Integrative physiological and transcriptome analysis unravels the mechanism of low nitrogen use efficiency in burley tobacco.

Burley tobacco, a chlorophyll-deficient mutant with impaired nitrogen use efficiency (NUE), generally requires three to five times more nitrogen fertilization than flue-cured tobacco to achieve a comparable yield, which generates serious environmental pollution and negatively affects human health. Therefore, exploring the mechanisms underlying NUE is an effective measure to reduce environmental pollution and an essential direction for burley tobacco plant improvement. Physiological and genetic factors affecting tobacco NUE were identified using two tobacco genotypes with contrasting NUE in hydroponic experiments. Nitrogen use inefficient genotype (TN90) had lower nitrogen uptake and transport efficiencies, reduced leaf and root biomass, lower nitrogen assimilation and photosynthesis capacity, and lower nitrogen remobilization ability than the nitrogen use efficient genotype (K326). Transcriptomic analysis revealed that genes associated with photosynthesis, carbon fixation, and nitrogen metabolism are implicated in NUE. Three nitrate transporter genes in the leaves (NPF2.11, NPF2.13, and NPF3.1) and three nitrate transporter genes (NPF6.3, NRT2.1, and NRT2.4) in roots were down-regulated by nitrogen starvation, all of which showed lower expression in TN90 than in K326. In addition, the protein-protein interaction (PPI) network diagram identified eight key genes (TPIP1, GAPB, HEMB, PGK3, PSBO, PSBP2, PSAG, and GLN2) that may affect NUE. Less advantageous changes in nitrogen uptake, nitrogen assimilation in combination with nitrogen remobilization, and maintenance of photosynthesis in response to nitrogen deficiency led to a lower NUE in TN90. The key genes (TPIP1, GAPB, PGK3, PSBO, PSBP2, PSAG, and GLN2) were associated with improving photosynthesis and nitrogen metabolism in tobacco plants grown under N-deficient conditions.

Stabilization of RRBP1 mRNA via an m6A-dependent manner in prostate cancer constitutes a therapeutic vulnerability amenable to small-peptide inhibition of METTL3.

Mounting evidence has implicated the RNA m6A methylation catalyzed by METTL3 in a wide range of physiological and pathological processes, including tumorigenesis. The detailed m6A landscape and molecular mechanism of METTL3 in prostate cancer (PCa) remains ill-defined. We find that METTL3 is overexpressed in PCa and correlates with worse patient survival. Functional studies establish METTL3 as an oncoprotein dependent on its m6A enzymatic activity in both AR+ and AR- PCa cells. To dissect the regulatory network of m6A pathway in PCa, we map the m6A landscape in clinical tumor samples using m6A-seq and identify genome-wide METTL3-binding transcripts via RIP-seq. Mechanistically, we discover RRBP1 as a direct METTL3 target in which METTL3 stabilizes RRBP1 mRNA in an m6A-dependent manner. RRBP1 positively correlates with METTL3 expression in PCa cohorts and exerts an oncogenic role in aggressive PCa cells. Leveraging the 3D structural protein-protein interaction between METTL3 and METTL14, we successfully develop two potential METTL3 peptide inhibitors (RM3 and RSM3) that effectively suppress cancer cell proliferation in vitro and tumor growth in vivo. Collectively, our study reveals a novel METTL3/m6A/RRBP1 axis in enhancing aggressive traits of PCa, which can be therapeutically targeted by small-peptide METTL3 antagonists.

FAM72A degrades UNG2 through the GID/CTLH complex to promote mutagenic repair during antibody maturation.

A diverse antibody repertoire is essential for humoral immunity. Antibody diversification requires the introduction of deoxyuridine (dU) mutations within immunoglobulin genes to initiate somatic hypermutation (SHM) and class switch recombination (CSR). dUs are normally recognized and excised by the base excision repair (BER) protein uracil-DNA glycosylase 2 (UNG2). However, FAM72A downregulates UNG2 permitting dUs to persist and trigger SHM and CSR. How FAM72A promotes UNG2 degradation is unknown. Here, we show that FAM72A recruits a C-terminal to LisH (CTLH) E3 ligase complex to target UNG2 for proteasomal degradation. Deficiency in CTLH complex components result in elevated UNG2 and reduced SHM and CSR. Cryo-EM structural analysis reveals FAM72A directly binds to MKLN1 within the CTLH complex to recruit and ubiquitinate UNG2. Our study further suggests that FAM72A hijacks the CTLH complex to promote mutagenesis in cancer. These findings show that FAM72A is an E3 ligase substrate adaptor critical for humoral immunity and cancer development.

Mutant p53 achieves function by regulating EGR1 to induce epithelial mesenchymal transition.

The epithelial-mesenchymal transition (EMT) plays a crucial role in lung cancer metastasis, rendering it a promising therapeutic target. Research has shown that non-small cell lung cancer (NSCLC) with p53 mutations exhibits an increased tendency for cancer metastasis. However, the exact contribution of the p53-R273H mutation to tumor metastasis remains uncertain in the current literature. Our study established the H1299-p53-R273H cell model successfully by transfecting the p53-R273H plasmid into H1299 cells. We observed that p53-R273H promotes cell proliferation, migration, invasion, and EMT through CCK-8, wound healing, transwell, western blot and immunofluorescence assays. Notably, the expression of EGR1 was increased in H1299-p53-R273H cells. Knocking out EGR1 in these cells hindered the progression of EMT. ChIP-PCR experiments revealed that p53-R273H binds to the EGR1 promoter sequence, thereby regulating its expression. These findings suggest that p53-R273H triggers EMT by activating EGR1, thereby offering a potential therapeutic approach for lung cancer treatment.

Peptide Degrader-Based Targeting of METTL3/14 Improves Immunotherapy Response in Cutaneous Melanoma.

METTL3 has emerged as a promising therapeutic target in cancer treatment, although its oncogenic functions in melanoma development and potential for therapeutic targeting drug have not been fully explored. In this study, we define the oncogenic role of METTL3 in melanoma development and progression. Building on this insight, we examine our recently designed peptide inhibitor RM3, which targets the binding interface of METTL3/14 complex for disruption and subsequent ubiquitin-mediated proteasomal degradation via the E3 ligase STUB1. RM3 treatment reduces proliferation, migration, and invasion, and induces apoptosis in melanoma cells in vitro and in vivo. Subsequent transcriptomic analysis identified changes in immuno-related genes following RM3-mediated suppression of METTL3/14 N6-methyladenosine (m6A) methyltransferase activity, suggesting a potential for interaction with immunotherapy. A combination treatment of RM3 with anti-PD-1 antibody results in significantly higher beneficial tumor response in vivo, with a good safety profile. Collectively, these findings not only delineate the oncogenic role of METTL3 in melanoma but also showcase RM3, acting as a peptide degrader, as a novel and promising strategy for melanoma treatment.

Whole-Genome Resequencing Reveals Genetic Diversity and Growth Trait-Related Genes in Pinan Cattle.

The breeding of high-quality beef cattle breeds is crucial for the development of animal husbandry, and whole-genome resequencing is widely applicated in the field of molecular breeding. Advantages in growth and reproductive traits exist in Pinan cattle compared with other cattle breeds, but there is limited research on its genomic mechanism. Using whole-genome resequencing, the genetic structure and genomic selection signatures in Pinan cattle were investigated in this study. Phylogenetic, cluster, and admixture analysis results indicated that Pinan cattle have a closer genetic relationship with Kholmogory cattle and China north cattle breeds. Through a selective sweep strategy, 207 and 54 candidate genes related to growth and reproduction and immunity, respectively, were identified in the Pinan cattle population. Given the crucial role of the glutamate-cysteine ligase catalytic (GCLC) gene in muscle antioxidative defense, the high frequency of allele T of the GCLC c.429 C>T locus in the Pinan cattle population might partially contribute to the advantages of Pinan cattle in growth performance. This study laid the foundation for the genetic improvement in Chinese local beef cattle and provide background for the studies on the growth and development of Pinan cattle.

The role of liquid-liquid phase separation in defining cancer EMT.

Cancer EMT is a pivotal process that drives carcinogenesis, metastasis, and cancer recurrence, with its initiation and regulation intricately governed by biochemical pathways in a precise spatiotemporal manner. Recently, the membrane-less biomolecular condensates formed via liquid-liquid phase separation (LLPS) have emerged as a universal mechanism underlying the spatiotemporal collaboration of biological activities in cancer EMT. In this review, we first elucidate the current understanding of LLPS formation and its cellular functions, followed by an overview of valuable tools for investigating LLPS. Secondly, we examine in detail the LLPS-mediated biological processes crucial for the initiation and regulation of cancer EMT. Lastly, we address current challenges in advancing LLPS research and explore the potential modulation of LLPS using therapeutic agents.

Multifunctional Hydrogel of Recombinant Humanized Collagen Loaded with MSCs and MnO2 Accelerates Chronic Diabetic Wound Healing.

Chronic wound repair is a clinical treatment challenge. The development of multifunctional hydrogels is of great significance in the key aspects of treating chronic wounds, including reducing oxidative stress, promoting angiogenesis, and improving the natural remodeling of extracellular matrix and immune regulation. In this study, we prepared a composite hydrogel, sodium alginate (SA)@MnO2/recombinant humanized collagen III (RHC)/mesenchymal stem cells (MSCs), composed of SA, MnO2 nanoparticles, RHC, and MSCs. The hydrogel has high mechanical properties and good biocompatibility. In vitro, SA@MnO2/RHC/MSCs hydrogel effectively enhanced the formation of intricate tubular structures and angiogenesis and showed synergistic effects on cell proliferation and migration. In vivo, the SA@MnO2/RHC/MSCs hydrogel enhanced diabetes wound healing, rapid re-epithelization, favorable collagen deposition, and abundant wound angiogenesis. These findings demonstrated that the combined effects of SA, MnO2, RHC, and MSCs synergistically accelerate healing, resulting in a reduced healing time. These observed healing effects demonstrated the potential of this multifunctional hydrogel to transform chronic wound care and improve patient outcomes.

A Stapled Peptide Inhibitor Targeting the Binding Interface of N6-Adenosine-Methyltransferase Subunits METTL3 and METTL14 for Cancer Therapy.

METTL3, a primary methyltransferase catalyzing the RNA N6-methyladenosine (m6A) modification, has been identified as an oncogene in several cancer types and thus nominated as a potentially effective target for therapeutic inhibition. However, current options using this strategy are limited. In this study, we targeted protein-protein interactions at the METTL3-METTL14 binding interface to inhibit complex formation and subsequent catalysis of the RNA m6A modification. Among candidate peptides, RM3 exhibited the highest anti-cancer potency, inhibiting METTL3 activity while also facilitating its proteasomal degradation. We then designed a stapled peptide inhibitor (RSM3) with enhanced peptide stability and formation of the α-helical secondary structure required for METTL3 interaction. Functional and transcriptomic analysis in vivo indicated that RSM3 induced upregulation of programmed cell death-related genes while inhibiting cancer-promoting signals. Furthermore, tumor growth was significantly suppressed while apoptosis was enhanced upon RSM3 treatment, accompanied by increased METTL3 degradation, and reduced global RNA methylation levels in two in vivo tumor models. This peptide inhibitor thus exploits a mechanism distinct from other small-molecule competitive inhibitors to inhibit oncogenic METTL3 activity. Our findings collectively highlight the potential of targeting METTL3 in cancer therapies through peptide-based inhibition of complex formation and proteolytic degradation.

Eco-friendly bacterial cellulose/MXene aerogel with excellent photothermal and electrothermal conversion capabilities for efficient separation of crude oil/seawater mixture.

Developing novel absorbent materials targeting high-efficiency, low-energy-consumption, and environmental-friendly oil spill cleanup is still a global issue. Porous absorbents endowed with self-heating function are an attractive option because of that they are able to in-situ heat crude oil and dramatically reduce oil viscosity for efficient remediation. Herein, we facilely prepared an eco-friendly multifunctional bacterial cellulose/MXene aerogel (P-SBC/MXene aerogel) for rapid oil recovery. Thanks to excellent full solar spectrum absorption (average absorbance = 96.6 %), efficient photo-thermal conversion, and superior electrical conductivity (electrical resistance = 36 Ω), P-SBC/MXene aerogel exhibited outstanding photothermal and electrothermal capabilities. Its surface temperature could quickly reach 93 °C under 1.0 kW/m2 solar irradiation and 124 °C under 3.0 V voltage respectively, enabling effective heat transfer toward spilled oil. The produced heat significantly decreased crude oil viscosity, allowing P-SBC/MXene aerogel to rapidly absorb oil. By combining solar heating and Joule heating, P-SBC/MXene aerogel connected to a pump-assisted absorption device was capable of achieving all-weather crude oil removal from seawater (crude oil flux = 630 kg m-2 h-1). More notably, P-SBC/MXene aerogel showed splendid outdoor crude oil separation performance. Based on remarkable crude oil/seawater separation ability, the versatile aerogel provides a promising way to deal with large-area oil spills.

A Patient Similarity Network (CHDmap) to Predict Outcomes After Congenital Heart Surgery: Development and Validation Study.

Background: Although evidence-based medicine proposes personalized care that considers the best evidence, it still fails to address personal treatment in many real clinical scenarios where the complexity of the situation makes none of the available evidence applicable. "Medicine-based evidence" (MBE), in which big data and machine learning techniques are embraced to derive treatment responses from appropriately matched patients in real-world clinical practice, was proposed. However, many challenges remain in translating this conceptual framework into practice. Objective: This study aimed to technically translate the MBE conceptual framework into practice and evaluate its performance in providing general decision support services for outcomes after congenital heart disease (CHD) surgery. Methods: Data from 4774 CHD surgeries were collected. A total of 66 indicators and all diagnoses were extracted from each echocardiographic report using natural language processing technology. Combined with some basic clinical and surgical information, the distances between each patient were measured by a series of calculation formulas. Inspired by structure-mapping theory, the fusion of distances between different dimensions can be modulated by clinical experts. In addition to supporting direct analogical reasoning, a machine learning model can be constructed based on similar patients to provide personalized prediction. A user-operable patient similarity network (PSN) of CHD called CHDmap was proposed and developed to provide general decision support services based on the MBE approach. Results: Using 256 CHD cases, CHDmap was evaluated on 2 different types of postoperative prognostic prediction tasks: a binary classification task to predict postoperative complications and a multiple classification task to predict mechanical ventilation duration. A simple poll of the k-most similar patients provided by the PSN can achieve better prediction results than the average performance of 3 clinicians. Constructing logistic regression models for prediction using similar patients obtained from the PSN can further improve the performance of the 2 tasks (best area under the receiver operating characteristic curve=0.810 and 0.926, respectively). With the support of CHDmap, clinicians substantially improved their predictive capabilities. Conclusions: Without individual optimization, CHDmap demonstrates competitive performance compared to clinical experts. In addition, CHDmap has the advantage of enabling clinicians to use their superior cognitive abilities in conjunction with it to make decisions that are sometimes even superior to those made using artificial intelligence models. The MBE approach can be embraced in clinical practice, and its full potential can be realized.

Enhanced gene transfection and induction of apoptosis in melanoma cells by branched poly(ß-amino ester)s with uniformly distributed branching units.

Melanoma, one of the most devastating forms of skin cancer, currently lacks effective clinical treatments. Delivery of functional genes to modulate specific protein expression to induce melanoma cell apoptosis could be a promising therapeutic approach. However, transfecting melanoma cells using non-viral methods, particularly with cationic polymers, presents significant challenges. In this study, we synthesized three branched poly(ß-amino ester)s (HPAEs) with evenly distributed branching units but varying space lengths through a two-step "oligomer combination" strategy. The unique topological structure enables HPAEs to condense DNA to form nano-sized polyplexes with favorable physiochemical properties. Notably, HPAEs, especially HPAE-2 with intermediate branching unit space length, demonstrated significantly higher gene transfection efficiency than the leading commercial gene transfection reagent, jetPRIME, in human melanoma cells. Furthermore, HPAE-2 efficiently delivered the Bax-encoding plasmid into melanoma cells, leading to a pronounced pro-apoptotic effect without causing noticeable cytotoxicity. This study establishes a potent non-viral platform for gene transfection of melanoma cells by harnessing the distribution of branching units, paving the way for potential clinical applications of gene therapy in melanoma treatment.

Single-cell transcriptome analyses reveal cellular and molecular responses to low nitrogen in burley tobacco leaves.

Tobacco (Nicotiana tabacum) is cultivated and consumed worldwide. It requires great amounts of nitrogen (N) to achieve the best yield and quality. With a view to sustainable and environmentally friendly agriculture, developing new genotypes with high productivity under low N conditions is an important approach. It is unclear how genes in tobacco are expressed at the cellular level and the precise mechanisms by which cells respond to environmental stress, especially in the case of low N. Here, we characterized the transcriptomes in tobacco leaves grown in normal and low-N conditions by performing scRNA-seq. We identified 10 cell types with 17 transcriptionally distinct cell clusters with the assistance of marker genes and constructed the first single-cell atlas of tobacco leaves. Distinct gene expression patterns of cell clusters were observed under low-N conditions, and the mesophyll cells were the most important responsive cell type and displayed heterogene responses among its three subtypes. Pseudo-time trajectory analysis revealed low-N stress decelerates the differentiation towards mesophyll cells. In combination with scRNA-seq, WGCNA, and bulk RNA-seq results, we found that genes involved in porphyrin metabolism, nitrogen metabolism, carbon fixation, photosynthesis, and photosynthesis-antenna pathway play an essential role in response to low N. Moreover, we identified COL16, GATA24, MYB73, and GLK1 as key TFs in the regulation of N-responsive genes. Collectively, our findings are the first observation of the cellular and molecular responses of tobacco leaves under low N stress and lay the cornerstone for future tobacco scRNA-seq investigations.

Reducing nitrate and tobacco-specific nitrosamine level in burley tobacco leaves through grafting on flue-cured tobacco rootstock.

Nitrosation of pyridine alkaloids in tobacco generates tobacco-specific nitrosamines (TSNAs), which are notable toxicants in tobacco products and smoke. Burley tobacco, a chloroplast- and nitrogen (N)-deficient phenotype that accumulates high levels of nitrate-nitrogen (NO3-N) in its leaves, is particularly susceptible to TSNAs formation. In this study, reciprocal pot and field grafting experiments were conducted using burley tobacco Eyan No.1 and flue-cured tobacco K326 to investigate whether grafting burley tobacco scions on flue-cured tobacco rootstocks could enhance pigment biosynthesis and photosynthesis, while reducing the NO3-N level in burley tobacco leaves. Grafting burley tobacco scions on flue-cured tobacco rootstocks significantly increased the total pigment content, photosynthetic rate, biomass, nitrate reductase and glutamine synthetase activities, as well as ammonium-nitrogen (NH4-N), total soluble and reducing sugar, and soluble protein levels in burley tobacco leaves compared with burley tobacco self-rooting, while decreasing the NO3-N level and nitrate-N to total N ratio. Transcriptomic analysis revealed that grafting resulted in upregulated expression of genes involved in starch, sucrose, porphyrin, chlorophyll, and N metabolism, as well as carbon fixation and carotenoid biosynthesis. The findings suggest that grafting on high N use efficiency rootstock is an exceptionally promising means of decreasing NO3-N accumulation by improving photosynthesis and N metabolism in the scion, thereby reducing the levels of harmful TSNAs.

The hepatitis B virus pre-core protein p22 suppresses TNFα-induced apoptosis by regulating the NF-κB pathway.

OBJECTIVE: Cell apoptosis is strongly associated with hepatocellular carcinoma (HCC) progress. Thus, gaining a comprehensive understanding of the virus interfering with the apoptotic process is important for the development of effective anti-tumor therapies. The objective of this study is to explore the potential involvement of HBeAg-p22 (HBV-p22) in TNFα-induced apoptosis. METHODS: Protein expression was detected using western blot. Cell viability and apoptosis were assessed by employing Cell Counting Kit-8 (CCK8) and flow cytometry, respectively. Evaluation of protein-protein interactions was accomplished through co-immunoprecipitation and glutathione-S-transferase (GST) pull-down assays. RESULTS: In this study, it was shown that HBV-p22 inhibited apoptosis of human hepatoma cell lines after tumor necrosis factor-alpha (TNF-α) stimulation. Mechanistically, HBV-p22 suppressed Jun N-terminal kinases (JNK) signaling and enhanced nuclear factor kappa-B (NF-κB) signaling. Moreover, HBV-p22 interacted with I-kappa B kinase α (IKKα) and increased its phosphorylation. CONCLUSIONS: Collectively, HBV-p22, whereby the mechanism contributing to anti-apoptotic effect was regulation of the NF-κB pathway via enhancing the phosphorylation of IKKα.

Quercetin-enriched Lactobacillus aviarius alleviates hyperuricemia by hydrolase-mediated degradation of purine nucleosides.

The development of hyperuricemia (HUA) and gout is associated with dysbiosis of the gut microbiota. Quercetin can reduce serum uric acid levels and thus alleviate HUA by modulating the gut microbiota. However, the detailed mechanisms involved in this process are not fully understood. Here, we showed that quercetin significantly reduced the serum uric acid level in a chicken HUA model by altering the chicken cecal microbiota structure and function and increasing the abundance of Lactobacillus aviarius. An L. aviarius strain, CML180, was isolated from the quercetin-treated chicken gut microbiota. Strain characterization indicated that quercetin promoted the growth of L. aviarius CML180 and increased its adhesion, hydrophobicity, and co-aggregation abilities. Gavage of live L. aviarius CML180 to a mouse model of HUA-established by adenosine and potassium oxonate-reduced the serum uric acid level and alleviated HUA. The ability of L. aviarius CML180 to decrease the level of uric acid was due to its degradation of purine nucleosides, which are the precursors for uric acid production. A nucleoside hydrolase gene, nhy69, was identified from the genome of L. aviarius CML180, and the resulting protein, Nhy69, exhibited strong purine nucleoside-hydrolyzing activity at mesophilic temperature and neutral pH conditions. These findings provide mechanistic insights into the potential of quercetin to treat HUA or gout diseases via a specific gut microbe.

pH-Triggered Size-Transformable and Bioactivity-Switchable Self-Assembling Chimeric Peptide Nanoassemblies for Combating Drug-Resistant Bacteria and Biofilms.

Drug-resistant bacteria and biofilm-associated infections are prominent problems in the field of antibacterial medicine, seriously affecting human and animal health. Despite the great potential of nanomaterials in the antibacterial field, overcoming the paradox of size and charge, efficient penetration, and retention within biofilms remain a formidable challenge. Here, self-assembling chimeric peptide nanoassemblies composed of multiple functional fragments are designed for the treatment of drug-resistant bacteria and biofilm-associated infections. Notably, the chimeric peptide self-assembles into nanofibers at pH 7.4 and is transformable into nanoparticles in the acidic biofilm-infected microenvironment at pH 5.0, and thus achieves a size reduction and charge increase, improving the penetration into the bacterial biofilms and killing drug-resistant bacteria by a mechanism dominated by membrane cleavage. In vivo mouse and piglet infection models confirm the ability of chimeric peptide nanoassemblies to reduce bacterial load within biofilms. Collectively, this research on pathological-environment-driven nanostructural transformations may provide a theoretical basis for designing high-performance antibacterial nanomaterials and advance the application of peptide-based nanomaterials in medicine and animal husbandry.

Physiological, transcriptome and co-expression network analysis of chlorophyll-deficient mutants in flue-cured tobacco.

BACKGROUND: Photosynthetic pigments in higher plants, including chlorophyll (Chl) and carotenoids, are crucial for photosynthesis and photoprotection. Chl-deficient tobacco seedlings generally have a lower photosynthesis rate and higher nitrate-nitrogen (NO3-N) content, which causes a profound influence on tobacco yield and quality. In this study, a stable albino leaf mutant (Al) and slight-green leaf mutant (SG) obtained from the common flue-cured tobacco (Nicotiana tabacum L.) cultivar 'Zhongyan 100' (ZY100) by mutagenesis with ethyl methanesulfonate (EMS) were used as materials. The differences between the Chl-deficient mutants and the wild-type (WT) were analyzed in terms of biomass, photosynthetic fluorescence parameters, and carbon- and nitrogen-related physiological parameters. RNA sequencing (RNA-seq) and weighted gene co-expression network analysis (WGCNA) were used to explore the key pathways and candidate genes regulating differentiated chlorophyll and nitrate content. RESULTS: The results showed that, when compared to the WT, the Chl content and biomass of mutant plants were considerably lower while the NO3-N content was substantially elevated. The net photosynthetic rate, photosynthetic fluorescence parameters, carbohydrate, soluble protein, and carbon- and nitrogen-related enzyme activities all decreased in leaves of mutants and the development of chloroplasts was abnormal. Applying more nitrogen improved the growth and development of mutants, whereas NO3-N content distinctively increased compared with that of the WT. Through transcriptome sequencing, the downregulated genes in mutants were enriched in plant hormone signal transduction and nitrogen metabolism, which are involved in pigment biosynthesis and the carbon fixation pathway. In addition, two hub genes and seven transcription factors identified from the blue module through WGCNA were likely to be key candidate factors involved in chlorophyll synthesis and nitrate accumulation. CONCLUSION: Our results demonstrated that differences in chlorophyll and nitrate content were caused by the combined effects of chloroplast development, photosynthesis, as well as related biological activity. In addition, transcriptome results provide a bioinformatics resource for further functional identification of key pathways and genes responsible for differences in chlorophyll and nitrate content in tobacco plants.

Intraoperative Transfusion of Autologous Blood Protects from Acute Kidney Injury after Pediatric Congenital Heart Surgery.

Background: Acute kidney injury (AKI) is a common complication after pediatric cardiac surgery. And autologous blood transfusion (ABT) is an important predictor of postoperative AKI. Unlike previous studies, which mainly focused on the correlation between ABT and AKI, the current study focuses heavily on the causal relationship between them, thus providing guidance for the treatment of patients during hospitalization to reduce the occurrence of AKI. Methods: A retrospective cohort of 3386 patients extracted from the Pediatric Intensive Care database was used for statistical analysis, multifactorial analysis, and causal inference. Characteristics that were correlated with ABT and AKI were categorized as confounders, instrumental variables, and effect modifiers, and were entered into the DoWhy causal inference model to determine causality. The calculated average treatment effect (ATE) was compared with the results of the multifactorial analysis. Results: The adjusted odds ratio (OR) for ABT volume was obtained by multifactorial analysis as 0.964. The DoWhy model refute test was able to indicate a causal relationship between ABT and AKI. Any ABT reduces AKI about 15.3%-18.8% by different estimation methods. The ATE regarding the amount of ABT was -0.0088, suggesting that every 1 mL/kg of ABT reduced the risk of AKI by 0.88%. Conclusions: Intraoperative transfusion of autologous blood can have a protective effect against postoperative AKI.

Recombinant Photolyase-Thymine Alleviated UVB-Induced Photodamage in Mice by Repairing CPD Photoproducts and Ameliorating Oxidative Stress.

Cyclobutane pyrimidine dimers (CPDs) are the main mutagenic DNA photoproducts caused by ultraviolet B (UVB) radiation and represent the major cause of photoaging and skin carcinogenesis. CPD photolyase can efficiently and rapidly repair CPD products. Therefore, they are candidates for the prevention of photodamage. However, these photolyases are not present in placental mammals. In this study, we produced a recombinant photolyase-thymine (rPHO) from Thermus thermophilus (T. thermophilus). The rPHO displayed CPD photorepair activity. It prevented UVB-induced DNA damage by repairing CPD photoproducts to pyrimidine monomers. Furthermore, it inhibited UVB-induced ROS production, lipid peroxidation, inflammatory responses, and apoptosis. UVB-induced wrinkle formation, epidermal hyperplasia, and collagen degradation in mice skin was significantly inhibited when the photolyase was applied topically to the skin. These results demonstrated that rPHO has promising protective effects against UVB-induced photodamage and may contribute to the development of anti-UVB skin photodamage drugs and cosmetic products.