc converter, relying solely on capacitive energy considerations, substantially underestimates the required ZVS current values, with errors reaching up to 50%. The proposed analysis is verified through both simulation and hardware testing. The hardware testing is conducted on a 20-kW 3-$\phi$ unfolding-based ac-dc converter designed for high-power electric vehicle battery charging applications. The ZVS analysis is verified at various grid angles with the proposed analysis ensuring a complete ZVS operation of the ac-dc system throughout the grid cycle.

Serious hazards of transfusion(SHOT)in the United Kingdom has been received reporting of the adverse events of delayed transfusion for more than ten years. Hemovigilance Module Surveillance Protocol in Biovigilance Component in National Healthcare Safety Network in the United States updated the incident codes to include under-transfusion with the creation of a new process code: no blood (NB) and four incident codes in October 2022. This review introduces the monitoring practice of delayed transfusion/under-transfusion in the UK and the USA, makes a suggestion to incorporate delayed transfusion/under-transfusion due to blood shortage into the national health standard on the classification of transfusion reactions and haemovigilance protocol in China, and to do a national survey as well, therefore the real world data and evidences would be obtained and used for further policy making.

Cow dung liquid mulch (CDLM), which uses cow dung as a raw material, has a good degradability and is a potential alternative to traditional plastic agricultural mulch, but there is a lack of research on the effects of CDLM on rhizosphere soil physicochemical properties, rhizosphere soil microbial functions, and crop yields. In this study, the link between maize yield, environmental factors, and functional genes as well as the responses of microbial community functions to CDLM and polyethylene mulch (PE) were studied using metagenomic sequencing. Functional annotation was also performed on clusters of orthologous groups of proteins, the Kyoto Encyclopedia of Genes and Genomes, and carbohydrate-active enzyme sequencing data. The results showed that CDLM significantly increased maize yield by 30.9% compared to CK while maintaining lower soil microplastic levels. CDLM promotes the enrichment of beneficial microorganisms such as Mycolicibacterium and Pseudomonas. The relative abundance of functional genes related to microbial metabolism, soil element cycling pathways, and organic matter degradation was significantly higher in CDLM than in CK. Microbial functional genes were positively correlated with maize yield and environmental factors such as soil nutrients. These results suggested that CDLM can improve maize yield by enriching beneficial microorganisms, reducing rhizosphere soil environmental risks, and enhancing rhizosphere soil microbial function. Rhizosphere soil nutrients and microbial functional genes together mediated the positive response of maize yield to CDLM. This study can provide a scientific basis and data support for the safe use of mulch in the future.

To assess the consequences of nutrient reduction strategies on water quality under climate change, we investigated the long-term dynamics of dissolved oxygen (DO) and pH in Narragansett Bay (NB), a warming urbanized estuary in Rhode Island, where nitrogen loads have declined due to extensive wastewater treatment plant upgrades. We use 15 years (January 2005-December 2019) of measurements from the Narragansett Bay Fixed Site Monitoring network. Nutrient-enhanced phytoplankton growth can increase DO in the upper water column while subsequent respiration can reduce water column DO and enhance bottom water acidification, and vice-versa. We observed significant decreases in surface DO levels, concurrent with a significant increase in bottom DO, associated with the nitrogen load reduction. Surface DO decline was primarily attributed to reduced intensity of primary productivity, supported by a concurrent decrease in surface chlorophyll concentrations. Meanwhile, the influence of reduced organic matter respiration led to the increase of bottom DO levels by 9 µmol kg-1 (approximately 0.2 mg L-1 for typical summer temperature and salinity) over a 15-year period, which overcame the opposite influence of oxygen reduction from solubility decreases due to warming temperatures. In contrast, long-term changes in surface pH have not exhibited discernible trends beyond natural variability, likely due to the complex and sometimes opposing influences of biological activity and changing river flow conditions. We observed a slight increase in bottom pH, associated with the increase in DO in bottom water. Notably, future variations in freshwater discharge, particularly linked to extreme precipitation events, may further influence water carbonate chemistry and thereby impact pH dynamics. This study highlights the necessity of long-term time series measurements in helping understand the impacts of environmental management practices in improving water quality in coastal regions during a changing climate.

The increasing number of older adult migrants is rapidly changing regional demographic and social structures in China. There is an urgent need to understand the spatial patterns and factors that influence older adults to migrate, especially the role of environmental health. However, this issue has been under-studied. This study focused on intra-provincial and inter-provincial older adult migrants as research subjects, estimated their spatial concentration index based on the iterative proportional fitting approach, and explored the factors influencing their migration using the GeoDetector Model. The results showed the following: (1) In 2015, more than 76% of inter-provincial older adult migrants were distributed in Eastern China, and most intra-provincial older adult migrants were scattered in sub-provincial cities. (2) Compared to factors relating to economy and amenities, environmental health by itself played a relatively weak role in the migration of older adults, but the interaction among environmental health, economy, and amenities was a key driving force of older adult migration. (3) There were significant differences in the dominant environmental health factors between inter-provincial migration and intra-provincial migration, which were temperature and altitude, respectively. Our findings can help policymakers focus on the composition of older adult migrants based on urban environmental health characteristics and rationally optimize older adult care facilities to promote supply-demand matching.

Conventional stud connectors were proved to be inconvenient for the later disassembly and replacement in ultra-high performance concrete (UHPC) bridge decks. In this study, the headless studs which is a type of studs with their heads removed were employed as a substitute for conventional stud connectors, aiming to enhance the detachability of the bridge decks on the premise of ensuring the anti-lift bearing capacity of the decks. Three push-out specimens containing the headless studs with a diameter of 13 mm were carried out to study the mechanical properties of headless studs. In addition, the finite element model was developed to reveal the failure mechanism of headless studs in UHPC. Results indicated that the load-slip curve of headless stud connector can be divided into elastic stage, plastic stage and failure stage. The failure mode of headless studs was the shear fracture at the root of stud shank. Headless stud connections under cyclic loading can produce greater plastic deformation. The ultimate shear capacity and shear stiffness of headless studs were lower than those of conventional studs. Additionally, the UHPC slabs configured with headless studs have a small quantity of separation at the steel-UHPC interface, so it is suggested to use headless studs and conventional studs together in UHPC slabs to ensure the necessary anti-lift bearing capacity. Finite element analysis indicated that in the elastic stage, the bearing capacity of the push-specimen was dominated by the material properties of the headless stud. After entering the plastic stage, the bearing capacity of the push-specimen was mainly controlled by the UHPC below the headless stud.

A novel composite sulfur-manganese carbonate autotrophic denitrification (SMAD) system was developed to reduce sulfate production and provide pH buffer function while improving denitrification efficiency without external organics. The average removal efficiency of total nitrogen (TN) was 98.09% and 96.29%, and that of NO3−-N was 99.53% and 97.77%, respectively, in the SMAD system with a hydraulic retention time (HRT) of 6 h and 3 h. They were significantly higher than that in the controls (quartz sand, manganese carbonate ore, and sulfur systems). The H+ produced by the sulfur autotrophic denitrification (SAD) process promoted the release of Mn2+ in the SMAD system. And this system had a stable pH with no accumulation of NO2−-N. The decrease of sulfate and formation of Mn oxides through Mn2+ electron donation confirmed the presence of the manganese autotrophic denitrification (MAD) process in the SMAD system. Dominant functional bacteria in the SMAD system were Thiobacillus, Chlorobium, and Sulfurimonas, which were linked to nitrogen, sulfur, and manganese conversion and promoted denitrification. Meanwhile, Flavobacterium participating in Mn2+ oxidation was found only in the SMAD system. The SMAD system provided a new strategy for advanced tailwater treatment.

U.S. Food and Drug Administration recently issued a guidance on alternative procedures for the manufacture of cold-stored platelets intended for the treatment of active bleeding when conventional platelets are not available or their use is not practical. It was allowed to use platelets stored at 1 ℃ to 6 ℃, with a storage period of up to 14 days from the date of collection.The validation and quality monitoring of platelet manufacture retained pH items testing at the end of the storage, and platelet count and actual plasma volume testing items were not required. The guidance provided the recommendations and considerations for the manufacture, labeling, storage, transportation, bacterial contamination control, process validation, and quality monitoring sampling of cold-stored platelets, as well as the further research needs for its efficacy, particularly when conventional platelets are available and their use is practical. The scientific and regulatory considerations on cold-stored platelets in the guidance would be informative and instructive to the development of blood regulation and standards related with urgent transfusion in China.

Abstract Ceramic aerogels are highly efficient, lightweight, and chemically stable thermal insulation materials but their application is hindered by their brittleness and low strength. Flexible nanostructure-assembled compressible aerogels have been developed to overcome the brittleness but they still show low strength, leading to insufficient load-bearing capacity. Here we designed and fabricated a laminated SiC-SiOx nanowire aerogel that exhibits reversible compressibility, recoverable buckling deformation, ductile tensile deformation, and simultaneous high strength of up to an order of magnitude larger than other ceramic aerogels. The aerogel also shows good thermal stability ranging from −196 °C in liquid nitrogen to above 1200 °C in butane blow torch, and good thermal insulation performance with a thermal conductivity of 39.3 ± 0.4 mW m−1 K−1. These integrated properties make the aerogel a promising candidate for mechanically robust and highly efficient flexible thermal insulation materials.

With the development of aerospace technology, the Mach number of aircraft continues to increase, which puts forward higher performance requirements for high-temperature wave-transparent materials. Silicon nitrides have excellent mechanical properties, high-temperature stability, and oxidation resistance, but their brittleness and high dielectric constant impede their practical applications. Herein, by employing a template-assisted precursor pyrolysis method, we prepared a class of Si3N4@SiO2 nanowire aerogels (Si3N4@SiO2 NWAGs) that are assembled by Si3N4@SiO2 nanowires with diameters ranging from 386 to 631 nm. Si3N4@SiO2 NWAGs have low density of 12–31 mg∙cm−3, specific surface area of 4.13 m2∙g−1, and average pore size of 68.9 μm. Mechanical properties characterization shows that the aerogels exhibit reversible compressibility from 60% compressive strain and good fatigue resistance even when being compressed 100 times at set strain of 20%. The aerogels also show good thermal insulation performance (0.032 W·m−1∙K−1 at room temperature), ablation resistance (butane blow torch), and high-temperature stability (maximum service temperature in air over 1200 ℃). The dielectric constant and loss of the aerogels are 1.02–1.06 and 4.3×10−5–1.4×10−3 at room temperature, respectively. The combination of good mechanical, thermal, and dielectric properties makes Si3N4@SiO2 NWAGs promising ultralight wave-transparent and thermally insulating materials for applications at high temperatures.

Aims: Osteoporosis is characterized by decreased trabecular bone volume, and microarchitectural deterioration in the medullary cavity. Interleukin-19 (IL-19), a member of the IL-10 family, is an anti-inflammatory cytokine produced primarily by macrophages. The aim of our study was to investigate the effect of IL-19 on osteoporosis. Methods: Blood and femoral bone marrow suspension IL-19 levels were first measured in the lipopolysaccharide (LPS)-induced bone loss model. Small interfering RNA (siRNA) was applied to knock down IL-19 for further validation. Thereafter, osteoclast production was stimulated with IL-19 in combination with mouse macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). The effect of IL-19 was subsequently evaluated using tartrate-resistant acid phosphatase (TRAP) staining and quantitative real-time polymerase chain reaction (RT-qPCR). The effect of IL-19 on osteoprotegerin (OPG) was then assessed using in vitro recombinant IL-19 treatment of primary osteoblasts and MLO-Y4 osteoblast cell line. Finally, transient transfection experiments and chromatin immunoprecipitation (ChIP) experiments were used to examine the exact mechanism of action. Results: In the LPS-induced bone loss mouse model, the levels of IL-19 in peripheral blood serum and femoral bone marrow suspension were significantly increased. The in vivo results indicated that global IL-19 deletion had no significant effect on RANKL content in the serum and bone marrow, but could increase the content of OPG in serum and femoral bone marrow, suggesting that IL-19 inhibits OPG expression in bone marrow mesenchymal stem cells (BMSCs) and thus increases bone resorption. Conclusion: IL-19 promotes bone resorption by suppressing OPG expression in BMSCs in a LPS-induced bone loss mouse model, which highlights the potential benefits and side effects of IL-19 for future clinical applications. Cite this article: Bone Joint Res 2023;12(11):691–701.

Abstract We aimed to explore the effects of perioperative exercise on cardiorespiratory endurance in children with congenital heart disease (CHD) in plateau areas after surgical repair. Fifty children with CHD in the plateau admitted to our hospital were randomly divided into the exercise and control groups. The exercise group received a perioperative exercise intervention beginning within 24 h postoperatively, while the control group received routine nursing and treatment alone. To assess the 6 min walk distance (6MWD) at baseline and at end of intervention, children participated in a 6-min walk test before cardiac repair and at 1 week after general ward transfer. A subset of children in the study underwent the cardiopulmonary exercise test pre-operatively. The 6MWD of children with CHD at baseline was positively correlated with the peak oxygen uptake pre-operatively. No significant difference was reported in the preoperative baseline data of both groups. The 6MWD of the exercise group was significantly higher than that of the control group. Early exercise therapy after cardiac repair could significantly improve the cardiorespiratory endurance and exercise capacity of children with CHD in plateau areas.

Currently, multiple myeloma (MM) is a prevalent hematopoietic system malignancy, known for its insidious onset and unfavorable prognosis. Recently developed chemotherapy drugs for MM have exhibited promising therapeutic outcomes. Nevertheless, to overcome the shortcomings of traditional clinical drug treatment, such as off-target effects, multiple drug resistance, and systemic toxicity, targeted drug delivery systems are optimizing the conventional pharmaceuticals for precise delivery to designated sites at controlled rates, striving for maximal efficacy and safety, presenting a promising approach for MM treatment. This review will delve into the outstanding performance of antibody–drug conjugates, peptide–drug conjugates, aptamer–drug conjugates, and nanocarrier drug delivery systems in preclinical studies or clinical trials for MM and monitor their adverse reactions during treatment.

Ecological restoration in dredging areas has attracted increasing attention. The reconstruction of a submerged plant ecosystem is an important method for aquatic ecosystem restoration. This study has systematically investigated the effect of biochar-improved sediment on the plant growth and decontamination efficiency of a constructed ecosystem. Microbial community composition and structure in the sediment were detected. The results showed that a supplement of 20 mg/g of biochar significantly increased the biomass of the submerged plants compared with other doses (0, 10, and 40 mg/g). The biomass and chlorophyll content were significantly inhibited by supplementing 40 mg/g of biochar. In the Ceratophyllum demersum L. system, TP and NH4+-N concentrations were significantly lower after treatment with 20 mg/g of biochar compared to other doses. In Vallisneria spiralis L. and Hydrilla verticillata (L. f.) Royle systems, NH4+-N, TP, and DO concentrations were significantly different among different biochar treatments. In general, 20 mg/g of biochar improved water quality in different submerged plant systems, while 40 mg/g of biochar had adverse effects on water quality, such as higher NH4+-N and TP concentrations. The dominant microbial community included Proteobacteria, Acidobacteria, Chloroflexi, Actinobacteriota, and Bacteroidota. The structure and function of microbial communities were different among submerged plants and biochar treatments. Our results proposed a construction strategy of submerged plants in the dredging area.

Abstract Background White clover (Trifolium repens L.), an excellent perennial legume forage, is an allotetraploid native to southeastern Europe and southern Asia. It has high nutritional, ecological, genetic breeding, and medicinal values and exhibits excellent resistance to cold, drought, trample, and weed infestation. Thus, white clover is widely planted in Europe, America, and China; however, the lack of reference genome limits its breeding and cultivation. This study generated a white clover de novo genome assembly at the chromosomal level and annotated its components. Results The PacBio third-generation Hi-Fi assembly and sequencing methods generated a 1096 Mb genome size of T. repens, with contigs of N50 = 14 Mb, scaffolds of N50 = 65 Mb, and BUSCO value of 98.5%. The newly assembled genome has better continuity and integrity than the previously reported white clover reference genome; thus provides important resources for the molecular breeding and evolution of white clover and other forage. Additionally, we annotated 90,128 high-confidence gene models from the genome. White clover was closely related to Trifolium pratense and Trifolium medium but distantly related to Glycine max, Vigna radiata, Medicago truncatula, and Cicer arietinum. The expansion, contraction, and GO functional enrichment analysis of the gene families showed that T. repens gene families were associated with biological processes, molecular function, cellular components, and environmental resistance, which explained its excellent agronomic traits. Conclusions This study reports a high-quality de novo assembly of white clover genome obtained at the chromosomal level using PacBio Hi-Fi sequencing, a third-generation sequencing. The generated high-quality genome assembly of white clover provides a key basis for accelerating the research and molecular breeding of this important forage crop. The genome is also valuable for future studies on legume forage biology, evolution, and genome-wide mapping of quantitative trait loci associated with the relevant agronomic traits.

Abstract Carbon aerogels are elastic, mechanically robust and fatigue resistant and are known for their promising applications in the fields of soft robotics, pressure sensors etc. However, these aerogels are generally fragile and/or easily deformable, which limits their applications. Here, we report a synthesis strategy for fabricating highly compressible and fatigue-resistant aerogels by assembling interconnected carbon tubes. The carbon tube aerogels demonstrate near-zero Poisson’s ratio, exhibit a maximum strength over 20 MPa and a completely recoverable strain up to 99%. They show high fatigue resistance (less than 1.5% permanent degradation after 1000 cycles at 99% strain) and are thermally stable up to 2500 °C in an Ar atmosphere. Additionally, they possess tunable conductivity and electromagnetic shielding. The combined mechanical and multi-functional properties offer an attractive material for the use in harsh environments.

Abstract Objective Performing long‐term video‐electroencephalographic monitoring (LTVEM) to obtain the ictal electroencephalogram (EEG) is important for presurgical evaluation. This study aimed at investigating the safety and efficacy of our protocol developed at Peking University First Hospital (PUFH) for rapid withdrawal of antiseizure medications (ASMs) during LTVEM to induce seizures in children with drug‐resistant epilepsy (DRE) exhibiting nondaily seizures. Methods Children with DRE who followed the PUFH protocol for rapid withdrawal of ASMs during LTVEM between 2018 and 2021 were enrolled. The occurrence of seizures, number of ASMs withdrawn, seizure onset time after ASM tapering initiation, changes in interictal epileptiform discharge (IED), and adverse events were evaluated during LTVEM. Results Among 80 children evaluated in this study, seizures were induced successfully in 72 (90%) children. Furthermore, no change in IED sites was observed in these 72 children following the initiation of ASM tapering while 2 children exhibited secondary bilateral tonic‐clonic seizures. The median time from ASM tapering initiation to the onset of the first seizure was found to be 3 days (2–4), while the median number of ASMs withdrawn was 2 (1–2). Finally, 66 children (91.7%) had habitual seizures while 6 children had nonhabitual seizure semiology. Significance The PUFH protocol can be used for the rapid withdrawal of ASMs during LTVEM in children with DRE. Using this protocol, ictal EEG patterns can be obtained in a relatively short time for most patients with fewer adverse effects during LTVEM, which may provide meaningful electro‐clinical information for presurgical evaluation.

In previous studies, we achieved safe and efficient in vivo hematopoietic stem cell (HSC) transduction in mobilized mice and macaques with intravenously injected helper-dependent adenovirus HDAd5/35++ vectors. These vectors are derivatives of serotype Ad5-containing CD46-affinity enhanced Ad35 fiber knob domains. Considering the impact of anti-Ad5/HDAd5/35++ neutralizing serum antibodies present in the human population, we generated HSC-retargeted HDAd6/35++ vectors derived from serotype 6. We found a lower prevalence and titers of serum anti-HDAd6/35++ in human samples compared with HDAd5/35++. HDAd6/35++ vectors efficiently transduced human and rhesus CD34+ cells in vitro. Intravenous injection of HDAd5/35++-GFP or HDAd6/35++-GFP vectors after G-CSF/AMD3100 mobilization of mice with established human hematopoiesis or human CD46 transgenic mice resulted in comparable GFP marking rates in HSCs in the bone marrow and spleen. In long-term in vivo HSC transduction and selection studies with integrating vectors, stable GFP expression in >75% of PBMCs was show for both vectors. In contrast with HDAd5/35++, undesired transduction of hepatocytes was minimal with HDAd6/35++. Furthermore, HDAd6/35++ allowed for efficient in vivo HSC transduction in Ad5-pre-immune mice. These features, together with the straightforward production of HDAd6/35++ vectors at high yield, make this new HDAd vector platform attractive for clinical translation of the in vivo approach.

Background: The pathogenesis of metabolic syndrome was strongly associated with compromised metabolism homeostasis and gut microbiota imbalance. NAFLD is a progressive metabolic liver disease for which effective interventions are lacking. Bile acids exhibited appreciable metabolic regulatory effects and selective antimicrobial activity. Aim of the study: This study was designed to investigate the effect of BBBP, which mainly contained bile acids, on NAFLD from the perspectives of gut microbiota and metabolomics. Materials and methods: The present study was initiated on the anti-NAFLD effect of BBBP in HFD-fed mice. The efficacy of BBBP was evaluated by mice phenotypes, liver histopathological analysis and serum lipid and glucose levels. The activation of bile acid receptors such as Nr1h4, Nr1i2 and S1pr2 were detected by qRT-PCR analysis. Subsequently, untargeted metabolomics coupled with microbiomics was used to explore the mechanism of BBBP against NAFLD. Human L02 hepatocytes induced by OA and PA were used to investigate the effect of GABA on reducing lipid accumulation in vitro. Results: BBBP significantly and dose-dependently alleviated the obese phenotype, lipid accumulation and liver injury in mice subjected to 18 weeks HFD diet. Untargeted metabolomics and microbiomics analysis revealed that BBBP could alleviate the disturbance of lipid and amino acid metabolism and the imbalance of gut microbiota. Furthermore, BBBP oral gavage activated liver bile acid receptors, as indicated by elevated mRNA levels of Nr1h4, Nr1i2 and S1pr2. Surprisingly, we determined that BBBP, which mainly contained bile acids that possessed antimicrobial activity, could promote the growth of Lactobacillus. Correlation analysis showed a remarkable correlation between Lactobacillus and endogenous metabolites such as valine, serine, glutamine, et al. Among them, GABA which could be produced by Lactobacillus significantly reduced the lipid accumulation in L02 cells. Conclusions: The role of BBBP in regulating lipid metabolism might be achieved by activating bile acid receptors, or partially by promoting the levels of Lactobacillus and its metabolites such as GABA. Our study provided evidence that BBBP could be a novel therapeutic candidate for the treatment of NAFLD.

In lunar science, volatiles are defined as chemical elements and unstable compounds, evaporating, sublimating, or flowing in other ways at low temperature. At moderate temperature, volatiles transfers its flowing elements from solid materials to coexisting gas phases. Such substances include S, Cu, Zn, As, Se, Ag, Cd, In, Te, Hg, Ti, Pb, Bi, and halogens (F, C L, Br, and I). These volatile substances are mainly added by small impactors, so they should be uniformly deposited in lunar regolith. In the permanently shaded regions (PSRs) of the lunar polar region, the extremely low temperature may allow the solar activity record to be kept longer. When the lunar soil is heated, it will release volatile elements in the form of gas, especially the particles injected into the lunar soil by the solar wind. In deeper lunar soil, it means that these particles were implanted in different periods of solar evolution. The study of regolith in polar PSRs may help to solve this problem, because it has not been widely heated and therefore may not be subjected to postimplantation modification. The research on volatiles detection in lunar polar region can help us confirm the content and distribution of water ice in the permanent shadow region of the lunar polar region, and the composition, distribution, source, transport and loss mechanism of other volatiles in this region, as well as the relationship between lunar soil in the polar region and the ancient solar wind environment, and the environment and mineral resources in the region. Chandrayaan-3 provided important assistance to the conceptualization of this project. At the end of the article, we discussed the lunar orbit.

Cavitation limits the efficient and stable operation of rotating machinery. The exploration of control methods for hydrofoil cavitation is important for improving the performance of hydraulic machinery. The leading-edge protuberances of the humpback flipper and the spine structure of the tail fin of sailfish are two common bionic structures for cavitation control; however, the control effects of both have limitations. Accordingly, in this study, a passive control method for hydrofoil cavitation was developed by combining the two bionic structures. With the large eddy simulation method, the cavitation processes of wavy leading-edge hydrofoil, bionic fin spine structure hydrofoil, and novel bionic combined structure hydrofoil were studied under a cavitation number of σ = 0.8. The control mechanisms of the three bionic structures for the hydrofoil cavitation were investigated. The results indicated that the novel bionic combined hydrofoil realised the superposition and complementation of the control effects of the two single bionic structures and achieved a better cavitation inhibition effect, reducing the total volume of cavitation by 43 %. In addition, it enhanced the stability of the flow field and reduced the standard deviation of the pressure coefficient on the suction surface by up to 46.55 %. This research provides theoretical support for the optimisation and modification of the blades of hydraulic machinery, such as propellers and pump turbines.

As archaeology in China has developed, experimental archaeology, as a research method of archaeology, has attracted more and more attention from Chinese archaeologists. The strength of a discipline's development is reflected not only in academic contributions but also in how it enhances the lives of the public. The experimental archaeology museum in Baoding, China attempts to integrate experimental archaeology into primary education and at the same time to create a new way of participating in archaeological work in social and cultural education.

NASH is a highly prevalent metabolic syndrome that has no specific approved agents up to now. BBBP, which mainly contains bile acids, possess various pharmacological properties and some bile acids are available for NASH treatment. Herein, the therapeutic effects and underlying mechanisms of BBBP against NASH were systemically evaluated. In this study, mice received an HFHS diet over a 20-week period to induce NASH with or without BBBP intervention were used to evaluate the effect and underlying mechanisms of BBBP against NASH. Our results demonstrated that BBBP attenuated hepatic steatosis, reduced body weight gain and lipid concentrations, and improved sensitivity to insulin and tolerance to glucose in mice fed an HFHS diet. Metabolomics and transcriptomic analysis revealed that BBBP suppressed the arginine biosynthesis by up-regulating NOS3 expression and the PI3K-Akt signaling pathway was also regulated by BBBP, as indicated by 55 DEGs. Bioinformatic analysis predicted the regulatory effect of the FXR/PXR-PI3K-AKT-NOS3 axis on arginine biosynthesis-related metabolites. These results were further confirmed by the significantly increased mRNA and protein levels of NOS3, PI3K (Pik3r2), and AKT1. And the increased levels of arginine biosynthesis related-metabolites, such as urea, aspartic acid, glutamic acid, citrulline, arginine, and ornithine, were confirmed accurately based on targeted metabolomics analysis. Together, our study uncoded the complicated mechanisms of anti-NASH activities of BBBP, and provided critical evidence inspiring the discovery of innovative therapies based on BBBP in the treatment of NASH.

Ultra-high performance concrete (UHPC) as a joint material for precast bridge decks might reduce the width of the joint and improve its connection performance and durability. This study proposes a type of compact UHPC wet joint based on the mechanical properties of UHPC and the force characteristics of transverse joints in prefabricated bridge decks. The shear behavior of the novel joint was investigated through experimental study and numerical simulation. In addition, the shear properties of compact UHPC wet joints were compared with epoxy joints. The results indicated that the shear resistances of compact UHPC joints are comparable to those of epoxy joints. The failure process of the precast bridge deck with new joint might be divided into three stages: elastic stage, working stage with cracks, and yield stage. No interface cracks or reinforcement slippage was observed throughout the loading process, indicating that the UHPC joint and the epoxy joint exhibited adequate shear resistance. The ultimate load capacity and corresponding mid-span deflection of UHPC joint specimens were respectively increased by 8.6 % and 75.0 %, when compared with the epoxy joint specimens. Finite element analysis reveals that the transverse shear transfer range of the compact UHPC joints is within 57.1 %. Bending failure due to the yielding of the transverse reinforcement at the bottom of the precast bridge deck is the primary failure mode for both specimens. Moreover, the stresses applied to the deck system have good continuity at the joint.

The dynamic characteristics of running away pump turbines (PTs) with a large head variable amplitude have not been understood thus far, primarily because of two difficulties in simulation and analysis. The first is how to provide accurate time-varying boundary conditions for transient simulation of the turbine runaway process (TRP). The other is how to determine the specific appearance time of each frequency component of the complex pressure fluctuations. This study presented a one- and three-dimensional (1D-3D) coupled approach considering waterway dynamics to provide accurate unsteady boundary conditions for the transient flow simulation of a PT with a large head variable amplitude. The short-time Fourier transformation (STFT) approach was adopted to analyse the time-frequency characteristics of the transient pressures and impeller forces. The study found that the fluctuations of pressures and impeller forces during the TRP of the PT with a large head variable amplitude contained two exclusive fluctuation frequency components. The former was approximately three times the rated rotational frequency of the impeller. The later was a series of integer fold transient rotational frequencies of the impeller, which was irrelevant to the rotor-stator interactions. The findings have important value for controlling the pressure fluctuations during the TRP of PTs.

Abstract The treatment outcome of hepatocellular carcinoma (HCC) is severely hampered due to its etiology, and thus in depth understanding of the genetic mechanisms underlying response of HCC to various anticancer agents is needed. Here, we have identified Phosphotyrosine interaction domain-containing protein 1 (PID1) as a novel regulator involved in modulation of apoptosis induced by anticancer agents in a context-dependent manner. PID1 relieved chemotherapy-induced ROS production, mitochondrial outer membrane permeability and mitochondrial respiratory depression. In addition, PID1 restricted AKT-mediated inhibition on Raf-1 through interacting with PDPK1 at phosphorylated tyrosine sites, thus enhancing Raf-1-mediated BAD inhibition. Interestingly, AKT, Bcl2 inhibition or Raf-1 silencing abolished PID1-mediated anti-apoptotic effects. However, PID1 altered the rhythmicity of pharmacological activity of Sorafenib on various survival-related kinases, thus resulting in AKT blockade via Raf-1/BRAF/ERK/MEK pathway. BRAF inhibition or Raf-1 depletion disrupted PID1-mediated barrier in AKT activation in response to Sorafenib. Moreover, in vivo study indicated that PID1 deficiency led to increased survival rate upon Doxorubicin treatment but reduced efficacy of Sorafenib. Overall, we propose that PID1 can function as an underlying biomarker of resistance to conventional chemotherapeutic agents but sensitivity towards Sorafenib.

Background and objectiveCardiovascular disease is the leading cause of morbidity and mortality globally. Echocardiography is a commonly used method for assessing the condition of patients with cardiovascular disease. However, little is known about the population characteristics of patients who are recommended for echocardiographic examinations.MethodsThe National Ambulatory Medical Care Survey was a cross-sectional survey previously undertaken in the USA. In this study, publicly accessible data from the National Ambulatory Medical Care Survey database (for 2007–2016 and 2018–2019; data for 2017 was not published) were utilized to create a nomogram based on significant risk predictors. The study was performed in accordance with the relevant guidelines and regulations stipulated in the National Ambulatory Medical Care Survey database. Patients were randomly assigned to one of two groups: training cohort or validation cohort. The latter was used to assess the reliability of the prediction nomogram. Decision curve analysis was performed to evaluate the net benefit. Propensity score matching analysis was used to evaluate the relevance of echocardiography to clinical decision-making.ResultsA total of 217,178 outpatients were enrolled. Multivariable logistic regression analysis demonstrated that hypertension, hyperlipidemia, coronary artery disease/ischemic heart disease/history of myocardial infarction, congestive heart failure, major reason for visit, metropolitan statistical area, cerebrovascular disease/history of stroke or transient ischemic attack, previously assessed, insurance, referred, diagnosis, and reason for visit were all predictors of echocardiogram prescription in outpatients. The reliability of the predictive nomogram was confirmed in the validation cohort. After propensity score matching, there was a significant difference in new cardiovascular agent prescriptions between the echocardiogram and no echocardiogram groups (P

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic hepatic disease characterized by excessive fat accumulation, and is the major risk for cardiovascular and metabolic disorders. We explored the therapeutic effect of gypenosides (Gyps) in combination with capsaicinoids (Caps) against high-fat-diet (HFD)-induced rat hyperlipidemia and oxidized low-density lipoprotein (ox-LDL)-treated Raw264.7 cells. Network pharmacology analysis predicted that the potential molecular mechanism of Gyps/Caps combination against hyperlipidemia was mainly associated with steroid metabolism, lipid synthesis and inflammatory response. Animal experiment demonstrated that Gyps/Caps combination lowered the liver weight, liver index, serum lipid profile and hepatic cholesterol content, improved liver function by reducing the serum markers of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), thereby relieving the hepatic injury. Moreover, Gyps/Caps combination inhibited oxidative stress by decreasing the lactic dehydrogenase (LDH) activity and increasing the superoxide dismutase (SOD) activity. Western blotting result suggested that Gyps/Caps combination could upregulate the expressions of peroxisome proliferator-activated receptors γ (PPARγ), liver X receptor α (LXRα), ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1) in the liver tissue. Cellular experiment revealed that the combination treatment protected RAW264.7 cells from ox-LDL induction through inhibiting apoptosis, lipid-decreasing and anti-inflammation, and caused the dramatic enhancement on PPARγ expression. Notably, the combined use of Gyps and Caps did not influence the pharmacological outcomes of each other, but significantly enhanced the overall therapeutic effect in ameliorating HFD-induced hyperlipidemia. Our research provided an experimental basis for advanced research and clinical application of Gyps/Caps combination. Importantly, our cumulative data indicated that combination use of Gyps and Caps may be an effective therapeutic strategy for alleviating hyperlipidemia-induced NAFLD.

SiC ceramics are attractive electromagnetic (EM) absorption materials for the application in harsh environment because of their low density, good dielectric tunable performance, and chemical stability. However, the performance of current SiC-based materials to absorb EM wave is generally unsatisfactory due to poor impedance matching. Herein, we report ultralight SiC/Si3N4 composite aerogels (~15 mg·cm−3) consisting of numerous interweaving SiC nanowires and Si3N4 nanoribbons. Aerogels were prepared via siloxane pyrolysis and chemical vapor reaction through the template method. The optimal aerogel exhibits excellent EM wave absorption properties with a strong reflection loss (RL, −48.6 dB) and a wide effective absorption band (EAB, 7.4 GHz) at a thickness of 2 mm, attributed to good impedance matching and multi attenuation mechanisms of waves within the unique network structure. In addition, the aerogel exhibits high thermal stability in air until 1000 ℃ and excellent thermal insulation performance (0.030 W·m−1·K−1). These superior performances make the SiC/Si3N4 composite aerogel promising to become a new generation of absorption material served under extreme conditions.