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The effect of no- and reduced tillage (NT/RT) on greenhouse gas (GHG) emission was highly variable and may depend on other agronomy practices. However, how the other practices affect the effect of NT/RT on GHG emission remains elusive. Therefore, we conducted a global meta-analysis (including 49 papers with 196 comparisons) to assess the effect of five options (i.e. cropping system, crop residue management, split application of N fertilizer, irrigation, and tillage duration) on the effect of NT/RT on CH4 and N2O emissions from agricultural fields. The results showed that NT/RT significantly mitigated the overall global warming potential (GWP) of CH4 and N2O emissions by 6.6% as compared with conventional tillage (CT). Rotation cropping systems and crop straw remove facilitated no-tillage (NT) to reduce the CH4, N2O, or overall GWP both in upland and paddy field. NT significantly mitigated the overall GWP when the percentage of basal N fertilizer (PBN) >50%, when tillage duration > 10 years or rainfed in upland, while when PBN

Ventricular septal defect (VSD), one of the most common types of congenital heart disease (CHD), results from a combination of environmental and genetic factors. Recent studies demonstrated that microRNAs (miRNAs) are involved in development of CHD. This study was to characterize the expression of miRNAs that might be involved in the development or reflect the consequences of VSD.MiRNA microarray analysis and reverse transcription-polymerase chain reaction (RT-PCR) were employed to determine the miRNA expression profile from 3 patients with VSD and 3 VSD-free controls. 3 target gene databases were employed to predict the target genes of differentially expressed miRNAs. miRNAs that were generally consensus across the three databases were selected and then independently validated using real time PCR in plasma samples from 20 VSD patients and 15 VSD-free controls. Target genes of validated 8 miRNAs were predicted using bioinformatic methods.36 differentially expressed miRNAs were found in the patients with VSD and the VSD-free controls. Compared with VSD-free controls, expression of 15 miRNAs were up-regulated and 21 miRNAs were downregulated in the VSD group. 15 miRNAs were selected based on database analysis results and expression levels of 8 miRNAs were validated. The results of the real time PCR were consistent with those of the microarray analysis. Gene ontology analysis indicated that the top target genes were mainly related to cardiac right ventricle morphogenesis. NOTCH1, HAND1, ZFPM2, and GATA3 were predicted as targets of hsa-let-7e-5p, hsa-miR-222-3p and hsa-miR-433.We report for the first time the circulating miRNA profile for patients with VSD and showed that 7 miRNAs were downregulated and 1 upregulated when matched to VSD-free controls. Analysis revealed target genes involved in cardiac development were probably regulated by these miRNAs.

Abstract This retrospective study analyzed a large population of gastric cancer (GC) patients treated between 2010 and 2015 to investigate the clinical features and predictive risk factors for developing secondary primary malignancies (SPMs). The cumulative incidence of SPM was assessed using Kaplan–Meier analysis. Competing risk analyses adjusted for mortality were conducted using stratified Cox proportional hazard regression models and multivariate analyses to identify independent predictors of SPM. A total of 3289 out of 167,747 GC patients were included in the analytic cohort, with 155 patients diagnosed with SPM. Patients whose histologic type other than adenocarcinomas (AC) and signet ring cell carcinoma (SRCC) emerged as an independent risk factor for developing SPM (hazard ratio [HR] 2.262, 95% confidence interval [CI] 1.146–4.465, P = 0.019) in multivariate Cox regression analysis. The surgical method, including biopsy/local excision (HR 2.3, [CI] 1.291–4.095, P = 0.005) and subtotal/total resection ([HR] 1.947, [CI] 1.028–3.687, P = 0.041), chemotherapy ([HR] 1.527, [CI] 1.006–2.316, P = 0.047), and histologic type ([HR] 2.318, [CI] 1.193–4.504, P = 0.013)), were identified as independent risk factors in the competitive risk model. Subgroup analyses, stratified by chemotherapy, revealed an increased risk of SPM among older patients. Furthermore, a nomogram was developed and internally validated to predict the cumulative incidence of SPM in GC patients (C-index = 0.73 for 72 months). These findings suggested that in specific histologic types of GC, the lymph node infiltration region missed after local surgical resection, and concomitant chemotherapy would have an increased risk of SPM for cancer survivors.

Abstract Adipose tissue plays critical roles in an individual’s aging process. In this research, we use single-nucleus RNA sequencing to create highly detailed transcriptional maps of subcutaneous adipose tissue and visceral adipose tissue in young and aged mice. We comprehensively identify the various cell types within the white adipose tissue of mice, our study has elucidated seven distinct cell types within this tissue. Further analyses focus on adipocytes, fibro-adipogenic progenitors, and immune cells, revealing age-related declines in the synthetic metabolic activity of adipocytes, diminished immune regulation, and reduced maturation or proliferation of fibroblasts in undifferentiated adipocytes. We confirm the presence of distinct subpopulations of adipocytes, highlighting decreases in adipogenesis subgroups due to aging. Additionally, we uncover a reduction in immune cell subpopulations, driven by age-associated immune system dysregulation. Furthermore, pseudo-time analyses indicate that Adipocyte1 represents the 'nascent' phase of adipocyte development, while Adipocyte2 represents the 'mature' phase. We use cell–cell interaction to explore the age-dependent complexities of the interactions between FAPs and adipocytes, and observed increased expression of the inflammation-related Retn-Tlr4 interaction in older mice, while the anti-inflammatory Angpt1-Tek interaction was only detected in young mice. These transcriptional profiles serve as a valuable resource for understanding the functional genomics underlying metabolic disorders associated with aging in human adipose tissue.

Abstract The utilization of low-energy photons in light-driven reactions is an effective strategy for improving the efficiency of solar energy conversion. In nature, photosynthetic organisms use chlorophylls to harvest the red portion of sunlight, which ultimately drives the reduction of CO2. However, a molecular system that mimics such function is extremely rare in non-noble-metal catalysis. Here we report a series of synthetic fluorinated chlorins as biomimetic chromophores for CO2 reduction, which catalytically produces CO under both 630 nm and 730 nm light irradiation, with turnover numbers of 1790 and 510, respectively. Under appropriate conditions, the system lasts over 240 h and stays active under 1% concentration of CO2. Mechanistic studies reveal that chlorin and chlorinphlorin are two key intermediates in red-light-driven CO2 reduction, while corresponding porphyrin and bacteriochlorin are much less active forms of chromophores.

Abstract In response to abundant freshwater input from rainfall and river discharge, the northern Bay of Bengal (BoB) is featured by low sea surface salinity (SSS) and strong intraseasonal variability (ISV). This study investigates the characteristic and dynamic mechanisms of SSS ISV in the northern BoB based on satellite observations and the output of Simple Ocean Data Assimilation (SODA). The strong SSS ISV is mainly concentrated near the mouth of the Ganges–Brahmaputra River and along the east coast of India, where the horizontal salinity gradient varies greatly. SSS ISV in the northern BoB is notably in phase with freshwater transport, which peaks from July to November. The contribution of riverine freshwater is significant both geographically and temporally. The SSS budget analysis indicates that the horizontal advection plays a dominant role in SSS ISV. Once currents cross the salinity field, large horizontal advection anomalies become important and favor SSS ISV. Altered SSS patterns can impact water density, potentially influencing the strength and direction of currents. This, in turn, may have cascading effects on local and regional climate patterns.

Abstract Laser Sintering (LS) is a type of Additive Manufacturing (AM) exploiting laser processing of polymeric particles to produce 3D objects. Because of its ease of processability and thermo-physical properties, polyamide-12 (PA-12) represents ~95% of the polymeric materials used in LS. This constrains the functionality of the items produced, including limited available colours. Moreover, PA-12 objects tend to biofoul in wet environments. Therefore, a key challenge is to develop an inexpensive route to introduce desirable functionality to PA-12. We report a facile, clean, and scalable approach to modification of PA-12, exploiting supercritical carbon dioxide (scCO2) and free radical polymerizations to yield functionalised PA-12 materials. These can be easily printed using commercial apparatus. We demonstrate the potential by creating coloured PA-12 materials and show that the same approach can be utilized to create anti-biofouling objects. Our approach to functionalise materials could open significant new applications for AM.

Abstract Optimization of magnetic coupling mechanism is an important way to improve the performance of a dynamic wireless power transfer system. Inspired by the common radial magnetic core for circular coils, a new radial magnetic core for rectangular coils is adopt. Through simulation and experimental results comparison, which has higher coupling coefficient with the same core area. Combined with the magnetic circuit analysis, the magnetic flux leakage and conduction regions are divided into magnetic fluxes with different shapes, which magnetic resistances are calculated respectively. Based on the simulation results, parameter distributions of fluxes under different conditions are obtained. Therefore, the expressions of the coupling coefficient k of the adopt magnetic cores and coils and the design parameters of coils and cores are obtained. Taking the maximum k and the minimum rate of change of coupling coefficient with 100 mm displacement as the optimization objectives, a multi-objective optimization solution is carried out by using NSGA-II algorithm. The coil optimization scheme is obtained and verified by experiments. k and Δk are 0.442 and 6.8% respectively, and the errors are less than 5%. In the optimization process, there is no simulation model constructed. The optimization modeling combined of magnetic field segmentation method and parameter fitting has lower complexity and calculation time of optimization.

Abstract Early and accurate diagnosis of focal liver lesions is crucial for effective treatment and prognosis. We developed and validated a fully automated diagnostic system named Liver Artificial Intelligence Diagnosis System (LiAIDS) based on a diverse sample of 12,610 patients from 18 hospitals, both retrospectively and prospectively. In this study, LiAIDS achieved an F1-score of 0.940 for benign and 0.692 for malignant lesions, outperforming junior radiologists (benign: 0.830-0.890, malignant: 0.230-0.360) and being on par with senior radiologists (benign: 0.920-0.950, malignant: 0.550-0.650). Furthermore, with the assistance of LiAIDS, the diagnostic accuracy of all radiologists improved. For benign and malignant lesions, junior radiologists’ F1-scores improved to 0.936-0.946 and 0.667-0.680 respectively, while seniors improved to 0.950-0.961 and 0.679-0.753. Additionally, in a triage study of 13,192 consecutive patients, LiAIDS automatically classified 76.46% of patients as low risk with a high NPV of 99.0%. The evidence suggests that LiAIDS can serve as a routine diagnostic tool and enhance the diagnostic capabilities of radiologists for liver lesions.

Polymer-derived ceramics (PDCs) can be used in wide applications due to their high hardness and stable chemical properties. However, these characteristics lead to the challenging controllable deformation of additively manufactured PDCs. Herein, ultraviolet (UV)-curable polymer precursors were developed and a pyrolysis strategy was proposed. Through the two-stage folding-assisted pyrolysis strategy, the printed precursor can deform with programmable shape to attain 4D printing. Regardless of very low precursor ceramic yield (13.5 wt%), leading to a huge pyrolysis shrinkage (59.91%), the SiOC ceramics with dense, crack-free complex programmable shapes were successfully obtained. The working mechanism of the two-stage pyrolysis was explained by characterising and analysing the chemical bond status. The effects of unpyrolyzed, first-pyrolysed and second-pyrolysed samples on the skeleton shrinkage, weight loss, and mechanical properties were also studied and compared. The proposed strategy provides a feasible way for the preparation of PDCs with complex programmable shapes that are dense and crack-free by photopolymerization 4D printing.

Abstract Haplotype‐resolved 3D chromatin architecture related to allelic differences in avian skeletal muscle development has not been addressed so far, although chicken husbandry for meat consumption has been prevalent feature of cultures on every continent for more than thousands of years. Here, high‐resolution Hi‐C diploid maps (1.2‐kb maximum resolution) are generated for skeletal muscle tissues in chicken across three developmental stages (embryonic day 15 to day 30 post‐hatching). The sequence features governing spatial arrangement of chromosomes and characterize homolog pairing in the nucleus, are identified. Multi‐scale characterization of chromatin reorganization between stages from myogenesis in the fetus to myofiber hypertrophy after hatching show concordant changes in transcriptional regulation by relevant signaling pathways. Further interrogation of parent‐of‐origin‐specific chromatin conformation supported that genomic imprinting is absent in birds. This study also reveals promoter‐enhancer interaction (PEI) differences between broiler and layer haplotypes in skeletal muscle development‐related genes are related to genetic variation between breeds, however, only a minority of breed‐specific variations likely contribute to phenotypic divergence in skeletal muscle potentially via allelic PEI rewiring. Beyond defining the haplotype‐specific 3D chromatin architecture in chicken, this study provides a rich resource for investigating allelic regulatory divergence among chicken breeds.

Summary: Immunotherapy has revolutionized cancer treatment but its efficacy depends on a robust immune response in the tumor. Silencing of the tumor suppressor p53 is common in tumors and can affect the recruitment and activation of different immune cells, leading to immune evasion and poor therapy response. We found that the p53 activating stapled peptide MDM2/MDMX inhibitor Sulanemadlin (ALRN-6924) inhibited p53 wild-type cancer cell growth in vitro and in vivo. In mice carrying p53 wild-type CT26.WT tumors, monotherapy with the PD-1 inhibitor DX400 or Sulanemadlin delayed tumor doubling time by 50% and 37%, respectively, while combination therapy decreased tumor doubling time by 93% leading to an increased median survival time. Sulanemadlin treatment led to increased immunogenicity and combination treatment with PD-1 inhibition resulted in an increased tumor infiltration of lymphocytes. This combination treatment strategy could potentially turn partial responders into responders of immunotherapy, expanding the patient target group for PD-1-targeting immunotherapy.

Abstract Gallstone disease (GSD) is thought to be associated with the risk of coronary heart disease (CHD) or acute myocardial infarction (AMI), which may be due to abnormal cholesterol metabolism. We used multiple Mendelian randomization (MR) methods based on publicly available genome-wide association study data to assess whether this association is genetically causal and to search for loci driving causality. Pooled data for GSD were obtained from FinnGen Biobank and Biobank Japan, while CHD and AMI were obtained as pooled data from the CARDIoGRAMplusC4D consortium. In this MR study, we found a significant negative causal effect of genetic susceptibility to GSD on AMI in the Finnish population, but no causal effect was found on CHD. This causal effect was not confounded by reverse causality and the same findings were obtained in the Japanese population. Furthermore, the negative causal effect of GSD on AMI risk may be driven by the rs4245791-regulated ABCG5/8 protein. In conclusion, the results of this MR study support a negative causal effect of GSD on AMI and suggest that rs4245791 is the causal driver locus of this effect, which provides new ideas and evidence for the prevention and etiologic study of AMI in patients with GSD.

Abstract Using an adult female miniature pig model with diet-induced weight gain/weight loss, we investigated the regulatory mechanisms of three-dimensional (3D) genome architecture in adipose tissues (ATs) associated with obesity. We generated 249 high-resolution in situ Hi-C chromatin contact maps of subcutaneous AT and three visceral ATs, analyzing transcriptomic and chromatin architectural changes under different nutritional treatments. We find that chromatin architecture remodeling underpins transcriptomic divergence in ATs, potentially linked to metabolic risks in obesity development. Analysis of chromatin architecture among subcutaneous ATs of different mammals suggests the presence of transcriptional regulatory divergence that could explain phenotypic, physiological, and functional differences in ATs. Regulatory element conservation analysis in pigs and humans reveals similarities in the regulatory circuitry of genes responsible for the obesity phenotype and identified non-conserved elements in species-specific gene sets that underpin AT specialization. This work provides a data-rich tool for discovering obesity-related regulatory elements in humans and pigs.

Environmental seasonality can promote the evolution of larger brains through cognitive and behavioral flexibility but can also hamper it when temporary food shortage is buffered by stored energy. Multiple hypotheses linking brain evolution with resource acquisition and allocation have been proposed for warm-blooded organisms, but it remains unclear how these extend to cold-blooded taxa whose metabolism is tightly linked to ambient temperature. Here, we integrated these hypotheses across frogs and toads in the context of varying brumation (hibernation) durations and their environmental correlates. We showed that protracted brumation covaried negatively with brain size but positively with reproductive investment, likely in response to brumation-dependent changes in the socio-ecological context and associated selection on different tissues. Our results provide novel insights into resource allocation strategies and possible constraints in trait diversification, which may have important implications for the adaptability of species under sustained environmental change.

Abstract Activation of p53 by small molecule MDM2 inhibitors can induce cell cycle arrest or death in p53 wildtype cancer cells. However, cancer cells exposed to hypoxia can develop resistance to other small molecules, such as chemotherapies, that activate p53. Here, we evaluated whether hypoxia could render cancer cells insensitive to two MDM2 inhibitors with different potencies, nutlin-3a and navtemadlin. Inhibitor efficacy and potency were evaluated under short-term hypoxic conditions in human and mouse cancer cells expressing different p53 genotypes (wild-type, mutant, or null). Treatment of wild-type p53 cancer cells with MDM2 inhibitors reduced cell growth by > 75% in hypoxia through activation of the p53–p21 signaling pathway; no inhibitor-induced growth reduction was observed in hypoxic mutant or null p53 cells except at very high concentrations. The concentration of inhibitors needed to induce the maximal p53 response was not significantly different in hypoxia compared to normoxia. However, inhibitor efficacy varied by species and by cell line, with stronger effects at lower concentrations observed in human cell lines than in mouse cell lines grown as 2D and 3D cultures. Together, these results indicate that MDM2 inhibitors retain efficacy in hypoxia, suggesting they could be useful for targeting acutely hypoxic cancer cells.

Abstract Sepsis‐induced muscle atrophy often increases morbidity and mortality in intensive care unit (ICU) patients, yet neither therapeutic target nor optimal animal model is available for this disease. Here, by modifying the surgical strategy of cecal ligation and puncture (CLP), a novel sepsis pig model is created that for the first time recapitulates the whole course of sepsis in humans. With this model and sepsis patients, increased levels of the transcription factor zinc finger BED‐type containing 6 (ZBED6) in skeletal muscle are shown. Protection against sepsis‐induced muscle wasting in ZBED6‐deficient pigs is further demonstrated. Mechanistically, integrated analysis of RNA‐seq and ChIP‐seq reveals dedicator of cytokinesis 3 (DOCK3) as the direct target of ZBED6. In septic ZBED6‐deficient pigs, DOCK3 expression is increased in skeletal muscle and myocytes, activating the RAC1/PI3K/AKT pathway and protecting against sepsis‐induced muscle wasting. Conversely, opposite gene expression patterns and exacerbated muscle wasting are observed in septic ZBED6‐overexpressing myotubes. Notably, sepsis patients show increased ZBED6 expression along with reduced DOCK3 and downregulated RAC1/PI3K/AKT pathway. These findings suggest that ZBED6 is a potential therapeutic target for sepsis‐induced muscle atrophy, and the established sepsis pig model is a valuable tool for understanding sepsis pathogenesis and developing its therapeutics.

Abstract Deciphering variations in chromosome conformations based on bulk three‐dimensional (3D) genomic data from heterogenous tissues is a key to understanding cell‐type specific genome architecture and dynamics. Surprisingly, computational deconvolution methods for high‐throughput chromosome conformation capture (Hi‐C) data remain very rare in the literature. Here, a deep convolutional neural network (CNN), deconvolve bulk Hi‐C data (deCOOC) that remarkably outperformed all the state‐of‐the‐art tools in the deconvolution task is developed. Interestingly, it is noticed that the chromatin accessibility or the Hi‐C contact frequency alone is insufficient to explain the power of deCOOC, suggesting the existence of a latent embedded layer of information pertaining to the cell type specific 3D genome architecture. By applying deCOOC to in‐house‐generated bulk Hi‐C data from visceral and subcutaneous adipose tissues, it is found that the characteristic chromatin features of M2 cells in the two anatomical loci are distinctively bound to different physiological functionalities. Taken together, deCOOC is both a reliable Hi‐C data deconvolution method and a powerful tool for functional extraction of 3D genome architecture.

The authors developed an optical-fiber-based photoacoustic endoscope for gastroenterology. It can noninvasively view the internal vascular structures and visualize the hemodynamic response in a lesion.

Measurement(s) mRNA Expression Technology Type(s) spatial transcriptomics Sample Characteristic - Organism Homo sapiens

Cancer cells and macrophages can infiltrate and remodel the extracellular matrix (ECM). Here, by using native basement membrane-interstitial matrix explants as model and live cell confocal imaging, the authors reveal divergent mechanisms used by cancer cells and macrophages to penetrate native basement membrane barriers.

Fifteen rhodamine B hydrazide hydrazone (RhBHH) derivatives (compounds a–o) with various substituent groups at different position and their photochromic property triggered by Cu2+ were studied to illustrate the structure photochromic response relationship (SPRR). Three of them (compounds f–h) with a para-position hydroxyl group and two meta-position halogen substituents display Cu2+-triggered photochromic which is significantly different from the previous reports. It was found that halogen atoms, which were generally considered to have no remarkable regulation effect, exhibited great influences on the photochromic behaviour of RhBHH derivatives. Detail photochromic properties of the developed photochromic system were revealed by using compound g as the model substrate, and only Cu2+ displayed high selective trigger effect. Good reversible photochromic phenomenon was observed after stimulated with visible light irradiation and dark (or heat) bleaching consecutively. Furthermore, this photochromic system could be used in the preparation of photochromic glass, special security ink, molecular logic gate and two-dimensional code for security information storage.

The geographic variation in life-history traits of organisms and the mechanisms underlying adaptation are interesting ideas in evolutionary biology. This study investigated age and body size of the Asian common toad (Duttaphrynus melanostictus) among five populations along a geographical gradient. We found that geographical variation in age was non-significant among populations but there was a significant and positive correlation between mean age and body size. Although the body size values at 1043 m are quite different from other sites, after controlling for age effects, there was a significant positive correlation between altitude and body size. Our findings followed the predictions of Bergmann’s rule, suggesting that the body size of D. melanostictus is potentially influenced by the low air temperatures at higher altitudes.

Seasonal patterns of marine net primary production (NPP) are crucial for understanding the marine ecosystem and biogeochemical cycles. Uncoupling of seasonal variations between NPP and phytoplankton chlorophyll-a over different areas has attracted much attention. In this study, following a review of previous studies, monthly climatological NPP data from 2003 to 2020, estimated using the Size-fractioned Phytoplankton Pigment Absorption (aph)-based NPP Model (SABPM), were selected to study the seasonal variability of NPP in the South China Sea (SCS). Results showed the spatial differences of NPP seasonality and its departures from climatology in extreme El Niño-Southern Oscillation (ENSO) and Indian Ocean Dipole (IOD) years. Cluster analysis for climatological monthly data identified significant differences of NPP seasonality in five typical regions. In coastal regions along the northern SCS and off eastern Vietnam, NPP exhibited the most obvious seasonal cycle with maximum (minimum) values in summer (winter), attributable mainly to river discharge and summer upwelling. In regions off northwestern Luzon and coast of southern SCS, NPP showed peaks in winter, which were related to strong mixing and upwelling. In northwestern SCS, NPP was high during May–September in phase with sea surface temperature and the primary controlling factors were found to be shallow nutricline depth and wind-driven mixing. Owing to the deep nutricline depth in the central basin, NPP exhibited little seasonal variability; only a weak signal was observed in spring in phase with photosynthetically active radiation. Local dynamics on regulating the nutrient supply and light availability contribute to these regional differences in NPP seasonality, which could also be affected by extreme climate events. The largest anomalies of the NPP seasonal cycle coincide with 2015/2016 ENSO and super IOD in 2020. During these events, enhanced (weakened) westerly winds caused fall (rise) of SLA and increase (decrease) of NPP in coastal regions along the northern SCS and that off eastern Vietnam. Overall, the aph-based model shows a new perspective to study the spatiotemporal variations of NPP in the SCS.

The domestic chicken Gallus gallus domesticus is a classic model for the study of folliculogenesis. Here the authors integrate multi-omics analyses characterizing the dynamic transcriptome and chromatin architecture in granulosa cells during chicken folliculogenesis.

Metabolic conditions associated with alterations of the gut microbiome, such as obesity and diabetes, predispose to gallstone disease. Here the authors demonstrate that the gut microbiome, in particular the genus Desulfovibrionale, contribute to gallstone formation in mice.

Summary: Homozygous familial hypercholesterolemia (HoFH) is an extremely rare metabolism disorder usually caused by low-density lipoprotein receptor (LDLR) mutations. LDLR genotype is commonly known to determine blood concentrations of LDL cholesterol. However, effects of LDLR genotype on holistic metabolome remain unclear. Herein, we present metabolomic, genetic, and clinical datasets from a large multi-center panel of 142 patients with LDLR-mutated HoFH. We found that true homozygotes and compound heterozygotes showed few differences in clinical and metabolomic phenotypes. Compared with defective/defective mutation carriers, patients carrying one or two null mutation showed profound alterations in clinical laboratory lipids and serum cholesterol esters, lysophosphocholines, bile acids, and amino acids. Importantly, these altered metabolites are implicated in multiple biochemical reactions and associated with LDL cholesterol. This study extends the first map of different LDLR genotypes influencing the metabolome and suggests that the small-molecule metabolites serve as potential targets to mitigate the deleterious impact of LDLR mutations on HoFH.

In view of the deformation and instability law of hard roof without side filling retaining roadway, based on the systematic construction and analysis of the force and bearing model of roadway retaining structure, this article proposes the control mechanical model and calculation method of roadway retaining, which takes the anchor roof beam and the key block above to form the cantilever beam together, with the anchor solid coal side as the foundation support. The research and practice show that under the condition of hard roof, the mechanical connection between the roof of gob-side entry retaining and the roof of mining face can be effectively cut off so as to improve the structural configuration and mechanical properties of the lateral roof of gob-side entry retaining and the key blocks above, and reduce the damage of upper strata subsidence and goaf roof collapse to the roof of roadway. Then, through strengthening by anchor to significantly enhance solid coal side, bearing capacity of anchor roof beam, so they can share the upper strata caused by the load and deflection of mining influence, in addition, the roof bolting, reinforcement of waste rock bolting supporting role can better improve the structure for stability, adaptability and engineering applicability, this method is successfully applied in engineering practice. It is worthy of further research and application.

Positioning photosensitizer and catalyst complexes in photocatalytic systems is a promising method to direct desired electron transfers. Here, authors employ a dynamic coordinative interaction between molecular components to improve CO2 photoreduction to CO with a high quantum efficiency of 27.9%.

Optoacoustic sensing applications are limited by weak electrostrictive force. Here, the authors induce photothermally acoustic vibrations with a focused pulsed laser, and via scanning demonstrate sensing of acoustic impedance at 10 µm spatial resolution, allowing for visualisation of diffusion dynamics.

A comprehensive transcriptomic survey of the pig could enable mechanistic understanding of tissue specialization and accelerate its use as a biomedical model. Here the authors characterize four distinct transcript types in 31 adult pig tissues to dissect their distinct structural and transcriptional features and uncover transcriptomic variability related to tissue physiology.

Designing highly efficient chromophores comprising earth-abundant elements is essential for both light harvesting and electron transfer reactions. Here, authors prepare a copper purpurin complex that shows enhanced photocatalytic activity for CO2 reduction to CO with a high selectivity.

Interpretation of Computed Tomography Angiography for intracranial aneurysm diagnosis can be time-consuming and challenging. Here, the authors present a deep-learning-based framework achieving improved performance compared to that of radiologists and expert neurosurgeons.

The lithofacies assemblages in the lacustrine shale of the Shahejie Formation in the Dongying Depression have different compositions due to the complex depositional climate, lake water conditions, and sediment supply. Hence, the lithofacies types and depositional conditions were analyzed based on parasequence division and lithofacies classification. According to gamma ray integrated prediction error filter analysis (INPEFA), handheld x-ray fluorescence (XRF) measurements, mineral composition, total organic carbon (TOC) content, and sedimentary structures, six parasequences (P1–P6 from bottom to top) were identified, and seven lithofacies are recognized: (1) organic-poor thin-bedded calcareous mudstone, (2) organic-poor laminated calcareous mudstone, (3) intermediate-organic laminated calcareous mudstone, (4) organic-rich laminated calcareous mudstone, (5) organic-rich calcareous shale, (6) organic-rich laminated carbonate-bearing mudstone, and (7) laminated silty mudstone. When the climate became warm and wet, the water level of the lake increased with a decrease in salinity, and the corresponding lithofacies assemblages in the P1 to P2 parasequences gradually changed from organic-poor thin-bedded and laminated calcareous mudstone to intermediate-organic and organic-rich calcareous shale. When the climate became humid and warmer, resulting in an increasing water level and terrigenous input, the lithofacies assemblages in the P3–P4 parasequences changed from organic-rich calcareous shale and laminated carbonate-bearing mudstone to laminated silty mudstone and calcareous mudstone. At the end, the climate became slightly drier and cooler with a decrease in the water level, and the P5 and P6 parasequences were dominated by intermediate-organic and organic-poor laminated calcareous mudstones. Through elemental analysis and lithofacies observation, we found that the redox conditions of the water may have changed over time. Among the parasequences, the water column of the P2 parasequence was mainly stratified by salinity, that of the P4 parasequence was mainly stratified by temperature, and that of the P3 parasequence was in transition. The synergistic effect of various factors played a key role in the enrichment of organic matter. This study highlights the depositional processes of the lithofacies assemblages in a lacustrine shale and contributes to the understanding of shale oil accumulation in lacustrine shale.

Modeling sea surface height (SSH) and tides is important but challenging in shelf seas. The Eastern China Seas (ECSs) is such a shelf sea with large inter-model deviations in prior studies. In order to assess and compare the possible uncertainty sources, numerical scenarios of varying the open boundary forcing, bottom roughness length scale, atmospheric forcing, grid resolution, and regional bathymetry were conducted in a hydrodynamic model of the ECSs. Results indicate that bathymetry data and open boundary forcing with inadequate accuracy generate uncertainties in SSH and tides locally and throughout the basin. An increase in bottom roughness enhances tidal dissipation and shifts amphidromes to the left relative to the incoming Kelvin waves, causing SSH variations in the ECSs. Refining the model resolution from 4 to 2 km mainly affects nearshore SSH and tides due to minor changes in depicted coastlines. Using different reanalysis meteorological data appears more important on the episodic than annual scale. It is highlighted that some uncertainty sources have opposing effects on SSH or tides and counteract their individual biases, making it difficult to achieve a realistic simulation. For example, increasing bottom roughness can not only compensate effects of overestimated tidal amplitude at open boundaries, but also balance out the overestimated M2 phase along the West Coast of Korea in a coarser-resolution model. Based on findings in this study, suggestions are provided for further reducing uncertainties in SSH and tide modeling in the ECSs and other shelf seas.

Heteroatom-bearing molecular loops and belts are fascinating but generally difficult to synthesize. Here, the authors demonstrate that O,S-bridged double-stranded molecular belts—cyclophenoxathiins—can be successfully constructed and employed as versatile supramolecular hosts.

Single-atom catalysts (SACs) with high metal loading are highly desired to improve catalytic performance. Here, the authors report a dual protection strategy by nanocasting SiO2 into metal–organic frameworks to prepare high-loading SACs with excellent catalytic performance toward oxygen reduction.

In this study, we discovered that a certain concentration of Na+ (15 mM) significantly improved the bond strength (12.94 ± 0.93 MPa), thermal stability (72.68 °C), rheological properties, and textural attributes of walnut protein isolate (WNPI)-κ-carrageenan (KC) composite gel. Electrostatic force, hydrophobic interaction, hydrogen bond, and disulfide bond were also significantly strengthened; the α-helix decreased, and the β-sheet increased in the secondary structure, indicating that the protein molecules in the gel system aggregated in an orderly manner, which led to a much denser and more uniform gel network as well as improved water-holding capacity. In this experimental research, we developed a new type of walnut protein gel that could provide technical support for the high-value utilization and quality control of walnut protein.

In cold regions, saturated fractured rock is prone to crack initiation, extension, and branching along the original fracture end under the effect of freeze-thaw (F-T) cycles and cyclic fatigue loadings. The resulting strength deterioration is accompanied by large amounts of pore growth, which results in localized damage and fracturing along the crack end and even causes overall failure. To study the fatigue damage behaviors of fractured rocks under F-T cycles and cyclic loadings, single-joint quasi-sandstone specimens with joint angles of 45° and 90° were prepared. Subsequently, F-T damage tests with 0, 10, and 20 cycles and cyclic loading tests with different stress levels were performed. The F-T damage features are discussed based on the binarization image of localized damage along the joint ends and their wave velocity variations. It is found that the frost damage of single-joint quasi-sandstone tends toward a strip with localized fatigue characteristics. Moreover, the changes of strain compliance and dissipated energy are studied under the effect of loading-unloading fatigue. Some of the interesting phenomena observed are as follows: (i) during the early stage of cyclic loading, the joint can be compacted; nevertheless, it tends to expand along the fracture direction once it passes the elastic stage, and the irreversible plastic deformation is stable at this stage. (ii) The cracks caused by F-T damage in the 45° single-joint samples deflect along the fracture direction, in contrast to the 90° single-joint specimens. Moreover, the samples with a 45° single joint are more susceptible to original fracture at the early stage of the failure process, which results in a different failure mode from that of the 90° single-joint samples. (iii) The F-T cycles and cyclic loadings have a coupling effect on the single-joint sandstone. The strain compliance and hysteresis energy keep increasing uniformly after the F-T cycles and cyclic loadings.

Algal pigment composition is an indicator of phytoplankton community structure that can be estimated from optical observations. Assessing the potential capability to retrieve different types of pigments from phytoplankton absorption is critical for further applications. This study investigated the performance of three models and the utility of hyperspectral in vivo phytoplankton absorption spectra for retrieving pigment composition using a large database (n = 1392). Models based on chlorophyll-a (Chl-a model), Gaussian decomposition (Gaussian model), and partial least squares (PLS) regression (PLS model) were compared. Both the Gaussian model and the PLS model were applied to hyperspectral phytoplankton absorption data. Statistical analysis revealed the advantages and limitations of each model. The Chl-a model performed well for chlorophyll-c (Chl-c), diadinoxanthin, fucoxanthin, photosynthetic carotenoids (PSC), and photoprotective carotenoids (PPC), with a median absolute percent difference for cross-validation (MAPDCV) < 58%. The Gaussian model yielded good results for predicting Chl-a, Chl-c, PSC, and PPC (MAPDCV < 43%). The performance of the PLS model was comparable to that of the Chl-a model, and it exhibited improved retrievals of chlorophyll-b, alloxanthin, peridinin, and zeaxanthin. Additional work undertaken with the PLS model revealed the prospects of hyperspectral-resolution data and spectral derivative analyses for retrieving marker pigment concentrations. This study demonstrated the applicability of in situ hyperspectral phytoplankton absorption data for retrieving pigment composition and provided useful insights regarding the development of bio-optical algorithms from hyperspectral and satellite-based ocean-colour observations.

Abstract Recent studies showed many cirrhosis patients may have diabetes mellitus (DM), however, the effect of DM on brain in cirrhotic patients is unclear. This study included 34 cirrhosis patients (17 with DM, 17 without DM) and 17 age-, sex-matched healthy controls. MRI examination and neuropsychological tests were performed. Fractional amplitude of low-frequency fluctuation (fALFF) and voxel-based morphometry algorithms were used to obtain fALFF values and gray matter volume, which were compared and correlated with clinical variables. In cirrhosis patients with and without DM, fALFF values were decreased in the left postcentral gyrus, right precentral gyrus, left supramarginal gyrus, bilateral lingual gyri and occipital lobe, while increased in the left orbital frontal gyrus. Gray matter volume was decreased in bilateral caudates and putamen, while increased in bilateral thalami. Compared with non-DM cirrhosis patients, DM cirrhosis patients showed decreased fALFF values in bilateral caudates and decreased gray matter volume in bilateral thalami. The blood glucose levels of cirrhosis patients showed negative correlations with fALFF values in bilateral caudates and gray matter volume in bilateral thalami. In conclusion, DM aggravates brain damage in cirrhosis patients. Thus, it is important to pay more attention to the management of DM in cirrhotic patients.

Abstract Periphyton comprises a broad range of autotrophic and heterotrophic organisms that grow on submerged surfaces in aquatic environments. To investigate the ecological roles of periphyton and their symbiotic bacterial assemblages related to the control of cyanobacterial blooms, mesocosm experiments were performed in a eutrophic lake that is usually infested with harmful cyanobacterial blooms. Our results showed that periphyton, together with their symbionts, reduced Chl-a concentrations (up to 94%), improved water clarity and effectively controlled cyanobacterial blooms in the treatment mesocosm. Planktonic bacterial compositions varied greatly in the pre-bloom/bloom/post-bloom periods in both mesocosms and were mainly influenced by total dissolved nitrogen (TDN) concentrations. The phylum Cyanobacteria was the major component in the water samples until bloom peak, but it was replaced by Actinobacteria in the post-bloom period. However, periphyton niches were dominated by Alphaproteobacteria throughout the experiments, Cyanobacteria proportion being lower. Overall, the results indicated that periphyton and their unique bacterial partners could effectively compete with cyanobacteria and improve water quality. Their underlying interaction mechanism was also suggested to explain how periphyton and their symbionts can reduce cyanobacterial blooms in eutrophic water.

Abstract The physiological role of miRNAs is widely understood to include fine-tuning the post-transcriptional regulation of a wide array of biological processes. Extensive studies have indicated that exosomal miRNAs in the bodily fluids of various organisms can be transferred between living cells for the delivery of gene silencing signals. Here, we illustrated the expression characteristics of exosomal miRNAs in giant panda breast milk during distinct lactation periods and highlighted the enrichment of immune- and development-related endogenous miRNAs in colostral and mature giant panda milk. These miRNAs are stable, even under certain harsh conditions, via the protection of extracellular vesicles. These findings indicate that breast milk may facilitate the dietary intake of maternal miRNAs by infants for the regulation of postnatal development. We also detected exogenous plant miRNAs from the primary food source of the giant panda (bamboo) in the exosomes of giant panda breast milk that were associated with regulatory roles in basic metabolism and neuron development. This result suggested that dietary plant miRNAs are absorbed by host cells and subsequently secreted into bodily fluids as potential cross-kingdom regulators. In conclusion, exosomal miRNAs in giant panda breast milk may be crucial maternal regulators for the development of intrinsic ‘slink’ newborn cubs.

Abstract Chemical sensors detect a variety of chemicals across numerous fields, such as automobile, aerospace, safety, indoor air quality, environmental control, food, industrial production and medicine. We successfully assemble an alcohol-sensing device comprising a thin-film sensor made of graphene nanosheets (GNs) and bacterial cellulose nanofibers (BCNs). We show that the GN/BCN sensor has a high selectivity to ethanol by distinguishing liquid–phase or vapor–phase ethanol (C2H6O) from water (H2O) intelligently with accurate transformation into electrical signals in devices. The BCN component of the film amplifies the ethanol sensitivity of the film, whereby the GN/BCN sensor has 12400% sensitivity for vapor-phase ethanol compared to the pure GN sensor, which has only 21% sensitivity. Finally, GN/BCN sensors demonstrate fast response/recovery times and a wide range of alcohol detection (10–100%). The superior sensing ability of GN/BCN compared to GNs alone is due to the improved wettability of BCNs and the ionization of liquids. We prove a facile, green, low-cost route for the assembly of ethanol-sensing devices with potential for vast application.

Abstract Adiponectin (APN), also known as apM1, Acrp30, GBP28 and adipoQ, is a circulating hormone that is predominantly produced by adipose tissue. Many pharmacological studies have demonstrated that this protein possesses potent anti-diabetic, anti-atherogenic and anti-inflammatory properties. Although several studies have demonstrated the antioxidative activity of this protein, the regulatory mechanisms have not yet been defined in skeletal muscles. The aim of the present study was to examine the cytoprotective effects of APN against damage induced by oxidative stress in mouse-derived C2C12 myoblasts. APN attenuated H2O2-induced growth inhibition and exhibited scavenging activity against intracellular reactive oxygen species that were induced by H2O2. Furthermore, treating C2C12 cells with APN significantly induced heme oxygenase-1 (HO-1) and nuclear factor-erythroid 2 related factor 2 (Nrf2). APN also suppressed H2O2-induced mitophagy and partially inhibited the colocalization of mitochondria with autophagosomes/lysosomes, correlating with the expression of Pink1 and Parkin and mtDNA. Moreover, APN protected C2C12 myoblasts against oxidative stress-induced apoptosis. Furthermore, APN significantly reduced the mRNA and protein expression levels of Bax. These data suggest that APN has a moderate regulatory role in oxidative stress-induced mitophagy and suppresses apoptosis. These findings demonstrate the antioxidant potential of APN in oxidative stress-associated skeletal muscle diseases.

Abstract MicroRNAs are a class of small RNAs that are important in post-transcriptional gene regulation in animals and plants. These single-stranded molecules are widely distributed in organisms and influence fundamental biological processes. Interestingly, recent studies have reported that diet-derived plant miRNAs could regulate mammalian gene expression, and these studies have broadened our view of cross-kingdom communication. In the present study, we evaluated miRNA levels in cooked maize-containing chow diets, and found that plant miRNAs were resistant to the harsh cooking conditions to a certain extent. After feeding fresh maize to pigs (7 days), maize-derived miRNAs could be detected in porcine tissues and serum, and the authenticity of these plant miRNAs was confirmed by using oxidization reactions. Furthermore, in vivo and in vitro experiments demonstrated that dietary maize miRNAs could cross the gastrointestinal tract and enter the porcine bloodstream. In the porcine cells, we found that plant miRNAs are very likely to specifically target their endogenous porcine mRNAs and influence gene expression in a fashion similar to that of mammalian miRNAs. Our results indicate that maize-derived miRNAs can cross the gastrointestinal tract and present in pigs, and these exogenous miRNAs have the potential to regulate mammalian gene expression.

Abstract Deteriorating knee stability is a local risk factor that reflects the occurrence and aggregative of osteoarthritis (OA). Despite the many biomechanics-based methods for assessing the structural stability of knee joints in clinics, these methods have many limitations. The stability of the knee joint relies on not only biomechanical factors, but also proprioception and the central nervous system. In this study, we attempt to depict the stability of knee joint from a holistic viewpoint, and a novel index of knee joint stability (IKJS) was thus extracted. We compared the differences of IKJS in 57 healthy volunteers and 55 patients with OA before and after total knee replacement (TKR). Analysis of Variance results demonstrated that there existed significant differences in IKJS among the three participating groups (

The spatiotemporal variability of phytoplankton biomass has been widely studied because of its importance in biogeochemical cycles. Chlorophyll a (Chl-a)—an essential pigment present in photoautotrophic organisms—is widely used as an indicator for oceanic phytoplankton biomass because it could be easily measured with calibrated optical sensors. However, the intracellular Chl-a content varies with light, nutrient levels, and temperature and could misrepresent phytoplankton biomass. In this study, we estimated the concentration of phytoplankton carbon—a more suitable indicator for phytoplankton biomass—using a regionally adjusted bio-optical algorithm with satellite data in the South China Sea (SCS). Phytoplankton carbon and the carbon-to-Chl-a ratio (θ) exhibited considerable variability spatially and seasonally. Generally, phytoplankton carbon in the northern SCS was higher than that in the western and central parts. The regional monthly mean phytoplankton carbon in the northern SCS showed a prominent peak during December and January. A similar pattern was shown in the central part of SCS, but its peak was weaker. Besides the winter peak, the western part of SCS had a secondary maximum of phytoplankton carbon during summer. θ exhibited significant seasonal variability in the northern SCS, but a relatively weak seasonal change in the western and central parts. θ had a peak in September and a trough in January in the northern and central parts of SCS, whereas in the western SCS the minimum and maximum θ was found in August and during October–April of the following year, respectively. Overall, θ ranged from 26.06 to 123.99 in the SCS, which implies that the carbon content could vary up to four times given a specific Chl-a value. The variations in θ were found to be related to changing phytoplankton community composition, as well as dynamic phytoplankton physiological activities in response to environmental influences; which also exhibit much spatial differences in the SCS. Our results imply that the spatiotemporal variability of θ should be considered, rather than simply used a single value when converting Chl-a to phytoplankton carbon biomass in the SCS, especially, when verifying the simulation results of biogeochemical models.