Cobalt-Catalyzed Asymmetric Hydrogenation of Ketones Enabled by the Synergism of an N-H Functionality and a Redox-Active Ligand.

The transition metal-catalyzed asymmetric hydrogenation (AH) of ketones to produce enantioenriched alcohols is an important reaction in organic chemistry with applications in the pharmaceutical and agrochemical fields. Using earth-abundant, biorelevant cobalt as the central metal in the catalyst has a high potential to improve sustainability and achieve hydrogenation reactions that are scalable. However, due to the high d-electron count, designing cobalt catalysts that exhibit turnover numbers (TONs, ≥1000) and enantioselectivities (≥90%) sufficient for synthetic utility and practical scalability (≥1 kg scale) remains a challenge. In this work, an efficient catalyst design strategy utilizing an amino(imino)diphosphine Co(II) bromide precatalyst is presented to achieve this goal. The quantitative production of a wide range of secondary chiral alcohols with TONs of up to 150,000 and an enantiomeric excess (e.e.) of up to 99% at a scale of up to 1.35 kg was achieved, indicating that the proposed cobalt catalyst is highly promising for AH and scale-up reactions. A mechanistic study revealed that the synergism of an N-H functionality and a redox-active ligand endows the cobalt catalyst with a high productivity and excellent enantioselectivity.

Isomerization Engineering of Oxygen-Enriched Carbon Quantum Dots for Efficient Electrochemical Hydrogen Peroxide Production.

Hydrogen peroxide (H2O2) has emerged as a kind of multi-functional green oxidants with extensive industrial utility. Oxidized carbon materials exhibit promises as electrocatalysts in the two-electron (2e-) oxygen reduction reaction (ORR) for H2O2 production. However, the precise identification and fabrication of active sites that selectively yield H2O2 present a serious challenge. Herein, a structural engineering strategy is employed to synthesize oxygen-doped carbon quantum dots (o-CQD) for the 2e- ORR. The surface electronic structure of the o-CQDs is systematically modulated by varying isomerization precursors, thereby demonstrating excellent electrocatalyst performance. Notably, o-CQD-3 emerges as the most promising candidate, showcasing a remarkable H2O2 selectivity of 96.2% (n = 2.07) at 0.68 V versus RHE, coupled with a low Tafel diagram of 66.95 mV dec-1. In the flow cell configuration, o-CQD-3 achieves a H2O2 productivity of 338.7 mmol gcatalyst -1 h-1, maintaining consistent production stability over an impressive 120-hour duration. Utilizing in situ technology and density functional theory calculations, it is unveil that edge sites of o-CQD-3 are facilely functionalized by C-O-C groups under alkaline ORR conditions. This isomerization engineering approach advances the forefront of sustainable catalysis and provides a profound insight into the carbon-based catalyst design for environmental-friendly chemical synthesis processes.

Synergistic Effects of Amine Functional Groups and Enriched-Atomic-Iron Sites in Carbon Dots for Industrial-Current-Density CO2 Electroreduction.

Metal phthalocyanine molecules with Me-N4 centers have shown promise in electrocatalytic CO2 reduction (eCO2R) for CO generation. However, iron phthalocyanine (FePc) is an exception, exhibiting negligible eCO2R activity due to a higher CO2 to *COOH conversion barrier and stronger *CO binding energy. Here, amine functional groups onto atomic-Fe-rich carbon dots (Af-Fe-CDs) are introduced via a one-step solvothermal molecule fusion approach. Af-Fe-CDs feature well-defined Fe-N4 active sites and an impressive Fe loading (up to 8.5 wt%). The synergistic effect between Fe-N4 active centers and electron-donating amine functional groups in Af-Fe-CDs yielded outstanding CO2-to-CO conversion performance. At industrial-relevant current densities exceeding 400 mA cm-2 in a flow cell, Af-Fe-CDs achieved >92% selectivity, surpassing state-of-the-art CO2-to-CO electrocatalysts. The in situ electrochemical FTIR characterization combined with theoretical calculations elucidated that Fe-N4 integration with amine functional groups in Af-Fe-CDs significantly reduced energy barriers for *COOH intermediate formation and *CO desorption, enhancing eCO2R efficiency. The proposed synergistic effect offers a promising avenue for high-efficiency catalysts with elevated atomic-metal loadings.

Radiation-Synthesized Metal-Organic Frameworks with Ligand-Induced Lewis Pairs for Selective CO2 Electroreduction.

The electrochemical activation of inert CO2 molecules through C─C coupling reactions under ambient conditions remains a significant challenge but holds great promise for sustainable development and the reduction of CO2 emission. Lewis pairs can capture and react with CO2, offering a novel strategy for the electrosynthesis of high-value-added C2 products. Herein, an electron-beam irradiation strategy is presented for rapidly synthesizing a metal-organic framework (MOF) with well-defined Lewis pairs (i.e., Cu- Npyridinic). The synthesized MOFs exhibit a total C2 product faradic efficiency of 70.0% at -0.88 V versus RHE. In situ attenuated total reflection Fourier transform infrared and Raman spectra reveal that the electron-deficient Lewis acidic Cu sites and electron-rich Lewis basic pyridinic N sites in the ligand facilitate the targeted chemisorption, activation, and conversion of CO2 molecules. DFT calculations further elucidate the electronic interactions of key intermediates in the CO2 reduction reaction. The work not only advances Lewis pair-site MOFs as a new platform for CO2 electrochemical conversion, but also provides pioneering insights into the underlying mechanisms of electron-beam irradiated synthesis of advanced nanomaterials.

Conversion of estriol to estrone: A bacterial strategy for the catabolism of estriol.

Natural estrogens, including estrone (E1), 17ß-estradiol (E2), and estriol (E3), are potentially carcinogenic pollutants commonly found in water and soil environments. Bacterial metabolic pathway of E2 has been studied; however, the catabolic products of E3 have not been discovered thus far. In this study, Novosphingobium sp. ES2-1 was used as the target strain to investigate its catabolic pathway of E3. The metabolites of E3 were identified by high performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS) combined with stable 13C3-labeling. Strain ES2-1 could almost completely degrade 20 mg∙L-1 of E3 within 72 h under the optimal conditions of 30°C and pH 7.0. When inoculated with strain ES2-1, E3 was initially converted to E1 and then to 4-hydroxyestrone (4-OH-E1), which was then cleaved to HIP (metabolite A6) via the 4, 5-seco pathway or cleaved to the B loop via the 9,10-seco pathway to produce metabolite with a long-chain ketone structure (metabolite B4). Although the ring-opening sequence of the above two metabolic pathways was different, the metabolism of E3 was achieved especially through continuous oxidation reactions. This study reveals that, E3 could be firstly converted to E1 and then to 4-OH-E1, and finally degraded into small molecule metabolites through two alternative pathways, thereby reducing E3 pollution in water and soil environments.

Triplet-Induced Singlet Oxygen Photobleaches Near-Infrared Dye-Sensitized Upconversion Nanosystems.

The rapid photobleaching of near-infrared (NIR) dye-sensitized upconversion nanosystems is one of the crucial problems that has blocked their technological applications. Uncovering the photophysical and photochemical pathways of NIR dyes would help to elucidate the photobleaching mechanism and thereby improve the photostability of the system. Here we investigate the triplet dynamics of NIR dyes and their interaction with triplet oxygen in the typically investigated IR806-sensitized upconversion nanoparticle (UCNP) nanosystem. Low-temperature fluorescence at 77 K provides direct proof of the generation of singlet oxygen (1O2) under 808 nm laser irradiation. Mass spectrometry indicates that all three double bonds in the structure of IR806 can be broken in the photochemical process. Coupling IR806 to the surface of UCNPs can accelerate its triplet dynamics, thus producing more 1O2 to photocleave IR806. Importantly, we find that the addition of ß-carotene can scavenge the generated 1O2, thereby providing a simple method to effectively inhibit photobleaching.

[Cerebellar ferroptosis of hypertension mice following lead exposure].

OBJECTIVE: Exploring the changes in cerebellar ferroptosis in hypertensive mice after lead exposure. METHODS: Twenty-five healthy C57 male mice were selected to construct a hypertensive model by intraperitoneal injection of angiotensin II(Ang II) at a concentration of 0.05 mg/kg for 7 consecutive days. After a systolic blood pressure of 140 mmHg, 20 hypertensive mice were randomly divided into a hypertensive control group and a hypertensive lead exposure group. Twenty C57 mice with normal blood pressure were randomly divided into a blood pressure normal control group and a blood pressure normal lead exposure group. The mice in the normal blood pressure control group and the hypertensive control group drank water freely. Mice in the lead exposure group with normal blood pressure and the lead exposure group with hypertension drank lead acetate water containing 250 mg/L. Ang II was injected intraperitoneally every two days in the hypertensive control group and hypertensive lead exposed group mice. Each group of mice was poisoned for 12 weeks. Using open field experiments and balance beam experiments to detect motor dysfunction in mice. Using a reagent kit to detect the levels of divalent iron(Fe~(2+)), malondialdehyde(MDA), and glutathione(GSH) in the cerebellum of different groups of mice. Western blot was used to determine the protein expression of member 11 of the solute carrier family 7(SLC7A11), glutathione peroxidase 4(GPX4), nuclear receptor coactivator 4(NCOA4), microtubule associated protein 1 light chain 3B(LC3B), and ferritin heavy chain 1(FTH1) in mouse cerebellar tissue. RESULTS: The result of the open field experiment showed that the activity distance(1013.04 cm) of mice in the hypertensive lead exposure group was significantly lower than that of the hypertensive control group(1351.18 cm) and the lead exposure group with normal blood pressure(1287.35 cm). And the lead exposure group with hypertension also extended the time through the balance beam, which was 29.40 seconds(P<0.05). In addition, the Fe~(2+)content in the cerebellum of mice in the hypertensive lead exposure group was 3.33 µmol/g prot, which was 1.54 times that of the hypertensive control group and 1.14 times that of the lead exposure group with normal blood pressure. The MDA content was 4.71 nmol/mg prot, higher than that of the hypertensive control group and the lead exposure group with normal blood pressure. The GSH content was 5.36 µmol/g prot, lower than that of the hypertensive control group and the lead exposure group with normal blood pressure(P<0.05). Western blot result showed that compared with the hypertensive control group and the lead exposure group with normal blood pressure, the protein expression of SLC7A11 and GPX4 in the hypertensive lead exposure group was significantly reduced(P<0.05). In addition, compared with the control group with normal blood pressure, the expression of NCOA4 and LC3B proteins in the cerebellum of mice in the hypertension control group and lead exposure group with normal blood pressure increased, while the expression of FTH1 protein decreased(P<0.05). The expression of NCOA4 and LC3B proteins in the hypertensive lead exposure group was higher than that in the hypertensive control group and the lead exposure group with normal blood pressure, while the expression of FTH1 protein decreased(P<0.05). CONCLUSION: Lead exposure can exacerbate iron death in the cerebellar tissue of hypertensive mice, and iron autophagy may be involved in its occurrence and development.

Solvent Engineering of Oxygen-Enriched Carbon Dots for Efficient Electrochemical Hydrogen Peroxide Production.

The development of cost-effective and reliable metal-free carbon-based electrocatalysts has gained significant attention for electrochemical hydrogen peroxide (H2 O2 ) generation through a two-electron oxygen reduction reaction. In this study, a scalable solvent engineering strategy is employed to fabricate oxygen-doped carbon dots (O-CDs) that exhibit excellent performance as electrocatalysts. By adjusting the ratio of ethanol and acetone solvents during the synthesis, the surface electronic structure of the resulting O-CDs can be systematically tuned. The amount of edge active CO group was strongly correlated with the selectivity and activity of the O-CDs. The optimum O-CDs-3 exhibited extraordinary H2 O2 selectivity of up to 96.55% (n = 2.06) at 0.65 V (vs RHE) and achieved a remarkably low Tafel plot of 64.8 mV dec-1 . Furthermore, the realistic H2 O2 productivity yield of flow cell is measured to be as high as 111.18 mg h-1  cm-2 for a duration of 10 h. The findings highlight the potential of universal solvent engineering approach for enabling the development of carbon-based electrocatalytic materials with improved performance. Further studies will be undertaken to explore the practical implications of the findings for advancing the field of carbon-based electrocatalysis.

Spin-orbit charge-transfer intersystem crossing in heavy-atom-free orthogonal covalent boron-dipyrromethene heterodimers.

Boron-dipyrromethene (BODIPY) derivatives are prospective organic-based triplet photosensitizers. Since the triplet generation yield of the parent BODIPY is low, heavy atoms are widely used to improve the triplet yield. However, the dimerization of BODIPYs can also significantly improve their ability to produce triplets. Through a comparative study of the triplet formation dynamics of two heavy-atom-free orthogonal covalent BODIPY heterodimers that differ in their dihedral angles, we have demonstrated that the mechanism of spin-orbit charge-transfer intersystem crossing (SOCT-ISC) promotes the triplet generation of BODIPY heterodimers in solution. Different from the general understanding of SOCT-ISC, the heterodimer with a smaller dihedral angle and low structural rigidity showed better triplet generation due to (a) the stronger inter-chromophoric interaction in the heterodimer, which promoted the formation of a solvent-stabilized charge-transfer (CT) state, (b) the more favorable energy level alignment with sizeable spin-orbit coupling strength, and (c) the balance between the stabilized singlet CT state and limited direct charge recombination to the ground state in a weakly polar solvent. The complete spectral characterization of the triplet formation dynamics clarified the SOCT-ISC mechanism and important factors affecting the triplet generation in BODIPY heterodimers.

Toxic effects of three perfluorinated or polyfluorinated compounds (PFCs) on two strains of freshwater algae: Implications for ecological risk assessments.

Perfluorinated or polyfluorinated compounds (PFCs) continue entering to the environmental as individuals or mixtures, but their toxicological information remains largely unknown. Here, we investigated the toxic effects and ecological risks of Perfluorooctane sulfonic acid (PFOS) and its substitutes on prokaryotes (Chlorella vulgaris) and eukaryotes (Microcystis aeruginosa). Based on the calculated EC50 values, the results showed that PFOS was significantly more toxic to both algae than its alternatives including Perfluorobutane sulfonic acid (PFBS) and 6:2 Fluoromodulated sulfonates (6:2 FTS), and the PFOS-PFBS mixture was more toxic to both algae than the other two PFC mixtures. The action mode of binary PFC mixtures on Chlorella vulgaris was mainly shown as antagonistic and on Microcystis aeruginosa as synergistic, by using Combination index (CI) model coupled with Monte Carlo simulation. The mean risk quotient (RQ) value of three individual PFCs and their mixtures were all below the threshold of 10-1, but the risk of those binary mixtures were higher than that of PFCs individually because of their synergistic effect. Our findings contribute to enhance the understanding of the toxicological information and ecological risks of emerging PFCs and provide a scientific basis for their pollution control.

The AMIGO1 adhesion protein activates Kv2.1 voltage sensors.

Kv2 voltage-gated potassium channels are modulated by amphoterin-induced gene and open reading frame (AMIGO) neuronal adhesion proteins. Here, we identify steps in the conductance activation pathway of Kv2.1 channels that are modulated by AMIGO1 using voltage-clamp recordings and spectroscopy of heterologously expressed Kv2.1 and AMIGO1 in mammalian cell lines. AMIGO1 speeds early voltage-sensor movements and shifts the gating charge-voltage relationship to more negative voltages. The gating charge-voltage relationship indicates that AMIGO1 exerts a larger energetic effect on voltage-sensor movement than is apparent from the midpoint of the conductance-voltage relationship. When voltage sensors are detained at rest by voltage-sensor toxins, AMIGO1 has a greater impact on the conductance-voltage relationship. Fluorescence measurements from voltage-sensor toxins bound to Kv2.1 indicate that with AMIGO1, the voltage sensors enter their earliest resting conformation, yet this conformation is less stable upon voltage stimulation. We conclude that AMIGO1 modulates the Kv2.1 conductance activation pathway by destabilizing the earliest resting state of the voltage sensors.

CO2 Laser-Induced Graphene with an Appropriate Oxygen Species as an Efficient Electrocatalyst for Hydrogen Peroxide Synthesis.

Oxygen species functionalized graphene (O-G) is an effective electrocatalyst for electrochemically synthesizing hydrogen peroxide (H2 O2 ) by a 2 e- oxygen reduction reaction (ORR). The type of oxygen species and degree of carbon crystallinity in O-G are two key factors for the high catalytic performance of the 2 e- ORR. However, the general preparing method of O-G by the precursor of graphite has the disadvantages of consuming massive strong oxidant and washing water. Herein, the biomass-based graphene with tunable oxygen species is rapidly fabricated by a CO2 laser. In a flow cell setup, the laser-induced graphene (LIG) with abundant active oxygen species and graphene structure shows high catalytic performance including high Faraday efficiency (over 78 %) and high mass activity (814 mmolgcatalyst -1  h-1 ), superior to most of the reported carbon-based electrocatalysts. Density function theory demonstrates the meta-C atoms at nearby C-O, O-C=O species are the key catalytic sites. Therefore, we develop one facile method to rapidly convert biomass to graphene electrocatalyst used for H2 O2 synthesis.

Short-term outcomes of medium-low rectal cancer treated by taTME and experience of 22 cases.

BACKGROUND AND METHODS: Transanal total mesorectal excision (taTME) is a novel radical resection technique that may address the unsatisfactory functional and oncological outcomes of medium-low rectal cancers. Although its oncological safety remains unclear, taTME has demonstrable value in surgery, complications, and oncological outcomes. Here, we explore the short-term outcomes of rectal cancer after taTME and discuss the surgical experience. Twenty-two patients with medium-low rectal cancer who underwent taTME were retrospectively evaluated. Comprehensive demographic, oncological, and clinical data were analyzed and the perioperative state and postoperative follow-up were evaluated. RESULTS: Over a median follow-up period of 24.4 (4-36) months, local recurrence occurred in one patient at 6 months postsurgery. Fecal incontinence was the most common postoperative complication, and 3-6 months of pelvic-floor-rehabilitation training greatly improved  anal function CONCLUSIONS: taTME achieved satisfactory short-term outcomes in oncological complications and postoperative functions. Accurate intraoperative anatomical location, identification of the rectovesical fascia, and neuroprotection are critical. However, this procedure has a steep learning curve, and large samples and multicenter studies are required to substantiate its effectiveness. DISCUSSION: We retrospectively analyzed the oncological and functional prognosis of 22 patients with colorectal cancer undergoing taTME surgery and preliminarily concluded taTME can be regarded as a safe and feasible treatment.

Near infrared light fluorescence imaging-guided biomimetic nanoparticles of extracellular vesicles deliver indocyanine green and paclitaxel for hyperthermia combined with chemotherapy against glioma.

BACKGROUND: We investigated the therapeutic effect of targeting extracellular vesicles (EVs) loaded with indocyanine green (ICG) and paclitaxel (PTX) on glioma. METHODS: Raw264.7 cells were harvested to extract EVs for the preparation of ICG/PTX@RGE-EV by electroporation and click chemistry. We evaluated the success of modifying Neuropilin-1 targeting peptide (RGE) on the EV membrane of ICG/PTX@RGE-EV using super-resolution fluorescence microscopy and flow cytometry. Spectrophotometry and high performance liquid chromatography (HPLC) were implemented for qualitative and quantitative analysis of the ICG and PTX loaded in EVs. Photothermal properties of the vesicles were evaluated by exposing to 808-nm laser light. Western blot analysis, cell counting kit 8 (CCK-8), Calcein Acetoxymethyl Ester/propidium iodide (Calcein-AM/PI) staining, and flow cytometry were utilized for assessing effects of vesicle treatment on cellular behaviors. A nude mouse model bearing glioma was established to test the targeting ability and anti-tumor action of ICG/PTX@RGE-EV in vivo. RESULTS: Under exposure to 808-nm laser light, ICG/PTX@RGE-EV showed good photothermal properties and promotion of PTX release from EVs. ICG/PTX@RGE-EV effectively targeted U251 cells, with activation of the Caspase-3 pathway and elevated apoptosis in U251 cells through chemotherapy combined with hyperthermia. The anti-tumor function of ICG/PTX@RGE-EV was confirmed in the glioma mice via increased accumulation of PTX in the ICG/PTX@RGE-EV group and an increased median survival of 48 days in the ICG/PTX@RGE-EV group as compared to 25 days in the PBS group. CONCLUSION: ICG/PTX@RGE-EV might actively target glioma to repress tumor growth by accelerating glioma cell apoptosis through combined chemotherapy-hyperthermia.

Autophagy inhibition enhances anti-pituitary adenoma effect of tetrandrine.

Pituitary adenoma (PA) is a benign intracranial neoplasm originated from pituitary gland. Surgery is the first-line therapy for most of PAs, but lead to unsatisfactory prognosis in some cases. Tetrandrine (Tet) has anticancer effect on some cancers. However, growth inhibition effect on PA is unknown. To elucidate the inhibitory effect of Tet on the growth of PA and its potential mechanisms, we validated the in vitro and in vivo anti-PA effect of Tet and illustrated the cellular and molecular alterations by confocal microscopy observation, flow cytometry, and RNA interference. Tet inhibited PA cell growth in vitro and tumor progression in vivo. Tet induced autophagy and apoptosis in a dose-dependent manner. Low dosage (1.25 µM) of Tet induced PA cell autophagy by down-regulation of MAPK/STAT3 signal. While, higher dosage (5.0 µM) of Tet partially induced PA cell death through caspase-dependent apoptosis. Autophagy inhibitors enhanced Tet-induced caspase activity and apoptotic cell death. These findings demonstrated that Tet has anti-PA effect by inducing autophagy and apoptosis through MAPK/STAT3 signaling pathway attenuation and autophagy inhibition might enhance its anti-PA effect, indicating that Tet (or combined with autophagy inhibitor) is a potential therapeutic regimen for PAs.

Reappraisal of the Optimal Dose of Meropenem in Critically Ill Infants and Children: a Developmental Pharmacokinetic-Pharmacodynamic Analysis.

Data of developmental pharmacokinetics (PK) of meropenem in critically ill infants and children with severe infections are limited. We assessed the population PK and defined the appropriate regimen to optimize treatment in this population based on developmental PK-pharmacodynamic (PD) analysis. Blood samples were collected from pediatric intensive care unit patients with severe infection treated with standard dosage regimens for meropenem. Population PK data were analyzed using NONMEM software. Fifty-seven patients (mean age, 2.96 years [range, 0.101 to 14.4]; mean body weight, 15.8 kg [range, 5.0 to 65.0]) were included. A total of 135 meropenem concentrations were obtainable for population PK modeling. The median number of samples per patients was 2 (range, 1 to 4). A two-compartment model with first-order elimination was optimal for PK modeling. Weight and creatinine clearance (estimated by the Schwartz formula) were significantly correlated with the PK parameters of meropenem. The probabilities of target attainment for pathogens with low MICs of 1 and 2 µg/ml were 87.5% and 68.6% following administration of 40 mg/kg/dose (every 8 h [q8h]) as a 4-h infusion and 98.0% and 73.3% with high MICs of 4 and 8 µg/ml following administration of 110 mg/kg/day as a continuous infusion in critically ill infants and children under 70% fT>MIC (the free time during which the plasma concentration of meropenem exceeds the MIC), respectively. The standard dosage regimens for meropenem did not meet an appropriate PD target, and an optimal dosing regimen was established in critically ill infants and children. (This study has been registered at ClinicalTrials.gov under identifier NCT03643497.).

Glioma exosomal microRNA-148a-3p promotes tumor angiogenesis through activating the EGFR/MAPK signaling pathway via inhibiting ERRFI1.

BACKGROUND: Glioma is the most frequent and lethal primary brain malignancy. Amounting evidence has highlighted the importance of exosomal microRNAs (miRNAs or miRs) in this malignancy. This study aimed to investigate the regulatory role of exosomal miR-148a-3p in glioma. METHODS: Bioinformatics analysis was firstly used to predict the target genes of miR-148a-3p. Exosomes were then extracted from normal human astrocytes and glioma cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was applied to determine the expression patterns of miR-148a-3p and ERBB receptor feedback inhibitor 1 (ERRFI1). Dual-luciferase reporter gene assay was applied to verify the direct binding between miR-148a-3p and ERRFI1. Cell counting kit-8 and tube formation assays were further conducted to assess the proliferation and angiogenic properties of human umbilical vein endothelial cells (HUVECs) in the co-culture system with exosomes. Lastly, glioma tumor models were established in BALB/c nude mice to study the role of exosomal miR-148a-3p in vivo. RESULTS: miR-148a-3p was highly expressed, while ERRFI1 was poorly expressed in glioma. miR-148a-3p was found to be enriched in glioma cells-derived exosomes and could be transferred to HUVECs via exosomes to promote their proliferation and angiogenesis. ERRFI1 was identified as a target gene of miR-148a-3p. In addition, miR-148a-3p activated the epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK) signaling pathway by inhibiting ERRFI1. In the co-culture system, our data demonstrated that glioma cells-derived exosomal miR-148a-3p down-regulated ERRFI1 and activated the EGFR/MAPK signaling pathway, so as to promote cell proliferation and angiogenesis. In vivo experimentation further demonstrated that this mechanism was responsible for the promotive role of exosomal miR-148a-3p in tumorigenesis and angiogenesis. CONCLUSION: Taken together, glioma-derived exosomal miR-148a-3p promoted tumor angiogenesis through activation of the EGFR/MAPK signaling pathway by ERRFI1 inhibition.

Diastereoselective Synthesis of P-Chirogenic and Atropisomeric 2,2'-Bisphosphino-1,1'-binaphthyls Enabled by Internal Phosphine Oxide Directing Groups.

Diphosphine ligands that merge both axial and P-centered chirality may exhibit superior or unique properties. Herein we report the diastereoselective introduction of P-centered chirality at the 2-position of the axially chiral 2'-(phosphine oxide)-1,1'-binaphthyl scaffold. A lithium-bromide exchange reaction of a 2-bromo-2'-(phosphine oxide)-1,1'-binaphthyl and treatment with dichlorophosphines followed by a nucleophilic organometallic reagent afforded unsymmetrical 2-phosphino-2'-(phosphine oxide)-1,1'-binaphthyls with binaphthyl axial chirality and one or two phosphorus stereocenters with a variety of P substituents. The final diastereomerically pure 2,2'-bisphosphino-1,1'-binaphthyls were obtained by reduction of the phosphine oxide directing group. Preliminary results demonstrated that a ligand with this hybrid chirality could induce higher stereoselectivity in the metal-complex-catalyzed asymmetric hydrogenation of a dialkyl ketone.

Clinical features, radiologic findings, and treatment of pediatric germ cell tumors involving the basal ganglia and thalamus: a retrospective series of 15 cases at a single center.

PURPOSE: Pediatric germ cell tumors (GCTs) involving the basal ganglia and thalamus are relatively rare neoplasms which have not been extensively described. We here summarize the clinical and radiological features of a series of such tumors and discuss optimal treatment strategies based upon our experience. METHODS: A total of 15 pediatric patients with basal ganglionic and thalamic GCTs were treated between 2011 and 2016 at West China Hospital. Epidemiological characteristics, clinical features, imaging findings, and treatment strategies were reviewed retrospectively. RESULTS: GCTs constituted 28% (15/53) of pediatric basal ganglionic and thalamic tumors in our institution between 2011 and 2016. There were 12 males and 3 females with mean age of 11.7 ± 2.8 years (range, 7-16 years). The most common initial manifestation was hemiparesis (n = 13, 86.7%), followed by headache (n = 5, 33.3%), vomiting (n = 3, 20.0%), cognitive disturbance (n = 2, 13.3%), and seizure (n = 1, 6.7%). No tumors were incidentally detected. The mean duration of the symptoms before diagnosis was 4.4 ± 3.9 months (range from 9 days to 13 months). The maximum diameters of the lesions ranged from 3.2 to 6.5 cm (mean 4.7 ± 1.1 cm). Cysts were seen in tumors in MRIs in 11 patients (73%), intratumoral hemorrhages in 3 (20%), calcification in 2 (13%), and there was obstructive hydrocephalus in 1 (7%). Of note, hemiatrophy was observed in 9 cases (60.0%). The mean follow-up for the 15 patients was 28 months (range, 9-54 months), and no patients were lost. During the follow-up period, all patients (9 cases) with germinomas responded well to radiotherapy, and no recurrence was observed. Among 4 patients with mixed nongerminomatous germ cell tumor, 2 suffered tumor recurrence after treatment. Neurological deficits improved or remained unchanged in 12 patients but 3 developed new dysfunction including significant cognitive disturbance and hemiparesis. CONCLUSIONS: Pediatric GCTs in the basal ganglia and thalamus are not as rare as previously considered. Tumor markers should be tested routinely for tumors in these sites in young patients. Optimal treatment strategy based on accurate diagnosis and comprehensive clinical assessment should be recommended.

Amine-Functionalized Metal-Free Nanocarbon to Boost Selective CO2 Electroreduction to CO in a Flow Cell.

Highly efficient electrochemical CO2-to-CO conversion is a promising approach for achieving carbon neutrality. While nonmetallic carbon electrocatalysts have shown potential for CO2-to-CO utilization in H-type cells, achieving efficient conversion in flow cells at an industrial scale remains challenging. In this study, we present a cost-effective synthesis strategy for preparing ultrathin 2D carbon nanosheet catalysts through simple amine functionalization. The optimized catalyst, NCNs-2.5, demonstrates exceptional CO selectivity with a maximum Faradaic efficiency of 98% and achieves a high current density of 55 mA cm-2 in a flow cell. Furthermore, the catalyst exhibits excellent long-term stability, operating continuously for 50 h while maintaining a CO selectivity above 90%. The superior catalytic activity of NCNs-2.5 is attributed to the presence of amine-N active sites within the carbon lattice structure. This work establishes a foundation for the rational design of cost-effective nonmetallic carbon catalysts as sustainable alternatives to metals in energy conversion systems.