Learning heterogeneous reaction kinetics from X-ray videos pixel by pixel.

Reaction rates at spatially heterogeneous, unstable interfaces are notoriously difficult to quantify, yet are essential in engineering many chemical systems, such as batteries1 and electrocatalysts2. Experimental characterizations of such materials by operando microscopy produce rich image datasets3-6, but data-driven methods to learn physics from these images are still lacking because of the complex coupling of reaction kinetics, surface chemistry and phase separation7. Here we show that heterogeneous reaction kinetics can be learned from in situ scanning transmission X-ray microscopy (STXM) images of carbon-coated lithium iron phosphate (LFP) nanoparticles. Combining a large dataset of STXM images with a thermodynamically consistent electrochemical phase-field model, partial differential equation (PDE)-constrained optimization and uncertainty quantification, we extract the free-energy landscape and reaction kinetics and verify their consistency with theoretical models. We also simultaneously learn the spatial heterogeneity of the reaction rate, which closely matches the carbon-coating thickness profiles obtained through Auger electron microscopy (AEM). Across 180,000 image pixels, the mean discrepancy with the learned model is remarkably small (<7%) and comparable with experimental noise. Our results open the possibility of learning nonequilibrium material properties beyond the reach of traditional experimental methods and offer a new non-destructive technique for characterizing and optimizing heterogeneous reactive surfaces.

The Isolation, Structural Characterization and Anti-Inflammatory Potentials of Neutral Polysaccharides from the Roots of Isatis indigotica Fort.

Polysaccharides have been assessed as a potential natural active component in Chinese herbal medicine with anti-inflammatory properties. However, the complex and indefinite structures of polysaccharides limit their applications. This study explains the structures and anti-inflammatory potentials of three neutral polysaccharides, RIP-A1 (Mw 1.8 × 104 Da), RIP-B1 (Mw 7.4 × 104 Da) and RIP-B2 (Mw 9.3 × 104 Da), which were isolated from the roots of Isatis indigotica Fort. with sequenced ultrafiltration membrane columns, DEAE-52 and Sephadex G-100. The planar structures and microstructures of RIP-A1, RIP-B1 and RIP-B2 were further determined by HPGPC, GC-MS, methylation analysis, FT-IR, SEM and AFM, in which the structure of RIP-A1 was elucidated in detail using 1D/2D NMR. The Raw 264.7 cells were used for the anti-inflammatory activity in vitro. The results showed that RIP-A1, RIP-B1 and RIP-B2 are all neutral polysaccharides, with RIP-A1 having the smallest Mw and the simplest monosaccharide composition of the three. RIP-A1 is mainly composed of Ara and Gal, except for a small quantity of Rha. Its main structure is covered with glycosidic linkages of T-α-Araf, 1,2-α-Rhap, 1,5-α-Araf, T-ß-Galp, 1,2,4-α-Rhap, 1,3,5-α-Araf and 1,6-ß-Galp with 0.33:0.12:1.02:0.09:0.45:11.41:10.23. RIP-A1 significantly inhibited pro-inflammatory cytokines (NO, TNF-α, IL-6 and IL-1ß) and increased anti-inflammatory cytokines (IL-4) in LPS-stimulated RAW 264.7 cells. Moreover, RIP-A1 could significantly inhibit the mRNA expression of TNF-α, IL-6 and L-1ß. It could also activate IKK, p65 and IκBα (the components of the NF-κB signaling pathway). In conclusion, the above results show the structural characterization and anti-inflammatory potentials of RIP-A1 as an effective natural anti-inflammatory drug.

Correlative image learning of chemo-mechanics in phase-transforming solids.

Constitutive laws underlie most physical processes in nature. However, learning such equations in heterogeneous solids (for example, due to phase separation) is challenging. One such relationship is between composition and eigenstrain, which governs the chemo-mechanical expansion in solids. Here we developed a generalizable, physically constrained image-learning framework to algorithmically learn the chemo-mechanical constitutive law at the nanoscale from correlative four-dimensional scanning transmission electron microscopy and X-ray spectro-ptychography images. We demonstrated this approach on LiXFePO4, a technologically relevant battery positive electrode material. We uncovered the functional form of the composition-eigenstrain relation in this two-phase binary solid across the entire composition range (0 ≤ X ≤ 1), including inside the thermodynamically unstable miscibility gap. The learned relation directly validates Vegard's law of linear response at the nanoscale. Our physics-constrained data-driven approach directly visualizes the residual strain field (by removing the compositional and coherency strain), which is otherwise impossible to quantify. Heterogeneities in the residual strain arise from misfit dislocations and were independently verified by X-ray diffraction line profile analysis. Our work provides the means to simultaneously quantify chemical expansion, coherency strain and dislocations in battery electrodes, which has implications on rate capabilities and lifetime. Broadly, this work also highlights the potential of integrating correlative microscopy and image learning for extracting material properties and physics.

Chemotactic Motility-Induced Phase Separation.

Collectives of actively moving particles can spontaneously separate into dilute and dense phases-a fascinating phenomenon known as motility-induced phase separation (MIPS). MIPS is well-studied for randomly moving particles with no directional bias. However, many forms of active matter exhibit collective chemotaxis, directed motion along a chemical gradient that the constituent particles can generate themselves. Here, using theory and simulations, we demonstrate that collective chemotaxis strongly competes with MIPS-in some cases, arresting or completely suppressing phase separation, or in other cases, generating fundamentally new dynamic instabilities. We establish principles describing this competition, thereby helping to reveal and clarify the rich physics underlying active matter systems that perform chemotaxis, ranging from cells to robots.

MMP-Responsive Nanoparticle-Loaded, Injectable, Adhesive, Self-Healing Hydrogel Wound Dressing Based on Dynamic Covalent Bonds.

Developing a multifunctional hydrogel wound dressing with good injectability, self-healing, tissue adhesion, biocompatibility, and fast skin wound healing efficiency remains challenging. In this work, an injectable adhesive dopamine-functionalized oxidized hyaluronic acid/carboxymethyl chitosan/collagen (AHADA/CCS/Col) hydrogel was constructed. The Schiff dynamic bond between AHADA and CCS, the N-Ag-N bond between CCS and Ag ions, and the S-Ag-S dynamic bond between sulfhydryl-modified collagen (ColSH) and Ag ions allowed the hydrogel to be both injectable and self-healing. Moreover, the aldehyde groups and catechol groups presented in the hydrogel could generate force with several groups on the tissue interface; therefore, the hydrogel also had good tissue adhesion. In vitro experiments proved that this hydrogel exhibited good biocompatibility and could promote cell proliferation. Additionally, curcumin (Cur)-loaded gelatin nanoparticles (Cur@Gel NPs) were prepared, which could respond to matrix metalloproteinases (MMPs) and controllably release Cur to hasten wound healing efficiency. Animal experiment results showed that this AHADA/CCS/Col hydrogel loaded with Cur@Gel NPs promoted wound repairing better, indicating its potential as a wound dressing.

A novel two-dimensional NiCl2O8 lattice with negative Poisson's ratio and magnetic modulation.

Two-dimensional (2D) materials with simultaneous magnetic semiconducting properties and a negative Poisson's ratio are crucial for fabricating multifunctional electronic devices. However, progress in this area has been generally constrained. Based on first-principles calculations, we engineered a 2D Ni-based oxyhalide with a honeycomb lattice structure. It was observed that the NiCl2O8 monolayer exhibits both high- and low-buckling states in its geometry, along with intrinsic magnetic semiconductor properties in its electronic structure. Importantly, we demonstrated that the magnetic ordering of the NiCl2O8 lattice is susceptible to applied strain, which resulted in a phase transition from paramagnetic to ferromagnetic under biaxial strain. The Curie temperature was also evaluated using Monte Carlo simulations within the Ising model. Additionally, our research uncovered that the 2D NiCl2O8 lattice chain displays a negative Poisson's ratio (NPR) along the z-direction. The triangular hinge structure in its centrosymmetric configuration was identified as the origin of this unique phenomenon. The coexistence of NPR and magnetic phase transition properties in the NiCl2O8 lattice makes it quite promising for applications in nanoelectronic and spintronic devices.

Temperature regulation of carotenoid accumulation in the petals of sweet osmanthus via modulating expression of carotenoid biosynthesis and degradation genes.

BACKGROUND: Temperature is involved in the regulation of carotenoid accumulation in many plants. The floral color of sweet osmanthus (Osmanthus fragrans Lour.) which is mainly contributed by carotenoid content, is affected by temperature in autumn. However, the mechanism remains unknown. Here, to reveal how temperature regulates the floral color of sweet osmanthus, potted sweet osmanthus 'Jinqiu Gui' were treated by different temperatures (15 °C, 19 °C or 32 °C). The floral color, carotenoid content, and the expression level of carotenoid-related genes in petals of sweet osmanthus 'Jinqiu Gui' under different temperature treatments were investigated. RESULTS: Compared to the control (19 °C), high temperature (32 °C) changed the floral color from yellow to yellowish-white with higher lightness (L*) value and lower redness (a*) value, while low temperature (15 °C) turned the floral color from yellow to pale orange with decreased L* value and increased a* value. Total carotenoid content and the content of individual carotenoids (α-carotene, ß-carotene, α-cryptoxanthin, ß-cryptoxanthin, lutein and zeaxanthin) were inhibited by high temperature, but were enhanced by low temperature. Lower carotenoid accumulation under high temperature was probably attributed to transcriptional down-regulation of the biosynthesis gene OfPSY1, OfZ-ISO1 and OfLCYB1, and up-regulation of degradation genes OfNCED3, OfCCD1-1, OfCCD1-2, and OfCCD4-1. Up-regulation of OfLCYB1, and down-regulation of OfNCED3 and OfCCD4-1 were predicted to be involved in low-temperature-regulated carotenoid accumulation. Luciferase assays showed that the promoter activity of OfLCYB1 was activated by low temperature, and repressed by high temperature. However, the promoter activity of OfCCD4-1 was repressed by low temperature, and activated by high temperature. CONCLUSIONS: Our study revealed that high temperature suppressed the floral coloration by repressing the expression of carotenoid biosynthesis genes, and activating the expression of carotenoid degradation genes. However, the relative low temperature had opposite effects on floral coloration and carotenoid biosynthesis in sweet osmanthus. These results will help reveal the regulatory mechanism of temperature on carotenoid accumulation in the petals of sweet osmanthus.

Efferent neurons control hearing sensitivity and protect hearing from noise through the regulation of gap junctions between cochlear supporting cells.

It is critical for hearing that the descending cochlear efferent system provides a negative feedback to hair cells to regulate hearing sensitivity and protect hearing from noise. The medial olivocochlear (MOC) efferent nerves project to outer hair cells (OHCs) to regulate OHC electromotility, which is an active cochlear amplifier and can increase hearing sensitivity. Here, we report that the MOC efferent nerves also could innervate supporting cells (SCs) in the vicinity of OHCs to regulate hearing sensitivity. MOC nerve fibers are cholinergic, and acetylcholine (ACh) is a primary neurotransmitter. Immunofluorescent staining showed that MOC nerve endings, presynaptic vesicular acetylcholine transporters (VAChTs), and postsynaptic ACh receptors were visible at SCs and in the SC area. Application of ACh in SCs could evoke a typical inward current and reduce gap junctions (GJs) between them, which consequently enhanced the direct effect of ACh on OHCs to shift but not eliminate OHC electromotility. This indirect, GJ-mediated inhibition had a long-lasting influence. In vivo experiments further demonstrated that deficiency of this GJ-mediated efferent pathway decreased the regulation of active cochlear amplification and compromised the protection against noise. In particular, distortion product otoacoustic emission (DPOAE) showed a delayed reduction after noise exposure. Our findings reveal a new pathway for the MOC efferent system via innervating SCs to control active cochlear amplification and hearing sensitivity. These data also suggest that this SC GJ-mediated efferent pathway may play a critical role in long-term efferent inhibition and is required for protection of hearing from noise trauma.NEW & NOTEWORTHY The cochlear efferent system provides a negative feedback to control hair cell activity and hearing sensitivity and plays a critical role in noise protection. We reveal a new efferent control pathway in which medial olivocochlear efferent fibers have innervations with cochlear supporting cells to control their gap junctions, therefore regulating outer hair cell electromotility and hearing sensitivity. This supporting cell gap junction-mediated efferent control pathway is required for the protection of hearing from noise.

Fictitious phase separation in Li layered oxides driven by electro-autocatalysis.

Layered oxides widely used as lithium-ion battery electrodes are designed to be cycled under conditions that avoid phase transitions. Although the desired single-phase composition ranges are well established near equilibrium, operando diffraction studies on many-particle porous electrodes have suggested phase separation during delithiation. Notably, the separation is not always observed, and never during lithiation. These anomalies have been attributed to irreversible processes during the first delithiation or reversible concentration-dependent diffusion. However, these explanations are not consistent with all experimental observations such as rate and path dependencies and particle-by-particle lithium concentration changes. Here, we show that the apparent phase separation is a dynamical artefact occurring in a many-particle system driven by autocatalytic electrochemical reactions, that is, an interfacial exchange current that increases with the extent of delithiation. We experimentally validate this population-dynamics model using the single-phase material Lix(Ni1/3Mn1/3Co1/3)O2 (0.5 < x < 1) and demonstrate generality with other transition-metal compositions. Operando diffraction and nanoscale oxidation-state mapping unambiguously prove that this fictitious phase separation is a repeatable non-equilibrium effect. We quantitatively confirm the theory with multiple-datastream-driven model extraction. More generally, our study experimentally demonstrates the control of ensemble stability by electro-autocatalysis, highlighting the importance of population dynamics in battery electrodes (even non-phase-separating ones).

Comparative transcriptomics analysis reveals a calcineurin B-like gene to positively regulate constitutive and acclimated freezing tolerance in potato.

Freezing stress is a major limiting factor in crop production. To increase frost-hardiness of crops via breeding, deciphering the genes conferring freezing-tolerance is vital. Potato cultivars (Solanum tuberosum) are generally freezing-sensitive, but some potato wild species are freezing-tolerant, including Solanum commersonii, Solanum malmeanum and Solanum acaule. However, the underlying molecular mechanisms conferring the freezing-tolerance to the wild species remain to be deciphered. In this study, five representative genotypes of the above-mentioned species with distinct freezing-tolerance were investigated. Comparative transcriptomics analysis showed that SaCBL1-like (calcineurin B-like protein) was upregulated substantially in all of the freezing-tolerant genotypes. Transgenic overexpression and known-down lines of SaCBL1-like were examined. SaCBL1-like was shown to confer freezing-tolerance without significantly impacting main agricultural traits. A functional mechanism analysis showed that SaCBL1-like increases the expression of the C-repeat binding factor-regulon as well as causes a prolonged higher expression of CBF1 after exposure to cold conditions. Furthermore, SaCBL1-like was found to only interact with SaCIPK3-1 (CBL-interacting protein kinase) among all apparent cold-responsive SaCIPKs. Our study identifies SaCBL1-like to play a vital role in conferring freezing tolerance in potato, which may provide a basis for a targeted potato breeding for frost-hardiness.

PLAC8 promotes the autophagic activity and improves the growth priority of human trophoblast cells.

Autophagy plays an important role in the normal development and function of trophoblast cells and is precisely regulated during pregnancy. Dysregulated autophagy contributes to the abnormal proliferation of trophoblasts, which is closely related to the occurrence of pregnancy-related diseases. Placenta specific 8 (PLAC8, Onzin) is a multifaceted protein proven to promote autophagy and potentiate various tumor progression. Its role in trophoblasts remains elusive. In our present study, PLAC8 expression was detected in tissues of first-trimester placentas (n = 5), term placentas (n = 5), choriocarcinoma (n = 5), and placental site trophoblastic tumor (n = 5). PLAC8 expression was increased in gestational neoplasms compared with normal pregnancies. mCherry-EGFP-LC3B reporter and transmission electron microscopy confirmed PLAC8 promoted the autophagic flux of human trophoblast cells. Both gain-of-function and loss-of-function experiments demonstrated PLAC8-regulated autophagy-related genes, including ATG5, ATG12, and Beclin-1. In addition, our data showed that PLAC8 co-localized with p53 and promoted its degradation, and p53 re-expression partially abrogated the PLAC8-induced autophagy activity. Furthermore, the overexpression of PLAC8 promoted cell viability and proliferation, acting as a protective mechanism of trophoblasts against the cytotoxicity of etoposide (VP-16). Such a phenomenon was effectively abrogated by autophagy inhibitors 3-methyladenine (3-MA) and chloroquine (CQ). In conclusion, PLAC8-induced autophagy to promote the proliferation of trophoblasts. This study provided insights into the mechanism of PLAC8-induced autophagy in trophoblasts, which is significant for a wide range of gestational diseases and may contribute to developing novel treatment strategies for trophoblastic diseases.

Expression profiling of lncRNAs and mRNAs in placental site trophoblastic tumor (PSTT) by microarray.

As a rare type of gestational trophoblastic disease, placental site trophoblastic tumor (PSTT) is originated from intermediate trophoblast cells. Long noncoding RNAs (lncRNAs) regulate numerous biological process. However, the role of lncRNAs in PSTT remains poorly understood. In the present study, expression levels of lncRNAs and mRNAs in four human PSTT tissues and four normal placental villi were investigated. The results of microarray were validated by the reverse transcription and quantitative real-time polymerase reaction (RT-qPCR) and immunohistochemistry analyses. Furthermore, GO and KEGG pathway analyses were performed to identify the underlying biological processes and signaling pathways of aberrantly expressed lncRNAs and mRNAs. We also conducted the coding-non-coding gene co-expression (CNC) network to explore the interaction of altered lncRNAs and mRNAs. In total, we identified 1247 up-regulated lncRNAs and 1013 down-regulated lncRNAs as well as 828 up-regulated mRNAs and 1393 down-regulated mRNAs in PSTT tissues compared to normal villi (fold change ≥ 2.0, p < 0.05). GO analysis showed that mitochondrion was the most significantly down-regulated GO term, and immune response was the most significantly up-regulated term. A CNC network profile based on six confirmed lncRNAs (NONHSAT114519, NR_103711, NONHSAT003875, NONHSAT136587, NONHSAT134431, NONHSAT102500) as well as 354 mRNAs was composed of 497 edges. GO and KEGG analyses indicated that interacted mRNAs were enriched in the signal-recognition particle (SRP)-dependent cotranslational protein targeting to membrane and Ribosome pathway. It contributes to expand the understanding of the aberrant lncRNAs and mRNAs profiles of PSTT, which may be helpful for the exploration of new diagnosis and treatment of PSTT.

MicroRNA-146a and microRNA-146b deficiency correlates with exacerbated disease activity, and their longitude increment relates to etanercept response in psoriasis patients.

BACKGROUND: MicroRNA (miR)-146a and miR-146b regulate autoimmunity, inflammation, and keratinocytes proliferation to engage in psoriasis pathology. The current study aimed to investigate their correlation with disease risk and clinical features, and the linkage of their longitudinal changes with clinical response to etanercept in psoriasis patients. METHODS: Plasma samples were collected from 84 moderate-to-severe psoriasis patients who underwent etanercept treatment (at baseline (M0), 1 month (M1), 3 months (M3), and 6 months (M6)), 80 disease controls and 80 health controls (both after enrollment); afterward, miR-146a and miR-146b expressions were detected by RT-qPCR. Furthermore, PASI75 and PASI90 responses were assessed in psoriasis patients. RESULTS: Both miR-146a and miR-146b were decreased in psoriasis patients compared with disease controls and health controls (all p < 0.001), which also distinguished psoriasis patients from disease controls and health controls by receiver-operating characteristic analyses. Furthermore, miR-146a positively correlated with miR-146b in psoriasis patients (p < 0.001) and disease controls (p = 0.005) but not in healthy controls (p = 0.062). In psoriasis patients, miR-146a negatively related to psoriatic body surface area (p = 0.011) and PASI score (p = 0.003); miR-146b negatively linked with PASI score (p = 0.020). At M1, M3, and M6 after etanercept treatment, PASI75 response rate was 14.3%, 32.1%, and 69.0%, respectively; PASI90 response rate was 1.2%, 17.9%, and 36.9%, respectively. During etanercept treatment, both miR-146a and miR-146b elevated gradually over time and their longitude increments were associated with PASI75 response (all p < 0.001). CONCLUSION: MiR-146a and miR-146b might serve as indicators for optimizing etanercept application and improving treatment outcomes in psoriasis patients.

Overexpression CPT1A reduces lipid accumulation via PPARα/CD36 axis to suppress the cell proliferation in ccRCC.

Clear cell renal carcinoma (ccRCC) is histologically defined by its cytoplasmic lipid deposits. Lipid metabolism disorder largely increases the risk of ccRCC. In this study, we aimed to investigate the biological functions and molecular mechanisms of carnitine palmitoyl transferase 1A (CPT1A) in ccRCC. Our results showed that CPT1A is decreased in ccRCC clinical samples and cell lines compared with that in normal samples. Lentivirus overexpressing CPT1A was used to investigate the neoplastic phenotypes of ccRCC, and the results showed that lipid accumulation and tumor growth are attenuated both and . In addition, CPT1A prevents cholesterol uptake and lipid accumulation by increasing the peroxisome proliferator-activated receptor α (PPARα) level through regulation of Class B scavenger receptor type 1 (SRB1) and cluster of differentiation 36 (CD36). Furthermore, PI3K/Akt signaling pathway promotes tumor cell proliferation in ccRCC, which is related to the enhanced expression of CD36. Functionally, weakened CPT1A expression is critical for lipid accumulation to promote ccRCC development. Collectively, our research unveiled a novel function of CPT1A in lipid metabolism via PPARα/CD36 axis, which provides a new theoretical explanation for the pathogenesis of ccRCC. Targeting CPT1A may be a potential therapeutic strategy to treat ccRCC.

Genome-Wide Identification of Switchgrass Laccases Involved in Lignin Biosynthesis and Heavy-Metal Responses.

Plant laccase genes belong to a multigene family, play key roles in lignin polymerization, and participate in the resistance of plants to biotic and abiotic stresses. Switchgrass is an important resource for forage and bioenergy production, yet information about the switchgrass laccase gene family is scarce. Using bioinformatic approaches, a genome-wide analysis of the laccase multigene family in switchgrass was carried out in this study. In total, 49 laccase genes (PvLac1 to PvLac49) were identified; these can be divided into five subclades, and 20 of them were identified as targets of miR397. The tandem and segmental duplication of laccase genes on Chr05 and Chr08 contributed to the expansion of the laccase family. The laccase proteins shared conserved signature sequences but displayed relatively low sequence similarity, indicating the potential functional diversity of switchgrass laccases. Switchgrass laccases exhibited distinct tissue/organ expression patterns, revealing that some laccases might be involved in the lignification process during stem development. All five of the laccase isoforms selected from different subclades responded to heavy metal. The immediate response of lignin-related laccases, as well as the delayed response of low-abundance laccases, to heavy-metal treatment shed light on the multiple roles of laccase isoforms in response to heavy-metal stress.

Comparative Transcriptome Analysis of CCCH Family in Roles of Flower Opening and Abiotic Stress in Osmanthus fragrans.

CCCH is a zinc finger family with a typical CCCH-type motif which performs a variety of roles in plant growth and development and responses to environmental stressors. However, the information about this family has not been reported for Osmanthus fragrans. In this study, a total of 66 CCCH predicted genes were identified from the O. fragrans genome, the majority of which had multiple CCCH motifs. The 66 OfCCCHs were found to be unevenly distributed on 21 chromosomes and were clustered into nine groups based on their phylogenetic analysis. In each group, the gene structure and domain makeup were comparatively conserved. The expression profiles of the OfCCCH genes were examined in various tissues, the flower-opening processes, and under various abiotic stresses using transcriptome sequencing and qRT-PCR (quantitative real-time PCR). The results demonstrated the widespread expression of OfCCCHs in various tissues, the differential expression of 22 OfCCCHs during flower-opening stages, and the identification of 4, 5, and 13 OfCCCHs after ABA, salt, and drought stress treatment, respectively. Furthermore, characterization of the representative OfCCCHs (OfCCCH8, 23, 27, and 36) revealed that they were all localized in the nucleus and that the majority of them had transcriptional activation in the yeast system. Our research offers the first thorough examination of the OfCCCH family and lays the groundwork for future investigations regarding the functions of CCCH genes in O. fragrans.

Integrated Transcriptome and Metabolome Analysis of Color Change and Low-Temperature Response during Flowering of Prunus mume.

In China, Prunus mume is a famous flowering tree that has been cultivated for 3000 years. P. mume grows in tropical and subtropical regions, and most varieties lack cold resistance; thus, it is necessary to study the low-temperature response mechanism of P. mume to expand the scope of its cultivation. We used the integrated transcriptomic and metabolomic analysis of a cold-resistant variety of P. mume 'Meiren', to identify key genes and metabolites associated with low temperatures during flowering. The 'Meiren' cultivar responded in a timely manner to temperature by way of a low-temperature signal transduction pathway. After experiencing low temperatures, the petals fade and wilt, resulting in low ornamental value. At the same time, in the cold response pathway, the activities of related transcription factors up- or downregulate genes and metabolites related to low temperature-induced proteins, osmotic regulators, protective enzyme systems, and biosynthesis and metabolism of sugars and acids. Our findings promote research on the adaptation of P. mume to low temperatures during wintering and early flowering for domestication and breeding.

Salicylic Acid Improves the Constitutive Freezing Tolerance of Potato as Revealed by Transcriptomics and Metabolomics Analyses.

Freezing severely impacts potato production. Deciphering the pathways and metabolites that regulate the freezing tolerance of potato is useful in cultivation and breeding for hardiness. In the present study, Solanum acaule was identified to be more freezing tolerant than S. tuberosum. Furthermore, the two genotypes before/after exposure to 4 °C for 7 d with additional -1 °C for 12 h were analysed by RNA-seq and metabolomics, and the results were compared with the previous -1 °C for 12 h. The results showed that S. acaule activated numerous genes that differed from those of S. tuberosum. Among the genes, five pathways, such as the hormone signalling pathway, which includes salicylic acid, were enriched. Further metabolomics analysis showed that the content of salicylic acid was improved in S. acaule in response to -1 °C for 12 h. Moreover, exogenous application of 0.1 mM salicylic acid to potato was shown to improve constitutive freezing tolerance and increase the expression of HSFC1. Following transcriptome and metabolome analyses, it was documented that the content of SA that increased in freezing-tolerant S. acaule after exposure to cold condition, associated with the SA signalling pathway, enhanced potato freezing tolerance, probably through HSFC1.

Integrative analysis and experiments to explore angiogenesis regulators correlated with poor prognosis, immune infiltration and cancer progression in lung adenocarcinoma.

Angiogenesis is the process of capillary sprouting from pre-existing vessels and it plays a critical role in the carcinogenic process of lung adenocarcinoma (LUAD). However, the association of angiogenesis regulators with the prognosis and progression of LUAD needs to be further elucidated. In this study, we adopted differential expression analysis, Cox proportional hazards (PH) regression analysis and experimental validation to identify angiogenesis regulators correlated with a poor prognosis, immune infiltration and cancer progression in LUAD. These results showed that the diagnostic and prognostic models based on COL5A2 and EPHB2 served as independent biomarkers with superior predictive ability. The patients in the high-risk group exhibited a worse prognosis in the TCGA cohort (P < 0.001, HR = 1.72, 95% CI 1.28-2.30), GSE310210 cohort (P = 0.005, HR = 2.87, 95% CI 1.46-5.61), and GSE31019 cohort (P = 0.01, HR = 2.14, 95% CI 1.19-3.86) than patients in the low-risk group. The high prognostic risk patients had a higher TMB (P < 0.001); higher fractions of M0 macrophages, neutrophils, NK cells resting, and T cells CD4 memory activated (P < 0.05); and higher expression of immune checkpoints PD-1, PDL-1, PDL-2, and B7H3 (P < 0.001). Patients in the high-risk group were more sensitive to chemotherapeutic drugs and molecular targeted drugs such as cisplatin, doxorubicin, gefitinib, and bosutinib (P < 0.0001). In addition, inhibition of COL5A2 and EPHB2 effectively suppressed the proliferation and migration of LUAD cells. The current study identified angiogenesis regulators as potential biomarkers and therapeutic targets for LUAD and may help to further optimize cancer therapy.

In Situ Forming Cellulose Nanofibril-Reinforced Hyaluronic Acid Hydrogel for Cartilage Regeneration.

Hyaluronic acid (HA) based hydrogels are one of most functional natural biomaterials in the field of cartilage tissue engineering (CTE). Even with the promising advantages of HA hydrogels, the complicated mechanical properties of the native cartilage have not been realized, and fabricating HA hydrogels with excellent mechanical properties to make them practical in CTE still remains a current challenge. Here, a strategy that integrates hydrogels and nanomaterials is shown to form a HA hydrogel with sufficient mechanical loading for cartilage tissue production and recombination. Cellulose nanofibrils (CNFs) are promising nanomaterial candidates as they possess high mechanical strength and excellent biocompatibility. In this study, we developed methacrylate-functionalized CNFs that are able to photo-crosslink with methacrylated HA to fabricate HA/CNF nanocomposite hydrogels. The present composite hydrogels with a compressive modulus of 0.46 ± 0.05 MPa showed adequate compressive strength (0.198 ± 0.009 MPa) and restorability, which can be expected to employ as a stress-bearing tissue such as articular cartilage. Besides, this nanocomposite hydrogel could provide a good microenvironment for bone marrow mesenchymal stem cell proliferation, as well as chondrogenic differentiation, and exhibit prominent repair effect in the full-thickness cartilage defect model of SD rats. These results suggest that the HA/CNF nanocomposite hydrogel creates a new possibility for fabricating a scaffold in CTE.