Pro-aromaticity Enabled Dealkenylative Functionalizations via Photo-Excitation and Oxidation.

A general and practical approach for diverse dealkenylative functionalization of olefin-containing substrates has been developed through the one-pot formation and utilization of pro-aromatic 1,4-dihydropyridazines using tetrazine as the key cycloaddition reagent. Triggered by either excitation or oxidation, the targeted C-C bonds in the 1,4-dihydropyridazine intermediates could be readily cleaved to generate alkyl radicals for subsequent transformations. Diverse carbon-carbon and carbon-hetero bond forming protocols, including Giese-type addition, hydrazination, borylation, Minisci-type alkylation, copper-catalyzed NH alkylation, acylation, alkynylation, cyanation, and azidation, are achieved in a highly modular fashion.

Loss of Hepatic Angiotensinogen Attenuates Sepsis-Induced Myocardial Dysfunction.

[Figure: see text].

Enantioselective Total Syntheses of Grayanane Diterpenoids and (+)-Kalmanol: Evolution of the Bridgehead Carbocation-Based Cyclization and Late-Stage Functional Group Manipulation Strategies.

Grayanane diterpenoids contain over 300 highly oxidized and structurally complex members, many of which possess important biological activities. Full details are provided for the development of the concise, enantioselective and divergent total syntheses of grayanane diterpenoids and (+)-kalmanol. The unique 7-endo-trig cyclization based on a bridgehead carbocation was designed and implemented to construct the 5/7/6/5 tetracyclic skeleton, demonstrating the practical value of the bridgehead carbocation-based cyclization strategy. Extensive studies of late-stage functional group manipulation were performed to forge the C1 stereogenic center, during which a photoexcited intramolecular hydrogen atom transfer reaction was discovered and the mechanism was further studied through density functional theory (DFT) calculations. The biomimetic 1,2-rearrangement from the grayanoid skeleton provided a 5/8/5/5 tetracyclic framework and resulted in the first total synthesis of (+)-kalmanol.

Ray-Stretching Statistics and Hot-Spot Formation in Weak Random Disorder.

Weak scattering in a random disordered medium and the associated extreme-event statistics are of great interest in various physical contexts. Here, in the context of non-relativistic particle motion through a weakly correlated random potential, we show how extreme events in particle densities are strongly related to the stretching exponents, where the 'hot spots' in the intensity profile correspond to minima in the stretching exponents. This strong connection is expected to be valid for different random potential distributions, as long as the disorder is correlated and weak, and is also expected to apply to other physical contexts, such as deep ocean waves.

Total Synthesis of (+)-Mutilin: A Transannular [2+2] Cycloaddition/Fragmentation Approach.

A new and enantioselective total synthesis of the diterpenoid (+)-mutilin is described. Following a Claisen rearrangement approach to construct the 6,9-bicycle, a transannular [2+2] photocycloaddition and the ensuing ring-opening reaction were implemented to forge the characteristic 5-6-8 propellane-like skeleton. Subsequent late-stage alkylations and reduction completed the synthesis.

Scalable Total Synthesis of (-)-Triptonide: Serendipitous Discovery of a Visible-Light-Promoted Olefin Coupling Initiated by Metal-Catalyzed Hydrogen Atom Transfer (MHAT).

An efficient and scalable total synthesis of (-)-triptonide is accomplished based on a metal-catalyzed hydrogen atom transfer (MHAT)-initiated radical cyclization. During the optimization of the key step, we discovered that blue LEDs significantly promoted the efficiency of reaction initiated by Co(TPP)-catalyzed MHAT. Further exploration and optimization of this catalytic system led to development of a dehydrogenative MHAT-initiated Giese reaction.

Dealkenylative Ni-Catalyzed Cross-Coupling Enabled by Tetrazine and Photoexcitation.

A new and general method to functionalize the C(sp3)-C(sp2) bond of alkyl and alkene linkages has been developed, leading to the dealkenylative generation of carbon-centered radicals that can be intercepted to undergo Ni-catalyzed C(sp3)-C(sp2) cross-coupling. This one-pot protocol leverages the easily procured alkene feedstocks for organic synthesis with excellent functional group compatibility without the need for a photoredox catalyst.

Total Synthesis of (-)-Batrachotoxinin A: A Local-Desymmetrization Approach.

An enantioselective total synthesis of (-)-batrachotoxinin A is accomplished based on a key photoredox coupling reaction and the subsequent local-desymmetrization operation. After the expedient assembly of the highly oxidized steroid skeleton, a delicate sequence of redox manipulations was carried out to deliver a late-stage intermediate on gram scale-and ultimately (-)-batrachotoxinin A in an efficient manner.

Enantioselective syntheses and application of 4-epi-galiellalactone and the corresponding activity-based probe: from strained bicycles to strained tricycles.

The [6,5,5] tricyclic fungal metabolite galiellalactone is a Michael acceptor that has been demonstrated to be a covalent inhibitor for Signal Transducer and Activator of Transcription 3 (STAT3). Recognizing the ring strain associated with the skeleton of this natural product, we utilized 1R-5S-bicyclo[3.1.0]hexan-2-one as the starting material and developed two novel approaches to accomplish the enantioselective total synthesis of the C4 epimer of galiellalactone in 5 and 7 steps, respectively, which capitalized on an efficient radical cyclization/fragmentation cascade reaction. Furthermore, an activity-based probe of 4-epi-galiellalactone with a terminal alkyne tag was successfully prepared to enable the experiments of activity-based protein profiling (ABPP). Through western blot and proteomic analysis, we not only confirmed the known target STAT3, but also identified a new target protein ataxin-7, which formed a covalent bond with the probe in intact cells via the Cys-129 residue.

Redox-Active Ligand Assisted Multielectron Catalysis: A Case of CoIII Complex as Water Oxidation Catalyst.

Water oxidation is the key step in both natural and artificial photosynthesis to capture solar energy for fuel production. The design of highly efficient and stable molecular catalysts for water oxidation based on nonprecious metals is still a great challenge. In this article, the electrocatalytic oxidation of water by Na[(L4-)CoIII], where L is a substituted tetraamido macrocyclic ligand, was investigated in aqueous solution (pH 7.0). We found that Na[(L4-)CoIII] is a stable and efficient homogeneous catalyst for electrocatalytic water oxidation with 380 mV onset overpotential in 0.1 M phosphate buffer (pH 7.0). Both ligand- and metal-centered redox features are involved in the catalytic cycle. In this cycle, Na[(L4-)CoIII] was first oxidized to [(L2-)CoIIIOH] via a ligand-centered proton-coupled electron transfer process in the presence of water. After further losing an electron and a proton, the resting state, [(L2-)CoIIIOH], was converted to [(L2-)CoIV═O]. Density functional theory (DFT) calculations at the B3LYP-D3(BJ)/6-311++G(2df,2p)//B3LYP/6-31+G(d,p) level of theory confirmed the proposed catalytic cycle. According to both experimental and DFT results, phosphate-assisted water nucleophilic attack to [(L2-)CoIV═O] played a key role in O-O bond formation.

Divergent Total Syntheses of Enmein-Type Natural Products: (-)-Enmein, (-)-Isodocarpin, and (-)-Sculponin†R.

Divergent total syntheses of the enmein-type natural products (-)-enmein, (-)-isodocarpin, and (-)-sculponin R have been achieved in a concise fashion. Key features of the strategy include 1) an efficient early-stage cage formation to control succeeding diastereoselectivity, 2) a one-pot acylation/akylation/lactonization to construct the C-ring and C8 quarternary center, 3) a reductive alkenylation approach to construct the enmain D/E rings and 4) a flexible route to allow divergent syntheses of three natural products.

Total Synthesis of (+)-Minfiensine: Construction of the Tetracyclic Core Structure by an Asymmetric Cascade Cyclization.

A new method for one-step construction of the tetracyclic core structure of the indole alkaloid (+)-minfiensine was developed utilizing a palladium-catalyzed asymmetric indole dearomatization/iminium cyclization cascade. An efficient total synthesis of (+)-minfiensine was realized using this strategy. The present method enables access to the common core structure of a series of monoterpene indole alkaloids, such as vincorine, echitamine, and aspidosphylline A.

Murine double minute 2 rs2279744 polymorphism and hepatocellular carcinoma risk in East Asians: a meta-analysis.

Murine double minute 2 (MDM2) is a crucial negative regulator of p53 function through several mechanisms. There are many studies performed to assess the association between MDM2 rs2279744 polymorphism and hepatocellular carcinoma risk, but the impact of MDM2 rs2279744 polymorphism on hepatocellular carcinoma in East Asians is unclear owing to the inconsistent findings from previous studies. We conducted a comprehensive meta-analysis of epidemiological studies to shed some light on these contradicting results. We used pooled odds ratio (OR) with its 95 % confidence intervals (95 % CI) to assess the association. Overall, seven studies with a total of 4,993 subjects were finally included. The meta-analysis suggested that MDM2 rs2279744 polymorphism was significantly associated with increased risk of hepatocellular carcinoma in East Asians (G versus T: OR = 1.27, 95 % CI 1.06-1.52, P = 0.01; GG versus TT: OR = 1.59, 95 % CI 1.11-2.27, P = 0.01; GG/GT versus TT: OR = 1.41, 95 % CI 1.07-1.87, P = 0.02; GG versus TT/GT: OR = 1.32, 95 % CI 1.08-1.62, P = 0.008). Sensitivity analysis by excluding low-quality study still suggested that the association above was still significant. Thus, the findings from the meta-analysis support that MDM2 rs2279744 polymorphism is significantly associated with increased risk of hepatocellular carcinoma in East Asians.

Universality of finite-time ray focusing statistics in two-dimensional and one-dimensional potential flows.

In the investigation of extreme density or wave height statistics in a disordered medium, of special interest is the search for universal or fundamental properties shared by different types of disorder. In previous work [Chen and Kaplan, Entropy 25, 161 (2023)1099-430010.3390/e25010161] we have established a direct connection between the degree of stretching or focusing of ray trajectories and the density distribution. Here we demonstrate the universality of this connection for different physical contexts, and both analytically and numerically show a universal scaling relationship for the stretching exponent distribution in weak, small-angle scattering at finite times for different dispersion relations. We observe that the mean, skewness, and kurtosis of the stretching exponent all display universal nonmonotonic behavior on timescales comparable to the time of first caustic formation, corresponding to the first generation of hot spots in the density profile. In particular, the mean stretching exponent attains negative values before beginning its linear rise at large times. Using the correspondence between two-dimensional small-angle scattering and a one-dimensional kicked model, we show how higher moments of the distribution of the second derivative of the potential affect the statistics of the stretching exponents.

A Wearable Asynchronous Brain-Computer Interface Based on EEG-EOG Signals With Fewer Channels.

OBJECTIVE: Brain-computer interfaces (BCIs) have tremendous application potential in communication, mechatronic control and rehabilitation. However, existing BCI systems are bulky, expensive and require laborious preparation before use. This study proposes a practical and user-friendly BCI system without compromising performance. METHODS: A hybrid asynchronous BCI system was developed based on an elaborately designed wearable electroencephalography (EEG) amplifier that is compact, easy to use and offers a high signal-to-noise ratio (SNR). The wearable BCI system can detect P300 signals by processing EEG signals from three channels and operates asynchronously by integrating blink detection. RESULT: The wearable EEG amplifier obtains high quality EEG signals and introduces preprocessing capabilities to BCI systems. The wearable BCI system achieves an average accuracy of 94.03±4.65%, an average information transfer rate (ITR) of 31.42±7.39 bits/min and an average false-positive rate (FPR) of 1.78%. CONCLUSION: The experimental results demonstrate the feasibility and practicality of the developed wearable EEG amplifier and BCI system. SIGNIFICANCE: Wearable asynchronous BCI systems with fewer channels are possible, indicating that BCI applications can be transferred from the laboratory to real-world scenarios.

Aperiodic Component Analysis in Quantification of Steady-State Visually Evoked Potentials.

OBJECTIVE: In this study, we aimed to investigate whether and how the aperiodic component in electroencephalograms affects different quantitative processes of steady-state visually evoked potentials and the performance of corresponding brain-computer interfaces. METHODS: We applied the Fitting Oscillations & One-Over-F method to parameterize power spectra as a combination of periodic oscillations and an aperiodic component. Electroencephalographic responses and system performance were measured and compared using four prevailing methods: power spectral density analysis, canonical correlation analysis, filter bank canonical correlation analysis and the state-of-the-art method, task discriminant component analysis. RESULTS: We found that controlling for the aperiodic component prominently downgraded the performance of brain-computer interfaces measured by canonical correlation analysis (94.9% to 82.8%), filter bank canonical correlation analysis (94.1% to 87.6%), and task discriminant component analysis (96.5% to 70.3%). However, it had almost no effect on that measured by power spectral density analysis (80.4% to 78.7%). This was accompanied by a differential aperiodic impact between power spectral density analysis and the other three methods on the differentiation of the target and non-target stimuli. CONCLUSION: The aperiodic component distinctly impacts the quantification of steady-state visually evoked potentials and the performance of corresponding brain-computer interfaces. SIGNIFICANCE: Our work underscores the significance of taking into account the dynamic nature of aperiodic activities in research related to the quantification of steady-state visually evoked potentials. The source code for our approach is available at https://github.com/didi226/scut_ssvep_aperiod.

Identification, characterization and hypolipidemic effect of novel peptides in protein hydrolysate from Protaetia brevitarsis larvae.

The proteins were mainly derived from Protaetia brevitarsis larval extracts obtained using two empty intestine methods (traditional static method: TSM or salt immersion stress method: SISM) and extraction solvents (water: W or 50 % water-ethanol: W:E), and the proteins were used as objects to investigate the effect of emptying intestine methods on hypolipidemic peptides. The results revealed that the F-2 fractions of protein hydrolysate had stronger in vitro hypolipidemic activity, with the peptides obtained by SISM possessing a stronger cholesterol micelle solubility inhibition rate, especially in SISM-W:E-P. Moreover, a total of 106 peptides were tentatively identified, among which SISM identified more peptides with an amino acid number < 8. Meanwhile, five novel peptides (YPPFH, YPGFGK, KYPF, SPLPGPR and VPPP) exhibited good hypolipidemic activity in vitro and in vivo, among which YPPFH, VPPP and KYPF had strong inhibitory activities on pancreatic lipase (PL) and cholesteryl esterase (CE), and KYPF, SPLPGPR and VPPP could significantly reduce the TG content in Caenorhabditis elegans. Thus, P. brevitarsis can be developed as a naturally derived hypolipidemic component for the development and application in functional foods.

Physical and chemical characterization of chitin and chitosan extracted under different treatments from black soldier fly.

The shell of Hermetia illucens L. contains considerable amounts of chitin, which has various biological activities. So far, few studies have focused on chitin of Hermetia illucens L. as a source of chitosan and oligosaccharides. There is great potential for utilizing Hermetia illucens L. chitin to produce chitosan films in biomaterials. We studied different extraction conditions for chitin and extracted it from black soldier fly (BSF) (Hermetia illucens L.). Three processing steps were adopted: (1) demineralization, (2) deproteinization, and (3) decolorization. The chemical components (moisture, ash, protein, fat, residual protein, and residual mineral contents) and physicochemical characteristics of the chitin and chitosan extracted under these three conditions were determined. In addition, Fourier transform infrared spectroscopy and X-ray diffraction were used to analyze the extracted chitin and commercial samples, and the results showed that demineralization-deproteinization-decolorization treatments could achieve the highest chitin yield (7.18 ±â€¯0.11 %), chitosan yield (64.22 ±â€¯0.79 %), and the best purity (residual protein 0.56 ±â€¯0.01 % and residual ash 0.58 ±â€¯0.04 %), making it the best treatment method. Using this method, the residues produced from farmed BSF can be recycled and used as a new source of chitin.

[Effects of Straw and Biochar Amendments on Characteristics of Soil Fungal Community and Organic Carbon Pool in Jasminum sambac Garden].

In order to elucidate the changes in the soil fungal community and soil organic carbon components of a Jasminum sambac garden after straw and biochar application, we measured the organic carbon components and soil fungal community of the 0-15 cm soil layer in a J. sambac garden, which was divided into a control group, straw treatment group, and biochar treatment group. The carbon pool management index （CPMI） was also calculated. The results showed that the diversity of the soil fungal community was decreased after straw and biochar application, and the structure of dominant fungal genera was changed in each treatment. The soil fungal community structure in the biochar treatment was significantly different from that in the straw treatment and control groups. Redundancy analysis （RDA） showed that soil fungal community structure was mainly affected by soil bulk density, C∶N, salinity, and TN. Secondly, compared with that in the control group, soil labile organic carbon （LOC） in the straw treatment group was significantly increased by 87.44% （P<0.05）, whereas soil dissolved organic carbon （DOC） and microbial biomass carbon （MBC） in the biochar treatment group were significantly increased by 22.27% and 23.17% （P<0.05）, respectively. Further, compared with that in the control group, the carbon pool activity （L） under straw treatment was significantly increased （P<0.05）, and the carbon pool index （CPI） under biochar treatment was significantly increased （P<0.05）. Spearman correlation analysis showed that the distribution characteristics of soil organic carbon active components were regulated by the dominant fungi. FUNGuild functional prediction results showed that saprophytic and its facultative nutritional fungi had an important impact on soil organic carbon active components and carbon pool management index after straw and biochar application.

Combination therapy with toripalimab and anlotinib in advanced esophageal squamous cell carcinoma: A case report.

BACKGROUND: Toripalimab and anlotinib have shown good response in esophageal cancer, with high objective response rate and progression free survival. Thus, they have been approved as second-line or above-line therapy for advanced or unresectable esophageal carcinoma. Combination of these two drugs may have synergistic effects, but evidence of which is lacking. CASE SUMMARY: Here, we report on a 73-year-old male, newly diagnosed with advanced esophageal squamous cell carcinoma (ESCC), who received a combination of toripalimab and anlotinib. Complete response was achieved after treatment for 3 mo and remission was maintained up to 14 mo. CONCLUSION: The combination therapy of toripalimab and anlotinib is a promising treatment for unresectable ESCC and related clinical trials are warranted.