Targeted protein degradation reveals RNA Pol II heterogeneity and functional diversity.

RNA polymerase II (RNA Pol II) subunits are thought to be involved in various transcription-associated processes, but it is unclear whether they play different regulatory roles in modulating gene expression. Here, we performed nascent and mature transcript sequencing after the acute degradation of 12 mammalian RNA Pol II subunits and profiled their genomic binding sites and protein interactomes to dissect their molecular functions. We found that RNA Pol II subunits contribute differently to RNA Pol II cellular localization and transcription processes and preferentially regulate RNA processing (such as RNA splicing and 3' end maturation). Genes sensitive to the depletion of different RNA Pol II subunits tend to be involved in diverse biological functions and show different RNA half-lives. Sequences, associated protein factors, and RNA structures are correlated with RNA Pol II subunit-mediated differential gene expression. These findings collectively suggest that the heterogeneity of RNA Pol II and different genes appear to depend on some of the subunits.

Real-time label-free detection of dynamic aptamer-small molecule interactions using a nanopore nucleic acid conformational sensor.

Nucleic acids can undergo conformational changes upon binding small molecules. These conformational changes can be exploited to develop new therapeutic strategies through control of gene expression or triggering of cellular responses and can also be used to develop sensors for small molecules such as neurotransmitters. Many analytical approaches can detect dynamic conformational change of nucleic acids, but they need labeling, are expensive, and have limited time resolution. The nanopore approach can provide a conformational snapshot for each nucleic acid molecule detected, but has not been reported to detect dynamic nucleic acid conformational change in response to small -molecule binding. Here we demonstrate a modular, label-free, nucleic acid-docked nanopore capable of revealing time-resolved, small molecule-induced, single nucleic acid molecule conformational transitions with millisecond resolution. By using the dopamine-, serotonin-, and theophylline-binding aptamers as testbeds, we found that these nucleic acids scaffolds can be noncovalently docked inside the MspA protein pore by a cluster of site-specific charged residues. This docking mechanism enables the ion current through the pore to characteristically vary as the aptamer undergoes conformational changes, resulting in a sequence of current fluctuations that report binding and release of single ligand molecules from the aptamer. This nanopore tool can quantify specific ligands such as neurotransmitters, elucidate nucleic acid-ligand interactions, and pinpoint the nucleic acid motifs for ligand binding, showing the potential for small molecule biosensing, drug discovery assayed via RNA and DNA conformational changes, and the design of artificial riboswitch effectors in synthetic biology.

Multiomic analysis of cohesin reveals that ZBTB transcription factors contribute to chromatin interactions.

One bottleneck in understanding the principles of 3D chromatin structures is caused by the paucity of known regulators. Cohesin is essential for 3D chromatin organization, and its interacting partners are candidate regulators. Here, we performed proteomic profiling of the cohesin in chromatin and identified transcription factors, RNA-binding proteins and chromatin regulators associated with cohesin. Acute protein degradation followed by time-series genomic binding quantitation and BAT Hi-C analysis were conducted, and the results showed that the transcription factor ZBTB21 contributes to cohesin chromatin binding, 3D chromatin interactions and transcriptional repression. Strikingly, multiomic analyses revealed that the other four ZBTB factors interacted with cohesin, and double degradation of ZBTB21 and ZBTB7B led to a further decrease in cohesin chromatin occupancy. We propose that multiple ZBTB transcription factors orchestrate the chromatin binding of cohesin to regulate chromatin interactions, and we provide a catalog of many additional proteins associated with cohesin that warrant further investigation.

Synchronous filtering method for improving the optical signal-to-noise ratio of a tunable laser based on the Fabry-Pérot interferometer.

Optical measurements are closely related to the optical signal-to-noise ratio (OSNR) of the laser, which can be improved using a tunable optical filter (TOF) to suppress frequency noise. For an external-cavity tunable laser with a tuning range larger than the TOF bandwidth, the wavelength at the center of the TOF passband must be varied based on the laser tuning. This study proposes a tunable-laser OSNR-enhancement method based on the Fabry-Pérot (FP) interferometer. The FP signal contains the wavelength information of the swept laser, which can be used to determine the real-time driving voltage of the TOF. Notably, the laser needs to be continuously tunable without mode hopping, and the free spectral range of the FP interferometer must be smaller than the TOF bandwidth.

Phase tracking using a Kalman filter based on probability density distribution in frequency-scanning interferometry.

Frequency-scanning interferometry (FSI) utilizing external cavity diode lasers (ECDL) stands out as a potent technique for absolute distance measurement. Nevertheless, the inherent scanning nonlinearity of ECDL and phase noise pose a challenge, as it can compromise the accuracy of phase extraction from interference signals, thereby reducing the measurement accuracy of FSI. In this study, we propose a composite algorithm aimed at mitigating non-orthogonal errors by integrating the least-squares and Heydemann correction technique. Furthermore, we employ Kalman filtering for precise phase tracking. We introduce a parameter selection strategy based on the statistical distribution of instantaneous frequency to achieve the fusion estimation of phase observation values and theoretical models, which starts a new perspective for the application of multi-dimensional data fusion in FSI measurement. Through simulation and experimental validation, the efficacy of this approach is confirmed. The experimental results show promising outcomes: with an average phase error of 0.12%, a standard deviation of less than 1.7 µm in absolute distance measurement, and an average positioning accuracy error of 0.29 µm.

The role and regulation of SIRT1 in pulmonary fibrosis.

Pulmonary fibrosis (PF) is a progressive and fatal lung disease with high incidence and a lack of effective treatment, which is a severe public health problem. PF has caused a huge socio-economic burden, and its pathogenesis has become a research hotspot. SIRT1 is a nicotinamide adenosine dinucleotide (NAD)-dependent sirtuin essential in tumours, Epithelial mesenchymal transition (EMT), and anti-aging. Numerous studies have demonstrated after extensive research that it is crucial in preventing the progression of pulmonary fibrosis. This article reviews the biological roles and mechanisms of SIRT1 in regulating the progression of pulmonary fibrosis in terms of EMT, oxidative stress, inflammation, aging, autophagy, and discusses the potential of SIRT1 as a therapeutic target for pulmonary fibrosis, and provides a new perspective on therapeutic drugs and prognosis prospects.

Functional characterization of Helicoverpa assulta CYP6B6 in insecticide metabolism.

The oriental tobacco budworm Helicoverpa assulta (Lepidoptera: Noctuidae) is a specialist pest that may cause serious damages to important crops such as chili pepper and tobacco. Various man-made insecticides have been applied to control the infestation of this pest. To understand how this pest copes with insecticides, it is required to identify key players involved in insecticide transformation. In this study, a P450 gene of CYP6B subfamily was identified in the oriental tobacco budworm, and its expression pattern was revealed. Moreover, the activities of HassCYP6B6 against 12 insecticides were explored using recombinant enzymes produced in the facile Escherichia coli. Data from metabolic experiments showed that HassCYP6B6 was able to metabolize conventional insecticides including organophosporates (diazinon, malathion, phoxim), carbamate propoxur, and pyrethroid esfenvalerate, while no significant metabolism was observed towards new-type pesticides such as neonicotinoids (acetamiprid, imidacloprid), diamides (chlorantraniliprole, cyantraniliprole), macrocyclic lactone (emamectin benzoate, ivermectin), and metaflumizone. Structures of metabolites were proposed based on mass spectrometry analyses. The results demonstrate that HassCYP6B6 plays important roles in the transformation of multiple insecticides via substrate-dependent catalytic mechanisms including dehydrogenation, hydroxylation and oxidative desulfurization. The findings have important applied implications for the usage of insecticides.

The Application of "Table Tennis Racquet" Random Skin Flap in the Treatment of Facial Skin Carcinoma.

BACKGROUND: The repair of facial skin and soft tissue defects remains a clinical challenge. The author introduced a novel "table tennis racquet" random skin flap for wound repair after facial skin cancer excision and discussed its survival mechanisms. METHODS: A lateral mandibular neck skin flap shaped like a table tennis racquet with no well-known blood vessels at the narrow pedicle was designed in 31 cases to repair tissue defects. Among them, there were 8 cases of skin carcinoma in the frontotemporal area and 23 cases of skin carcinoma in the cheek. The flap area was 8.0 × 7.0 cm at maximum and 3.0 × 2.5 cm at minimum, with a pedicle width of 1.0-2.0 cm and a pedicle length of 2.0-6.0 cm. RESULTS: All 31 "table tennis racquet" random skin flaps survived, although there were 3 cases with delayed healing of distal flap bruising. All of them had an ideal local shape after repair with a concealed donor area and inconspicuous scars. CONCLUSIONS: This flap has a "table tennis racquet" shape with a pedicle without well-known blood vessels and has a length-to-width ratio that exceeds that of conventional random flaps, making it unconventional. Because of its long and narrow pedicle, it not only has a large rotation and coverage area but also can be designed away from the defect area, avoiding the defect of no donor tissue being localized near the defect. Overall, this approach is an ideal option for repairing tissue defects after enlarged excision of facial skin carcinoma.

Autologous i-PRF promotes healing of radiation-induced skin injury.

Skin, as an exposed tissue, often suffers damage after exposure to radiotherapy and accidental events, which may lead to the formation of chronic refractory wounds. However, effective treatment options are usually limited for severe radiation-induced skin injury (RSI). Platelet-rich plasma (PRP) has been identified to promote wound healing, but whether a new generation of blood-derived biomaterial, injectable platelet-rich fibrin (i-PRF), is effective in repairing RSI remains unclear. In this study, blood was drawn from humans and Sprague-Dawley rats to prepare PRP and i-PRF, and the regenerative functions of PRP and i-PRF were investigated by exposing the dorsal skin of SD rats to local radiation (45 Gy) and exposing HDF-α cells and human umbilical vein endothelial cells (HUVECs) cells to X-rays (10 Gy). The healing effect of i-PRF on RSI was analysed by tube formation assay, cell migration and apoptosis assays, ROS assay, wound healing assay, histological characterisation and immunostaining. The results showed that exposure to high doses of radiation reduced cell viability, increased ROS levels and induced cell apoptosis, thereby causing dorsal trauma of rats. However, both PRP and i-PRF could resisted RSI, and they were capable of reducing inflammation and promoting angiogenesis and vascular regeneration. i-PRF has a higher concentration of platelets and platelet-derived growth factors, which has a more convenient preparation method and better repair effect and possesses a good application prospect for the repair of RSI.

High-Suspicion Subcentimeter Thyroid Nodules: Cost Effectiveness of Active Surveillance versus Fine Needle Aspiration.

PURPOSE: To compare the cost-benefit of active surveillance (AS) against immediate fine needle aspiration (FNA) of sonographically suspicious subcentimeter thyroid nodules. MATERIALS AND METHODS: A Markov model was constructed to compare the cost-benefit of 3 strategies from the point of discovery until death: (a) Surveillance of all nodules, (b) Surveillance of nodules with positive cytology, and (c) Surgery of nodules with positive cytology. The reference case was a 40-year-old woman with a sonographically suspicious subcentimeter thyroid nodule. Transition probabilities, costs, and health state utilities were derived from the literature. Sensitivity analyses were performed to evaluate model uncertainty. Willingness-to-pay threshold was set at $100,000/quality-adjusted life year. RESULTS: Surveillance of nodules with positive cytology dominated in the reference scenario and was cost-beneficial over Surveillance of all nodules, independent of the utility of AS. Surveillance of all nodules was cost-beneficial only at a life expectancy of <2.6 years or surveillance duration of <4 years. CONCLUSIONS: While current guidelines recommend AS of sonographically suspicious subcentimeter nodules, the results of this study suggest that immediate FNA (Surveillance of nodules with positive cytology) is more cost-beneficial than AS (Surveillance of all nodules). Patients with positive cytology on FNA may subsequently opt for AS (Surveillance of nodules with positive cytology) or surgery (Surgery of nodules with positive cytology) according to their level of comfort (ie, utility) with AS.

THFS-carbon: a theoretical prediction of metallic carbon allotrope with half-auxeticity, planar tetracoordinate carbon, and potential application as anode for sodium-ion batteries.

Two-dimensional (2D) carbon materials integrated with planar tetracoordinate carbon (ptC) and negative Poisson's ratio (NPR) provide a cornerstone for constructing multifunctional energy-storage devices. As a typical 2D carbon material, the pristine graphene is chemically inert, hindering its application in metal-ion batteries. Introducing the ptC in graphene can break the extended conjugation of π-electrons and lead to an enhanced surface reactivity. Inspired by the unique geometry of [4.6.4.6] fenestrane skeleton with ptC, we theoretically design a ptC-containing 2D carbon allotrope, namely THFS-carbon. It is intrinsically metallic with excellent dynamical, thermal, and mechanical stabilities. The Young's modulus along the x direction (311.37 N m-1) is comparable to that of graphene. Intriguingly, THFS-carbon possesses an in-plane half-NPR distinct from most other 2D crystals. As a promising anode for sodium-ion batteries, THFS-carbon delivers an ultra-high theoretical storage capacity (2233 mA h g-1), a low diffusion energy barrier (0.03-0.05 eV), a low open-circuit voltage (0.14-0.40 V), and a good reversibility for Na insertion/extraction.

Ground-to-satellite quantum teleportation.

An arbitrary unknown quantum state cannot be measured precisely or replicated perfectly. However, quantum teleportation enables unknown quantum states to be transferred reliably from one object to another over long distances, without physical travelling of the object itself. Long-distance teleportation is a fundamental element of protocols such as large-scale quantum networks and distributed quantum computation. But the distances over which transmission was achieved in previous teleportation experiments, which used optical fibres and terrestrial free-space channels, were limited to about 100 kilometres, owing to the photon loss of these channels. To realize a global-scale 'quantum internet' the range of quantum teleportation needs to be greatly extended. A promising way of doing so involves using satellite platforms and space-based links, which can connect two remote points on Earth with greatly reduced channel loss because most of the propagation path of the photons is in empty space. Here we report quantum teleportation of independent single-photon qubits from a ground observatory to a low-Earth-orbit satellite, through an uplink channel, over distances of up to 1,400 kilometres. To optimize the efficiency of the link and to counter the atmospheric turbulence in the uplink, we use a compact ultra-bright source of entangled photons, a narrow beam divergence and high-bandwidth and high-accuracy acquiring, pointing and tracking. We demonstrate successful quantum teleportation of six input states in mutually unbiased bases with an average fidelity of 0.80 ± 0.01, well above the optimal state-estimation fidelity on a single copy of a qubit (the classical limit). Our demonstration of a ground-to-satellite uplink for reliable and ultra-long-distance quantum teleportation is an essential step towards a global-scale quantum internet.

SIRT3-dependent mitochondrial redox homeostasis mitigates CHK1 inhibition combined with gemcitabine treatment induced cardiotoxicity in hiPSC-CMs and mice.

Administration of CHK1-targeted anticancer therapies is associated with an increased cumulative risk of cardiac complications, which is further amplified when combined with gemcitabine. However, the underlying mechanisms remain elusive. In this study, we generated hiPSC-CMs and murine models to elucidate the mechanisms underlying CHK1 inhibition combined with gemcitabine-induced cardiotoxicity and identify potential targets for cardioprotection. Mice were intraperitoneally injected with 25 mg/kg CHK1 inhibitor AZD7762 and 20 mg/kg gemcitabine for 3 weeks. hiPSC-CMs and NMCMs were incubated with 0.5 uM AZD7762 and 0.1 uM gemcitabine for 24 h. Both pharmacological inhibition or genetic deletion of CHK1 and administration of gemcitabine induced mtROS overproduction and pyroptosis in cardiomyocytes by disrupting mitochondrial respiration, ultimately causing heart atrophy and cardiac dysfunction in mice. These toxic effects were further exacerbated with combination administration. Using mitochondria-targeting sequence-directed vectors to overexpress CHK1 in cardiomyocyte (CM) mitochondria, we identified the localization of CHK1 in CM mitochondria and its crucial role in maintaining mitochondrial redox homeostasis for the first time. Mitochondrial CHK1 function loss mediated the cardiotoxicity induced by AZD7762 and CHK1-knockout. Mechanistically, mitochondrial CHK1 directly phosphorylates SIRT3 and promotes its expression within mitochondria. On the contrary, both AZD7762 or CHK1-knockout and gemcitabine decreased mitochondrial SIRT3 abundance, thus resulting in respiration dysfunction. Further hiPSC-CMs and mice experiments demonstrated that SIRT3 overexpression maintained mitochondrial function while alleviating CM pyroptosis, and thereby improving mice cardiac function. In summary, our results suggest that targeting SIRT3 could represent a novel therapeutic approach for clinical prevention and treatment of cardiotoxicity induced by CHK1 inhibition and gemcitabine.

First report of powdery mildew caused by Podosphaera fusca on Coreopsis tinctoria in China.

Coreopsis tinctoria is an annual herb and commonly cultivated in gardens due to its attractive flowers, its capitula also have been used as a traditional medicine in China, Asia, North America and Europe (Shen et al. 2021). In June 2023, severe powdery mildew infection was observed on C. tinctoria in a hillside near headwork of the middle route of the South to North Water Diversion Project (32°40'55''N, 111°41'59''E). Abundant irregular white spots were found on adaxial surface of the leaves and tender stems. Approximately 75% of the observed C. tinctoria plants showed these signs and symptoms. Generative hyphae were thin-walled, smooth or almost so, and 5 to 9 µm wide. Conidiophores were unbranched, straight, 80.5 to 162.5 × 9.3 to 12.9 µm (n=25), and produced one to three immature conidia. Foot-cells of conidiophores were cylindrical, 38.5 to 62.3 µm (n=20) long. Conidia were ellipsoid to ovoid, 25.1 to 31.9 × 15.2 to 19.5 µm (n=30). The morphological characteristics of asexual structures corresponded to Podosphaera sp. (Braun and Cook 2012). For further identification, genomic DNA was extracted directly from the mycelia and conidia using Chelex 100 (Sigma Aldrich, Shanghai, China). The internal transcribed spacer (ITS) regions and 28S large subunit (LSU) of ribosomal DNA from the specimen (CT2302) were amplified using the primers ITS1/ITS4 (expected amplicon size 566 bp) (White et al. 1990) and NL1/NL4 (expected amplicon size 618 bp) (Baten et al. 2014), respectively. The sequences of ITS (GenBank accession no. OR649304) and LSU (GenBank accession no. OR649305) showed 99.63% and 100% identity values to the Podosphaera fusca isolate HMNWAFU-CF2012074 in the NCBI database (KR048109 for ITS and KR048178 for LSU), respectively. Phylogenetic analyses based on the combined ITS and LSU sequences using MEGA 7.0 software indicated that CT2302 formed a monophyletic clade together with isolates of P. fusca. Therefore, this fungus was identified as P. fusca based on the morphological and molecular characteristics. Pathogenicity tests were performed by gently pressing the infected leaves onto 15 young leaves of five healthy plants and three noninoculated plants were used as controls. All plants were maintained in a greenhouse (25℃ and 70% relative humidity). Powdery mildew symptoms similar to those of originally diseased plants were observed on all inoculated leaves after 12 days, whereas no symptoms were observed on the control leaves. Powdery mildew caused by P. fusca (previously Sphaerotheca fusca) on C. tinctoria has been reported in Russia, Poland, Korea, Romania and Ukraine (Cho and Shin 2004; Rusanov and Bulgakow 2008). To our knowledge, this is the first report of P. fusca on C. tinctoria in China. The identification of P. fusca as the causal agent on C. tinctoria is critical to the prevention and control of this disease in the future.

Antinociceptive activity of doliroside B.

CONTEXT: Dolichos trilobus Linn (Leguminosae) is often used in Yi ethnic medicine to treat pain, fracture, and rheumatism. OBJECTIVE: To explore the therapeutic potential of doliroside B (DB) from D. trilobus and its disodium salt (DBDS) and the underlying mechanism in pain. MATERIALS AND METHODS: In the writhing test, Kunming mice were orally treated with DB and DBDS at doses of 0.31, 0.62, 1.25, 2.5, and 5 mg/kg. Vehicle, morphine, indomethacin, and acetylsalicylic acid were used as negative and positive control on the nociception-induced models, respectively. In the hot plate test, mice were orally treated with DB and DBDS at doses of 2.5, 5, 10, and 20 mg/kg. In the formalin test, mice were orally treated with DB and DBDS at doses of 2.5, 5, 10, and 20 mg/kg. In the meanwhile, lipopolysaccharide-induced inflammatory model in RAW264.7 macrophages was adopted to study the mechanism of pain alleviation for DBDS. RESULTS: DBDS (5 mg/kg) inhibited the writhing number by 80.2%, which exhibited the highest antinociceptive activity in pain models. DBDS could selectively inhibite the activity of COX-1. Meanwhile, it also reduced the production of NO, iNOS, and IL-6 by 55.8%, 69.0%, and 49.9% inhibition, respectively. It was found that DBDS also positively modulated the function of GABAA1 receptor. DISCUSSION AND CONCLUSIONS: DBDS displayed antinociceptive activity by acting on both the peripheral and central nervous systems, which may act on multitargets. Further work is warranted for developing DBDS into a potential drug for the treatment of pain.

MNK2-eIF4E axis promotes cardiac repair in the infarcted mouse heart by activating cyclin D1.

Adult mammals have limited potential for cardiac regeneration after injury. In contrast, neonatal mouse heart, up to 7 days post birth, can completely regenerate after injury. Therefore, identifying the key factors promoting the proliferation of endogenous cardiomyocytes (CMs) is a critical step in the development of cardiac regeneration therapies. In our previous study, we predicted that mitogen-activated protein kinase (MAPK) interacting serine/threonine-protein kinase 2 (MNK2) has the potential of promoting regeneration by using phosphoproteomics and iGPS algorithm. Here, we aimed to clarify the role of MNK2 in cardiac regeneration and explore the underlying mechanism. In vitro, MNK2 overexpression promoted, and MNK2 knockdown suppressed cardiomyocyte proliferation. In vivo, inhibition of MNK2 in CMs impaired myocardial regeneration in neonatal mice. In adult myocardial infarcted mice, MNK2 overexpression in CMs in the infarct border zone activated cardiomyocyte proliferation and improved cardiac repair. In CMs, MNK2 binded to eIF4E and regulated its phosphorylation level. Knockdown of eukaryotic translation initiation factor (eIF4E) impaired the proliferation-promoting effect of MNK2 in CMs. MNK2-eIF4E axis stimulated CMs proliferation by activating cyclin D1. Our study demonstrated that MNK2 kinase played a critical role in cardiac regeneration. Over-expression of MNK2 promoted cardiomyocyte proliferation in vitro and in vivo, at least partly, by activating the eIF4E-cyclin D1 axis. This investigation identified a novel target for heart regenerative therapy.

LncRNA FAF attenuates hypoxia/ischaemia-induced pyroptosis via the miR-185-5p/PAK2 axis in cardiomyocytes.

Pyroptosis is associated with various cardiovascular diseases. Increasing evidence suggests that long noncoding RNAs (lncRNAs) have been implicated in gene regulation, but how lncRNAs participate in the regulation of pyroptosis in the heart remains largely unknown. In this study, we aimed to explore the antipyroptotic effects of lncRNA FGF9-associated factor (FAF) in acute myocardial infarction (AMI). The expression patterns of lncRNA FAF, miR-185-5p and P21 activated kinase 2 (PAK2) were detected in hypoxia/ischaemia-induced cardiomyocytes. Hoechst 33342/PI staining, lactate dehydrogenase (LDH) release assay, immunofluorescence and Western blotting were conducted to assay cell pyroptosis. The interaction between lncRNA FAF, miR-185-5p and PAK2 was verified by bioinformatics analysis, small RNA sequencing luciferase reporter assay and qRT-PCR. The expression of LncRNA FAF was downregulated in hypoxic cardiomyocytes and myocardial tissues. Overexpression of lncRNA FAF could attenuate cardiomyocyte pyroptosis, improve cell viability and reduce infarct size during the procession of AMI. Moreover, lncRNA FAF was confirmed as a sponge of miR-185-5p and promoted PAK2 expression in cardiomyocytes. Collectively, our findings reveal a novel lncRNA FAF/miR-185-5p/PAK2 axis as a crucial regulator in cardiomyocyte pyroptosis, which might be a potential therapeutic target of AMI.

Single-cell transcriptome atlas reveals developmental trajectories and a novel metabolic pathway of catechin esters in tea leaves.

The tea plant is an economically important woody beverage crop. The unique taste of tea is evoked by certain metabolites, especially catechin esters, whereas their precise formation mechanism in different cell types remains unclear. Here, a fast protoplast isolation method was established and the transcriptional profiles of 16 977 single cells from 1st and 3rd leaves were investigated. We first identified 79 marker genes based on six isolated tissues and constructed a transcriptome atlas, mapped developmental trajectories and further delineated the distribution of different cell types during leaf differentiation and genes associated with cell fate transformation. Interestingly, eight differently expressed genes were found to co-exist at four branch points. Genes involved in the biosynthesis of certain metabolites showed cell- and development-specific characteristics. An unexpected catechin ester glycosyltransferase was characterized for the first time in plants by a gene co-expression network in mesophyll cells. Thus, the first single-cell transcriptional landscape in woody crop leave was reported and a novel metabolism pathway of catechin esters in plants was discovered.

Hydrogen sulfide plays a potential alternative for the treatment of metabolic disorders of diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) is a cardiovascular complication that tends to occur in patients with diabetes, obesity, or insulin resistance, with a higher late mortality rate. Sustained hyperglycemia, increased free fatty acids, or insulin resistance induces metabolic disorders in cardiac tissues and cells, leading to myocardial fibrosis, left ventricular hypertrophy, diastolic and/or systolic dysfunction, and finally develop into congestive heart failure. The close connection between all signaling pathways and the complex pathogenesis of DCM cause difficulties in finding effective targets for the treatment of DCM. It reported that hydrogen sulfide (H2S) could regulate cell energy substrate metabolism, reduce insulin resistance, protect cardiomyocytes, and improve myocardial function by acting on related key proteins such as differentiation cluster 36 (CD36) and glucose transporter 4 (GLUT4). In this article, the relative mechanisms of H2S in alleviating metabolic disorders of DCM were reviewed, and how H2S can better prevent and treat DCM in clinical practice will be discussed.

Fibrous Structure and Stiffness of Designer Protein Hydrogels Synergize to Regulate Endothelial Differentiation of Bone Marrow Mesenchymal Stem Cells.

Matrix stiffness and fibrous structure provided by the native extracellular matrix have been increasingly appreciated as important cues in regulating cell behaviors. Recapitulating these physical cues for cell fate regulation remains a challenge due to the inherent difficulties in making mimetic hydrogels with well-defined compositions, tunable stiffness, and structures. Here, we present two series of fibrous and porous hydrogels with tunable stiffness based on genetically engineered resilin-silk-like and resilin-like protein polymers. Using these hydrogels as substrates, the mechanoresponses of bone marrow mesenchymal stem cells to stiffness and fibrous structure were systematically studied. For both hydrogel series, increasing compression modulus from 8.5 to 14.5 and 23 kPa consistently promoted cell proliferation and differentiation. Nonetheless, the promoting effects were more pronounced on the fibrous gels than their porous counterparts at all three stiffness levels. More interestingly, even the softest fibrous gel (8.5 kPa) allowed the stem cells to exhibit higher endothelial differentiation capability than the toughest porous gel (23 kPa). The predominant role of fibrous structure on the synergistic regulation of endothelial differentiation was further explored. It was found that the stiffness signal activated Yes-associated protein (YAP), the main regulator of endothelial differentiation, via spreading of focal adhesions, whereas fibrous structure reinforced YAP activation by promoting the maturation of focal adhesions and associated F-actin alignment. Therefore, our results shed light on the interplay of physical cues in regulating stem cells and may guide the fabrication of designer proteinaceous matrices toward regenerative medicine.