GABA-receptive microglia selectively sculpt developing inhibitory circuits.

Microglia, the resident immune cells of the brain, have emerged as crucial regulators of synaptic refinement and brain wiring. However, whether the remodeling of distinct synapse types during development is mediated by specialized microglia is unknown. Here, we show that GABA-receptive microglia selectively interact with inhibitory cortical synapses during a critical window of mouse postnatal development. GABA initiates a transcriptional synapse remodeling program within these specialized microglia, which in turn sculpt inhibitory connectivity without impacting excitatory synapses. Ablation of GABAB receptors within microglia impairs this process and leads to behavioral abnormalities. These findings demonstrate that brain wiring relies on the selective communication between matched neuronal and glial cell types.

Iron, Tungsten Dual-Doped Nickel Sulfide as Efficient Bifunctional Catalyst for Overall Water Splitting.

Developing low-cost and highly efficient bifunctional catalysts for both the oxygen evolution reaction (OER) and the hydrogen evolution reaction (HER) is a challenging problem in electrochemical overall water splitting. Here, iron, tungsten dual-doped nickel sulfide catalyst (Fe/W-Ni3S2) is synthesized on the nickel foam, and it exhibits excellent OER and HER performance. As a result, the water electrolyze based on Fe/W-Ni3S2 bifunctional catalyst illustrates 10 mA cm-2 at 1.69 V (without iR-compensation) and highly durable overall water splitting over 100 h tested under 500 mA cm-2. Experimental results and DFT calculations indicate that the synergistic interaction between Fe doping and Ni vacancy induced by W leaching during the in situ oxidation process can maximize exposed OER active sites on the reconstructed NiOOH species for accelerating OER kinetics, while the Fe/W dual-doping optimizes the electronic structure of Fe/W-Ni3S2 and the binding strength of intermediates for boosting HER. This study unlocks the different promoting mechanisms of incorporating Fe and W for boosting the OER and HER activity of Ni3S2 for water splitting, which provides significant guidance for designing high-performance bifunctional catalysts for overall water splitting.

The glycosylation deficiency of flavivirus NS1 attenuates virus replication through interfering with the formation of viral replication compartments.

BACKGROUND: Flavivirus is a challenge all over the world. The replication of flavivirus takes place within membranous replication compartments (RCs) derived from endoplasmic reticulum (ER). Flavivirus NS1 proteins have been proven essential for the formation of viral RCs by remodeling the ER. The glycosylation of flavivirus NS1 proteins is important for viral replication, yet the underlying mechanism remains unclear. METHODS: HeLa cells were used to visualize the ER remodeling effects induced by NS1 expression. ZIKV replicon luciferase assay was performed with BHK-21 cells. rZIKV was generated from BHK-21 cells and the plaque assay was done with Vero Cells. Liposome co-floating assay was performed with purified NS1 proteins from 293T cells. RESULTS: We found that the glycosylation of flavivirus NS1 contributes to its ER remodeling activity. Glycosylation deficiency of NS1, either through N-glycosylation sites mutations or tunicamycin treatment, compromises its ER remodeling activity and interferes with viral RCs formation. Disruption of NS1 glycosylation results in abnormal aggregation of NS1, rather than reducing its membrane-binding activity. Consequently, deficiency in NS1 glycosylation impairs virus replication. CONCLUSIONS: In summary, our results highlight the significance of NS1 glycosylation in flavivirus replication and elucidate the underlying mechanism. This provides a new strategy for combating flavivirus infections.

Preoperative and intraoperative tirofiban during endovascular thrombectomy in large vessel occlusion stroke due to large artery atherosclerosis.

BACKGROUND AND PURPOSE: The aim of this study is to investigate the efficacy and safety of preoperative versus intraoperative tirofiban in patients with large vessel occlusion (LVO) due to large artery atherosclerosis (LAA). METHODS: This is a retrospective multicenter cohort study based on the RESCUE-RE (Registration Study for Critical Care of Acute Ischemic Stroke After Recanalization) trial enrolling patients with anterior circulation LVO classified as LAA within 24 h of onset. Patients were divided into three groups: preoperative tirofiban (PT), intraoperative tirofiban (IT), and no tirofiban (NT). Propensity score matching (PSM) was used to balance baseline characteristics. The efficacy outcomes included 90-day functional independence (modified Rankin Scale score = 0-2) and early partial recanalization (EPR; defined as a modified Thrombolysis in Cerebral Infarction score = 1-2a). The safety outcomes included symptomatic intracranial hemorrhage (sICH). RESULTS: A total of 104 matched triplets were obtained through PSM. Compared with NT, PT increased 90-day functional independence (60.8% vs. 42.3%, p = 0.008) and EPR (42.7% vs. 18.3%, p < 0.001) rate, with a tendency to increase the asymptomatic intracranial hemorrhage (aICH) proportion (28.8% vs. 18.3%, p = 0.072). Compared with IT, PT had a higher 90-day functional independence (60.8% vs. 45.2%, p = 0.025) and EPR (42.7% vs. 20.2%, p = 0.001) rate, with no significant difference in sICH (14.4% vs. 7.7%, p = 0.122) and aICH (28.8% vs. 21.2%, p = 0.200). Compared with NT, IT had a lower 90-day mortality rate (9.6% vs. 24.0%, p = 0.005). CONCLUSIONS: Tirofiban shows good adjuvant therapy potential in acute ischemic stroke-LVO due to LAA patients. PT is associated with higher rates of EPR and better therapeutic efficacy. In addition, EPR may be a potential way to improve prognosis.

Artery diameter ratio after recanalization in endovascular therapy for acute ischemic stroke: a new predictor of clinical outcomes.

PURPOSE: This study aimed to investigate the relationship between the artery diameter ratio (ADR) after recanalization and clinical outcomes. METHODS: Patients with middle cerebral artery occlusion confirmed by DSA from 1 January 2018, to 31 December 2019, were retrospectively analyzed. All patients confirmed TICI grade 2b or 3. The ADR was calculated as M2 segment diameter/M1 segment diameter. Multivariate regression analysis was used to describe clinical outcomes of two groups (ADR < 0.6 and ≥ 0.6). ROC curves were used to compare different models and find the best cutoff. RESULTS: A total of 143 patients were included in the study, including 77 males and 66 females, with an average age of 67.79 ± 12 years. The NIHSS at discharge was significantly higher in the ADR < 0.6 group than another group (mean, 16.37 vs. 6.19, P < 0.001). At 90 days, the cases of functional independence was significantly less in the ADR < 0.6 group (20.97% vs. 83.95%, OR 0.05, 95% CI 0.02-0.12, P < 0.001). The ADR < 0.6 group had a higher incidence of cerebral edema (P = 0.027) and sICH (P = 0.038). The ADR had the strongest power to distinguish mRS > 2 (AUC = 0.851) and DC (AUC = 0.805), and the best cutoff value are 0.6 (specificity 85.19%, sensitivity 75.81%) and 0.58 (specificity 65.96%, sensitivity 100%), respectively. CONCLUSION: The low ADR is associated with poor outcomes. The decrease in ADR may be an indirect manifestation of the loss of cerebrovascular autoregulation.

Clinical effect of successful reperfusion in patients presenting with NIHSS < 6 and large vessel occlusion.

PURPOSE: The purpose of this study was to evaluate the impact of reperfusion in patients with large vessel occlusion (LVO) of the anterior circulation and National Institutes of Health Stroke Scale (NIHSS)< 6. METHODS: It was a retrospective cohort study. The reperfusion grade was determined using the modified thrombolysis in cerebral infarction (TICI) score. The modified Rankin Score (mRS) ≤1 were defined as excellent and (mRS) ≤2 as favorable outcome at 3-month. Meanwhile, the all-cause mortality, intracerebral hemorrhage, and complications were recorded. Multivariate logistic regression analyses were performed to evaluate outcomes. RESULTS: Seventy-six patients (86.4%) achieved reperfusion (TICI2B/3). Excellent outcome was achieved in 62 (70.5%) and favorable outcome in 69 (78.4%). All-cause death occurred in 2 (2.3%). The rate of excellent outcome in patients with TICI0,1,2A was 41.7%, with TICI2B 69.2%, and with TICI3 78.0% (p < 0.05). In a multivariate logistic regression analysis related to excellent outcome, the OR(95% CI) was 5.68(1.35,23.95) for TICI3; the test for linear trend by entering categorical variables as continuous variables in the adjusted model (p for trend=0.02<0.05), defining TICI0,1,2A as reference. Subgroup analyses showed without intravenous thrombolysis (IVT) (OR, 14.29; 95% CI, 1.76-116.37) and with middle cerebral artery (MCA) occlusion (OR, 7.97; 95% CI,1.26-50.32), the excellent outcome further improved with TICI3. Findings were similar in favorable outcome. CONCLUSIONS: Our results indicated that successful reperfusion was intensely connected with better functional outcomes for patients with LVO presenting with NIHSS<6 in the anterior circulation, especially MCA occlusion and pretreatment without IVT.

Iron Minerals Mediated Interfacial Hydrolysis of Chloramphenicol Antibiotic under Limited Moisture Conditions.

Iron minerals are important soil components; however, little information is available for the transformation of antibiotics on iron mineral surfaces, especially under limited moisture conditions. In this study, we investigated the catalytic performance of four iron minerals (maghemite, hematite, goethite, and siderite) for the hydrolysis of chloramphenicol (CAP) antibiotic at different moisture conditions. All the iron oxides could efficiently catalyze CAP hydrolysis with the half-lives <6 days when the surface water content was limited, which was controlled by the atmospheric relative humidity of 33-76%. Different minerals exhibited distinctive catalytic processes, depending on the surface properties. H-bonding or Lewis acid catalysis was proposed for surface hydrolytic reaction on iron oxides, which however was almost completely inhibited when the surface water content was >10 wt % due to the competition of water molecules for surface reactive sites. For siderite, the CAP hydrolysis was resistant to excessive surface water. A bidentate H-bonding interaction mechanism would account for CAP hydrolysis on siderite. The results of this study highlight the importance of surface moisture on the catalytic performance of iron minerals. The current study also reveals a potential degradation pathway for antibiotics in natural soil, which has been neglected before.

Effects of Oral Antiplatelet Agents and Tirofiban on Functional Outcomes of Patients with Non-Disabling Minor Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Over half of patients with acute ischemic stroke present with minor neurologic deficits. We investigated the effects of oral antiplatelet agents vs. tirofiban, a highly selective GP IIb/IIIa antiplatelet drug, on functional outcomes of stroke patients with non-disabling neurologic deficits. METHODS: This retrospective study analyzed data of 125 patients with minor stroke who had National Institutes of Health Stroke Scale (NIHSS) scores of 5 or less within 6 hours of stroke symptom onset between January 2010 and June 2018. All patients were selected from the Department of Neurology at the Third Affiliated Hospital of Army Medical University. There were 54 cases in each group after propensity score matching, in which patients received oral antiplatelet agents (n = 64) and tirofiban (n = 61). Safety outcomes were assessed by incident intracranial hemorrhage, systemic bleeding and death. Efficacy outcomes were assessed using the NIHSS score at 24 hrs, 7 days or at discharge, and clinical deterioration. The modified rankin scale (mRs) was assessed at 90 days. RESULTS: No significant differences were found in the incidence of intracranial hemorrhage, systemic bleeding or death between groups (P>0.05). Although neurological function improved significantly in both groups, NIHSS scores were lower in the tirofiban group compared with those in the oral antiplatelet agents group at 24 hrs (1 versus 3, P = 0.000), 7 days or at discharge (0 versus 2, P = 0.000). The clinical deterioration rate was higher in the oral antiplatelet agents group than in the tirofiban group, but without significance (16.7% versus 5.6%, P = 0.126). Functional outcomes (mRs = 0) were more favorable in the tirofiban group than in the oral antiplatelet agents group (66.7% vs. 44.4%; adjusted odds ratio 3.32; 95% CI: 1.38-7.99; P = 0. 008). CONCLUSION: Intravenous tirofiban seems to be safe and effective with more favorable functional outcomes than oral antiplatelet agents, suggesting that tirofiban is a viable treatment choice for selected patients with non-disabling minor acute ischemic stroke.

Substituted Aromatic-Facilitated Dissemination of Mobile Antibiotic Resistance Genes via an Antihydrolysis Mechanism Across an Extracellular Polymeric Substance Permeable Barrier.

Mobile antibiotic resistance genes (ARGs) in environmental systems may pose a threat to public health. The coexisting substituted aromatic pollutants may help the ARGs cross the extracellular polymeric substance (EPS) permeable barrier into the interior of cells, facilitating ARG dissemination, but the mechanism is still unknown. Here, we demonstrated that a specific antihydrolysis mechanism of mobile plasmid in the extracellular matrix makes a greater contribution to this facilitated dissemination. Specifically, fluorescence microtitration with a Tb3+-labeled pUC19 plasmid was used to study the formation of substituted aromatic-plasmid complexes associated with ARG dissemination. Manipulations of the endA gene and an EPS confirmed that these forming complexes antagonize the EPS-mediated hydrolysis of the plasmid. Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and computational chemistry demonstrated that substituents alter the polarity of aromatic molecules, making the carbon at the 6-position of 1,3-dichlorobenzene as well as the labile protons (-NH2/-OH) of m-phenylenediamine, aniline, and 2-naphthol interact with the deprotonated hydroxy group of the phosphate (P-O···H-C/N/O), mainly via hydrogen bonds. Linear correlations among ARG disseminations, association constants, and bonding energies highlight the quantitative dependency of ARG proliferation on a combination of functionalities templated by d-ribose-phosphate.

Safety and Preliminary Efficacy of Early Tirofiban Treatment After Alteplase in Acute Ischemic Stroke Patients.

BACKGROUND AND PURPOSE: We investigated whether early initiation of tirofiban, a glycoprotein IIb/IIIa antagonist, is safe, can reduce the risk of reocclusion, and improve outcomes in acute ischemic stroke patients after alteplase. METHODS: Forty-one patients received alteplase followed by intravenous tirofiban infusion for at least 24 hours. The incidence of symptomatic intracranial hemorrhage, systematic bleedings, and death was recorded. The National Institutes of Health stroke scale score was evaluated at 24 hours and at day 7 (or discharge). Modified Rankin scale was assessed at 3 months. Outcomes for these patients were compared with a propensity score-matched historical cohort with alteplase only. RESULTS: The incidence of symptomatic intracranial hemorrhage, death, or systematic bleedings (P=1.00) was not increased in the alteplase/tirofiban group. At 24 hours, fewer patients experienced reocclusion in the alteplase/tirofiban group (2.4% versus 22.0%; P=0.025). At day 7 or discharge, the median National Institutes of Health stroke scale score was significantly lower in the alteplase/tirofiban group (1 versus 6; P=0.002). At 3 months, more patients had favorable outcomes of modified Rankin scale 0 to 1 (70.7% versus 46.2%; P=0.026). CONCLUSIONS: Intravenous tirofiban immediately after alteplase seems to be safe and potentially more effective when compared with alteplase alone for selected stroke patients. CLINICAL TRIAL REGISTRATION: URL: http://www.chictr.org.cn/. Unique identifier: ChiCTR-TRC-14004630.

Primary jejunal gastrinoma: a case report and review of the literature.

BACKGROUND: Primary jejunal gastrinomas are exceedingly rare, and data for long-term follow-up is limited. Until now, only six cases of gastrinomas arising from the jejunum have been reported in the English literature. CASE PRESENTATION: Presented is a case of a primary gastrinoma located in the proximal jejunum. After surgical resection of the tumor, eugastrinemia was quickly achieved and after a 10-year follow-up period, the patient was still disease-free. CONCLUSIONS: This case report demonstrates that surgical resection of a primary jejunal gastrinoma without evidence of metastasis can be curative, with a good long-term prognosis.

Layer 1 neocortex: Gating and integrating multidimensional signals.

Layer 1 (L1) of the neocortex acts as a nexus for the collection and processing of widespread information. By integrating ascending inputs with extensive top-down activity, this layer likely provides critical information regulating how the perception of sensory inputs is reconciled with expectation. This is accomplished by sorting, directing, and integrating the complex network of excitatory inputs that converge onto L1. These signals are combined with neuromodulatory afferents and gated by the wealth of inhibitory interneurons that either are embedded within L1 or send axons from other cortical layers. Together, these interactions dynamically calibrate information flow throughout the neocortex. This review will primarily focus on L1 within the primary sensory cortex and will use these insights to understand L1 in other cortical areas.

A Protective Layer of UIO-66/Reduced Graphene Oxide to Stabilize Zinc-Metal Anodes toward High-Performance Aqueous Zinc-Ion Batteries.

Rechargeable aqueous Zn-ion batteries with a Zn anode hold great promise as promising candidates for advanced energy storage systems. The construction of protective layer coatings on Zn anode is an effective way to suppress the growth of Zn dendrites and water-induced side reactions. Herein, we reported a series of UIO-66 materials with different concentrations of reduced graphene oxide (rG) coated onto the surface of Zn foil (Zn@UIO-66/rGx; x = 0.05, 0.1, and 0.2). Benefiting from the synergistic effect of UIO-66 and rG, symmetric cells with Zn@UIO-66/rGx (x = 0.1) electrodes exhibit excellent reversibility (e.g., long cycling life over 1100 h at 1 mA cm-2/1 mAh cm-2) and superior rate capability (e.g., over 1100 and 400 h at 5 mA cm-2/2.5 mAh cm-2 and 10 mA cm-2/5 mAh cm-2, respectively). When the Zn@UIO-66/rG0.1 anode was paired with the NaV3O8·1.5H2O (NVO) cathode, the Zn@UIO-66/rG0.1||NVO cell also delivered a high reversible capacity of 189.9 mAh g-1 with an initial capacity retention of 61.3% after 500 cycles at 1 A g-1, compared to the bare Zn||NVO cell with only 92 cycles.

Hierarchical and dynamic graph attention network for drug-disease association prediction.

In the realm of biomedicine, the prediction of associations between drugs and diseases holds significant importance. Yet, conventional wet lab experiments often fall short of meeting the stringent demands for prediction accuracy and efficiency. Many prior studies have predominantly focused on drug and disease similarities to predict drug-disease associations, but overlooking the crucial interactions between drugs and diseases that are essential for enhancing prediction accuracy. Hence, in this paper, a resilient and effective model named Hierarchical and Dynamic Graph Attention Network (HDGAT) has been proposed to predict drug-disease associations. Firstly, it establishes a heterogeneous graph by leveraging the interplay of drug and disease similarities and associations. Subsequently, it harnesses the capabilities of graph convolutional networks and bidirectional long short-term memory networks (Bi-LSTM) to aggregate node-level information within the heterogeneous graph comprehensively. Furthermore, it incorporates a hierarchical attention mechanism between convolutional layers and a dynamic attention mechanism between nodes to learn embeddings for drugs and diseases. The hierarchical attention mechanism assigns varying weights to embeddings learned from different convolutional layers, and the dynamic attention mechanism efficiently prioritizes inter-node information by allocating each node with varying rankings of attention coefficients for neighbour nodes. Moreover, it employs residual connections to alleviate the over-smoothing issue in graph convolution operations. The latent drug-disease associations are quantified through the fusion of these embeddings ultimately. By conducting 5-fold cross-validation, HDGAT's performance surpasses the performance of existing state-of-the-art models across various evaluation metrics, which substantiates the exceptional efficacy of HDGAT in predicting drug-disease associations.

Enhancing Optical and Thermal Stability of Blue-Emitting Perovskite Nanocrystals through Surface Passivation with Sulfonate or Sulfonic Acid Ligands.

This study aims to enhance the optical and thermal properties of cesium-based perovskite nanocrystals (NCs) through surface passivation with organic sulfonate (or sulfonic acid) ligands. Four different phenylated ligands, including sodium ß-styrenesulfonate (SbSS), sodium benzenesulfonate (SBS), sodium p-toluenesulfonate (SPTS), and 4-dodecylbenzenesulfonic acid (DBSA), were employed to modify blue-emitting CsPbBr1.5Cl1.5 perovskite NCs, resulting in improved size uniformity and surface functionalization. Transmission electron microscopy and X-ray photoelectron spectroscopy confirmed the successful anchoring of sulfonate or sulfonic acid ligands on the surface of perovskite NCs. Moreover, the photoluminescence quantum yield increased from 32% of the original perovskite NCs to 63% of the SPTS-modified ones due to effective surface passivation. Time-resolved photoluminescence decay measurements revealed extended PL lifetimes for ligand-modified NCs, indicative of reduced nonradiative recombination. Thermal stability studies demonstrated that the SPTS-modified NCs retained nearly 80% of the initial PL intensity when heated at 60 °C for 10 min, surpassing the performance of the original NCs. These findings emphasize the optical and thermal stability enhancement of cesium-based perovskite NCs through surface passivation with suitable sulfonate ligands.

From graphite of used lithium-ion batteries to holey graphite coated by carbon with enhanced lithium storage capability.

The efficient recycling of waste graphite anode from used lithium-ion batteries (LIBs) has attracted considerable concerns mainly owing to the environment protection and reutilization of resources. Herein, we reported a rational and facile strategy for the synthesis of holey graphite coated by carbon (hG0.01@C0.10) through the separation, purification and creation of holey structures of waste graphite by using NaOH and carbon-coating by using phenolic resin. The holey structures facilitate the hG0.01@C0.10 with the quick penetration of electrolytes and rapid diffusion of Li+. The carbon coating is more favorable for hG0.01@C0.10 with improved electronic conductivity and less alleviated volume during the cycles. Benefiting from the synergistic effect of holey structures and carbon coating, the hG0.01@C0.10 as anode for LIBs displays a high reversible capacity of 377.6 mAh g-1 at 0.5 C and superior rate capabilities (e.g., 348.0 and 274.7 mAh g-1 at 1 and 2 C, respectively) and maintains a high reversible capacity of 278.7 mAh g-1 at 1 C after 300 cycles with an initial capacity retention of 80.0 %.

Chronic radiation proctitis refractory to steroid enema was successfully treated by metformin and sodium butyrate: a case report.

BACKGROUND: Radiation proctitis (RP) is a significant complication of pelvic radiation. Effective treatments for chronic RP are currently lacking. We report a case where chronic RP was successfully managed by metformin and butyrate (M-B) enema and suppository therapy. CASE PRESENTATION: A 70-year-old Asian male was diagnosed with prostate cancer of bilateral lobes, underwent definitive radiotherapy to the prostate of 76 Gy in 38 fractions and six months of androgen deprivation therapy. Despite a stable PSA nadir of 0.2 ng/mL for 10 months post-radiotherapy, he developed intermittent rectal bleeding, and was diagnosed as chronic RP. Symptoms persisted despite two months of oral mesalamine, mesalamine enema and hydrocortisone enema treatment. Transition to daily 2% metformin and butyrate (M-B) enema for one week led to significant improvement, followed by maintenance therapy with daily 2.0% M-B suppository for three weeks, resulting in continued reduction of rectal bleeding. Endoscopic examination and biopsy demonstrated a good therapeutic effect. CONCLUSIONS: M-B enema and suppository may be an effective treatment for chronic RP.

An immune biomarker associated with EMT serves as a predictor for prognosis and drug response in bladder cancer.

BACKGROUND: Bladder cancer (BLCA), which develops from the upper endometrial of the bladder, is the sixth most prevalent cancer across the globe. WDHD1 (WD repeat and HMG-box DNA binding protein 1 gene) directly affects signaling, the cell cycle, and the development of the cell skeleton. Uncertainty surrounds WDHD1's function in BLCA immunity and prognosis, though. MATERIALS AND METHODS: Using weighed gene co-expression network analysis (WGCNA), initially, we first identified 32 risk factors in genes with differential expression for this investigation. Then, using a variety of bioinformatic techniques and experimental validation, we examined the connections between WDHD1 and BLCA expression, clinical pathological traits, WDHD1-related proteins, upper-skin-intermediate conversion (EMT), immune cell immersion, convergence factors, immune markers, and drug sensitivity. RESULT: The findings demonstrated that we constructed a 32-gene risk-predicting model where WDHD1 was elevated as a representative gene expression in BLCA and related to a range of clinical traits. Furthermore, high WDHD1 expression was a standalone predictor associated with a worse survival rate. The most commonly recruited cells and their evolutionary patterns were highlighted to better comprehend WDHD1's function in cancer. High WDHD1 expression was associated with many aspects of immunology. Finally, the study found that individuals with high expression of WDHD1 were drug-sensitive to four different broad-spectrum anti-cancer drugs. CONCLUSION: These results describe dynamic changes in the tumor microenvironment in BLCA and provide evidence for the hypothesis that WDHD1 is a novel biomarker of tumor development. WDHD1 may therefore be a useful target for the detection and management of BLCA.