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In this study, three types of three-layer functionally graded materials (FGMs) were designed by mainting the average content of the reinforcement constant and changing the span of the composition. The B4C particle-reinforced Al-matrix FGMs and a homogeneous composite (HC) with the same average composition were prepared using the laser additive manufacturing technique. The FGMs had a higher average secondary-phase content and grain size than the HC. Large (black) and reticulated (white) secondary phases corresponding to B4C phase, T phase, and MgZn2 were observed in the as-deposited FGM samples. The content of the secondary phase in the middle layer was generally low. The bottom layer, which was in direct contact with the substrate, exhibited the smallest grain size. The hardness and wear resistance significantly improved owing to the high B4C content in the top layer. The flexural behaviors of each layer of the FGM in different directions were systematically studied. The plasticity of the single-layer material decreased with increase in the B4C content. When the bottom layer had a high B4C content, the flexural ability significantly reduced. Among all the samples, G2 with 8% B4C particle content in the top layer exhibited the best comprehensive mechanical properties. The hardness value, wear rate of the top layer, maximum bending stress, and maximum bending strain of the FGM were 177.5 HV, 0.367 × 10−3mm3/(N·m), 585.6 MPa, and 7.36%, respectively. This study can provide a reference value for the future design and development of wear-resistant gradient materials for aerospace applications.

Three types of 7185+TiB2/TiC aluminum matrix composites with different Zn/Mg ratios were prepared in this work through a water-cooled copper casting process. The effects of Zn/Mg ratio on the microstructure and mechanical properties of 20-mm-thick composites were studied by optical microscopy, electron back scattering diffraction, transmission electron microscopy, and tensile mechanical testing. The results showed that the addition of appropriate TiB2/TiC particles refined the as-cast microstructure of the alloy, and with a decrease in Zn/Mg ratio, the grain size distribution became more uniform, the crystalline phase content gradually increased, and the uniformity of the alloy increased. After aging, as the Zn/Mg ratio decreased, the size of the precipitated phase decreased, and the strengthening effect of the alloy improved. The tensile strengths of the surface layer, 1/4 layer, and center position of the A3 alloy were 558, 568, and 572 MPa, respectively. The strength difference among the different thickness layers was the smallest, and the elongation rate was greater than 12%, resulting in the best uniformity.

Exploring the impact of elevated CO2 on photosynthesis is vital for understanding plant responses to climate change. In C3 plants, elevated CO2 concentrations generally enhance CO2 assimilation by increasing chloroplast CO2 concentration. However, the underlying mechanisms are complex since photosynthesis involves multiple physiological processes operating at different time scales and varying among plant species. In this review, we focused on the responses of key photosynthetic processes in crop, including CO2 diffusion conductances such as stomatal conductance (gs), mesophyll conductance (gm), photochemical reactions, the Calvin-Benson cycle, and related metabolic pathways. Short-term exposure to elevated CO2 often decreases gs and gm while increasing the electron transport rate. However, long-term exposure to elevated CO2 can decrease photosynthetic capacity due to coordinated downregulation of multiple processes, particularly when the sink‒source ratio declines. To enhance plant productivity under elevated CO2, it is crucial to maintain or enhance sink activity and understand the CO2 response mechanisms at the molecular, physiological, and morphological levels. This review provides an update on the short- and long-term responses of gs, gm, electron transport system, and carbon assimilation metabolism to elevated CO2. Furthermore, it offers a perspective on improving crop production in the future with elevated CO2 levels.

Objective: To provide a synthesis of randomized controlled trials (RCTs) investigating statin-associated muscle symptoms (SAMS) in adults who underwent exercise training intervention. Patients and Methods: We systematically searched 5 electronic databases for placebo-controlled RCTs through January 31, 2023. We included short-term and long-term exercise interventions that compared the efficacy and safety of exercise+statin vs exercise+placebo in healthy adults and reported SAMS preintervention and postintervention. Publication bias and methodological study quality assessments were performed. Results: Five of 454 potentially qualifying RCTs met the inclusion criteria, all short-term exercise RCTs. Participants were predominantly physically inactive young to middle-aged (M=37.2 y) men (57%), 252 (49%) who were on statin therapy, and 271 (53%) on placebo. Of the 3 RCTs providing qualitative SAMS results, 19 (9%) out of 220 participants reported SAMS on exercise+statin and 10 (4%) out of 234 reported SAMS on exercise+placebo. There was no difference between exercise+statin vs exercise+placebo for maximal oxygen consumption (d=−0.18; 95% CI, −0.37 to 0.00; P=.06) or creatine kinase after short-term exercise (d=0.59; 95% CI, −0.06 to 1.25; P=.08). Participants in the exercise+statin group reduced low-density lipoprotein cholesterol vs exercise+placebo (d=−1.84; 95% CI, −2.28 to −1.39; P

Background: Exposure to endocrine-disrupting chemicals (EDCs) has been found to be associated with growth and developmental abnormalities in children. However, the potential mechanisms by which exposure to EDCs during pregnancy increases the risk of obesity in children remain unclear. Objective: We aimed to explore associations between prenatal EDC exposure and the body mass index (BMI) of children at age two, and to further explore the potential impact of DNA methylation (DNAm). Method: This study included 285 mother–child pairs from a birth cohort conducted in Wuhan, China. The BMI of each child was assessed at around 24 months of age. The concentrations of sixteen EDCs at the 1st, 2nd, and 3rd trimesters were measured using ultra-high performance liquid chromatography coupled to a triple quadrupole mass spectrometer. The research utilized general linear models, weighted quantile sum regression, and Bayesian Kernel Machine Regression to assess the association between prenatal EDC exposure and childhood BMI z-scores (BMIz). Cord blood DNAm was measured using the Human Methylation EPIC BeadChip array. An epigenome-wide DNAm association study related to BMIz was performed using robust linear models. Mediation analysis was then applied to explore potential mediators of DNAm. Results: Urinary concentrations of seven EDCs were positively associated with BMIz in the 1st trimester, which remained significant in the WQS model. A total of 641 differential DNAm positions were associated with elevated BMIz. Twelve CpG positions (annotated to DUXA, TMEM132C, SEC13, ID4, GRM4, C2CD2, PRAC1&PRAC2, TSPAN6 and DNAH10) mediated the associations between urine BP-3/BPS/MEP/TCS and elevated BMIz (P

Vegetation can reduce the adverse effect of climate change. Under the frequent droughts and global warming, it is critical to clear vegetation dynamics and response to climatic variables. However, it is unclear how drought and climatic variables affect vegetation dynamics. In this study, we used the vegetation condition index (VCI) to examine vegetation dynamics in China between 2001 and 2020. The average annual value of VCI had increased during the period of 2001 to 2020, and 90.63% of the study regions had a rising trend in VCI. A large portion of the area had a 3-month time lag between VCI and temperature and precipitation. The time-lag response of VCI to drought was mainly 9 months, with a cumulative effect on drought of 1 month and 12 months. The VCI of evergreen needleleaf forests (ENF), deciduous needleleaf forests (DNF), deciduous broadleaf forests (DBF), and mixed forests (MF) in northern China displayed long time-lag response to drought. Except for DBF in the north and DNF in the central south regions, the cumulative effect of drought on other forest VCI was great in northern China. Except for DNF, DBF, and MF in the central south and DBF in the southwest regions, drought had less time-lag effects on VCI for ENF, evergreen broadleaf forests (EBF), DNF, and MF in southern China. The cumulative effect of drought on VCI of forests in southern China was short. The responses of various types of the grassland and shrubland to drought were similar as those of forests. However, the time-lag effect of drought on grassland and shrubland VCI was shorter than that of forests, making the grassland and shrubland more vulnerable to the short-term cumulative effects of drought. The result of this study can help us understand how the vegetation responds to climate change and drought under global warming scenarios.

The fishery resources in the Yangtze River Estuary (YRE) have declined drastically because of overfishing and environmental changes, leading to ecosystem degradation of the YRE, and bringing numerous rare fish species to the brink of extinction. As a new technology with great prospects for popularization and application, environmental DNA (eDNA) technology has been utilized and proven by many studies to have high potential in revealing the various species' biodiversity. In this study, we analyzed the species composition and diversity of the Yangtze River Estuary using a combination of eDNA technology and bottom trawling approaches, and later, the comparison of both methods. The results showed that combining eDNA technology and bottom trawling, 30 fish species from 7 orders and 11 families were identified. Among the 30 fish species, a total of six species of fish could be observed in catches from both methods. Perciformes were the most abundant and Coilia mystus was the dominant species. According to diversity indices, the eDNA technology reveals significant differences in fish community richness and diversity in the Yangtze River Estuary compared to the bottom trawl. In summary, the eDNA technology is feasible for monitoring fishery resources in the waters of the Yangtze River Estuary, thereby serving as a valuable supplementary tool for conducting comprehensive surveys in this region. Moreover, it holds significant implications and promising prospects for conserving the diverse ecosystem of the YRE in future conservation efforts.

Background: Homer protein homolog 3 (HOMER3), a factor implicated in both physiological and pathological processes, has been studied extensively to determine the relationship between its expression level and the prognosis of various malignancies. However, the significance and clinicopathological role of HOMER3 in colorectal adenocarcinoma remain unclear. Methods: In this study, bioinformatics techniques were used to find the correlation between high HOMER3 expression levels and clinicopathological features of colorectal adenocarcinoma (COAD) patients. Results: Cellular experiments confirmed the differential expression of HOMER3 in tumor cells compared to normal cells. HOMER3 overexpression was significantly associated with COAD staging and carcinoembryonic antigen (CEA) levels. Patients with high HOMER3 expression levels have a poor prognosis. HOMER3 expression levels can be distinguished more accurately between tumor and non-tumor tissues (AUC = 0.634). The HOMER3 gene variation rate in COAD tissue was 0.7 %. Moreover, 16 of the 22 DNA methylation sites in HOMER3 were associated with COAD prognosis. Our findings confirmed that HOMER3 was positively correlated with immune cell infiltration and immune checkpoints (PD-1, CTLA-4, LMTK3, and LAG3) in COAD, Specifically, we will clearly state that while there is statistical significance, the actual strength of the correlations is weak. During KEGG enrichment analysis, HOMER3 was enriched along with DLG4 and SHANK1 in glutamatergic synapses. Additionally, upstream microRNAs that could bind to HOMER3 were predicted. These findings suggest that HOMER3 might be involved in COAD development and immune regulation. Conclusions: HOMER3 acts as a potential biomarker that can facilitate innovative developments in the diagnosis and prognostic assessment of COAD.

Summary: Background: Early detection of nasopharyngeal carcinoma (NPC) poses a significant challenge. The absence of highly sensitive and specific diagnostic biomarkers for nasopharyngeal carcinoma contributes to the unfavourable prognosis of NPC patients. Here, we aimed to establish a non-invasive approach for detecting NPC using circulating cell-free DNA (cfDNA). Methods: We investigated the potential of next-generation sequencing (NGS) of peripheral blood cells as a diagnostic tool for NPC. We collected data on genome-wide nucleosome footprint (NF), 5′-end motifs, fragmentation patterns, CNV information, and EBV content from 553 Chinese subjects, including 234 NPC patients and 319 healthy individuals. Through case–control analysis, we developed a diagnostic model for NPC, and validated its detection capability. Findings: Our findings revealed that the frequencies of NF, fragmentation, and motifs were significantly higher in NPC patients compared to healthy controls. We developed an NPC score based on these parameters that accurately distinguished NPC from non-NPC cases according to the American Joint Committee on Cancer staging system from non-NPC (validation set: area under curve (AUC) = 99.9% (95% CI: 99.8%–100%), se: 98.15%, sp: 100%). This model showed superior performance over plasma EBV DNA. Additionally, the NPC score effectively differentiated between NPC patients and healthy controls, even after clinical treatment. Furthermore, the NPC score was found to be independent of potential confounders such as age, sex, or TNM stage. Interpretation: We have developed and verified a non-invasive approach with substantial potential for clinical application in detecting NPC. Funding: A full list of funding bodies that contributed to this study can be found in Funding section.

Leaf anatomical traits are susceptible to environmental changes and can reflect plant adaptation strategies to the environment. Populus euphratica plays a key role in maintaining ecosystem processes and functions in arid zones, but the variations in leaf anatomical traits of Populus euphratica and their drivers at large scales remain unclear. Here, we investigated 10 leaf anatomical traits of Populus euphratica from 12 sampling sites in the arid zone of China, and explored how they were affected by geographic, climatic, and soil factors. Our results showed that these traits differed significantly between sites (P < 0.05), which was mainly determined by climate and soil factors that together explained 41.4 % of the trait variation. The impact of climate factors is the most critical, as they can directly influence the variation in leaf anatomical traits and indirectly affect trait variation by influencing soil factors. Among them, the max temperature of the warmest month (BIO5), soil available phosphorus (SAP) and soil moisture content (SM) had the most critical effect. Besides, temperature was the major influencing factor for the ratio of spongy tissue thickness to leaf thickness (SR), palisade tissue thickness (PT), the ratio of palisade tissue thickness to spongy tissue thickness (PSR), and the ratio of palisade tissue thickness to leaf thickness (CTR), while soil nutrient was the major influencing factor for leaf thickness (LT), lower epidermis thickness (LET), and spongy tissue thickness (ST). Our results provide important insights into the response of dryland forests to climate change, and suggest that climate warming and declining soil quality may have a stronger effect on Populus euphratica.

Duchenne muscular dystrophy (DMD) is the most prevalent herediatry disease in men, characterized by dystrophin deficiency, progressive muscle wasting, cardiac insufficiency, and premature mortality, with no effective therapeutic options. Here, we investigated whether adenine base editing can correct pathological nonsense point mutations leading to premature stop codons in the dystrophin gene. We identified 27 causative nonsense mutations in our DMD patient cohort. Treatment with adenine base editor (ABE) could restore dystrophin expression by direct A-to-G editing of pathological nonsense mutations in cardiomyocytes generated from DMD patient-derived induced pluripotent stem cells. We also generated two humanized mouse models of DMD expressing mutation-bearing exons 23 or 30 of human dystrophin gene. Intramuscular administration of ABE, driven by ubiquitous or muscle-specific promoters could correct these nonsense mutations in vivo, albeit with higher efficiency in exon 30, restoring dystrophin expression in skeletal fibers of humanized DMD mice. Moreover, a single systemic delivery of ABE with human single guide RNA (sgRNA) could induce body-wide dystrophin expression and improve muscle function in rotarod tests of humanized DMD mice. These findings demonstrate that ABE with human sgRNAs can confer therapeutic alleviation of DMD in mice, providing a basis for development of adenine base editing therapies in monogenic diseases.

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.

In this study, six bimetallic rare earth (RE = La, Ce, Pr, Nd, Sm, Eu) cobalt nitrogen doped carbon nanotubes (RECo-NCNTs) were synthesized with g-C3N4 derivative method. These RECo-NCNTs were characterized by SEM, BET, XPS, XRD and Raman. In addition, their catalytic performances for oxygen reduction reaction (ORR) had also been tested. The introduction of rare earths did not destroy the structure of nanotubes but apparently change their ORR performances. The PrCo-NCNTs showed the significant improvement in catalytic ability for ORR (onset potential of 0.95 V and half-wave potential of 0.79 V), which is very close to that of commercial 20 % Pt/C. Moreover, PrCo-NCNTs exhibits an excellent catalytic stability (no activity decay after 10000st cycles) and an outstanding methanol toxic tolerance. Assembled in metal–air batteries (Zn-air, Al-air and Mg-air), the PrCo-NCNTs electrode also presents high power densities and discharge voltages.

Multimodal imaging, which combines the strengths of two or more imaging modalities to provide complementary anatomical and molecular information, has emerged as a robust technology for enhancing diagnostic sensitivity and accuracy, as well as improving treatment monitoring. Moreover, the application of multimodal imaging in guiding precision tumor treatment can prevent under- or over-treatment, thereby maximizing the benefits for tumor patients. In recent years, several intriguing magneto-optical nanosystems with both magnetic and optical properties have been developed, leading to significant breakthroughs in the field of multimodal imaging and image-guided tumor therapy. These advancements pave the way for precise tumor medicine. This review summarizes various types of magneto-optical nanosystems developed recently and describes their applications as probes for multimodal imaging and agents for image-guided therapeutic interventions. Finally, future research and development prospects of magneto-optical nanosystems are discussed along with an outlook on their further applications in the biomedical field.

Background: Poria acid (PAC) is a triterpene compound found in Poria cocos, a traditional Chinese medicine (TCM). The current study aims to explore the therapeutic effects and potential mechanisms of PAC on the migration and proliferation of human renal cell carcinoma (RCC) cells as well as tumor growth in animal model. Methods: Cell viability and proliferative capacity of normal renal cells and RCC cells were investigated by MTT assay. In addition, 786-O cells were divided into four groups and treated with different concentrations of PAC (0, 20, 40, and 60 μM) for 48 h. Cell scratch test and cell invasion assay were performed to evaluate the effects of PAC on the invasion and migration of RCC cells, respectively. The effects of PAC on apoptosis of RCC cells and expression levels of PI3K/Akt/NF-kB signaling pathway-related biomarkers were investigated using TUNEL staining and Western blotting methods, respectively. Effects of PAC on the inhibitory activity of RCC tumor in mice were evaluated in a 786-O CDX model. Results: The study found that PAC inhibited the viability of RCC cells in a dose-dependent manner, as demonstrated by in vitro cell assays (p 0.05). PAC also significantly inhibited the migration and invasion of RCC via EMT/MMP signaling pathways (p

Endogenous immune defenses provide an intrinsic barrier against external entity invasion. Microplastics in the environment, especially those at the nanoscale (nanoplastics or NPs), may pose latent health risks through direct exposure. While links between nanoplastics and inflammatory processes have been established, detailed insights into how they may perturb the innate immune mechanisms remain uncharted. Employing murine and macrophage (RAW264.7) cellular models subjected to polystyrene nanoplastics (PS-NPs), our investigative approach encompassed an array of techniques: Cell Counting Kit-8 assays, flow cytometric analysis, acridine orange/ethidium bromide (AO/EB) fluorescence staining, cell transfection, cell cycle scrutiny, genetic manipulation, messenger RNA expression profiling via quantitative real-time PCR, and protein expression evaluation through western blotting. The results showed that PS-NPs caused RAW264.7 cell apoptosis, leading to cell cycle arrest, and activated the cGAS-STING pathway. This resulted in NF-κB signaling activation and increased pro-inflammatory mediator expression. Importantly, PS-NPs-induced activation of NF-κB and its downstream inflammatory cascade were markedly diminished after the silencing of the STING gene. Our findings highlight the critical role of the cGAS-STING pathway in the immunotoxic effects induced by PS-NPs. We outline a new mechanism whereby nanoplastics may trigger dysregulated innate immune and inflammatory responses via the cGAS/STING pathway.

INFAT®PLUS, is a sn-2 palmitate enriched fat ingredient intended for infant formula. A battery of toxicological studies was conducted in accordance with the Food Safety Toxicological Assessment GB-15193 (China), to confirm the safety of INFAT®PLUS. In the acute oral toxicity test, the LD50 of INFAT® PLUS was higher than 53.4 g /kg BW and 26.7 g/kg BW for ICR mice and SD rats, respectively. In a subchronic study, INFAT® PLUS was administered by oral gavage to SD rats with maximal daily dose of 8.90 g/kg BW for 90 days. No treatment-related clinical signs or mortalities were observed. The no-observed-adverse-effect level (NOAEL) was set at 8.90 g/kg BW. Similarly, no evidence of genotoxicity effect was noted in several in vitro and in vivo tests, including bacterial reverse mutation (Ames) test, mouse erythrocyte micronucleus test, and chromosome aberration test of mouse spermatogonia/spermatocyte. For the teratogenic evaluations, no toxicological signs were observed in both pregnant SD rat and fetuses, and the NOAEL of INFAT® PLUS was determined to be 8.90 g/kg BW. Based on the obtained results we concluded that INFAT® PLUS was found non-toxic under the experimental conditions, and the totality of the safety data supports its use for infant nutrition.

The evolution of the microstructure, texture and mechanical properties of the Al–Cu–Li alloy sheets by nanoscale TiC + TiB2 ceramic particles during solid solution treatment was systematically investigated by characterization, texture measurements and mechanical performance tests. The yield strength, tensile strength, and elongation of the A1 alloy with the addition of nanoscale TiC + TiB2 ceramic particles under T4P conditions were 312 MPa, 420 MPa, and 21.9%, respectively, which were 35.6%, 27.6%, and 2.8% higher than those of the A0 alloy, respectively. The recrystallization mechanism of both alloys was mainly the particle stimulated nucleation (PSN) mechanism, but the nanoscale TiC + TiB2 in the A1 alloy led to a stronger Zener dragging effect, which hindered the growth of CubeND nuclei, and P-oriented grains dominated. Thus, the A0 alloy sheet was dominated by CubeND components, while the A1 alloy sheet was dominated by P recrystallized grains, which led to the two alloy sheets showing opposite variation trends of the deep drawing properties with increasing solid solution treatment time. The short-time solid-solution process is more likely to provide better properties to the alloy with TiC + TiB2 added particles better properties in terms of various aspects, such as microstructure, mechanical properties, and electrical conductivity.

Background: The prevalence of food allergy (FA) has risen in recent decades, yet there is limited data on the cognition and beliefs of FA among the parents of FA children. Objective: To investigate the prevalence of FA and assess the knowledge and perception of FA among parents of FA children in Wuhan, China. Methods: Online questionnaires were conducted for the parents of 3- to 16-year-old children. They reported symptoms of suspected FA in the screening questionnaire were interviewed for further diagnostic evaluation. All the parents of the suspected FA children completed the subsequent assessments of the knowledge and perception on FA as well as their attitude towards the current online platforms. Results: A total of 1963 children were recruited. The prevalence of self-reported FA was 10.2% (95% CI: 8.1–12.4%) and the physician-diagnosed FA was 6.2% (95% CI: 5.1–7.2%) in 3- to 16-year-olds in Wuhan. And the children with family history (57.9%) were predisposed to developing FA (P＜0.001). The total Brief Illness Perception Questionnaire (B-IPQ) score was 41.3 ± 10.0 among the parents. The B-IPQ scores correlated with symptom onset, but not with family history or other atopic comorbidities. The parents who never sought treatments obtained lower B-IPQ scores on most items compared to those who received treatments. The accuracy rate of the FA knowledge questionnaire was 56.7%. 11.6% of participants reported that children's FA had an impact on their lives. 67.2% of participants had searched information of FA online, among whom 80% expected to obtain professional suggestions on management and prevention strategies of FA from online platform. Conclusion: In 3- to 16-year-old children in Wuhan, the prevalence of self-reported and physician-diagnosed FA was 10.2% and 6.2% respectively. Parents’ knowledge of FA was insufficient and only a small proportion of parents perceived that their lives and careers have been affected considerably by FA of their children. Patient education and current online platforms should be improved among parents of FA children.

Summary: Background: Liver cirrhosis (LC) is the highest risk factor for hepatocellular carcinoma (HCC) development worldwide. The efficacy of the guideline-recommended surveillance methods for patients with LC remains unpromising. Methods: A total of 4367 LCs not previously known to have HCC and 510 HCCs from 16 hospitals across 11 provinces of China were recruited in this multi-center, large-scale, cross-sectional study. Participants were divided into Stage Ⅰ cohort (510 HCCs and 2074 LCs) and Stage Ⅱ cohort (2293 LCs) according to their enrollment time and underwent Tri-phasic CT/enhanced MRI, US, AFP, and cell-free DNA (cfDNA). A screening model called PreCar Score was established based on five features of cfDNA using Stage Ⅰ cohort. Surveillance performance of PreCar Score alone or in combination with US/AFP was evaluated in Stage Ⅱ cohort. Findings: PreCar Score showed a significantly higher sensitivity for the detection of early/very early HCC (Barcelona stage A/0) in contrast to US (sensitivity of 51.32% [95% CI: 39.66%–62.84%] at 95.53% [95% CI: 94.62%–96.38%] specificity for PreCar Score; sensitivity of 23.68% [95% CI: 14.99%–35.07%] at 99.37% [95% CI: 98.91%–99.64%] specificity for US) (P

Understanding an ecosystem’s trophic structure is essential for determining the dynamic interplay between natural and human-induced changes. However, limited knowledge of local food web structures, especially the seasonal trophic structure, hinders our understanding of ecosystem’ stability and dynamics. The offshore waters of southern Zhejiang Province of China are amongst the important fishing waters in China, which are undergoing multiple stressors, such as over-exploitation, global warming, and acidification. This study investigated the seasonal changes in the trophic structure and trophic spectrum of fishery community in this region based on δ13C–δ15N isotope metrics and identified the key types of organisms determining the stability of food webs in different seasons. The results showed that the trophic structure in summer significantly diverged from those of other seasons, with benthivorous fish predominating, higher trophic positions, and feeding specialization of predators. The lowest trophic level and length of the trophic spectrum were observed in spring and were is attribute to the generally smaller size of the species in the community. The winter community showed maximal resource occupancy but the lowest trophic redundancy due to specialized top predators, suggesting higher vulnerability to disturbance. Based on the bi-plot of δ13C–δ15N isotope values, it can be found that Planktivorous and benthivorous fish occupy a key position in the food web structure. Seasonal fluctuations in the trophic structure of fishery community illustrated the diversity and complexity of food webs, and our study provided insights for characterizing marine ecological processes, which were conducive to the restoration of offshore fisheries and the development of management strategies.

Summary: Background: Frail elderly patients with newly diagnosed multiple myeloma (NDMM) have inferior survival and less benefit from high-dose therapies. This prospective study aimed to investigate the efficacy, safety, and quality of life (QoL) of induction treatment of ixazomib/lenalidomide/dexamethasone (IRd) and ixazomib/pegylated liposomal doxorubicin/dexamethasone (IDd) followed by ixazomib/dexamethasone (Id) maintenance therapy in frail, elderly patients with NDMM. Methods: From July 2019 to December 2021, this non-randomized concurrent controlled clinical study enrolled 120 NDMM patients aged ≥65 years with frailty defined by the International Myeloma Working Group (IMWG) frailty score or Mayo geriatric scoring system. The enrolled patients received 6–8 cycles of IRd or IDd followed by Id maintenance therapy for a minimum of 2 years at the discretion of physicians based on patient's clinical characteristics (chiCTR1900024917). Findings: The median age was 71 years and 55% of the patients were males. The overall response rate (ORR) was 82% and 77%, complete response (CR) rate was 25% and 12% for IRd and IDd groups, respectively. The difference in ORR of the Idd group minus the IRd group was −5.36% (95% CI: −18.9% to 8.19%), indicating that the ORR of the IDd group was neither inferior nor non-inferior to the IRd group. After a median follow-up of 34.3 months, the median progression-free survival (PFS) was 21.6 and 13.9 months, OS was not reached and 29.2 months in IRd and IDd groups, respectively. 28 and 33 patients discontinued induction therapy, 20 and 19 discontinued maintenance therapy in IRd and IDd groups, respectively. Cumulative Grade 3 or higher hematological adverse events (AEs) occurred in 10 of the 60 patients (17%) and non-hematological AEs occurred in 15 of the 60 patients (25%) in the IRd group, while 13 of the 60 patients (22%) and 21 of the 60 patients (35%) in the IDd group. Patients were observed with clinically significant improvement in QoL when compared with that at baseline in both IRd and IDd groups by evaluation per cycle (P

Colorectal cancer is a common malignancy with significant rates of morbidity and mortality. A number of factors, including the tumor microenvironment, chemokines, the inflammatory response, have an impact on the development of colorectal cancer. A critical component of the tumor microenvironment is chemokines. Various cell subsets are attracted to the tumor microenvironment through interactions with chemokine receptors. These cells have varying effects on the development of the tumor and the effectiveness of treatment. Additionally, chemokines can participate in inflammatory processes and have effects that are either pro- or anti-tumor. Chemokines can be exploited as targets for medication resistance and treatment in colorectal cancer. In this review, we discuss the expression of chemokines and chemokine receptors, and their relationship with immune cells in the tumor microenvironment. At the same time, we also collect and discuss the significance of chemokines and chemokine receptors in colorectal cancer progression, and their potential as molecular targets for CRC treatment.

This study investigated the effect of intermediate annealing (IA) during a special thermo-mechanical treatment on the microstructure and properties of 7185 Al alloy. The results show that after IA, many sub-structures are formed in the alloy and many particles are precipitated. The particle size increases and the width of the dislocation wall becomes narrower with increasing IA time and temperature. After the second stage of deformation, the dislocations are ordered again and generate micro shear bands (MSBs). The final T6 treated alloy under IA2 process (holding time for 40 min at 400 °C) has good plasticity and corrosion resistance. The tensile strength is 523 MPa, the yield strength is 458 MPa, the elongation is 17.6%, the depth of intergranular corrosion layer is 15.6 μm, and the corrosion grade after 6 and 12 h exfoliation corrosion is N, PC.

Summary: To investigate whole-slide-level prediction in the field of artificial intelligence identification of dMMR/pMMR from hematoxylin and eosin (H&E) in colorectal cancer (CRC), we established a segmentation-based dMMR/pMMR deep learning detector (SPEED). Our model was approximately 1,700 times faster than that of the classification-based model. For the internal validation cohort, our model yielded an overall AUC of 0.989. For the external validation cohort, the model exhibited a high performance, with an AUC of 0.865. The human‒machine strategy further improved the model performance for external validation by an AUC up to 0.988. Our whole-slide-level prediction model provided an approach for dMMR/pMMR detection from H&E whole slide images with excellent predictive performance and less computer processing time in patients with CRC.

The increasing global prevalence of nonalcoholic fatty liver disease (NAFLD) starves for effective therapy, but no agent has been approved yet. We sought to evaluate the therapy of cefminox sodium (CMNX) on fatty accumulation in animal and cell models and explore the underlying mechanisms. The results revealed that CMNX reduced the gain of the liver and alleviated fatty accumulation both in high-fat high-sugar diet (HFHSD) mice's livers and WRL-68 cells. In HFHSD mice's livers and FFAs exposure hepatic cells, ACC1, SREBP-1c, and CYP2E1 were enhanced expression, which were reversed by CMNX treatment. In addition, PPARγ, PPARα, PCK1, and ACSL4 expressions were increased in CMNX-treated WRL-68 cells. These findings suggest that CMNX improves fatty accumulation in HFHSD mice/hepatic cells by restraining fatty acid synthesis and facilitating fatty acid oxidation.

Summary: Background: Sintilimab is an antibody against programmed cell death protein 1. We assessed the efficacy and safety of sintilimab plus albumin-bound (nab)-paclitaxel for the treatment of recurrent or metastatic cervical cancer. Methods: This multicenter, open-label, single-arm, phase II study (ClinicalTrials.gov identifier NCT04341883) enrolled patients with recurrent or metastatic cervical cancer who progressed after at least one line of systemic therapy. The patients received sintilimab 200 mg and nab-paclitaxel 260 mg/m2 body surface area every 3 weeks. The primary endpoint was objective response rate (ORR) assessed by investigators per Response Evaluation Criteria in Solid Tumors version 1.1. Key secondary endpoints were progression-free survival (PFS), overall survival (OS), duration of response (DoR), and safety. Findings: From January 13, 2020 to February 21, 2022, 27 patients were enrolled and received treatment. Median patient age was 50 years (range, 34–68 years). By data cut-off (May 22, 2022), in intention-to-treat population, ORR was 44.4% (95% CI, 24.4%–64.5%). The disease control rate was 88.9% (95% CI, 70.8%–97.6%). Median PFS was 5.2 months (95% CI, 2.7–7.7 months). Median DoR was 3.8 months (95% CI, 0.7–6.9 months), and median OS was 13.1 months (95% CI, 5.8–20.4 months). Treatment-related grade 3 or 4 adverse events (AEs) occurred in 44.4% of the patients, and the most common AEs were decreased neutrophil count (22.2%), decreased white blood cell count (14.8%), and anemia (7.4%). The most common potential immune-related AEs were grade 1–2 hypothyroidism (18.5%), neutropenia (11.1%), and rash (7.4%). Interpretation: Sintilimab plus nab-paclitaxel treatment shows promising antitumor activity and manageable toxicity in patients with advanced cervical cancer. Larger randomized controlled trials are required for validation. Funding: Innovent Biologics Co., Ltd.; Csps Holdings Co., Ltd.

Polar organic chemical integrative sampler (POCIS) represents a promising passive sampling approach for the monitoring of per- and polyfluoroalkyl substances (PFAS) in water. However, the use of polymer membranes has limited the long-term application of conventional POCIS in the field. This work aimed to develop ceramic membranes with controllable PFAS diffusion and mass transfer suitable for PFAS passive sampling applications. Our results showed that PFAS diffusion through ceramic membranes was strongly dependent on membrane structures and properties, particularly membrane porosity. Through controlling membrane fabrication conditions, including particle size and morphology of the membrane material and sintering temperature, ceramic membranes with a range of PFAS diffusivities and mass transfer rates were obtained that varied by over two orders of magnitude, which substantially expanded the limits of polyethersulfone (PES) membranes. Further, modification of ceramic membranes with a thin TiO2 layer did not influence the PFAS mass transfer. Integrative passive samplers consisting of ceramic membranes and a sorbent receiving phase were then developed and assessed through calibration studies. The passive samplers showed linear uptake of PFAS over an extended period of time up to 25 days, and the PFAS sampling rates were affected by both the type of ceramic membranes and the PFAS structures. Results of this study demonstrated the proof-of-concept of the use of ceramic membranes in PFAS passive sampling applications.

Opioids are widely used in clinical practice by activating opioid receptors (OPRs), but their clinical application is limited by a series of side effects. Researchers have been making tremendous efforts to promote the development and application of opioids. Fortunately, recent studies have identified the additional effects of opioids in addition to anesthesia and analgesia, particularly in terms of organ protection against ischemia-reperfusion (I/R) injury, with unique advantages. I/R injury in vital organs not only leads to cell dysfunction and structural damage but also induces acute and chronic organ failure, even death. Early prevention and appropriate therapeutic targets for I/R injury are crucial for organ protection. Opioids have shown cardioprotective effects for over 20 years, especially remifentanil, a derivative of fentanyl, which is a new ultra-short-acting opioid analgesic widely used in clinical anesthesia induction and maintenance. In this review, we provide current knowledge about the physiological effects related to OPR-mediated organ protection, focusing on the protective effect and mechanism of remifentanil on I/R injury in the heart and other vital organs. Herein, we also explored the potential application of remifentanil in clinical I/R injury. These findings provide a theoretical basis for the use of remifentanil to inhibit or alleviate organ I/R injury during the perioperative period and provide insights for opioid-induced human organ protection and drug development.

Asthma is a common disease that seriously threatens public health. With significant developments in bronchoscopy, different interventional pulmonology techniques for refractory asthma treatment have been developed. These technologies achieve therapeutic purposes by targeting diverse aspects of asthma pathophysiology. However, even though these newer techniques have shown appreciable clinical effects, their differences in mechanisms and mutual commonalities still deserve to be carefully explored. Therefore, in this review, we summarized the potential mechanisms of bronchial thermoplasty, targeted lung denervation, and cryoablation, and analyzed the relationship between these different methods. Based on available evidence, we speculated that the main pathway of chronic airway inflammation and other pathophysiologic processes in asthma is sensory nerve-related neurotransmitter release that forms a “neuro-immunity crosstalk” and amplifies airway neurogenic inflammation. The mechanism of completely blocking neuro-immunity crosstalk through dual-ablation of both efferent and afferent fibers may have a leading role in the clinical efficacy of interventional pulmonology in the treatment of asthma and deserves further investigation.

The effects of different cooling rates (0.3–66.2 K/s) on the solidification behavior, microstructural evolution, and mechanical properties of Al–Zn–Mg–Cu alloys during a short-flow process were investigated in detail. With the increasing cooling rate, the grain size first increased, then decreased, and finally, again increased, whereas the secondary dendrite arm spacing and the crystalline phase size were greatly reduced. Relatively high cooling rates (3.4–66.2 K/s) significantly increased elemental micro-segregation in α-Al due to the transition of the solidification mode from near-equilibrium to the Scheil mode. Moreover, the element trapping capacity at the end of solidification was enhanced at high cooling rates, especially for alloy D (66.2 K/s). Hence, the crystalline phase content first increased and then decreased at high cooling rates. During the short-flow process, the refinement of the crystalline phase and dendrites significantly promoted the re-dissolution of the crystalline phase and the elemental diffusion process, leading to improved mechanical properties. The yield strength, the tensile strength, and the elongation were improved from 420 MPa, 460 MPa, and 4.5% for alloy A to 457 MPa, 524 MPa, and 11.3% for alloy D, respectively.

bZIP proteins are widely distributed in eukaryotic organisms and regulate a diverse range of physiological processes. Several bZIP proteins have previously been identified in Ustilaginoidea virens. However, the biological roles of these bZIP proteins in this pathogen are still unknown. Here, one of these bZIP protein coding genes, UvATF21, was functionally characterized. Targeted deletion of UvATF21 resulted in reduced conidiation and pathogenicity despite of the increased vegetative growth. The deletion mutants also significantly decreased the sensitivity to osmotic and oxidative stresses. Interestingly, deletion of UvATF21 exhibited different performances to cell wall integrity stress. These results indicated that UvATF21 played crucial roles in vegetative growth, conidiation, stress response, and full virulence in U. virens.

Soil fungal communities play a crucial role in maintaining and regulating ecosystem functions. The soil fungal structure of different plant communities in forests has been widely studied. However, the drivers of changes in soil fungal community dynamics in warm temperate secondary forests and the pathways influencing them remain to be explored. The Illumina high-throughput sequencing and FUNGuild platform were used to characterize the soil fungal diversity and community composition of six typical plant communities (JM, Juglans mandshurica; PD, Populus davidiana; QM, Quercus mongolica; MB, mixed broadleaf forest; MC, mixed conifer forest; PT, Pinus tabuliformis) in warm temperate secondary forests. The drivers of structural changes in dominant fungal taxa and functional groups were also explored. The pathways through which forest type, soil properties, altitude, climate, and plant diversity affected fungal community structure were further clarified. The results suggested that Ascomycota, Basidiomycota, and Zygomycota dominated the soil fungal communities in warm temperate secondary forests. Except for symbiotic fungi, there was no significant difference in soil fungal α-diversity among forest types. However, there were significant differences in total fungi and functional group community composition. The drivers of diversity and community composition of different soil fungal taxa in warm temperate secondary forests differed. In addition, the partial least squares path model indicated that the composition of soil fungal community in warm temperate secondary forests was directly influenced by forest type and was less dependent on soil properties. Collectively, our study highlights the importance of forest type, soil properties, and other factors (climate, altitude, plant diversity) in driving changes in soil fungal community structure.

Colorectal cancer (CRC) is one of the most common digestive diseases worldwide. It has steadily ascended to the top three cancers in terms of incidence and mortality. The primary cause is the inability to diagnose it at an early stage. Therefore, early detection and diagnosis are essential for colorectal cancer prevention. Although there are now various methods for CRC early detection, in addition to recent developments in surgical and multimodal therapy, the poor prognosis and late detection of CRC still remain significant. Thus, it is important to investigate novel technologies and biomarkers to improve the sensitization and specification of CRC diagnosis. Here, we present some common methods and biomarkers for early detection and diagnosis of CRC, we hope this review will encourage the adoption of screening programs and the clinical use of these potential molecules as biomarkers for CRC early detection and prognosis.

The application of surface texture technology can cut down the friction of journal bearing in internal combustion engines, so as to reduce energy consumption and improve effective. A three-dimensional simulation model of the lubrication characteristics is established so as to investigate the effect of surface texture on the load capacity of journal bearing. The accuracy of the simulation model is verified by comparing with the test. On this basis, through the establishment of a two-dimensional texture unit lubrication characteristics simulation model, the influence law of four different texture shapes, such as triangle, arc, rectangle and trapezoid, and typical structural parameters on the load capacity of the load capacity is studied. Finally, a three-dimensional simulation model of lubrication characteristics of the rectangular textured journal bearing is established. Based on this model, the effect of texture distribution position on the load capacity is studied. It shows that the position of the texture will affect the load capacity. The maximum pressure and load capacity are increased when the texture is in the wedge gap convergence region, but they will decrease when in the divergence region.

The application of surface texture technology can cut down the friction of journal bearing in internal combustion engines, so as to reduce energy consumption and improve effective. A three-dimensional simulation model of the lubrication characteristics is established so as to investigate the effect of surface texture on the load capacity of journal bearing. The accuracy of the simulation model is verified by comparing with the test. On this basis, through the establishment of a two-dimensional texture unit lubrication characteristics simulation model, the influence law of four different texture shapes, such as triangle, arc, rectangle and trapezoid, and typical structural parameters on the load capacity of the load capacity is studied. Finally, a three-dimensional simulation model of lubrication characteristics of the rectangular textured journal bearing is established. Based on this model, the effect of texture distribution position on the load capacity is studied. It shows that the position of the texture will affect the load capacity. The maximum pressure and load capacity are increased when the texture is in the wedge gap convergence region, but they will decrease when in the divergence region.

Purpose: This study aimed to develop quality indicators for the care of older adults with disabilities in long-term care facilities (LTCFs) based on Maslow’s hierarchy of needs. Methods: The draft of the quality indicators was drawn up based on a literature review and research group discussion. The quality indicators were finalized by two rounds of expert consultation (involving 15 experts) using the Delphi method. The Analytic Hierarchy Process was applied to calculate the indicators’ weight. Results: The response rates of the two rounds of consultation were 100% and 93%, and the expert authority coefficients were 0.86 and 0.87. After two rounds of consultation, the expert opinion coordination coefficients of the first-, second- and third-level indicators were 0.42, 0.25, and 0.96, respectively (P

Al–Zn–Mg–Cu alloys were fabricated with water-cooled copper casting. The microstructure of the alloys was characterized by electron probe microanalysis (EPMA), scanning electron microscope (SEM), transmission electron microscopy (TEM), and X-ray diffractometry (XRD). The mechanical properties were studied with by tensile and hardness tests. The results showed an enhanced effect of solid solution strengthening and precipitation strengthening with increased Cu content. The distribution spacing of the grain boundary precipitates (GBPs) increased, but the width of the precipitate-free zone (PFZ) decreased. The process enhanced the strength and plasticity of the alloy. The impact of precipitation strengthening decreased and the grain size and width of the PFZ decreased as the Zn/Mg ratio increased. Thus, the strength of the alloy decreased and its plasticity increased with increasing Zn/Mg ratios.

A 50-year-old male patient was admitted to the Cardiology Department of our hospital for intermittent chest pain for 9 days. Coronary angiography showed approximately 70% stenosis in the middle part of the left anterior descending branch. When the procedure was about to end, the patient experienced dyspnea, facial flushing and fall of blood pressure suddenly. At this time, the angiography showed severe spasm and stenosis of the left coronary artery. With antianaphylaxis, pressor therapy, fluid resuscitation and intracoronary administration of nitroglycerin, the left coronary spasm was relieved. A diagnosis of type II kounis syndrome induced by ioversol with cardiogenic shock was made.

Seminal work in the 1990’s found alterations in the cerebellum of individuals with social disorders including autism spectrum disorder and schizophrenia. In neurotypical populations, distinct portions of the posterior cerebellum are consistently activated in fMRI studies of social cognition and it has been hypothesized that the cerebellum plays an essential role in social cognition, particularly in theory of mind. Here we review the lesion literature and find that the effect of cerebellar damage on social cognition is strongly linked to the age of insult, with dramatic impairments observed after prenatal insult, strong deficits observed after childhood damage, and mild and inconsistent deficits observed following damage to the adult cerebellum. To explain the developmental gradient, we propose that early in life, the forward model dominates cerebellar computations. The forward model learns and uses errors to help build schemas of our interpersonal worlds. Subsequently, we argue that once these schemas have been built up, the inverse model, which is the foundation of automatic processing, becomes dominant. We provide suggestions for how to test this, and also outline directions for future research.

The tumor microenvironment (TME) is a well-recognized system that plays an essential role in tumor initiation, development, and progression. Intense intercellular communication between tumor cells and other cells (especially macrophages) occurs in the TME and is mediated by cell-to-cell contact and/or soluble messengers. Emerging evidence indicates that noncoding RNAs (ncRNAs) are critical regulators of the relationship between cells within the TME. In this review, we provide an update on the regulation of ncRNAs (primarily micro RNAs [miRNAs], long ncRNAs [lncRNAs], and circular RNAs [circRNAs]) in the crosstalk between macrophages and tumor cells in hepatocellular carcinoma (HCC). These ncRNAs are derived from macrophages or tumor cells and act as oncogenes or tumor suppressors, contributing to tumor progression not only by regulating the physiological and pathological processes of tumor cells but also by controlling macrophage infiltration, activation, polarization, and function. Herein, we also explore the options available for clinical therapeutic strategies targeting crosstalk-related ncRNAs to treat HCC. A better understanding of the relationship between macrophages and tumor cells mediated by ncRNAs will uncover new diagnostic biomarkers and pharmacological targets in cancer.

Additive and subtractive hybrid manufacturing (ASHM) technology has attracted extensive attention in industry and academia because of its vast design freedom and surface accuracy. The powder bed fusion (PBF) process has high forming accuracy, the ASHM of PBF process is more suitable for integrated precision manufacturing of components with complex internal structures. However, existing process planning for ASHM are not suitable for the ASHM of PBF process because of the limitation by the powder bed. This research work focused on planning the process for the ASHM of the PBF process, while dividing it into three stages. Firstly, a model adaptive compensation algorithm is proposed to retain the finish machining allowance. Then, considering tool accessibility and constraint of the powder bed, the compensation model is decomposed into several sub-models and the hybrid manufacturing of sub-models in the sequence of construction. Finally, some unprocessed parts of the internal structure could be re-process after removing the parts from the powder bed. Combined with experiments and examples, this hybrid manufacturing process planning can provide technical support for the integrated precision manufacturing of components with a complex internal structure based on the ASHM of the PBF process.

Summary: There are currently no effective therapies for COVID-19 or antivirals against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and vaccines appear less effective against new SARS-CoV-2 variants; thus, there is an urgent need to understand better the virulence mechanisms of SARS-CoV-2 and the host response to develop therapeutic agents. Herein, we show that host Neu1 regulates coronavirus replication by controlling sialylation on coronavirus nucleocapsid protein. Coronavirus nucleocapsid proteins in COVID-19 patients and in coronavirus HCoV-OC43-infected cells were heavily sialylated; this sialylation controlled the RNA-binding activity and replication of coronavirus. Neu1 overexpression increased HCoV-OC43 replication, whereas Neu1 knockdown reduced HCoV-OC43 replication. Moreover, a newly developed Neu1 inhibitor, Neu5Ac2en-OAcOMe, selectively targeted intracellular sialidase, which dramatically reduced HCoV-OC43 and SARS-CoV-2 replication in vitro and rescued mice from HCoV-OC43 infection-induced death. Our findings suggest Neu1 inhibitors could be used to limit SARS-CoV-2 replication in patients with COVID-19, making Neu1 a potential therapeutic target for COVID-19 and future coronavirus pandemics.

Silymarin, a milk thistle extract, has anti-inflammatory, immunomodulatory, anti-lipid peroxidative, anti-fibrotic, anti-oxidative, and anti-proliferative properties. Silymarin exhibits not only anti-cancer functions through modulating various hallmarks of cancer, including cell cycle, metastasis, angiogenesis, apoptosis, and autophagy, by targeting a plethora of molecules, but also plays protective roles against chemotherapy-induced toxicity, such as nephrotoxicity, hepatotoxicity, cardiotoxicity, and neurotoxicity. One of the problems of silymarin in (pre)clinical studies is its poor water solubility, leading to low intestinal absorption and, therefore, low bioavailability. To address these challenges, silymarin nanoformulations have emerged with added benefits, including excellent drug loading, sustained release, improved cellular uptake, and targeting tumor cells. Besides the chemical and biological properties, here we summarized the anti-cancer functions and the mechanism of action of silymarin in both free form and nanoformulations and its protective roles against chemotherapy-induced toxicity.