Abscisic Acid Induces DNA Methylation Alteration in Genes Related to Berry Ripening and Stress Response in Grape (Vitis vinifera L).

Abscisic acid (ABA) is a major regulator of nonclimacteric fruit ripening, with its processes involving epigenetic mechanisms. It remains unclear whether DNA methylation is associated with ABA-regulated ripening. In this study, we investigated the patterns of DNA methylation and gene expression following ABA treatment in grape berries by using whole-genome bisulfite sequencing and RNA-sequencing. ABA application changed global DNA methylation in grapes. The hyper-/hypo-differently methylated regions were enriched in defense-related metabolism, degreening processes, or ripening-related metabolic pathways. Many differentially expressed genes showed an alteration in DNA methylation after ABA treatment. Specifically, ten downregulated genes with hypermethylation in promoters were involved in the ripening process, ABA homeostasis/signaling, and stress response. Nine upregulated genes exhibiting hypo-methylation in promoters were related to the ripening process and stress response. These findings demonstrated ABA-induced DNA alteration of ripening related and stress-responsive genes during grape ripening, which provides new insights of the epigenetic regulation of ABA on fruit ripening.

Electroacupuncture improves low-grade duodenal inflammation in FD rats by reshaping intestinal flora through the NF-κB p65/NLRP3 pyroptosis pathway.

Electroacupuncture (EA) is an effective alternative for the treatment of functional dyspepsia (FD). It reduces low-grade duodenal inflammation and improves the symptoms of FD by downregulating the expression of NF-κB p65 and NLRP3, but its mechanism needs to be elucidated. To examine the regulatory effect of electroacupuncture (EA) on intestinal flora and NF-κB p65/NLRP3 pyroptosis pathway in FD rats. The FD rat model was established via multi-factor stress intervention for two weeks. The rats were randomly divided into the NC group, model group, NF-kB inhibitor group (NF-κB inhibitor BAY 11-7082 was administered), EA group, and EA + NF-kB inhibitor group. After 14 days of treatment, the rats were sacrificed, and the protein and mRNA levels of NF-κB p65, IκB, and NLRP3 in the duodenum were evaluated by Western blotting assays and real-time fluorescent quantitative PCR. The Illumina MiSeq sequencing platform was used to analyze the V4 region of the 16S rRNA gene of intestinal flora and predict functional genes. The concentration of short-chain fatty acids (SCFAs) in feces was assessed by metabolomics. EA can decrease low-grade duodenal inflammation and promote gastrointestinal motility in FD rats. This effect is mediated by inhibition of the NF-κB p65/NLRP3 pyroptosis pathway, an increase in the alpha and beta diversity of gut microbiota in the duodenum, an increase in the abundance of beneficial bacteria at the phylum and genus levels, and an increase in the content of SCFAs. The protective effect of EA against FD might involve multiple hierarchy and pathways. EA may remodel intestinal flora by inhibiting the NF-κB p65/NLRP3 pyroptosis pathway, thereby improving low-grade duodenal inflammation in FD rats.

Effect of quercetin on the protein-substrate interactions in SIRT6: Insight from MD simulations.

SIRT6 is of interest for its promising effect in the treatment of aging-related diseases. Studies have shown quercetin (QUE) and its derivatives have varying degrees of effect on the catalytic effect of SIRT6. In the research, the effect of QUE on the protein-substrate interaction in the SIRT6-mediated mono-ADP ribosylation system was investigated by conventional molecular dynamics (MD) simulations combined with MM/PBSA binding free energy calculations. The results show that QUE can bind stably to SIRT6 with the binding energy of -22.8 kcal/mol and further affect the atomic interaction between SIRT6 and NAD+ (or H3K9), resulting in an increased affinity between SIRT6-NAD+ and decreased SIRT6-H3K9 binding capacity. At the same time, the binding of QUE can also alter some structural characteristics of the protein, with large shifts occurring in the residue regions involving the N-terminal (residues 1-27), Rossmann fold regions (residues 55-92), and ZBD (residues 164-179). Thus, QUE shows great potential as a scaffold for the design of novel potent SIRT6 modulators.

Theoretical Investigations on the Rh(III)-Catalyzed Oxidative C-H Activation/Annulation of Salicylaldehydes with Masked Enynes: Mechanism Insights and Regioselectivity Origins.

The mechanism underlying the rhodium(III)-catalyzed reaction of the C-H alkenylation/annulation reaction of salicylaldehydes with enynes has been thoroughly investigated using DFT calculations. Based on mechanistic studies, our focus primarily lies on the regioselectivity of asymmetric alkynes inserting into the Rh-C bond and the involvement of the auxiliary group OAc- in these reactions. Our theoretical study uncovers that, with acetate assistance, a stepwise SN2' cyclization, 1,3-Rh migration, ß-H elimination, and reductive elimination process occur. Furthermore, we also explore the role of substitution at Cα (CH3 vs H) in the reaction. As demonstrated in this work, these findings are applicable to other related reactions.

Electroacupuncture regulates hepatic cholesterol synthesis by HMGCR deubiquitination in rats.

This experiment was designed to explore the effect and mechanism of electroacupuncture (EA) for hyperlipidemia and hepatic cholesterol synthesis in rats. Liver and adipose tissues were assessed histologically, and body and liver weight, serum and liver lipid levels, expression of mTOR/ubiquitin-specific peptidase 20 (USP20)/recombinant 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), and phosphorylation of mTOR and USP20 were measured. In vitro deubiquitination assays with liver cytosol were conducted. EA at Fenglong point ameliorated hyperlipidemia and hepatocyte steatosis, and decreased p-USP20, p-mTOR and HMGCR expression in the liver by reducing deubiquitination. Furthermore, EA decreased feeding-induced lipid biosynthesis in the liver. Concomitantly, EA prevented the induction of phosphorylated USP20 and mTOR, and HMGCR expression; and reduced the deubiquitination of HMGCR after re-feeding. This experiment demonstrated that EA can effectively improve hyperlipidemia and reduce hepatic cholesterol synthesis by counteracting the deubiquitination activity of HMGCR in hyperlipidemic rats.

The molecular mechanism of non-covalent inhibitor WU-04 targeting SARS-CoV-2 3CLpro and computational evaluation of its effectiveness against mainstream coronaviruses.

There is an urgent need for highly effective therapeutic agents to interrupt the continued spread of SARS-CoV-2. As a pivotal protease in the replication process of coronaviruses, the 3CLpro protein is considered as a potential target of drug development to stop the spread and infection of the virus. In this work, molecular dynamics (MD) simulations were used to elucidate the molecular mechanism of a novel and highly effective non-covalent inhibitor, WU-04, targeting the SARS-CoV-2 3CLpro protein. The difference in dynamic behavior between the apo-3CLpro and the holo-3CLpro systems suggests that the presence of WU-04 inhibits the motion amplitude of the 3CLpro protein relative to the apo-3CLpro system, thus maintaining a stable conformational binding state. The energy calculations and interaction analysis show that the hot-spot residues Q189, M165, M49, E166, and H41 and the warm-spot residues H163 and C145 have a strong binding capacity to WU-04 by forming multiple hydrogen bonds and hydrophobic interactions, which stabilizes the binding of the inhibitor. After that, the resistance of WU-04 to the six SARS-CoV-2 variants (Alpha, Beta, Gamma, Delta, Lambda, and Omicron) and two other mainstream coronavirus (SARS-CoV and MERS-CoV) 3CLpro proteins was further investigated. Excitingly, the slight difference in energy values relative to the SARS-CoV-2 system indicates that WU-04 is still highly effective against the coronaviruses, which becomes crucial evidence that WU-04 is a pan-inhibitor of the 3CLpro protein in various SARS-CoV-2 variants and other mainstream coronaviruses. The study will hopefully provide theoretical insights for the future rational design and improvement of novel non-covalent inhibitors targeting the 3CLpro protein.

Investigating the influence of substituent groups in TTM based radicals for the excitation process: a theoretical study.

Tri-(2,4,6-trichlorophenyl)methyl (TTM) based radicals can be promising in providing relatively high fluorescence quantum efficiency. In this study, we have evaluated the photoluminescence properties of a series of TTM-based radicals by means of DFT and TD-DFT methods. The optimized structures of the ground states (D0) and the first excited states (D1) of all the radicals are calculated and the computed emission bands are comparable with previous experimental results. knr is determined from transition dipole moments (µ12) and the energy gaps between D0 and D1 (ΔE), both of which can be regulated by the conjugated structures from the substituent groups. knr was derived from the mode-averaging method and is consistent with the experimental results. Factors influencing kr and knr, including the potential energy differences (ΔG0), the vibrational reorganization energies (λ) and the electron coupling term (Hab), are discussed. By comparing kr and knr in solvents with different polarities (cyclohexane, toluene, and chloroform), TTM based radicals in cyclohexane exhibit the most promising fluorescence efficiencies. Besides, two substituted radicals, namely 2Br-TTM-3PCz and 2F-TTM-3PCz, have been fabricated. The results show that fluorine atoms are able to increase ΔG0 and a considerably small knr has been predicted. We expect that our calculation can benefit the design of light-emitting molecules in further experiments.

GABAergic Neurons in the Nucleus Accumbens are Involved in the General Anesthesia Effect of Propofol.

The mechanism underlying the hypnosis effect of propofol is still not fully understood. In essence, the nucleus accumbens (NAc) is crucial for regulating wakefulness and may be directly engaged in the principle of general anesthesia. However, the role of NAc in the process of propofol-induced anesthesia is still unknown. We used immunofluorescence, western blotting, and patch-clamp to access the activities of NAc GABAergic neurons during propofol anesthesia, and then we utilized chemogenetic and optogenetic methods to explore the role of NAc GABAergic neurons in regulating propofol-induced general anesthesia states. Moreover, we also conducted behavioral tests to analyze anesthetic induction and emergence. We found out that c-Fos expression was considerably dropped in NAc GABAergic neurons after propofol injection. Meanwhile, patch-clamp recording of brain slices showed that firing frequency induced by step currents in NAc GABAergic neurons significantly decreased after propofol perfusion. Notably, chemically selective stimulation of NAc GABAergic neurons during propofol anesthesia lowered propofol sensitivity, prolonged the induction of propofol anesthesia, and facilitated recovery; the inhibition of NAc GABAergic neurons exerted opposite effects. Furthermore, optogenetic activation of NAc GABAergic neurons promoted emergence whereas the result of optogenetic inhibition was the opposite. Our results demonstrate that NAc GABAergic neurons modulate propofol anesthesia induction and emergence.

Mechanistic Study on CpRh(III)-Catalyzed [3 + 2] Annulation of Aniline Derivatives with Vinylsilanes: A DFT Study.

The rhodium(III)-catalyzed reaction of aniline derivatives that contain a pyrimidine-directing group with vinylsilanes results in the formation of C3-substituted indoline derivatives. The reaction path and formation of the indoline product with density functional theory calculations were analyzed. This study reveals that the whole catalysis can be characterized in the following stages: (I) C-H activation via concerted metalation deprotonation, (II) 2,1-vinylsilane insertion, (III) deprotonation of the NH amide proton, (IV) the oxidation of Ag+, and (V) reductive elimination. These steps are kinetically and thermodynamically feasible for experimental realization under mild conditions, and the insertion step with a barrier of 22.0 kcal/mol should not only be the critical step of regioselectivity but also the rate-determining step during the whole catalysis. Computations reveal that the Ag+ oxidation can accelerate the reductive elimination step after the formation of natural intermediate, thus highlighting the role of Ag+ as a catalytic promoter for the oxidatively induced reactivity of the Rh catalyst in C3-substituted indoline synthesis.

In silico design of miniprotein to inhibit SARS-CoV-2 variant Omicron spike protein.

Omicron is a novel variant of SARS-CoV-2 that is currently spreading globally as the dominant strain. The virus first enters the host cell through the receptor binding domain (RBD) of the spike protein by interacting with the angiotensin-converting enzyme 2 (ACE2). Thus, the RBD protein is an ideal target for the design of drugs against the Omicron variant. Here, we designed several miniprotein inhibitors in silico to combat the SARS-CoV-2 Omicron variant using single- and double-point mutation approaches, based on the structure of the initial inhibitor AHB2. Also, two parallel molecular dynamics (MD) simulations were performed for each system to reproduce the calculated results, and the binding free energy was evaluated with the MM/PBSA method. The evaluated values showed that all inhibitors, including AHB2, M7E, M7E + M43W, and M7E + M43Y, were energetically more beneficial to the binding with the RBD than ACE2. In particular, the mutant inhibitor M7E + M43Y possessed the highest binding affinity to RBD and was selected as the most promising "best" inhibitor among all inhibitors. In addition, the combination of multiple analysis methods, such as free energy landscape analysis (FEL), principal component analysis (PCA), dynamic cross-correlation matrix analysis (DCCM), and hydrogen bond, salt bridge, and hydrophobic interaction analysis, also demonstrated that the mutations significantly affect the dynamical behavior and binding pattern of the inhibitor binding to the RBD protein. The current work suggested that miniprotein inhibitors can form stable complex structures with the RBD protein and exert a blocking or inhibitory effect on the SARS-CoV-2 variant Omicron. In conclusion, this study has identified several novel mutant inhibitors with enhanced affinity to the RBD protein, and provided potential guidance and insights for the rational design of therapeutic approaches for the new SARS-CoV-2 variant Omicron.

[Posterior cervical pedicle screw rod short-segment internal fixation for the treatment of atlantoaxial fracture and dislocation].

OBJECTIVE: To investigate the clinical efficacy of posterior cervical pedicle screw short-segment internal fixation for the treatment of atlantoaxial fracture and dislocation. METHODS: The clinical data of 60 patients with atlantoaxial vertebral fracture and dislocation underwent surgery between January 2015 and January 2018 were retrospectively analyzed. The patients were divided into study group and control group according to different surgical methods. There were 30 patients in study group, including 13 males and 17 females, with an average age of (39.32±2.85) years old, were underwent short-segment internal fixation with posterior cervical pedicle screws. There were 30 patients in control group, including 12 males and 18 females, with an average age of (39.57±2.90) years old, were underwent posterior lamina clip internal fixation of the atlas. The operation time, intraoperative blood loss, postoperative ambulation time, hospitalization time and complications between two groups were recorded and compared. The pain visual analogue scale(VAS), Japanese Orthopedic Association(JOA) score of neurological function, and fusion status were evaluated between two groups. RESULTS: All patients were followed up for at least 12 months. The study group was better than control group in operation time, intraoperative blood loss, postoperative off-bed activity time, and hospital stay (P=0.000). One case of respiratory tract injury occurred in study group. In control group, 2 cases occurred incision infection, 3 cases occurred respiratory tract injury, and 3 cases occurred adjacent segmental joint degeneration. The incidence of complications in study group was lower than that in control group (χ2=4.705, P=0.030). At 1, 3, 7 days after operation, VAS of study group was lower than that of control group(P=0.000). At 1, 3 months after operation, JOA score of study group was higher than that of control group(P=0.000). At 12 months after operation, all the patients in the study group achieved bony fusion. In control group, there were 3 cases of poor bony fusion and 3 cases of internal fixation fracture, the incidence rate was 20.00%(6/30). The difference between two groups was statistically significant (χ2=4.629, P=0.031). CONCLUSION: Posterior cervical short-segment pedicle screw fixation for atlantoaxial fracture and dislocation has the advantages of less trauma, shorter operation time, fewer complications, and less pain, and can promote the recovery of nerve function as soon as possible.

Theoretical Study on Zigzag Boron Nitride Nanowires.

In this work, two kinds of BN-nanowires (BNnws): a-BNnw and d-BNnw, respectively composed of azo (N-N) and diboron (B-B) bonds, are proposed with the aid of the first-principles simulations. Their structural stabilities are carefully verified from the energetics, lattice dynamics, and thermodynamic perspectives. Similar to the other common boron nitride polymorph, the a-BNnw and d-BNnw are semiconductors with relatively wide band gaps of 3.256 and 4.631 eV at the HSE06 level, respectively. The corresponding projected DOS patterns point out that their band edges are composed of different atomic species, which can help with the separation of their excitons. The band gaps can be manipulated monotonically by axial strains within the elastic ranges. The major charge carriers are electron holes. Significantly, a-BNnw possesses very high carrier mobilities around 0.44×104  cm2 V-1 s-1 .

Investigation on the interaction mechanism of different SARS-CoV-2 spike variants with hACE2: insights from molecular dynamics simulations.

Since the COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), SARS-CoV-2 has evolved by acquiring genomic mutations, resulting in the recent emergence of several SARS-CoV-2 variants with improved transmissibility and infectivity relative to the original strain. An underlying mechanism may be the increased ability of the mutants to bind the receptor proteins and infect the host cell. In this work, we implemented all-atom molecular dynamics (MD) simulations to study the binding and interaction of the receptor binding domain (RBD) of the SARS-CoV-2 spike protein singly (D614G), doubly (D614G + L452R and D614G + N501Y), triply (D614G + N501Y + E484K), and quadruply (D614G + N501Y + E484K + K417T) mutated variants with the human angiotensin-converting enzyme 2 (hACE2) receptor protein in the host cell. A combination of multiple analysis approaches elucidated the effects of mutations and the extent of molecular divergence from multiple perspectives, including the dynamic correlated motions, interaction patterns, dominant motions, free energy landscape, and charge distribution on the electrostatic potential surface between the hACE2 and all RBD variants. Moreover, free energy calculations using the MM/PBSA method evaluated the binding affinity between these RBD variants and hACE2. The results showed that the D614G + N501Y + E484K variant possessed the lowest free energy value (highest affinity) compared to the D614G + N501Y + E484K + K417T, D614G + L452R, D614G + N501Y, and D614G mutants. The residue-based energy decomposition also indicated that the energy contribution of residues at the mutation site to the total binding energy was highly variable. The interaction mechanisms between the different RBD variants and hACE2 elucidated in this study will provide some insights into the development of drugs targeting the new SARS-CoV-2 variants.

A theoretical study based on DFT calculations on the different influence of functional groups on the C-H activation process via Pd-catalysed ß-X elimination.

We have performed a series of theoretical calculations for palladium-catalyzed ß-X elimination reactions. The DFT calculation combined with energy decomposition analysis shows the determining factors of reactivity. Such as, the elemental composition, the structure of different functional groups and the stronger steric repulsions contribution.

Computational Design of Miniprotein Inhibitors Targeting SARS-CoV-2 Spike Protein.

The ongoing pandemic of COVID-19 caused by SARS-CoV-2 has become a global health problem. There is an urgent need to develop therapeutic drugs, effective therapies, and vaccines to prevent the spread of the virus. The virus first enters the host cell through the interaction between the receptor binding domain (RBD) of spike protein and the peptidase domain (PD) of the angiotensin-converting enzyme 2 (ACE2). Therefore, blocking the binding of RBD and ACE2 is a promising strategy to inhibit the invasion and infection of the virus in the host cell. In the study, we designed several miniprotein inhibitors against SARS-CoV-2 by single/double/triple-point mutant, based on the initial inhibitor LCB3. Molecular dynamics (MD) simulations and trajectory analysis were performed for an in-depth analysis of the structural stability, essential protein motions, and per-residue energy decomposition involved in the interaction of inhibitors with the RBD. The results showed that the inhibitors have adapted the protein RBD in the binding interface, thereby forming stable complexes. These inhibitors display low binding free energy in the MM/PBSA calculations, substantiating their strong interaction with RBD. Moreover, the binding affinity of the best miniprotein inhibitor, H6Y-M7L-L17F mutant, to RBD was ∼45 980 times (ΔG = RT ln Ki) higher than that of the initial inhibitor LCB3. Following H6Y-M7L-L17F mutant, the inhibitors with strong binding activity are successively H6Y-L17F, L17F, H6Y, and F30Y mutants. Our research proves that the miniprotein inhibitors can maintain their secondary structure and have a highly stable blocking (binding) effect on SARS-CoV-2. This study proposes novel miniprotein mutant inhibitors with enhanced binding to spike protein and provides potential guidance for the rational design of new SARS-CoV-2 spike protein inhibitors.

Molecular Dynamics Simulation Investigation of the Binding and Interaction of the EphA6-Odin Protein Complex.

Protein-protein interaction plays an important role in the development of almost all cells. Elucidating the dynamic binding and affinity of a protein-protein complex is essential for understanding the biological functions of proteins. EphA6 and Odin proteins are members of the Eph (erythropoietin-producing hepatocyte) receptor family and the Anks (ankyrin repeat and sterile α motif domain-containing) family, respectively. Odin significantly functions in regulating endocytosis, degradation, and stability of EphA receptors. In this work, the key residues of the interaction interface were determined through a hydrogen bond, root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), and dynamic correlation analysis of the conventional molecular dynamics (MD) simulations. The calculated standard binding free energy, -7.92 kcal/mol, between EphA6 and Odin is quite consistent with the experimental measurement value, -8.73 kcal/mol. By the combination of several MD simulation techniques, our investigation of the binding process reveals the detailed representative characteristics of the entire binding pathway at the molecular level. Based on the obtained potential of the mean force (PMF) curve, the analysis of the simulation trajectories shows that the residue Arg1013 in the receptor EphA6 is responsible for capturing Asp739 and Asp740 in the ligand Odin during the initial stage of binding. In the later stage of binding, the hydrogen bonds and salt bridges between a series of residues Lys973, Leu1007, Gly1009, His1010, and Arg1012 in the receptor and residues Leu735, Asn736, Asp739, Asp740, and Asp753 in the ligand mainly contribute to the stability of the protein complex. In addition, the specific change process of the receptor-ligand-binding mode is also clarified during the binding process. Our present simulation will promote a deep understanding of the protein-protein interaction, and the identified key interresidue interaction will be theoretical guidance for the design of protein drugs.

Investigation of the adsorption properties of gemcitabine anticancer drug with metal-doped boron nitride fullerenes as a drug-delivery carrier: a DFT study.

Anticancer-drug delivery is now becoming a challenging approach for researchers as it allows controlled drug delivery near cancerous cells with minimized generic collection and the avoidance of secondary side effects. Hence in this work, the applications of nanostructures as anticancer drug-delivery carriers were widely investigated to target cancerous tissues. Based on DFT calculations, we investigated the transition metal-doped boron nitride nanostructure as a drug-delivery agent for the gemcitabine drug utilizing the B3LYP/6-31G (d, p) level of theory. In this research, the adsorption energy and electronic parameters of gemcitabine on the interaction with the metal-doped BN nanostructures were studied. It has been observed that metal doping significantly enhances the drug-delivery properties of BN nanostructures. Among the investigated nanostructures, Ni-BN has been found to be the most prominent nanostructure to transport gemcitabine with an elevated value of adsorption energy in both the gas phase (-45.79) and water media (-32.46). The interaction between gemcitabine and BN nanostructures was confirmed through frontier molecular orbitals and stabilization energy analysis. The fractional charge transfer, MEP, NCI, and NBO analyses exposed the charge transfer from drug molecule to the BN nanostructures. Transition density maps and UV-VIS spectra were also plotted to investigate the excited-state properties of the designed complexes. Thus, the present study provides an in-depth interaction mechanism of the gemcitabine drug with BN, which reveals that metal-doped BN nanostructures can be a favorable drug-delivery vehicle for the gemcitabine anticancer drug.

Refine the evaluation of photophysical properties of organometallic chromophores under confined molecular crystal conditions.

Many impressive results have been achieved in the researches and developments of luminescent chromophore materials by combining experimental synthesis and characterization with the cooperative theoretical calculation. However, the existing theoretical studies are usually based on the intrinsic properties of isolated molecules and extend their properties to the whole molecular material directly, which will lead to the persistence of errors and affect the computational design of molecular materials with different morphology. Therefore, the study of multimolecular systems needs to further consider the environmental effects on molecules. This work is based on the calculation of a series of crystalline Ir(III) complexes under background charge conditions to reveal how the surrounding charge affects the photophysical properties of a series of transition metal Ir(III) complex materials. Through this method, the study of crystalline complexes is found to be more authentically reproduced the charge transfer state, energy level, and reorganization energy, etc., and shows the changes of luminescence characteristics and efficiency. The change of the electronic structure of the target molecule would be characterized more comprehensively, thus obtaining more accurate results for the excited states properties of molecular materials.

Altered task modulation of global signal topography in the default-mode network of unmedicated major depressive disorder.

BACKGROUND: Altered global signal (GS) topography features in the resting-state fMRI of major depressive disorder (MDD), showing abnormally strong global signal representation in the default-mode network (DMN). Whether the abnormal local to global change also shapes activity during task states, and how it relates to psychopathological symptoms, e.g., abnormally slow time speed of motor, cognitive, and affective symptoms, remains unknown. METHODS: We investigated fMRI-based GS with its topographical representation during task states in unmedicated 51 MDD subjects and 28 healthy subjects. Task-related global signal correlation (GSCORR) was probed by a novel paradigm testing the processing of negative/neutral emotions during different time speeds, i.e., slow and fast. RESULTS: We observed a significant interaction between time speed and emotion of GSCORR in various DMN regions in healthy subjects. Next, we showed that MDD exhibits reduced task-related GSCORR in various DMN regions during specifically the fast processing of negative emotions. Finally, we demonstrated that GSCORR in DMN and other brain regions (motor-related regions, inferior frontal cortex) correlated with the degree of psychomotor retardation especially during the fast emotional stimuli. LIMITATIONS: The measurement of interoceptive variables like respiration rate or heart rate were not included in our fMRI acquisition. CONCLUSION: Together, we demonstrated the functional relevance of GS topography by showing reduced GSCORR in DMN during specifically the fast processing of negative emotions in MDD, suggesting the abnormal slowness, i.e., reduced time speed, to be a key feature of both brain and symptoms in MDD.

C2-C3 Anterior Cervical Diskectomy and Fusion for Hangman's Fractures with C2 Posterior Dislocation: Technical Notes.

BACKGROUND: The overwhelming majority of hangman's fractures cause anterior dislocation of C2. Hangman's fracture with C2 posterior dislocation is extremely rare; only 1 pediatric case was reported in 2018 to date. This kind of injury cannot be cataloged using current classification schemes, and no established treatment recommendations exist. The purpose of this article is to report a rare case of a hangman's fracture with C2 posterior dislocation, which does not fit into existing classification systems and discuss management technical notes to avoid pitfalls. METHODS: We describe this case, review relevant literature, and share our experience. RESULTS: A 31-year-old male sustained a hangman's fracture with C2 posterior dislocation after he fell into a 50-cm deep roadside ditch when riding a motorcycle. Radiograph and computed tomography on admission showed fractures through both pars of C2 and C2 posterior dislocation. Magnetic resonance imaging on admission showed high T2-weighted signal intensity of cervical spinal cord and compression of the cervical spinal cord by posterior dislocation of the C2 vertebral body. A C2-3 anterior cervical diskectomy and fusion was performed. At 6 months after operation, bony fusion was achieved and magnetic resonance imaging showed the T2-weighted signal hyperintensity of cervical spinal cord before surgery disappeared. CONCLUSIONS: C2-C3 anterior cervical diskectomy and fusion is recommended for hangman's fractures with C2 posterior dislocation. Traction before surgery is not recommended.