Rhodium-Catalyzed Highly Enantioselective Hydroboration of Acyclic Tetrasubstituted Alkenes Directed by an Amide.

Although progress has been made in enantioselective hydroboration of di- and trisubstituted alkenes over the past decades, enantioselective hydroboration of tetrasubstituted alkenes with high diastereo- and enantioselectivities continues as an unmet challenge since the 1950s due to its extremely low reactivity and the difficulties to simultaneously control the regio- and stereoselectivity of a tetrasubstituted alkene. Here, we report highly regio-, diastereo-, and enantioselective catalytic hydroboration of diverse acyclic tetrasubstituted alkenes. The delicate interplay of an electron-rich rhodium complex and coordination-assistance forms a highly adaptive catalyst that effectively overcomes the low reactivity and controls the stereoselectivity. The generality of the catalyst system is exemplified by its efficacy across various tetrasubstituted alkenes with diverse steric and electronic properties.

Genome-wide DNA methylation association study of recent and cumulative marijuana use in middle aged adults.

Marijuana is a widely used psychoactive substance in the US and medical and recreational legalization has risen over the past decade. Despite the growing number of individuals using marijuana, studies investigating the association between epigenetic factors and recent and cumulative marijuana use remain limited. We therefore investigated the association between recent and cumulative marijuana use and DNA methylation levels. Participants from the Coronary Artery Risk Development in Young Adults Study with whole blood collected at examination years (Y) 15 and Y20 were randomly selected to undergo DNA methylation profiling at both timepoints using the Illumina MethylationEPIC BeadChip. Recent use of marijuana was queried at each examination and used to estimate cumulative marijuana use from Y0 to Y15 and Y20. At Y15 (n = 1023), we observed 22 and 31 methylation markers associated (FDR P ≤ 0.05) with recent and cumulative marijuana use and 132 and 16 methylation markers at Y20 (n = 883), respectively. We replicated 8 previously reported methylation markers associated with marijuana use. We further identified 640 cis-meQTLs and 198 DMRs associated with recent and cumulative use at Y15 and Y20. Differentially methylated genes were statistically overrepresented in pathways relating to cellular proliferation, hormone signaling, and infections as well as schizophrenia, bipolar disorder, and substance-related disorders. We identified numerous methylation markers, pathways, and diseases associated with recent and cumulative marijuana use in middle-aged adults, providing additional insight into the association between marijuana use and the epigenome. These results provide novel insights into the role marijuana has on the epigenome and related health conditions.

High-Resolution Rovibronic Cross Sections of the MgH+ Molecular Cation.

The high-resolution rovibronic line lists of the MgH+ molecular cation are presented in our work. The potential energy curves are calculated by the method of multireference configuration interaction and Davidson correction (MRCI+Q) with the spin-orbit coupling (SOC) effect. Spectroscopy constants are fitted and the results are in good agreement with experiments, ensuring the accuracy of the electronic structure. On account of potential energy curves and transition dipole moments, the Franck-Condon factors and Einstein coefficients of transition are obtained. These calculations are used to obtain an accurate partition functions and line lists for molecules. Using the partition functions and line lists, the absorption cross-sections under different temperatures and pressures were simulated. Our work could provide some theoretical insights into solar and cold planet spectrum.

Development and evaluation of a program based on a generative pre-trained transformer model from a public natural language processing platform for efficiency enhancement in post-procedural quality control of esophageal endoscopic submucosal dissection.

BACKGROUND: Post-procedural quality control of endoscopic submucosal dissection (ESD) is emphasized in guidelines. However, this process can be tedious and time-consuming. Recently, a pre-training model called generative pre-trained transformer (GPT) on a public natural language processing platform has emerged and garnered significant attention, whose capabilities align well with the post-procedural quality control process and have the potential to streamline it. Therefore, we developed a simple program utilizing this platform and evaluated its performance. METHODS: Esophageal ESDs were retrospectively included. The manual quality control process was performed and act as reference standard. GPT's prompt was optimized through multiple iterations. A Python program was developed to automatically submit prompt with pathological report of each ESD procedure and collect quality control information provided by GPT. Its performance on quality control was evaluated with accuracy, precision, recall, and F-1 score. RESULTS: 165 cases were involved into the dataset, of which 5 were utilized as the prompt optimization dataset and 160 as the validation dataset. Definitive prompt was achieved through seven iterations. Time spent on the validation dataset by GPT was 13.47 ± 2.43 min. Accuracies of pathological diagnosis, invasion depth, horizontal margin, vertical margin, vascular invasion, and lymphatic invasion of the quality control program were (0.940, 0.952) (95% CI), (0.925, 0.945) (95% CI), 0.931, 1.0, and 1.0, respectively. Precisions were (0.965, 0.969) (95% CI), (0.934, 0.954) (95% CI), and 0.957 for pathological diagnosis, invasion depth, and horizontal margin, respectively. Recalls were (0.940, 0.952) (95% CI), (0.925, 0.945) (95% CI), and 0.931 for factors as mentioned, respectively. F1-score were (0.945, 0.957) (95% CI), (0.928, 0.948) (95% CI), and 0.941 for factors as mentioned, respectively. CONCLUSIONS: This quality control program was qualified of post-procedural quality control of esophageal ESDs. GPT can be easily applied to this quality control process and reduce workload of the endoscopists.

The development of commitment: Attention for intention.

Adhering to a partially defined plan requires an intentional commitment that curbs distracting desires conflicting with the planned course of action, enabling humans to act coherently over time. Two studies (N = 50, 27 girls, ages 5-6, Han Chinese, in Hangzhou, China, 2022.02-2022.03) explored the development of commitment to partial plans in a sequential decision-making task and the underlying cognitive capacity focusing on its correlation to attentional control. Results suggest that only 6-year-olds committed to partial plans (d = .51), and children's commitment ratio was positively correlated with the use of proactive control (r = .40). These findings indicate that intentional commitment does not develop simultaneously with intention understanding, but rather matures gradually with the development of attentional control.

Pancreatic Neuroendocrine Tumors: Signaling Pathways and Epigenetic Regulation.

Pancreatic neuroendocrine tumors (PNETs) are characterized by dysregulated signaling pathways that are crucial for tumor formation and progression. The efficacy of traditional therapies is limited, particularly in the treatment of PNETs at an advanced stage. Epigenetic alterations profoundly impact the activity of signaling pathways in cancer development, offering potential opportunities for drug development. There is currently a lack of extensive research on epigenetic regulation in PNETs. To fill this gap, we first summarize major signaling events that are involved in PNET development. Then, we discuss the epigenetic regulation of these signaling pathways in the context of both PNETs and commonly occurring-and therefore more extensively studied-malignancies. Finally, we will offer a perspective on the future research direction of the PNET epigenome and its potential applications in patient care.

Precisely Engineering Asymmetric Atomic CoN4 by Electron Donating and Extracting for Oxygen Reduction Reaction.

The development of nonpyrolytic catalysts featuring precisely defined active sites represents an effective strategy for investigating the fundamental relationship between the catalytic activity of oxygen reduction reaction (ORR) catalysts and their local coordination environments. In this study, we have synthesized a series of model electrocatalysts with well-defined CoN4 centers and nonplanar symmetric coordination structures. These catalysts were prepared by a sequential process involving the chelation of cobalt salts and 1,10-phenanthroline-based ligands with various substituent groups (phen(X), where X=OH, CH3, H, Br, Cl) onto covalent triazine frameworks (CTFs). By modulating the electron-donating or electron-withdrawing properties of the substituent groups on the phen-based ligands, the electron density surrounding the CoN4 centers was effectively controlled. Our results demonstrated a direct correlation between the catalytic activity of the CoN4 centers and the electron-donating ability of the substituent group on the phenanthroline ligands. Notably, the catalyst denoted as BCTF-Co-phen(OH), featuring the electron-donating OH group, exhibited the highest ORR catalytic activity. This custom-crafted catalyst achieved a remarkable half-wave potential of up to 0.80 V vs. RHE and an impressive turnover frequency (TOF) value of 47.4×10-3 Hz at 0.80 V vs. RHE in an alkaline environment.

Association of Cardiovascular Health Through Young Adulthood With Genome-Wide DNA Methylation Patterns in Midlife: The CARDIA Study.

BACKGROUND: Cardiovascular health (CVH) from young adulthood is strongly associated with an individual's future risk of cardiovascular disease (CVD) and total mortality. Defining epigenomic biomarkers of lifelong CVH exposure and understanding their roles in CVD development may help develop preventive and therapeutic strategies for CVD. METHODS: In 1085 CARDIA study (Coronary Artery Risk Development in Young Adults) participants, we defined a clinical cumulative CVH score that combines body mass index, blood pressure, total cholesterol, and fasting glucose measured longitudinally from young adulthood through middle age over 20 years (mean age, 25-45). Blood DNA methylation at >840 000 methylation markers was measured twice over 5 years (mean age, 40 and 45). Epigenome-wide association analyses on the cumulative CVH score were performed in CARDIA and compared in the FHS (Framingham Heart Study). We used penalized regression to build a methylation-based risk score to evaluate the risk of incident coronary artery calcification and clinical CVD events. RESULTS: We identified 45 methylation markers associated with cumulative CVH at false discovery rate <0.01 (P=4.7E-7-5.8E-17) in CARDIA and replicated in FHS. These associations were more pronounced with methylation measured at an older age. CPT1A, ABCG1, and SREBF1 appeared as the most prominent genes. The 45 methylation markers were mostly located in transcriptionally active chromatin and involved lipid metabolism, insulin secretion, and cytokine production pathways. Three methylation markers located in genes SARS1, SOCS3, and LINC-PINT statistically mediated 20.4% of the total effect between CVH and risk of incident coronary artery calcification. The methylation risk score added information and significantly (P=0.004) improved the discrimination capacity of coronary artery calcification status versus CVH score alone and showed association with risk of incident coronary artery calcification 5 to 10 years later independent of cumulative CVH score (odds ratio, 1.87; P=9.66E-09). The methylation risk score was also associated with incident clinical CVD in FHS (hazard ratio, 1.28; P=1.22E-05). CONCLUSIONS: Cumulative CVH from young adulthood contributes to midlife epigenetic programming over time. Our findings demonstrate the role of epigenetic markers in response to CVH changes and highlight the potential of epigenomic markers for precision CVD prevention, and earlier detection of subclinical CVD, as well.

Fabrication of Channeled and Three-Dimensional Electrodes for the Integrated Capture and Detection of Invasive Circulating Tumor Cells during Hematogenous Metastasis.

Hematogenous metastasis is the main route of cancer spreading, causing majority death of cancer patients. During this process, platelets in the blood are found increasingly essential to promote hematogenous metastasis by forming platelet-interacted circulating tumor cells (CTCs). Hence, we aim to fabricate an integrated method for the availability of capture and detection of such invasive CTCs. Specifically, a new form of channeled and conductive three-dimensional (3D) electrode is constructed by modifying a conductive layer and capture antibody on the templated and channeled poly(dimethylsiloxane) scaffold. The modified antibody enables the capture of the platelet-interacted CTC hybrid, while the conductive layer significantly facilitates electron transfer from electro-active signal molecules that are targeting platelets. Therefore, sensitive electrochemical detection of platelet-interacted CTCs has been realized. Efficient capture and sensitive detection have been demonstrated by this work. Additionally, dynamic analysis of patients' CTCs has also been conducted to provide accurate information about disease assessment and efficacy evaluation. The cut-off line was set as 5.15 nA based on the sample signals from healthy volunteers. Thus, stage III cancer patients with high risk of hematogenous metastasis have been identified. Together, this work shows the development of a new strategy for simultaneous capture and detection of the invasive CTC subtype form patient blood, which favors precise monitoring of hematogenous metastasis.

Bio-Inspired Electrochemical Detection of Nitric Oxide Promoted by Coordinating the Histamine-Iron Phthalocyanine Catalytic Center on Microelectrode.

Biomimetic structures to fabricate bioelectronic interfaces that allow sensors to electrically communicate with electrodes have potential applications in the development of biosensors. Herein, inspired by the structure feature of nitric oxide (NO) sensory protein, we constructed a biomimetically catalytic center, the histamine coordinated iron phthalocyanine (FePc), for efficient and sensitive detection of NO. In specific, NO is recognized by axial tethered FePc, and the oxidative signal of NO on FePc is converted into output signal through electrocatalytic oxidation. Based on the fabricated catalytic structure on the carbon fiber electrode, on one hand, the macrocyclic π system of FePc enabled a rapid redox process, which facilitates electron transfer, thereby greatly improving sensitivity. On the other hand, by coordination with histamine on the electrode surface, FePc can enhance the electrochemical oxidation activity toward NO and promote catalytic detection, which have been revealed by electrochemical characterizations and density functional theory theoretical calculations. The designed electrochemical microsensor exhibits a low limit of detection (0.03 nM) and shows a wide detection range (0.1 nM-2 µM). In addition, the electrochemical microsensor has been successfully used for real-time monitoring of NO release by live cells. So, this work shows a new strategy for the design of bio-inspired electrochemical microsensors that may provide a potential analytical tool for tracing biological signal molecules with enzyme-free biomimetically catalytic centers.

Epigenetic Age Acceleration Reflects Long-Term Cardiovascular Health.

[Figure: see text].

Theoretic Study of Sulfur-Doped Graphdiynes by X-ray Spectroscopy.

Sulfur-doped graphdiyne at different sites has a tremendous impact on its electronic structure and properties. Due to the large number of S-doping sites, there is no comprehensive and systematic experimental and theoretical study regarding the identification of S-doped graphdiyne configurations. In this paper, X-ray photoelectron (XPS) and near-edge X-ray absorption fine structure (NEXAFS) spectra as well as geometries of 10 sulfur-doped graphdiyne molecules have been simulated at the density functional theory (DFT) level. Different types of carbon spectra were theoretically modeled to analyze the contribution of the spectra. Calculated results show that the NEXAFS spectra exhibit a clear dependence on the local structure. The theoretically simulated XPS spectra are in good agreement with the experimental spectra. The XPS spectra combined with the NEXAFS spectra can provide effective information for identifying the 10 S-doped conformations. Our research results provide further theoretical prediction and guidance for the experimental synthesis of S-doped graphdiyne, which solves the difficult problem of identification of S-doped carbon-based materials.

Investigation on external quantum efficiency droops and inactivation efficiencies of AlGaN-based ultraviolet-c LEDs at 265-285 nm.

The temperature-dependent external quantum efficiency (EQE) droops of 265 nm, 275 nm, 280 nm, and 285 nm AlGaN-based ultraviolet-c light-emitting diodes (UVC-LEDs) differed in Al contents have been comprehensively investigated. The modifiedABCmodel (R = An+Bn2+Cn3) with the current-leakage related term,f(n)= Dn4, has been employed to analyze the recombination mechanisms in these UVC-LED samples. Experimental results reveal that, at relatively low electrical-current levels, the contribution of Shockley-Read-Hall (SRH) recombination exceeds those of the Auger recombination and carrier leakage. At relatively high electrical-current levels, the Auger recombination and carrier leakage jointly dominate the EQE droop phenomenon. Moreover, the inactivation efficiencies of 222 nm excimer lamp, 254 nm portable Mercury lamp, 265 nm, 280 nm, and 285 nm UVC-LED arrays in the inactivation ofEscherichia colihave been experimentally investigated, which could provide a technical reference for fighting against the new COVID-19.

Potential rules for stable transition metal hexafluorides with high oxidation states under high pressures.

High pressure is a powerful tool in material sciences which can lead to the discovery of novel inorganic species in high oxidation states. Based on the prediction of the stability of PdF6 with a high Pd oxidation state of +6, we propose three potential guiding rules for finding stable transition metal (TM) fluorides with high +6 oxidation states: (1) the existence of a large (>7 eV) valence orbitals energy differences of atoms between the TM d orbital and the F 2p orbital; (2) an appropriate number of valence electrons within the range of 6-11; and (3) suitable electronegativity values less than 2.3 on the Pauli scale. More importantly, by synergistically invoking all of these rules, we predict, by combining a particle swarm optimization algorithm with first-principles calculation on the phase stabilities of the various TM-F compounds, a collection of new TMF6 species with the space group Pnma that have a +6 oxidation state. Subsequently, we develop an understanding of the high +6 oxidation state for the TM elements. These findings are expected to play a crucial role in the predictive discoveries of new fluorides with high oxidation states of +6.

A chemically stabilized sulfur cathode for lean electrolyte lithium sulfur batteries.

Lithium sulfur batteries (LSBs) are promising next-generation rechargeable batteries due to the high gravimetric energy, low cost, abundance, nontoxicity, and high sustainability of sulfur. However, the dissolution of high-order polysulfide in electrolytes and low Coulombic efficiency of Li anode require excess electrolytes and Li metal, which significantly reduce the energy density of LSBs. Quasi-solid-state LSBs, where sulfur is encapsulated in the micropores of carbon matrix and sealed by solid electrolyte interphase, can operate under lean electrolyte conditions, but a low sulfur loading in carbon matrix (<40 wt %) and low sulfur unitization (<70%) still limit the energy density in a cell level. Here, we significantly increase the sulfur loading in carbon to 60 wt % and sulfur utilization to ∼87% by dispersing sulfur in an oxygen-rich dense carbon host at a molecular level through strong chemical interactions of C-S and O-S. In an all-fluorinated organic lean electrolyte, the C/S cathode experiences a solid-state lithiation/delithiation reaction after the formation of solid electrolyte interphase in the first deep lithiation, completely avoiding the shuttle reaction. The chemically stabilized C/S composite retains a high reversible capacity of 541 mAh⋅g-1 (based on the total weight of the C/S composite) for 200 cycles under lean electrolyte conditions, corresponding to a high energy density of 974 Wh⋅kg-1 The superior electrochemical performance of the chemical bonding-stabilized C/S composite renders it a promising cathode material for high-energy and long-cycle-life LSBs.

The significance of the best puncture side bone cement/vertebral volume ratio to prevent paravertebral vein leakage of bone cement during vertebroplasty: a retrospective study.

OBJECTIVES: To verify the clinical significance of the best puncture-side bone cement/vertebral volume ratio (PSBCV/VV%) and bone cement leakage in paravertebral veins during vertebroplasty. METHODS: This was a retrospective analysis of a total of 210 patients from September 2021 to December 2022, who were divided into an observation group (110 patients) and a control group (100 patients). In the observation group, patients' preoperative computed tomography (CT) data were imported into Mimics software, and the VV was calculated using the three-dimensional (3D) reconstruction function. Then, based on the best PSBCV/VV% of 13.68% determined in a previous study, the optimal PSBCV to be injected during vertebroplasty was calculated. In the control group, vertebroplasty was performed directly using the conventional method. The incidence of cement leakage into paravertebral veins was observed postoperatively in both groups. RESULTS: There were no statistically significant differences (P > 0.05) in the evaluated indicators between the two groups pre- or postoperatively, including the anterior vertebral margin height, mid-vertebral height, injured vertebral Cobb angle, visual analogue scale (VAS) score, and Oswestry Disability Index (ODI). Intragroup comparisons showed improvements in the anterior vertebral height, mid-vertebral height, injured vertebral Cobb angle, VAS score, and ODI after surgery compared with before surgery (P < 0.05). In the observation group, there were 3 cases of cement leakage into the paravertebral veins, for a leakage rate of 2.7%. In the control group, there were 11 cases of cement leakage into the paravertebral veins, for a leakage rate of 11%. The difference in the leakage rate between the two groups was statistically significant (P = 0.016). CONCLUSION: In vertebroplasty, preoperative VV calculations using Mimics software, combined with calculation of the PSBCV according to the best PSBCV/VV% (13.68%), can effectively prevent leakage of bone cement into paravertebral veins and further prevent serious life-threatening complications such as pulmonary embolism.

Antifungal activities of metconazole against the emerging wheat pathogen Fusarium pseudograminearum.

Fusarium crown rot of wheat is a serious fungal disease that occurs worldwide. The disease has been emerging in the major wheat-growing areas in China since 2010. Fusarium pseudogramineaum is the predominant causative pathogen of crown rot of wheat in China. The 14α-demethylation inhibitor (DMI) fungicide metconazole has been shown to be effective against Fusarium spp., but little is known about its specific activity against F. pseudogramineaum. Metconazole exhibited strong antifungal activities against all thirty-nine F. pseudogramineaum strains collected from the major wheat-growing areas in China. Metconazole inhibited mycelial growth and conidial germ tube elongation of F. pseudograminearum. Metconazole treatment significantly reduced the production of major toxins and the expression levels of toxin biosynthesis genes. Genome-wide transcriptional profiling of F. pseudograminearum in response to metconazole indicated that the expression of genes involved in ergosterol biosynthesis, including fungicide target genes (cyp51 genes), was significantly induced by metconazole. Nine ATP-binding cassette (ABC) transporter-encoding genes were significantly expressed in response to metconazole treatment. Reduced ergosterol production and antioxidant enzyme activities were observed after metconazole treatment. Greenhouse experiments indicated a significant reduction in crown rot occurrence in wheat after seed treatment with metconazole. This study evaluated the potential of metconazole to manage wheat crown rot and provides information to understand its antifungal activities and mechanism of action against F. pseudograminearum.

Antifungal activities of a novel triazole fungicide, mefentrifluconazole, against the major maize pathogen Fusarium verticillioides.

Fusarium ear rot (FER) is a serious fungal disease occurring the late growth stage of maize. FER not only reduces the yield of maize but also causes mycotoxin contamination, which affects the quality of maize and threatens human and animal health. Fusarium verticillioides is the predominant causative pathogen of FER worldwide. At present, there is no registered fungicide for use against maize FER in China. The novel isopropyl alcohol-triazole fungicide mefentrifluconazole (MFZ) has been shown to be effective against several Fusarium spp., but little is known about its specific activity against F. verticillioides. MFZ exhibited strong antifungal activities against 50 strains of F. verticillioides collected from the major maize-growing areas in China. MFZ inhibited mycelial growth, conidium production, germination and germ tube elongation of F. verticillioides. MFZ treatment significantly reduced fumonisin production and the expression levels of fumonisin biosynthetic genes. Genome-wide transcriptional profiling of F. verticillioides in response to MFZ indicated that the expression of genes involved in ergosterol biosynthesis, including fungicide target genes (cyp51 genes), was significantly downregulated by MFZ. MFZ treatment resulted in reduced ergosterol production and increased glycerol and malonaldehyde production as well as relative conductivity in F. verticillioides. A 2-year field experiment showed a significant reduction in FER severity in maize after spraying with MFZ at the tasseling stage. This study evaluated the potential of MFZ to control FER in maize and provides insights into its antifungal activities and mechanism of action against F. verticillioides.

Peptide Assembled in a Nano-confined Space as a Molecular Rectifier for the Availability of Ionic Current Modulation.

Bioinspired nanochannels have emerged as a powerful tool for bioengineering and biomedical research due to their robust mechanical and controllable chemical properties. Inspired by inward-rectifier potassium (K+) channels, herein, the charged peptide assembly has been introduced into a nano-confined space for the modulation of ion current rectification (ICR). Peptide-responsive reaction-triggered sequence changes can contribute to polarity conversion of the surface charge; therefore, ICR reversal (ICRR) is generated. Compared with other responsive elements, natural charged peptides show the merit of controllable charge polarity. By electrochemically monitoring the ICRR as an output signal, one can utilize the peptide assembly-mediated ICRR to construct an ionic sensory platform. In addition, a logic gate has been established to demonstrate the availability of an ionic sensory platform for inhibitor screening. As peptide nanoassemblies may also have various structures and functions due to their diverse properties, the ionic modulation system can provide alternatives for the assay of peptide-associated biotargets with biomedical applications.

Characterization and Anti-Aging Activity of Polysaccharides from Akebia trifoliata Fruit Separated by an Aqueous Two-Phase System.

Bioactive polysaccharides have numerous pharmacological effects that are beneficial to human health. Akebia trifoliata (Thunb.) Koidz. has great development prospects as a food resource with medicinal value. The polysaccharides (ATFP) were extracted from A. trifoliata fruit by an aqueous two-phase system. ATFP-3, purified with DEAE-52 and Sephadex G-200 from ATFP, was mainly composed of glucose (47.55%) and galactose (20.39%). Its hydroxyl radical scavenging rate was 89.30% at 1.60 mg/mL and its IC50 was 0.29 mg/mL. ATFP-3 significantly enhanced the survival rate of Caenorhabditis elegans under thermal or oxidative stress. Furthermore, ATFP-3 could prolong the lifespan of C. elegans and improve the activities of the antioxidant enzyme, while also decrease the accumulation of lipofuscin and the level of malondialdehyde (MDA) in aging worms. Thus, ATFP-3 has application potential in health benefits for humans.