Regulating the Electronic Structure of Metal-Organic Frameworks by Introducing Mn for Enhanced Oxygen Evolution Activity.

The construction of low-cost and highly efficient oxygen evolution electrocatalysts is paramount for clean and sustainable hydrogen energy. In recent years, metal-organic framework (MOF) OER electrocatalysts have attracted tremendous research attention. Herein, we report a simple and facile strategy to construct bimetallic MOFs (named CoMn0.01) for enhancing OER catalytic performance. Significantly, CoMn0.01 exhibited remarkable OER activity (255 mV at 10 mA cm-2) and a low Tafel slope of 66 mV dec-1, superior to those of commercial benchmark electrocatalysts (RuO2, 352 mV, 178 mV dec-1). Besides, the catalyst demonstrated outstanding longevity for 144 h at a current density of 100 mA cm -2. Mn doping can regulate the electronic structure of Co MOFs, which optimizes charge transfer capability and improves conductivity.

Tunable valley polarization effect and second-order topological state in monolayer FeClSH.

In two-dimensional (2D) materials, breaking the inversion symmetry plays an important role in valleytronics. Ferrovalley (FV) materials can achieve spontaneous valley polarization (VP) without additional modulation due to the magnetic exchange interaction and strong spin-orbit coupling. Using first-principles calculations, we predict a new 2D material, Janus FeClSH, which exhibits a large spontaneous VP. This monolayer is a perfect FV material, where the valence band maximum and conduction band minimum are located at the K/K' point. A large VP of 102.95 meV is spontaneously generated for the case of out-of-plane magnetization. Additionally, we propose that the irradiating circularly polarized light can be used to realize VP for the case of in-plane magnetization. Remarkably, a triangular nanoflake of FeClSH with armchair edges can show nontrivial corner states, exhibiting a second-order topological insulator (SOTI) state. The VP effect and SOTI state are tunable with the Hubbard U parameter, making the FeClSH monolayer promising for the study of the coupling between VP and SOTI.

Palonosetron is nonsuperior to ondansetron in acute phase but provides superior antiemetic control in delayed phase for pediatric patients administered highly emetogenic chemotherapy.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) in children remains to be a major side effect despite antiemetic treatment. Palonosetron is a new generation 5-HT3 receptor antagonists effective against acute and delayed nausea and vomiting. This study aimed to compare the therapeutic values of palonosetron and ondansetron in preventing pediatric CINV. METHODS: A prospective, randomized, double-blind, parallel controlled study was conducted in 0-18 years old cancer patients administered highly emetogenic chemotherapy, with different dosage of palonosetron or ondansetron, both followed by dexamethasone. The patients were observed for vomiting and nausea from 0 to 120 hr after chemotherapy initiation. All adverse events (AEs) during the study period were recorded. This study was registered with the Chinese Clinical Trial Registry, number ChiCTR-TRC-14004891. RESULTS: Between August 2014 and July 2016, 565 patients were randomly assigned to receive 5 µg/kg palonosetron (n = 185), 10 µg/kg palonosetron (n = 186), and 3 × 150 µg/kg ondansetron (n = 194), of whom 181, 185, and 189, respectively, were included in the efficacy analysis. Complete response (CR) rates during the acute phase were 69.1, 69.7, and 64.6%, respectively, in the 5 µg/kg palonosetron, 10 µg/kg palonosetron, and ondansetron groups. In the delayed phase, 10 µg/kg palonosetron (CR, 53.5%) showed superiority to 5 µg/kg palonosetron (CR, 39.8%) and ondansetron (CR, 32.8%) groups (P < 0.05). The most frequently observed drug-related AEs were nervous system disorders, mainly headache, with an incidence of 2.8, 2.2, and 2.6% in each group, respectively. CONCLUSION: Combination of palonosetron plus dexamethasone is highly effective in controlling acute and delayed CINV, with palonosetron superior to ondansetron.

A high-vacuum wound drainage system reduces pain and length of treatment for pediatric soft tissue abscesses.

Open incision and drainage (I&D) and wound packing is accepted as the standard treatment for soft tissue abscesses. However, conventional I&D has a number of problems in practice which prompt us to improve the I&D methods that would minimize the pain associated with packing during dressing changes. In order to compare the pain associated with dressing changes in the conventional I&D group to the vacuum system group and the treatment time of both groups, we performed a randomized trial in pediatric patients between 0 and 18 years of age who are undergoing abscess drainage in the operating room from April 2011 to April 2015. Patients treated with open I&D (n = 648) were compared to those treated with placement of high-vacuum wound drainage system (n = 776) through the abscess cavities. Both groups received equivalent antibiotic treatment, and all patients were followed up in the outpatient clinics until the infection has been resolved. The mean FACES scale pain scores were significantly higher in the open I&D group than in the vacuum system group. The vacuum system group had a shorter length of stay and less need for community doctor or outpatient dressing changes than the open I&D group (p < 0.001). No recurrent abscesses were observed in the vacuum system group, and 10 patients in the open I&D group required another drainage at the exact same location. CONCLUSION: High-vacuum wound drainage system was an efficient and safe alternative to the traditional I&D for community-acquired soft tissue abscesses with few complications in short term. What is Known: • Open incision and drainage (I&D) followed by irrigation and wound packing is the standard treatment for soft tissue abscesses. • The painful daily packing may cause emotional trauma to the child and lead to an unwelcoming challenge to the caretakers and health care providers. What is New: • We modified the method of I&D by adding primary suturing of the wound and placement of a high-vacuum wound drainage system. • This technique was proved to be an efficient and safe alternative to the traditional I&D method for soft tissue abscesses with small complications in short term.

First experience of high-intensity focused ultrasound combined with transcatheter arterial embolization as local control for hepatoblastoma.

UNLABELLED: The purpose of this study was to assess the effectiveness of high-intensity focused ultrasound (HIFU) combined with transarterial chemoembolization (TACE) in treating pediatric hepatoblastoma. Twelve patients with initially unresectable hepatoblastoma were enrolled in the study. All patients received chemotherapy, TACE, and HIFU ablation. Follow-up materials were obtained in all patients. The tumor response, survival rate, and complications were analyzed. Complete ablation was achieved in 10 patients (83.3%), and the alpha-fetoprotein level was also decreased to normal in these patients. The mean follow-up time was 13.3 ± 1.8 months (range, 2-25 months). At the end of follow-up, two patients died from tumor progression, the other 10 patients were alive. One patient was found to have lung metastasis after HIFU and had an operation to remove the lesion. The median survival time was 14 months, and the 1- and 2-year survival rates were 91.7% and 83.3%, respectively. Complications included fever, transient impairment of hepatic function, and mild malformation of ribs. CONCLUSION: HIFU combined with TACE is a safe and promising method with a low rate of severe complications. As a noninvasive approach, it may provide a novel local therapy for patients with unresectable hepatoblastoma.

Spin transport properties in lower n-acene-graphene nanojunctions.

A series of n-acene-graphene (n = 3, 4, 5, 6) devices, in which n-acene molecules are sandwiched between two zigzag graphene nanoribbon (ZGNR) electrodes, are modeled through the spin polarized density functional theory combined with the non-equilibrium Green's function technique. Our theoretical results show that for n-acene molecules ranging from anthracene to hexacene, the spin-polarized electronic states near the Fermi level can be induced by the spin-polarized ZGNR electrodes, which strengthen gradually to facilitate the electronic transport. A nearly 100% spin filtering ratio and a dual-orientation spin-rectifying effect are observed in a wide range of bias voltage. Importantly, an over 8000% giant magnetoresistance is obtained in the low bias range from -0.1 V to +0.1 V. Moreover, negative differential resistance behaviors are detected in these devices. The potential mechanisms of these intriguing phenomena are proposed and these findings would be instructive for the design and synthesis of high-performance graphene-based spin-related devices.

Rectification inversion in oxygen substituted graphyne-graphene-based heterojunctions.

Current rectification is found in oxygen-substituted zigzag graphyne nanoribbon/hydrogen-terminated zigzag graphene nanoribbon heterostructure junctions, from the application of nonequilibrium Green's function formalism combined with density functional theory. This behavior could be tuned by varying the number and location of oxygen atoms in the zigzag graphyne nanoribbon parts, and the rectification direction could be reversed due to the parity limitation tunneling effect. Moreover, an obvious negative differential resistance behavior is found and may be explained by two different mechanisms.

Super-Klein Tunneling in a Black-Phosphorus-Based N-P Junction Modulated by Linearly Polarized Light.

We investigate the role of the black-phosphorus-based n-p (BP-np) junction modulated by linearly polarized light (LPL) in governing the quantum transport behaviors. Following the analysis of the band structures, we find that the LPL can adjust the gap between the conduction and valence bands by reducing the impact of momentum mismatch caused by the band gap. In addition, LPL can also eliminate the angle dependence of transmission. This means that for BP with a fixed band gap, the transmission-forbidden region can be reduced and the transmission probability can be increased by applying LPL modulation of the band gap to achieve all-angle perfect transmission, i.e., super-Klein tunneling (SKT). Our investigation also found that the SKT is robust to different incident energies, resulting in a larger conductance platform. These findings could be useful for the development and application of optical-like electronic devices.

[Mutational Signatures Analysis of Micropapillary Components and Exploration of ZNF469 Gene in Early-stage Lung Adenocarcinoma with Ground-glass Opacities].

BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS: The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.

Impact of vaccination with different types of rotavirus vaccines on the incidence of intussusception: a randomized controlled meta-analysis.

Background: Intussusception is a prevalent pediatric issue causing acute abdominal pain, with potential links to rotavirus vaccines. The variety of these vaccines has grown in recent years. This meta-analysis study aims to evaluate the impact of various rotavirus vaccines on intussusception incidence. Methods: We executed a thorough search across databases like PubMed, Cochrane Library, Embase, and Web of Science, leading to the selection of 15 credible randomized controlled trials (RCTs) that encompass various types of rotavirus vaccines. From each study, we extracted essential details such as vaccine types and intussusception occurrences. We assessed the risk of bias using the Cochrane Collaboration's tool, conducted statistical analysis with R (version 4.2.3), determined relative risk (RR) using a random effects model, and performed a subgroup analysis for vaccines of differing brands and types. Results: We included 15 randomized controlled studies from various countries. While intussusception incidence differed between vaccinated and control groups, this difference was not statistically significant. The overall risk ratio (RR), calculated using a random effects model, was 0.81, with a 95% confidence interval of [0.53, 1.23]. This crossing 1 shows that vaccination didn't notably change disease risk. Additionally, the 0% group heterogeneity suggests consistency across studies, strengthening our conclusions. Subgroup analysis for different vaccine brands and types (RV1 (Rotarix, Rotavac, RV3-BB), RV3 (LLR3), RV5 (RotasiiL, RotaTeq), and RV6) showed no significant variation in intussusception incidence. Despite variations in RR among subgroups, these differences were not statistically significant (P > 0.05). Conclusions: Our study indicates that rotavirus vaccination does not significantly increase the incidence of intussusception. Despite varying impacts across different vaccine brands and types, these variations are insignificant. Given the substantial benefits outweighing the risks, promoting the use of newly developed rotavirus vaccines remains highly valuable. Systematic Review Registration: www.crd.york.ac.uk/prospero/, Identifier CRD42023425279.

Dual ultrasound-guided totally implantable venous access ports via the right internal jugular vein in pediatric patients with cancer: a preliminary experience in a single institution.

Objective: To assess the efficacy and safety of dual ultrasound-guided (DUG) totally implantable venous access port (TIVAP) implantation (namely, using ultrasound-guided percutaneous puncture with transesophageal echocardiography-guided catheterization) via the right internal jugular vein (IJV) in pediatric patients with cancer. Methods: Fifty-five children with cancer requiring chemotherapy underwent DUG-TIVAP implantation via the right IJV. Clinical data were recorded, including the procedure success rate, first attempt success rate, and perioperative and postoperative complications. Results: All 55 cases were successfully operated on. The first puncture success rate was 100%. The operation time was 22-41 min, with a mean time of 30.8±5.5 min. The mean TIVAP implantation time was 253±145 days (range 42-520 days). There were no perioperative complications. The postoperative complication rate was 5.4% (3/55), including skin infections around the port in one case, catheter-related infection in one case, and fibrin sheath formation in one case. The ports were all preserved after anti-infection or thrombolytic therapy. No unplanned port withdrawal was recorded in this study. Conclusions: DUG-TIVAP implantation is a technique with a high success rate and a low complication rate; therefore, it provides an alternative for children with cancer. Further randomized controlled studies are needed to confirm the efficacy and safety of DUG-TIVAP via the right IJV in children.

[Short-term effectiveness of lateral raft plate combined with Jail screw fixation in treatment of tibial plateau collapse fractures involved posterior-lateral column].

Objective: To investigate the short-term effectiveness of proximal tibial lateral raft plate combined combined with or without Jail screw fixation in the treatment of tibial plateau collapse fractures involved posterior-lateral column. Methods: A retrospective analysis was performed on 106 patients (106 knees) with tibial plateau collapse fracture involved posterior-lateral column admitted between January 2016 and January 2021. According to the combination with Jail screw fixation or not, patients were divided into control group (treated by lateral raft plate without Jail screw fixation, 52 cases) and study group (treated by lateral raft plate with Jail screw fixation, 54 cases). There was no significant difference between the two groups in terms of gender, age, affected knee side, cause of injury, Schatzker classification, Tscherne-Gotzen classification, time from injury to operation, and preoperative lateral tibial plateau posterior slope angle (PSA), tibial plateau varus angle (TPVA), Rasmussen anatomical score (P>0.05). The operation time, cumulative fluoroscopy time, intraoperative blood loss, hospitalization stay, fracture healing time, complications, and lateral tibial plateau PSA, TPVA, Rasmussen anatomical score detected by X-ray films and CT before operation and at 1 year after operation of the two groups were recorded and compared. The number of cases of articular surface collapse in the two groups was recorded at 1 year after operation, and the effectiveness was evaluated by American Special Surgery Hospital (HSS) score. Results: All patients were followed up 12-32 months (mean, 19.5 months). There was no significant difference between the two groups in operation time, cumulative fluoroscopy time, intraoperative blood loss, hospitalization stay, and fracture healing time (P>0.05). There were 2 patients (3.7%) in the study group and 3 patients (5.8%) in the control group with superficial wound infection, which were cured after debridement and dressing change. There was no significant difference in the incidence between the two groups (χ2=0.252, P=0.616). There was no complication such as vascular and nerve injury, internal fixation failure, nonunion or malunion of fracture, and deep vein thrombosis of lower limbs in both groups. At 1 year after operation, 9 cases (17.3%) in the control group had joint collapse of 2-3 mm, while only 2 cases (3.7%) in the study group had joint collapse, showing significant difference (χ2=5.271, P=0.022). At 1 year after operation, the PSA, TPVA, and Rasmussen anatomical scores of the two groups were significantly improved when compared with preoperative ones (P<0.05); the differences of pre- and post-operative PSA, TPVA, Rasmussen anatomical score, and postoperative HSS score in the study group were significantly better than those in the control group (P<0.05). Conclusion: The lateral raft plate combined with or without Jail screw fixation can achieve satisfactory short-term effectiveness in the treatment of tibial plateau collapse fractures involved posterior-lateral column. Combined with Jail screw, it can enhance the fixation and avoid the occurrence of secondary articular surface collapse, which can be used as a better choice.

Dysfunction of GluN3A subunit is involved in depression-like behaviors through synaptic deficits.

BACKGROUND: N-methyl-d-aspartate receptor (NMDAR) has been implicated in the pathophysiology of depression. However, as the unique inhibitory subunit of NMDARs, the role of GluN3A in depression is largely unclear. METHODS: Firstly, expression of GluN3A was examined in a mouse model of depression induced by chronic restraint stress (CRS). Then, rescue experiment with rAAV-Grin3a injection into hippocampus of CRS mice was carried out. Lastly, GluN3A knockout (KO) mouse was generated via CRISPR/Cas9 technique, and the molecular mechanism underlying involvement of GluN3A in depression was initially explored using RNA-seq technique, RT-PCR and western blotting. RESULTS: GluN3A expression in hippocampus was significantly decreased in CRS mice. Depression-like behaviors induced by CRS were ameliorated when the decrease of GluN3A expression in mice exposed to CRS was restored. GluN3A KO mice exhibited symptoms of anhedonia reported as reduced sucrose preference, and symptoms of despair assayed by a longer immobility time in FST. Transcriptome analysis revealed genetic ablation of GluN3A was associated with downregulation of genes implicated in synapse and axon development. Postsynaptic protein PSD95 was decreased in GluN3A KO mice. More importantly, reduction of PSD95 in CRS mice can be rescued by viral mediated Grin3a re-expression. LIMITATIONS: The mechanism underlying GluN3A involvement in depression is not fully determined. CONCLUSIONS: Our data suggested that GluN3A dysfunction is involved in depression, which might be mediated by synaptic deficits. These findings will facilitate the understanding of the role of GluN3A in depression, and they might provide a new strategy for the development of subunit-selective NMDAR antagonists as antidepressant drugs.

Preoperative high-intensity strength training combined with balance training can improve early outcomes after total knee arthroplasty.

BACKGROUND: To investigate the effect of preoperative high-intensity strength training combined with balance training on the knee function of end-stage knee osteoarthritis (KOA) patients after total knee arthroplasty (TKA). METHODS: A prospective study was conducted on end-stage KOA patients awaiting TKA. The patients were divided into an experimental group and a control group according to whether they received a preoperative training intervention. The differences in knee flexor-extensor strength, knee range of motion (ROM), timed up and go (TUG) test result, stair ascend/descend test result, Knee Society score (KSS) and Berg balance scale (BBS) score were assessed in both groups at baseline (T1), before operation (T2), 3 months after operation (T3), and 1 year after operation (T4). RESULTS: After high-intensity strength training and balance training, the knee flexor-extensor strength, TUG test result, stair ascend/descend test result, and KSS were all significantly improved at T2 in the experimental group over the control group. At T3, the knee ROM, knee flexor-extensor strength, TUG test result, BBS score, and KSS clinical and functional scores were all significantly superior in the experimental group. The experimental group enjoyed a superiority in KSS clinical and functional scores until T4. Group × time and between-group interactions were found in all assessment indicators in both groups (p < 0.01). CONCLUSION: Preoperative high-intensity strength training combined with balance training can enhance the knee flexor-extensor strength and balance of patients with end-stage KOA in the short term and help improve early outcomes after KOA. Trial registration ChiCTR2000032857, 2020-05-13.

[Correlation between Immune Microenvironment Features and EGFR Mutation Status 
in Lung Adenocarcinoma].

BACKGROUND: The morbidity and mortality rates of lung cancer remain high worldwide, and lung adenocarcinoma is one of the most important tissue subtypes of lung cancer. Epidermal growth factor receptor (EGFR) mutation is an important driver gene mutation for lung adenocarcinoma. In recent years, immune checkpoint inhibitors (ICIs), such as programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors, have achieved remarkable efficacy in some lung cancer patients. Patients with EGFR mutations enjoyed limited benefits from immunotherapy according to recent studies. This study aimed to explore the relationship between EGFR mutation status and the spatial distribution as well as infiltration number of various immune cells in patients with EGFR mutant lung adenocarcinoma. METHODS: This study included 62 lung adenocarcinoma patients who underwent surgery. Through multi-point sampling of surgically removed tumor tissues in different areas, 223 tumor tissue samples were finally obtained. We aquired EGFR mutations status including variant allele frequency (VAF) and mutation subtype in each tumor tissue by genetic test. Afterwards, hematoxylin-eosin (HE) staining, immunohistochemical staining and multiplex fluorescence immunohistochemistry staining have been performed, therefore the infiltration of various immune cells and the distribution of tertiary lymphoid structure (TLS) in tumor tissues were obtained by calculating the immunohistochemical score. RESULTS: Compared with EGFR wild-type patients, patients with EGFR-mutant lung adenocarcinoma had more infiltration of CD68+ macrophages and major histocompatibility complex (MHC) class II antigen-presenting cells and higher spatial distribution heterogeneity of MHC class II antigen presenting cells in tumor tissues, while CD56+ natural killer cells and CD8+ T cells had lower infiltration. Tumor tissues with higher EGFR VAF were associated with lower cell infiltration such as CD3+ T cells, CD20+ B cells, CD56+ natural killer cells, CD68+ macrophages, CD8+ T cells, and only CD3+ T cells showed a lower spatial distribution heterogeneity. For the two common subtypes of EGFR mutations in Chinese population, tumor tissues with EGFR exon 19 deletion mutations have lower immune cell infiltration but higher spatial distribution heterogeneity of CD3+ T cells, CD56+ natural killer cells, CD68+ macrophages, and CD8+ T cells than that in EGFR exon 21 L858R mutant tumor tissues. Prognostic analysis found that patients with EGFR mutations with high degree of CD3+ T cells, CD20+ B cell infiltration and larger numbers of TLS formation and high spatial distribution heterogeneity of CD8+ T cell had longer disease-free survival. CONCLUSIONS: EGFR-mutated lung adenocarcinoma had a unique "non-inflammatory" tumor microenvironment with low infiltration of immune cells, and there was also heterogeneity in the tumor microenvironment among the tumors with different mutation subtypes and mutation abundance. These differences were not only reflected in the number but also the spatial distribution of immune cell infiltration. Hence, further studies on the immune microenvironment of EGFR-mutant lung adenocarcinoma were of great significance for improving the efficacy of immunotherapy in EGFR-mutant lung adenocarcinoma patients in the future.

Aberrant adenosine signaling in patients with focal cortical dysplasia.

Focal cortical dysplasia (FCD), a common malformation of cortical development, is frequently associated with pharmacoresistant epilepsy in both children and adults. Adenosine is an inhibitory modulator of brain activity and a prospective anti-seizure agent with potential for clinical translation. Our previous results demonstrated that the major adenosine-metabolizing enzyme adenosine kinase (ADK) was upregulated in balloon cells (BCs) within FCD type IIB lesions, suggesting that dysfunction of the adenosine system is implicated in the pathophysiology of FCD. In our current study, we therefore performed a comprehensive analysis of adenosine signaling in surgically resected cortical specimens from patients with FCD type I and type II via immunohistochemistry and immunoblot analysis. Adenosine enzyme signaling was assessed by quantifying the levels of the key enzymes of adenosine metabolism, i.e., ADK, adenosine deaminase (ADA), and ecto-5'-nucleotidase (CD73). Adenosine receptor signaling was assessed by quantifying the levels of adenosine A2A receptor (A2AR) and putative downstream mediators of adenosine, namely, glutamate transporter-1 (GLT-1) and mammalian target of rapamycin (mTOR). Within lesions in FCD specimens, we found that the adenosine-metabolizing enzymes ADK and ADA, as well as the adenosine-producing enzyme CD73, were upregulated. We also observed an increase in A2AR density, as well as a decrease in GLT-1 levels and an increase in mTOR levels, in FCD specimens compared with control tissue. These results suggest that dysregulation of the adenosine system is a common pathologic feature of both FCD type I and type II. The adenosine system might therefore be a therapeutic target for the treatment of epilepsy associated with FCD.

Alteration in NMDAR subunits in different brain regions of chronic unpredictable mild stress (CUMS) rat model.

N-Methyl-d-aspartate receptor (NMDAR) signaling pathway has been implicated in the pathogenesis and treatment of depression. However, the role of NMDAR subunits in depression is still unclear. In this study, alteration in all seven NMDAR subunits in several brain areas of rats exposed to chronic unpredictable mild stress (CUMS), an animal model of depression, was detected. Our findings demonstrated that: (1) CUMS could induce a reduction in sucrose preference, an indicator of typical depression-like behaviors; (2) CUMS significantly reduced the NMDAR subunits of GluN2B and GluN3 in the medial prefrontal cortex (mPFC), but not altered all seven NMDAR subunits in hippocampus and corpus callosum of rats; (3) subunit composition of NMDARs in corpus callosum was different from that in mPFC, PFC and hippocampus; and (4) the mRNA expressions of GluN2B, GluN3A and GluN3B in mPFC as well as mRNA expression of GluN2C in corpus callosum were correlated to sucrose preference in rats. These findings suggested that GluN2B and GluN3 in mPFC may contribute to the pathophysiology of depression.

[Forecasting of Emission Co-reduction of Greenhouse Gases and Pollutants for the Road Transport Sector in Lanzhou Based on the LEAP Model].

With the continuous increase in transportation activities, the transportation sector has become an important source of global greenhouse gases. In 2019, road vehicles accounted for nearly three-quarters of the CO2 emissions of the entire transportation sector and will be the key to achieving carbon peaks in the transportation sector. At the same time, air pollutants emitted by road vehicles are also one of the threats to the environment and human health. Based on the long-range energy alternatives planning system (LEAP) model, we constructed the baseline (BAU) scenario, low-carbon (LC) scenario, and enhanced low-carbon (ELC) scenario for the development of the road transport sector in Lanzhou from 2015 to 2040 and simulated energy consumption and emission co-reduction of greenhouse gases and pollutants under policies and measures. The results showed that the energy consumption and CO2 emissions of the LC scenario will peak in 2026, whereas those in the ELC scenario will peak in 2020. In these two scenarios, pollutant emissions such as NOx, CO, HC, PM2.5, and PM10 began to decline sharply between 2015 and 2017, and the downward trend will slow down gradually around 2023. Based on the feasibility of measures and the cost of abatement, the LC scenario can be used as a road vehicle carbon peak scenario in Lanzhou. In this scenario, the reduction rates of energy consumption, CO2, NOx, CO, HC, PM2.5, and PM10 emissions will reach -24.17%, -26.57%, -55.38%, -65.91%, -72.87%, -76.66%, and -77.18% compared with those under the BAU scenario by 2040. At present, the road vehicles in Lanzhou City should focus on structural optimization measures such as clean-energy use of public transportation, electrification of small passenger cars, and phasing out old cars, as well as vigorously promoting low-carbon travel and improving energy efficiency accompanying the development of automotive technology. These efforts will effectively control CO2 and pollutant emissions by road vehicles, and carbon peaks will be achieved as soon as possible. In addition, it is necessary to pay attention to the changes in vehicle types during the implementation of these measures, which most contribute CO2 and various pollutants, in order to make the measures more targeted by changing the number or the market share of new energy of focused vehicle types.

Vagus nerve stimulation for pharmacoresistant epilepsy secondary to encephalomalacia: A single-center retrospective study.

Objective: Vagus nerve stimulation (VNS) is an adjunctive treatment for pharmacoresistant epilepsy. Encephalomalacia is one of the most common MRI findings in the preoperative evaluation of patients with pharmacoresistant epilepsy. This is the first study that aimed to determine the effectiveness of VNS for pharmacoresistant epilepsy secondary to encephalomalacia and evaluate the potential predictors of VNS effectiveness. Methods: We retrospectively analyzed the seizure outcomes of VNS with at least 1 year of follow-up in all patients with pharmacoresistant epilepsy secondary to encephalomalacia. Based on the effectiveness of VNS (≥50% or <50% reduction in seizure frequency), patients were divided into two subgroups: responders and non-responders. Preoperative data were analyzed to screen for potential predictors of VNS effectiveness. Results: A total of 93 patients with epilepsy secondary to encephalomalacia who underwent VNS therapy were recruited. Responders were found in 64.5% of patients, and 16.1% of patients achieved seizure freedom at the last follow-up. In addition, the responder rate increased over time, with 36.6, 50.5, 64.5, and 65.4% at the 3-, 6-, 12-, and 24-month follow-ups, respectively. After multivariate analysis, seizure onset in adults (>18 years old) (OR: 0.236, 95%CI: 0.059-0.949) was found to be a positive predictor, and the bilateral interictal epileptic discharges (IEDs) (OR: 3.397, 95%CI: 1.148-10.054) and the bilateral encephalomalacia on MRI (OR: 3.193, 95%CI: 1.217-8.381) were found to be negative predictors of VNS effectiveness. Conclusion: The results demonstrated the effectiveness and safety of VNS therapy in patients with pharmacoresistant epilepsy secondary to encephalomalacia. Patients with seizure onset in adults (>18 years old), unilateral IEDs, or unilateral encephalomalacia on MRI were found to have better seizure outcomes after VNS therapy.