Photouranium-Catalyzed C–F Activation Hydroxylation via Water Splitting

The C–F bond is the strongest covalent single bond (126 kcal/mol) in carbon-centered bonds, in which the highest electronegativity of fluorine (χ = 4) gives rise to the shortest bond length (1.38 Å) and the smallest van der Waals radius (rw = 1.47 Å), resulting in enormous challenges for activation and transformation. Herein, C–F conversion was realized via photouranium-catalyzed hydroxylation of unactivated aryl fluorides using water as a hydroxyl source to deliver multifunctional phenols under ambient conditions. The activation featured cascade sequences of single electron transfer (SET)/hydrogen atom transfer (HAT)/oxygen atom transfer (OAT), highly integrated from the excited uranyl cation. The *UO22+ prompted water splitting under mild photoexcitation, caging the active oxygen in a peroxo-bridged manner for the critical OAT process and releasing hydrogen via the HAT process

Datasheet1_Greater alteration of gut microbiota occurs in childhood obesity than in adulthood obesity.docx

The children's gut microbiota, associated with the development of obesity, is in maturation. The impact of obesity on the gut microbiota in childhood could have a more significant effect than on adulthood and eventually be lifelong lasting, but it has been rarely studied. Aimed to discover the difference in gut microbiota between children and adults with obesity, we collected published amplicon sequencing data from National Center for Biotechnology Information (NCBI) and re-analyzed them using a uniform bioinformatic pipeline, as well as predicted the obesity using gut microbiota based on the random forest model. Summarizing common points among these cohorts, we found that the gut microbiota had a significant difference between children with and without obesity, but this difference was not observed in adult cohorts. Based on the random forest model, it was more challenging to predict childhood obesity using gut microbiota than adulthood obesity. Our results suggest that gut microbiota in childhood is more easily affected than in adulthood. Early intervention for childhood obesity is essential to improve children's health and lifelong gut microbiota-related health.</p

Table1_Greater alteration of gut microbiota occurs in childhood obesity than in adulthood obesity.xlsx

The children's gut microbiota, associated with the development of obesity, is in maturation. The impact of obesity on the gut microbiota in childhood could have a more significant effect than on adulthood and eventually be lifelong lasting, but it has been rarely studied. Aimed to discover the difference in gut microbiota between children and adults with obesity, we collected published amplicon sequencing data from National Center for Biotechnology Information (NCBI) and re-analyzed them using a uniform bioinformatic pipeline, as well as predicted the obesity using gut microbiota based on the random forest model. Summarizing common points among these cohorts, we found that the gut microbiota had a significant difference between children with and without obesity, but this difference was not observed in adult cohorts. Based on the random forest model, it was more challenging to predict childhood obesity using gut microbiota than adulthood obesity. Our results suggest that gut microbiota in childhood is more easily affected than in adulthood. Early intervention for childhood obesity is essential to improve children's health and lifelong gut microbiota-related health.</p

Regulating Photosensitizer Metabolism with DNAzyme-Loaded Nanoparticles for Amplified Mitochondria-Targeting Photodynamic Immunotherapy

Mitochondria-specific photosensitizer accumulation is highly recommended for photodynamic therapy and mitochondrial DNA (mtDNA) oxidative damage-based innate immunotherapy but remains challenging. 5-Aminolevulinic acid (ALA), precursor of photosensitizer protoporphyrin IX (PpIX), can induce the exclusive biosynthesis of PpIX in mitochondria. Nevertheless, its photodynamic effect is limited by the intracellular biotransformation of ALA in tumors. Here, we report a photosensitizer metabolism-regulating strategy using ALA/DNAzyme-co-loaded nanoparticles (ALA&Dz@ZIF-PEG) for mitochondria-targeting photodynamic immunotherapy. The zeolitic imidazolate framework (ZIF-8) nanoparticles can be disassembled and release large amounts of zinc ions (Zn2+) within tumor cells. Notably, Zn2+ can relieve tumor hypoxia for promoting the conversion of ALA to PpIX. Moreover, Zn2+ acts as a cofactor of rationally designed DNAzyme for silencing excessive ferrochelatase (FECH; which catalyzes PpIX into photoinactive Heme), cooperatively promoting the exclusive accumulation of PpIX in mitochondria via the “open source and reduced expenditure” manner. Subsequently, the photodynamic effects derived from PpIX lead to the damage and release of mtDNA and activate the innate immune response. In addition, the released Zn2+ further enhances the mtDNA/cGAS-STING pathway mediated innate immunity. The ALA&Dz@ZIF-PEG system induced 3 times more PpIX accumulation than ALA-loaded liposome, significantly enhancing tumor regression in xenograft tumor models

Table_1_Growth Pattern in Chinese Children With 5α-Reductase Type 2 Deficiency: A Retrospective Multicenter Study.docx

Background5α-reductase type 2 deficiency (5αRD) is an autosomal recessive hereditary disease of the group of 46, XY disorders of sex development (DSD).ObjectiveTo study the growth pattern in Chinese pediatric patients with 5αRD.SubjectsData were obtained from 141 patients with 5αRD (age: 0–16 years old) who visited eight pediatric endocrine centers from January 2010 to December 2017.MethodsIn this retrospective cohort study, height, weight, and other relevant data were collected from the multicenter hospital registration database. Baseline luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T), and dihydrotestosterone (DHT) after human chorionic gonadotropin (HCG) stimulation test were measured by enzyme enhanced chemiluminescence assay. Bone age (BA) was assessed using the Greulich-Pyle (G-P) atlas. Growth curve was constructed based on λ-median-coefficient of variation method (LMS).ResultsThe height standard deviation scores (HtSDS) and weight standard deviation scores (WtSDS) in 5αRD children were in the normal range as compared to normal boys. Significantly higher HtSDS was observed in patients with 5αRD who were ConclusionChildren with 5αRD had a special growth pattern that was affected by high levels of T, while DHT played a very small role in it. Their growth accelerated at age <1 year, followed by slowing growth and fluctuating height near normal median boys’ height. The BA was delayed in 5αRD children. Androgen treatment, which may be considered anyway for male 5αRD patients with a micropenis, may also be beneficial for growth.</p

Data_Sheet_1_Identification and Characterization of Genes Involved in Benzylisoquinoline Alkaloid Biosynthesis in Coptis Species.DOC

The dried rhizomes of Coptis chinensis have been extensively used in heat clearing, dampness drying, fire draining, and detoxification by virtue of their major bioactive components, benzylisoquinoline alkaloids (BIAs). However, C. teeta and C. chinensis are occasionally interchanged, and current understanding of the molecular basis of BIA biosynthesis in these two species is limited. Here, berberine, coptisine, jatrorrhizine, and palmatine were detected in two species, and showed the highest contents in the roots, while epiberberine were found only in C. chinensis. Comprehensive transcriptome analysis of the roots and leaves of C. teeta and C. chinensis, respectively, identified 53 and 52 unigenes encoding enzymes potentially involved in BIA biosynthesis. By integrating probable biosynthetic pathways for BIAs, the jatrorrhizine biosynthesis ill-informed previously was further characterized. Two genes encoding norcoclaurine/norlaudanosoline 6-O-methyltransferases (Cc6OMT1 and Cc6OMT2) and one gene encoding norcoclaurine-7OMT (Ct7OMT) catalyzed enzymatically O-methylate (S)-norcoclaurine at C6 that yield (S)-coclaurine, along with a smaller amount of O-methylation occurred at C7, thereby forming its isomer (isococlaurine). In addition, scoulerine 9-OMT (CtSOMT) was determined to show strict substrate specificity, targeting (S)-scoulerine to yield (S)-tetrahydrocolumbamine. Taken together, the integration of the transcriptome and enzyme activity assays further provides new insight into molecular mechanisms underlying BIA biosynthesis in plants and identifies candidate genes for the study of synthetic biology in microorganisms.</p

Additional file 1 of Copper-based metal–organic framework impedes triple-negative breast cancer metastasis via local estrogen deprivation and platelets blockade

Additional file 1: Fig. S1 FTIR spectra of Pt, Arg and PA. Fig. S2 (a) Transmission electron micrographs (TEM) of Cu-GA and (b) CPA nanoparticles. Fig. S3 XPS spectra of Cu-GA. Fig. S4 Size (a) and zeta potential (b) of IGBN with different dosage of DSPE-PEG2000 (n = 3). (c) The long-term stability of IGBN in FBS at 4℃ during 7 days measured by dynamic light scattering (n = 3). Fig. S5 (a) Cumulative Cu2+ and (b) PA release from IGBN with different pH values (n = 3). Fig. S6 (a) NO producing ability of PA in the present or absent of GSH (n = 3). (b) PA and H2O2 concentration dependent NO release in the present of 10 mM GSH (n = 3). Fig. S7 (a) The cell viability of 4T1 cells with exposed to E2 and (b) Pt at different concentrations. Data are presented as the mean ± SD (n = 6). Fig. S8 (a) Qualitative Western blot data of Capn4 and MMP-2 in 4T1 cells after different concentrations of E2 treated for 24 h. (b) Corresponding quantification of Capn-4 and MMP-2 calculated by Image J (n = 3). Fig. S9 (a) The corresponding mean fluorescence intensity of H2O2 and (b) NO in 4T1 cells with different treatments (n = 3). Fig S10. Representative morphology of 4T1 tumor cells with different treatments. Fig. S11 The corresponding gray analysis of E-cadherin, N-cadherin, and Vimentin by ImageJ (n = 3). Fig. S12 Cell viability of 4T1 cells after treated with CD, CPD, IGBN, respectively (n = 6). Fig. S13 (a) The fluorescent imaging of 4T1 tumor-bearing mice were administered a single intravenous injection of free IR783 (upper panel) or CIR783D (lower panel) at 1, 3, 6, 9, 12, 24, and 48 h post-injection. White circle: tumor site. (b) Ex vivo images of the tumor and major organs after injection for 48 h. Fig. S14 Corresponding mean fluorescence intensity analysis of TUNEL staining in tumors on day 14 after treatments (n = 5). Fig. S15 Changes in body weights of 4T1 tumor-bearing mice treated with Saline, CD, PA, CPD and IGBN (n = 5). Fig. S16 Major organs (heart, liver, spleen, and kidney) harvested from the mice after the last treatment were subjected to H&E staining pathological analysis. Fig. S17 Blood routine examination and blood biochemistry analysis

Data_Sheet_2_Identification and Characterization of Genes Involved in Benzylisoquinoline Alkaloid Biosynthesis in Coptis Species.XLS

<p>The dried rhizomes of Coptis chinensis have been extensively used in heat clearing, dampness drying, fire draining, and detoxification by virtue of their major bioactive components, benzylisoquinoline alkaloids (BIAs). However, C. teeta and C. chinensis are occasionally interchanged, and current understanding of the molecular basis of BIA biosynthesis in these two species is limited. Here, berberine, coptisine, jatrorrhizine, and palmatine were detected in two species, and showed the highest contents in the roots, while epiberberine were found only in C. chinensis. Comprehensive transcriptome analysis of the roots and leaves of C. teeta and C. chinensis, respectively, identified 53 and 52 unigenes encoding enzymes potentially involved in BIA biosynthesis. By integrating probable biosynthetic pathways for BIAs, the jatrorrhizine biosynthesis ill-informed previously was further characterized. Two genes encoding norcoclaurine/norlaudanosoline 6-O-methyltransferases (Cc6OMT1 and Cc6OMT2) and one gene encoding norcoclaurine-7OMT (Ct7OMT) catalyzed enzymatically O-methylate (S)-norcoclaurine at C6 that yield (S)-coclaurine, along with a smaller amount of O-methylation occurred at C7, thereby forming its isomer (isococlaurine). In addition, scoulerine 9-OMT (CtSOMT) was determined to show strict substrate specificity, targeting (S)-scoulerine to yield (S)-tetrahydrocolumbamine. Taken together, the integration of the transcriptome and enzyme activity assays further provides new insight into molecular mechanisms underlying BIA biosynthesis in plants and identifies candidate genes for the study of synthetic biology in microorganisms.</p