Catalytic Asymmetric Dearomative [2 + 2] Photocycloaddition/Ring-Expansion Sequence of Indoles with Diversified Alkenes.

Developing novel strategies for catalytic asymmetric dearomatization (CADA) reactions is highly valuable. Visible light-mediated photocatalysis is demonstrated to be a powerful tool to activate aromatic compounds for further synthetic transformations. Herein, a catalytic asymmetric dearomative [2 + 2] photocycloaddition/ring-expansion sequence of indoles with simple alkenes was reported, providing a facile access to enantioenriched cyclopenta[b]indoles with good to high yields and enantioselectivities by means of chiral lanthanide photocatalysis. This protocol exhibited a broad substrate scope and good functional group tolerance, as well as potential applications in the synthesis of bioactive molecules. Mechanistic studies, including control experiments, UV-vis absorption spectroscopy, emission spectroscopy, and DFT calculations, were carried out, shedding insights into the reaction mechanism and the origin of enantioselectivity.

Large potential of strengthening the land carbon sink in China through anthropogenic interventions.

The terrestrial ecosystem in China mitigates 21%-45% of the national contemporary fossil fuel CO2 emissions every year. Maintaining and strengthening the land carbon sink is essential for reaching China's target of carbon neutrality. However, this sink is subject to large uncertainties due to the joint impacts of climate change, air pollution, and human activities. Here, we explore the potential of strengthening land carbon sink in China through anthropogenic interventions, including forestation, ozone reduction, and litter removal, taking advantage of a well-validated dynamic vegetation model and meteorological forcings from 16 climate models. Without anthropogenic interventions, considering Shared Socioeconomic Pathways (SSP) scenarios, the land sink is projected to be 0.26-0.56 Pg C a-1 at 2060, to which climate change contributes 0.06-0.13 Pg C a-1 and CO2 fertilization contributes 0.08-0.44 Pg C a-1 with the stronger effects for higher emission scenarios. With anthropogenic interventions, under a close-to-neutral emission scenario (SSP1-2.6), the land sink becomes 0.47-0.57 Pg C a-1 at 2060, including the contributions of 0.12 Pg C a-1 by conservative forestation, 0.07 Pg C a-1 by ozone pollution control, and 0.06-0.16 Pg C a-1 by 20% litter removal over planted forest. This sink can mitigate 90%-110% of the residue anthropogenic carbon emissions in 2060, providing a solid foundation for the carbon neutrality in China.

How Molecular Orientation Affects the Static Permittivity Profile of the Polar and Nonpolar Liquid-Liquid Interface.

The dielectric permittivity across the liquid-liquid interface presents an intrinsic response, with respect to the instantaneous interface reference. We hypothesize that dielectric responses across the nonpolar and polar liquid-liquid interfaces have different behaviors and underlying mechanisms. Molecular dynamics simulations were used to compare and contrast the dielectric response of a nonpolar (1,2-dichloroethane/water) and a polar (1-octanol/water) liquid-liquid interface system. We found that the enhanced dielectric permittivity at the nonpolar interface is attributed to the increased water dipole orientation and polarization density. In the case of the polar interface, strong association of the immiscible solvents inhibits the molecular dipole orientation, counteracting the effect from the enhanced surface water polarization density and resulting in a standard dielectric response. Detailed knowledge of the hydrogen bond networks and molecular dipole orientation with respect to the specific instantaneous interfacial and bulk regions reveals the effect of molecular proximity and the interaction with the opposing interfacial molecules on the mechanism of the dielectric permittivity response across the liquid-liquid interface phase boundary.

Crystallization and electrochemical properties of KxV2O5 nano-ribbons obtained via a solvothermal process as a promising cathode for PIBs.

In this research, a series of K+-intercalated quasi-1D vanadium-based nano-ribbons (KxV2O5 NRs) were synthesized via a facile solvothermal method. The solvation and reductive effects of vanadium oxide precursors (V2O5 powder) on the crystallization and growth of KxV2O5 NRs were studied. Besides, post-heat treatment was performed to improve the crystallinity of KxV2O5 NRs. These KxV2O5 NRs were adopted as active cathodes for potassium-ion batteries (PIBs), whose K+ storage properties were systematically evaluated using various electrochemical methods. The relationship among the morphology, crystallinity, working voltage window and electrochemical reversible K+ storage performance of KxV2O5 NRs was studied and established. Results reveal that KxV2O5-HG, which was prepared via a solvothermal reaction involving a solvation process (using H2O2) and a proper reducing condition (proper dose of glucose) with V2O5 powder as the raw material, would be more beneficial for the reversible storage of K+ when used as the cathode for PIBs compared to other contrast samples. In addition, the enhanced crystallinity and slightly broadened working voltage window of KxV2O5-HG could hinder its long-term cycling stability upon repeated K+ insertions/extractions.

Nickel-Catalyzed Enantioconvergent Allenylic Amination of Allenols Activated by Hydrogen-Bonding Interaction with Methanol.

The ubiquitous nature of amines in drug compounds, bioactive molecules and natural products has fueled intense interest in their synthesis. Herein, we introduce a nickel-catalyzed enantioconvergent allenylic amination of methanol-activated allenols. This protocol affords a diverse array of functionalized allenylic amines in high yields and with excellent enantioselectivities. The synthetic potential of this method is demonstrated by employing bioactive amines as nucleophiles and conducting gram-scale reactions. Furthermore, mechanistic investigations and DFT calculations elucidate the role of methanol as an activator in the nickel-catalyzed reaction, facilitating the oxidative addition of the C-O bond of allenols through hydrogen-bonding interactions. The remarkable outcomes arise from a rapid racemization of allenols enabled by the nickel catalyst and from highly enantioselective dynamic kinetic asymmetric transformation of η3-alkadienylnickel intermediates.

Empagliflozin rescues pro-arrhythmic and Ca2+ homeostatic effects of transverse aortic constriction in intact murine hearts.

We explored physiological effects of the sodium-glucose co-transporter-2 inhibitor empagliflozin on intact experimentally hypertrophic murine hearts following transverse aortic constriction (TAC). Postoperative drug (2-6 weeks) challenge resulted in reduced late Na+ currents, and increased phosphorylated (p-)CaMK-II and Nav1.5 but not total (t)-CaMK-II, and Na+/Ca2+ exchanger expression, confirming previous cardiomyocyte-level reports. It rescued TAC-induced reductions in echocardiographic ejection fraction and fractional shortening, and diastolic anterior and posterior wall thickening. Dual voltage- and Ca2+-optical mapping of Langendorff-perfused hearts demonstrated that empagliflozin rescued TAC-induced increases in action potential durations at 80% recovery (APD80), Ca2+ transient peak signals and durations at 80% recovery (CaTD80), times to peak Ca2+ (TTP100) and Ca2+ decay constants (Decay30-90) during regular 10-Hz stimulation, and Ca2+ transient alternans with shortening cycle length. Isoproterenol shortened APD80 in sham-operated and TAC-only hearts, shortening CaTD80 and Decay30-90 but sparing TTP100 and Ca2+ transient alternans in all groups. All groups showed similar APD80, and TAC-only hearts showed greater CaTD80, heterogeneities following isoproterenol challenge. Empagliflozin abolished or reduced ventricular tachycardia and premature ventricular contractions and associated re-entrant conduction patterns, in isoproterenol-challenged TAC-operated hearts following successive burst pacing episodes. Empagliflozin thus rescues TAC-induced ventricular hypertrophy and systolic functional, Ca2+ homeostatic, and pro-arrhythmogenic changes in intact hearts.

Local Management for Diabetic Foot Ulcers: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: This study evaluated the efficacy of various local management strategies for diabetic foot ulcers (DFUs). BACKGROUND: Several surgical and non-surgical local interventional approaches are available for the treatment of DFUs. The comparative effectiveness of different treatments is unknown, and it remains unclear which approach is the optimal choice for DFUs treatment due to limited direct comparisons. METHODS: We did a systematic review and meta-analysis to select the optimal approach to DFUs local management. We searched Medline, Embase, Web of Science, and ClinicalTrials.gov from inception to September 1, 2023, to identify relevant randomized controlled trials (RCTs). We analysed data by pairwise meta-analyses with a random-effects model. A network meta-analysis using the surface under the cumulative ranking curve (SUCRA) was performed to evaluate the comparative efficacy of different interventional approaches in the early (within 12 wk) and late stages (over 12 wk). RESULTS: 141 RCTs involving 14076 patients and exploring 14 interventional strategies were eligible for inclusion. Most studies (102/141) had at least one risk-of-bias dimension. Good consistency was observed during the analysis. Local pairwise comparisons demonstrated obvious differences in the early-stage healing rate and early- and late-stage healing times, while no significant difference in the late-stage healing rate or adverse events were noted. SUCRAs identified the standard of care (SOC) + decellularized dressing (DD), off-loading (OL), and autogenous graft (AG) as the three most effective interventions within 12 weeks for both healing rate (97%, mean rank: 1.4; 90%, mean rank: 2.3; 80.8%, mean rank: 3.5, respectively) and healing time (96.7%, mean rank: 1.4; 83.0%, mean rank: 3.0; 76.8%, mean rank: 3.8, respectively). After 12 weeks, local drug therapy (LDT) (89.5%, mean rank: 2.4) and OL (82.4%, mean rank: 3.3) ranked the highest for healing rate, and OL (100.0%, mean rank: 1.0) for healing time. With respect to adverse events, moderate and high risks were detected in the SOC + DD (53.7%, mean rank: 7.0) and OL (24.4%, mean rank: 10.8) groups, respectively. CONCLUSION: The findings suggest that OL provided considerable benefits for DFU healing in both the early and late stages, but the high risk of adverse events warrants caution. SOC+DD may be the preferred option in the early stages, with an acceptable risk of adverse events.

Oropharyngeal cancer and human papillomavirus: a visualization based on bibliometric analysis and topic modeling.

Objectives: The incidence of oropharyngeal cancer (OPC) is increasing. This study used bibliometric analysis and topic modeling to explore the research trends and advancements in this disease over the past 10 years, providing valuable insights to guide future investigations. Methods: 7,355 English articles from 2013 to 2022 were retrieved from the Web of Science Core Collection for bibliometric analysis. Topic modeling was applied to 1,681 articles from high-impact journals, followed by an assessment of topic significance ranking (TSR). Medical Subject Headings (MeSH) terms were extracted using R and Python, followed by an analysis of the terms associated with each topic and on an annual basis. Additionally, genes were extracted and the number of genes appearing each year and the newly emerged genes were counted. Results: The bibliometric analysis suggested that the United States and several European countries hold pivotal positions in research. Current research is focused on refining treatments, staging and stratification. Topic modeling revealed 12 topics, emphasizing human papillomavirus (HPV) and side effect reduction. MeSH analysis revealed a growing emphasis on prognosis and quality of life. No new MeSH terms emerged after 2018, suggesting that the existing terms have covered most of the core concepts within the field of oropharyngeal cancers. Gene analysis identified TP53 and EGFR as the most extensively studied genes, with no novel genes discovered after 2019. However, CD69 and CXCL9 emerged as new genes of interest in 2019, reflecting recent research trends and directions. Conclusion: HPV-positive oropharyngeal cancer research, particularly treatment de-escalation, has gained significant attention. However, there are still challenges in diagnosis and treatment that need to be addressed. In the future, more research will focus on this issue, indicating that this field still holds potential as a research hotspot.

Beneficial In Vitro Effects of Polysaccharide and Non-Polysaccharide Components of Dendrobium huoshanense on Gut Microbiota of Rats with Type 1 Diabetes as Opposed to Metformin.

The extract of Dendrobium huoshanense, a traditional Chinese medicinal and food homologous plant belonging to the family Orchidaceae, was previously reported to have hypoglycemic and antioxidant effects. In this study, the direct effects of polysaccharide (DHP) and non-polysaccharide (NDHP) components of D. huoshanense, as well as its water extract (DHWE) were compared with that of metformin (an antidiabetic drug) on the gut microbiota (collected from fecal flora) of rats with streptozotocin-induced type 1 diabetes (T1D) using an in vitro fermentation method. The results showed that DHWE, DHP, and NDHP reduced pH and increased bacterial proliferation and short-chain fatty acid (SCFA) content in fermentation broth. DHWE, DHP, NDHP and metformin promoted the production of acetic and propionic acid, acetic acid, propionic acid and butyric acid, and propionic acid, respectively. DHWE, DHP, and NDHP reduced the abundance of Proteobacteria (subdominant pathogenic bacteria) and increased the abundance of Firmicutes (dominant beneficial gut bacteria). NDHP also reduced the abundance of Bacteroidetes (beneficial and conditional pathogenic). Metformin increased the abundance of Proteobacteria and reduced the abundance of Firmicutes and Bacteroidetes. At the genus level, NDHP promoted the proliferation of Megamonas and Megasphaera and decreased harmful bacteria (e.g., Klebsiella), and DHP increased the abundance of Prevotellaceae (opportunistic and usually harmless). By contrast, metformin increased the abundance of harmful bacteria (e.g., Citrobacter) and reduced the abundance of beneficial bacteria (e.g., Oscillospira). Our study indicates that DHWE, DHP, and NDHP are potentially more beneficial than metformin on the gut microbiota of T1D rats in vitro.

Structural basis for odorant recognition of the insect odorant receptor OR-Orco heterocomplex.

Insects detect and discriminate a diverse array of chemicals using odorant receptors (ORs), which are ligand-gated ion channels comprising a divergent odorant-sensing OR and a conserved odorant receptor co-receptor (Orco). In this work, we report structures of the ApOR5-Orco heterocomplex from the pea aphid Acyrthosiphon pisum alone and bound to its known activating ligand, geranyl acetate. In these structures, three ApOrco subunits serve as scaffold components that cannot bind the ligand and remain relatively unchanged. Upon ligand binding, the pore-forming helix S7b of ApOR5 shifts outward from the central pore axis, causing an asymmetrical pore opening for ion influx. Our study provides insights into odorant recognition and channel gating of the OR-Orco heterocomplex and offers structural resources to support development of innovative insecticides and repellents for pest control.

Efficient Genetic Transformation and Suicide Plasmid-mediated Genome Editing System for Non-model Microorganism Erwinia persicina.

Erwinia persicina is a gram-negative bacterium that causes diseases in plants. Recently, E. persicina BST187 was shown to exhibit broad-spectrum antibacterial activity due to its inhibitory effects on bacterial acetyl-CoA carboxylase, demonstrating promising potential as a biological control agent. However, the lack of suitable genetic manipulation techniques limits its exploitation and industrial application. Here, we developed an efficient transformation system for E. persicina. Using pET28a as the starting vector, the expression cassette of the red fluorescent protein-encoding gene with the strong promoter J23119 was constructed and transformed into BST187 competent cells to verify the overexpression system. Moreover, suicide plasmid-mediated genome editing systems was developed, and lacZ was knocked out of BST187 genome by parental conjugation transfer using the recombinant suicide vector pKNOCK-sacB-km-lacZ. Therefore, both the transformation and suicide plasmid-mediated genome editing system will greatly facilitate genetic manipulations in E. persicina and promote its development and application. Key features • Our studies establish a genetic manipulation system for Erwinia persicina, providing a versatile tool for studying the gene function of non-model microorganisms. • Requires approximately 6-10 days to complete modification of a chromosome locus.

PACSIN1 promotes immunosuppression in gastric cancer by degrading MHC-I.

Gastric cancer (GC) is a common gastrointestinal system malignancy. PACSIN1 functions as an oncogene in various cancers. This study aims to investigate the potential of PACSIN1 as a target in GC treatment. Gene expression is determined by RT-qPCR, immunofluorescence staining, and immunohistochemistry assay. FISH is performed to determine the colocalization of PACSIN1 and the major histocompatibility complex (MHC-I). Cytokine release and cell functions are analyzed by flow cytometry. In vivo assays are also conducted. Histological analysis is performed using H&E staining. The results show that PACSIN1 is overexpressed in GC patients, especially in those with immunologically-cold tumors. A high level of PACSIN1 is associated with poor prognosis. PACSIN1 deficiency inhibits autophagy but increases antigen presentation in GC cells. Moreover, PACSIN1 deficiency inhibits the lysosomal fusion and selective autophagy of MHC-I, increases CD8 + T-cell infiltration, and suppresses tumor growth and liver metastasis in vivo. Additionally, PACSIN1 knockout enhances the chemosensitivity of cells to immune checkpoint blockade. In summary, PACSIN1 mediates lysosomal fusion and selective autophagy of MHC-I and suppresses antigen presentation and CD8 + T-cell infiltration, thus inhibiting antitumor immunity in GC.

Photoinduced Decatungstate Anion-Catalyzed 1,4-Difunctionalization of 1,3-Butadienes via C-H Activation.

This paper outlines an innovative three-component coupling strategy for the 1,4-difunctionalization of 1,3-butadiene, utilizing sodium decatungstate (NaDT) as a hydrogen atom transfer (HAT) photocatalyst. The photoinduced process efficiently generates homoallylic amino acid esters with 100% atom economy, employing readily available components under mild reaction conditions. This light-induced protocol eliminates the need for an additional transition metal catalysts, additives, or equivalent reducing agents. The study explored various C(sp3)-H bearing partners, butadienes, and α-iminoesters, demonstrating the versatility and synthetic utility of this method.

Inorganic Composition Modulation of Solid Electrolyte Interphase for Fast Charging Lithium Metal Batteries.

The solid electrolyte interphase (SEI) with lithium fluoride (LiF) is critical to the performance of lithium metal batteries (LMBs) due to its high stability and mechanical properties. However, the low Li ion conductivity of LiF impedes the rapid diffusion of Li ions in the SEI, which leads to localized Li ion oversaturation dendritic deposition and hinders the practical applications of LMBs at high-current regions (>3 C). To address this issue, a fluorophosphated SEI rich with fast ion-diffusing inorganic grain boundaries (LiF/Li3P) is introduced. By utilizing a sol electrolyte that contains highly dispersed porous LiF nanoparticles modified with phosphorus-containing functional groups, a fluorophosphated SEI is constructed and the presence of electrochemically active Li within these fast ion-diffusing grain boundaries (GBs-Li) that are non-nucleated is demonstrated, ensuring the stability of the Li || NCM811 cell for over 1000 cycles at fast-charging rates of 5 C (11 mA cm-2). Additionally, a practical, long cycling, and intrinsically safe LMB pouch cell with high energy density (400 Wh kg-1) is fabricated. The work reveals how SEI components and structure design can enable fast-charging LMBs.

Multi-Type Stochastic Resonances for Noise-Enhanced Mechanical, Optical, and Acoustic Sensing.

Stochastic resonance (SR) typically manifests in nonlinear systems, wherein the detection of a weak signal is bolstered by the addition of noise. Since its first discovery in a study of ice ages on Earth, various types of SRs have been observed in biological and physical systems and have been implemented in sensors to benefit from noise. However, a universally designed sensor architecture capable of accommodating different types of SRs has not been proposed, and the widespread applications of SRs in daily environments have not yet been demonstrated. Here, we propose a sensor architecture to simultaneously realize multi-type SRs and demonstrate their wide applications in mechanical, optical, and acoustic sensing domains. In particular, we find the coexistence of excitable SR and bistable SR in a sensor architecture composed of wirelessly coupled inductor-capacitor resonators connected to a nonlinearly saturable amplifier. In both types of SRs, adding noise to the system leads to a characteristic noise-enhanced signal-to-noise ratio (SNR). We further validate our findings through mechanical, optical, and acoustic sensing experiments and obtain noise-enhanced SNR by 9 dB, 3 dB, and 7 dB, respectively, compared to the standard methods devoid of SR integration. Our findings provide a general strategy to design various types of SRs and pave the way for the development of a distinctive class of sensors leveraging environmental noise, with potential applications ranging from biomedical devices to ambient sensing.

Proline inhibits postharvest physiological deterioration of cassava by improving antioxidant capacity.

Cassava (Manihot esculenta Crantz), a crucial global tuber crop, encounters significant economic losses attributed to postharvest physiological deterioration (PPD). The PPD phenomenon in cassava is closely related to the accumulation of reactive oxygen species (ROS), and amino acids play a pivotal role in regulating signaling pathways and eliminating ROS. In this study, the storage performance of eight cassava varieties were conducted. Cassava cultivar SC5 showed the best storage performance among the eight cassava varieties, but the edible cassava cultivar SC9 performed much worse. Comparative analysis of free amino acids was conducted in eight cassava varieties, revealing changes in proline, aspartic acid, histidine, glutamic acid, threonine, and serine. Exogenous supplementation of these six amino acids was performed to inhibit PPD of SC9. Proline was confirmed as the key amino acid for inhibiting PPD. Treatment with optimal exogenous proline of 5 g/L resulted in a 17.9% decrease in the deterioration rate compared to untreated cassava. Accompanied by a decrease in H2O2 content and an increase in catalase, superoxide dismutase and ascorbate peroxidase activity. Proline treatment proved to be an effective approach to alleviate cell oxidative damage, inhibit PPD in cassava, and prolong shelf life.

PFKFB3 controls acinar IP3R-mediated Ca2+ overload to regulate acute pancreatitis severity.

Acute pancreatitis (AP) is among the most common hospital gastrointestinal diagnoses; understanding the mechanisms underlying the severity of AP is critical for development of new treatment options for this disease. Here, we evaluate the biological function of phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) in AP pathogenesis in 2 independent genetically engineered mouse models of AP. PFKFB3 was elevated in AP and severe AP (SAP), and KO of Pfkfb3 abrogated the severity of alcoholic SAP (FAEE-SAP). Using a combination of genetic, pharmacological, and molecular studies, we defined the interaction of PFKFB3 with inositol 1,4,5-trisphosphate receptor (IP3R) as a key event mediating this phenomenon. Further analysis demonstrated that the interaction between PFKFB3 and IP3R promotes FAEE-SAP severity by altering intracellular calcium homeostasis in acinar cells. Together, our results support a PFKFB3-driven mechanism controlling AP pathobiology and define this enzyme as a therapeutic target to ameliorate the severity of this condition.

Rational modification of melatonin for broad-spectrum antifungal agents discovery.

Natural products, known for their environmental safety, are regarded as a significant basis for the modification and advancement of fungicides. Melatonin, as a low-cost natural indole, exhibits diverse biological functions, including antifungal activity. However, its potential as an antifungal agent has not been fully explored. In this study, a series of melatonin derivatives targeting the mitogen-activated protein kinase (Mps1) protein of fungal pathogens were synthesized based on properties of melatonin, among which the trifluoromethyl-substituted derivative Mt-23 exhibited antifungal activity against seven plant pathogenic fungi, and effectively reduced the severity of crop diseases, including rice blast, Fusarium head blight of wheat and gray mold of tomato. In particular, its EC50 (5.4 µM) against the rice blast fungus Magnaporthe oryzae is only one-fourth that of isoprothiolane (22 µM), a commercial fungicide. Comparative analyzes revealed that Mt-23 simultaneously targets the conserved protein kinase Mps1 and lipid protein Cap20. Surface plasmon resonance assays showed that Mt-23 directly binds to Mps1 and Cap20. In this study, we provide a strategy for developing antifungal agents by modifying melatonin, and the resultant melatonin derivative Mt-23 is a commercially valuable, eco-friendly and broad-spectrum antifungal agent to combat crop disease.

Drivers of natural gas use in U.S. residential buildings.

Natural gas is the primary fuel used in U.S. residences, yet little is known about its consumption patterns and drivers. We use daily county-level gas consumption data to assess the spatial patterns of the relationships and the sensitivities of gas consumption to outdoor air temperature across U.S. households. We fitted linear-plus-plateau functions to daily gas consumption data in 1000 counties, and derived two key coefficients: the heating temperature threshold (Tcrit) and the gas consumption rate change per 1°C temperature drop (Slope). We identified the main predictors of Tcrit and Slope (like income, employment rate, and building type) using interpretable machine learning models built on census data. Finally, we estimated a potential 2.47 million MtCO2 annual emission reduction in U.S. residences by gas savings due to household insulation improvements and hypothetical behavioral change toward reduced consumption by adopting a 1°C lower Tcrit than the current value.