Single-Cell Transcriptome Atlas and Regulatory Dynamics in Developing Cotton Anthers.

Plant anthers are composed of different specialized cell types with distinct roles in plant reproduction. High temperature (HT) stress causes male sterility, resulting in crop yield reduction. However, the spatial expression atlas and regulatory dynamics during anther development and in response to HT remain largely unknown. Here, the first single-cell transcriptome atlas and chromatin accessibility survey in cotton anther are established, depicting the specific expression and epigenetic landscape of each type of cell in anthers. The reconstruction of meiotic cells, tapetal cells, and middle layer cell developmental trajectories not only identifies novel expressed genes, but also elucidates the precise degradation period of middle layer and reveals a rapid function transition of tapetal cells during the tetrad stage. By applying HT, heterogeneity in HT response is shown among cells of anthers, with tapetal cells responsible for pollen wall synthesis are most sensitive to HT. Specifically, HT shuts down the chromatin accessibility of genes specifically expressed in the tapetal cells responsible for pollen wall synthesis, such as QUARTET 3 (QRT3) and CYTOCHROME P450 703A2 (CYP703A2), resulting in a silent expression of these genes, ultimately leading to abnormal pollen wall and male sterility. Collectively, this study provides substantial information on anthers and provides clues for heat-tolerant crop creation.

Pirin Inhibits FAS-Mediated Apoptosis to Support Colorectal Cancer Survival.

Resistance to immunotherapy in colorectal cancer (CRC) is associated with obstruction of FAS (Apo-1 or CD95)-dependent apoptosis, a hallmark of cancer. Here it is demonstrated that the upregulation of pirin (PIR) protein in colon cancers promotes tumorigenesis. Knockout or inhibition of PIR dramatically increases FAS expression, FAS-dependent apoptosis and attenuates colorectal tumor formation in mice. Specifically, NFκB2 is a direct transcriptional activator of FAS and robustly suppressed by PIR in dual mechanisms. One is the disruption of NFκB2 complex (p52-RELB) association with FAS promoter, the other is the inhibition of NIK-mediated NFκB2 activation and nuclear translocation, leading to the inability of active NFκB2 complex toward the transcription of FAS. Furthermore, PIR interacts with FAS and recruits it in cytosol, preventing its membrane translocation and assembling. Importantly, knockdown or knockout of PIR dramatically sensitizes cells to FAS mAb- or active CD8+ T cells-triggered cell death. Taken together, a PIR-NIK-NFκB2-FAS survival pathway is established, which plays a key role in supporting CRC survival.

Hepatic conversion of acetyl-CoA to acetate plays crucial roles in energy stress.

Accumulating evidence indicates that acetate is increased under energy stress conditions such as those that occur in diabetes mellitus and prolonged starvation. However, how and where acetate is produced and the nature of its biological significance are largely unknown. We observed overproduction of acetate to concentrations comparable to those of ketone bodies in patients and mice with diabetes or starvation. Mechanistically, ACOT12 and ACOT8 are dramatically upregulated in the liver to convert free fatty acid-derived acetyl-CoA to acetate and CoA. This conversion not only provides a large amount of acetate, which preferentially fuels the brain rather than muscle, but also recycles CoA, which is required for sustained fatty acid oxidation and ketogenesis. We suggest that acetate is an emerging novel 'ketone body' that may be used as a parameter to evaluate the progression of energy stress.

Sjogren's Syndrome Complicated With Aldosterone-Producing Adenoma: A Case Report.

Hypokalemia may be present in some patients with Sjogren's syndrome. When a patient with Sjogren's syndrome presents with hypokalemia, we would first consider it to be a result of the renal involvement of Sjogren's syndrome. However, in this case report, we present a young woman with Sjogren's syndrome who presented with hypokalemia that was not caused by renal tubular acidosis but by the presence of a coexisting aldosterone-producing adenoma. Cases of Sjogren's syndrome coexisting with aldosterone-producing adenoma are extremely rare. This finding underscores the need for more careful differential diagnosis in patients with Sjogren's syndrome who also have hypokalemia.

Molecular mechanism underlying epithelial-mesenchymal transformation and cisplatin resistance in esophageal squamous cell carcinoma.

Esophageal cancer (EC) occupies the seventh spot of the most prevalent malignancy cancer ailments worldwide and the sixth leading cause of cancer-related death. Esophageal squamous cell carcinoma (ESCC) is also the most predominant histological subtype of EC, and cisplatin (DDP) is commonly used as a first-line chemotherapeutic drug for the late advanced stages of the disease. However, the emergence of drug resistance during clinical treatment possesses a significant challenge to the therapeutic success and patient outcomes. Collectively, the epithelial-mesenchymal transformation (EMT) is a process in which transcription factors are induced to regulate the expression of epithelial and stromal markers to promote the differentiation of epithelial cells into stromal cells. Recent studies have demonstrated a close association between EMT and chemotherapy resistance in tumor cells, with concrete evidence of reciprocal reinforcement. Therefore, in this review, we elucidate the molecular mechanism underlying ESCC, shed light on the mechanisms driving DDP resistance, and provide insights into the intricate interplay between EMT and ESCC. We have aimed to provide some new hypotheses and perspectives that may address-inform future therapeutic strategies for ESCC treatment.

Quantitative Acetylomics Reveals Substrates of Lysine Acetyltransferase GCN5 in Adult and Aging Drosophila.

Protein lysine acetylation is a dynamic post-translational modification (PTM) that regulates a wide spectrum of cellular events including aging. General control nonderepressible 5 (GCN5) is a highly conserved lysine acetyltransferase (KAT). However, the acetylation substrates of GCN5 in vivo remain poorly studied, and moreover, how lysine acetylation changes with age and the contribution of KATs to aging remain to be addressed. Here, using Drosophila, we perform label-free quantitative acetylomic analysis, identifying new substrates of GCN5 in the adult and aging process. We further characterize the dynamics of protein acetylation with age, which exhibits a trend of increase. Since the expression of endogenous fly Gcn5 progressively increases during aging, we reason that, by combining the substrate analysis, the increase in acetylation with age is triggered, at least in part, by GCN5. Collectively, our study substantially expands the atlas of GCN5 substrates in vivo, provides a resource of protein acetylation that naturally occurs with age, and demonstrates how individual KAT contributes to the aging acetylome.

Pyrimidinergic receptor P2Y6 expression is elevated in lung adenocarcinoma and is associated with poor prognosis.

BACKGROUD: Previous in vitro studies have indicated that pyrimidinergic receptor P2Y6 (P2RY6, P2Y6 receptor) may function as a cancer-promoting factor in lung adenocarcinoma (LUAD). However, the prognostic significance of P2RY6 expression in LUAD has not been investigated. OBJECTIVE: This study aimed to assess the impact of P2RY6 expression on the survival of patients with LUAD. METHODS: First, we assessed P2RY6 mRNA and protein expression in LUAD and non-cancerous lung tissues using the online bioinformatics analysis tool GEPIA, fresh LUAD tissues, and LUAD tissue microarrays (TMAs). Second, we investigated the correlation between P2RY6 expression and clinicopathological parameters of LUAD patients based on data from The Cancer Genome Atlas (TCGA) database and TMAs. Finally, we analyzed the prognostic significance of P2RY6 expression in LUAD using the online survival analysis tool Kaplan-Meier Plotter and data from TMAs. RESULTS: We demonstrated that P2RY6 mRNA and protein expression levels in LUAD tissues were significantly higher than those in non-cancerous lung tissues. The expression of P2RY6 in LUAD was positively correlated with poor differentiation, more lymph node metastasis, and more advanced clinical stage. Higher P2RY6 expression level was correlated with shorter survival of the LUAD patients. Univariate and multivariate Cox regression analyses indicated that higher P2RY6 tumor expression was an independent unfavorable prognostic factor for LUAD patients. CONCLUSIONS: P2RY6 expression was elevated in LUAD and correlated with poor prognosis.

Hydrothermal Pretreatment of KOH for the Preparation of PAC and Its Adsorption on TC.

The environment has been heavily contaminated with tetracycline (TC) due to its excessive use; however, activated carbon possessing well-developed pores can effectively adsorb TC. This study synthesized pinecone-derived activated carbon (PAC) with high specific surface area (1744.659 cm2/g, 1688.427 cm2/g) and high adsorption properties (840.62 mg/g, 827.33 mg/g) via hydrothermal pretreatment methods utilizing pinecones as precursors. The results showed that PAC treated with 6% KOH solution had excellent adsorption properties. It is found that the adsorption process accords with the PSO model, and a large amount of C=C in PAC provides the carrier for π-πEDA interaction. The results of characterization and the isothermal model show that TC plays a key role in the adsorption process of PAC. It is concluded that the adsorption process of TC on PAC prepared by hydrothermal pretreatment is mainly pore filling and π-πEDA interaction, which makes it a promising adsorbent for TC adsorption.

Histone H3 lysine 27 trimethylation suppresses jasmonate biosynthesis and signaling to affect male fertility under high temperature in cotton.

High-temperature (HT) stress causes male sterility in crops, thus decreasing yields. To explore the possible contribution of histone modifications to male fertility under HT conditions, we defined the histone methylation landscape for the marks histone H3 lysine 27 trimethylation (H3K27me3) and histone H3 lysine 4 trimethylation (H3K4me3) by chromatin immunoprecipitation sequencing (ChIP-seq) in two differing upland cotton (Gossypium hirsutum) varieties. We observed a global disruption in H3K4me3 and H3K27me3 modifications, especially H3K27me3, in cotton anthers subjected to HT. HT affected the bivalent H3K4me3-H3K27me3 modification more than either monovalent modification. We determined that removal of H3K27me3 at the promoters of jasmonate-related genes increased their expression, maintaining male fertility under HT in the HT-tolerant variety at the anther dehiscence stage. Modulating jasmonate homeostasis or signaling resulted in an anther indehiscence phenotype under HT. Chemical suppression of H3K27me3 deposition increased jasmonic acid contents and maintained male fertility under HT. In summary, our study provides new insights into the regulation of male fertility by histone modifications under HT and suggests a potential strategy for improving cotton HT tolerance.

Co-Pyrolysis for Pine Sawdust with Potassium Chloride: Insight into Interactions and Assisting Biochar Graphitization.

This effort aimed to explore the activation and catalytic graphitization mechanisms of non-toxic salts in converting biomass to biochar from the perspective of pyrolysis kinetics using renewable biomass as feedstock. Consequently, thermogravimetric analysis (TGA) was used to monitor the thermal behaviors of the pine sawdust (PS) and PS/KCl blends. The model-free integration methods and master plots were used to obtain the activation energy (E) values and reaction models, respectively. Further, the pre-exponential factor (A), enthalpy (ΔH), Gibbs free energy (ΔG), entropy (ΔS), and graphitization were evaluated. When the KCl content was above 50%, the presence of KCl decreased the resistance to biochar deposition. In addition, the differences in the dominant reaction mechanisms of the samples were not significant at low (α ≤ 0.5) and high (α ≥ 0.5) conversion rates. Interestingly, the lnA value showed a linearly positive correlation with the E values. The PS and PS/KCl blends possessed positive ΔG and ΔH values, and KCl was able to assist biochar graphitization. Encouragingly, the co-pyrolysis of the PS/KCl blends allows us to target-tune the yield of the three-phase product during biomass pyrolysis.

Remote-Triggered Domino-like Cyclodehydrogenation in Second-Layer Topological Graphene Nanoribbons.

Cyclodehydrogenation reactions in the on-surface synthesis of graphene nanoribbons (GNRs) usually involve a series of Csp2-Csp2 and/or Csp2-Csp3 couplings and just happen on uncovered metal or metal oxide surfaces. It is still a big challenge to extend the growth of second-layer GNRs in the absence of necessary catalytic sites. Here, we demonstrate the direct growth of topologically nontrivial GNRs via multistep Csp2-Csp2 and Csp2-Csp3 couplings in the second layer by annealing designed bowtie-shaped precursor molecules over one monolayer on the Au(111) surface. After annealing at 700 K, most of the polymerized chains that appear in the second layer covalently link to the first-layer GNRs that have partially undergone graphitization. Following annealing at 780 K, the second-layer GNRs are formed and linked to the first-layer GNRs. Benefiting from the minimized local steric hindrance of the precursors, we suggest that the second-layer GNRs undergo domino-like cyclodehydrogenation reactions that are remotely triggered at the link. We confirm the quasi-freestanding behaviors in the second-layer GNRs by measuring the quasiparticle energy gap of topological bands and the tunable Kondo resonance from topological end spins using scanning tunneling microscopy/spectroscopy combined with first-principles calculations. Our findings pave the avenue to diverse multilayer graphene nanostructures with designer quantum spins and topological states for quantum information science.

Enhancement of anaerobic digestion of rice straw by amino acid-derived ionic liquid.

This study proposes a novel method to enhance methane production from anaerobic digestion using an amino acid-derived ionic liquid, glycine hydrochloride, ([Gly][Cl]), as an exogenous additive. After 40 days of digestion with 5% [Gly][Cl], the cumulative methane production was 115.56 mL/g VS, which was 73% higher than that of the control group (without additive). Specifically, the peak activities of cellulase, xylanase, and lignin peroxidase were significantly higher than those of the control group. The addition of [Gly][Cl] increased bacterial diversity and reduced archaeal diversity. Synergistota represented by Syner-01, Fibrobacterota represented by BBMC-4, Bacteroides, and unclassified_f__Lachnospiraceae significantly increased in relative abundance. It suggested that [Gly][Cl] stimulated the activities of protein-hydrolyzing and acid-producing bacteria. [Gly][Cl] also increased the abundance of methanogens and archaea, converting more lignocellulose to methane. Methanobacterium, that metabolizes H2 and CO2 to CH4, was more abundant. Therefore, [Gly][Cl] can improve methane yield as an anaerobic digestion additive.

ß-Carboline alkaloids from Picrasma quassioides and their 3D-QSAR study on anti-inflammation in LPS-induced RAW 264.7 cells.

Two new ß-carboline alkaloids (1-2), 1-pyrrolidone propionyl-ß-carboline (1) and 1-(3-hydroxy-2-oxopiperidine-1-ethyl)-4,8-dimethoxyl-ß-carboline (2), named kumujantine W and J respectively, together with ten known compounds (3-12) were isolated from the stems of Picrasma quassioides (D. Don) Benn. Their structures were elucidated from spectral data including 1D and 2D NMR, UV, IR, HR-ESI-MS spectroscopic analysis and ECD calculations as well as by comparison to the reference databases or literature. The anti-inflammatory effects of these alkaloids (1-12) and six other ß-carboline alkaloids (13-18) in LPS-induced RAW 264.7 cells were evaluated by measuring nitric oxide (NO) concentrations. Among them, compounds 1, 3, 6, 15, and 17 could inhibit the secretion of NO, displaying significant anti-inflammatory activity without affecting cell viability in vitro, and 3D-QSAR analysis further revealed the influence of groups on the activity in ß-carboline alkaloids.

Advances in the Application of Preclinical Models in Photodynamic Therapy for Tumor: A Narrative Review.

Photodynamic therapy (PDT) is a non-invasive laser light local treatment that has been utilized in the management of a wide variety of solid tumors. Moreover, the evaluation of efficacy, adverse reactions, the development of new photosensitizers and the latest therapeutic regimens are inseparable from the preliminary exploration in preclinical studies. Therefore, our aim was to better comprehend the characteristics and limitations of these models and to provide a reference for related research. METHODS: We searched the databases, including PubMed, Web of Science and Scopus for the past 25 years of original research articles on the feasibility of PDT in tumor treatment based on preclinical experiments and animal models. We provided insights into inclusion and exclusion criteria and ultimately selected 40 articles for data synthesis. RESULTS: After summarizing and comparing the methods and results of these studies, the experimental model selection map was drawn. There are 7 main preclinical models, which are used for different research objectives according to their characteristics. CONCLUSIONS: Based on this narrative review, preclinical experimental models are crucial to the development and promotion of PDT for tumors. The traditional animal models have some limitations, and the emergence of organoids may be a promising new insight.

A comparative study of Liandan Xiaoyan Formula metabolic profiles in control and colitis rats by UPLC-Q-TOF-MS combined with chemometrics.

Liandan Xiaoyan Formula (LDXYF) is a traditional Chinese medicine prescription (TCMP) consisting of Herba Andrographis (dried herb of Andrographis paniculata) and Picrasmae ramulus et folium (dried twiggeries and leaves of Picrasma quassioides). It is used to treat diarrhea, acute gastroenteritis, colitis, and dysentery, among other inflammatory gastrointestinal diseases. However, because of less research on the in vitro chemical composition and holistic metabolism of LDXYF, in vivo mechanisms of action and quality control of LDXYF have not yet been fully assessed due to the lack of studies into its bioactive components. In this study, ultra-performance liquid chromatography coupled with quadruple time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was established for comprehensive analysis of chemical compounds of LDXYF and their metabolites in serum and urine samples of control and colitis rats. As a result, totally 94 compounds in LDXYF were unambiguously identified or tentatively characterized. And a total of 91 LDXYF-related xenobiotics were characterized, including 61 (16 prototypes and 45 metabolites) in serum, and 72 (26 prototypes and 46 metabolites) in urine. Besides, we compared the exposure of metabolites in normal and colitis rats by chemometrics and summarize similarities and differences of metabolic pathways of mainly compounds in normal and colitis conditions, and found that in control and colitis conditions, alkaloids predominantly went through phase I reaction combined phase II reaction (hydroxylation and sulfation, hydroxylation and glucuronidation, demethylation and glucuronidation), while the major metabolic reaction of diterpene lactones were phase Ⅱ reactions (glucuronidation, sulfation). And there were no significant differences in metabolic pathways between control and colitis groups, just the exposure of prototype and their metabolites absorbed into serum or excreted through the urine were different, and 17 alkaloids and 6 diterpene lactone prototypes and their metabolites in serum could be considered as potential pharmacodynamic substances. A comprehensive analysis of the compounds and metabolic characteristics of LDXYF was conducted in our study, and the results laid the chemical foundation for further research into effective substances and the action mechanism of LDXYF.

Radiomics-based prediction of response to immune checkpoint inhibitor treatment for solid cancers using computed tomography: a real-world study of two centers.

BACKGROUND: Immune checkpoint inhibitors (ICIs) represent an approved treatment for various cancers; however, only a small proportion of the population is responsive to such treatment. We aimed to develop and validate a plain CT-based tool for predicting the response to ICI treatment among cancer patients. METHODS: Data for patients with solid cancers treated with ICIs at two centers from October 2019 to October 2021 were randomly divided into training and validation sets. Radiomic features were extracted from pretreatment CT images of the tumor of interest. After feature selection, a radiomics signature was constructed based on the least absolute shrinkage and selection operator regression model, and the signature and clinical factors were incorporated into a radiomics nomogram. Model performance was evaluated using the training and validation sets. The Kaplan-Meier method was used to visualize associations with survival. RESULTS: Data for 122 and 30 patients were included in the training and validation sets, respectively. Both the radiomics signature (radscore) and nomogram exhibited good discrimination of response status, with areas under the curve (AUC) of 0.790 and 0.814 for the training set and 0.831 and 0.847 for the validation set, respectively. The calibration evaluation indicated goodness-of-fit for both models, while the decision curves indicated that clinical application was favorable. Both models were associated with the overall survival of patients in the validation set. CONCLUSIONS: We developed a radiomics model for early prediction of the response to ICI treatment. This model may aid in identifying the patients most likely to benefit from immunotherapy.

A Scientometric Review: Biomass Gasification Study from 2006 to 2020.

Biomass gasification represents a significant way to produce energy from biomass. It features renewable properties and offers great potential for utilization. The application of biomass gasification products, design of the gasifier, type of biomass feedstock, gasification agents, and gasification parameters are key for the biomass gasification process. This work applies bibliometric approaches to provide a comprehensive and objective analysis of worldwide biomass gasification study trends over the period from 2006 to 2020 according to the Web Of Science core collection data. A total of 3222 articles associated with biomass gasification was retrieved, and its number grew annually. The subjects of study are diversified, primarily classified into "Energy & Fuels", "Engineering Chemical", and "Green Sustainable Science Technology". Moreover, Energy was a top published journal in the field of biomass gasification. Austrian contributors had the majority of publications, next to China and the USA. Liejin Luo from Xi'an Jiaotong University possessed the greatest H-index. Keyword evaluation showed that biomass gasification is a current hotspot, among which life-cycle assessment, sustainability, and deep processing of gasification products are future research directions. This work is predicted to offer further research interest in biomass gasification.

Clinical Indications for Extubation in Coma Patients with Severe Neurological Craniocerebral Injury with Meta-Analysis.

Computer searches of the PubMed, Cochrane Library, and Embase databases for randomized controlled studies on the effects of intensive nutrition on clinical outcomes in patients with severe craniocerebral injury were conducted from the time of database creation to June 11, 2022, along with manual searches of the relevant literature. Two investigators independently screened the literature, extracted data, and evaluated the risk of bias of the included studies before the effect sizes were combined using RevMan 5.3 statistical software provided by the Cochrane Collaboration Network, and publication bias was detected using Stata 12.0 software. Meta-analysis showed that total protein levels were higher in the intensive nutrition group than in the regular nutrition group (WMD = 4.96 g/L (1.57-8.34), P < 0.001); IgA levels were significantly higher in the intensive nutrition group than in the regular nutrition group (SMD = 0.79 (0.51-1.07), P < 0.001; SMD = 0.98 (0.58-1.38), P < 0.001); IgG levels were significantly higher in the fortified group than in the regular group (SMD = 0.98 (0.58-1.38), P < 0.001); CD4/CD8 was significantly higher in the fortified patients than in the regular patients with a combined effect size of WMD = 0.33 (0.18-0.48) (P < RR = 0.45 (0.27-0.75), P = 0.002). The results show that effective support of early enteral nutrition can reduce the occurrence of gastrointestinal complications in patients, give them a better adaptation process to the gastrointestinal tract, and ensure the degree of tolerance of their gastric mucosa, thus absorbing more nutrition. Fortification significantly reduced the incidence of gastric retention in patients with craniocerebral injury (RR = 0.19 (0.07-0.49), P < 0.001). In the subgroup analysis of the three groups, it was shown that, depending on the starting time, the total protein level and IgG level were better in the early nutrition at 24 h than in the late nutrition above 24h and that, depending on the starting dose, the total protein level, IgA, IgG, and CD4/CD8 were better in the intervention at doses above 30 mL/h, using the starting dose of 30 mL/h as the cut-off point. In the subgroup analysis based on different nutrition methods (enteral and parenteral nutrition), IgA levels and the incidence of bloating and diarrhea were better than those of parenteral nutrition in the indicators of enteral nutrition.

Diterpenoid alkaloids isolated from Delphinium trichophorum alleviate pulmonary fibrosis via the TGF-ß/Smad pathway in 3T6 and HFL-1 cells.

Delphinium trichophorum Franch (DTF), a species endemic to China, has been widely used for centuries in Tibet as an indigenous medicine for treating cough, pneumonia, and pulmonary fibrosis. Hetisine-type C20-diterpenoid alkaloids have been reported to be characteristic and active ingredients. Herein, five ones with relatively high contents in D. trichophorum, including 2α,11α,13ß-triacetylhetisine (DTF1), trichodelphinine A (DTF2), trichodelphinine D (DTF3), 2α-acetyl-11α,13ß-dihydroxyhetisine (DTF4), and trichodelphinine C (DTF5), were investigated for anti-fibrosis effects using fibroblasts induced by TGF-ß1 or LPS for the first time. The results showed that all five tested compounds decreased hydroxyproline (HYP) levels and inhibited the abnormal proliferation of 3T6 and HFL-1 cells induced by either TGF-ß1 or LPS. Moreover, DTF1 and DTF2 attenuated the production of collagen (Col-1 and Col-3) at relatively low doses, suggesting their higher efficiency among the five alkaloids. Based on large-scale ligand-based pharmacophore modeling, TGFBR1 was screened as a potential target for these tested alkaloids. The molecular docking results also exhibited high-affinity interactions between TGFBR1 and five alkaloids, especially DTF1 and DTF2. Further experiments revealed that DTF1 and DTF2 could inhibit the expression of TGF-ß1 and α-SMA and the phosphorylation of Smad3 and Smad4 while restoring the expression of Smad7 protein. Overall, DTF1 and DTF2 may reduce collagen generation and delay the development of pulmonary fibrosis by inhibiting the activation of the TGF-ß/Smad signaling pathway. Our results provide experimental and theoretical evidence for DTF1 and DTF2 as superior candidates for further development of anti-fibrotic drugs.