Topology Prediction of Gas-Separating Metal-Organic Frameworks with Low Symmetry Vertices.

Topology serves as a blueprint for the construction of reticular structures such as metal-organic frameworks, especially for those based on building blocks with highly symmetrical shapes. However, it remains a challenge to predict the topology of the frameworks from less symmetrical units, because their corresponding vertex figures are largely deformed from the perfect geometries with no "default" net embedding. Furthermore, vertices involving flexible units may have multiple shape choices, and the competition among their designated topologies makes the structure prediction in large uncertainty. Herein, the deformation index is proposed to characterize the symmetry loss of the vertex figure by comparing it with its ideal geometry. The mathematical index is employed to predict the shapes of two in situ formed Co-based metalloligands (pseudo-tetrahedron and pseudo-square), which further dictate the framework topology (flu and scu) when they are joined with the [Zr6O8]-based cuboid units. The two frameworks with very similar constituents provide an ideal platform to investigate how the pore shapes and interconnectivity influence the gas separation. The net with cylindrical channels outperforms the other with discreate cages in C3H8/C2H6/CH4 separation, benefiting from the facile accessibility of its interaction sites to the guests imposed by the specific framework topology.

Targeting the MCP-GPX4/HMGB1 Axis for Effectively Triggering Immunogenic Ferroptosis in Pancreatic Ductal Adenocarcinoma.

Induction of ferroptosis can inhibit cancer cells in vitro, however, the role of ferroptosis in treatment in vivo is controversial. The immunosuppressive cells activated by the ferroptotic tumor cells can promote the growth of residual tumor cells, hindering the application of ferroptosis stimulation in tumor treatment. In this study, a new strategy is aimed to be identified for effectively triggering immunogenic ferroptosis in pancreatic ductal adenocarcinoma (PDAC) and simultaneously stimulating antitumor immune responses. Toward this, several molecular and biochemical experiments are performed using patient-derived organoid models and a KPC mouse model (LSL-KrasG12D /+, LSL-Trp53R172H/+, Pdx-1-Cre). It is observed that the inhibition of macrophage-capping protein (MCP) suppressed the ubiquitin fold modifier (UFM)ylation of pirin (PIR), a newly identified substrate of UFM1, thereby decreasing the transcription of GPX4, a marker of ferroptosis, and promoting the cytoplasmic transportation of HMGB1, a damage-associated molecular pattern. GPX4 deficiency triggered ferroptosis, and the pre-accumulated cytosolic HMGB1 is released rapidly. This altered release pattern of HMGB1 facilitated the pro-inflammatory M1-like polarization of macrophages. Thus, therapeutic inhibition of MCP yielded dual antitumor effects by stimulating ferroptosis and activating antitumor pro-inflammatory M1-like macrophages. The nanosystem developed for specifically silencing MCP is a promising tool for treating PDAC.

Carrageenan oligosaccharide alleviates intestinal damage via gut microflora through activating IMD/relish pathway in female Drosophila melanogaster.

Recent evidence suggests the anti-inflammatory effect of carrageenan oligosaccharides (COS). The effects of COS on intestinal injury induced by 0.6% sodium dodecyl sulfate (SDS) and the molecular mechanisms involved were investigated in this study. 0.625, 1.25, and 2.5 mg/mL COS in diet had no toxic effect in flies, and they could all prolong SDS-treated female flies' survival rate. 1.25 mg/mL COS prevented the development of inflammation by improving the intestinal barrier integrity and maintaining the intestinal morphology stability, inhibited the proliferation of intestine stem cells (ISCs), and the production of lysosomes induced by SDS, accompanied by a decrease in the expression of autophagy-related genes. Moreover, COS decreased the active oxygen species (ROS) content in gut and increased the antioxidant activity in SDS-induced female flies, while COS still played a role in increasing survival rate and decreasing intestinal leakage in CncC-RNAi flies. The improvement of anti-inflammation capacity may be associated with the regulation of intestinal microflora with COS supplementation for Drosophila melanogaster. COS changed the gut microbiota composition, and COS had no effect on germ-free (GF) flies. It is highlighted that COS could not work in Relish-RNAi flies, indicating relish is required for COS to perform beneficial effects. These results provide insights into the study of gut microbiota interacting with COS to modulate intestinal inflammation in specific hosts.

Structural Conjugation Tuning in Covalent Organic Frameworks Boosts Charge Transfer and Photocatalysis Performances.

Structural conjugation greatly affects the optical and electronic properties of the COF photocatalyst. Herein, we show that 2D hydrazone COFs with either π-extended biphenyl (BPh-COF) or acetylene (AC-COF) frameworks demonstrated distinct charge transfer and photocatalytic performances. The two COFs show good crystallinity and decent porosity as their frameworks are enforced by intra/interlayers hydrogen bonding. However, computational and experimental data reveal that AC-COF managed broader visible-light absorption and narrower optical bandgaps and performed efficient photoinduced charge separation and transfer in comparison with BPh-COF, meaning that the ethynyl skeleton with enhanced planarity better improves the π-conjugation of the whole structure. As a result, AC-COF exhibited an ideal bandgap for rapid oxidative coupling of amines under visible-light irradiation. Furthermore, taking advantage of its better charge transfer properties, AC-COF demonstrated considerable enhanced product conversion and notable functional tolerance for metallaphotocatalytic C-O cross-coupling of a wide range of both aryl bromides and chlorides with alcohols. More importantly, besides being recoverable, AC-COF showcased the previously inaccessible etherification of dihaloarene. This report shows a facile approach for manipulating the structure-activity relationship and paves the way for the development of a COF photocatalyst for solar-to-chemical energy conversion.

Long-Range Epitaxial MOF Electronics for Continuous Monitoring of Human Breath Ammonia.

As an important biomarker, ammonia exhibits a strong correlation with protein metabolism and specific organ dysfunction. Limited by the immobile instrumental structure, invasive and complicated procedures, and unsatisfactory online sensitivity and selectivity, current medical diagnosis fails to monitor this chemical in real time efficiently. Herein, we present the successful synthesis of a long-range epitaxial metal-organic framework on a millimeter domain-sized single-crystalline graphene substrate (LR-epi-MOF). With a perfect 30° epitaxial angle and a mere 2.8% coincidence site lattice mismatch between the MOF and graphene, this long-range-ordered epitaxial structure boosts the charge transfer from ammonia to the MOF and then to graphene, thereby promoting the overall charge delocalization and exhibiting extraordinary electrical global coupling properties. This unique characteristic imparts a remarkable sensitivity of 0.1 ppb toward ammonia. The sub-ppb detecting capability and high anti-interference ability enable continuous information recording of breath ammonia that is strongly correlated with the intriguing human lifestyle. Wearable electronics based on the LR-epi-MOF could accurately portray the active protein metabolism pattern in real time and provide personal assistance in health management.

Stepwise construction of coordinative linkages and dynamic covalent linkages for a porous metal-organic framework.

A cyclic trinuclear complex is synthesized from AgI and 1H-pyrazole-4-carbaldehyde. Reticulation of the complex with 1,3,5-tris(4-aminophenyl)benzene through Schiff-base reaction affords a porous FDM-72 framework. Amine choice is systematically investigated as it may initiate metal reduction. This study proposes a new route and its amine selection criterion to synthesize Ag-based frameworks.

Target Design of Multinary Metal-Organic Frameworks for Near-Infrared Imaging and Chemodynamic Therapy.

Imaging-guided chemodynamic therapy is widely considered a promising modality for personalized and precision cancer treatment. Combining both imaging and chemodynamic functions in one system conventionally relies on the hybrid materials approach. However, the heterogeneous, ill-defined, and dissociative/disintegrative nature of the composites tends to complicate their action proceedings in biological environments and thus makes the treatment imprecise and ineffective. Herein, a strategy to employ two kinds of inorganic units with different functions─reactive oxygen species generation and characteristic emission─has achieved two single-crystalline metal-organic frameworks (MOFs), demonstrating the competency of reticular chemistry in creating multifunctional materials with atomic precision. The multinary MOFs could not only catalyze the transformation from H2O2 to hydroxyl radicals by utilizing the redox-active Cu-based units but also emit characteristic tissue-penetrating near-infrared luminescence brought by the Yb4 clusters in the scaffolds. Dual functions of MOF nanoparticles are further evidenced by pronounced cell imaging signals, elevated intracellular reactive oxygen species levels, significant cell apoptosis, and reduced cell viabilities when they are taken up by the HeLa cells. In vivo NIR imaging is demonstrated after the MOF nanoparticles are further functionalized. The independent yet interconnected modules in the intact MOFs could operate concurrently at the same cellular site, achieving a high spatiotemporal consistency. Overall, our work suggests a new method to effectively accommodate both imaging and therapy functions in one well-defined material for precise treatment.

Endothelial exosomes work as a functional mediator to activate macrophages.

Introduction: Intercellular communication is essential for almost all physiological and pathological processes. Endothelial cell (EC)-derived exosomes, working as mediators for intercellular information exchange, are involved in the pathophysiological mechanisms of atherosclerosis. However, the effect of inflamed endothelial exosomes on the function of macrophages (Mϕ) is poorly defined. This study aims to unravel how exosomes derived from tumor necrosis factor-α (TNF-α)-stimulated ECs (exo-T) affect Mϕ in vitro. Methods and results: Exosomes derived from untreated ECs (exo) and exo-T were identified by using TEM, NTA, and western blot, and we observed that PKH67-labeled exo/exo-T were taken up by Mϕ. Exposure to exo-T for 24 h not only skewed Mϕ to the M1 subtype and exacerbated lipid deposition, but also promoted Mϕ apoptosis, while it did not significantly affect Mϕ migration, as detected by RT-qPCR, Dil-ox-LDL uptake assay, flow cytometry, wound healing assay, and transwell assay, respectively. In addition, exo/exo-T-related microRNA-Seq revealed 104 significantly differentially expressed microRNAs (DE-miRNAs). The target genes of DE-miRNAs were mainly enriched functionally in metabolic pathways, MAPK signaling pathway, etc., as determined using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. We further demonstrated by immunoblotting that exo-T intervention improves the phosphorylation of MAPK/NF-κB-related proteins. Discussion and conclusion: Collectively, this study reveals that inflamed endothelial exosomes (TNF-α-stimulated EC-derived exosomes) work as a functional mediator to affect Mϕ function and may activate Mϕ through MAPK/NF-κB signaling pathways.

Circular RNA transcriptome across multiple tissues reveal skeletal muscle-specific circPSME4 regulating myogenesis.

There are significant differences in meat production, growth rate and other traits between Western commercial pigs and Chinese local pigs. Comparative transcriptome approaches have identified many coding and non-coding candidate genes associated various traits. However, the expression and function of circular RNAs (circRNAs) in different pig tissues are largely unknown. In this study, we conducted a comprehensive analysis of the genome-wide circRNA expression profile across ten tissues in Luchuan (a Chinese local breed) and Duroc (a Western commercial breed) pigs. We identified a total of 56,254 circRNAs, of which 42.9 % were not previously annotated. We found that 33.7 % of these circRNAs were differentially expressed. Enrichment analysis revealed that differentially expressed circRNAs might contribute to the phenotypic differentiation between Luchuan and Duroc pigs. We identified 538 tissue-specific circRNAs, most of which were specifically expressed in the brain and skeletal muscle. Competitive endogenous RNA network analysis suggested that skeletal muscle-specific circPSME4 was co-expressed with MYOD1 and targeted by ssc-miR-181d-3p. Functional analysis revealed that circPSME4 knockdown could promote the proliferation and differentiation of myoblasts. Together, our findings provide valuable resources of circRNAs for animal breeding and biomedical research. We demonstrated that circPSME4 is a novel regulator of skeletal muscle development.

Unraveling the difference in flavor characteristics of Huangjiu fermented with different rice varieties using dynamic sensory evaluation and comprehensive two-dimensional gas chromatography-quadrupole mass spectrometry.

To investigate the specific differences in flavor characteristics of Huangjiu fermented with different rice varieties, dynamic sensory evaluation, comprehensive two-dimensional gas chromatography-quadrupole mass spectrometry (GC × GC-qMS) and multivariate statistical analysis were employed. Dynamic sensory evaluation methods including temporal dominance of sensations (TDS) and temporal check all that apply (TCATA) were applied to explore the differences and variations in sensory attributes. The sensory results showed that the intensity of astringency and post-bitterness in the Huangjiu fermented with glutinous rice was weaker while ester and alcoholic aroma were more prominent than the one fermented with japonica rice. The results of free amino acids and aroma compounds analysis indicated that the amino acids were mainly sweet and bitter amino acids, and some key aroma compounds were predominant in the Huangjiu fermented with glutinous rice, such as ethyl butyrate (OAV: 38-59), 3-methylthiopropionaldehyde (OAV: 47-96), ethyl caprylate (OAV: 30-38), while nonanal, phenyl acetaldehyde and vanillin contributed significantly to the Huangjiu fermented with japonica rice. The multivariate statistical analysis further confirmed that 17 compounds (VIP > 1 and p < 0.05) could be supposed to be the key compouns that cause significant flavor differences in Huangjiu samples fermented with different brewing rice. Moreover, partial least-squares analysis revealed that most compounds (ethyl butyrate, 3-penten-2-one, isoamyl acetate, and so on) correlated with ester and alcoholic aroma. The results could provide basic data and theoretical basis for the selection of raw materials in Huangjiu.

Generation of Site-Selective Structural Vacancies in a Multinary Metal-Organic Framework for Enhanced Catalysis.

Generating structural vacancies in metal-organic frameworks (MOFs) by partially removing the inorganic and organic units from the scaffolds is an effective strategy to modulate the pore parameters of the extended structures. However, pore enlargement is accomplished at the cost of loss in the number of active sites in typical MOFs, since dissociations of coordination linkages to create vacancies are not site-selective. Here, we performed site-specific vacancy generation in a multinary MOF (FDM-6) by selectively hydrolyzing the weak Zn─carboxylate linkages and keeping the strong Cu─pyrazolate linkages untouched. Surface area and pore size range of the materials could be systematically tuned by adjusting the water content and hydrolysis time. More than 56% of the Zn(II) sites in FDM-6 could be vacant, as evidenced by the atom occupancy analysis using powder X-ray diffraction, while most of the redox-active Cu sites are held in the backbone. The vacancies create highly connected mesopores, thus guaranteeing facile transportation of the guest molecules toward the active sites. Compared with the pristine MOF, FDM-6 with site-selective vacancies shows enhanced catalytic activity in bulky aromatic alcohol oxidation. Overall, the multinary MOF provides a platform in which both pore size enhancement and full retainment of active sites could be delivered in one framework by simple vacancy engineering.

Metallaphotocatalytic Amination of Aryl Chlorides Enabled by Highly Crystalline Acetylene-Based Hydrazone-Linked Covalent Organic Frameworks.

Amination of aryl chlorides by metallaphotocatalysis is highly desired but remains practically challenging. Meanwhile, relying on soluble noble-metal photocatalysts suffers from resource scarcity and structural instability which limit their practical application. Here in, a highly crystalline acetylene-based hydrazone-linked covalent organic framewok-1 (AC-COF-1) is reported that enables metallaphotocatalytic amination of aryl chlorides. The non-planar effect of hydrazone linkage and weak interlayer attraction of acetylene bond are minimized by intralayer hydrogen-bonding. As a result, the COF shows not only improved crystallinity and porosity, but also enhanced optical and electronic properties compared to a COF analog without hydrogen-bonding. Notably, dual AC-COF-1/Ni system affords CN coupling products from broad aryl chloride substrates in excellent yields (up to 99%) and good functional tolerance. Furthermore, AC-COF-1 is recoverable and reusable for seven times photocatalysis cycles. This report demonstrates simple approach to tune the structure-activity relationship in COFs at molecular level.

Resveratrol Attenuates Chronic Unpredictable Mild Stress-Induced Alterations in the SIRT1/PGC1α/SIRT3 Pathway and Associated Mitochondrial Dysfunction in Mice.

Environmental challenges, specifically chronic stress, have long been associated with neuropsychiatric disorders, including anxiety and depression. Sirtuin-1 (SIRT1) is a NAD+-dependent deacetylase that is widely distributed in the cortex and is involved in stress responses and neuropsychiatric disorders. Nevertheless, how chronic stress modulates the SIRT1 pathway and associated signaling remains unclear. In this study, we first explored the impact of chronic unpredictable mild stress (CUMS) on the SIRT1/PGC1α/SIRT3 pathway, on GABAergic mechanisms, and on mitophagy, autophagy and apoptosis in mice. We also asked whether activation of SIRT1 by resveratrol (RSV) can attenuate CUMS-induced molecular and behavioral alterations. Two-month-old C57/BL6J mice were subjected to three weeks of CUMS and one week of RSV treatment (30 mg/kg; i.p.) during the third week of CUMS. CUMS caused downregulation of the SIRT1/PGC1α/SIRT3 pathway leading to impaired mitochondrial morphology and function. CUMS also resulted in a reduction in numbers of parvalbumin-positive interneurons and increased oxidative stress leading to reduced expression of autophagy- and mitophagy-related proteins. Strikingly, activation of SIRT1 by RSV ameliorated expression of SIRT1/PGC1α/SIRT3, and also improved mitochondrial function, GABAergic mechanisms, mitophagy, autophagy and apoptosis. RSV also rescued CUMS-induced anxiety-like and depressive-like behavior in mice. Our results raise the compelling possibility that RSV treatment might be a viable therapeutic method of blocking stress-induced behavioral alterations.

Site-specific anisotropic assembly of amorphous mesoporous subunits on crystalline metal-organic framework.

As an important branch of anisotropic nanohybrids (ANHs) with multiple surfaces and functions, the porous ANHs (p-ANHs) have attracted extensive attentions because of the unique characteristics of high surface area, tunable pore structures and controllable framework compositions, etc. However, due to the large surface-chemistry and lattice mismatches between the crystalline and amorphous porous nanomaterials, the site-specific anisotropic assembly of amorphous subunits on crystalline host is challenging. Here, we report a selective occupation strategy to achieve site-specific anisotropic growth of amorphous mesoporous subunits on crystalline metal-organic framework (MOF). The amorphous polydopamine (mPDA) building blocks can be controllably grown on the {100} (type 1) or {110} (type 2) facets of crystalline ZIF-8 to form the binary super-structured p-ANHs. Based on the secondary epitaxial growth of tertiary MOF building blocks on type 1 and 2 nanostructures, the ternary p-ANHs with controllable compositions and architectures are also rationally synthesized (type 3 and 4). These intricate and unprecedented superstructures provide a good platform for the construction of nanocomposites with multiple functionalities and understanding of the structure-property-function relationships.

Dynamic analysis of volatile metabolites and microbial community and their correlations during the fermentation process of traditional Huangjiu (Chinese rice wine) produced around Winter Solstice.

Traditional Huangjiu produced around Winter Solstice has higher quality and a more harmonious aroma. To investigate the variations of volatile metabolites and microbial communities during fermentation, gas chromatography-ion migration chromatography (GC-IMS), gas chromatography-mass spectroscopy (GC-MS) and high-throughput sequencing were employed. Aroma compounds results showed that alcohols and phenols increased before 45 days of fermentation and then decreased after 45 days, while esters gradually increased. Fungal genera Saccharomyces, Aspergillu, and Rhizomucor were dominant, whereas Staphylococcus, Pediococcus and Weissella were the dominant bacterial genera in the late stage. In addition, 11 genera such as Lactobacillus, Saccharopolyspora and Aspergillus (|r| > 0.6, p < 0.05) may contributed to traditional Huangjiu ecosystem stability. Moreover, correlation analysis indicated the dominant microorganisms (Saccharopolyspora, Staphylococcus, Lactobacillus, Saccharomyces and Aspergillus) were positively correlated with key compounds. These results provided theoretical guidance for further study on the flavor regulation of traditional Huangjiu via microbial community level and microbial augmentation.

Water-Harvesting Metal-Organic Frameworks with Gigantic Al24 Units and their Deconstruction into Molecular Clusters.

In contrast to the vast Al-oxo molecular cluster chemistry, Al-based building units for metal-organic framework (MOF) construction are limited in structural diversity and complexity. Synthesis of single crystalline MOFs based on this "hard" metal is further complicated by the poor reversibility of the Al-organic coordination linkages. Here, a strategy to employ two kinds of linkages with distinct strength-strong Al-carboxylate linkage and weak Cu-pyrazol N linkage-gives FDM-91 (FDM=Fudan Materials) with gigantic Al24 -based units. After replacing the weak moieties with organic linkers post-synthetically, two new stable MOFs with exceptional water harvesting capacity (up to 0.53 g g-1 ) and outstanding cycling performance are developed. Linkage-selective dissociation of FDM-91 further leads to the isolation of the Al24 molecular clusters. The versatile chemistry performed here to reinforce or deconstruct MOFs provides a new way to make important extended and discrete structures.

The Role of MR Assessments of Cardiac Morphology, Function, and Tissue Characteristics on Exercise Capacity in Well-Functioning Older Adults.

BACKGROUND: The relationship between resting cardiac indices and exercise capacity in older adults was still not well understood. New developments in cardiac magnetic resonance imaging (MRI) enable a much fuller assessment of cardiac characteristics. PURPOSE/HYPOTHESIS: To assess the association between exercise capacity and specific aspects of resting cardiac structure, function, and tissue. STUDY TYPE: Cross-sectional study. POPULATION: A total of 112 well-functioning older adults (mean age 69 years, 52 men). FIELD STRENGTH/SEQUENCE: All participants underwent 3.0 T MRI, using scan protocols including balanced steady-state free precession cine sequence, modified look-locker inversion recovery, and T2-prepared single-shot balanced steady-state free precession. ASSESSMENT: Demographic and geriatric characteristics were collected. Blood samples were assayed for lipid and glucose related biomarkers. All participants performed a symptom-limited cardiopulmonary exercise test to achieve peakVO2 . Cardiac MRI parameters were measured with semi-automatic software by S.Y., an 18-year experienced radiologist. STATISTICAL TESTS: Demographic, geriatric characteristics and MR measurements were compared among quartiles of peakVO2, with different methods according to the data type. Spearman's partial correlation and least absolute shrinkage selection operator regression were performed to select significant MR features associated with peakVO2 . Mediation effect analysis was conducted to test any indirect connection between age and peakVO2 . A two-sided P value of <0.05 was defined statistical significance. RESULTS: Epicardial fat volume, left atrial volume indexed to height, right ventricular end-systolic volume indexed to body surface area and global circumferential strain (GCS) were correlated with peakVO2 (regression coefficients were -0.040, -0.093, 0.127, and 0.408, respectively). Mediation analysis showed that the total effect of peakVO2 change was 43.6% from the change of age. The proportion of indirect effect from epicardial fat volume and GCS were 11.8% and 15.1% in total effect, respectively. DATA CONCLUSION: PeakVO2 was associated with epicardial fat volume, left atrial volume, right ventricular volume and GCS of left ventricle. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 5.

Identification of circRNAs Associated with Adipogenesis Based on RNA-seq Data in Pigs.

Adipocytes or fat cells play a vital role in the storage and release of energy in pigs, and many circular RNAs (circRNAs) have emerged as important regulators in various tissues and cell types in pigs. However, the spatio-temporal expression pattern of circRNAs between different adipose deposition breeds remains elusive. In this study, RNA sequencing (RNA-seq) produced transcriptome profiles of Western Landrace (lean-type) and Chinese Songliao black pigs (obese-type) with different thicknesses of subcutaneous fat tissues and were used to identify circRNAs involved in the regulation of adipogenesis. Gene expression analysis revealed 883 circRNAs, among which 26 and 11 circRNAs were differentially expressed between Landrace vs. Songliao pigs and high- vs. low-thickness groups, respectively. We also analyzed the interaction between circRNAs and microRNAs (miRNAs) and constructed their interaction network in adipogenesis; gene ontology classification and pathway analysis revealed two vital circRNAs, with the majority of their target genes enriched in biological functions such as fatty acids biosynthesis, fatty acid metabolism, and Wnt/TGF-ß signaling pathways. These candidate circRNAs can be taken as potential targets for further experimental studies. Our results show that circRNAs are dynamically expressed and provide a valuable basis for understanding the molecular mechanism of circRNAs in pig adipose biology.

Characterization of Bitter Compounds in Shaoxing Huangjiu by Quantitative Measurements, Taste Recombination, and Omission Experiments.

Excessive and uncoordinated bitterness of Shaoxing Huangjiu, a traditional Chinese rice wine, reduces its acceptance by consumers. To determine the compounds responsible for this bitterness, gas chromatography-mass spectrometry and high-performance liquid chromatography were performed on four types of Shaoxing Huangjiu (Yuanhong, Huadiao, Shanniang, and Xiangxue wine) for targeted quantitation of candidate compounds known to contribute to bitterness. Calculations of dose-over-threshold factors revealed that isoamyl alcohol, 1-hexanol, phenylethanol, ethyl butyrate, ethyl lactate, furfural, histidine, and arginine were important bitter compounds. Taste recombination experiments demonstrated that a recombination model constructed using the screened known bitter compounds showed good similarity with the original sample in bitter taste. Furthermore, omission experiments revealed that isobutanol, isoamyl alcohol, 1-hexanol, phenylethanol, ethyl acetate, ethyl butyrate, ethyl lactate, furfural, arginine, and valine were the compounds affecting the bitter taste perception. This study provides a certain guiding effect on the bitterness control and taste improvement of Shaoxing Huangjiu.

Integration of multi-omics data reveals cis-regulatory variants that are associated with phenotypic differentiation of eastern from western pigs.

BACKGROUND: The genetic mechanisms that underlie phenotypic differentiation in breeding animals have important implications in evolutionary biology and agriculture. However, the contribution of cis-regulatory variants to pig phenotypes is poorly understood. Therefore, our aim was to elucidate the molecular mechanisms by which non-coding variants cause phenotypic differences in pigs by combining evolutionary biology analyses and functional genomics. RESULTS: We obtained a high-resolution phased chromosome-scale reference genome with a contig N50 of 18.03 Mb for the Luchuan pig breed (a representative eastern breed) and profiled potential selective sweeps in eastern and western pigs by resequencing the genomes of 234 pigs. Multi-tissue transcriptome and chromatin accessibility analyses of these regions suggest that tissue-specific selection pressure is mediated by promoters and distal cis-regulatory elements. Promoter variants that are associated with increased expression of the lysozyme (LYZ) gene in the small intestine might enhance the immunity of the gastrointestinal tract and roughage tolerance in pigs. In skeletal muscle, an enhancer-modulating single-nucleotide polymorphism that is associated with up-regulation of the expression of the troponin C1, slow skeletal and cardiac type (TNNC1) gene might increase the proportion of slow muscle fibers and affect meat quality. CONCLUSIONS: Our work sheds light on the molecular mechanisms by which non-coding variants shape phenotypic differences in pigs and provides valuable resources and novel perspectives to dissect the role of gene regulatory evolution in animal domestication and breeding.