Photoredox Synthesis of Silicon-Containing Isoindolin-1-ones and Deuterated Analogues Through Hydrosilylation and Deuterium-silylation.

An efficient, practical, and metal-free protocol for the synthesis of silicon-containing isoindolin-1-ones and deuterated analogues via the synergistic combination of an organic photoredox and hydrogen atom transfer process is described. This strategy features mild reaction conditions, high atom economy, and excellent functional group compatibility, delivering a myriad of structurally diverse and valuable products with good to excellent yields.

Enantioselective transformation of phytoplankton-derived dihydroxypropanesulfonate by marine bacteria.

Chirality, a fundamental property of matter, is often overlooked in the studies of marine organic matter cycles. Dihydroxypropanesulfonate (DHPS), a globally abundant organosulfur compound, serves as an ecologically important currency for nutrient and energy transfer from phytoplankton to bacteria in the ocean. However, the chirality of DHPS in nature and its transformation remain unclear. Here, we developed a novel approach using chiral phosphorus-reagent labeling to separate DHPS enantiomers. Our findings demonstrated that at least one enantiomer of DHPS is present in marine diatoms and coccolithophores, and that both enantiomers are widespread in marine environments. A novel chiral-selective DHPS catabolic pathway was identified in marine Roseobacteraceae strains, where HpsO and HpsP dehydrogenases at the gateway to DHPS catabolism act specifically on R-DHPS and S-DHPS, respectively. R-DHPS is also a substrate for the dehydrogenase HpsN. All three dehydrogenases generate stable hydrogen bonds between the chirality-center hydroxyls of DHPS and highly conserved residues, and HpsP also form coordinate-covalent bonds between the chirality-center hydroxyls and Zn2+, which determines the mechanistic basis of strict stereoselectivity. We further illustrated the role of enzymatic promiscuity in the evolution of DHPS metabolism in Roseobacteraceae and SAR11. This study provides the first evidence of chirality's involvement in phytoplankton-bacteria metabolic currencies, opening a new avenue for understanding the ocean organosulfur cycle.

Differential bioaccumulation and tolerances of massive and branching scleractinian corals to polycyclic aromatic hydrocarbons in situ.

Scleractinian corals are capable of accumulating polycyclic aromatic hydrocarbons (PAHs) in reef environments; however, the mechanism behind their PAHs tolerance is unknown. This study investigated the occurrence and bioaccumulation of PAHs in coral reef ecosystems and examined the physiological responses induced by PAHs in coral hosts and their algal symbionts, the massive coral Galaxea fascicularis and branching coral Pocillopora damicornis. G. fascicularis had a higher PAHs accumulation capacity than P. damicornis. Both the coral hosts and algal symbionts preferentially accumulated acenaphthene, dibenzo(a,h)anthracene, and benzo(a)pyrene. The accumulated PAHs by G. fascicularis and P. damicornis hosts was accompanied by a reduction in detoxification ability. The accumulated PAHs could induce oxidative stress in P. damicorni hosts, thus G. fascicularis demonstrated a greater tolerance to PAHs compared to P. damicornis. Meanwhile, their algal symbionts had fewer physiological responses to accumulated PAHs than the coral hosts. Negative effects were not observed with benzo(a)pyrene. Taken together, these results suggest massive and branching scleractinian corals have different PAHs bioaccumulation and tolerance mechanisms, and indicate that long-term PAHs pollution could cause significant alterations of community structures in coral reef ecosystems.

Terrihabitans rhizophilus sp. nov., isolated from the rhizosphere soil of plant in temperate semi-arid steppe.

A bacterial strain PJ23T was isolated from the rhizosphere soil of Elymus dahuricus Turcz. sampled from a temperate semi-arid steppe in the northern of Inner Mongolia Autonomous Region, China. The strain is Gram-stain-negative, aerobic, light-pink, short rod-shaped, and non-spore-forming. Cell growth could be observed at 4-29℃ (optimal at 24℃), pH 6.0-8.6 (optimal at 8.0) and in the presence of 0-5.0% (w/v) NaCl (optimal at 2.5%). The major cellular fatty acids of strain PJ23T were Summed feature 8 (C18:1 ω6c and/or C18:1 ω7c) (39.42%) and C16:0 (9.60%). The polar lipids were phosphatidylcholine, two unidentified glycolipids, one unidentified aminophospholipid, and two other unidentified polar lipids. The major respiratory quinone was ubiquinone-10. Phylogeny analysis based on 16S rRNA gene sequences retrieved from the genomes showed that, the strain was closely related to the species Terrihabitans soli IZ6T and Flaviflagellibacter deserti SYSU D60017T, with the sequence similarities of 96.79% and 96.15%, respectively. The G + C content was 65.23 mol% calculated on draft genome sequencing. Between the strains PJ23T and Terrihabitans soli IZ6T, the average nucleotide identity (ANI), amino acid identity (AAI) and digital DNA-DNA hybridization (dDDH) was 73.39%,71.12% and 15.7%, these values were lower than the proposed and generally accepted species boundaries of ANI, AAI and dDDH, respectively. Based on phenotypic, chemotaxonomic, and phylogenetic characteristics, strain PJ23T represents a novel species of Terrihabitans, for which the name Terrihabitans rhizophilus sp. nov. is proposed. The type strain is PJ23T (= KCTC 92977 T = CGMCC 1.61577 T).

Roseihalotalea indica gen. nov., sp. nov., a halophilic Bacteroidetes from mesopelagic Southwest Indian Ocean with higher carbohydrate metabolic potential.

The pink-colored and strictly aerobic bacterium strain, designated as TK19036T, was isolated from mesopelagic layer of the Southwest Indian Ocean. This novel isolate can grow at 10-45 °C (optimum, 30 °C), pH 6.0-8.0 (optimum, pH 7.0), and 2-14% NaCl concentrations (w/v) (optimum, 6%). The predominant respiratory quinone was Menaquinone-7. Major polar lipid profiles contained two aminolipids, aminophospholipid, two glycolipids, phosphatidylethanolamine, and three unknown polar lipids. The preponderant cellular fatty acids were iso-C15:0, C16:1 ω5c and iso-C17:0 3-OH. Phylogenetic analyses based on 16S rRNA gene sequence uncovered that the strain TK19036T pertained to the family Catalinimonadaceae under phylum Bacteroidota, and formed a distinct lineage with the closed species Tunicatimonas pelagia NBRC 107804T. The up-to-bacteria-core gene phylogenetic trees also demonstrated a deep and novel branch formed by the strain TK19036T within the family Catalinimonadaceae. Based on chemotaxonomic, phylogenetic and genomic features presented above, strain TK19036T represents a novel species from a novel genus of the family Catalinimonadaceae, for which the name Roseihalotalea indica gen. nov. sp. nov. is proposed. The type strain is TK19036T (= CGMCC 1.18940T = NBRC 116371T).

Protocol for isolating small cytosolic dsDNA from cultured murine cells.

We recently identified a class of small cytosolic double-stranded DNA (scDNA) approximately 20-40 bp in size in human and mouse cells. Here, we present a protocol for scDNA isolation from cultured murine cells. We describe steps for cytosolic compartment separation, DNA isolation in the cytosolic fraction using phenol-chloroform extraction, and ethanol precipitation. We then detail procedures for denaturing purified cytosolic DNA through urea polyacrylamide gel electrophoresis and obtaining scDNA in the cytosolic DNA fraction via gel purification. For complete details on the use and execution of this protocol, please refer to Liu et al.1.

Interfacial Effects of Nanostructured Doubly Reentrant Surfaces on the Evolution of Local Concentration and Fluid Flow in an Evaporating Droplet.

Surface modification, such as bioinspired nanostructured doubly reentrant surfaces that have presented superhydrophobic wettability even under low-surface-tension liquid, is a very promising technology for controlling droplet dynamics, heat transfer, and evaporation. In this article, we investigate the interfacial effects of nanostructured doubly reentrant surfaces on the flow behaviors and local concentration evolution during the evaporation of an ethanol/water multicomponent droplet. Using particle image velocimetry (PIV) and novel aggregate-induced emission-based (AIE) techniques, the flow patterns and local concentration distributions on both hydrophobic and nanostructured doubly reentrant surfaces were probed and compared. It is found that in addition to the established Marangoni flow-dominated stage, transition stage, and buoyancy-induced flow-dominated stage, a new transition stage and a rolling stage for the nanostructured doubly reentrant surface are detected in the late evaporation period. Differences in the local concentration distribution evolution occur depending on the hydrophobicity of the surface on which the droplet is placed. For the hydrophobic surface, a nonuniform local concentration distribution exists consistently, with a high water fraction in a shell-shaped region near the liquid-air interface and a secondary concentration gradient within this shell-shaped region. The concentration distribution on the nanostructured doubly reentrant surface evolves in a more complex manner, with a strip-shaped region of high water fraction forming in the intermediate stage and then reorganized by rolling flow in the late stage. Finally, theoretical analysis combining PIV and AIE visualization results reveals that the variations in droplet concentration distributions on surfaces with different hydrophobicities exert a significant impact on evaporative behaviors. These behaviors, in turn, affect the evolution of the local concentration distribution.

Circulating tumor cells with metastasis-initiating competence survive fluid shear stress during hematogenous dissemination through CXCR4-PI3K/AKT signaling.

To seed lethal secondary lesions, circulating tumor cells (CTCs) must survive all rate-limiting factors during hematogenous dissemination, including fluid shear stress (FSS) that poses a grand challenge to their survival. We thus hypothesized that CTCs with the ability to survive FSS in vasculature might hold metastasis-initiating competence. This study reported that FSS of physiologic magnitude selected a small subpopulation of suspended tumor cells in vitro with the traits of metastasis-initiating cells, including stemness, migration/invasion potential, cellular plasticity, and biophysical properties. These shear-selected cells generated local and metastatic tumors at the primary and distal sites efficiently, implicating their metastasis competence. Mechanistically, FSS activated the mechanosensitive protein CXCR4 and the downstream PI3K/AKT signaling, which were essential in shear-mediated selection of metastasis-competent CTCs. In summary, these findings conclude that CTCs with metastasis-initiating competence survive FSS during hematogenous dissemination through CXCR4-PI3K/AKT signaling, which may provide new therapeutic targets for the early prevention of tumor metastasis.

Investigating organic sulfur in estuarine and offshore environments: A combined field and cultivation approach.

Estuarine-offshore sediments accumulate substantial particulate organic matter, containing organic sulfur as a key component. However, the distribution and sources of organic sulfur in such environments remain poorly understood. This study investigated organic sulfur in the Yangtze River Estuary and adjacent East China Sea. Dissolved organic sulfur varied from 0.65 to 1.99 µmol/L (molar S:C 0.006-0.018), while particulate organic sulfur ranged from 0.42 to 2.69 µmol/L (molar S:C 0.007-0.082). Sedimentary organic sulfur exhibited a similar molar S:C ratio (0.014-0.071) to particulate organic sulfur in bottom water, implying that particulate matter deposition is a potential source. Furthermore, sediments exposed to frequent hypoxia harbored significantly higher organic sulfur and S:C values compared to non-hypoxic areas. Laboratory incubation experiments revealed the underlying mechanism: sustained activity of sulfate-reducing bacteria in hypoxic sediments led to a substantial increase in sedimentary organic sulfur (from 15 to 53 µmol/g) within 600 days. This microbially driven sulfurization rendered over 90 % of the organic sulfur resistant to acid hydrolysis. Therefore, this study demonstrates that, alongside particle deposition, microbial sulfurization significantly contributes to organic sulfur enrichment and likely promotes organic matter preservation in estuarine-offshore sediments, particularly under hypoxic conditions. This finding advances our understanding of organic sulfur sources in these vital ecosystems.

Ginsenoside Rg1 promotes neurite growth of retinal ganglion cells through cAMP/PKA/CREB pathways.

Background: Mechanisms of synaptic plasticity in retinal ganglion cells (RGCs) are complex and the current knowledge cannot explain. Growth and regeneration of dendrites together with synaptic formation are the most important parameters for evaluating the cellular protective effects of various molecules. The effect of ginsenoside Rg1 (Rg1) on the growth of retinal ganglion cell processes has been poorly understood. Therefore, we investigated the effect of ginsenoside Rg1 on the neurite growth of RGCs. Methods: Expression of proteins and mRNA were detected by Western blot and qPCR. cAMP levels were determined by ELISA. In vivo effects of Rg1 on RGCs were evaluated by hematoxylin and eosin, and immunohistochemistry staining. Results: This study found that Rg1 promoted the growth and synaptic plasticity of RGCs neurite by activating the cAMP/PKA/CREB pathways. Meanwhile, Rg1 upregulated the expression of GAP43, Rac1 and PAX6, which are closely related to the growth of neurons. Meantime, H89, an antagonist of PKA, could block this effect of Rg1. In addition, we preliminarily explored the effect of Rg1 on enhancing the glycolysis of RGCs, which could be one of the mechanisms for its neuroprotective effects. Conclusion: Rg1 promoted neurite growth of RGCs through cAMP/PKA/CREB pathways. This study may lay a foundation for its clinical use of optic nerve diseases in the future.

Sustainable bioelectric activation of periodate for highly efficient micropollutant abatement.

The periodate (PI)-based advanced oxidation process is valued for environmental remediation, but current activation methods involve high costs, secondary contamination risks, and limited applicability due to external energy inputs (e.g., UV), catalyst incorporation (e.g., Fe2+), or environmental modifications (e.g., freezing). In this work, novel bioelectric activation of PI using the electrons generated by electroactive bacteria was developed and investigated for rapid removal of carbamazepine (CBZ), achieving 100 %, 100 %, and 76 % removal efficiency for 4.22 µM of CBZ in 20 min at pH 2, 120 min at pH 6.4, and HRT of 30 min at pH 8.5, respectively, with a 1 mM PI dose and without an input voltage. It was deduced that electrons derived from bacteria could directly activate PI using Ti mesh electrodes and generate •IO3 via single electron transfer under strongly acidic conditions (e.g., pH 2). Nevertheless, under weak alkaline conditions (e.g., pH 8.5), biogenic electrons indirectly activated PI by generating OH-via 4e-reduction at the Ti mesh cathode, resulting in the formation of •O2- and 1O2. In addition to the metal cathode, a carbon-based cathode finely modulates the 2e-reduction, yielding H2O2 and activating PI to mainly form •OH. Moreover, primarily non-toxic IO3- was produced during treatment, while no detectable reactive iodine species (HOI, I2, and I3-) were observed. Furthermore, the bioelectric activation of PI demonstrated its capability to remove various micropollutants present in secondary-treated municipal wastewater, showcasing its broad-spectrum degradation ability. This study introduces a novel, cost-effective, and environmentally friendly PI activation technique with promising applicability for micropollutant elimination in water treatment.

Impacts of Inflammatory Cytokines Variants on Systemic Inflammatory Profile and COVID-19 Severity.

BACKGROUND: Cytokine storm is known to impact the prognosis of coronavirus disease 2019 (COVID-19), since pro-inflammatory cytokine variants are associated with cytokine storm. It is tempting to speculate that pro-inflammatory cytokines variants may impact COVID-19 outcomes by modulating cytokine storm. Here, we verified this hypothesis via a comprehensive analysis. METHODS: PubMed, Cochrane Library, Central, CINAHL, and ClinicalTrials.gov were searched until December 15, 2023. Case-control or cohort studies that investigated the impacts of rs1800795 or rs1800629 on COVID-19 susceptibility, severity, mortality, IL-6, TNF-α, or CRP levels were included after an anonymous review by two independent reviewers and consultations of disagreement by a third independent reviewer. RESULTS: 47 studies (8305 COVID-19 individuals and 17,846 non-COVID-19 individuals) were analyzed. The rs1800629 A allele (adenine at the -308 position of the promoter was encoded by the A allele) was associated with higher levels of tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP). In contrast, the rs1800795 C allele (cytosine at the -174 position of the promoter was encoded by the C allele) was linked to higher levels of interleukin-6 (IL-6) and CRP. In addition, the A allele of rs1800629 increased the severity and mortality of COVID-19. However, the C allele of rs1800795 only increased COVID-19 susceptibility. CONCLUSIONS: rs1800629 and rs1800795 variants of pro-inflammatory cytokines have significant impacts on systemic inflammatory profile and COVID-19 clinical outcomes. rs1800629 may serve as a genetic marker for severe COVID-19.

A Portable Electrochemical Dopamine Detector Using a Fish Scale-Derived Graphitized Carbon-Modified Screen-Printed Carbon Electrode.

In this paper, a highly conductive alkali-activated graphitized carbon (a-GC) was prepared using tilapia fish scales as precursors through enzymolysis, activation and pyrolytic carbonization methods. The prepared a-GC was modified on the surface of a screen-printed carbon electrode to construct a flexible portable electrochemical sensing platform, which was applied to the differential pulse voltametric detection of dopamine (DA) using a U-disk electrochemical workstation combined with a smart phone and Bluetooth. The prepared a-GC possesses good electrical conductivity, a large specific surface area and abundant active sites, which are beneficial for the electrooxidation of DA molecules and result in excellent sensitivity and high selectivity for DA analysis. Under the optimal conditions, the oxidation peak current of DA increased gradually, with its concentrations in the range from 1.0 µmol/L to 1000.0 µmol/L, with the detection limit as low as 0.25 µmol/L (3S/N). The proposed sensor was further applied to the determination of DA in human sweat samples, with satisfactory results, which provided an opportunity for developing noninvasive early diagnosis and nursing equipment.

Selective enrichment of bacteria and antibiotic resistance genes in microplastic biofilms and their potential hazards in coral reef ecosystems.

Microplastics become hotspots for bacteria to trigger a series of ecological effects, but few studies have focused on the potential impacts of microplastic biofilms in coral reef ecosystems. Here, we measured the bacterial communities and antibiotic resistance genes (ARGs) in the seawater and microplastic biofilms. Results showed that microbial biofilms were formed on the surface of microplastics. The alpha diversity of the bacterial community in the microplastic biofilms was lower than that in the seawater, and the bacterial communities were distinct between the two. Further analysis revealed that several bacteria in the microplastic biofilms carried ARGs, and the proportion of which was correlated to the concentration of antibiotics in the seawater. Specifically, Vibrio was positively correlated to sul1 in the microplastic biofilms under higher concentrations of sulfonamides. Pathway analysis reflected significant overrepresentation of human disease related pathways in the bacterial community of microplastic biofilms. These results suggest that the microplastic biofilms could selectively enrich bacteria from the reef environments, causing the development of ARGs under antibiotic driving. This may pose a serious threat to coral reef ecosystems and human health. Our study provides new insights into the ecological impacts of microplastic biofilms in coral reef ecosystems.

Human papillomavirus (HPV) DNA methylation changes in HPV-associated head and neck cancer.

Despite the rising incidence, currently, there are no early detection methods for HPV-driven HNC (HPV-HNC). Cervical cancer studies suggest that HPV DNA methylation changes can be used as a biomarker to discriminate cancer patients from HPV-infected individuals. As such, this study was designed to establish a protocol to evaluate DNA methylation changes in HPV late genes and long control region (LCR) in saliva samples of HPV-HNC patients and HPV-positive controls. Higher methylation levels were detected in HPV late genes (L1 and L2) in both tumour and saliva samples of HPV-HNC patients compared with HPV-positive controls. Moreover, methylation patterns between tumours and corresponding saliva samples were observed to have a strong correlation (Passing-Bablok regression analysis; τ = 0.7483, P < 0.0001). Considering the differences between HNC and controls in methylation levels in late genes, and considering primer amplification efficiencies, 13 CpG sites located at L1 and L2 genes were selected for further evaluation. A total of 18 HNC saliva samples and 10 control saliva samples were assessed for the methylation levels in the selected sites. From the CpG sites evaluated statistically significant differences were identified for CpG sites at L2-CpG 6 (P = 0.0004), L1-CpG 3 (P = 0.0144), L1-CpG 2 (P = 0.0395) and L2-CpG 19 (P = 0.0455). Our pilot data indicate that higher levels of DNA methylation in HPV late genes are indicative of HPV-HNC risk, and it is a potential supplementary biomarker for salivary HPV detection-based HPV-HNC screening.

An Antenna-Enriched Chemosensory Protein Plays Important Roles in the Perception of Host Plant Volatiles in Bactrocera dorsalis (Diptera: Tephritidae).

Olfaction plays indispensable roles in insect behavior such as host location, foraging, oviposition, and avoiding predators. Chemosensory proteins (CSPs) can discriminate the hydrophobic odorants and transfer them to the odorant receptors. Presently, CSPs have been identified in many insect species. However, their presence and functions remain unknown in Bactrocera dorsalis, a destructive and invasive insect pest in the fruit and vegetable industry. Here, we annotated eight CSP genes in the genome of B. dorsalis. The results of quantitative real-time polymerase chain reaction (RT-qPCR) showed that BdorCSP3 was highly expressed in the antennae. Molecular docking and in vitro binding assays showed that BdorCSP3 had a good binding ability to host volatiles methyl eugenol (ME, male-specific attractant) and ß-caryophyllene (potential female attractant). Subsequently, CRISPR/Cas9 was used to generate BdorCSP3-/- mutants. Electroantennograms (EAGs) and behavioral assays revealed that male mutants significantly reduced the preference for ME, while female mutants lost their oviposition preference to ß-caryophyllene. Our data indicated that BdorCSP3 played important roles in the perception of ME and ß-caryophyllene. The results not only expanded our knowledge of the olfaction perception mechanism of insect CSPs but also provided a potential molecular target for the control of B. dorsalis.

Discovery of a novel marine Bacteroidetes with a rich repertoire of carbohydrate-active enzymes.

Members of the phylum Bacteroidetes play a key role in the marine carbon cycle through their degradation of polysaccharides via carbohydrate-active enzymes (CAZymes) and polysaccharide utilization loci (PULs). The discovery of novel CAZymes and PULs is important for our understanding of the marine carbon cycle. In this study, we isolated and identified a potential new genus of the family Catalimonadaceae, in the phylum Bacteroidetes, from the southwest Indian Ocean. Strain TK19036, the type strain of the new genus, is predicted to encode CAZymes that are relatively abundant in marine Bacteroidetes genomes. Tunicatimonas pelagia NBRC 107804T, Porifericola rhodea NBRC 107748T and Catalinimonas niigatensis NBRC 109829T, which exhibit 16 S rRNA similarities exceeding 90% with strain TK19036, and belong to the same family, were selected as reference strains. These organisms possess a highly diverse repertoire of CAZymes and PULs, which may enable them to degrade a wide range of polysaccharides, especially pectin and alginate. In addition, some secretory CAZymes in strain TK19036 and its relatives were predicted to be transported by type IX secretion system (T9SS). Further, to the best of our knowledge, we propose the first reported "hybrid" PUL targeting alginates in T. pelagia NBRC 107804T. Our findings provide new insights into the polysaccharide degradation capacity of marine Bacteroidetes, and suggest that T9SS may play a more important role in this process than previously believed.

Esculetin Alleviates IL-1ß-Evoked Nucleus Pulposus Cell Death, Extracellular Matrix Remodeling, and Inflammation by Activating Nrf2/HO-1/NF-kb.

Inflammation, extracellular matrix metabolic dysfunction, and oxidative stress are key pathogenic characteristics of intervertebral disk degeneration (IVDD), a major pathogenic cause of low back pain. Esculetin possesses anti-injury, anti-inflammation, and antinociceptive properties. This study aimed to explore its role in IVDD. In this research, esculetin exhibited little cytotoxicity to human nucleus pulposus cells (NPCs). Moreover, esculetin increased cell viability under IL-1ß stimulation but attenuated IL-1ß-induced cell apoptosis and caspase-3 activity. Furthermore, IL-1ß-evoked increases in intracellular reactive oxygen species and malondialdehyde (MDA) levels, and decreases in superoxide dismutase (SOD) activity were reversed after esculetin treatment, indicating the antioxidative stress efficacy of esculetin. Esculetin alleviated the inhibitory effects of IL-1ß on the transcription and protein expression of anabolic biomarkers (collagen II and aggrecan), accompanied by decreases in expression and release of catabolic biomarkers MMP-3 and MMP-13 from NPCs. Moreover, IL-1ß exposure enhanced the expression levels of the inflammatory mediator nitric oxide and inflammatory cytokine IL-6 and TNF-α, which were overturned after esculetin treatment. Additionally, esculetin activated the nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) to inhibit the activation of nuclear factor κB (NF-κB) signaling in NPCs. Importantly, suppression of Nrf2 signaling reversed the protective efficacy of esculetin against IL-1ß-mediated oxidative injury, matrix metabolism disruption, and inflammatory response in NPCs. Together, esculetin may alleviate IL-1ß-induced dysfunction in NPCs by regulating the Nrf2/HO-1/NF-kb signaling, indicating its potential as a promising therapeutic agent against IVDD.

Amide C-N bonds activation by A new variant of bifunctional N-heterocyclic carbene.

We report an organocatalyst that combines a triazolium N-heterocyclic carbene (NHC) with a squaramide as a hydrogen-bonding donor (HBD), which can effectively catalyze the atroposelective ring-opening of biaryl lactams via a unique amide C-N bond cleavage mode. The free carbene species attacks the amide carbonyl, forming an axially chiral acyl-azolium intermediate. Various axially chiral biaryl amines can be accessed by this methodology with up to 99% ee and 99% yield. By using mercaptan as a catalyst turnover agent, the resulting thioester synthon can be transformed into several interesting atropisomers. Both control experiments and theoretical calculations reveal the crucial role of the hybrid NHC-HBD skeleton, which activates the amide via H-bonding and brings it spatially close to the carbene centre. This discovery illustrates the potential of the NHC-HBD chimera and demonstrates a complementary strategy for amide bond activation and manipulation.

Aberrant resting-state co-activation network dynamics in major depressive disorder.

Major depressive disorder (MDD) is a globally prevalent and highly disabling disease characterized by dysfunction of large-scale brain networks. Previous studies have found that static functional connectivity is not sufficient to reflect the complicated and time-varying properties of the brain. The underlying dynamic interactions between brain functional networks of MDD remain largely unknown, and it is also unclear whether neuroimaging-based dynamic properties are sufficiently robust to discriminate individuals with MDD from healthy controls since the diagnosis of MDD mainly depends on symptom-based criteria evaluated by clinical observation. Resting-state functional magnetic resonance imaging (fMRI) data of 221 MDD patients and 215 healthy controls were shared by REST-meta-MDD consortium. We investigated the spatial-temporal dynamics of MDD using co-activation pattern analysis and made individual diagnoses using support vector machine (SVM). We found that MDD patients exhibited aberrant dynamic properties (such as dwell time, occurrence rate, transition probability, and entropy of Markov trajectories) in some transient networks including subcortical network (SCN), activated default mode network (DMN), de-activated SCN-cerebellum network, a joint network, activated attention network (ATN), and de-activated DMN-ATN, where some dynamic properties were indicative of depressive symptoms. The trajectories of other networks to deactivated DMN-ATN were more accessible in MDD patients. Subgroup analyses also showed subtle dynamic changes in first-episode drug-naïve (FEDN) MDD patients. Finally, SVM achieved preferable accuracies of 84.69%, 76.77%, and 88.10% in discriminating patients with MDD, FEDN MDD, and recurrent MDD from healthy controls with their dynamic metrics. Our findings reveal that MDD is characterized by aberrant dynamic fluctuations of brain network and the feasibility of discriminating MDD patients using dynamic properties, which provide novel insights into the neural mechanism of MDD.