Condensate interfacial forces reposition DNA loci and probe chromatin viscoelasticity.

Biomolecular condensates assemble in living cells through phase separation and related phase transitions. An underappreciated feature of these dynamic molecular assemblies is that they form interfaces with other cellular structures, including membranes, cytoskeleton, DNA and RNA, and other membraneless compartments. These interfaces are expected to give rise to capillary forces, but there are few ways of quantifying and harnessing these forces in living cells. Here, we introduce viscoelastic chromatin tethering and organization (VECTOR), which uses light-inducible biomolecular condensates to generate capillary forces at targeted DNA loci. VECTOR can be utilized to programmably reposition genomic loci on a timescale of seconds to minutes, quantitatively revealing local heterogeneity in the viscoelastic material properties of chromatin. These synthetic condensates are built from components that naturally form liquid-like structures in living cells, highlighting the potential role for native condensates to generate forces and do work to reorganize the genome and impact chromatin architecture.

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.

Host-Guest Interaction Mediated Perovskite@Metal-Organic Framework Z-Scheme Heterojunction Enabled Paper-Based Photoelectrochemical Sensing.

Exploring the high-performance photoelectronic properties of perovskite quantum dots (QDs) is desirable for paper-based photoelectrochemical (PEC) sensing;however, challenges remain in improving their stability and fundamental performance. Herein, a novel Z-scheme heterostructure with host-guest interaction by the confinement of CH3NH3PbBr3 QDs within Cu3(BTC)2 metal-organic framework (MOF) crystal (MAPbBr3@Cu3(BTC)2) is successfully constructed on the paper-based PEC device for ultrasensitive detection of Ochratoxin A (OTA), with the assistance of the exciton-plasmon interaction (EPI) effect. The host-guest interaction is estabilished by encapsulating MAPbBr3 QDs as guests within Cu3(BTC)2 MOF as a host, which prevents MAPbBr3 QDs from being damaged in the polar system, offering access to long-term stability with high-performance PEC properties. Benefiting from the precise alignment of energy levels, the photogenerated charge carriers can migrate according to the Z-scheme charge-transfer pathway under the driving force of the internal electric field, achieving a high photoelectric conversion efficiency. Upon OTA recognition, the EPI effect is activated to modulate the exciton response in MAPbBr3 QDs by accelerating radiative decay, finally achieving sensitive OTA sensing with a detection limit of 0.017 pg mL-1. We believe this work renders new insight into designing host-guest Z-scheme heterojunctions in constructing the paper-based PEC sensing platforms for environmental monitoring.

Crystal structure and function of a phosphate starvation responsive protein phosphatase, GmHAD1-2 regulating soybean root development and flavonoid metabolism.

Phosphate (Pi) availability is well known to regulate plant root growth. However, it remains largely unknown how flavonoid synthesis participates in affecting plant root growth in response to Pi starvation. In the study, the crystal structure of a plant protein phosphatase, GmHAD1-2, was dissected using X-ray crystallography for the first time. It was revealed that GmHAD1-2 contained a modified Rossmannoid class of α/ß folds with three layered α/ß sandwich. Transcripts of GmHAD1-2 were increased by Pi starvation in soybean roots, especially in lateral root tips. GmHAD1-2 suppression or overexpression significantly influenced soybean lateral root length and number, as well as phosphorus (P) content. Furthermore, GmHAD1-2 was found to interact with a chalcone reductase, GmCHR1. Suppression of GmHAD1-2 significantly changed the flavonoid biosynthesis pathway in soybean roots. Taken together, the results highlight that GmHAD1-2 can regulate soybean root growth by influencing flavonoid metabolism.

An EIL Family Transcription Factor From Switchgrass Affects Sulphur Assimilation and Root Development in Arabidopsis.

Sulphur limitation 1 (SLIM1), a member of ethylene-insensitive3-like (EIN3/EIL) protein family, is recognised as the pivotal transcription factor regulating sulphur assimilation, essential for maintaining sulphur homoeostasis in Arabidopsis. However, the function of its monocot homologues is largely unknown. In this study, we identified PvEIL3a, a homologous gene of AtSLIM1, from switchgrass (Panicum virgatum L.), a significant perennial bioenergy crop. Our results demonstrated that introducing PvEIL3a into Arabidopsis slim1 mutants significantly increased the expression of genes responsive to sulphur deficiency, and transgenic plants exhibited shortened root length and delayed development. Moreover, PvEIL3a activated the expression of AtAPR1, AtSULTR1;1 and AtBGLU30, which plays an important role in sulphur assimilation and glucosinolate metabolism. Results of transcriptome and metabonomic analysis further indicated a perturbation in the metabolic pathways of tryptophan-dependent indole glucosinolates (IGs), camalexin and auxin. In addition, PvEIL3a conservatively regulated sulphur assimilation and the biosynthesis of tryptophan pathway-derived secondary metabolites, which reduced the biosynthesis of indole-3-acetic acid (IAA) and inhibited the root elongation of transgenic Arabidopsis. In conclusion, this study highlights the functional difference of the ethylene-insensitive 3-like (EIL) family gene in monocot and dicot plants, thereby deepening the understanding of the specific biological roles of EIL3 in monocot plant species.

The inertial-based gait normalcy index of dual task cost during turning quantifies gait automaticity improvement in early-stage Parkinson's rehabilitation.

BACKGROUND: The loss of gait automaticity is a key cause of motor deficits in Parkinson's disease (PD) patients, even at the early stage of the disease. Action observation training (AOT) shows promise in enhancing gait automaticity. However, effective assessment methods are lacking. We aimed to propose a novel gait normalcy index based on dual task cost (NIDTC) and evaluate its validity and responsiveness for early-stage PD rehabilitation. METHODS: Thirty early-stage PD patients were recruited and randomly assigned to the AOT or active control (CON) group. The proposed NIDTC during straight walking and turning tasks and clinical scale scores were measured before and after 12 weeks of rehabilitation. The correlations between the NIDTCs and clinical scores were analyzed with Pearson correlation coefficient analysis to evaluate the construct validity. The rehabilitative changes were assessed using repeated-measures ANOVA, while the responsiveness of NIDTC was further compared by t tests. RESULTS: The turning-based NIDTC was significantly correlated with multiple clinical scales. Significant group-time interactions were observed for the turning-based NIDTC (F = 4.669, p = 0.042), BBS (F = 6.050, p = 0.022) and PDQ-39 (F = 7.772, p = 0.011) tests. The turning-based NIDTC reflected different rehabilitation effects between the AOT and CON groups, with the largest effect size (p = 0.020, Cohen's d = 0.933). CONCLUSION: The turning-based NIDTC exhibited the highest responsiveness for identifying gait automaticity improvement by providing a comprehensive representation of motor ability during dual tasks. It has great potential as a valid measure for early-stage PD diagnosis and rehabilitation assessment. Trial registration Chinese Clinical Trial Registry: ChiCTR2300067657.

Study on the role of microbial metabolites in in-situ noncontact bioleaching of ion-adsorption rare earth ore.

Ion adsorption rare earth ore nearly satisfy global market demand for heavy rare earth elements (HREEs). Bio-leaching has important potential for the clean and efficient extraction of ion-adsorption rare earth ore. However, the complexities of in-situ mining restrict the use of contact/direct bio-leaching, and non-contact/indirect bio-leaching would be the best choice. This study explore the potential of fermentation broths prepared by Yarrowia lipolytica (ATCC 30162) for the bio-leaching of ion-adsorption rare earth ore, and three typical metabolites (potassium citrate (K3Cit), sodium citrate (Na3Cit) and ammonium citrate ((NH4)3Cit) of Yarrowia lipolytica were further evaluated in simulated bioleaching (non-contact bioleaching) of ion-adsorption rare earth ore, including leaching behavior, seepage rule and rare earth elements (REEs) morphological transformation. The column leaching experiments shown that direct leaching of REEs using fermentation broths results in incomplete leaching of REEs due to the influence of impurities. Using the purified and prepared metabolites as lixiviant, REEs can be effectively extracted (leaching efficiency >90%) at cation concentration was only 10 % of the commonly used ammonium sulfate concentration (45 mM). Cation type had less effect on leaching efficiency. During the ion-adsorption rare earth ore leaching process, rare earth ions form a variety of complex chelates with citrate, thus transferring rare earth elements from the mineral surface to the leachate. Experimental results showed that pH and concentration together determined the type and form of rare earth chelates, which in turn affect the leaching behavior of REEs and solution seepage rule. This study helps to provide a theoretical basis for the regulation and enhancement of ion-adsorption rare earth ore non-contact bioleaching process.

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.

Modification of the lesser curvature incision line enhanced gastric conduit perfusion as determined by indocyanine green fluorescence imaging and decreased the incidence of anastomotic leakage following esophagectomy.

AIM: This study aimed to investigate the effectiveness of a modified incision line on the lesser curvature for gastric conduit formation during esophagectomy in enhancing the perfusion of gastric conduit as determined by indocyanine green fluorescence imaging and reducing the incidence of anastomotic leakage. METHODS: A total of 272 patients who underwent esophagectomy at our institute between 2014 and 2022 were enrolled in this study. These patients were divided based on two different types of cutlines on the lesser curvature: conventional group (n = 141) following the traditional cutline and modified group (n = 131) adopting a modified cutline. Gastric conduit perfusion was assessed by ICG fluorescence imaging, and clinical outcomes after esophagectomy were evaluated. RESULTS: The distance from the pylorus to the cutline was significantly longer in the modified group compared with the conventional group (median: 9.0 cm vs. 5.0 cm, p < 0.001). The blood flow speed in the gastric conduit wall was significantly higher in the modified group than that in the conventional group (median: 2.81 cm/s vs. 2.54 cm/s, p = 0.001). Furthermore, anastomotic leakage was significantly lower (p = 0.024) and hospital stay was significantly shorter (p < 0.001) in the modified group compared with the conventional group. Multivariate analysis identified blood flow speed in the gastric conduit wall as the only variable significantly associated with anastomotic leakage. CONCLUSIONS: ICG fluorescence imaging is a feasible, reliable method for the assessment of gastric conduit perfusion. Modified lesser curvature cutline could enhance gastric conduit perfusion, promote blood circulation around the anastomotic site, and reduce the risk of anastomotic leakage after esophagectomy.

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.