Augmented pathogen detection in brain abscess using metagenomic next-generation sequencing: a retrospective cohort study.

Brain abscess is a severe infection characterized by the accumulation of pus within the brain parenchyma. Accurate identification of the causative pathogens is crucial for effective treatment and improved patient outcomes. This 10-year retrospective, single-center study aimed to compare the detection performance of conventional culture methods and metagenomic next-generation sequencing (mNGS) in brain abscess. We reviewed 612 patients diagnosed with brain abscess and identified 174 cases with confirmed etiology. The median age was 52 years, with 69.5% males. Culture tests predominately identified gram-positive bacteria, particularly Streptococcus spp. Gram-negative bacteria, including Klebsiella spp., were also detected. However, mNGS revealed a more diverse pathogen spectrum, focusing on anaerobes (e.g., Fusobacterium spp., Parvimonas spp., Porphyromonas spp., Prevotella spp., and Tannerella spp.). mNGS exhibited significantly higher overall pathogen-positive rates in pus samples (85.0% vs 50.0%, P = 0.0181) and CSF samples (84.2% vs 7.9%, P < 0.0001) compared to culture. Furthermore, the detection rates for anaerobes displayed a notable disparity, with mNGS yielding significantly higher positive detections in both pus samples (50.0% vs 10%, P = 0.0058) and CSF samples (18.4% vs 0%, P = 0.0115) when compared to culture methods. The assistance of mNGS in pathogen detection, particularly anaerobes in brain abscess, was evident in our findings. mNGS demonstrated the ability to identify rare and fastidious pathogens, even in culture-negative cases. These results emphasize the clinical value of mNGS as a supplement for brain abscess, enabling more comprehensive and accurate pathogen identification.IMPORTANCEThe accurate identification of pathogens causing brain abscess is crucial for effective treatment and improved patient outcomes. In this 10-year retrospective study, the detection performance of conventional culture methods and metagenomic next-generation sequencing (mNGS) was compared. The study analyzed 612 patients with brain abscess and confirmed etiology in 174 cases. The results showed that culture tests predominantly identified gram-positive bacteria, while mNGS unveiled a broader diverse pathogen spectrum, particularly anaerobes. The mNGS method exhibited significantly higher overall rates of pathogen positivity both in pus and cerebrospinal fluid (CSF) samples, surpassing the culture methods. Notably, mNGS detected a significantly higher number of anaerobes in both pus and CSF samples compared to culture methods. These findings underscore the clinical value of mNGS as a supplement for brain abscess diagnosis, enabling more comprehensive and accurate pathogen identification, particularly for rare and fastidious pathogens that evade detection by conventional culture methods.

Metabolic network rewiring and temperature-dependent regulation for enhanced 3-dehydroshikimate production in Escherichia coli.

The cyclohexane organic acid 3-dehydroshikimate (DHS) has potent antioxidant activity and is widely utilised in chemical and pharmaceutical industries. However, its production requires a long fermentation with a suboptimal yield and low productivity, and a disproportionate growth-to-production ratio impedes the upscaling of DHS synthesis in microbial cell factories. To overcome these limitations, competing and degradation pathways were knocked-out and key enzymes were balanced in an engineered Escherichia coli production strain, resulting in 12.2 g/L DHS. Furthermore, to achieve equilibrium between cell growth and DHS production, a CRISPRi-based temperature-responsive multi-component repressor system was developed to dynamically control the expression of critical genes (pykF and aroE), resulting in a 30-fold increase in DHS titer. After 33 h fermentation in 5 L bioreactor, the DHS titer, productivity and yield reached 94.2 g/L, 2.8 g/L/h and 55 % glucose conversion, respectively. The results provided valuable insight into the production of DHS and its derivatives.

The copepod Acartia spinicauda feeds less and dies more under the influences of solar ultraviolet radiation and elevated pCO2.

While solar ultraviolet radiation (UVR) is known to impact zooplankton, little has been documented on its impacts under elevated pCO2. Here, we show that exposure to UVR decreased the feeding and survival rates of the copepod Acartia spinicauda, that artificial UV-B of 2.25 W·m-2 for 4 h resulted in a 52 % inhibition of its grazing rates and a 45 % reduction in survival rates compared to visible light alone. On the other hand, an increase in pCO2 to 1000 µatm (pH drop of 0.4) immediately and significantly increased the UVR-induced inhibition of feeding. Subsequently, the combination of the high pCO2 (1000 µatm) and UVR resulted in about 65 % lethal impact, with UV-A contributing 21 % and UV-B 44 % compared to the visible light alone and ambient pCO2 conditions. While the copepod was shown to be able to sense and escape from UV-exposed areas, these findings suggest that UVR impacts on the copepod can be exacerbated with progressive ocean acidification or in high CO2 waters, including upwelled regions.

Effects of Electrochemical Hydrogen Charging Parameters on the Mechanical Behaviors of High-Strength Steel.

Extended exposure to seawater results in the erosion of the structural high-strength steels utilized in marine equipment, primarily due to the infiltration of hydrogen. Consequently, this erosion leads to a decrease in the mechanical properties of the material. In this investigation, the mechanical responses of Q690 structural high-strength steel specimens were investigated by considering various hydrogen charging parameters, such as the current density, charging duration, and solution concentration values. The findings highlighted the significant impacts of electrochemical hydrogen charging parameters on the mechanical behaviors of Q690 steel samples. Specifically, a linear relationship was observed between the mechanical properties and the hydrogen charging current densities, while the associations with the charging duration and solution concentration were nonlinear. Additionally, the fracture morphology under various hydrogen charging parameters was analyzed and discussed. The results demonstrate that the mechanical properties of the material degrade with increasing hydrogen charging parameters, with tensile strength and yield stress decreasing by approximately 2-4%, and elongation after fracture reducing by about 20%. The findings also reveal that macroscopic fractures exhibit significant necking in uncharged conditions. As hydrogen charging parameters increase, macroscopic necking gradually diminishes, the number of microscopic dimples decreases, and the material ultimately transitions to a fully brittle fracture.

Liquid-liquid phase separation is essential for reovirus viroplasm formation and immune evasion.

Grass carp reovirus (GCRV) is the most virulent pathogen in the genus Aquareovirus, belonging to the family Spinareoviridae. Members of the Spinareoviridae family are known to replicate and assemble in cytoplasmic inclusion bodies termed viroplasms; however, the detailed mechanism underlying GCRV viroplasm formation and its specific roles in virus infection remains largely unknown. Here, we demonstrate that GCRV viroplasms form through liquid-liquid phase separation (LLPS) of the nonstructural protein NS80 and elucidate the specific role of LLPS during reovirus infection and immune evasion. We observe that viroplasms coalesce within the cytoplasm of GCRV-infected cells. Immunofluorescence and transmission electron microscopy indicate that GCRV viroplasms are membraneless structures. Live-cell imaging and fluorescence recovery after photobleaching assay reveal that GCRV viroplasms exhibit liquid-like properties and are highly dynamic structures undergoing fusion and fission. Furthermore, by using a reagent to inhibit the LLPS process and constructing an NS80 mutant defective in LLPS, we confirm that the liquid-like properties of viroplasms are essential for recruiting viral dsRNA, viral RdRp, and viral proteins to participate in viral genome replication and virion assembly, as well as for sequestering host antiviral factors for immune evasion. Collectively, our findings provide detailed insights into reovirus viroplasm formation and reveal the specific functions of LLPS during virus infection and immune evasion, identifying potential targets for the prevention and control of this virus. IMPORTANCE: Grass carp reovirus (GCRV) poses a significant threat to the aquaculture industry, particularly in China, where grass carp is a vital commercial fish species. However, detailed information regarding how GCRV viroplasms form and their specific roles in GCRV infection remains largely unknown. We discovered that GCRV viroplasms exhibit liquid-like properties and are formed through a physico-chemical biological phenomenon known as liquid-liquid phase separation (LLPS), primarily driven by the nonstructural protein NS80. Furthermore, we confirmed that the liquid-like properties of viroplasms are essential for virus replication, assembly, and immune evasion. Our study not only contributes to a deeper understanding of GCRV infection but also sheds light on broader aspects of viroplasm biology. Given that viroplasms are a universal feature of reovirus infection, inhibiting LLPS and then blocking viroplasms formation may serve as a potential pan-reovirus inhibition strategy.

Altered lipid metabolism promoting cardiac fibrosis is mediated by CD34+ cell-derived FABP4+ fibroblasts.

Hyperlipidemia and hypertension might play a role in cardiac fibrosis, in which a heterogeneous population of fibroblasts seems important. However, it is unknown whether CD34+ progenitor cells are involved in the pathogenesis of heart fibrosis. This study aimed to explore the mechanism of CD34+ cell differentiation in cardiac fibrosis during hyperlipidemia. Through the analysis of transcriptomes from 50,870 single cells extracted from mouse hearts and 76,851 single cells from human hearts, we have effectively demonstrated the evolving cellular landscape throughout cardiac fibrosis. Disturbances in lipid metabolism can accelerate the development of fibrosis. Through the integration of bone marrow transplantation models and lineage tracing, our study showed that hyperlipidemia can expedite the differentiation of non-bone marrow-derived CD34+ cells into fibroblasts, particularly FABP4+ fibroblasts, in response to angiotensin II. Interestingly, the partial depletion of CD34+ cells led to a notable reduction in triglycerides in the heart, mitigated fibrosis, and improved cardiac function. Furthermore, immunostaining of human heart tissue revealed colocalization of CD34+ cells and fibroblasts. Mechanistically, our investigation of single-cell RNA sequencing data through pseudotime analysis combined with in vitro cellular studies revealed the crucial role of the PPARγ/Akt/Gsk3ß pathway in orchestrating the differentiation of CD34+ cells into FABP4+ fibroblasts. Through our study, we generated valuable insights into the cellular landscape of CD34+ cell-derived cells in the hypertrophic heart with hyperlipidemia, indicating that the differentiation of non-bone marrow-derived CD34+ cells into FABP4+ fibroblasts during this process accelerates lipid accumulation and promotes heart failure via the PPARγ/Akt/Gsk3ß pathway.

High Quality Epitaxial Piezoelectric and Ferroelectric Wurtzite Al1- xScxN Thin Films.

Piezoelectric and ferroelectric wurtzite are promising to reshape modern microelectronics because they can be easily integrated with mainstream semiconductor technology. Sc doped AlN (Al1- xScxN) has attracted much attention for its enhanced piezoelectric and emerging ferroelectric properties, yet the commonly used sputtering results in polycrystalline Al1- xScxN films with high leakage current. Here, the pulsed laser deposition of single crystalline epitaxial Al1- xScxN thin films on sapphire and 4H-SiC substrates is reported. Pure wurtzite phase is maintained up to x = 0.3 with ≤0.1 at% oxygen contamination. Polarization is estimated to be 140 µC cm-2 via atomic scale microscopy imaging and found to be switchable via a scanning probe. The piezoelectric coefficient is found to be five times of the undoped one when x = 0.3, making it desirable for high-frequency radiofrequency (RF) filters and 3D nonvolatile memories.

The induction of drug uptake transporter OATP1A2 by radiation is mediated by non-receptor tyrosine kinase YES-1.

Organic anion transporting polypeptides (OATP, gene symbol SLCO) are well-recognized key determinants for the absorption, distribution, and excretion of a wide spectrum of endogenous and exogenous compounds including many antineoplastic agents. It was therefore proposed as a potential drug target for cancer therapy. In our previous study, it was found that low-dose X-ray and carbon ion irradiation both up-regulated the expression of OATP family member OATP1A2 and in turn, led to a more dramatic killing effect when cancer cells were co-treated with antitumor drugs such as methotrexate. In the present study, the underlying mechanism of the phenomenon was explored in breast cancer cell line MCF-7. It was found that the non-receptor tyrosine kinase YES-1 was temporally coordinated with the change of OATP1A2 after irradiation. The over-expression of YES-1 significantly increased OATP1A2 both at the mRNA and protein level. The signal transducer and activator of transcription 3 (STAT3) pathway is likely the downstream target of YES-1 since phosphorylation and nuclear accumulation of STAT3 were both enhanced after over-expressing YES-1 in MCF-7 cells. Further investigation revealed that there are two possible binding sites of STAT3 localized at the upstream sequence of SLCO1A2, the encoding gene of OATP1A2. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) analysis suggested that these two sites bound to STAT3 specifically and the over-expression of YES-1 significantly increased the association of the transcription factor with the putative binding sites. Finally, inhibition or knock-down of YES-1 attenuated the induction effect of radiation on the expression of OATP1A2. Significance Statement The current study found that the effect of X-rays on YES-1 and OATP1A2 is temporally coordinated. YES-1 phosphorylates and increases the nuclear accumulation of STAT3, which in turn binds to the upstream regulatory sequences of SLCO1A2, the coding gene for OATP1A2. Hence, inhibitors of YES-1 may suppress the radiation induction effect on OATP1A2.

Navß2 Intracellular Fragments Contribute to Aß1-42-Induced Cognitive Impairment and Synaptic Deficit Through Transcriptional Suppression of BDNF.

A pathological hallmark of Alzheimer's disease (AD) is the region-specific accumulation of the amyloid-beta protein (Aß), which triggers aberrant neuronal excitability, synaptic impairment, and progressive cognitive decline. Previous works have demonstrated that Aß pathology induced aberrant elevation in the levels and excessive enzymatic hydrolysis of voltage-gated sodium channel type 2 beta subunit (Navß2) in the brain of AD models, accompanied by alteration in excitability of hippocampal neurons, synaptic deficits, and subsequently, cognitive dysfunction. However, the mechanism is unclear. In this research, by employing cell models treated with toxic Aß1-42 and AD mice, the possible effects and potential mechanisms induced by Navß2. The results reveal that Aß1-42 induces remarkable increases in Navß2 intracellular domain (Navß2-ICD) and decreases in both BDNF exons and protein levels, as well as phosphorylated tropomyosin-related kinase B (pTrkB) expression in cells and mice, coupled with cognitive impairments, synaptic deficits, and aberrant neuronal excitability. Administration with exogenous Navß2-ICD further enhances these effects induced by Aß1-42, while interfering the generation of Navß2-ICD and/or complementing BDNF neutralize the Navß2-ICD-conducted effects. Luciferase reporter assay verifies that Navß2-ICD regulates BDNF transcription and expression by targeting its promoter. Collectively, our findings partially elucidate that abnormal enzymatic hydrolysis of Navß2 induced by Aß1-42-associated AD pathology leads to intracellular Navß2-ICD overload, which may responsible to abnormal neuronal excitability, synaptic deficit, and cognition dysfunction, through its transcriptional suppression on BDNF. Therefore, this work supplies novel evidences that Navß2 plays crucial roles in the occurrence and progression of cognitive impairment of AD by transcriptional regulatory activity of its cleaved ICD.

Screening of ent-copalyl diphosphate synthase and metabolic engineering to achieve de novo biosynthesis of ent-copalol in Saccharomyces cerevisiae.

The diterpene ent-copalol is an important precursor to the synthesis of andrographolide and is found only in green chiretta (Andrographis paniculata). De novo biosynthesis of ent-copalol has not been reported, because the catalytic activity of ent-copalyl diphosphate synthase (CPS) is very low in microorganisms. In order to achieve the biosynthesis of ent-copalol, Saccharomyces cerevisiae was selected as the chassis strain, because its endogenous mevalonate pathway and dephosphorylases could provide natural promotion for the synthesis of ent-copalol. The strain capable of synthesizing diterpene geranylgeranyl pyrophosphate was constructed by strengthening the mevalonate pathway genes and weakening the competing pathway. Five full-length ApCPSs were screened by transcriptome sequencing of A. paniculata and ApCPS2 had the best activity and produced ent-CPP exclusively. The peak area of ent-copalol was increased after the ApCPS2 saturation mutation and its configuration was determined by NMR and ESI-MS detection. By appropriately optimizing acetyl-CoA supply and fusion-expressing key enzymes, 35.6 mg/L ent-copalol was generated. In this study, de novo biosynthesis and identification of ent-copalol were achieved and the highest titer ever reported. It provides a platform strain for the further pathway analysis of andrographolide and derivatives and provides a reference for the synthesis of other pharmaceutical intermediates.

Engineering Gluconbacter oxydans with efficient co-utilization of glucose and sorbitol for one-step biosynthesis of 2-keto-L-gulonic.

As the highest-demand vitamin, the development of a one-step vitamin C synthesis process has been slow for a long time. In previous research, a Gluconobacter oxydans strain (GKLG9) was constructed that can directly synthesize 2-keto-L-gulonic acid (2-KLG) from glucose, but carbon source utilization remained low. Therefore, this study first identified the gene 4kas (4-keto-D-arabate synthase) to reduce the loss of extracellular carbon and inhibit the browning of fermentation broth. Then, promoter engineering was conducted to enhance the intracellular glucose transport pathway and concentrate intracellular glucose metabolism on the pentose phosphate pathway to provide more reducing power. Finally, by introducing the D-sorbitol pathway, the titer of 2-KLG was increased to 38.6 g/L within 60 h in a 5-L bioreactor, with a glucose-to-2-KLG conversion rate of about 46 %. This study is an important step in the development of single-bacterial one-step fermentation to produce 2-KLG.

Freezing Hu ram semen: influence of different penetrating cryoprotectants and egg yolk level on the post-thaw quality of sperm.

OBJECTIVE: The Hu sheep is a renowned breed known for its high reproductive rate. It is in estrus all year round, and its breeding population is gradually expanding. However, the current techniques for cryopreserving semen have limited effectiveness, which hinders the continuous development of this species. The purpose of this study is to explore the effects of different penetrating cryoprotectants (CPAs) and egg yolk (EY) concentrations on the cryopreservation of Hu ram semen to determine the most effective combination. METHODS: In this study, the effects of glycerol (GLY), ethylene glycol (EG), dimethylacetamide, dimethyl sulfoxide, different proportions of GLY and EG, EY on sperm quality after thawing were investigated by detecting sperm total motility (TM), progressive motility (PM), straight-line velocity, curvilinear velocity, average path velocity, amplitude of lateral head displacement, wobble movement coefficient, average motion degree, functional integrity (plasma membrane integrity, acrosome integrity) and reactive oxygen species (ROS) level. RESULTS: When GLY and EG were added together, compared to other concentration groups, 6% GLY significantly (p<0.05) increased TM, PM, plasma membrane integrity, and acrosome integrity of thawed sperm. Additionally, it significantly (p<0.05) decreased the ROS level of sperm. In this study, the TM, PM, and membrane integrity of the 6% EG were significantly (p<0.05) higher than those of the control, 1% GLY+5% EG and 6% GLY+6% EG groups. Compared to other concentration groups, 20% EY significantly (p<0.05) improved the TM, PM, and plasma membrane integrity of thawed sperm. However, the integrity of the acrosome increased with the higher concentration of EY. CONCLUSION: In conclusion, the post-thawed Hu ram semen diluted with a diluent containing 6% GLY and 20% EY exhibited higher quality compared to the other groups.

Use of Intravoxel Incoherent Motion Diffusion-Weighted Imaging to Assess Mesenchymal Stromal Cells Promoting Liver Regeneration in a Rat Model.

RATIONALE AND OBJECTIVES: Mesenchymal stem cells (MSCs) have the potential to promote liver regeneration, but the process is unclear. This study aims to explore the therapeutic effects and dynamic processes of MSCs in liver regeneration through intravoxel incoherent motion (IVIM) imaging. ANIMAL MODEL: 70 adult Sprague-Dawley rats were randomly divided into either the control or MSC group (n = 35/group). All rats received a partial hepatectomy (PH) with the left lateral and middle lobes removed. Each group was divided into seven subgroups: pre-PH and 1, 2, 3, 5, 7, and 14 days post-PH (n = 5 rats/subgroup). Magnetic resonance imaging (MRI) was performed before obtaining pathological specimens at each time point on postoperative days 1, 2, 3, 5, 7, and 14. The MRI parameters for the pure diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (PF) were calculated. Correlation analysis was conducted for the biochemical markers (alanine transaminase [ALT], aspartate transaminase [AST], and total bilirubin [TBIL]), histopathological findings (hepatocyte size and Ki-67 proliferation index), liver volume (LV) and liver regeneration rate (LLR). RESULTS: Liver D, D* , and PF differed significantly between the control and MSC groups at all time points (all P < 0.05). After PH, the D increased, then decreased, and the D* and PF decreased, then increased in both groups. The hepatocyte Ki-67 proliferation index of the MSC group was lower on day 2 post-PH, but higher on days 3 and 5 post-PH than that of the control group. Starting from day 3 post-PH, both the LV and LLR in the MSC group were greater than those in the control group (all P < 0.05). Hepatocytes were larger in the MSC group than in the control group on days 2 and 7 post-PH. In the MSC group, the D, D* , and PF were correlated with the AST levels, Ki-67 index and hepatocyte size (|r|=0.35-0.71; P < 0.05). In the control group, the D and D* were correlated with ALT levels, AST levels, Ki-67 index, LLR, LV, and hepatocyte size (|r|=0.34-0.95; P < 0.05). CONCLUSION: Bone marrow MSC therapy can promote hepatocyte hypertrophy and prolong liver proliferation post-PH. IVIM parameters allow non-invasively evaluating the efficacy of MSCs in promoting LR.

BinsFormer: Revisiting Adaptive Bins for Monocular Depth Estimation.

Monocular depth estimation (MDE) is a fundamental task in computer vision and has drawn increasing attention. Recently, some methods reformulate it as a classification-regression task to boost the model performance, where continuous depth is estimated via a linear combination of predicted probability distributions and discrete bins. In this paper, we present a novel framework called BinsFormer, tailored for the classification-regression-based depth estimation. It mainly focuses on two crucial components in the specific task: 1) proper generation of adaptive bins; and 2) sufficient interaction between probability distribution and bins predictions. To specify, we employ a Transformer decoder to generate bins, novelly viewing it as a direct set-to-set prediction problem. We further integrate a multi-scale decoder structure to achieve a comprehensive understanding of spatial geometry information and estimate depth maps in a coarse-to-fine manner. Moreover, an extra scene understanding query is proposed to improve the estimation accuracy, which turns out that models can implicitly learn useful information from the auxiliary environment classification task. Extensive experiments on the KITTI, NYU, and SUN RGB-D datasets demonstrate that BinsFormer surpasses state-of-the-art MDE methods with prominent margins. Code and pretrained models are made publicly available at https://github.com/zhyever/ Monocular-Depth-Estimation-Toolbox/tree/main/configs/ binsformer.

Effects of Different Diluents and Freezing Methods on Cryopreservation of Hu Ram Semen.

The purpose of this study was to investigate the effects of different diluents and freezing methods on the quality of thawed sperm after cryopreservation and find an inexpensive and practical method for freezing Hu ram semen for use in inseminations under farm conditions. Ejaculates were collected from five Hu rams. In experiment I, ejaculates were diluted with eight different freezing diluents (basic diluents A, B, C, D, E, F, G, and H). After dilution and cooling, the samples were loaded into 0.25 mL straws and frozen using the liquid nitrogen fumigation method. In experiment II, diluent C was used as the basic diluent and the semen was frozen using liquid nitrogen fumigation and two program-controlled cooling methods. For analysis, frozen samples were evaluated in terms of motility parameters (total motility (TM), progressive motility (PM)), biokinetic characteristics (straight-line velocity (VSL), average path velocity (VAP), curvilinear velocity (VCL), amplitude of lateral head displacement (ALH), wobble movement coefficient (WOB), average motion degree (MAD)), reactive oxygen species (ROS) level, and membrane and acrosome integrity. In experiment I, diluent C had higher TM, PM, and acrosome and membrane integrity and lower ROS compared to other extenders (p < 0.05) except diluent A. Diluent C exhibited higher (p < 0.05) VCL, VAP, ALH, WOB, and MAD compared to diluents B, D, E, and F. In experiment II, TM and all biokinetic characteristics did not show significant differences (p > 0.05) amongst the three freezing methods. Liquid nitrogen fumigation resulted in higher (p < 0.05) PM, membrane integrity, acrosome integrity, and lower ROS level compared to the program. In conclusion, the thawed semen diluted with diluent C had higher quality compared to other diluents. The liquid nitrogen fumigation demonstrated superior semen cryopreservation effects compared to the program-controlled cooling method using diluent C.

Individualized Structural Perturbations on Normative Brain Connectome Restrict Deep Brain Stimulation Outcomes in Parkinson's Disease.

BACKGROUND: Patients with Parkinson's disease (PD) respond to deep brain stimulation (DBS) variably. However, how brain substrates restrict DBS outcomes remains unclear. OBJECTIVE: In this article, we aim to identify prognostic brain signatures for explaining the response variability. METHODS: We retrospectively investigated a cohort of patients with PD (n = 141) between 2017 and 2022, and defined DBS outcomes as the improvement ratio of clinical motor scores. We used a deviation index to quantify individual perturbations on a reference structural covariance network acquired with preoperative T1-weighted magnetic resonance imaging. The neurobiological perturbations of patients were represented as z scored indices based on the chronological perturbations measured on a group of normal aging adults. RESULTS: After applying stringent statistical tests (z > 2.5) and correcting for false discoveries (P < 0.01), we found that accelerated deviations mainly affected the prefrontal cortex, motor strip, limbic system, and cerebellum in PD. Particularly, a negative network within the accelerated deviations, expressed as "more preoperative deviations, less postoperative improvements," could predict DBS outcomes (mean absolute error = 0.09, R2 = 0.15). Moreover, a fusion of personal brain predictors and medical responses significantly improved traditional evaluations of DBS outcomes. Notably, the most important brain predictor, a pathway connecting the cognitive unit (prefrontal cortex) and motor control unit (cerebellum and motor strip), partially mediates DBS outcomes with the age at surgery. CONCLUSIONS: Our findings suggest that individual structural perturbations on the cognitive motor control circuit are critical for modulating DBS outcomes. Interventions toward the circuit have the potential for additional clinical improvements. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Dynamic causal modeling analysis reveals the modulation of motor cortex and integration in superior temporal gyrus during multisensory speech perception.

The processing of speech information from various sensory modalities is crucial for human communication. Both left posterior superior temporal gyrus (pSTG) and motor cortex importantly involve in the multisensory speech perception. However, the dynamic integration of primary sensory regions to pSTG and the motor cortex remain unclear. Here, we implemented a behavioral experiment of classical McGurk effect paradigm and acquired the task functional magnetic resonance imaging (fMRI) data during synchronized audiovisual syllabic perception from 63 normal adults. We conducted dynamic causal modeling (DCM) analysis to explore the cross-modal interactions among the left pSTG, left precentral gyrus (PrG), left middle superior temporal gyrus (mSTG), and left fusiform gyrus (FuG). Bayesian model selection favored a winning model that included modulations of connections to PrG (mSTG → PrG, FuG → PrG), from PrG (PrG → mSTG, PrG → FuG), and to pSTG (mSTG → pSTG, FuG → pSTG). Moreover, the coupling strength of the above connections correlated with behavioral McGurk susceptibility. In addition, significant differences were found in the coupling strength of these connections between strong and weak McGurk perceivers. Strong perceivers modulated less inhibitory visual influence, allowed less excitatory auditory information flowing into PrG, but integrated more audiovisual information in pSTG. Taken together, our findings show that the PrG and pSTG interact dynamically with primary cortices during audiovisual speech, and support the motor cortex plays a specifically functional role in modulating the gain and salience between auditory and visual modalities. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-023-09945-z.

Bisgermylene-Stabilized Stannylone: Catalytic Reduction of Nitrous Oxide and Nitro Compounds via Element-Ligand Cooperativity.

This study describes the synthesis, structural characterization, and catalytic application of a bis(germylene)-stabilized stannylone (2). The reduction of digermylated stannylene (1) with 2.2 equiv of potassium graphite (KC8) leads to the formation of stannylone 2 as a green solid in 78% yield. Computational studies showed that stannylone 2 possesses a formal Sn(0) center and a delocalized 3-c-2-e π-bond in the Ge2Sn core, which arises from back-donation of the p-type lone pair electrons on the Sn atom to the vacant orbitals of the Ge atoms. Stannylone 2 can serve as an efficient precatalyst for the selective reduction of nitrous oxide (N2O) and nitroarenes (ArNO2) with the formation of dinitrogen (N2) and hydrazines (ArNH-NHAr), respectively. Exposure of 2 with N2O (1 atm) resulted in the insertion of two oxygen atoms into the Ge-Ge and Ge-Sn bonds, yielding the germyl(oxyl)stannylene (3). Moreover, the stoichiometric reaction of 2 with 1-chloro-4-nitrobenzene afforded an amido(oxyl)stannylene (4) through the complete scission of the N-O bonds of the nitroarene. Stannylenes 3 and 4 serve as catalytically active species for the catalytic reduction of nitrous oxide and nitroarenes, respectively. Mechanistic studies reveal that the cooperation of the low-valent Ge and Sn centers allows for multiple electron transfers to cleave the N-O bonds of N2O and ArNO2. This approach presents a new strategy for catalyzing the deoxygenation of N2O and ArNO2 using a zerovalent tin compound.

Analysis of nonlinear bending behavior of nano-switches considering surface effects.

Nano-switch structures are important control elements in nanoelectromechanical systems and have potential applications in future nanodevices. This paper analyzes the effects of surface effects, geometric nonlinearity, electrostatic forces, and intermolecular forces on the nonlinear bending behavior and adhesion stability of nano-switches. Based on the Von Karman geometric nonlinearity theory, four types of boundary conditions for the nano-switch structure were specifically calculated. The results show that surface effects have a significant impact on the nonlinear bending and adhesion stability of nano-switches. Surface effects increase the adhesion voltage of the nano-switch and decrease its adhesion displacement, and as the size of the nano-switch structure increases, the impact of surface effects decreases. A comparative analysis of the linear theory and the nonlinear theory results shows that the adhesion voltage predicted by the linear theory is smaller than that predicted by the nonlinear theory. The effect of geometric nonlinearity increases as the size of the nano-switch structure increases, as the distance between the electrodes increases, and as the aspect ratio of the nano-switch structure increases. These findings provide theoretical support and reference for the design and use of future nanodevices and nanoelectromechanical systems.