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Room‐temperature phosphorescence (RTP) materials have attracted significant attention due to their applications in various fields such as information storage and encryption, organic light‐emitting diode (OLED), sensing, lighting and display, biological imaging, and photodynamic therapy. Traditionally, RTP materials can be efficiently developed using inorganic systems with noble metals or rare earth elements. Recently, many efforts have been devoted to the development of RTP materials based on small organic molecules. The strategies to construct RTP materials include hydrogen bonding, heavy atom effect, n–π* transitions, π–π stacking, donor–acceptor effect, and host–guest doping. Herein, we summarize the recent examples of RTP materials based on small organic molecules primarily focusing on their design strategies and properties. Moreover, their promising applications in information encryption, OLED, as well as bio‐imaging and phototherapy are discussed. The challenges and perspectives are given to provide inspiration toward the future development of organic RTP materials. This review summarizes the design strategies to construct room‐temperature phosphorescence (RTP) materials based on small organic molecules and their promising applications in information encryption, organic light‐emitting diode, as well as bio‐imaging and phototherapy. The challenges and perspectives are given to provide inspiration toward the future development of organic RTP materials.

Red yeasts demonstrate considerable potential in industrial and biotechnological applications, particularly in the biosynthesis of carotenoids and lipids, which are valuable secondary metabolites with a wide range of applications. In the oleaginous red yeast Rhodosporidium kratochvilovae YM25235, the acetyl-CoA synthetases RkACS1 and RkACS2 play critical roles in converting acetate into acetyl-CoA, a key precursor for the synthesis of various metabolites, including carotenoids and lipids. This study explores the physiological functions and metabolic regulation of RkACS1 and RkACS2, revealing distinct roles for these isoenzymes in metabolic processes. RkACS1 is essential for utilizing non-fermentable carbon sources such as acetate, ethanol, and glycerol, exhibiting high affinity for acetate and being activated by acetate while inhibited by glucose. Additionally, RkACS1 is involved in carotenoid biosynthesis. In contrast, RkACS2, while not specific to particular carbon sources, is primarily involved in lipid and fatty acid synthesis. It also influences gene expression through histone acetylation in the nucleus. Notably, these two isoenzymes exhibit functional redundancy and mutual regulation. These findings provide valuable insights into the metabolic regulation of acetyl-CoA synthesis, offering a foundation for engineering strategies aimed at optimizing secondary metabolite production in oleaginous red yeasts. Key points • RkACS1 is related to carotenoid biosynthesis and essential for non-fermentable carbon sources • RkACS2 supports lipid and fatty acid biosynthesis and regulates histone acetylation in the nucleus • Functional redundancy and mutual regulation exist between RkACS1 and RkACS2 isoenzymes

Graph neural networks (GNNs) have exhibited remarkable performance in addressing diverse graph learning tasks. However, inevitable missing information in graph networks hinders GNNs from aggregating more abundant feature information, limiting GNNs’ performance. Moreover, missing information further exacerbates the risk of overfitting in GNNs. In this manuscript, we devote to presenting a novel framework, i.e., G raph N eural N etworks via Adaptive Feature P erturbation and High-way L inks (PLGNN), to tackle these challenges. We introduce an efficient high-way links strategy to augment the graph, which enhances the features aggregation of GNNs, thereby improving the performance of PLGNN. Subsequently, an adaptive feature perturbation strategy is proposed to reduce model’s overfitting and also improve robustness of PLGNN. Then, we perform experiments on ten real-world datasets to reveal the superiority of PLGNN, with the corresponding performance being compared with that of state-of-the-art ones. Specifically, the Accuracy improved by an average of 2.6% on five node classification datasets, and an average of 2.1% on five graph classification datasets.

Objective To identify the prognostic indicators of esophageal adenocarcinoma (EAC) for future EAC diagnosis and treatment. Methods The EAC dataset from The Cancer Genome Atlas was screened for differentially expressed microRNAs (miRNAs) and mRNAs associated with EAC. Weighted gene coexpression network analysis was performed to cluster miRNAs or mRNA with similar expression patterns to identify the miRNAs or mRNA that are highly associated with EAC. Prognostic miRNAs for overall survival (OS) were identified using Cox proportional-hazards regression analysis and least absolute shrinkage and selection operator based on survival duration and status. Two types of miRNAs were selected to develop a prognostic signature model for EAC using multiple Cox regression analysis. Furthermore, the signature was validated using internal validation sets 1 and 2. The receiver operating characteristic curve and concordance index were used to evaluate the accuracy of the signature and validation sets. The expression of miR-421, miR-550a-3p, and miR-550a-5p was assessed using quantitative polymerase chain reaction (qPCR). The proliferation, invasion, and migration of EAC cells were assessed using CCK8 and transwell assays. The OS of target mRNAs was assessed using Kaplan–Meier analysis. Functional enrichment analysis of the target mRNAs was performed using Metascape. Results The prognostic signature and validation sets comprising mir-421 and mir-550a-1 had favorable predictive power in OS. Compared with the patients with EAC in the high-expression group, those assigned to the low-expression group displayed increased OS according to survival analysis. Differential and qPCR analysis showed that miR-421, miR-550a-3p, and miR-550a-5p were highly expressed in the EAC tissues and cell lines. Moreover, the downregulation of miR-421 and miR-550a-3p with inhibitor markedly suppressed the proliferation, invasion, and migration in OE33 cells compared with the negative control. A total of 20 target mRNAs of three miRNAs were predicted, among which seven target mRNAs— ASAP3 , BCL2L2 , LMF1 , PPM1L , PTPN21 , SLC18A2, and NR3C2 —had prognostic value; PRKACB , PDCD4 , RPS6KA5 , and BCL2L2 were enriched in the miRNA cancer pathway. Conclusion Prognostic indicators of EAC may be useful in future EAC diagnosis and treatment.

Background: Diabetic nephropathy (DN) is a major cause of end-stage renal disease and proteinuria is one of the most prominent clinical manifestations. The expression of Vitamin D receptor (VDR) in patients with chronic kidney diseases was decreased, while VDR agonists could partially alleviate the proteinuria of DN in animal models. The present study was designed to determine the expression of VDR in renal tissues and its relationship with proteinuria the diabetic model db/db mice. Methods: The regulation effects of VDR on the Wnt signaling pathway were analyzed using RNA interference and VDR agonist paricalcitol. Results: With the increase in age of the db/db mice, the VDR protein and mRNA levels in renal tissues were decreased, proteinuria increased, and the protein and mRNA levels of GSK-3β of and β-catenin increased. Paricalcitol treatment resulted in the up-regulation of VDR and down-regulation of GSK-3β and β-catenin, indicating that VDR had a regulatory effect on the Wnt signaling pathway. Conclusion: VDR activation could reduce proteinuria of DN mice and alleviate high-glucose-induced injury of kidneys and podocytes by regulating the key molecules of Wnt signaling pathway.

Rhodotorula glutinis is an important oleaginous yeast that can synthesize various valuable compounds, including carotenoids, lipids, and exopolysaccharides. The effect of combined heat stress and glucose starvation on carotenoid biosynthesis in R. glutinis was investigated in this study. Carotenoid production in R. glutinis was promoted by heat stress, and this effect was further enhanced when glucose starvation was applied to the strain. The results of multiomics analysis revealed that the effects of heat stress and glucose starvation on promoting carotenoid biosynthesis appeared to be additive, with the combined stress leading to a further increase in reactive oxygen species (ROS) levels and a reduction in enzymatic antioxidant capacity, while carotenoid biosynthesis was prioritized simultaneously. The key responses of R. glutinis to combined stress include the regulation of the cell cycle and energy metabolism, maintenance of membrane integrity, an increase in ROS scavenging capacity, and non-enzymatic antioxidant activity. Additionally, several candidate genes and metabolites associated with the combined stress response were identified. To summarize, we provided new insights into optimizing fermentation processes for increased carotenoid production in Rhodotorula glutinis and established a molecular basis for further genetic engineering to increase carotenoid yield.

Microorganisms adopt diverse mechanisms to adapt to fluctuations of nutrients. Glucose is the preferred carbon and energy source for yeast. Yeast cells have developed many strategies to protect themselves from the negative impact of glucose starvation. Studies have indicated a significant increase of carotenoids in red yeast under glucose starvation. However, their regulatory mechanism is still unclear. In this study, we investigated the regulatory mechanism of carotenoid biosynthesis in Rhodosporidium kratochvilovae YM25235 under glucose starvation. More intracellular reactive oxygen species (ROS) was produced when glucose was exhausted. Enzymatic and non-enzymatic (mainly carotenoids) antioxidant systems in YM25235 were induced to protect cells from ROS-related damage. Transcriptome analysis revealed massive gene expression rearrangement in YM25235 under glucose starvation, leading to alterations in alternative carbon metabolic pathways. Some potential pathways for acetyl-CoA and then carotenoid biosynthesis, including fatty acid β-oxidation, amino acid metabolism, and pyruvate metabolism, were significantly enriched in KEGG analysis. Overexpression of the fatty acyl-CoA oxidase gene (RkACOX2), the first key rate-limiting enzyme of peroxisomal fatty acid β-oxidation, demonstrated that fatty acid β-oxidation could increase the acetyl-CoA and carotenoid concentration in YM25235. These findings contribute to a better understanding of the overall response of red yeast to glucose starvation and the regulatory mechanisms governing carotenoid biosynthesis under glucose starvation.

The performance of chromatographic media affects the efficiency of purification. In this study, based on a T-type microfluidic droplet generation system, agarose microspheres with large pore size and high load were prepared by adjusting the viscosity of a 4% agarose solution to 70 mPa·s at high temperature. Optical microscopy revealed that the self-made agarose microspheres had a good spherical structure with an average particle size of 82.81 μm and a CV value of 0.0576. Subsequently, the stability and mechanical strength of the self-made agarose microspheres were improved by cross-linking and activation with epichlorohydrin. After the cross-linking and activation, the agarose microspheres were grafted with Protein A to make it have specific adsorption capacity for IgG. The adsorption capacity of the self-made agarose microspheres grafted with Protein A for IgG was 87 mg/g. In the complex serum environment, the agarose microspheres grafted with Protein A still maintained good IgG adsorption capacity and selectivity, demonstrating their potential in practical applications. This study demonstrates the great potential of microfluidic technology in the design and preparation of bio-separation media. By precisely controlling the particle size and pore size of the microspheres, the purification efficiency and selectivity can be significantly improved, providing a new solution for the efficient purification of bio-products. Graphical abstract

Hybrid histidine kinases (HHKs) are major sensor proteins for fungi that contribute to stress tolerance. In the present work, we investigated the roles and mechanisms of the HHK HisK2301 in cold-adapted Rhodosporidium kratochvilovae strain YM25235. The HisK2301 deletion strain was constructed by homologous recombination method and arranged for multiple stress tests. We analysed the content of carotenoid using UV–Vis and HPLC. Relative transcript levels of genes phytoene desaturase (RKCrtI) and phytoene synthase and lycopene cyclase (RKCrtYB) were analysed by RT-qPCR. Intracellular reactive oxygen species (ROS) generation was measured using 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA). Our results clearly indicated that YM25235 produces γ-carotene, torulene, β-carotene and torularhodin, with the latter two components strongly related to adapt to cold. HisK2301 is crucial for YM25235 adaptation to different types of stress such as cold, salt, osmotic and oxidative stress. Growth at low temperature clearly induced oxidative stress in YM25235, as more ROS accumulated at cold. During cold stress, HisK2301 is suggested to sense cold-induced ROS signals and then promote carotenoid production partially by RKCrtI and RKCrtYB to scavenge excessive ROS production. Such an inducible protective system may confer YM25235 fast response and better adaptation to cold stress. To conclude, our findings give the first insight into the effect of HisK2301 on carotenoid biosynthesis and cold-induced oxidative stress in fungi under low temperature and suggest the potential use of the cold-adapted HHK HisK2301 in industrial production of carotenoid.

Microorganisms adopt diverse mechanisms to adapt to fluctuations of nutrients. Glucose is the preferred carbon and energy source for yeast. Yeast cells have developed many strategies to protect themselves from the negative impact of glucose starvation. Studies have indicated a significant increase of carotenoids in red yeast under glucose starvation. However, their regulatory mechanism is still unclear. In this study, we investigated the regulatory mechanism of carotenoid biosynthesis in Rhodosporidium kratochvilovae YM25235 under glucose starvation. More intracellular reactive oxygen species (ROS) was produced when glucose was exhausted. Enzymatic and non-enzymatic (mainly carotenoids) antioxidant systems in YM25235 were induced to protect cells from ROS-related damage. Transcriptome analysis revealed massive gene expression rearrangement in YM25235 under glucose starvation, leading to alterations in alternative carbon metabolic pathways. Some potential pathways for acetyl-CoA and then carotenoid biosynthesis, including fatty acid β-oxidation, amino acid metabolism, and pyruvate metabolism, were significantly enriched in KEGG analysis. Overexpression of the fatty acyl-CoA oxidase gene (RkACOX2), the first key rate-limiting enzyme of peroxisomal fatty acid β-oxidation, demonstrated that fatty acid β-oxidation could increase the acetyl-CoA and carotenoid concentration in YM25235. These findings contribute to a better understanding of the overall response of red yeast to glucose starvation and the regulatory mechanisms governing carotenoid biosynthesis under glucose starvation.