Conversion of Propargylic Amines with CO2 Catalyzed by a Highly Stable Copper(I) Iodide Thorium-Based Heterometal-Organic Framework.

The conversion of CO2 to generate high-value-added chemicals has become one of the hot research topics in green synthesis. Thereinto, the cyclization reaction of propargylic amines with CO2 is highly attractive because the resultant oxazolidinones are widely found in pharmaceutical chemistry. Cu(I)-based metal-organic frameworks (MOFs) as catalysts exhibit promising application prospects for CO2 conversion. However, their practical application was greatly limited due to Cu(I) being liable to disproportionation or oxidization. Herein, the solid copper(I) iodide thorium-based porous framework {[Cu5I6Th6(µ3-O)4(µ3-OH)4(H2O)10(L)10]·OH·4DMF·H2O}n (1) (HL = 2-methylpyridine-4-carboxylic acid) constructed by [Th6] clusters and [CuxIy] subunits was successfully prepared and structurally characterized. To our knowledge, this is the first copper(I) iodide-based actinide organic framework. Catalytic investigations indicate that 1 can effectively catalyze the cyclization of propargylic amines with CO2 under ambient conditions, which can be reused at least five times without a remarkable decline of catalytic activity. Importantly, 1 exhibits excellent chemical stability and the oxidation state of Cu(I) in it can remain stable under various conditions. This work can provide a valuable strategy for the synthesis of stable Cu(I)-MOF materials.

Discovery of a novel BTK inhibitor S-016 and identification of a new strategy for the treatment of lymphomas including BTK inhibitor-resistant lymphomas.

Bruton's tyrosine kinase (BTK) has emerged as a therapeutic target for B-cell malignancies, which is substantiated by the efficacy of various irreversible or reversible BTK inhibitors. However, on-target BTK mutations facilitating evasion from BTK inhibition lead to resistance that limits the therapeutic efficacy of BTK inhibitors. In this study we employed structure-based drug design strategies based on established BTK inhibitors and yielded a series of BTK targeting compounds. Among them, compound S-016 bearing a unique tricyclic structure exhibited potent BTK kinase inhibitory activity with an IC50 value of 0.5 nM, comparable to a commercially available BTK inhibitor ibrutinib (IC50 = 0.4 nM). S-016, as a novel irreversible BTK inhibitor, displayed superior kinase selectivity compared to ibrutinib and significant therapeutic effects against B-cell lymphoma both in vitro and in vivo. Furthermore, we generated BTK inhibitor-resistant lymphoma cells harboring BTK C481F or A428D to explore strategies for overcoming resistance. Co-culture of these DLBCL cells with M0 macrophages led to the polarization of M0 macrophages toward the M2 phenotype, a process known to support tumor progression. Intriguingly, we demonstrated that SYHA1813, a compound targeting both VEGFR and CSF1R, effectively reshaped the tumor microenvironment (TME) and significantly overcame the acquired resistance to BTK inhibitors in both BTK-mutated and wild-type BTK DLBCL models by inhibiting angiogenesis and modulating macrophage polarization. Overall, this study not only promotes the development of new BTK inhibitors but also offers innovative treatment strategies for B-cell lymphomas, including those with BTK mutations.

Association between central serous chorioretinopathy and Helicobacter pylori infection: a systematic review and Meta-analysis.

AIM: To investigate the association between central serous chorioretinopathy (CSC) and Helicobacter pylori (Hp) by summarizing all available evidence. METHODS: The Scopus, Embase, EBSCO, PubMed, Web of Science, and Cochrane Library databases for all relevant studies published from inception to October 2022 were searched, and manually searched for relevant reference lists as a supplement. Studies investigating the association between CSC and Hp infection were included. Finally, 8 case-control studies were included in the Meta-analysis after study selection. RESULTS: The results showed no significant correlation between Hp infection and CSC [odds ratio (OR) 1.89, 95% confidential interval (CI) 0.58-6.15, I 2=96%, P=0.29]. After subgroup analysis based on the degree of development of the study (developing/developed countries), it was found that the results of the two subgroups were the same as the whole, and no significant difference between the two subgroups existed. Meta-regression showed that the effect of sample size on heterogeneity among studies was more prominent (P<0.01, adjusted R 2=89.72%), which can explain 89.72% of the sources of heterogeneity. CONCLUSION: This Meta-analysis reveals no significant correlation between Hp infection and CSC, which still warrants further well-designed extensive sample studies to reach a more reliable conclusion and promote a better understanding of the treatment of CSC.

Targeted isolation, identification, and antioxidant evaluation of aromatic polyketides from a plant-derived fungus Ophiobolus cirsii LZU-1509.

There are >350 species of the Ophiobolus genus, which is not yet very well-known and lacks research reports on secondary metabolites. Three new 3,4-benzofuran polyketides 1-3, a new 3,4-benzofuran polyketide racemate 4, two new pairs of polyketide enantiomers (±)-5 and (±)-7, two new acetophenone derivatives 6 and 8, and three novel 1,4-dioxane aromatic polyketides 9-11, were isolated from a fungus Ophiobolus cirsii LZU-1509 derived from an important medicinal and economic crop Anaphalis lactea. The isolation was guided by LC-MS/MS-based GNPS molecular networking analysis. The planar structures and relative configurations were mainly elucidated by NMR and HR-ESI-MS data. Their absolute configurations were determined by using X-ray diffraction analysis and via comparing computational and experimental ECD, NMR, and specific optical rotation data. 9 possesses an unreported 5/6/6/6/5 five-ring framework with a 1,4-dioxane, and 10 and 11 feature unprecedented 6/6/6/5 and 6/6/5/6 four-ring frames containing a 1,4-dioxane. The biosynthetic pathways of 9-11 were proposed. 1-11 were nontoxic in HT-1080 and HepG2 tumor cells at a concentration of 20 µM, whereas 3 and 5 exerted higher antioxidant properties in the hydrogen peroxide-stimulated model in the neuron-like PC12 cells. They could be potential antioxidant agents for neuroprotection.

The impact of different states of type 2 diabetes when stratified by baseline HbA1c on the periodontal outcomes of non-surgical periodontal treatment: A systematic review and network meta-analysis.

BACKGROUND: Type 2 diabetes mellitus (T2DM) has been considered by many studies to have a bidirectional relationship with periodontitis. This systematic review and network meta-analysis aimed to investigate the impact of different states of T2DM when stratified by baseline HbA1c on the clinical outcomes of non-surgical periodontal treatment (NSPT). METHODS: This study followed the Preferred Reporting Items for Meta-Analyses (PRISMA) guidelines and involved an electronic literature search (from inception to the 2nd of January 2023). The study included at least two groups of patients: chronic periodontitis only (No-DM) or periodontitis and well-controlled/poorly controlled type 2 diabetes mellitus (WC/PC-T2DM). Clinical outcomes included probing depth (PD) reduction, bleeding on probing reduction, and clinical attachment level (CAL) gain. Direct and indirect comparisons between groups were assessed by network meta-analysis, thus allowing us to establish a treatment ranking. RESULTS: Ten prospective cohort studies (11 data sets) were included for qualitative analysis and network meta-analysis. The data included in this study had high consistency; in addition, a funnel plot and Egger's test showed that the articles had low publication bias. Network meta-analysis showed that the effect of NSPT in the No-DM group was significantly better than the WC-T2DM group [weighted mean difference (WMD) = 0.09, 95% confidence interval (CI) (0.01, 0.18)] and the PC-T2DM group [WMD = 0.09, 95% CI (0.01, 0.18)] in terms of CAL gain and better than the PC-T2DM group [WMD = 0.15, 95% CI (0.02, 0.28)] in terms of PD reduction. According to the surface under the cumulative ranking value, the No-DM group had the highest probability of achieving the best outcome following NSPT. CONCLUSIONS: Collectively, our analyses show that T2DM exerts significant effects on the outcomes of NSPT.

Glaucoma drainage device implantation and cyclophotocoagulation in the management of refractory glaucoma after Descemet-stripping automated endothelial keratoplasty.

AIM: To compare the surgical outcomes of glaucoma drainage device implantation (GDI) and trans-scleral neodymium:YAG cyclophotocoagulation (CPC) in the management of refractory glaucoma after Descemet-stripping automated endothelial keratoplasty (DSAEK). METHODS: This retrospective study on observational case series enrolled 29 patients who underwent DSAEK and posterior anti-glaucoma surgery (15 with GDI and 14 with CPC). The main outcome measures were intraocular pressure (IOP), glaucoma surgery success rate (defined as IOP of 6-21 mm Hg without additional anti-glaucoma operation), number of glaucoma medications, endothelial graft status, and best-corrected visual acuity (BCVA). RESULTS: The mean follow-up time was 34.1 and 21.0mo for DSAEK or glaucoma surgeries, both for the GDI and CPC groups. Both groups showed significant IOP reduction after glaucoma surgery. The GDI group presented a significantly higher success rate in IOP control than the CPC group (60% vs 21.4%, P=0.03). Both procedures significantly decreased the number of glaucoma medications (P=0.03). Forty percent and 57% of cases in the GDI and the CPC group, respectively, experienced endothelial graft failure during follow-up (P=0.36). Significantly worse BCVA after surgery was observed in the CPC group but not in the GDI group. CONCLUSION: Both GDI and CPC significantly decrease IOP in eyes with glaucoma after DSAEK. GDI is preferable to CPC in refractory glaucoma cases after DSAEK, as it manifests a significantly higher success rate for IOP control, similar endothelial graft failure rate, and relatively preserves BCVA than CPC.

Impacts of Norway's extended free choice reform on waiting times and hospital visits.

Norway's extended free choice (EFC) reform extends the patient's choice of publicly funded hospitals for treatment to authorized private institutions (EFC providers). We study the effects of the reform on waiting times, number of visits, and patients' Charlson Comorbidity Index scores in public hospitals. We use a difference-in-differences model to compare changes over time for public hospitals with and without EFC providers in the catchment area. Focusing on five prevalent somatic services, we find that the EFC reform did not exert pressure on public hospitals to stimulate shorter waiting times and more visits. Moreover, we do not find that the sum of public and private visits increased. When we compare patient comorbidity between public hospitals and EFC providers, we find that for non-invasive diagnostic services, patient comorbidity is lower in EFC providers. For surgical services, we detect no difference in patient comorbidities between public and EFC providers.

Integrated Bioinformatics Analysis Reveals Diagnostic Biomarkers and Immune Cell Infiltration Characteristics of Solar Lentigines.

Background: Solar lentigines (SLs), serving as a prevalent characteristic of skin photoaging, present as cutaneous aberrant pigmentation. However, the underlying pathogenesis remains unclear and there is a dearth of reliable diagnostic biomarkers. Objective: The aim of this study was to identify diagnostic biomarkers for SLs and reveal its immunological features. Methods: In this study, gene expression profiling datasets (GSE192564 and GSE192565) of SLs were obtained from the GEO database. The GSE192564 was used as the training group for screening of differentially expressed genes (DEGs) and subsequent depth analysis. Gene set enrichment analysis (GSEA) was employed to explore the biological states associated with SLs. The weighted gene co-expression network analysis (WGCNA) was employed to identify the significant modules and hub genes. Then, the feature genes were further screened by the overlapping of hub genes and up-regulated differential genes. Subsequently, an artificial neural network was constructed for identifying SLs samples. The GSE192565 was used as the test group for validation of feature genes expression level and the model's classification performance. Furthermore, we conducted immune cell infiltration analysis to reveal the immune infiltration landscape of SLs. Results: The 9 feature genes were identified as diagnostic biomarkers for SLs in this study. And an artificial neural network based on diagnostic biomarkers was successfully constructed for identification of SLs. GSEA highlighted potential role of immune system in pathogenesis of SLs. SLs samples had a higher proportion of several immune cells, including activated CD8 T cell, dendritic cell, myeloid-derived suppressor cell and so on. And diagnostic biomarkers exhibited a strong relationship with the infiltration of most immune cells. Conclusion: Our study identified diagnostic biomarkers for SLs and explored its immunological features, enhancing the comprehension of its pathogenesis.

Single-Cell Plasmonic Immunosandwich Assay Reveals the Modulation of Nucleocytoplasmic Localization Fluctuation of ABL1 on Cell Migration.

Cell migration is an essential process of cancer metastasis. The spatiotemporal dynamics of signaling molecules influences cellular phenotypic outcomes. It has been increasingly documented that the Abelson (ABL) family kinases play critical roles in solid tumors. However, ABL1's shuttling dynamics in cell migration still remains unexplored. This is mainly because tools permitting the investigation of translocation dynamics of proteins in single living cells are lacking. Herein, to bridge this gap, we developed a unique multifunctional integrated single-cell analysis method that enables long-term observation of cell migration behavior and monitoring of signaling proteins and complexes at the subcellular level. We found that the shuttling of ABL1's to the cytoplasm results in a higher migration speed, while its trafficking back to the nucleus leads to a lower one. Furthermore, our results indicated that fluctuant protein-protein interactions between 14-3-3 and ABL1 modulate ABL1's nucleocytoplasmic fluctuation and eventually affect the cell speed. Importantly, based on these new insights, we demonstrated that disturbing ABL1's nuclear export traffic and 14-3-3-ABL1 complexes formation can effectively suppress cell migration. Thus, our method opens up a new possibility for simultaneous tracking of internal molecular mechanisms and cell behavior, providing a promising tool for the in-depth study of cancer.

Insights into In Vivo Environmental Effects on Quantitative Biochemistry in Single Cells.

Biomacromolecules exist and function in a crowded and spatially confined intracellular milieu. Single-cell analysis has been an essential tool for deciphering the molecular mechanisms of cell biology and cellular heterogeneity. However, a sound understanding of in vivo environmental effects on single-cell quantification has not been well established. In this study, via cell mimicking with giant unilamellar vesicles and single-cell analysis by an approach called plasmonic immunosandwich assay (PISA) that we developed previously, we investigated the effects of two in vivo environmental factors, i.e., molecular crowding and spatial confinement, on quantitative biochemistry in the cytoplasm of single cells. We find that molecular crowding greatly affects the biomolecular interactions and immunorecognition-based detection while the effect of spatial confinement in cell-sized space is negligible. Without considering the effect of molecular crowding, the results by PISA were found to be apparently under-quantitated, being only 29.5-50.0% of those by the calibration curve considering the effect of molecular crowding. We further demonstrated that the use of a calibration curve established with standard solutions containing 20% (wt) polyethylene glycol 6000 can well offset the effect of intracellular crowding and thereby provide a simple but accurate calibration for the PISA measurement. Thus, this study not only sheds light on how intracellular environmental factors influence biomolecular interactions and immunorecognition-based single-cell quantification but also provides a simple but effective strategy to make the single-cell analysis more accurate.

Transcriptome and metabolome analyses revealed the response mechanism of pepper roots to Phytophthora capsici infection.

BACKGROUND: Phytophthora root rot caused by the oomycete Phytophthora capsici is the most devastating disease in pepper production worldwide, and current management strategies have not been effective in preventing this disease. Therefore, the use of resistant varieties was regarded as an important part of disease management of P. capsici. However, our knowledge of the molecular mechanisms underlying the defense response of pepper roots to P. capsici infection is limited. METHODS: A comprehensive transcriptome and metabolome approaches were used to dissect the molecular response of pepper to P. capsici infection in the resistant genotype A204 and the susceptible genotype A198 at 0, 24 and 48 hours post-inoculation (hpi). RESULTS: More genes and metabolites were induced at 24 hpi in A204 than A198, suggesting the prompt activation of defense responses in the resistant genotype, which can attribute two proteases, subtilisin-like protease and xylem cysteine proteinase 1, involved in pathogen recognition and signal transduction in A204. Further analysis indicated that the resistant genotype responded to P. capsici with fine regulation by the Ca2+- and salicylic acid-mediated signaling pathways, and then activation of downstream defense responses, including cell wall reinforcement and defense-related genes expression and metabolites accumulation. Among them, differentially expressed genes and differentially accumulated metabolites involved in the flavonoid biosynthesis pathways were uniquely activated in the resistant genotype A204 at 24 hpi, indicating a significant role of the flavonoid biosynthesis pathways in pepper resistance to P. capsici. CONCLUSION: The candidate transcripts may provide genetic resources that may be useful in the improvement of Phytophthora root rot-resistant characters of pepper. In addition, the model proposed in this study provides new insight into the defense response against P. capsici in pepper, and enhance our current understanding of the interaction of pepper-P. capsici.

Three-dimensional in vivo evaluation of the cornea in patients with unilateral posterior interstitial keratitis.

Purpose: The purpose of this study was to investigate the in vivo morphologic features of the cornea in patients with unilateral posterior interstitial keratitis. Methods: Seven eyes of 7 patients with unilateral posterior interstitial keratitis were examined by slit-lamp biomicroscopy, anterior segment optical coherence tomography (AS-OCT), and in vivo confocal microscopy (IVCM). The imaging features of the cornea were evaluated and analyzed. Results: By slit-lamp examination, the posterior corneal stromal opacities were observed in all 7 eyes, and deep neovascularization in 4 eyes. The posterior stromal opacities showed higher reflectivity with an intact overlying epithelium by AS-OCT and did not invade the Bowman's layer in all cases. IVCM revealed highly reflective dispersed microdots, needle-shaped bodies, and increased reflectivity of keratocytes in the lesion site in all patients. Active Langerhans cells and an attenuated subbasal nerve plexus were observed in 5 eyes. After treatment, the active Langerhans cells disappeared; however, highly reflective microdots and needle-shaped bodies remained. Conclusion: The three-dimensional evaluation of slit-lamp biomicroscopy, AS-OCT, and IVCM may help in the early diagnosis of patients with posterior interstitial keratitis.

Genome-wide identification and analysis of the evolution and expression pattern of the SBP gene family in two Chimonanthus species.

BACKGROUND: Chimonanthus praecox and Chimonanthus salicifolius are closely related species that diverged approximately six million years ago. While both C. praecox and C. salicifolius could withstand brief periods of low temperatures of - 15 °C. Their flowering times are different, C. praecox blooms in early spring, whereas C. salicifolius blooms in autumn. The SBP-box (SQUAMOSA promoter-binding protein) is a plant-specific gene family that plays a crucial vital role in regulating plant flowering. Although extensively studied in various plants, the SBP gene family remains uncharacterized in Calycanthaceae. METHODS AND RESULTS: We conducted genome-wide identification of SBP genes in both C. praecox and C. salicifolius and comprehensively characterized the chromosomal localization, gene structure, conserved motifs, and domains of the identified SBP genes. In total, 15 and 18 SBP genes were identified in C. praecox and C. salicifolius, respectively. According to phylogenetic analysis, the SBP genes from Arabidopsis, C. praecox, and C. salicifolius were clustered into eight groups. Analysis of the gene structure and conserved protein motifs showed that SBP proteins of the same subfamily have similar motif structures. The expression patterns of SBP genes were analyzed using transcriptome data. The results revealed that more than half of the genes exhibited lower expression levels in leaves than in flowers, suggesting their potential involvement in the flower development process and may be linked to the winter and autumn flowering of C. praecox and C. salicifolius. CONCLUSION: Thirty-three SBPs were identified in C. praecox and C. salicifolius. The evolutionary characteristics and expression patterns were examined in this study. These results provide valuable information to elucidate the evolutionary relationships of the SBP family and help determine the functional characteristics of the SBP genes in subsequent studies.

Induced skin aging by blue-light irradiation in human skin fibroblasts via TGF-ß, JNK and EGFR pathways.

BACKGROUND: Studies indicate that blue light (BL) irradiation can damage human skins, but the impact of BL irradiation on skin aging is unknown. OBJECTIVES: This study aimed to give an insight to phenotypic characteristics and molecular mechanism of blue light-induced skin aging, and thus provide a theoretical basis for the precise protection of photodermatosis. METHODS: The effect of BL on skin photoaging in mice was evaluated by non-invasive measurement equipment and histopathology analysis. The effect of BL irradiation on the proliferation of HFF-1 cells was detected by the Real-Time Cell Analyzer. The expression and protein levels of genes associated with skin aging were examined. RESULTS: Our studies indicated photoaging caused by BL irradiation, including collagen disorder and increased MMP1. BL irradiation also inhibited cell proliferation and collagen expression in human skin fibroblasts by inhibiting TGF-ß signaling pathway, based on in vitro experiments. Importantly, BL irradiation promoted the degradation of collagen by increasing MMP1 activated by the JNK/c-Jun and EGFR pathways. Moreover, ROS levels were significantly increased after BL irradiation in human skin fibroblasts. Yet, the transcriptional change in human skin fibroblasts caused by BL irradiation was unable to be completely restored by ROS scavenger. CONCLUSION: BL irradiation down-regulated expression of type I collagen genes and up-regulated MMP1 expression to inhibit the proliferation of human skin fibroblasts. Multiple key pathways including TGF-ß, JNK, and EGFR signaling were involved in BL-induced skin aging. Our results provide theoretical bases for the protection of photoaging caused by BL irradiation.

Genome-wide identification and analysis of MIKC-type MADS-box genes expression in Chimonanthus salicifolius.

BACKGROUND: MIKC type MADS-box transcription factors are one of the largest gene families and play a pivotal role in flowering time and flower development. Chimonanthus salicifolius belongs to the family Calycanthaceae and has a unique flowering time and flowering morphology compared to other Chimonanthus species, but the research on MIKC type MADS-box gene family of C. salicifolius has not been reported. OBJECTIVE: Identification, comprehensive bioinformatic analysis, the expression pattern of MIKC-type MADS-box gene family from different tissues of C. salicifolius. METHODS: Genome-wide investigation and expression pattern under different tissues of the MIKC-type MADS-box gene family in C. salicifolius, and their phylogenetic relationships, evolutionary characteristics, gene structure, motif distribution, promoter cis-acting element were performed. RESULTS: A total of 29 MIKC-type MADS-box genes were identified from the whole genome sequencing. Interspecies synteny analysis revealed more significant collinearity between C. salicifolius and the magnoliids species compared to eudicots and monocots. MIKC-type MADS-box genes from the same subfamily share similar distribution patterns, gene structure, and expression patterns. Compared with Arabidopsis thaliana, Nymphaea colorata, and Chimonanthus praecox, the FLC genes were absent in C. salicifolius, while the AGL6 subfamily was expanded in C. salicifolius. The selectively expanded promoter (AGL6) and lack of repressor (FLC) genes may explain the earlier flowering in C. salicifolius. The loss of the AP3 homologous gene in C. salicifolius is probably the primary cause of the morphological distinction between C. salicifolius and C. praecox. The csAGL6a gene is specifically expressed in the flowering process and indicates the potential function of promoting flowering. CONCLUSION: This study offers a genome-wide identification and expression profiling of the MIKC-types MADS-box genes in the C. salicifolius, and establishes the foundation for screening flowering development genes and understanding the potential function of the MIKC-types MADS-box genes in the C. salicifolius.

Artificial intelligence - based ultrasound elastography for disease evaluation - a narrative review.

Ultrasound elastography (USE) provides complementary information of tissue stiffness and elasticity to conventional ultrasound imaging. It is noninvasive and free of radiation, and has become a valuable tool to improve diagnostic performance with conventional ultrasound imaging. However, the diagnostic accuracy will be reduced due to high operator-dependence and intra- and inter-observer variability in visual observations of radiologists. Artificial intelligence (AI) has great potential to perform automatic medical image analysis tasks to provide a more objective, accurate and intelligent diagnosis. More recently, the enhanced diagnostic performance of AI applied to USE have been demonstrated for various disease evaluations. This review provides an overview of the basic concepts of USE and AI techniques for clinical radiologists and then introduces the applications of AI in USE imaging that focus on the following anatomical sites: liver, breast, thyroid and other organs for lesion detection and segmentation, machine learning (ML) - assisted classification and prognosis prediction. In addition, the existing challenges and future trends of AI in USE are also discussed.

Boosting the epoxidation of squalene to produce triterpenoids in Saccharomyces cerevisiae.

BACKGROUND: Polycyclic triterpenoids (PTs) are common in plants, and have attracted considerable interest due to their remarkable biological activities. Currently, engineering the ergosterol synthesis pathway in Saccharomyces cerevisiae is a safe and cost-competitive way to produce triterpenoids. However, the strict regulation of ERG1 involved in the epoxidation of squalene limits the triterpenoid production. RESULTS: In this study, we found that the decrease in ERG7 protein level could dramatically boost the epoxidation of squalene by improving the protein stability of ERG1. We next explored the potential factors that affected the degradation process of ERG1 and confirmed that ERG7 was involved in the degradation process of ERG1. Subsequently, expression of four different triterpene cyclases utilizing either 2,3-oxidosqualene or 2,3:22,23-dioxidosqualene as the substrate in ERG7-degraded strains showed that the degradation of ERG7 to prompt the epoxidation of squalene could significantly increase triterpenoid production. To better display the potential of the strategy, we increased the supply of 2,3-oxidosqualene, optimized flux distribution between ergosterol synthesis pathway and ß-amyrin synthesis pathway, and modified the GAL-regulation system to separate the growth stage from the production stage. The best-performing strain ultimately produced 4216.6 ± 68.4 mg/L of ß-amyrin in a two-stage fed-fermentation (a 47-fold improvement over the initial strain). CONCLUSIONS: This study showed that deregulation of the native restriction in ergosterol pathway was an effective strategy to increase triterpenoid production in yeast, which provided a new insight into triterpenoids biosynthesis.

m6 A promotes planarian regeneration.

Regeneration is the regrowth of damaged tissues or organs, a vital process in response to damages from primitive organisms to higher mammals. Planarian possesses active whole-body regenerative capability owing to its vast reservoir of adult stem cells, neoblasts, providing an ideal model to delineate the underlying mechanisms for regeneration. RNA N6 -methyladenosine (m6 A) modification participates in many biological processes, including stem cell self-renewal and differentiation, in particular the regeneration of haematopoietic stem cells and axons. However, how m6 A controls regeneration at the whole-organism level remains largely unknown. Here, we demonstrate that the depletion of m6 A methyltransferase regulatory subunit wtap abolishes planarian regeneration, potentially through regulating genes related to cell-cell communication and cell cycle. Single-cell RNA-seq (scRNA-seq) analysis unveils that the wtap knockdown induces a unique type of neural progenitor-like cells (NP-like cells), characterized by specific expression of the cell-cell communication ligand grn. Intriguingly, the depletion of m6 A-modified transcripts grn, cdk9 or cdk7 partially rescues the defective regeneration of planarian caused by wtap knockdown. Overall, our study reveals an indispensable role of m6 A modification in regulating whole-organism regeneration.

The contribution of inner electron excitation to the electronic stopping power of palladium for protons.

The electronic stopping power of palladium (Pd) for protons is investigated based on time-dependent density functional theory combined with Ehrenfest molecular dynamics simulations. The electronic stopping power of Pd with explicitly considering inner electrons for protons is calculated and the excitation mechanism for the inner electrons of Pd is revealed. The velocity proportionality of the low-energy stopping power of Pd is reproduced. Our study verified that the inner electron excitation contributes significantly to the electronic stopping power of Pd in the high energy range, which is strongly dependent on the impact parameter. The electronic stopping power obtained from the off-channeling geometry is in quantitative agreement with the experimental data in a wide velocity range, and the discrepancy around the stopping maximum is further reduced by considering the relativistic correction on the binding energy of inner electrons. The velocity dependence of the mean steady-state charge of protons is quantified, and the results showed that the participation of 4p-electrons reduces the mean steady-state charge of protons, and consequently decreases the electronic stopping power of Pd in the low energy range.