Perturbational complexity index in assessing responsiveness to rTMS treatment in patients with disorders of consciousness: a cross-over randomized controlled trial study.

BACKGROUND: Disorders of Consciousness (DoC) caused by severe brain injuries represent a challenging clinical entity, which is easy to misdiagnosis and lacks effective treatment options. Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive neuroelectric stimulation method that shows promise in improving consciousness for DoC, especially in minimally conscious state (MCS). However, there is little evidence of its effectiveness, especially in RCT studies. METHODS: Twenty MCS patients participated in a double-blind, randomized, crossover, sham-controlled clinical study to evaluate the safety and efficacy of rTMS for MCS. Subjects were randomized into two groups: one group received rTMS-active for 10 consecutive days (n = 10), and the other group received rTMS-sham for 10 consecutive days (n = 10). After a 10-day washout period, the two groups were crossed over and received the opposite treatment. the rTMS protocol consisted of 2,000 pulses per day in the left dorsolateral prefrontal cortex (L-DLPFC), sent at 10 Hz. The stimulation intensity was 90% of the resting motor threshold. Coma Recovery Scale Revised (CRS-R), the main evaluation index, was evaluated before and after each phase in a double-blind manner. Meanwhile RS-EEG and TMS-EEG data were acquired and relative alpha power (RAP), and perturbational complexity index based on state transitions (PCIst) were caculated. RESULTS: One-way ANOVA revealed significantly higher scores in rTMS-active treatment compared to rTMS-sham across various measures, including CRS-R total score, RAP, PCIst (all P < 0.05). Among the 20 MCS patients, 7 (35%) were identified as responders following rTMS treatment. Compared to rTMS-sham, responder scores for CRS-R, RAP, and PCIst (all P < 0.05) were significantly elevated after rTMS-active treatment. Conversely, there was no significant difference observed in non-responders. Furthermore, post-hoc analysis revealed that baseline PCIst was significantly higher in responders than non-responders. Upon a 6-month follow-up, CRS-R scores significantly increased in all 20 patients (P = 0.026). However, the responder group exhibited a more favorable prognosis compared to the non-responder group (P = 0.031). CONCLUSIONS: Applying 10 Hz rTMS to L-DLPFC significantly increased consciousness level in MCS patients. PCIst is a neurophysiological index that has the potential to evaluate and predict therapeutic efficacy. TRIAL REGISTRATION: www. CLINICALTRIALS: gov , identifier: NCT05187000.

The complete mitochondrial genome of the Baishanzu horned toad Boulenophrys baishanzuensis (Anura: Megophryidae).

The mitochondrial genome (mitogenome) of Boulenophrys baishanzuensis (Anura: Megophryidae) was sequenced by the Illumina platform. The assembled circular mitogenome of B. baishanzuensis had a total length of 17,040 bp, with a GC content of 41.25%. It consisted of 13 protein-coding genes (PCGs), two rRNA genes, 22 tRNA genes, and a D-loop region. The majority of the PCGs were encoded by the H-strand, while one PCG (nad6) and eight tRNA genes (tRNA-Gln, tRNA-Ala, tRNA-Asn, tRNA-Cys, tRNA-Tyr, tRNA-Ser2, tRNA-Glu, and tRNA-Pro) were encoded in the L-strand. Phylogenetic analysis revealed that the newly sequenced species formed a clade with other Boulenophrys species, while the genus Boulenophrys itself formed a sister group with the genus Atympanophrys.

The ELOVL6 homolog in Penaeus vannamei plays a dual role in fatty acid metabolism and immune response.

In mammals, elongation of very long chain fatty acid protein 6 (ELOVL6), a key enzyme in long chain fatty acids elongation, has been reported to regulate other metabolism processes and immunity, including inflammation in vertebrates. However, little is currently known about the ELOVL6 homolog in invertebrates, especially its role in immune response. In this study, the ELOVL6 ortholog in Penaeus vannamei (designated PvELOVL6) was cloned and found to have an open reading frame (ORF) of 435 bp and encode a putative protein of 144 amino acids. Transcripts of PvELOVL6 are constitutively expressed in all shrimp tissues tested and induced in the hepatopancreas and hemocytes by Vibrio parahaemolyticus and Streptococcus iniae. Besides, PvELOVL6 knockdown followed by Vibrio parahaemolyticus challenge revealed that PvELOVL6 regulates the expression of several genes involved in fatty acid metabolism and immunity, including PvLGBP, PvLectin, PvMnSOD, PvProPO, PvFABP, PvLipase, PvCOX and PvGPDH. Moreover, transcript levels of PvELOVL6, fatty acids metabolism-related genes (i.e., PvGPDH, PvFABP, PvPERO and PvSPLA2), and immune-related genes (i.e., PvProPO, PvLectin, PvLGBP, PvLysozyme and PvCatalase) increased after silencing of the sterol regulatory element binding protein (PvSREBP). Thus, PvELOVL6 is involved in immune response and regulated by PvSREBP through an unknown mechanism in penaeid shrimp.

Total Syntheses of Polyhydroxylated Steroids by an Unsaturation-Functionalization Strategy.

Highly oxygenated cardiotonic steroids, such as ouabain, possess a wide spectrum of biological functions and remain significant synthetic challenges. Herein, we have applied an unsaturation-functionalization strategy and developed a synthetic method in addressing the C19-hydroxylation issue for efficient synthesis of polyhydroxylated steroids. An effective asymmetric dearomative cyclization allowed the construction of the C19-hydroxy unsaturated steroidal skeleton in only four steps from the Hajos-Parrish ketone ketal 7. The synthetic sequence featured C3-OH-directed hydrogenation/epoxidation, m-CPBA-triggered epoxidation/SN 2' nucleophilic substitution, Birch reduction of an enone, and regioselective LiAlH4 reduction to furnish the polyhydroxy functionalities on the steroid skeleton with high stereochemical control and efficiency. This approach ultimately enabled the total synthesis of 19-hydroxysarmentogenin and ouabagenin in 18 and 19 steps, respectively, overall. The synthesis of these polyhydroxylated steroids offers synthetic versatility and practicality in the search for new therapeutic agents.

Inverse Parameter Identification for Hyperelastic Model of a Polyurea.

An inverse procedure was proposed to identify the material parameters of polyurea materials. In this procedure, a polynomial hyperelastic model was chosen as the constitutive model. Both uniaxial tension and compression tests were performed for a polyurea. An iterative inverse method was presented to identify parameters for the tensile performance of the polyurea. This method adjusts parameters iteratively to achieve a good agreement between tensile forces from the tension test and its finite element (FE) model. A response surface-based inverse method was presented to identify parameters for the compression performance of the polyurea. This method constructs a radial basis function (RBF)-based response surface model for the error between compressive forces from the compression test and its FE model, and it employs the genetic algorithm to minimize the error. With the use of the two inverse methods, two sets of parameters were obtained. Then, a complete identified uniaxial stress-strain curve for both tensile and compressive deformations was obtained with the two sets of parameters. Fitting this curve with the constitutive equation gave the final material parameters. The present inverse procedure can simplify experimental configurations and consider effects of friction in compression tests. Moreover, it produces material parameters that can appropriately characterize both tensile and compressive behaviors of the polyurea.

Novel and versatile artificial intelligence algorithms for investigating possible GHSR1α and DRD1 agonists for Alzheimer's disease.

Hippocampal lesions are recognized as the earliest pathological changes in Alzheimer's disease (AD). Recent researches have shown that the co-activation of growth hormone secretagogue receptor 1α (GHSR1α) and dopamine receptor D1 (DRD1) could recover the function of hippocampal synaptic and cognition. We combined traditional virtual screening technology with artificial intelligence models to screen multi-target agonists for target proteins from TCM database and a novel boost Generalized Regression Neural Network (GRNN) model was proposed in this article to improve the poor adjustability of GRNN. R-square was chosen to evaluate the accuracy of these artificial intelligent models. For the GHSR1α agonist dataset, Adaptive Boosting (AdaBoost), Linear Ridge Regression (LRR), Support Vector Machine (SVM), and boost GRNN achieved good results; the R-square of the test set of these models reached 0.900, 0.813, 0.708, and 0.802, respectively. For the DRD1 agonist dataset, Gradient Boosting (GB), Random Forest (RF), SVM, and boost GRNN achieved good results; the R-square of the test set of these models reached 0.839, 0.781, 0.763, and 0.815, respectively. According to these values of R-square, it is obvious that boost GRNN and SVM have better adaptability for different data sets and boost GRNN is more accurate than SVM. To evaluate the reliability of screening results, molecular dynamics (MD) simulation experiments were performed to make sure that candidates were docked well in the protein binding site. By analyzing the results of these artificial intelligent models and MD experiments, we suggest that 2007_17103 and 2007_13380 are the possible dual-target drugs for Alzheimer's disease (AD).

9-(4-Fluoro-phen-yl)-3,3,6,6-tetra-methyl-10-p-tolyl-1,2,3,4,5,6,7,8,9,10-deca-hydroacridine-1,8-dione.

The title compound, C(30)H(32)FNO(2), was synthesized by the reaction of dimedone with 4-fluoro-benzaldehyde and p-toluidine in water. The dihydro-pyridine and both of the cyclo-hexenone rings are not planar and have flattened boat conformations. The dihedral angle between the planar aromatic rings is 15.33 (3)°. In the crystal structure, inter-molecular C-H⋯O hydrogen bonds link the mol-ecules into centrosymmetric dimers.