Transcription factor C/EBPα is required for the development of Ly6Chi monocytes but not Ly6Clo monocytes.

Monocytes comprise two major subsets, Ly6Chi classical monocytes and Ly6Clo nonclassical monocytes. Notch2 signaling in Ly6Chi monocytes triggers transition to Ly6Clo monocytes, which require Nr4a1, Bcl6, Irf2, and Cebpb. By comparison, less is known about transcriptional requirements for Ly6Chi monocytes. We find transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα) is highly expressed in Ly6Chi monocytes, but down-regulated in Ly6Clo monocytes. A few previous studies described the requirement of C/EBPα in the development of neutrophils and eosinophils. However, the role of C/EBPα for in vivo monocyte development has not been understood. We deleted the Cebpa +37 kb enhancer in mice, eliminating hematopoietic expression of C/EBPα, reproducing the expected neutrophil defect. Surprisingly, we also found a severe and selective loss of Ly6Chi monocytes, while preserving Ly6Clo monocytes. We find that BM progenitors from Cebpa +37-/- mice rapidly progress through the monocyte progenitor stage to develop directly into Ly6Clo monocytes even in the absence of Notch2 signaling. These results identify a previously unrecognized role for C/EBPα in maintaining Ly6Chi monocyte identity.

PBPK-PD model for predicting morphine pharmacokinetics, CNS effects and naloxone antagonism in humans.

Morphine and morphine-6-glucuronide (M6G) produce central nervous system (CNS) effects by activating mu-opioid receptors, while naloxone is used mainly for the reversal of opioid overdose, specifically for the fatal complication of respiratory depression, but also for alleviating opioid-induced side effects. In this study we developed a physiologically-based pharmacokinetic-pharmacodynamic (PBPK-PD) model to simultaneously predict pharmacokinetics and CNS effects (miosis, respiratory depression and analgesia) of morphine as well as antagonistic effects of naloxone against morphine. The pharmacokinetic and pharmacodynamic parameters were obtained from in vitro data, in silico, or animals. Pharmacokinetic and pharmacodynamic simulations were conducted using 39 and 36 clinical reports, respectively. The pharmacokinetics of morphine and M6G following oral or intravenous administration were simulated, and the PBPK-PD model was validated using clinical observations. The Emax model correlated CNS effects with free concentrations of morphine and M6G in brain parenchyma. The predicted CNS effects were compared with observations. Most clinical observations fell within the 5th-95th percentiles of simulations based on 1000 virtual individuals. Most of the simulated area under the concentration-time curve or peak concentrations also fell within 0.5-2-fold of observations. The contribution of morphine to CNS effects following intravenous or oral administration was larger than that of M6G. Pharmacokinetics and antagonistic effects of naloxone on CNS effects were also successfully predicted using the developed PBPK-PD model. In conclusion, the pharmacokinetics and pharmacodynamics of morphine and M6G, antagonistic effects of naloxone against morphine-induced CNS effects may be successfully predicted using the developed PBPK-PD model based on the parameters derived from in vitro, in silico, or animal studies.

Removal of diclofenac sodium from water using a polyacrylonitrile mixed-matrix membrane embedded with MOF-808.

MOF-808, owing to the synergistic effect of its large surface area and surface charge matching, showed a diclofenac sodium (DCF) removal capacity as high as 630 mg g-1, and the ability to adsorb 436 mg g-1 DCF in two hours, outperforming many common Zr-MOFs under the same conditions. Importantly, a series of free-standing mixed-matrix membranes made by combining polyacrylonitrile with MOF-808 were fabricated and exhibited high efficiency of removing DCF from water via an easily accessible filtration method.

Assessing recent recurrence after hepatectomy for hepatitis B-related hepatocellular carcinoma by a predictive model based on sarcopenia.

BACKGROUND: Sarcopenia may be associated with hepatocellular carcinoma (HCC) following hepatectomy. But traditional single clinical variables are still insufficient to predict recurrence. We still lack effective prediction models for recent recurrence (time to recurrence < 2 years) after hepatectomy for HCC. AIM: To establish an interventable prediction model to estimate recurrence-free survival (RFS) after hepatectomy for HCC based on sarcopenia. METHODS: We retrospectively analyzed 283 hepatitis B-related HCC patients who underwent curative hepatectomy for the first time, and the skeletal muscle index at the third lumbar spine was measured by preoperative computed tomography. 94 of these patients were enrolled for external validation. Cox multivariate analysis was per-formed to identify the risk factors of postoperative recurrence in training cohort. A nomogram model was developed to predict the RFS of HCC patients, and its predictive performance was validated. The predictive efficacy of this model was evaluated using the receiver operating characteristic curve. RESULTS: Multivariate analysis showed that sarcopenia [Hazard ratio(HR) = 1.767, 95%CI: 1.166-2.678, P < 0.05], alpha-fetoprotein ≥ 40 ng/mL (HR = 1.984, 95%CI: 1.307-3.011, P < 0.05), the maximum diameter of tumor > 5 cm (HR = 2.222, 95%CI: 1.285-3.842, P < 0.05), and hepatitis B virus DNA level ≥ 2000 IU/mL (HR = 2.1, 95%CI: 1.407-3.135, P < 0.05) were independent risk factors associated with postoperative recurrence of HCC. Based on the sarcopenia to assess the RFS model of hepatectomy with hepatitis B-related liver cancer disease (SAMD) was established combined with other the above risk factors. The area under the curve of the SAMD model was 0.782 (95%CI: 0.705-0.858) in the training cohort (sensitivity 81%, specificity 63%) and 0.773 (95%CI: 0.707-0.838) in the validation cohort. Besides, a SAMD score ≥ 110 was better to distinguish the high-risk group of postoperative recurrence of HCC. CONCLUSION: Sarcopenia is associated with recent recurrence after hepatectomy for hepatitis B-related HCC. A nutritional status-based prediction model is first established for postoperative recurrence of hepatitis B-related HCC, which is superior to other models and contributes to prognosis prediction.

Exploring the evolutionary mechanism of hepatitis B and gastric cancer based on Mendelian randomization combined with bioinformatics analysis.

Chronic hepatitis B virus infection (HBV) infection appears to be associated with extrahepatic cancers. This study aims to evaluate the causality and evolutionary mechanism of chronic HBV infection and gastric cancer through Mendelian randomization (MR) analysis and bioinformatics analysis. We conducted 2-sample MR to investigate the causal relationship between chronic HBV infection and gastric cancer. We identified 5 independent genetic variants closely associated with exposure (chronic HBV infection) as instrumental variables in a sample of 1371 cases and 2938 controls of East Asian descent in Korea. The genome wide association study (GWAS) data for the outcome variable came from the Japanese Biobank. Bioinformatics analysis was used to explore the evolutionary mechanism of chronic HBV infection and gastric cancer. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify key targets that are commonly associated with both diseases, and their biological functions were investigated. Multiple machine-learning models were employed to select hub genes. The MR analysis showed a positive causal relationship between chronic HBV infection and gastric cancer (IVW: OR = 1.165, 95% CI = 1.085-1.250, P < .001), and the result was robust in sensitivity analysis. According to the bioinformatics analysis, the 5 key targets were mainly enriched in Toll-like receptor signaling and PI3K-Akt signaling. Two hub genes, CXCL9 and COL6A2, were identified, and a high-performing predictive model was constructed. Chronic HBV infection is positively associated with gastric cancer, and the evolutionary mechanism may be related to Toll-like receptor signaling. Prospective studies are still needed to confirm these findings.

Coupling Ni Single Atomic Sites with Metallic Aggregates at Adjacent Geometry on Carbon Support for Efficient Hydrogen Peroxide Electrosynthesis.

Single atomic catalysts have shown great potential in efficiently electro-converting O2 to H2O2 with high selectivity. However, the impact of coordination environment and introduction of extra metallic aggregates on catalytic performance still remains unclear. Herein, first a series of carbon-based catalysts with embedded coupling Ni single atomic sites and corresponding metallic nanoparticles at adjacent geometry is synthesized. Careful performance evaluation reveals NiSA/NiNP-NSCNT catalyst with precisely controlled active centers of synergetic adjacent Ni-N4S single sites and crystalline Ni nanoparticles exhibits a high H2O2 selectivity over 92.7% within a wide potential range (maximum selectivity can reach 98.4%). Theoretical studies uncover that spatially coupling single atomic NiN4S sites with metallic Ni aggregates in close proximity can optimize the adsorption behavior of key intermediates *OOH to achieve a nearly ideal binding strength, which thus affording a kinetically favorable pathway for H2O2 production. This strategy of manipulating the interaction between single atoms and metallic aggregates offers a promising direction to design new high-performance catalysts for practical H2O2 electrosynthesis.

Endothelin-1-mediated Brainstem Glial Activation Produces Asthmatic Airway Vagal Hypertonia Via Enhanced ATP-P2X4 Receptor Signaling in Sprague-Dawley Rats.

The occurrence of major asthma symptoms is largely attributed to airway vagal hypertonia, of which the central mechanisms remain unclear. This study tests the hypotheses that endothelin-1-mediated brainstem glial activation produces asthmatic airway vagal hypertonia via enhanced action of adenosine 5'-triphosphate on neuronal purinergic P2X4 receptors. A rat model of asthma was prepared using ovalbumin. Airway vagal tone was evaluated by the recurrent laryngeal discharge and plethysmographic measurement of pulmonary function. The changes in the brainstem were examined using ELISA, Western blot, luciferin-luciferase, quantitative reverse transcription-polymerase chain reaction, enzyme activity assay and immunofluorescent staining, respectively. The results showed that in the medulla of rats, endothelin receptor type B and P2X4 receptors were primarily expressed in astrocytes and neurons, respectively, and both of which, along with endothelin-1 content, were significantly increased after ovalbumin sensitization. Ovalbumin sensitization significantly increased recurrent laryngeal discharge, which was blocked by acute intracisternal injection of P2X4 receptor antagonist 5-BDBD, knockdown of brainstem P2X4 receptors, and chronic intraperitoneal injection of endothelin receptor type B antagonist BQ788, respectively. Ovalbumin sensitization activated microglia and astrocytes and significantly decreased ecto-5'-nucleotidase activity in the medulla, and all of which, together with the increase of medullary P2X4 receptor expression and decrease of pulmonary function, were reversed by chronic BQ788 treatment. These results demonstrated that in rats, allergic airway challenge activates both microglia and astrocytes in the medulla via enhanced endothelin-1/endothelin receptor type B signaling, which subsequently causes airway vagal hypertonia via augmented adenosine 5'-triphosphate/P2X4 receptor signaling in central neurons of airway vagal reflex.

Observation of Nonlinear Exceptional Points with a Complete Basis in Dynamics.

The exotic physics associated with exceptional points (EPs) is always under the scrutiny of theoretical and experimental science. Recently, considerable effort has been invested in the combination of nonlinearity and non-Hermiticity. The concept of nonlinear EPs (NEPs) has been introduced, which can avoid the loss of completeness of the eigenbasis in dynamics while retaining the key features of linear EPs. Here, we present the first direct experimental demonstration of a NEP based on two non-Hermition coupled circuit resonators combined with a nonlinear saturable gain. At the NEP, the response of the eigenfrequency to perturbations demonstrates a third-order root law and the eigenbasis of the Hamiltonian governing the system dynamics is still complete. Our results bring this counterintuitive aspect of the NEP to light and possibly open new avenues for applications.

Laparoscopic left hemihepatectomy guided by indocyanine green fluorescence: A cranial-dorsal approach.

BACKGROUND: Advancements in laparoscopic technology and a deeper understanding of intrahepatic anatomy have led to the establishment of more precise laparoscopic hepatectomy (LH) techniques. The indocyanine green (ICG) fluorescence navigation technique has emerged as the most effective method for identifying hepatic regions, potentially overcoming the limitations of LH. While laparoscopic left hemihepatectomy (LLH) is a standardized procedure, there is a need for innovative strategies to enhance its outcomes. AIM: To investigate a standardized cranial-dorsal strategy for LLH, focusing on important anatomical markers, surgical skills, and ICG staining methods. METHODS: Thirty-seven patients who underwent ICG fluorescence-guided LLH at Qujing Second People's Hospital between January 2019 and February 2022 were retrospectively analyzed. The cranial-dorsal approach was performed which involves dissecting the left hepatic vein cephalad, isolating the Arantius ligament , exposing the middle hepatic vein, and dissecting the parenchyma from the dorsal to the foot in order to complete the anatomical LLH. The surgical methods, as well as intra- and post-surgical data, were recorded and analyzed. Our hospital's Medical Ethics Committee approved this study (Ethical review: 2022-019-01). RESULTS: Intraoperative blood loss during LLH was 335.68 ± 99.869 mL and the rates of transfusion and conversion to laparotomy were 13.5% and 0%, respectively. The overall incidence of complications throughout the follow-up (median of 18 months; range 1-36 months) was 21.6%. No mortality or severe complications (level IV) were reported. CONCLUSION: LLH has the potential to become a novel, standardized approach that can effectively, safely, and simply expose the middle hepatic vein and meet the requirements of precision surgery.

PI3K/AKT mediated De novo fatty acid synthesis regulates RIG-1/MDA-5-dependent type I IFN responses in BVDV-infected CD8+T cells.

Bovine viral diarrhea virus (BVDV) has caused massive economic losses in the cattle business worldwide. Fatty acid synthase (FASN), a key enzyme of the fatty acid synthesis (FAS) pathway, has been shown to support virus replication. To investigate the role of fatty acids (FAs) in BVDV infection, we infected CD8+T lymphocytes obtained from healthy cattle with BVDV in vitro. During early cytopathic (CP) and noncytopathic (NCP) BVDV infection in CD8+ T cells, there is an increase in de novo lipid biosynthesis, resulting in elevated levels of free fatty acids (FFAs) and triglycerides (TG). BVDV infection promotes de novo lipid biosynthesis in a dose-dependent manner. Treatment with the FASN inhibitor C75 significantly reduces the phosphorylation of PI3K and AKT in BVDV-infected CD8+ T cells, while inhibition of PI3K with LY294002 decreases FASN expression. Both CP and NCP BVDV strains promote de novo fatty acid synthesis by activating the PI3K/AKT pathway. Further investigation shows that pharmacological inhibitors targeting FASN and PI3K concurrently reduce FFAs, TG levels, and ATP production, effectively inhibiting BVDV replication. Conversely, the in vitro supplementation of oleic acid (OA) to replace fatty acids successfully restored BVDV replication, underscoring the impact of abnormal de novo fatty acid metabolism on BVDV replication. Intriguingly, during BVDV infection of CD8+T cells, the use of FASN inhibitors prompted the production of IFN-α and IFN-ß, as well as the expression of interferon-stimulated genes (ISGs). Moreover, FASN inhibitors induce TBK-1 phosphorylation through the activation of RIG-1 and MDA-5, subsequently activating IRF-3 and ultimately enhancing the IFN-1 response. In conclusion, our study demonstrates that BVDV infection activates the PI3K/AKT pathway to boost de novo fatty acid synthesis, and inhibition of FASN suppresses BVDV replication by activating the RIG-1/MDA-5-dependent IFN response.

[Lead Removal from Water by Calcium-containing Biochar with Saturated Phosphate].

Calcium-containing biochar （ES-BC） was prepared by pyrolyzing eggshell and kitchen wastes， and the ES-BC composite was used to remove phosphate （marked as ES-BC/P）. Based on the high affinity of phosphate and carbonate to lead， the ES-BC/P was then used to remove lead from the water. The results showed that， in the appropriate dosage， ES-BC/P could remove lead efficiently at different initial concentrations （1-100 mg·L-1）， and the removal efficiency could reach to 99%. Meanwhile， the release of phosphorus could be ignored after the reaction. As ES-BC/P was alkaline， and the lead-containing solution was weakly acidic， the addition of ES-BC/P could adjust the pH of the system automatically. The reaction kinetics and isotherm experiments showed that the lead removal by ES-BC/P was mainly monolayer chemisorption with a maximum adsorption capacity of 493.12 mg·g-1 （318 K）. The characterization results showed that lead was mainly removed through the ion exchanges of Pb2+ in the solution with Ca2+ in ES-BC/P. Then， the Pb2+ combined with CO32- and PO42- to form many precipitates， including Pb5（PO4）3OH， Pb10（PO4）6（OH）2， PbCO3， and Pb3（CO3）2（OH）2. In summary， the ES-BC/P material could achieve the efficient removal of lead from the water， thereby realizing the resource utilization of the wastes.

Sarcomatoid renal pelvis carcinoma: Experience of treatment at a single-institution.

OBJECTIVES: Sarcomatoid renal pelvis carcinoma (SRPC) is a rare variant of RPC. We aimed to summarize the clinicopathological features and prognostic factors of SRPC. METHODS: In this retrospective study, we collected data from 24 patients with SRPC who were treated at the Department of Urology, Affiliated Hospital of Qingdao University between 2008 and 2021. The clinicopathological features of the patients were obtained from their medical records to evaluate the diagnosis, prognostic factors, and response to systemic therapy. RESULTS: Immunohistochemical staining revealed that cytokeratin was expressed in 19 patients with SRPC, while vimentin was expressed in all patients. Computer tomography showed these tumors as low-density (n = 12) or mixed-density masses, with or without necrotic areas (n = 12). All patients showed different degrees of enhancement on computed tomography. Lymph node metastasis was present in 6 patients and distant metastasis in 5. The median survival of all patients was 28 months. Patients without metastasis had a median survival of 46 months compared with 18 months in those with metastasis (P < 0.05). Necrosis had no significant influence on prognosis (P > 0.05). The median survival of patients with and without hydronephrosis was 18 and 104 months (P < 0.05). Among patients without metastasis, those without hydronephrosis survived longer than those with hydronephrosis (104 vs 18 months, P < 0.05), and necrosis had no effect on prognosis. In patients with metastasis, necrosis and hydronephrosis had no effect on prognosis (P > 0.05). CONCLUSION: The prognosis of SRPC is poor, and the clinical stage, particularly the presence of distant metastasis, has a significant impact on prognosis.

Isolation, purification, and structural characterization of polysaccharides from Codonopsis pilosula and its therapeutic effects on non-alcoholic fatty liver disease in vitro and in vivo.

Codonopsis pilosula is a famous edible and medicinal plants, in which polysaccharides are recognized as one of the important active ingredients. A neutral polysaccharide (CPP-1) was purified from C. pilosula. The structure was characterized by HPSEC-MALLS-RID, UV, FT-IR, GC-MS, methylation analysis, and NMR. The results showed that CPP-1 was a homogeneous pure polysaccharide, mainly containing fructose and glucose, and a small amount of arabinose. Methylation analysis showed that CPP-1 composed of →1)-Fruf-(2→, Fruf-(1→ and Glcp-(1→ residues. Combined the NMR results the structure of CPP-1 was confirmed as α-D-Glcp-(1 â†’ [2)-ß-D-Fruf-(1 â†’ 2)-ß-D-Fruf-(1]26 â†’ 2)-ß-D-Fruf with the molecular weight of 4.890 × 103 Da. The model of AML12 hepatocyte fat damage was established in vitro. The results showed that CPP-1 could increase the activity of SOD and CAT antioxidant enzymes and reduce the content of MDA, thus protecting cells from oxidative damage. Subsequently, the liver protective effect of CPP-1 was studied in the mouse model of nonalcoholic fatty liver disease (NAFLD) induced by the high-fat diet. The results showed that CPP-1 significantly reduced the body weight, liver index, and body fat index of NAFLD mice, and significantly improved liver function. Therefore, CPP-1 should be a potential candidate for the treatment of NAFLD.

Partially knocking out NtPDK1a/1b/1c/1d simultaneously in Nicotiana tabacum using CRISPR/CAS9 technology results in auxin-related developmental defects.

The eukaryotic AGC protein kinase subfamily (protein kinase A/ protein kinase G/ protein kinase C-family) is involved in regulating numerous biological processes across kingdoms, including growth and development, and apoptosis. PDK1(3-phosphoinositide-dependent protein kinase 1) is a conserved serine/threonine kinase in eukaryotes, which is both a member of AGC kinase and a major regulator of many other downstream AGC protein kinase family members. Although extensively investigated in model plant Arabidopsis, detailed reports for tobacco PDK1s have been limited. To better understand the functions of PDK1s in tobacco, CRISPR/CAS9 transgenic lines were generated in tetraploid N. tabacum, cv. Samsun (NN) with 5-7 of the 8 copies of 4 homologous PDK1 genes in tobacco genome (NtPDK1a/1b/1c/1d homologs) simultaneously knocked out. Numerous developmental defects were observed in these NtPDK1a/1b/1c/1d CRISPR/CAS9 lines, including cotyledon fusion leaf shrinkage, uneven distribution of leaf veins, convex veins, root growth retardation, and reduced fertility, all of which reminiscence of impaired polar auxin transport. The severity of these defects was correlated with the number of knocked out alleles of NtPDK1a/1b/1c/1d. Consistent with the observation in Arabidopsis, it was found that the polar auxin transport, and not auxin biosynthesis, was significantly compromised in these knockout lines compared with the wild type tobacco plants. The fact that no homozygous plant with all 8 NtPDK1a/1b/1c/1d alleles being knocked out suggested that knocking out 8 alleles of NtPDK1a/1b/1c/1d could be lethal. In conclusion, our results indicated that NtPDK1s are versatile AGC kinases that participate in regulation of tobacco growth and development via modulating polar auxin transport. Our results also indicated that CRISPR/CAS9 technology is a powerful tool in resolving gene redundancy in polyploidy plants.

Polygonatum sibiricum (Huang Jing) polysaccharide reduces diabetic cardiomyopathy through increasing cyclic guanosine monophosphate-protein kinase G signaling in diabetic mice.

AIMS/INTRODUCTION: Diabetic cardiomyopathy (DCM) is a prevalent condition among individuals with diabetes, and is associated with a high mortality rate. The anti-oxidant properties of Jing Huang or Polygonatum sibiricum polysaccharide (PSP) have been extensively used to treat diabetes-related disorders; however, its potential effectiveness against DCM remains unknown. This study aimed to investigate PSP's therapeutic effects on DCM in an experimental diabetic mouse model. MATERIALS AND METHODS: To induce insulin resistance, mice were fed a high-fat diet for 3 months, followed by intraperitoneal streptozotocin injection to induce slight hyperglycemia and develop DCM. Both DCM and control mice were given PSP orally for 3 weeks. Western blotting was used to detect the protein expressions of protein kinase G, C/EBP homologous protein, glucose-regulated protein 78, phosphodiesterase type 5, protein kinase R-like endoplasmic reticulum (ER) kinase, and phospho-protein kinase R-like endoplasmic reticulum kinase in heart tissue. RESULTS: The results showed a reduction in bodyweight and blood glucose levels in the PSP therapy group compared with DCM group. PSP also improved cardiac function and had a negligible effect on malondialdehyde activity. Furthermore, the findings showed that PSP alleviated ER and oxidative stress observed in DCM mice hearts, leading to the inhibition of cyclic guanosine monophosphate-specific phosphodiesterase type 5 and cardiac cyclic guanosine monophosphate reactivation. Phosphodiesterase type 5 inhibition reduced high-fat diet-induced cardiac dysfunction and decreased ER stress. CONCLUSIONS: PSP could effectively protect diabetic myocardium by inhibiting endoplasmic reticulum stress. These findings provide crucial insights into the potential of PSP to ameliorate DCM conditions in diabetic mice by decreasing ER and oxidative stress, and enhancing cyclic guanosine monophosphate protein kinase G signaling.

Exploring the Differential Effects of Transcranial Direct Current Stimulation: A Comparative Analysis of Motor Cortex and Cerebellar Stimulation.

Background: Transcranial Direct Current Stimulation (tDCS) is a non-invasive brain stimulation technique. Constant electric current is passed through the patient's scalp with the aim of modulating cortical excitability. Stroke is a cerebrovascular disease characterized by hemorrhage or cerebral ischemia. This systematic review and meta-analysis are aimed at comparing the efficacy of motor cortex stimulation with that of cerebellar stimulation by using transcranial direct current stimulation. Method: Google Scholar, PubMed, EMBASE, Cochrane CENTRAL, and Physiotherapy Evidence Database (Pedro) databases were searched for studies. The extracted qualitative data was synthesized systematically. Cochrane RevMan software was used to conduct a meta-analysis of quantitative data. The fixed effects mean difference of the collected data was calculated at a 95% confidence interval (CI) for the changes in balance and side effects. Results: This research included 10 articles with seven studies assessing changes in balance (outcome measured in CoP and FMA scores) and side effects (tingling and itching were the most prevalent). There was no significant difference between the efficacy levels of m1-tDCS versus ctDCS (P = 0.18), m1-tDCS versus sham (P = 0.92), and ctDCS versus sham (P = 0.19). Itching and tingling sensation were the most common and were significantly prevalent in sham interventions (P < 0.00001). Conclusion: We found that motor cortex and cerebellar stimulations are both effective in improving motor function in stroke patients. There are no adverse effects to using the interventions besides mild itching and tingling experienced during the stimulation.

Bridging Atom Engineering for Low-Temperature Oxygen Activation in a Robust Metal-Organic Framework.

Achieving active site engineering at the atomic level poses a significant challenge in the design and optimization of catalysts for energy-efficient catalytic processes, especially for a reaction with two reactants competitively absorbed on catalytic active sites. Herein we show an example that tailoring the local environment of cobalt sites in a robust metal-organic framework through substituting the bridging atom from -Cl to -OH group leads to a highly active catalyst for oxygen activation in an oxidation reaction. Comprehensive characterizations reveal that this variation imparts drastic changes on the electronic structure of metal centers, the competitive reactant adsorption behavior, and the intermediate formation. As a result, exceptional low-temperature CO oxidation performance was achieved with T25(Temperature for 25% conversion) = 35°C and T100 (Temperature for 100% conversion) = 150°C, which stands out from existing MOF-based catalysts and even rivals many noble metal catalysts. This work provides a guidance for the rational design of catalysts for efficient oxygen activation for an oxidation reaction.

Dynamic nonreversibility view of intrinsic brain organization and brain dynamic analysis of repetitive transcranial magnitude stimulation.

Intrinsic neural activities are characterized as endless spontaneous fluctuation over multiple time scales. However, how the intrinsic brain organization changes over time under local perturbation remains an open question. By means of statistical physics, we proposed an approach to capture whole-brain dynamics based on estimating time-varying nonreversibility and k-means clustering of dynamic varying nonreversibility patterns. We first used synthetic fMRI to investigate the effects of window parameters on the temporal variability of varying nonreversibility. Second, using real test-retest fMRI data, we examined the reproducibility, reliability, biological, and physiological correlation of the varying nonreversibility substates. Finally, using repetitive transcranial magnetic stimulation-fMRI data, we investigated the modulation effects of repetitive transcranial magnetic stimulation on varying nonreversibility substate dynamics. The results show that: (i) as window length increased, the varying nonreversibility variance decreased, while the sliding step almost did not alter it; (ii) the global high varying nonreversibility states and low varying nonreversibility states were reproducible across multiple datasets and different window lengths; and (iii) there were increased low varying nonreversibility states and decreased high varying nonreversibility states when the left frontal lobe was stimulated, but not the occipital lobe. Taken together, these results provide a thermodynamic equilibrium perspective of intrinsic brain organization and reorganization under local perturbation.

The effect of lengths of branched-chain fatty alcohols on the efficacy and safety of docetaxel-prodrug nanoassemblies.

The self-assembly prodrugs are usually consisted of drug modules, activation modules, and assembly modules. Keeping the balance between efficacy and safety by selecting suitable modules remains a challenge for developing prodrug nanoassemblies. This study designed four docetaxel (DTX) prodrugs using disulfide bonds as activation modules and different lengths of branched-chain fatty alcohols as assembly modules (C16, C18, C20, and C24). The lengths of the assembly modules determined the self-assembly ability of prodrugs and affected the activation modules' sensitivity. The extension of the carbon chains improved the prodrugs' self-assembly ability and pharmacokinetic behavior while reducing the cytotoxicity and increased cumulative toxicity. The use of C20 can balance efficacy and safety. These results provide a great reference for the rational design of prodrug nanoassemblies.