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Abstract Single cell ATAC-seq (scATAC-seq) experimental designs have become increasingly complex, with multiple factors that might affect chromatin accessibility, including genotype, cell type, tissue of origin, sample location, batch, etc., whose compound effects are difficult to test by existing methods. In addition, current scATAC-seq data present statistical difficulties due to their sparsity and variations in individual sequence capture. To address these problems, we present a zero-adjusted statistical model, Probability model of Accessible Chromatin of Single cells (PACS), that allows complex hypothesis testing of accessibility-modulating factors while accounting for sparse and incomplete data. For differential accessibility analysis, PACS controls the false positive rate and achieves a 17% to 122% higher power on average than existing tools. We demonstrate the effectiveness of PACS through several analysis tasks, including supervised cell type annotation, compound hypothesis testing, batch effect correction, and spatiotemporal modeling. We apply PACS to datasets from various tissues and show its ability to reveal previously undiscovered insights in scATAC-seq data.

A randomized, double-blind, placebo-controlled clinical trial was conducted to investigate the efficacy of infliximab, abatacept, and cenicriviroc in treating patients hospitalized with COVID-19. The patient's clinical status was assessed daily on an 8-point ordinal scale. We evaluated the totality of evidence on the efficacy of the 3 immunomodulators by considering all possible changes in the clinical status of each patient over time. We demonstrated that infliximab accelerated improvement and reduced deterioration of clinical status when added to standard of care. There was also evidence for the benefit of abatacept. There was no evidence for the benefit of cenicriviroc.

In our previous study, we observed distinct lipid deposition pattern between Crane-top red goldfish (HDH) and Pearl-scale goldfish (PS), yet the regulatory mechanisms remained unclear. In this study, a comprehensive comparison between HDH and PS was conducted to elucidate the mechanisms driving this difference. Our findings revealed that the hepatopancreas lipid content, as well as the levels of triglyceride and total cholesterol, were significantly higher in HDH than in PS. Conversely, the total bile acid level was significantly higher in PS than in HDH. Transcriptome and proteome analysis identified 3174 differentially expressed genes (DEGs) and 816 differentially expressed proteins (DEPs) between HDH and PS, respectively, which were primarily enriched in pathways associated with PPAR signaling, primary bile acid biosynthesis, steroid hormone biosynthesis, taurine metabolism, and carbohydrate digestion and absorption. Notably, DEGs and DEPs related to bile acid synthesis were found to play a key role in the observed difference between HDH and PS. Specifically, the CYP27A1 gene and EBP, MSMO1, CYP7B1, and HSD3B7 proteins were up-regulated in PS goldfish, indicating an enhanced bile acid synthesis capacity. Additionally, the abundance of intestinal Cetobacterium, which is closely associated with host lipid deposition, was significantly higher in PS intestine than in HDH.

Highlights A hollow core–shell structure was constructed with C–Co as the exoskeleton to support the MXene and multiwalled carbon nanotubes (MWCNTs) endoskeleton, with MWCNTs growing toward the center of the sphere. A reflection loss of − 70.70 dB and an effective absorption bandwidth of 5.67 GHz were obtained when the thickness was only 2.04 mm. The powder filler ratio was only 15 wt%. The unique hollow core–shell structure enhanced multiple reflection and scattering losses.

Films of piezoelectric poly(vinylidene fluoride) (PVDF) and its copolymer P(VDF-TrFE) have been studied intensively for their potential application in piezoelectric sensing devices. The present work focuses on tuning the piezoelectric properties of P(VDF-TrFE) films via incorporating Ag and polydopamine co-decorated PZT (Ag@PDA@PZT) particles. Ag@PDA@PZT particles can effectively improve the β-phase content and piezoelectric properties of P(VDF-TrFE) films. The highest open-circuit voltage and short-circuit current of P(VDF-TrFE)-based flexible pressure sensors incorporating Ag@PDA@PZT particles are ~30 V and ~2.4 μA, respectively. The flexible sensors exhibit a response to different body movements, providing a practical and potentially useful basis for human−machine interface applications.

Abstract Progression of chronic kidney disease (CKD) portends myriad complications, including kidney failure. In this study, we analyze associations of 4638 plasma proteins among 3235 participants of the Chronic Renal Insufficiency Cohort Study with the primary outcome of 50% decline in estimated glomerular filtration rate or kidney failure over 10 years. We validate key findings in the Atherosclerosis Risk in the Communities study. We identify 100 circulating proteins that are associated with the primary outcome after multivariable adjustment, using a Bonferroni statistical threshold of significance. Individual protein associations and biological pathway analyses highlight the roles of bone morphogenetic proteins, ephrin signaling, and prothrombin activation. A 65-protein risk model for the primary outcome has excellent discrimination (C-statistic[95%CI] 0.862 [0.835, 0.889]), and 14/65 proteins are druggable targets. Potentially causal associations for five proteins, to our knowledge not previously reported, are supported by Mendelian randomization: EGFL9, LRP-11, MXRA7, IL-1 sRII and ILT-2. Modifiable protein risk markers can guide therapeutic drug development aimed at slowing CKD progression.

Abstract Flexible piezoelectric pressure sensors (FPPS) received a lot of attention because of their prominent performance in body motion detection and energy recovery. However, it has faced a huge challenge in manufacturing FPPS with high sensitivity, low cost, and high flexibility. Herein, a ternary flexible nanofiber composite with Sb nanosheets and BaTiO3 nanoparticles as the fillers of P(VDF‐TrFE) is prepared by electrospinning. An impressive open‐circuit voltage of 17.1 V and short‐circuit current of 4.4 µA is obtained based on the composite nanofiber mat at a pressure of 128 kPa with 2 Hz frequency. The FPPS not only exhibit a high sensitivity of 96 mV kPa−1 but also an ultrafast response time of 2 ms. Excellent flexibility and reliability are demonstrated by the unchanged open‐circuit voltage after 2400 cycles. The enhanced FPPS performance is owed to the interfacial polarization effect at the inorganic filler‐organic matrix interface, which also enhances the ferroelectric and dielectric properties. The present FPPS is further confirmed to be a real‐time motion monitor and voice recognizer, which can distinguish various actions and sounds according to distinct output voltage signals and is expected to be used in virtual reality devices, robotic electronic skin, haptic simulation, artificial throat, etc.

Betaine, a methyl donor, plays a crucial role in lipid metabolism. Previous studies have shown that appropriate betaine supplementation in a high-fat diet reduces triglycerides (TG) of serum and hepatopancreas in fish. However, the underlying mechanism remains unclear. This study examined whether betaine can enhance the secretion of very low-density lipoprotein (VLDL) and sought to identify the specific mechanisms through which this enhancement occurs. A lipid accumulation model was established in gibel carp and L8824 cells using a high-fat diet and oleic acid, respectively. Different doses of betaine (1, 4, and 16 g/kg in the diet; 400 μmol in cell culture) were administered, and measurements were taken for lipid deposition, gene expression of HNF4α, MTTP, and ApoB, as well as the regulation of Mttp and Apob promoters by HNF4α. The results showed that betaine supplementation mitigated lipid droplet accumulation, TG levels, and VLDL production induced by the high-fat diet in gibel carp hepatopancreas and L8824 cells. Moreover, betaine not only increased VLDL content in the cell culture supernatant but also reversed the inhibitory effects of the high-fat diet on protein expression of MTTP, ApoB, and HNF4α in both gibel carp hepatopancreas and L8824 cells. Additionally, HNF4α exhibits transactivating activity on the promoter of Mttp in gibel carp. These findings suggest that betaine supplementation exerts its effects through the HNF4α/MTTP/ApoB pathway, promoting the assembly and secretion of VLDL and effectively reducing lipid accumulation in the hepatopancreas of farmed gibel carp fed a high-fat diet.

This study aimed to compare the nutritional composition, digestive enzyme activity, nonspecific immunity, and intestinal microflora of Procambarus clarkii under different culture modes: crayfish and crab coculture, pond intensive farmed culture (PF), rice and crayfish coculture (RC), cement pond culture (CP), and wild-caught. The muscle, hepatopancreas, and intestine of crayfish with a mean weight of 25.35 ± 4.23 g were collected and examined. The results showed that the nutritive value of amino acids and fatty acids in the muscle was higher in the RC group than in the other groups. Moreover, muscle crude protein contents were the highest in the CP group. Trypsin activities in the intestines were significantly higher in the PF and CP groups than in the other groups (P

This paper proposed an efficient high-accuracy multidisciplinary design process for the integrated system of low speed permanent magnet synchronous motor (PMSM). The method combined the analytical models and numerical models together to get an efficient way to design the integrated motor. In the proposed method, a magnetic equivalent circuit (MEC) model of the motor is established first based on one modular structure of the motor, and the finite element analysis (FEA) numerical model is used to correct the results of the analytical model next. Then the iron loss, copper loss, and switching loss from the results of the electromagnetic model are loaded to a proposed simplified lumped parameter fluid-thermal model. This fluid-thermal coupled analytical model cuts the fluid flow into several parts depends on the parameters of the cooling path, each parts act as a current controlled voltage source coupled with these parameters. And because this coupled model has controlled sources, the conventional node voltage method is not suitable anymore, so a more universal list parameter calculation method is proposed for this coupled model. Finally, the computational fluid dynamics (CFD) model is used to correct the results of the analytical model as well. The aim of the above analytical models is to quickly get the suitable multidisciplinary pre-design or design trends, and this pre-work or trends will reduce the design process time of the high-accuracy numerical models.

An axial hybrid permanent magnet synchronous reluctance machine (AHPM-SynRM) is proposed in this paper. The structure is a combination of synchronous reluctance rotor and two permanent magnet rotors. The proposed design includes three axially parallel rotors, the reluctance axis coincides in phase with the permanent magnet axis by rotating the synchronous reluctance machine (SynRM) rotor, which could increase the average torque. In the condition of the volume of permanent magnets stays unchanged, the relationship between the axial length ratio of different rotor parts and the maximum torque is also analyzed. Moreover, air gap magnetic isolation is designed between each rotor part, so there is no serious magnetic field coupling between different rotors and each rotor part could be separately designed. The analysis results prove the proposed machine has significantly higher torque performance than the permanent magnet assisted machine. (PM-SynRM).

This study aimed to evaluate the effects of solid-state fermented commercial pelleted feed with Lactobacillus plantarum on growth performance, digestive physiology, antioxidant, and immune capacity, as well as morphology and microbiota in intestinal of Tachysurus fulvidraco. A total of 420 fish (49.96 ± 7.10 g) were randomly allocated to twelve 300 L buckets for a 60 d farming trial. The diets of three treatments were established: the untreated commercial diet (UCD), the commercial diet mixed with fermented liquid (MFLD), and the solid-state fermented commercial diet (SSFD). The results indicated that SSFD treatment had a significant positive effect on the growth performance of T. fulvidraco, with an increase of 15.69% to 16.57% (p < 0.05) compared with UCD and MFLD treatments. MFLD and SSFD treatments also showed higher total anti-oxygen capacity, catalase, and glutathione peroxidase activities in the intestine significantly compared with UCD treatment (p < 0.05). Furthermore, the activities of alkaline phosphatase and lysozyme activities both in the liver and intestine were significantly higher in MFLD and SSFD treatments than in UCD treatment (p < 0.05). The villus height in the midintestine was also greater in MFLD and SSFD treatments compared with UCD treatment (p < 0.05). Regarding the intestinal microbiota, the dominant bacteria in UCD treatment was Cetobacterium, with the highest abundance in whole intestinal segments. However, in MFLD and SSFD treatments, the abundance of Cetobacterium in the foreintestine significantly decreased (p < 0.05). In conclusion, this study elucidates that solid-state fermentation feed may not only improve the digestive capacity, antioxidant ability, immune function, and intestinal morphology of T. fulvidraco to enhance growth performance but also influence intestinal microbial composition. These findings provide beneficial proof for developing fermented feed of T. fulvidraco.

White-rot fungi are the most important group of lignin biodegraders. Phanerochaete sordida YK-624 has higher ligninolytic activity than that of model white-rot fungi. However, the underlying mechanism responsible for lignin degradation by white-rot fungi remains unknown, and the induced compounds isolated from white-rot fungi for lignin degradation have never been studied. In the present study, we tried to screen ligninolytic-inducing compounds produced by P. sordida YK-624. After large-scale incubation of P. sordida YK-624, the culture and mycelium were separated by filtration. After the separation and purification, purified compounds were analyzed by high-resolution electrospray ionization mass spectrometry and nuclear magnetic resonance. The sterilized unbleached hardwood kraft pulp was used for the initial evaluation of ligninolytic activity. Ergosterol was isolated and identified and it induced the lignin-degrading activity of this fungus. Moreover, we investigated ergosterol metabolites from P. sordida YK-624, and the ergosterol metabolites ergosta-4,7,22-triene-3,6-dione and ergosta-4,6,8(14),22-tetraen-3-one were identified and then chemically synthesized. These compounds significantly improved the lignin-degrading activity of the fungus. This is the first report on the ligninolytic-inducing compounds produced by white-rot fungi.

Polycyclic aromatic hydrocarbons (PAHs) are persistent environmental pollutants that pose a threat to human health. Among these PAHs, benzo[a]pyrene (BaP), a five-ring compound, exhibits high resistance to biodegradation. White-rot fungus Phlebia acerina S-LWZ20190614-6 has demonstrated higher BaP degradation capabilities compared with Phanerochaete chrysosporium and P. sordida YK-624, achieving a degradation rate of 57.7% after 32 days of incubation under a ligninolytic condition. To further enhance the biodegradation rate, three nonionic surfactants were used, and the addition of 1 or 2 g·L−1 of polyethylene glycol monododecyl ether (Brij 30) resulted in nearly complete BaP biodegradation by P. acerina S-LWZ20190614-6. Interestingly, Brij 30 did not significantly affect the activity of manganese peroxidase and lignin peroxidase, but it did decrease laccase activity. Furthermore, the impact of cytochrome P450 on BaP degradation by P. acerina S-LWZ20190614-6 was found to be relatively mild. Transcriptomic analysis provided insights into the degradation mechanism of BaP, revealing the involvement of genes related to energy production and the synthesis of active enzymes crucial for BaP degradation. The addition of Brij 30 significantly upregulated various transferase and binding protein genes in P. acerina S-LWZ20190614-6. Hence, the bioremediation potential of BaP by the white-rot fungus P. acerina S-LWZ20190614-6 holds promise and warrants further exploration.

Abstract In the design of electromagnetic (EM) wave absorbing materials, it is still a great challenge to optimize the relationship between the attenuation capability and impedance matching synergistically. Herein, a 3D porous MoS2/MXene hybrid aerogel architecture with conformal heterogeneous interface has been built by atomic layer deposition (ALD) based on specific porous templates to optimize the microwave absorption (MA) performance comprehensively. The original porous structure of pristine Ti3C2Tx aerogel used as templates can be preserved well during ALD fabrication, which prolongs the reflection and scattering path and ameliorates the dielectric loss. Meanwhile, plenty of heterointerfaces between MoS2 and Ti3C2Tx have been fabricated based on conformally ALD‐deposited MoS2 with controlled thickness on the porous surfaces of the templates, which can effectively optimize the impedance matching and transform its response to EM waves from shielding into absorbing. Moreover, the interaction between the attenuation capability and impedance matching can also be modulated by the number of ALD cycle in MoS2 fabrication. After optimization, MoS2/MXene hybrid aerogel obtained under 300 ALD cycles shows a minimum reflection loss of −61.65 dB at the thickness of 4.53 mm. In addition, its preferable lightweight, high surface area, mechanical, and hydrophobicity properties will also be conducive to further practical applications.

It is of great significance for the aquaculture industry to determine how rearing salinity impacts fish flesh quality. In the present study, largemouth bass was cultured in different salinities (0%, 0.3%, 0.9%) for 10 weeks, and the effect on flesh texture, flavor compounds, taste, and fatty acid composition was evaluated. We show that rearing salinity not only increased flesh water-holding capacity, but also enhanced muscle hardness, chewiness, gumminess, and adhesiveness, which was consistent with the finding in the shear value test. Morphology analysis further revealed that the effect of salinity on flesh texture was probably related to changes in myofibril diameter and density. As for the taste of the flesh, water salinity improved the contents of both sweet and umami amino acids, and reduced the contents of bitter amino acid. Meanwhile, the content of IMP, the dominant flavor nucleotide in largemouth bass muscle, was significantly higher in the 0.9% group. Interestingly, electronic-tongue analysis demonstrated that the positive effect of salinity on flavor compounds enhanced the umami taste and taste richness of flesh. Moreover, rearing salinity improved the contents of C20: 5n-3 (EPA) and C22: 6n-3 (DHA) in back muscle. Therefore, rearing largemouth bass in adequate salinity may be a practical approach to improving flesh quality.

TiO2 develops a higher efficiency when doping Bi into it by increasing the visible light absorption and inhibiting the recombination of photogenerated charges. Herein, a highly efficient Bi doped TiO2 photoanode was fabricated via a one-step modified sol-gel method and a screen-printing technique for the anode of photocatalytic fuel cell (PFC). A maximum degradation rate of 91.2% of Rhodamine B (RhB) and of 89% after being repeated 5 times with only 2% lost reflected an enhanced PFC performance and demonstrated an excellent stability under visible-light irradiation. The excellent degradation performance was attributed to the enhanced visible-light response and decreased electron-hole recombination rate. Meanwhile, an excellent linear correlation was observed between the efficient photocurrent of PFC and the chemical oxygen demand of solution when RhB is sufficient.

The fatty acid compositions of the fish muscle and liver are substantially affected by rearing environment. However, the mechanisms underlying this effect have not been thoroughly described. In this study, we investigated the effects of different culture patterns, i.e., marine cage culture and freshwater pond culture, on long-chain polyunsaturated fatty acids (LC-PUFA) biosynthesis in an aquaculturally important fish, the Japanese sea bass (Lateolabrax japonicus). Fish were obtained from two commercial farms in the Guangdong province, one of which raises Japanese sea bass in freshwater, while the other cultures sea bass in marine cages. Fish were fed the same commercial diet. We found that omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) levels in the livers and muscles of the marine cage cultured fish were significantly higher than those in the livers and muscles of the freshwater pond cultured fish. Quantitative real-time PCRs indicated that fatty acid desaturase 2 (FADS2) transcript abundance was significantly lower in the livers of the marine cage reared fish as compared to the freshwater pond reared fish, but that fatty acid elongase 5 (Elovl5) transcript abundance was significantly higher. Consistent with this, two of the 28 CpG loci in the FADS2 promoter region were heavily methylated in the marine cage cultured fish, but were only slightly methylated in freshwater pond cultured fish (n = 5 per group). Although the Elovl5 promoter was less methylated in the marine cage reared fish as compared to the freshwater pond reared fish, this difference was not significant. Thus, our results might indicate that Elovl5, not FADS2, plays an important role in the enhancing LC-PUFA synthesis in marine cage cultures.

Due to their unique physical and chemical properties, metal-organic cage structures have great potential for applications in various fields. However, current studies have mainly focused on highly symmetric structures assembled from single metal ions and organic ligands, limiting their diversity and complexity, and there are still relatively few studies on the dynamic formation process of metal-organic cages. Herein, we constructed a series of metal-organic cages with different sizes assembled from the highly-stable coordination of 2,2':6',2"-terpyridine-based tetratopic ligands and various metals ions such as Zn, Cu, Co and Fe. Furthermore, the intermolecular exchange process between the metal-organic cages was explored through the dynamic exchange of ligands, and the formation of a series of hybrid supramolecular nanocages together with their final tendency to form a predominant structure of M24L14L28 was observed. In addition, the binding of metal-organic cages with 5,10,15,20-tetrakis(3,4,5-trimethoxyphenyl) porphyrin-Zn was also investigated. This study not only expands the complexity and diversity of metal-organic cages, but also provides a new perspective for studying the dynamic behaviour of metal-organic cages. [ABSTRACT FROM AUTHOR]

The semiparametric Cox proportional hazards model, together with the partial likelihood principle, has been widely used to study the effects of potentially time-dependent covariates on a possibly censored event time. We propose a computationally efficient method for fitting the Cox model to big data involving millions of study subjects. Specifically, we perform maximum partial likelihood estimation on a small subset of the whole data and improve the initial estimator by incorporating the remaining data through one-step estimation with estimated efficient score functions. We show that the final estimator has the same asymptotic distribution as the conventional maximum partial likelihood estimator using the whole dataset but requires only a small fraction of computation time. We demonstrate the usefulness of the proposed method through extensive simulation studies and an application to the UK Biobank data. [ABSTRACT FROM AUTHOR]