STAG2 mutations regulate 3D genome organization, chromatin loops, and Polycomb signaling in glioblastoma multiforme.

Inactivating mutations of genes encoding the cohesin complex are common in a wide range of human cancers. STAG2 is the most commonly mutated subunit. Here we report the impact of stable correction of endogenous, naturally occurring STAG2 mutations on gene expression, 3D genome organization, chromatin loops, and Polycomb signaling in glioblastoma multiforme (GBM). In two GBM cell lines, correction of their STAG2 mutations significantly altered the expression of ∼10% of all expressed genes. Virtually all the most highly regulated genes were negatively regulated by STAG2 (i.e., expressed higher in STAG2-mutant cells), and one of them-HEPH-was regulated by STAG2 in uncultured GBM tumors as well. While STAG2 correction had little effect on large-scale features of 3D genome organization (A/B compartments, TADs), STAG2 correction did alter thousands of individual chromatin loops, some of which controlled the expression of adjacent genes. Loops specific to STAG2-mutant cells, which were regulated by STAG1-containing cohesin complexes, were very large, supporting prior findings that STAG1-containing cohesin complexes have greater loop extrusion processivity than STAG2-containing cohesin complexes and suggesting that long loops may be a general feature of STAG2-mutant cancers. Finally, STAG2 mutation activated Polycomb activity leading to increased H3K27me3 marks, identifying Polycomb signaling as a potential target for therapeutic intervention in STAG2-mutant GBM tumors. Together, these findings illuminate the landscape of STAG2-regulated genes, A/B compartments, chromatin loops, and pathways in GBM, providing important clues into the largely still unknown mechanism of STAG2 tumor suppression.

Re-Imagining Hospital Patient Room Design for People After stroke: A Randomized Controlled Study Using Virtual Reality.

BACKGROUND: The hospital's physical environment can impact health and well-being. Patients spend most of their time in their hospital rooms. However, little experimental evidence supports specific physical design variables in these rooms, particularly for people poststroke. The study aimed to explore the influence of patient room design variables modeled in virtual reality using a controlled experimental design. METHODS: Adults within 3 years of stroke who had spent >2 nights in hospital for stroke and were able to consent were included (Melbourne, Australia). Using a factorial design, we immersed participants in 16 different virtual hospital patient rooms in both daytime and nighttime conditions, systematically varying design attributes: patient room occupancy, social connectivity, room size (spaciousness), noise (nighttime), greenery outlook (daytime). While immersed, participants rated their affect (Pick-A-Mood Scale) and preference. Mixed-effect regression analyses were used to explore participant responses to design variables in both daytime and nighttime conditions. Feasibility and safety were monitored throughout. Australian New Zealand Clinical Trials Registry, Trial ID: ACTRN12620000375954. RESULTS: Forty-four adults (median age, 67 [interquartile range, 57.3-73.8] years, 61.4% male, and a third with stroke in the prior 3-6 months) completed the study in 2019-2020. We recorded and analyzed 701 observations of affective responses (Pick-A-Mood Scale) in the daytime (686 at night) and 698 observations of preference responses in the daytime (685 nighttime) while continuously immersed in the virtual reality scenarios. Although single rooms were most preferred overall (daytime and nighttime), the relationship between affective responses differed in response to different combinations of nighttime noise, social connectivity, and greenery outlook (daytime). The virtual reality scenario intervention was feasible and safe for stroke participants. CONCLUSIONS: Immediate affective responses can be influenced by exposure to physical design variables other than room occupancy alone. Virtual reality testing of how the physical environment influences patient responses and, ultimately, outcomes could inform how we design new interventions for people recovering after stroke. REGISTRATION: URL: https://anzctr.org.au; Unique identifier: ACTRN12620000375954.

2D-on-2D Al-Doped NiCo LDH Nanosheet Arrays for Fabricating High-Energy-Density, Wide Voltage Window, and Ultralong-Lifespan Supercapacitors.

Battery-type electrode materials with high capacity, wide potential windows, and good cyclic stability are crucial to breaking through energy storage limitations and achieving high energy density. Herein, a novel 2D-on-2D Al-doped NiCo layered double hydroxide (NiCoAlx LDH) nanosheet arrays with high-mass-loading are grown on a carbon cloth (CC) substrate via a two-step hydro/solvothermal deposition strategy, and the effect of Al doping is employed to modify the deposition behavior, hierarchical morphology, phase stability, and multi-metallic synergistic effect. The optimized NiCoAl0.1 LDH electrode exhibits capacities of 5.43, 6.52, and 7.25 C cm-2 (9.87, 10.88, and 11.15 F cm-2) under 0-0.55, 0-0.60, and 0-0.65 V potential windows, respectively, illustrating clearly the importance of the wide potential window. The differentiated deposition strategy reduces the leaching level of Al3+ cations in alkaline solutions, ensuring excellent cyclic performance (108% capacity retention after 40 000 cycles). The as-assembled NiCoAl0.1 LDH//activated carbon cloth (ACC) hybrid supercapacitor delivers 3.11 C cm-2 at 0-2.0 V, a large energy density of 0.84 mWh cm-2 at a power density of 10.00 mW cm-2, and excellent cyclic stability with ≈135% capacity retention after 150 000 cycles.

Growth patterns of facial muscles at the angle of the mouth: A histological study using midterm and near-term human fetuses.

At the angle of the mouth, spoke-like muscle bundles converge at the "modiolus," which is believed to appear in utero. The aim of this study was to investigate the growth of the modiolus histologically. We studied frontal histological sections of the face from 12 midterm and six near-term fetuses. At midterm, a convergence of the levator anguli oris (LAOM) and depressor anguli oris (DAOM) was frequently present, and another convergence of the LAOM with the platysma (PM) or orbicularis oris (OOM) was also often evident. At near-term, muscle fiber merging or interdigitation was classified into nine combinations, five of which were frequently seen: LAOM-PM, LAOM-DAOM, zygomaticus major (ZMM)-orbicularis oris (OOM), buccinator (BM)-LAOM, and BM-PM. These combinations existed at slightly different depths and/or sites, thus allowing the angle of the mouth to receive multiple muscles. Notably, tissues interposed between the muscle fibers were limited to a thin epimysium at each crossing or interdigitation. Therefore, the LAOM, DAOM, OOM, BM, and PM appear to form a basic configuration at birth, but the development and growth were much delayed than the classical description. The modiolus is not a specific fibromuscular structure but simply represents a cluster of muscle convergence sites. Even at meeting between an elevator and depressor, a specific fibrous structure seems unlikely to connect the epimysium for the muscle convergence. Instead, the central nervous system appears to regulate the activity of related muscles to minimize tension or friction stress at the meeting site.

CO2 Photoreduction over Semiconducting 2D Materials with Supported Single Atoms: Recent Progress and Challenges.

In the face of the growing energy crisis and environmental challenges, substantial efforts are now directed toward sustainable clean energy as a replacement for traditional fossil fuels. CO2 photoreduction into value-added chemicals and fuels is widely recognized as a promising approach to mitigate current energy and environmental concerns. Photocatalysts comprising single atoms (SAs) supported on two-dimensional (2D) semiconducting materials (SAs-2DSemi) have emerged as a novel frontier due to the combined merits of SA catalysts and 2D materials. In this study, we review advancements in metal SAs confined on 2DSemi substrates, categorized into four groups: (1) metal oxide-based, (2) g-C3N4-based, (3) emerging, and (4) hybridized 2DSemi, for photocatalytic CO2 conversion over the past few years. With a particular focus on highlighting the distinct advantages of SAs-2DSemi, we delve into the synthesis of state-of-the-art catalysts, their catalytic performances, and mechanistic elucidation facilitated by experimental characterizations and theoretical calculations. Following this, we outline the challenges in this field and offer perspectives on harnessing the potential of SAs-2DSemi as promising photocatalysts. This comprehensive review aims to provide valuable insights for the future development of 2D photocatalytic materials involving SAs for CO2 reduction.

Cardiovascular events of Bruton's tyrosine kinase inhibitors: A real-world study based on the United States Food and Drug Administration Adverse Event Reporting System database.

AIMS: Bruton's tyrosine kinase inhibitors (BTKIs), including first-generation ibrutinib, second-generation acalabrutinib and zanubrutinib, may be involved in the mechanisms of action related to adverse events (AEs) of the cardiovascular system. We aimed to characterize the cardiovascular AEs of BTKIs reported in the US Food and Drug Administration (FDA) Adverse Event Reporting System, and to compare the cardiovascular risks of BTKIs. METHODS: Across all indications of three FDA-approved BTKIs, primary suspect drugs were extracted over two periods: from January 2013 to December 2022 (after the approval of the first BTKI), and from January 2020 to December 2022 (all three BTKIs on the market). Disproportionality was measured by reporting odds ratios (RORs) and information components. Additional analyses were performed without incorporating patients with underlying cardiovascular disease (CVD). RESULTS: A total of 10 353 cases included the uses of ibrutinib, acalabrutinib and zanubrutinib. Ibrutinib was significantly associated with 47 cardiovascular AEs. Acalabrutinib was associated with new signals, including cardiac failure (ROR = 1.82 [1.13-2.93]), pulmonary oedema (ROR = 2.15 [1.19-3.88]), ventricular extrasystoles (ROR = 5.18 [2.15-12.44]), heart rate irregular (ROR = 3.05 [1.53-6.11]), angina pectoris (ROR = 3.18 [1.71-5.91]) and cardiotoxicity (ROR = 25.22 [17.14-37.10]). In addition, cardiovascular events had an earlier onset in acalabrutinib users. Zanubrutinib was only associated with atrial fibrillation. Acalabrutinib and zanubrutinib had lower ROR values than ibrutinib. The AE signals were generally consistent between the population receiving and not receiving CVD medications. CONCLUSIONS: Potential cardiovascular risks identified in this study were not clearly noted on the label of marketed acalabrutinib. Caution should be paid to the cardiovascular risks of BTKIs having been or being developed.

Modeling and mobile home monitoring of behavioral and psychological symptoms of dementia (BPSD).

With the increasing global aging population, dementia care has rapidly become a major social problem. Current diagnosis of Behavior and Psychological Symptoms of Dementia (BPSD) relies on clinical interviews, and behavioral rating scales based on a period of behavior observation, but these methods are not suitable for identification of occurrence of BPSD in the daily living, which is necessary for providing appropriate interventions for dementia, though, has been studied by few research groups in the literature. To address these issues, in this study developed a BPSD monitoring system consisting of a Psycho-Cognitive (PsyCo) BPSD model, a Behavior-Physio-Environment (BePhyEn) BPSD model, and an implementation platform. The PsyCo BPSD model provides BPSD assessment support to caregivers and care providers, while the BePhyEn BPSD model provides instantaneous alerts for BPSD enabled by a 24-hour home monitoring platform for early intervention, and thereby alleviation of burden to patients and caregivers. Data for acquiring the models were generated through extensive literature review and regularity determined. A mobile robot was utilized as the implementation platform for improving sensitivity of sensors for home monitoring, and elderly individual following algorithms were investigated. Experiments in a virtual home environment showed that, a virtual BPSD elderly individual can be followed safely by the robot, and BPSD occurrence could be identified accurately, demonstrating the possibility of modeling and identification of BPSD in home environment.

Effects of remimazolam tosilate on gastrointestinal hormones and gastrointestinal motility in patients undergoing gastrointestinal endoscopy with sedation: a randomized control trial.

PURPOSE: To investigate the impacts of remimazolam tosilate on gastrointestinal hormones and motility in patients undergoing gastrointestinal endoscopy with sedation. METHODS: A total of 262 American Society of Anesthesiologists Physical Status I or II patients, aged 18-65 years, scheduled for gastrointestinal endoscopy with sedation, were randomly allocated into two groups (n = 131 each): the remimazolam tosilate group (Group R) and the propofol group (Group P). Patients in Group R received 0.2-0.25 mg/Kg remimazolam tosilate intravenously, while those in Group P received 1.5-2.0 mg/kg propofol intravenously. The gastrointestinal endoscopy was performed when the Modified Observer's Assessment of Alertness/Sedation scores were ≤3. The primary endpoints included the endoscopic intestinal peristalsis rating by the endoscopist; serum motilin and gastrin levels at fasting without gastrointestinal preparation (T0), before gastrointestinal endoscopy (T1), and before leaving the Post Anesthesia Care Unit (T2); and the incidences of abdominal distension during Post Anesthesia Care Unit. RESULTS: Compared with Group P, intestinal peristalsis rating was higher in Group R (P < .001); Group R showed increased motilin and gastrin levels at T2 compared with Group P (P < .01). There was a rise in motilin and gastrin levels at T1 and T2 compared with T0 and at T2 compared with T1 in both groups (P < .01). The incidence of abdominal distension was lower in Group R (P < .05). CONCLUSION: Compared with propofol used during gastrointestinal endoscopy with sedation, remimazolam tosilate mildly inhibits the serum motilin and gastrin levels, potentially facilitating the recovery of gastrointestinal motility.

Transformation-Optics-Designed Plasmonic Singularities for Efficient Photocatalytic Hydrogen Evolution at Metal/Semiconductor Interfaces.

Inspired by transformation optics, we propose a new concept for plasmonic photocatalysis by creating a novel hybrid nanostructure with a plasmonic singularity. Our geometry enables broad and strong spectral light harvesting at the active site of a nearby semiconductor where the chemical reaction occurs. A proof-of-concept nanostructure comprising Cu2ZnSnS4 (CZTS) and Au-Au dimer (t-CZTS@Au-Au) is fabricated via a colloidal strategy combining templating and seeded growth. On the basis of numerical and experimental results of different related hybrid nanostructures, we show that both the sharpness of the singular feature and the relative position to the reactive site play a pivotal role in optimizing photocatalytic activity. Compared with bare CZTS, the hybrid nanostructure (t-CZTS@Au-Au) exhibits an enhancement of the photocatalytic hydrogen evolution rate by up to ∼9 times. The insights gained from this work might be beneficial for designing efficient composite plasmonic photocatalysts for diverse photocatalytic reactions.

Stroke Inpatient Rehabilitation Environments: Aligning Building Construction and Clinical Practice Guidelines Through Care Process Mapping.

BACKGROUND: Stroke inpatient rehabilitation is a complex process involving stroke survivors, staff, and family utilizing a common space for a shared purpose: to optimize recovery. This complex pathway is rarely fully described. Stroke care is ideally guided by Clinical Practice Guidelines, and the rehabilitation built environment should serve to optimize care delivery, patient and staff experience. We aimed to articulate the inpatient stroke rehabilitation process of care in a series of process maps, and to understand the degree to which current stroke clinical and building construction (ie, design) guidelines align to support inpatient stroke rehabilitation. METHODS: We used the Value-Focused Process Engineering methodology to create maps describing the events and activities that typically occur in the current stroke inpatient rehabilitation service model. These maps were completed through individual and group session consultations with stroke survivors, architects, policy makers, and clinical experts. We then determined which sections of the Australian Stroke Rehabilitation Guidelines and the Australasian Health Facility Design Guidelines could be aligned and applied to the process maps. RESULTS: We present a summary process map for stroke inpatient rehabilitation, alongside detailed process maps for 4 different phases of rehabilitation (admission, a normal weekday, a weekend day, and discharge) using Value-Focused Process Engineering notation. The integration of design and clinical guidelines with care pathway maps revealed where guidelines lack detail to be readily linked to current stroke inpatient care practice, providing an opportunity to design stroke inpatient rehabilitation spaces based on the activities occurring within them. CONCLUSIONS: Our findings highlight gaps where clinical and design experts should work together to use guidelines to their full potential; and to improve the process of planning for future stroke rehabilitation units.

Imparting Outstanding Dispersibility to Nanoscaled 2D COFs for Constructing Organic Solvent Forward Osmosis Membranes.

In the context of thin-film nanocomposite membranes with interlayer (TFNi), nanoparticles are deposited uniformly onto the support prior to the formation of the polyamide (PA) layer. The successful implementation of this approach relies on the ability of nanoparticles to meet strict requirements regarding their sizes, dispersibility, and compatibility. Nevertheless, the synthesis of covalent organic frameworks (COFs) that are well-dispersed, uniformly morphological, and exhibit improved affinity to the PA network, while preventing agglomeration, remains a significant challenge. In this work, a simple and efficient method is presented for the synthesis of well-dispersed, uniformly morphological, and amine-functionalized 2D imine-linked COFs regardless of the ligand composition, group type, or framework pore size, by utilizing a polyethyleneimine (PEI) shielded covalent self-assembly strategy. Subsequently, the as-prepared COFs are incorporated into TFNi for the recycling of pharmaceutical synthetic organic solvents. After optimization, the membrane exhibits a high rejection rate and a favorable solvent flux, making it a reliable method for efficient organic recovery and the concentration of active pharmaceutical ingredient (API) from the mother liquor through an organic solvent forward osmosis (OSFO) process. Notably, this study represents the first investigation of the impact of COF nanoparticles in TFNi on OSFO performance.

Analysis of traditional Chinese medicine syndrome types and frequency changes of CD8+ and CD25+ T cells in metabolic-related fatty liver disease.

This study aimed to observe and analyze the changes in traditional Chinese medicine (TCM) syndrome types and CD8+ and CD25+T cell frequencies of metabolic-related fatty liver disease. For this purpose, 100 patients with metabolic-related fatty liver disease and their TCM syndrome types who were screened for medical treatment were collected. Flow cytometry was used to detect the changes in the frequency of CD8+ and CD25+T cells in the peripheral blood of patients, as well as liver function, fasting blood glucose, and lipid index. The frequency differences of CD8+ and CD25+T cells in patients with different syndrome types were compared. To use partial correlation analysis to determine the correlation between CD8+, CD25+T cell frequencies and TCM syndrome types in patients. Results showed that a total of 30 cases of liver stagnation and spleen deficiency syndrome, 25 cases of phlegm turbidity internal obstruction syndrome, 20 cases of dampness heat stasis syndrome, and 25 cases of phlegm stasis mutual accumulation syndrome were included in the 100 MAFLD patients. There was statistical significance (P<0.01) in the comparison of ALT, AST, GGT, TC, TG, HDL-C, LDL-C, FPG, HOMA-IR, CD8+CD25+, CD8+CD25-, CD8-CD25+, and CD8-CD25- among patients with different TCM syndrome types. There is a positive correlation between TCM syndrome types and patients' CD8+CD25+, CD8+CD25-, and CD8-CD25+, while there is a negative correlation between them (P<0.05). From the chord diagram, the relationship between CD8+CD25+ and TCM syndrome types is the closest. The ROC curve was used to analyze and determine that the relevant standard for CD8+CD25+ in liver depression and spleen deficiency syndrome is <4.90%; The relevant standard for phlegm turbidity internal obstruction syndrome is 4.90%~7.88%; Damp heat stasis syndrome is 7.88%~8.20%; The syndrome of phlegm and blood stasis accumulation is more than 8.20%. The TCM syndrome types of metabolic-related fatty liver disease will vary with the frequency of CD8+ and CD25+T cells. In conclusion, TCM syndrome types are closely related to the severity of the patient's condition and immune function, providing a new perspective and means for understanding the pathogenesis of metabolic-related fatty liver disease and evaluating the condition.

Emission of VOCs from service stations in Beijing: Species characteristics and pollutants co-control based on SOA and O3.

Currently, air pollution is primarily characterized by PM2.5 and O3. Therefore, the co-control of PM2.5 and O3 has become an important task of atmosphere pollution prevention and control in China. However, few studies have been conducted on the emissions from vapor recovery and processes, which is an important source of VOCs. This paper analyzed the VOC emissions of three vapor process technologies in service stations and first proposed key pollutants for priority control based on the coordinated reactivity of O3 and SOA. The concentration of VOCs emitted from the vapor processor was 3.14-9.95 g m-3, compared to 631.2-717.8 g m-3 for uncontrolled vapor. Alkanes, alkenes, and halocarbons accounted for a high proportion of the vapor both before and after control. Among the emissions, i-pentane, n-butane, and i-butane were the most abundant species. Then, the species of OFP and SOAP were calculated through the maximum incremental reactivity (MIR) and fractional aerosol coefficient (FAC). The average source reactivity (SR) value of the VOC emissions from three service stations was 1.9 g g-1, while the OFP ranged from 8.2 to 13.9 g m-3 and SOAP ranged from 0.18 to 0.36 g m-3. By considering the coordinated chemical reactivity of O3 and SOA, a comprehensive control index (CCI) was proposed for the control of key pollutant species that have multiplier effects on environment. For adsorption, trans-2-butene and p-xylene were the key co-control pollutants, while toluene and trans-2-butene were the most important for membrane and condensation + membrane control. A 50% emission reduction of the top two key species that emission account for 4.3% averagely will reduce O3 by 18.4% and SOA by 17.9%.

Dynamics and Allosteric Information Pathways of Unphosphorylated c-Cbl.

Human c-Cbl is a RING-type ligase and plays a central role in the protein degradation cascade. To elucidate its conformational changes related to substrate binding, we performed molecular dynamics simulations of different variants/states of c-Cbl for a cumulative time of 68 µs. Our simulations demonstrate that before the substrate binds, the RING domain samples a broad set of conformational states at a biologically relevant salt concentration, including the closed, partially open, and fully open states, whereas substrate binding leads to a restricted conformational sampling. Phe378 and the C-terminal region play an essential role in stabilizing the partially open state. To visualize the allosteric signal transmission pathways from the substrate-binding site to the 40 Å apart RING domain and identify the critical residues for allostery, we have created a subgraph from the optimal and suboptimal paths. Redundant paths are seen in the SH2 domain where the substrate binds, while the major bottlenecks are found at the junction between the SH2 domain and the linker helix region as well as that between the SH2 domain and the 4H bundle. These bottlenecks separate the paths into two overall routes. The nodes/residues at the bottlenecks on the subgraph are considered allosteric hot spots. This subgraph approach provides a general tool for network visualization and determination of critical residues for allostery. The structurally and allosterically critical residues identified in our work are testable and would provide valuable insights into the emerging strategies for drug discovery, such as targeted protein degradation.

Polychromatic annular folded lenses using freeform gradient-index optics.

The annular folded lens (AFL) is a design form offering large aperture, high-resolution imaging in a very axially compact package. The folded optic can be made monolithic for easier fabrication and alignment, yet the introduction of refractive surfaces with a dispersive optical material gives way to chromatic aberrations. AFL designs using homogeneous media are generally limited to the monochromatic regime, with polychromatic performance greatly reduced. By introducing freeform gradient-index (F-GRIN) media, monolithic AFL designs can achieve higher monochromatic performance as well as provide color correction for diffraction-limited polychromatic imaging. Monochromatic and polychromatic design methodologies are surveyed where the F-GRIN is constrained to remain feasible for fabrication.

Freeform gradient-index media: a new frontier in freeform optics.

Freeform optics enable irregular system geometries and high optical performance by leveraging rotational variance. To this point, for both imaging and illumination, freeform optics has largely been synonymous with freeform surfaces. Here a new frontier in freeform optics is surveyed in the form of freeform gradient-index (F-GRIN) media. F-GRIN leverages arbitrary three-dimensional refractive index distributions to impart unique optical influence. When transversely variant, F-GRIN behaves similarly to freeform surfaces. By introducing a longitudinal refractive index variation as well, F-GRIN optical behavior deviates from that of freeform surfaces due to the effect of volume propagation. F-GRIN is a useful design tool that offers vast degrees of freedom and serves as an important complement to freeform surfaces in the design of advanced optical systems for both imaging and illumination.

Efficient representation of freeform gradient-index profiles for non-rotationally symmetric optical design.

Conventional optical designs with gradient index (GRIN) use rotationally-invariant GRIN profiles described by polynomials with no orthogonality. These GRIN profiles have limited effectiveness at correcting aberrations from tilted/decentered or freeform systems. In this paper, a three-dimensional orthogonal polynomial basis set (the FGRIN basis) is proposed, which enables the design of GRIN profiles with both rotational and axial variations. The FGRIN basis is then demonstrated via the design of a 3D GRIN corrector plate targeted to correct the rotationally-variant aberrations induced from a tilted spherical mirror. A sample corrector is manufactured and tested, showing significant correction of astigmatism. The FGRIN basis opens a new design space of 3D rotational variant GRIN profiles, which has the potential of replacing multiple freeform surfaces and simplifying complex systems.

Ultrafine PtRu Dilute Alloy Nanodendrites for Enhanced Electrocatalytic Methanol Oxidation.

Dilute alloy nanostructures have been demonstrated to possess distinct catalytic properties. Noble-metal-induced reduction is one effective synthesis strategy to construct dilute alloys and modify the catalytic performance of the host metal. Herein, we report the synthesis of ultrafine PtRu dilute alloy nanodendrites (PtRu NDs, molar ratio Ru/Pt is 1:199) by the reduction of RuIII ions induced by Pt metal. For the methanol oxidation reaction, PtRu NDs showed the highest forward peak current density (2.66 mA cm-2 , 1.14 A/mgPt ) and the best stability compared to those of pure-Pt nanodendrites (pure-Pt NDs), commercial PtRu/C and commercial Pt/C catalysts.

Glycosyl Cross-Coupling of Anomeric Nucleophiles: Scope, Mechanism, and Applications in the Synthesis of Aryl C-Glycosides.

Stereoselective manipulations at the C1 anomeric position of saccharides are one of the central goals of preparative carbohydrate chemistry. Historically, the majority of reactions forming a bond with anomeric carbon has focused on reactions of nucleophiles with saccharide donors equipped with a leaving group. Here, we describe a novel approach to stereoselective synthesis of C-aryl glycosides capitalizing on the highly stereospecific reaction of anomeric nucleophiles. First, methods for the preparation of anomeric stannanes have been developed and optimized to afford both anomers of common saccharides in high anomeric selectivities. We established that oligosaccharide stannanes could be prepared from monosaccharide stannanes via O-glycosylation with Schmidt-type donors, glycal epoxides, or under dehydrative conditions with C1 alcohols. Second, we identified a general set of catalytic conditions with Pd2(dba)3 (2.5 mol%) and a bulky ligand (JackiePhos, 10 mol%) controlling the ß-elimination pathway. We demonstrated that the glycosyl cross-coupling resulted in consistently high anomeric selectivities for both anomers with mono- and oligosaccharides, deoxysugars, saccharides with free hydroxyl groups, pyranose, and furanose substrates. The versatility of the glycosyl cross-coupling reaction was probed in the total synthesis of salmochelins (siderophores) and commercial anti-diabetic drugs (gliflozins). Combined experimental and computational studies revealed that the ß-elimination pathway is suppressed for biphenyl-type ligands due to the shielding of Pd(II) by sterically demanding JackiePhos, whereas smaller ligands, which allow for the formation of a Pd-F complex, predominantly result in a glycal product. Similar steric effects account for the diminished rates of cross-couplings of 1,2-cis C1-stannanes with aryl halides. DFT calculations also revealed that the transmetalation occurs via a cyclic transition state with retention of configuration at the anomeric position. Taken together, facile access to both anomers of various glycoside nucleophiles, a broad reaction scope, and uniformly high transfer of anomeric configuration make the glycosyl cross-coupling reaction a practical tool for the synthesis of bioactive natural products, drug candidates, allowing for late-stage glycodiversification studies with small molecules and biologics.

Highly Stereospecific Cross-Coupling Reactions of Anomeric Stannanes for the Synthesis of C-Aryl Glycosides.

We demonstrate that configurationally stable anomeric stannanes undergo a stereospecific cross-coupling reaction with aromatic halides in the presence of a palladium catalyst with exceptionally high levels of stereocontrol. In addition to a broad substrate scope (>40 examples), this reaction eliminates critical problems inherent to nucleophilic displacement methods and is applicable to (hetero)aromatics, peptides, pharmaceuticals, common monosaccharides, and saccharides containing free hydroxyl groups.