NRF1-mediated mitochondrial biogenesis antagonizes innate antiviral immunity.

Mitochondrial biogenesis is the process of generating new mitochondria to maintain cellular homeostasis. Here, we report that viruses exploit mitochondrial biogenesis to antagonize innate antiviral immunity. We found that nuclear respiratory factor-1 (NRF1), a vital transcriptional factor involved in nuclear-mitochondrial interactions, is essential for RNA (VSV) or DNA (HSV-1) virus-induced mitochondrial biogenesis. NRF1 deficiency resulted in enhanced innate immunity, a diminished viral load, and morbidity in mice. Mechanistically, the inhibition of NRF1-mediated mitochondrial biogenesis aggravated virus-induced mitochondrial damage, promoted the release of mitochondrial DNA (mtDNA), increased the production of mitochondrial reactive oxygen species (mtROS), and activated the innate immune response. Notably, virus-activated kinase TBK1 phosphorylated NRF1 at Ser318 and thereby triggered the inactivation of the NRF1-TFAM axis during HSV-1 infection. A knock-in (KI) strategy that mimicked TBK1-NRF1 signaling revealed that interrupting the TBK1-NRF1 connection ablated mtDNA release and thereby attenuated the HSV-1-induced innate antiviral response. Our study reveals a previously unidentified antiviral mechanism that utilizes a NRF1-mediated negative feedback loop to modulate mitochondrial biogenesis and antagonize innate immune response.

Saturated fatty acids increase LPI to reduce FUNDC1 dimerization and stability and mitochondrial function.

Ectopic lipid deposition and mitochondrial dysfunction are common etiologies of obesity and metabolic disorders. Excessive dietary uptake of saturated fatty acids (SFAs) causes mitochondrial dysfunction and metabolic disorders, while unsaturated fatty acids (UFAs) counterbalance these detrimental effects. It remains elusive how SFAs and UFAs differentially signal toward mitochondria for mitochondrial performance. We report here that saturated dietary fatty acids such as palmitic acid (PA), but not unsaturated oleic acid (OA), increase lysophosphatidylinositol (LPI) production to impact on the stability of the mitophagy receptor FUNDC1 and on mitochondrial quality. Mechanistically, PA shifts FUNDC1 from dimer to monomer via enhanced production of LPI. Monomeric FUNDC1 shows increased acetylation at K104 due to dissociation of HDAC3 and increased interaction with Tip60. Acetylated FUNDC1 can be further ubiquitinated by MARCH5 for proteasomal degradation. Conversely, OA antagonizes PA-induced accumulation of LPI, and FUNDC1 monomerization and degradation. A fructose-, palmitate-, and cholesterol-enriched (FPC) diet also affects FUNDC1 dimerization and promotes its degradation in a non-alcoholic steatohepatitis (NASH) mouse model. We thus uncover a signaling pathway that orchestrates lipid metabolism with mitochondrial quality.

APART-QSM: An improved sub-voxel quantitative susceptibility mapping for susceptibility source separation using an iterative data fitting method.

The brain tissue phase contrast in MRI sequences reflects the spatial distributions of multiple substances, such as iron, myelin, calcium, and proteins. These substances with paramagnetic and diamagnetic susceptibilities often colocalize in one voxel in brain regions. Both opposing susceptibilities play vital roles in brain development and neurodegenerative diseases. Conventional QSM methods only provide voxel-averaged susceptibility value and cannot disentangle intravoxel susceptibilities with opposite signs. Advanced susceptibility imaging methods have been recently developed to distinguish the contributions of opposing susceptibility sources for QSM. The basic concept of separating paramagnetic and diamagnetic susceptibility proportions is to include the relaxation rate R2* with R2' in QSM. The magnitude decay kernel, describing the proportionality coefficient between R2' and susceptibility, is an essential reconstruction coefficient for QSM separation methods. In this study, we proposed a more comprehensive complex signal model that describes the relationship between 3D GRE signal and the contributions of paramagnetic and diamagnetic susceptibility to the frequency shift and R2* relaxation. The algorithm is implemented as a constrained minimization problem in which the voxel-wise magnitude decay kernel and sub-voxel susceptibilities are determined alternately in each iteration until convergence. The calculated voxel-wise magnitude decay kernel could realistically model the relationship between the R2' relaxation and the volume susceptibility. Thus, the proposed method effectively prevents the errors of the magnitude decay kernel from propagating to the final susceptibility separation reconstruction. Phantom studies, ex vivo macaque brain experiments, and in vivo human brain imaging studies were conducted to evaluate the ability of the proposed method to distinguish paramagnetic and diamagnetic susceptibility sources. The results demonstrate that the proposed method provides state-of-the-art performances for quantifying brain iron and myelin compared to previous QSM separation methods. Our results show that the proposed method has the potential to simultaneously quantify whole brain iron and myelin during brain development and aging. The proposed model was also deployed with multiple-orientation complex GRE data input measurements, resulting in high-quality QSM separation maps with more faithful tissue delineation between brain structures compared to those reconstructed by single-orientation QSM separation methods.

Sub-voxel quantitative susceptibility mapping for assessing whole-brain magnetic susceptibility from ages 4 to 80.

The evolution of magnetic susceptibility of the brain is mainly determined by myelin in white matter (WM) and iron deposition in deep gray matter (DGM). However, existing imaging techniques have limited abilities to simultaneously quantify the myelination and iron deposition within a voxel throughout brain development and aging. For instance, the temporal trajectories of iron in the brain WM and myelination in DGM have not been investigated during the aging process. This study aimed to map the age-related iron and myelin changes in the whole brain, encompassing myelin in DGM and iron deposition in WM, using a novel sub-voxel quantitative susceptibility mapping (QSM) method. To achieve this, a cohort of 494 healthy adults (18-80 years old) was studied. The sub-voxel QSM method was employed to obtain the paramagnetic and diamagnetic susceptibility based on the approximated R 2 ' map from acquired R 2 * map. The linear relationship between R 2 * and R 2 ' maps was established from the regression coefficients on a small cohort data acquired with both 3D gradient recalled echo data and R 2 mapping. Large cohort sub-voxel susceptibility maps were used to create longitudinal and age-specific atlases via group-wise registration. To explore the differential developmental trajectories in the DGM and WM, we employed nonlinear models including exponential and Poisson functions, along with generalized additive models. The constructed atlases reveal the iron accumulation in the posterior part of the putamen and the gradual myelination process in the globus pallidus with aging. Interestingly, the developmental trajectories show that the rate of myelination differs among various DGM regions. Furthermore, the process of myelin synthesis is paralleled by an associated pattern of iron accumulation in the primary WM fiber bundles. In summary, our study offers significant insights into the distinctive developmental trajectories of iron in the brain's WM and myelination/demyelination in the DGM in vivo. These findings highlight the potential of using sub-voxel QSM to uncover new perspectives in neuroscience and improve our understanding of whole-brain myelination and iron deposit processes across the lifespan.

Intestinal recruitment of CCR6-expressing Th17 cells by suppressing miR-681 alleviates endotoxemia-induced intestinal injury and reduces mortality.

INTRODUCTION: Sepsis or endotoxemia can induce intestinal dysfunction in the epithelial and immune barrier. Th17 cells, a distinct subset of CD4+ T-helper cells, act as "border patrol" in the intestine under pathological condition and in the previous studies, Th17 cells exhibited an ambiguous function in intestinal inflammation. Our study will explore a specific role of Th17 cells and its relevant mechanism in endotoxemia-induced intestinal injury. MATERIALS AND METHODS: Lipopolysaccharide was used to establish mouse model of endotoxemia. miR-681 was analyzed by RT-PCR and northern blot analysis and its regulation by HIF-1α was determined by chromatin immunoprecipitation and luciferase reporter assay. Intestinal Th17 cells isolated from endotoxemic mice were quantitatively evaluated by flow cytometry and its recruitment to the intestine controlled by miR-681/CCR6 pathway was assessed by using anti-miRNA treatment and CCR6 knockout mice. Intestinal histopathology, villus length, intestinal inflammation, intestinal permeability, bacterial translocation and survival were investigated, by histology and TUNEL analysis, ELISA, measurement of diamine oxidase, bacterial culture, with or without anti-miR-681 treatment in endotoxemic wild-type and (or) CCR6 knockout mice. RESULTS: In this study, we found that miR-681 was significantly promoted in intestinal Th17 cells during endotoxemia, which was dependent on hypoxia-inducible factor-1α (HIF-1α). Interestingly, miR-681 could directly suppress CCR6, which was a critical modulator for Th17 cell recruitment to the intestines. In vivo, anti-miR-681 enhanced survival, increased number of intestinal Th17 cells, reduced crypt and villi apoptosis, decreased intestinal inflammation and bacterial translocation, resulting in protection against endotoxemia-induced intestinal injury in mice. However, CCR6 deficiency could neutralize the beneficial effect of anti-miR-681 on the intestine during endotoxemia, suggesting that the increment of intestinal Th17 cells caused by anti-miR-681 relies on CCR6 expression. CONCLUSION: The results of the study indicate that control of intestinal Th17 cells by regulating novel miR-681/CCR6 signaling attenuates endotoxemia-induced intestinal injury.

Sequence-Dependent Stereodivergent Allylic Alkylation/Fluorination of Acyclic Ketones.

The stereodivergent iridium-catalyzed allylic alkylation and fluorination of acyclic ketones is described. α-Pyridyl-α-fluoroketones with vicinal tertiary and quaternary stereocenters were obtained in moderate to excellent yields and stereoselectivities. Distinct from known stereodivergent synthesis, for which two different chiral catalysts are required in general, herein we report a sequence-dependent stereodivergent synthesis. With only a single chiral Ir catalyst, all four possible stereoisomers of the products were prepared from the same starting materials by simply adjusting the sequence of asymmetric allylic alkylation and fluorination and varying the absolute configuration of the Ir catalyst.

Association between serum magnesium and blood count: influence of type 2 diabetes and central obesity.

The relationship between serum Mg and blood cell counts in Chinese adult diabetes or central obesity was assessed by investigating 8163 subjects with China Health and Nutrition Survey (mean age 59⋅6 years, 54⋅9 % men). Participants were classified according to blood Mg (below 0⋅65 mmol/l, or 0⋅66-0⋅94 mmol/l or above 0⋅95 mmol/l), type 2 diabetes (yes/no) and central obesity (yes/no). Leucocytes, erythrocytes, platelets (PLT), Hb and glycated Hb (HbA1c) were determined using standardised methods and conditions. HbAc1, leucocytes and PLT were significantly higher among subjects with central obesity than without central obesity (P < 0⋅05). A significant increase for Hb, erythrocytes, PLT, but not leucocytes, across progressive Mg groups was observed in subjects without diabetes (P < 0⋅05). Hb, erythrocytes and HbAc1 were significantly higher among subjects with higher Mg than in subjects with lower Mg with diabetes (P < 0⋅05). Central obesity disturbed the positive association between PLT count and serum Mg. Type 2 diabetes caused metabolism disorder in serum Mg, blood sugar and blood cell count. Hb, erythrocytes and PLT, but not leucocytes, are positively correlated with serum Mg, but this association is somehow disturbed by type 2 diabetes or central obesity.

Effects of dietary mixed probiotics on growth, non-specific immunity, intestinal morphology and microbiota of juvenile pacific white shrimp, Litopenaeus vannamei.

This study was conducted to elucidate the effects of dietary mixed probiotics on growth, non-specific immunity, intestinal morphology and microbiota of juvenile pacific white shrimp, Litopenaeus vannamei. Juvenile shrimp (initial body weight 1.21 ±â€¯0.01 g) were fed diets containing graded probiotics (F1: 0 mg/kg probiotics; F2: 1000 mg/kg probiotics; F3: 2000 mg/kg probiotics; F4: 4000 mg/kg compound probiotics; F5: 6000 mg/kg probiotics; F6: 8000 mg/kg probiotics) for 8 weeks. The result of this trial showed that the growth performance (SGR, WG, FBW) of shrimp fed diets containing probiotics (F2∼F6) were significantly higher than that of shrimp fed diet without supplemental probiotics (F1) (P < 0.05), and the highest values of the growth performance (SGR, WG, FBW) and lowest FCR were found in shrimp fed the diet containing 2000 mg/kg probiotics. Total antioxidant capacity of shrimp fed diet F2 and F3 were significantly higher than that of shrimp fed the basal diets (P < 0.05). Superoxide dismutase in F4 treatment was significantly higher than that of basal treatment (P < 0.05). Catalase of shrimp in all probiotics supplemented (F2∼F6) treatments were significantly higher than that of the control one (F1) (P < 0.05). Malondialdehyde in F5 groups was significantly lower than that of F1 groups (P < 0.05). Alkline phosphatase and acid phosphatase in F3 treatments were significantly higher than those of the basal one (P < 0.05). Lysozyme of shrimp fed F2∼F6 were significantly higher than that of shrimp fed F1 diet (P < 0.05). The lipase and amylase activities in 2000 mg/kg probiotics groups showed the highest activities and were significantly higher than that of control one (P < 0.05). Intestinal villi height in F3∼F6 treatments were significantly higher than that of control one (P < 0.05). Alpha diversity indices including observed species, chao1, ACE and shannon indices showed that F2 and F3 groups had higher microbial diversity in their intestines, both richness and evenness. PCA plot showed that there was a clear shift of F2 and F3 groups from the control groups in microbial community structure. The dominant phyla in pacific white shrimp are proteobacteria, bacteroidetes and actinobacteria, the dominant genus were algoriphagus and vibrio. As the probiotics increased, the gemmatimonadetes, acidobacteria, deltaproteobacteria and xanthomonadales firstly increased and then decreased, with the highest content in F2 group, which was no significant difference to F3 group (P > 0.05) while significantly higher than other groups (P < 0.05). In conclusion, the supplement of mixed species probiotics can promote growth performance, enhance the non-specific immunity, influence the microbiota of the pacific white shrimps and the recommended optimum dosage in diet of Litopenaeus vannamei was 2000 mg/kg.

The First Transcriptome Assembly of Yenyuan Stream Salamander (Batrachuperus yenyuanensis) Provides Novel Insights into Its Molecular Evolution.

The Yenyuan stream salamander (Batrachuperus yenyuanensis) has been previously evaluated with regards to phylogeny, population genetics, and hematology, but genomic information is sparse due to the giant genome size of salamanders which contain highly repetitive sequences, thus resulting in the lack of a complete reference genome. This study evaluates the encoding genetic sequences and provides the first transcriptome assembly of Yenyuan stream salamander based on mixed samples from the liver, spermary, muscle and spleen tissues. Using this transcriptome assembly and available encoding sequences from other vertebrates, the gene families, phylogenetic status, and species divergence time were compared or estimated. A total of 13,750 encoding sequences were successfully obtained from the transcriptome assembly of Yenyuan stream salamander, estimated to contain 40.1% of the unigenes represented in tetrapod databases. A total of 88.79% of these genes could be annotated to a biological function by current databases. Through gene family clustering, we found multiple possible isoforms of the Scribble gene-whose function is related to regeneration-based on sequence similarity. Meanwhile, we constructed a robust phylogenetic tree based on 56 single-copy orthologues, which indicates that based on phylogenetic position, the Yenyuan stream salamander presents the closest relationship with the Chinese giant salamander (Andrias davidianus) of the investigated vertebrates. Based on the fossil-calibrated phylogeny, we estimated that the lineage divergence between the ancestral Yenyuan stream salamander and the Chinese giant salamander may have occurred during the Cretaceous period (~78.4 million years ago). In conclusion, this study not only provides a candidate gene that is valuable for exploring the remarkable capacity of regeneration in the future, but also gives an interesting insight into the understanding of Yenyuan stream salamander by this first transcriptome assembly.

Copper-Catalyzed Ring Opening of Benzofurans and an Enantioselective Hydroamination Cascade.

A copper(II) acetate/(R)-DTBM-SEGPHOS-catalyzed ring opening of benzofurans and enantioselective hydroamination cascade with dimethoxymethylsilane (DMMS) and hydroxylamine esters is described. Starting from readily available substituted benzofurans, a series of chiral N,N-dibenzylaminophenols, which are of high interest in pharmaceutical chemistry, were obtained with excellent enantioselectivities (up to 66 % yield, 94 % ee).

Povarov Reaction of Cycloiminium Formed in Situ via Hydroamination Cycloisomerization of Homopropargylic Amines with Electron-Rich Olefins.

A new, one-pot cascade reaction of homopropargylic amines with electron-rich olefins is developed in the presence of Cu(OTf)2 and affords a series of octahydrofuro[3,2-c]pyrrolo[1,2-a]quinoline derivatives in yields of 38-80%. This reaction proceeds through an intramolecular hydroamination cyclization of homopropargylic amine to generate a highly reactive cycloenamine intermediate in situ that subsequently isomerizes to the cycloiminium cation followed by the Povarov-type reaction with dihydrofuran, dihydropyran, or dihydropyrrole. Notably, the Al2O3 additive plays a key role for the effective inhibition of competitive self-dimerization of homoproargylic amines.

Organophotocatalytic α-deuteration of unprotected primary amines via H/D exchange with D2O.

We report a straightforward H/D exchange method for the synthesis of α-deuterated primary amines from a diverse set of primary amines with high levels of deuteration and chemo- and site selectivity and preparative utility. This cost-effective strategy enables the direct conversion of primary amines to α-deuterated counterparts using D2O as the deuterium source under mild reaction conditions without requiring additional functionality manipulation and with minimal byproduct production.

Use of Compressed Sensing Accelerated, Low-Velocity Encoded, Isotropic Resolution, Phase Contrast Magnetic Resonance Angiography for SEEG Electrode Implantation.

OBJECTIVE: We assessed the feasibility of using compressed sensing accelerated, low-velocity encoded, isotropic resolution phase contrast (CLIP) magnetic resonance angiography (MRA) for avascular trajectory planning of stereoelectroencephalography. METHODS: Ten healthy subjects (1 woman and 9 men; age, 33.6 ± 9.0 years) and 20 consecutive patients (12 female patients; age, 22 ± 13.6 years) were enrolled in the present study. The healthy subjects underwent CLIP-MRA, and 3 other phase contrast MRA protocols with conventional parallel imaging (PI) acceleration, including low resolution with twofold PI (PI2), high resolution (HR) with fivefold PI (PI5), and HR-PI2. The patients underwent CLIP-MRA and computed tomography angiography (CTA). The image qualities were evaluated. The numbers and locations of trajectory-vessel conflict detected using CLIP-MRA were noted. RESULTS: With similar scan durations, CLIP-MRA achieved higher spatial resolution compared with low resolution with PI2 and detected significantly more branches compared with HR-PI5. With the same spatial resolution, the signal/noise and contrast/noise ratios of CLIP-MRA were higher than those with HR-PI2 with a shorter scan duration. For the 12 adult patients (10 female patients; 28.8 ± 12.7 years), CLIP-MRA had better signal/noise and contrast/noise ratios than CTA. The trajectory had required modification for 14 of the 20 patients (70%), with a proportion of trajectory modification of 10.7% (23 of 215 electrodes). The middle meningeal artery, cortical vessel, and skull vessel were the main vessels with conflict (n = 11, n = 7, and n = 5, respectively). CONCLUSIONS: In the present study, CLIP-MRA provided a clear cortical vascular display noninvasively without intravascular contrast and radiation. The middle meningeal artery and diploic and emissary veins were the main conflict vessels and could be clearly displayed using CLIP-MRA but not CTA.

Obtaining superior high-density fused-ring energetic materials via the introduction of carbonyl, o-NH2-NO2 and nitroamino groups.

Two carbonyl and o-NH2-NO2-containing energetic materials and their analogues were effectively designed, synthesized and fully characterized with multinuclear NMR, IR and elemental analyses. Their structures were also further confirmed via X-ray diffraction. Among them, compound 7 exhibits good potential for application as a secondary explosive with extremely high density (2.04 g cm-3), good sensitivity (IS > 40 J, FS > 360 N), and excellent calculated detonation performance (Dv = 8943 m s-1, P = 35.0 GPa). Furthermore, a detailed comparative study based on X-ray diffraction, Hirshfeld surfaces and 2D fingerprint plots among compounds 4, 7 and 9 has demonstrated that the density and detonation performance could be effectively improved via introducing a carbonyl group into fused-ring compounds. More importantly, the sensitivity of the resulting energetic materials did not deteriorate. Obviously, this strategy via introducing carbonyl, o-NH2-NO2 and nitroamino groups into fused-ring energetic compounds will help in the design of next-generation high-energy and insensitive fused-ring energetic materials.

SEEG-RFTC in patients with refractory focal epilepsy: real-world outcomes from 121 cases.

OBJECTIVE: Radiofrequency thermocoagulation (RFTC) has emerged as an effective and safe treatment method for patients with refractory focal epilepsy, when stereo-electroencephalography (SEEG) is implanted. Although real-world research results are still limited, a considerable number of patients have shown favorable outcomes with this less invasive method. This study aims to describe the outcomes and predictive factors of SEEG-RFTC in real-world research. METHODS: A retrospective observational study was conducted on patients in the authors' epilepsy center. In total, 121 patients who underwent RFTC were included in the study. Post-RFTC outcomes were evaluated using the seizure-free rate and response rate (seizure frequency reduction more than 50%). Predictive factors influencing post-RFTC outcome were considered by comparing different variables. RESULTS: The mean follow-up period was 18.3 months. Eighty-two patients (67.8%) were responders and 54 (44.6%) were seizure free. In 36 patients with malformation of cortical development, the seizure-free rate and the response rate were 69.44% and 83.33%, respectively. In 20 patients with hippocampal sclerosis, 19 patients were responders and 14 (70%) patients were seizure free at the last follow-up. The MRI feature and etiology of epilepsy are correlated with the outcome. MR-positive is a predictive factor for seizure freedom (p < 0.01) and responders (p < 0.01). Other factors have no predictive value for post-RFTC outcome. INTERPRETATION: SEEG-RFTC is a safe procedure and yields favorable outcomes in numerous cases of focal DRE. The MRI feature and etiology of epilepsy are correlated with the seizure-free rate and response rate. And MRI positivity is the predictor for good RFTC outcome.

MK-2206 induces cell cycle arrest and apoptosis in HepG2 cells and sensitizes TRAIL-mediated cell death.

It has become evident that AKT inhibitors have great potential in cancer treatment. In this study, we investigate the anticancer activity of MK-2206, a novel AKT inhibitor, on HepG2 hepatocellular carcinoma cell, and to show whether MK-2206 enhances the apoptosis-inducing potential of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). The cell growth inhibition was evaluated by MTT assay and colony formation assay. Cell cycle distribution was assessed by propidium iodide flow cytometry. Apoptosis was determined by AnnexinV-FITC/PI double staining assay and caspase-9, casapse-7, caspase-3, and PARP cleavage. The results of present study showed that MK-2206-induced G1-phase arrest was associated with a marked decrease in the protein expression of cyclin D1 with concomitant induction of p21 and p27. MK-2206-induced apoptosis was characterized by cleavage of a pro-caspase in a concentration-dependent manner. Moreover, the MAP family kinases p38 kinase and JNK were activated by exposure to MK-2206. SB203580, an p38-specific inhibitor, partially blocked MK-2206-induced death of HepG2 cells and caspase activation. A combination of MK-2206 with TRAIL significantly inhibited growth of TRAIL resistant HepG2 cells. Taken together, our findings provide a new insight to better understand anticancer mechanisms of MK-2206, at least in HepG2 cell. Using of MK-2206 as a potent sensitizer to TRAIL-induced apoptotic cell death offers a promising means of enhancing the efficacy of TRAIL-based HCC treatments.

RankAxis: Towards a Systematic Combination of Projection and Ranking in Multi-Attribute Data Exploration.

Projection and ranking are frequently used analysis techniques in multi-attribute data exploration. Both families of techniques help analysts with tasks such as identifying similarities between observations and determining ordered subgroups, and have shown good performances in multi-attribute data exploration. However, they often exhibit problems such as distorted projection layouts, obscure semantic interpretations, and non-intuitive effects produced by selecting a subset of (weighted) attributes. Moreover, few studies have attempted to combine projection and ranking into the same exploration space to complement each other's strengths and weaknesses. For this reason, we propose RankAxis, a visual analytics system that systematically combines projection and ranking to facilitate the mutual interpretation of these two techniques and jointly support multi-attribute data exploration. A real-world case study, expert feedback, and a user study demonstrate the efficacy of RankAxis.

The accuracy of a novel self-tapping bone fiducial marker for frameless robot-assisted stereo-electro-encephalography implantation and registration techniques.

BACKGROUND: We aimed to evaluate the accuracy and safety of a novel self-tapping bone fiducial as a registration technique for stereoelectroencephalography (SEEG) implantation. METHODS: Each patient was installed with five bone fiducial markers. All procedures were performed using the same Sinovation robot system. The accuracy was determined by calculating the target point error (TPE) and the entry point error (EPE) of electrodes. RESULTS: Fourteen patients underwent SEEG implantation surgery; and the average installation time of the markers per patient was 86.1 s. In the operating theatre, the average registration time was 206.6 s, and the average registration error was 0.18 mm. The average TPE of 174 electrodes was 1.98 mm and the average EPE was 0.88 mm. CONCLUSION: Our study provided a bone fiducial marker installation and registration technique that was convenient and fast, highly accurate in registration, and highly tolerated by patients.

Frameless Robot-Assisted Asleep Centromedian Thalamic Nucleus Deep Brain Stimulation Surgery in Patients with Drug-Resistant Epilepsy: Technical Description and Short-Term Clinical Results.

INTRODUCTION: This purpose of this work is to give a detailed description of a surgical technique for frameless robot-assisted asleep deep brain stimulation (DBS) of the centromedian thalamic nucleus (CMT) in drug-resistant epilepsy (DRE). METHODS: Ten consecutively enrolled patients who underwent CMT-DBS were included in the study. The FreeSurfer "Thalamic Kernel Segmentation" module and experience target coordinates were used for locating the CMT, and quantitative susceptibility mapping (QSM) images were used to check the target. The patient's head was secured with a head clip, and electrode implantation was performed with the assistance of the neurosurgical robot Sinovation®. After opening the dura, the burr hole was continuously flushed with physiological saline to stop air from entering the skull. All procedures were performed under general anesthesia without intraoperative microelectrode recording (MER). RESULTS: The mean age of the patients at surgery and onset of seizures was 22 years (range 11-41 years) and 11 years (range 1-21 years), respectively. The median duration of seizures before CMT-DBS surgery was 10 years (2-26 years). CMT was successfully segmented, and its position was verified by experience target coordinates and QSM images in all ten patients. The mean surgical time for bilateral CMT-DBS in this cohort was 165 ± 18 min. The mean pneumocephalus volume was 2 cm3. The median absolute errors in the x-, y-, and z-axes were 0.7 mm, 0.5 mm, and 0.9 mm, respectively. The median Euclidean distance (ED) and radial error (RE) was 1.3 ± 0.5 mm and 1.0 ± 0.3 mm, respectively. No significant difference was found between right- and left-sided electrodes regarding the RE nor the ED. After a mean 12-month follow-up, the average reduction in seizures was 61%, and six patients experienced a ≥ 50% reduction in seizures, including one patient who had no seizures after the operation. All patients tolerated the anesthesia operation, and no permanent or serious complications were reported. CONCLUSIONS: Frameless robot-assisted asleep surgery is a precise and safe approach for placing CMT electrodes in patients with DRE, shortening the surgery time. The segmentation of the thalamic nuclei enables the precise location of the CMT, and the flow of physiological saline to seal the burr holes is a good way to reduce the influx of air. CMT-DBS is an effective method to reduce seizures.

Prognostic value of serum phosphate levels in sepsis: a systematic review and meta-analysis.

Background: There remain controversies over the conclusion of different serum phosphate levels as prognostic predictors of sepsis patients. As such, this study investigated the association between different serum phosphate and the prognosis of sepsis. Methods: Data from PubMed, Embase, Cochrane Library, and Web of Science were systematically retrieved from the inception of databases to June 1, 2023 and independently screened and extracted by two authors. Binary variables in the study were estimated as relative risk ratio (RR) and 95% confidence interval (CI), and continuous variables were estimated as mean and standard deviation. The Newcastle-Ottawa Scale (NOS) was employed to evaluate the quality of the included studies, and subgroup analysis and sensitivity analysis were performed for all outcomes to explore the sources of heterogeneity. Results: Ten studies were included in this study including 38,320 patients with sepsis or septic shock. Against normal serum phosphate levels, a high serum phosphate level was associated with an elevated all-cause mortality risk (RR = 1.46; 95% CI [1.22-1.74]; P = 0.000) and prolonged Intensive Care Unit (ICU) length of stay (LOS) (WMD = 0.63; 95% CI [0.27-0.98]; P = 0.001). However, there was no significant difference in the in-hospital LOS (WMD = 0.22; 95% CI [-0.61-1.05]; P = 0.609). A low serum phosphate level was not significantly associated with the all-cause mortality risk (RR = 0.97; 95% CI [0.86-1.09]; P = 0.588), ICU LOS (WMD = -0.23; 95% CI [-0.75-0.29]; P = 0.394) and in-hospital LOS (WMD = -0.62; 95% CI [-1.72-0.49]; P = 0.274). Conclusion: Sepsis patients with high serum phosphate levels before therapeutic interventions were associated with a significant increase in the all-cause mortality risk, prolonged ICU LOS, and no significant difference in in-hospital LOS. Sepsis patients with low serum phosphate levels before interventions may have a reduced risk of all-cause mortality, shorter ICU LOS, and in-hospital LOS, but the results were not statistically significant.