Dissecting microenvironment in cystadenomas and hepatic cysts based on single nucleus RNA-sequencing data.

Hepatic cystadenoma is a rare disease, accounting for about 5% of all cystic lesions, with a high tendency of malignant transformation. The preoperative diagnosis of cystadenoma is difficult, and some cystadenomas are easily misdiagnosed as hepatic cysts at first. Hepatic cyst is a relatively common liver disease, most of which are benign, but large hepatic cysts can lead to pressure on the bile duct, resulting in abnormal liver function. To better understand the difference between the microenvironment of cystadenomas and hepatic cysts, we performed single-nuclei RNA-sequencing on cystadenoma and hepatic cysts samples. In addition, we performed spatial transcriptome sequencing of hepatic cysts. Based on nucleus RNA-sequencing data, a total of seven major cell types were identified. Here we described the tumor microenvironment of cystadenomas and hepatic cysts, particularly the transcriptome signatures and regulators of immune cells and stromal cells. By inferring copy number variation, it was found that the malignant degree of hepatic stellate cells in cystadenoma was higher. Pseudotime trajectory analysis demonstrated dynamic transformation of hepatocytes in hepatic cysts and cystadenomas. Cystadenomas had higher immune infiltration than hepatic cysts, and T cells had a more complex regulatory mechanism in cystadenomas than hepatic cysts. Immunohistochemistry confirms a cystadenoma-specific T-cell immunoregulatory mechanism. These results provided a single-cell atlas of cystadenomas and hepatic cyst, revealed a more complex microenvironment in cystadenomas than in hepatic cysts, and provided new perspective for the molecular mechanisms of cystadenomas and hepatic cyst.

Disturbance observer based fixed-time control of stochastic systems.

In this paper, the novel fixed-time anti-disturbance control scheme is proposed for a class of stochastic systems subjected to multiple disturbances and faults, and the disturbances consist of derivative-bounded disturbances and multiply noise. Based on the pole placement method, the fixed-time disturbance observer (Fixed-time DO) is devised to estimate derivative-bounded disturbances and an adaptive law is employed to approach the time-varying fault. Then a composite fixed-time controller is constructed to make the system converge to equilibrium position within a pre-specified time. At the same time, simulation examples illustrate that the proposed controller is effective and the convergence time is not related to the initial states of the system.

Wnt5a deficiency in osteocalcin-expressing cells could not alleviate the osteoarthritic phenotype in a mouse model of post-traumatic osteoarthritis.

Objectives: Wnt5a, which regulates the activities of osteoblasts and osteoclasts, is reportedly overexpressed in osteoarthritis (OA) tissues. The purpose of this study was to elucidate its role in the development of OA by deleting Wnt5a in osteocalcin (OCN)-expressing cells. Materials and Methods: Knee OA was induced by anterior cruciate ligament transection (ACLT) in OCN-Cre;Wnt5afl/fl knockout (Wnt5a-cKO) mice and control littermates. Eight weeks after surgery, histological changes, cell apoptosis, and matrix metabolism of cartilage were evaluated by toluidine blue, TUNEL staining, and im-immunohistochemistry analyses, respectively. In addition, the subchondral bone microarchitecture of mice was examined by micro-computed tomography (micro-CT). Results: Histological scores show substantial cartilage degeneration occurred in ACLT knees, coupled with decreased collagen type II expression and enhanced matrix metalloproteinase 13 expression, as well as higher proportions of apoptotic cells. Micro-CT results show that ACLT resulted in decreased bone mineral density, bone volume/trabecular volume, trabecular number, and structure model index of subchondral bones in both Wnt5a-cKO and control littermates; although Wnt5a-cKO mice display lower BMD and BV/TV values, no significant difference was observed between Wnt5a-cKO and control mice for any of these values. Conclusion: Our findings indicate that Wnt5a deficiency in OCN-expressing cells could not prevent an osteoarthritic phenotype in a mouse model of post-traumatic OA.

Whole Blood Transcriptome Analysis in Patients with Trigeminal Neuralgia: a Prospective Clinical Study.

Trigeminal neuralgia (TN) brings a huge burden to patients, without long-term effective treatment. This study aimed to explore the differentially expressed genes (DEGs) and related enrichment pathways in patients with TN. This was a study of transcriptome sequencing and bioinformatics analysis of human samples. Whole blood samples were collected from the TN patients and pain-free controls. RNA was extracted to conduct the RNA-sequencing and the subsequent bioinformatics analysis. DEGs between the two groups were derived. Kyoto encyclopedia of genes and genomes (KEGG) and Gene ontology (GO) was used to find the enrichment pathways of DEGs. Protein protein interaction (PPI) network was used to depict the interaction between DEGs and find the most important gene, hub gene. Compared with the control group, there were 117 up-regulated DEGs and 103 down-regulated DEGs in the whole blood of patients in the TN group. Pathway enrichment analysis showed that DEGs were mainly enriched in the neuroimmune and metabolic pathways. The PPI network demonstrated that colony stimulating factor 2 (CSF2) was the most important hub gene in the whole blood of TN patients. This study shows the expression of the transcriptome in the whole blood samples of TN patients. The neuroimmune responses and key hub gene CSF2 in the whole blood cells play a vital role in the occurrence of TN. Our research provides a theoretical basis for the diagnosis and treatments of TN. This study was registered at clinicaltrials.gov in June 2021 (No. NCT04923399).

Data notes on the proteomics of Dendrobium huoshanense under pb treatment.

OBJECTIVES: Pb stress has a negative impact on plant growth by interfering with photosynthesis and releasing reactive oxygen species, causing major risks such as heavy metal ion accumulation in the soil matrix. A proteomics experiment was conducted to determine whether protein levels of Dendrobium huoshanense changed in response to Pb stress seven to fifteen days after being sprayed with a 200 mg/L Pb (NO3)2 solution. The proteomic data we gathered provides a model for investigations into the mechanisms underlying Dendrobium plant resistance to heavy metal stress. DATA DESCRIPTION: A label-free quantitative proteomics approach was employed to examine the variations in protein expression levels of D. huoshanense at different times of Pb(NO3)2 treatment. We submitted the raw data obtained from these proteomics sequencing experiments to the ProteomeXchange database with the accession number PXD047050. 63,194 mass spectra in total were compared after being imported into the Proteome Discoverer software for database search. A total of 12,402 spectral peptides were identified with a confidence level exceeding 99%, which resulted in the identification of 2,449 significantly differential proteins. These proteins can be utilized for screening, functional annotation, and enrichment analysis of differentially expressed proteins before and after heavy metal treatment experiments.

The CSF1-CSF1R pathway in the trigeminal ganglion mediates trigeminal neuralgia via inflammatory responses in mice.

BACKGROUND: Trigeminal neuralgia (TN) is the most severe type of neuropathic pain. The trigeminal ganglion (TG) is a crucial target for the pathogenesis and treatment of TN. The colony-stimulating factor 1 (CSF1) - colony-stimulating factor 1 receptor (CSF1R) pathway regulates lower limb pain development. However, the effect and mechanism of the CSF1-CSF1R pathway in TG on TN are unclear. METHODS: Partial transection of the infraorbital nerve (pT-ION) model was used to generate a mouse TN model. Mechanical and cold allodynia were used to measure pain behaviors. Pro-inflammatory factors (IL-6, TNF-a) were used to measure inflammatory responses in TG. PLX3397, an inhibitor of CSF1R, was applied to inhibit the CSF1-CSF1R pathway in TG. This pathway was activated in naïve mice by stereotactic injection of CSF1 into the TG. RESULTS: The TN model activated the CSF1-CSF1R pathway in the TG, leading to exacerbated mechanical and cold allodynia. TN activated inflammatory responses in the TG manifested as a significant increase in IL-6 and TNF-a levels. After using PLX3397 to inhibit CSF1R, CSF1R expression in the TG declined significantly. Inhibiting the CSF1-CSF1R pathway in the TG downregulated the expression of IL-6 and TNF-α to reduce allodynia-related behaviors. Finally, mechanical allodynia behaviors were exacerbated in naïve mice after activating the CSF1-CSF1R pathway in the TG. CONCLUSIONS: The CSF1-CSF1R pathway in the TG modulates TN by regulating neuroimmune responses. Our findings provide a theoretical basis for the development of treatments for TN in the TG.

Optimizing drug combination and mechanism analysis based on risk pathway crosstalk in pan cancer.

Combination therapy can greatly improve the efficacy of cancer treatment, so identifying the most effective drug combination and interaction can accelerate the development of combination therapy. Here we developed a computational network biological approach to identify the effective drug which inhibition risk pathway crosstalk of cancer, and then filtrated and optimized the drug combination for cancer treatment. We integrated high-throughput data concerning pan-cancer and drugs to construct miRNA-mediated crosstalk networks among cancer pathways and further construct networks for therapeutic drug. Screening by drug combination method, we obtained 687 optimized drug combinations of 83 first-line anticancer drugs in pan-cancer. Next, we analyzed drug combination mechanism, and confirmed that the targets of cancer-specific crosstalk network in drug combination were closely related to cancer prognosis by survival analysis. Finally, we save all the results to a webpage for query ( http://bio-bigdata.hrbmu.edu.cn/oDrugCP/ ). In conclusion, our study provided an effective method for screening precise drug combinations for various cancer treatments, which may have important scientific significance and clinical application value for tumor treatment.

Dual electrical stimulation at spinal-muscular interface reconstructs spinal sensorimotor circuits after spinal cord injury.

The neural signals produced by varying electrical stimulation parameters lead to characteristic neural circuit responses. However, the characteristics of neural circuits reconstructed by electrical signals remain poorly understood, which greatly limits the application of such electrical neuromodulation techniques for the treatment of spinal cord injury. Here, we develop a dual electrical stimulation system that combines epidural electrical and muscle stimulation to mimic feedforward and feedback electrical signals in spinal sensorimotor circuits. We demonstrate that a stimulus frequency of 10-20 Hz under dual stimulation conditions is required for structural and functional reconstruction of spinal sensorimotor circuits, which not only activates genes associated with axonal regeneration of motoneurons, but also improves the excitability of spinal neurons. Overall, the results provide insights into neural signal decoding during spinal sensorimotor circuit reconstruction, suggesting that the combination of epidural electrical and muscle stimulation is a promising method for the treatment of spinal cord injury.

Asymmetric Cyclodextrin-Dimer-Involved Nanoassemblies by Selective Host-Guest Interactions: Concentration-Dependent Morphology Evolution and Light-Regulated Biomedical Applications.

Supramolecular assembly has attracted significant attention and has been applied to various applications. Herein, a ß-γ-CD dimer was synthesized to complex different guest molecules, including single-strand polyethylene glycol (PEG)-modified C60 (PEG-C60), photothermal conversion reagent (IR780), and dexamethasone (Dexa), according to the complexation constant-dependent specific selectivity. Spherical or cylindrical nanoparticles, monolayer or bilayer vesicles, and bilayer fusion vesicles were discovered in succession if the concentration of PEG-C60 was varied. Moreover, if near-infrared light was employed to irradiate these nanoassemblies, the thermo-induced morphological evolution, subsequent cargo release, photothermal effect, and singlet oxygen (1O2) generation were successfully achieved. The in vitro cell experiments confirmed that these nanoparticles possessed excellent biocompatibility in a normal environment and achieved superior cytotoxicity by light regulation. Such proposed strategies for the construction of multilevel structures with different morphologies can open a new window to obtain various host-guest functional materials and achieve further use for disease treatment.

SUMOylation is enriched in the nuclear matrix and required for chromosome segregation.

As an important posttranslational modification, SUMOylation plays critical roles in almost all biological processes. Although it has been well-documented that SUMOylated proteins are mainly localized in the nucleus and have roles in chromatin-related processes, we showed recently that the SUMOylation machinery is actually enriched in the nuclear matrix rather than chromatin. Here, we provide compelling biochemical, cellular imaging and proteomic evidence that SUMOylated proteins are highly enriched in the nuclear matrix. We demonstrated that inactivation of SUMOylation by inhibiting SUMO-activating E1 enzyme or KO of SUMO-conjugating E2 enzyme UBC9 have only mild effect on nuclear matrix composition, indicating that SUMOylation is neither required for nuclear matrix formation nor for targeting proteins to nuclear matrix. Further characterization of UBC9 KO cells revealed that loss of SUMOylation did not result in significant DNA damage, but led to mitotic arrest and chromosome missegregation. Altogether, our study demonstrates that SUMOylated proteins are selectively enriched in the nuclear matrix and suggests a role of nuclear matrix in mediating SUMOylation and its regulated biological processes.

Resveratrol activation of SIRT1/MFN2 can improve mitochondria function, alleviating doxorubicin-induced myocardial injury.

Background: Doxorubicin is a widely used cytotoxic chemotherapy agent for treating different malignancies. However, its use is associated with dose-dependent cardiotoxicity, causing irreversible myocardial damage and significantly reducing the patient's quality of life and survival. In this study, an animal model of doxorubicin-induced cardiomyopathy was used to investigate the pathogenesis of doxorubicin-induced myocardial injury. This study also investigated a possible treatment strategy for alleviating myocardial injury through resveratrol therapy in vitro. Methods: Adult male C57BL/6J mice were randomly divided into a control group and a doxorubicin group. Body weight, echocardiography, surface electrocardiogram, and myocardial histomorphology were measured. The mechanisms of doxorubicin cardiotoxicity in H9c2 cell lines were explored by comparing three groups (phosphate-buffered saline, doxorubicin, and doxorubicin with resveratrol). Results: Compared to the control group, the doxorubicin group showed a lower body weight and higher systolic arterial pressure, associated with reduced left ventricular ejection fraction and left ventricular fractional shortening, prolonged PR interval, and QT interval. These abnormalities were associated with vacuolation and increased disorder in the mitochondria of cardiomyocytes, increased protein expression levels of α-smooth muscle actin and caspase 3, and reduced protein expression levels of Mitofusin2 (MFN2) and Sirtuin1 (SIRT1). Compared to the doxorubicin group, doxorubicin + resveratrol treatment reduced caspase 3 and manganese superoxide dismutase, and increased MFN2 and SIRT1 expression levels. Conclusion: Doxorubicin toxicity leads to abnormal mitochondrial morphology and dysfunction in cardiomyocytes and induces apoptosis by interfering with mitochondrial fusion. Resveratrol ameliorates doxorubicin-induced cardiotoxicity by activating SIRT1/MFN2 to improve mitochondria function.

Self-Assembled and Multilayer-Overlapped ESM-PDA@rGO Nanofilm-Based Flexible Wearable Sensor for Real-Time Body Temperature Monitoring.

There is an urgent need for wearable sensors that continuously monitor human physiological conditions in real time. Herein, an ESM-PDA@rGO-based flexible wearable temperature sensor was successfully constructed by integrating an eggshell membrane (ESM) with reduced graphene oxide (rGO) through dopamine (DA) polymerization. Depending on the "bridge effect" of diversified polydopamine (PDA) chains, on the one hand, a staggered arrangement of PDA-rGO frameworks and a lot of conductive pathways were produced and acted as an active layer. On the other hand, PDA-rGO frameworks were linked with ESM by PDA chains as a flexible sensing nanofilm. As a result, these mechanical merits of the ESM-PDA@rGO exhibited a 1.8-fold increase in Young' s modulus and 1.4-fold increase in tensile strength. Thereby, the conformability and performance of the temperature sensor were greatly enhanced, showing excellent sensitivity (-2.23%/°C), good linearity (R2 = 0.979), as well as stability. Especially, the flexible sensing nanofilm is evolved from the staggered arrangement of PDA-rGO frameworks, which endows it with rapid response (only 4-8 s), high resolution (0.1 °C), as well as excellent long-term durability (10 weeks). More importantly, the temperature sensor demonstrates insensitivity to bending deformation, ensuring reliable wearing stability. The sensor allows for online, real-time monitoring of human body temperature, encompassing both core (forehead, temple, cochlea, and exhale gas) and shell (palm and back of the hand, fingertip, and instep) temperatures. Particularly, it can accurately assess minor changes in peripheral body temperature before and after exercise, and it is capable of mapping daily patterns of body temperatures. The developed temperature sensor will provide us new materials design concepts and holds considerable promise in the fields of e-skin, disease surveillance, prediction, and diagnose.

Tumor biology, immune infiltration and liver function define seven hepatocellular carcinoma subtypes linked to distinct drivers, survival and drug response.

BACKGROUND & AIMS: Tumor heterogeneity is jointly determined by the components of the tumor ecosystem (TES) including tumor cells, immune cells, stromal cells, and non-cellular components. We aimed to identify subtypes using TES-related genes and determine subtype specific drivers and treatments for hepatocellular carcinoma (HCC). METHODS: We collected 68 genesets depicting tumor biology, immune infiltration, and liver function, totaling 2831 genes, and collected mRNA profiles and clinical data for over 6000 tumors from 65 datasets in the GEO, TCGA, ICGC, and several other databases. We designed a three-step clustering pipeline to identify subtypes. The microenvironment, genomic alteration, and drug response differences were systematically compared among subtypes. RESULTS: Seven subtypes (TES-1/2/3/4/5/6/7) were revealed in 159 tumors from the CHCC-HBV cohort. We constructed a single sample classifier using paired genes (sscpgsTES). TES subtypes were significantly associated with multiple clinical variables including etiology, and survival in 14 of 17 cohorts and the meta-cohort. TES-1 had the poorest prognosis and highest proliferation level. Both TES-2 and TES-7 were immune-enriched, however, TES-2 had a significantly worse prognosis, and hypoxic and immunosuppressive microenvironment. TES-4 had activated Wnt pathway, driven by CTNNB1 mutation. Good prognosis TES-6 exhibited the best differentiation. TES-5 and TES-3 were considered as novel subclasses by comparing with ten previous subtyping systems. TES-5 tumors had high AFP but good overall survival, and ∼45% of them harbored AXIN1 mutation. TES-3 was immune and stromal desert, may be driven by high copy number alteration burden, and had the poorest response to immune checkpoint inhibitor. TES-1 and TES-2 had significantly lower response to transarterial chemoembolization, but they showed significantly higher sensitivity to compound YM-155. CONCLUSIONS: Tumor ecosystem subtypes expand existing HCC subtyping systems, have distinct drivers, prognosis, and treatment vulnerabilities.

Genome sequencing-based transcriptomic analysis reveals novel genes in Peucedanum praeruptorum.

BACKGROUND: Peucedanum praeruptorum Dunn, a traditional Chinese herbal medicine, contains coumarin and volatile oil components that have clinical application value. However, early bolting often occurs in the medicinal materials of Apiaceae plants. The rhizomes of the medicinal parts are gradually lignified after bolting, resulting in a sharp decrease in the content of coumarins. At present, the link between coumarin biosynthesis and early bolting in P. praeruptorum has not been elucidated. RESULTS: Combining the genome sequencing and the previous transcriptome sequencing results, we reanalyzed the differential transcripts of P. praeruptorum before and after bolting. A total of 62,088 new transcripts were identified, of which 31,500 were unknown transcripts. Functional classification and annotation showed that many genes were involved in the regulation of transcription, defense response, and carbohydrate metabolic processes. The main domains are the pentatricopeptide repeat, protein kinase, RNA recognition motif, leucine-rich repeat, and ankyrin repeat domains, indicating their pivotal roles in protein modification and signal transduction. Gene structure analysis showed that skipped exon (SE) was the most dominant alternative splicing, followed by the alternative 3' splice site (A3SS) and the alternative 5' splice site (A5SS). Functional enrichment of differentially expressed genes showed that these differentially expressed genes mainly include transmembrane transporters, channel proteins, DNA-binding proteins, polysaccharide-binding proteins, etc. In addition, genes involved in peroxisome, hexose phosphate pathway, phosphatidylinositol signaling system, and inositol phosphate metabolism pathway were greatly enriched. A protein-protein interaction network analysis discoverd 1,457 pairs of proteins that interact with each other. The expression levels of six UbiA genes, three UGT genes, and four OMT genes were higher during the bolting stage. This observation suggests their potential involvement in the catalytic processes of prenylation, glycosylation, and methylation of coumarins, respectively. A total of 100 peroxidase (PRX) genes were identified being involved in lignin polymerization, but only nine PRX genes were highly expressed at the bolting stage. It is worth noting that 73 autophagy-related genes (ATGs) were first identified from the KEGG pathway-enriched genes. Some ATGs, such as BHQH00009837, BHQH00013830, and novel8944, had higher expression levels after bolting. CONCLUSIONS: Comparative transcriptome analysis and large-scale genome screening provide guidance and new opinions for the identification of bolting-related genes in P. praeruptorum.

Nitrogen Fixation by Benzene into Pyridine and Aniline in Water/Nitrogen Plasma.

We demonstrated direct conversion of benzene into pyridine and aniline, assisted through exact mass measurements (m/z 80.0494, 93.0574, and 94.0651, respectively), through the interaction of benzene with water/nitrogen vapor plasma produced by corona discharge. Systematic analysis using a series of isotopic standards indicated that formation of pyridine and aniline occurred through the reaction between neutral benzene and reactive N+(OH2)2 in water/nitrogen plasma; exact mass measurements of products and intermediates supported this hypothesis. As the proportion of water vapor in plasma increased over time, the reaction proceeded from exclusive formation of protonated pyridine to formation of protonated aniline as the main product; theoretical simulations indicated that the presence of water vapor promoted proton migration to elicit formation of protonated aniline. The reactions we discovered suggest a new mechanism for direct nitrogen fixation.

Identification and validation of lactate metabolism-related genes in oxygen-induced retinopathy.

Retinopathy of Prematurity (ROP) is a multifactorial disease characterized by abnormal retinal vascular growth in premature infants, which is one of the leading causes of childhood blindness. Lactic acid metabolism may play an imperative role in the development of ROP, but there are still few relevant studies. Our team use a dataset GSE158799 contained 284 genes in 3 P17_OIR mice and 3 P30_OIR mice to identify 41 potentially differentially expressed lactate metabolism-related genes (LMRGs) related to ROP. Then through bioinformatics analysis, we strive to reveal the interaction, the enriched pathways and the immune cell infiltration among these LMRGs, and predict their functions and internal mechanisms. These DEGs may regulate lactate metabolism, leading to the changes of metabolism and immunity, thereby inducing the development of ROP. Our results will expand our understanding of the intrinsic mechanism of ROP and may be helpful for the directions for treatment of ROP in the future.

Associations between modifiable risk factors and frailty: a Mendelian randomisation study.

BACKGROUND: Early identification of modifiable risk factors is essential for the prevention of frailty. This study aimed to explore the causal relationships between a spectrum of genetically predicted risk factors and frailty. METHODS: Univariable and multivariable Mendelian randomisation (MR) analyses were performed to explore the relationships between 22 potential risk factors and frailty, using summary genome-wide association statistics. Frailty was accessed by the frailty index. RESULTS: Genetic liability to coronary artery disease (CAD), type 2 diabetes mellitus (T2DM), ischaemic stroke, atrial fibrillation and regular smoking history, as well as genetically predicted 1-SD increase in body mass index, systolic blood pressure, diastolic blood pressure, low-density lipoprotein cholesterol, triglycerides, alcohol intake frequency and sleeplessness were significantly associated with increased risk of frailty (all p<0.001). In addition, there was a significant inverse association between genetically predicted college or university degree with risk of frailty (beta -0.474; 95% CI (-0.561 to -0.388); p<0.001), and a suggestive inverse association between high-density lipoprotein cholesterol level with risk of frailty (beta -0.032; 95% CI (-0.055 to -0.010); p=0.004). However, no significant causal associations were observed between coffee consumption, tea consumption, serum level of total testosterone, oestradiol, 25-hydroxyvitamin D, C reactive protein or moderate to vigorous physical activity level with frailty (all p>0.05). Results of the reverse directional MR suggested bidirectional causal associations between T2DM and CAD with frailty. CONCLUSIONS: This study provided genetic evidence for the causal associations between several modifiable risk factors with lifetime frailty risk. A multidimensional approach targeting these factors may hold a promising prospect for prevention frailty.

Trace Doping: Fluorine-Containing Hydrophobic Lewis Acid Enables Stable Perovskite Solar Cells.

With the rapid development in perovskite solar cell (PSC), high efficiency has been achieved, but the long-term operational stability is still the most important challenges for the commercialization of this emerging photovoltaic technology. So far, bi-dopants lithium bis(trifluoromethylsulfonyl)-imide (Li-TFSI)/4-tert-butylpyridine (t-BP)-doped hole-transporting materials (HTM) have led to state-of-the art efficiency in PSCs. However, such dopants have several drawbacks in terms of stability, including the complex oxidation process, undesirable ion migration and ultra-hygroscopic nature. Herein, a fluorine-containing organic Lewis acid dopant bis(pentafluorophenyl)zinc (Zn-FP) with hydrophobic property and high migration barrier has been employed as a potential alternative to widely employed bi-dopants Li-TFSI/t-BP for poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine] (PTAA). The resulting Zn-FP-based PSCs achieve a maximum PCE of 20.34 % with hysteresis-free current density-voltage (J-V) scans. Specifically, the unencapsulated device exhibits a significantly advanced of operational stability under the International Summit on Organic Photovoltaic Stability protocols (ISOS-L-1), maintaining over 90 % of the original efficiency after operation for 1000 h under continuous 1-sun equivalent illumination in N2 atmosphere in both forward and reverse J-V scan.

Insight into the regulatory mechanism of dynamic chromatin 3D interactions during cardiomyocyte differentiation in human.

Cardiogenesis is an extremely complicated process involved with DNA regulatory elements, and trans factors regulate gene expression pattern spatiotemporally. Enhancers, as the well-known DNA elements, activate target gene expression by transcription factors (TFs) occupied to organize dynamic three-dimensional (3D) interactions, which when affected or interrupted might cause heart defects or diseases. In this study, we integrated transcriptome, 3D genome, and regulatome to reorganize the global 3D genome in cardiomyogenesis, showing a gradually decreased trend of both chromatin interactions and topological associating domains (TADs) during cardiomyocyte differentiation. And almost all of the chromatin interactions occurred within the same or between adjacent TADs involved with enhancers, indicating that dynamical rewiring of enhancer-related chromatin interactions in the continuous expansive TADs is closely correlated to cardiogenesis. Moreover, we found stage-specific interactions activate stage-specific expression to be involved within corresponding biological functions, and the stage-specific combined regulations of enhancers and binding TFs form connected networks to control stage-specific expression and biological processes, which promote cardiomyocyte differentiation. Finally, we identified markers based on regulatory networks, which might drive cardiac development. This study demonstrates the power of enhancer interactome combined with active TFs to reveal insights into transcriptional regulatory networks during cardiomyogenesis.