Encoding of both analog- and digital-like behavioral outputs by one C. elegans interneuron.

Model organisms usually possess a small nervous system but nevertheless execute a large array of complex behaviors, suggesting that some neurons are likely multifunctional and may encode multiple behavioral outputs. Here, we show that the C. elegans interneuron AIY regulates two distinct behavioral outputs: locomotion speed and direction-switch by recruiting two different circuits. The "speed" circuit is excitatory with a wide dynamic range, which is well suited to encode speed, an analog-like output. The "direction-switch" circuit is inhibitory with a narrow dynamic range, which is ideal for encoding direction-switch, a digital-like output. Both circuits employ the neurotransmitter ACh but utilize distinct postsynaptic ACh receptors, whose distinct biophysical properties contribute to the distinct dynamic ranges of the two circuits. This mechanism enables graded C. elegans synapses to encode both analog- and digital-like outputs. Our studies illustrate how an interneuron in a simple organism encodes multiple behavioral outputs at the circuit, synaptic, and molecular levels.

Fusidic Acid and Its Major Active Metabolite Penetration into Cerebrospinal Fluid for Assessing Treatment of Intracranial Infections.

Fusidic acid (FA) had excellent antimicrobial effects due to its unique mechanism of action. Since 1962, FA has been widely used in the systemic and topical treatment of staphylococcal infections and exhibits a well-characterized potency against methicillin-susceptible Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and methicillin-resistant coagulase-negative Staphylococci. In view of the spectrum of activity, no cross-resistance with other clinically used antibiotics, and potential penetration into brain tissue, FA was used to treat possible gra-positive bacteria in 3 patients with intracranial infections in the present report. FA and its active metabolite (3-keto FA) were measured in plasma and cerebrospinal fluid (CSF) to assess the treatment of FA, and the results indicated that 1,500 mg per day of FA was sufficient to achieve therapeutic concentrations in both plasma and CSF in intracranial infection patients, while the dosage did not experience unexpected regimen-related toxicity.

Mapping knowledge of the stem cell in traumatic brain injury: a bibliometric and visualized analysis.

Background: Traumatic brain injury (TBI) is a brain function injury caused by external mechanical injury. Primary and secondary injuries cause neurological deficits that mature brain tissue cannot repair itself. Stem cells can self-renewal and differentiate, the research of stem cells in the pathogenesis and treatment of TBI has made significant progress in recent years. However, numerous articles must be summarized to analyze hot spots and predict trends. This study aims to provide a panorama of knowledge and research hotspots through bibliometrics. Method: We searched in the Web of Science Core Collection (WoSCC) database to identify articles pertaining to TBI and stem cells published between 2000 and 2022. Visualization knowledge maps, including co-authorship, co-citation, and co-occurrence analysis were generated by VOSviewer, CiteSpace, and the R package "bibliometrix." Results: We retrieved a total of 459 articles from 45 countries. The United States and China contributed the majority of publications. The number of publications related to TBI and stem cells is increasing yearly. Tianjin Medical University was the most prolific institution, and Professor Charles S. Cox, Jr. from the University of Texas Health Science Center at Houston was the most influential author. The Journal of Neurotrauma has published the most research articles on TBI and stem cells. Based on the burst references, "immunomodulation," "TBI," and "cellular therapy" have been regarded as research hotspots in the field. The keywords co-occurrence analysis revealed that "exosomes," "neuroinflammation," and "microglia" were essential research directions in the future. Conclusion: Research on TBI and stem cells has shown a rapid growth trend in recent years. Existing studies mainly focus on the activation mechanism of endogenous neural stem cells and how to make exogenous stem cell therapy more effective. The combination with bioengineering technology is the trend in this field. Topics related to exosomes and immune regulation may be the future focus of TBI and stem cell research.

Light-sensitive coupling of rhodopsin and melanopsin to G(i/o) and G(q) signal transduction in Caenorhabditis elegans.

Activation of G-protein-coupled receptors (GPCRs) initiates signal transduction cascades that affect many physiological responses. The worm Caenorhabditis elegans expresses >1000 of these receptors along with their cognate heterotrimeric G proteins. Here, we report properties of 9-cis-retinal regenerated bovine opsin [(b)isoRho] and human melanopsin [(h)Mo], two light-activated, heterologously expressed GPCRs in the nervous system of C. elegans with various genetically engineered alterations. Profound transient photoactivation of G(i/o) signaling by (b)isoRho led to a sudden and transient loss of worm motility dependent on cyclic adenosine monophosphate, whereas transient photoactivation of G(q) signaling by (h)Mo enhanced worm locomotion dependent on phospholipase Cß. These transgenic C. elegans models provide a unique way to study the consequences of G(i/o) and G(q) signaling in vivo with temporal and spatial precision and, by analogy, their relationship to human neuromotor function.

The effect of telerehabilitation on balance in stroke patients: is it more effective than the traditional rehabilitation model? A meta-analysis of randomized controlled trials published during the COVID-19 pandemic.

Objective: Telerehabilitation and telemedicine have gradually gained popularity. In 2019, the outbreak of COVID-19 started in Wuhan and then spread across the world. To date, most countries have opted to coexist with the virus. However, patients, especially those who have suffered a stroke, should take measures to avoid being infected with any disease as much as possible since any infectious disease can lead to adverse events for them. Telerehabilitation can be beneficial to stroke patients as they are less likely to be infected by the virus. In recent years, several studies on telerehabilitation have been conducted globally. This meta-analysis aimed to investigate the effects of telerehabilitation on the balance ability of stroke patients, compare the efficacy of conventional rehabilitation with telerehabilitation, explore the characteristics of telerehabilitation and conventional rehabilitation, and provide recommendations for rehabilitation programs in the context of the global pandemic. Methods: We searched Pubmed, Embase, the Web of Science, and The Cochrane Library databases from 1 January 2020 to 31 December 2022 for randomized controlled trials published in English that evaluated the improvement of balance function in stroke patients after telerehabilitation and compared the differences between telerehabilitation (TR) and conventional rehabilitation (CR). The random-effects model was utilized to calculate mean differences (MDs) with 95% confidence intervals (CIs) to estimate intervention effects. Statistical heterogeneity was assessed according to the I2 values. The risk of bias was measured using the Cochrane risk-of-bias assessment tool. Results: We included nine studies in the system evaluation, all of which were included in the pooled analysis. All outcomes in the experimental and control groups improved over time. The comparison between groups concluded that people who received the telerehabilitation intervention had a significant improvement in the Berg Balance Scale (MD = 2.80; 95% CI 0.61, 4.98, P < 0.05, I2 = 51.90%) and the Fugl-Meyer Assessment (MD = 8.12; 95% CI 6.35, 9.88, P < 0.05, I2 = 0) compared to controls. The Timed Up and Go test (MD = -4.59; 95% CI -5.93, -.25, P < 0.05, I2 = 0) and Tinetti Performance-Oriented Mobility Assessment-Balance (MD = 2.50; 95% CI 0.39, 4.61, P < 0.05) scored better in the control group than in the experimental group. There were no significant differences in other outcomes between the two groups. Conclusion: Studies on changes in medical conditions during the COVID-19 pandemic also demonstrated that, for stroke patients, telerehabilitation achieves similar effects as the conventional rehabilitation model and can act as a continuation of the conventional rehabilitation model. Owing to the different equipment and intervention programs of telerehabilitation, its curative effect on the static balance and reactive balance of stroke patients may be different. Currently, telerehabilitation may be more conducive to the rehabilitation of patients' static balance abilities, while conventional rehabilitation is more effective for the rehabilitation of patients' reactive balance. Therefore, further studies are needed for investigating the difference in efficacy between varied devices and telerehabilitation programs. Further research is needed on static and reactive balance. In addition, such research should have a large body of literature and a large sample size to support more definitive findings based on the context of the COVID-19 pandemic. Systematic review registration: CRD42023389456.

CT guided autologous blood localization of pulmonary ground glass nodules for video assisted thoracoscopic surgery compared to micro-coil localization.

OBJECTIVES: To investigate feasibility and safety of autologous blood in preoperative computed tomography (CT)-guided localization of pulmonary ground-glass nodules (GGNs) by comparing to mico-coil prior to video-assisted thoracoscopic surgery. METHODS: Clinical data of patients with GGNs who underwent video-assisted thoracoscopic surgery followed by preoperative CT-guided autologous blood or micro-coil localization was retrospectively reviewed in our department between September 2019 and November 2021. The localization duration, localization success rate, localization-related complication, localization cost, operation time, and conversion rate were compared between the 2 localization groups. RESULTS: Totally 65 patients with 65 GGNs were included in our study, with 34 patients in autologous blood group (group B) and 31 patients in micro-coil group (group M). There is no conversion to thoracotomy. The age, sex, nodule location, diameter of nodule and distance from the pleura between the 2 groups were statistically comparable. Compared with group M, group B had similar localization success rate (94.1% vs 83.9%, P = 0.183) but shorter localization time (14.50 ± 2.61 min vs 16.35 ± 2.30 min, P = 0.004), lower cost ($92.4 ± 3.2 vs $475.6 ± 8.5, P = 0.001), and lower incidence of puncture complications (3.0% vs 19.3%, P = 0.042). CONCLUSIONS: The autologous blood localization is an effective and more economical method for preoperative GGNs localization, and is associated with fewer complications compared to micro-coil localization.

The nematode C. elegans senses airborne sound.

Unlike olfaction, taste, touch, vision, and proprioception, which are widespread across animal phyla, hearing is found only in vertebrates and some arthropods. The vast majority of invertebrate species are thus considered insensitive to sound. Here, we challenge this conventional view by showing that the earless nematode C. elegans senses airborne sound at frequencies reaching the kHz range. Sound vibrates C. elegans skin, which acts as a pressure-to-displacement transducer similar to vertebrate eardrum, activates sound-sensitive FLP/PVD neurons attached to the skin, and evokes phonotaxis behavior. We identified two nAChRs that transduce sound signals independently of ACh, revealing an unexpected function of nAChRs in mechanosensation. Thus, the ability to sense airborne sound is not restricted to vertebrates and arthropods as previously thought, and might have evolved multiple times independently in the animal kingdom, suggesting convergent evolution. Our studies also demonstrate that animals without ears may not be presumed to be sound insensitive.

Hsa_circ_0043278 functions as competitive endogenous RNA to enhance glioblastoma multiforme progression by sponging miR-638.

Circular RNAs have a critical function in the pathogenesis of many diseases and can function as competing endogenous RNA or miRNA sponges to inhibit miRNA and therefore upregulate the expression of target genes. However, little is known about the role of has_circRNA_0043278 (circ_0043278) in glioblastoma multiforme (GBM) and its potential downstream miRNA targets. This work validated that circ_0043278 is highly expressed in GMB cell lines and tissues, while knockdown circ_0043278 inhibited GBM cell migration, proliferation, and invasion invitro and tumorigenesis invivo. Dual-luciferase reporter assay determined that circ_0043278 directly sponged miR-638 to upregulate the expression of HOXA9, which can activate downstream Wnt/ß-catenin signaling in GBM. Moreover, miR-638 inhibition reversed circ_0043278 silencing-induced impairment of malignant tumor behavior. These results showed that circ-0043278/miRNA-638/ Homeobox A9 (HOXA9) axis had a vital function in promoting GBM progression. Our findings may provide potential new targets for the diagnosis and therapy of GBM.

miR-128-3p inhibits glioma cell proliferation and differentiation by targeting NPTX1 through IRS-1/PI3K/AKT signaling pathway.

It has been reported that glioma has a higher morbidity and mortality than other types of malignant brain tumor. While glioma has been extensively researched, the exact molecular mechanisms of its genesis and progression have remained to be fully elucidated. In order to explore a novel glioma-associated pathway which may represent a therapeutic target, 61 pairs of tumor tissues and adjacent normal tissues of glioma patients were collected and subjected to reverse-transcription quantitative polymerase chain reaction analysis, indicating that the relative expression of microRNA (miR)-128-3p was significantly decreased in the tumor tissues. However, the expression of neuronal pentraxin 1 (NPTX1) was obviously elevated. Through a bioinformatics analysis using Targetscan and transfection experiments, it was confirmed that NPTX1 was targeted by miR-128-3p. In the U251 human glioma cell line, transfection with miR-128-3p mimics increased the levels of phosphorylated insulin receptor substrate 1 (p-IRS-1), phosphoinositide-3 kinase (PI3K) and p-AKT, as demonstrated by western blot analysis. In addition, the proliferation rate of the cells was notably decreased following transfection with miR-128-3p mimics. Conversely, transfection with miR-128-3p inhibitor significantly increased the levels of p-IRS-1, PI3K and p-AKT, accompanied by an elevated proliferation rate of the cells. Therefore, it was indicated that miR-128-3p could reversely regulate NPTX1 expression. After the expression of NPTX1 was inhibited with specific small interfering RNA, the levels of p-IRS-1, PI3K and p-AKT were obviously decreased, while the expression of miR-128-3p was not significantly changed. Overall, it was concluded that miR-128-3p suppresses glioma through the NPTX1/IRS-1/PI3K/AKT signaling pathway.

Brain tissue partial pressure of oxygen predicts the outcome of severe traumatic brain injury under mild hypothermia treatment.

OBJECTIVE: The aim of this study was to investigate the clinical significance and changes of brain tissue partial pressure of oxygen (PbtO2) in the course of mild hypothermia treatment (MHT) for treating severe traumatic brain injury (sTBI). METHODS: There were 68 cases with sTBI undergoing MHT. PbtO2, intracranial pressure (ICP), jugular venous oxygen saturation (SjvO2), and cerebral perfusion pressure (CPP) were continuously monitored, and clinical outcomes were evaluated using the Glasgow Outcome Scale score. RESULTS: Of 68 patients with sTBI, PbtO2, SjvO2, and CPP were obviously increased, but decreased ICP level was observed throughout the MHT. PbtO2 and ICP were negatively linearly correlated, while there was a positive linear correlation between PbtO2 and SjvO2. Monitoring CPP and SjvO2 was performed under normal circumstances, and a large proportion of patients were detected with low PbtO2. Decreased PbtO2 was also found after MHT. CONCLUSION: Continuous PbtO2 monitoring could be introduced to evaluate the condition of regional cerebral oxygen metabolism, thereby guiding the clinical treatment and predicting the outcome.

Monitoring intracranial pressure utilizing a novel pattern of brain multiparameters in the treatment of severe traumatic brain injury.

The aim of the study was to evaluate the clinical value of multiple brain parameters on monitoring intracranial pressure (ICP) procedures in the therapy of severe traumatic brain injury (sTBI) utilizing mild hypothermia treatment (MHT) alone or a combination strategy with other therapeutic techniques. A total of 62 patients with sTBI (Glasgow Coma Scale score <8) were treated using mild hypothermia alone or mild hypothermia combined with conventional ICP procedures such as dehydration using mannitol, hyperventilation, and decompressive craniectomy. The multiple brain parameters, which included ICP, cerebral perfusion pressure, transcranial Doppler, brain tissue partial pressure of oxygen, and jugular venous oxygen saturation, were detected and analyzed. All of these measures can control the ICP of sTBI patients to a certain extent, but multiparameters associated with brain environment and functions have to be critically monitored simultaneously because some procedures of reducing ICP can cause side effects for long-term recovery in sTBI patients. The result suggested that multimodality monitoring must be performed during the process of mild hypothermia combined with conventional ICP procedures in order to safely target different clinical methods to specific patients who may benefit from an individual therapy.

Combining Whole-Brain Radiotherapy with Gefitinib/Erlotinib for Brain Metastases from Non-Small-Cell Lung Cancer: A Meta-Analysis.

BACKGROUND: To comprehensively assess the efficacy and safety of whole-brain radiotherapy (WBRT) combined with gefitinib/erlotinib for treatment of brain metastases (BM) from non-small-cell lung cancer (NSCLC). METHODS: Databases including PubMed, EMBASE.com, Web of Science, and Cochrane Library were searched from inception to April 12, 2015. Studies on randomized controlled trials (RCTs) and case-control trials comparing WBRT combined with gefitinib/erlotinib versus WBRT alone for BM from NSCLC were included. Literature selection, data extraction, and quality assessment were performed independently by two trained reviewers. RevMan 5.3 software was used to analyze data. RESULTS: A total of 7 trials involving 622 patients were included. Compared with WBRT alone or WBRT plus chemotherapy, WBRT plus gefitinib/erlotinib could significantly improve response rate (OR = 2.16, 95% CI: 1.35-3.47; P = 0.001), remission rate of central nervous system (OR = 6.06, 95% CI: 2.57-14.29; P < 0.0001), disease control rate (OR = 3.34, 95% CI: 1.84-6.07; P < 0.0001), overall survival (HR = 0.72, 95% CI: 0.58-0.89; P = 0.002), and 1-year survival rate (OR = 2.43, 95% CI: 1.51-3.91; P = 0.0002). In adverse events (III-IV), statistically significant differences were not found, except for rash (OR = 7.96, 95% CI: 2.02-31.34; P = 0.003) and myelosuppression (OR = 0.19, 95% CI: 0.07-0.51; P = 0.0010). CONCLUSIONS: WBRT plus gefitinib/erlotinib was superior to WBRT alone and well tolerated in patients with BM from NSCLC.

A liquid phase based C. elegans behavioral analysis system identifies motor activity loss in a nematode Parkinson's disease model.

Motor activity of Caenorhabditis elegans is widely used to study the mechanisms ranging from basic neuronal functions to human neurodegenerative diseases. It may also serve as a paradigm to screen for potential therapeutic reagents treating these diseases. Here, we developed an automated, 96-well plate and liquid phase based system that quantifies nematode motor activity in real time. Using this system, we identified an adult-onset, ageing-associated motor activity loss in a transgenic nematode line expressing human pathogenic G2019S mutant LRRK2 (leucine-rich repeat kinase 2), the leading genetic cause of Parkinson's disease characterized by dopaminergic neurodegeneration associated motor deficient mainly in elder citizens. Thus, our system may be used as a platform to screen for potential therapeutic drugs treating Parkinson's disease. It can also be used to monitor motor activity of nematodes in liquid phase at similar scenario.

Calcium imaging of multiple neurons in freely behaving C. elegans.

Caenorhabditis elegans is a popular model organism to study how neural circuits and genes regulate behavior. To reliably correlate circuit function with behavior, it is important to record neuronal activity in freely behaving worms. As neural circuits are composed of multiple neurons that cooperate to process information, it is highly desirable to simultaneously record the activity of multiple neurons in the circuitry. However, such a system has not been available in C. elegans. Here, we report the CARIBN II (Calcium Ratiometric Imaging of Behaving Nematodes version II) system. This system provides smoother data collection and more importantly permits simultaneous imaging of calcium transients from multiple neurons in freely behaving worms. Using this system, we imaged the activity of AVA and RIM, two key neurons in the locomotion circuitry that regulate backward movement (reversal) in locomotion behavior. We found that AVA activity increases while RIM activity decreases during the same reversal events in spontaneous locomotion, consistent with the recent report that the AVA and RIM are involved in promoting the initiation of reversals. The CARIBN II system provides a valuable tool for dissecting the neural basis of behavior in C. elegans.