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Objectives: Patients with traumatic brain injury (TBI) often suffer memory and cognitive impairments, and oxiracetam‐like drugs are considered to have a positive impact on these symptoms potentially. However, the efficacy and safety of L‐oxiracetam and oxiracetam in TBI patients have not been sufficiently investigated. Methods: The study adopts a multicenter, randomized, double‐blind, parallel‐group, phase 3 clinical trial design in 74 centers across 51 hospitals in China. A total of 590 TBI patients meeting criteria will be randomly allocated into three groups in a 2:2:1 ratio: L‐oxiracetam group, oxiracetam group, and placebo group. The treatment period is 14 days, with a follow‐up period of 90 days. The primary outcome measure is the change in the Loewenstein Occupational Therapy Cognitive Assessment score at 90 days after treatment. Secondary outcomes include changes in other cognitive assessments, neurological function, activities of daily living, and safety assessments. Discussion: There is no robust evidence to suggest that L‐oxiracetam and oxiracetam can enhance memory and cognitive function in patients with mild to moderate TBI. This study has the potential to answer this crucial clinical question. Trial registration: chinadrugtrials.org.cn, identifier CTR20192539; ClinicalTrials.gov, identifier NCT04205565. [ABSTRACT FROM AUTHOR]

Aim: We aim to identify the specific CD4+ T‐cell subtype influenced by brain‐to‐CLN signaling and explore their role during the acute phase of traumatic brain injury (TBI). Method: Cervical lymphadenectomy or cervical afferent lymphatic ligation was performed before TBI. Cytokine array and western blot were used to detect cytokines, while the motor function was assessed using mNss and rotarod test. CD4+ T‐cell subtypes in blood, brain, and CLNs were analyzed with Cytometry by time‐of‐flight analysis (CyTOF) or fluorescence‐activated cell sorting (FACS). Brain edema and volume changes were measured by 9.4T MRI. Neuronal apoptosis was evaluated by terminal deoxynucleotidyl transferase‐mediated dUTP nick end labeling (TUNEL) staining. Results: Cervical lymphadenectomy and ligation of cervical lymphatic vessels resulted in a decreased infiltration of CD4+ T cells, specifically CD11b‐positive CD4+ T cells, within the affected region. The population of CD4+CD11b+ T cells increased in ligated CLNs, accompanied by a decrease in the average fluorescence intensity of sphingosine‐1‐phosphate receptor‐1 (S1PR1) on these cells. Administration of CD4+CD11b+ T cells sorted from CLNs into the lateral ventricle reversed the attenuated neurologic deficits, brain edema, and lesion volume following cervical lymphadenectomy. Conclusion: The infiltration of CD4+CD11b+ T cells exacerbates secondary brain damage in TBI, and this process is modulated by brain‐to‐CLN signaling. [ABSTRACT FROM AUTHOR]

Aim: We aimed to assess the effects of cerebral glucagon‐like peptide‐1 receptor (GLP‐1R) activation on the glymphatic system and whether this effect was therapeutic for traumatic brain injury (TBI). Methods: Immunofluorescence was employed to evaluate glymphatic system function. The blood–brain barrier (BBB) permeability, microvascular basement membrane, and tight junction expression were assessed using Evans blue extravasation, immunofluorescence, and western blot. Immunohistochemistry was performed to assess axonal damage. Neuronal apoptosis was evaluated using Nissl staining, terminal deoxynucleotidyl transferase‐mediated dUTP nick end labeling (TUNEL) staining, and western blot. Cognitive function was assessed using behavioral tests. Results: Cerebral GLP‐1R activation restored glymphatic transport following TBI, alleviating BBB disruption and neuronal apoptosis, thereby improving cognitive function following TBI. Glymphatic function suppression by treatment using aquaporin 4 inhibitor TGN‐020 abolished the protective effect of the GLP‐1R agonist against cognitive impairment. Conclusion: Cerebral GLP‐1R activation can effectively ameliorate neuropathological changes and cognitive impairment following TBI; the underlying mechanism could involve the repair of the glymphatic system damaged by TBI. [ABSTRACT FROM AUTHOR]

Remobilization of carbon (C) and nitrogen (N) from roots and crowns to regrowing shoots is an important strategy for grassland plants to tolerate herbivory. While this remobilization is thought to terminate once plants have the capacity to photosynthesize again and to take up N from the soil, this has rarely been quantified.Here we investigated the remobilization of C and N to regrowing shoots of a perennial grassland under two defoliation frequencies (every 15 and 30 days) and two N fertilization levels (0 and 2.8 g m−2) by growing intact plant–soil cores for 60 days in a growth chamber. We measured the C remobilization from roots and crowns to regrowing shoots using a novel continuous 13C labelling method, and quantified the N remobilization to regrowing shoots and plant N uptake from soil with a 15N tracer method.Regrowing shoots relied strongly on below‐ground C reserves, where up to 52% of C in regrowing shoots came from below‐ground during the first 30 days after defoliation. Below‐ground C was still remobilized when plant shoots had fully regrown and retained full capacity to photosynthesize. Plants relied more on C remobilization with shorter times between defoliation events at the expense of root biomass, particularly without N fertilization. Large amounts of C remobilization were accompanied by large amounts of N remobilization (up to 89% of total shoot N) that were positively related, suggesting a coupled C and N transfer from roots and crowns to shoots.Synthesis. The unexpectedly high dependency on C and N remobilization occurred continuously after defoliation and did not terminate once plants were fully regrown. Our results indicate that remobilization of C and N from below‐ground has profound effects on long‐term productivity and C sequestration that needs to be considered for managing similar grasslands worldwide. [ABSTRACT FROM AUTHOR]

Although positive buoyancy of young lithosphere near spreading centers does not favor spontaneous subduction, subduction initiation occurs easily near ridges due to their intrinsic rheological weakness when plate motion reverses from extension to compression. It has also been repeatedly proposed that inherited detachment faults may directly control the nucleation of new subduction zones near ridges subjected to forced compression. However, recent 3D numerical experiments suggested that direct inversion of a single detachment fault does not occur. Here we further investigate this controversy numerically by focusing on the influence of brittle‐ductile damage on the dynamics of near‐ridge subduction initiation. We self‐consistently model the inversion of tectonic patterns formed during oceanic spreading using 3D high‐resolution thermomechanical numerical models with strain weakening of faults and grain size evolution. Numerical results show that forced compression predominantly reactivates and rotates inherited extensional faults, shortening and thickening the weakest near‐ridge region of the oceanic lithosphere, thereby producing ridge swellings. As a result, a new megathrust zone is developed, which accommodates further shortening and subduction initiation. Furthermore, brittle/plastic strain weakening has a key impact on the collapse of the thickened ridge and the onset of near‐ridge subduction initiation. In contrast, grain size evolution of the mantle only slightly enhances the localization of shear zones at the brittle‐ductile transition and thus plays a subordinate role. Compared to the geological record, our numerical results provide new helpful insights into possible physical controls and dynamics of natural near‐ridge subduction initiation processes recorded by the Mirdita ophiolite of Albania. Plain Language Summary: Intra‐oceanic subduction comprises 40% of the subduction margins, but the mechanisms behind their initiation remain controversial. Although positive buoyancy of young oceanic plates compared to underlying mantle impedes the spontaneous subduction initiation near mid‐ocean ridges, the subduction can easily initiate there during the forced compression. In addition, the weak faults formed at the spreading stage facilitate the formation of subduction initiation. To clarify how subduction initiates at mid‐ocean ridges, we run 3D numerical models to self‐consistently explore the process of oceanic spreading followed by a gradual transition to forced plate convergence. Numerical results demonstrate that under such conditions, two previously diverging oceanic plates can subsequently collide and thicken at the spreading center, thereby producing a new lithospheric‐scale shear zone and causing the subsequent near‐ridge subduction initiation. Strong weakening of the shear zone rocks promotes the subduction initiation, which fails without such weakening. In turn, thermal and compositional heterogeneities inherited from the seafloor spreading stage control geometry and polarity of the resulting young subduction zone. Key Points: Under forced compression, subduction initiation starts along the newly formed shear zoneStrain weakening plays a key role in the new shear zone and subduction initiationGrain size reduction slightly enhances the localization of new shear zones [ABSTRACT FROM AUTHOR]

Five enterococcal strains ( E nterococcus faecalis LS15, PF03, BF10 and SL13 and E nterococcus faecium MM08) were isolated and identified from 130 probiotic products marketed in China. The determined biological characteristics were acid tolerance, bile tolerance, pepsin tolerance, trypsin tolerance, organic acid production and antimicrobial activity. Safety examination of potential virulence factors and antibiotic resistance were also performed. The five isolated strains showed good tolerance to biological barriers in vitro, and lactic acid was the most abundant organic acid (10-11 mg/m L) produced by these strains. The isolates exhibited antilisterial activities. Safety examinations revealed that certain potential virulence factors ( ace, gelE and efaA) were harbored in strains LS15, PF03, BF10 and SL13, and all of the isolates exhibited complete or intermediate resistance to gentamicin, ciprofloxacin, erythrocin and tetracycline. Compared with the other isolates, the E . faecium MM08 played the leading role as a probiotic strain. These antilisterial probiotic enterococcal strains had good tolerance to biological barriers, mainly produced lactic acid, exhibited antibiotic resistance traits and could harbor certain virulence factors. Practical Applications This study aimed to examine the biological characteristics and safety aspects of probiotic enterococcal strains isolated from probiotic products. Five isolates showed good probiotic characteristics, but its safety aspects need to be studied in the future. [ABSTRACT FROM AUTHOR]

Aim: We aim to identify the specific CD4 + T-cell subtype influenced by brain-to-CLN signaling and explore their role during the acute phase of traumatic brain injury (TBI)., Method: Cervical lymphadenectomy or cervical afferent lymphatic ligation was performed before TBI. Cytokine array and western blot were used to detect cytokines, while the motor function was assessed using mNss and rotarod test. CD4 + T-cell subtypes in blood, brain, and CLNs were analyzed with Cytometry by time-of-flight analysis (CyTOF) or fluorescence-activated cell sorting (FACS). Brain edema and volume changes were measured by 9.4T MRI. Neuronal apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining., Results: Cervical lymphadenectomy and ligation of cervical lymphatic vessels resulted in a decreased infiltration of CD4 + T cells, specifically CD11b-positive CD4 + T cells, within the affected region. The population of CD4 + CD11b + T cells increased in ligated CLNs, accompanied by a decrease in the average fluorescence intensity of sphingosine-1-phosphate receptor-1 (S1PR1) on these cells. Administration of CD4 + CD11b + T cells sorted from CLNs into the lateral ventricle reversed the attenuated neurologic deficits, brain edema, and lesion volume following cervical lymphadenectomy., Conclusion: The infiltration of CD4 + CD11b + T cells exacerbates secondary brain damage in TBI, and this process is modulated by brain-to-CLN signaling., (© 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)