In vitro investigation of the mechanics of fixed red blood cells based on optical trap micromanipulation and image analysis.

Erythrocyte deformability correlates with various diseases. Single-cell measurements via optical tweezers (OTs) enable quantitative exploration but may encounter inaccuracies due to erythrocyte life cycle mixing. We present a three-step methodology to address these challenges. Firstly, density gradient centrifugation minimizes erythrocyte variations. Secondly, OTs measure membrane shear force across layers. Thirdly, MATLAB analyzes dynamic cell areas. Results combined with membrane shear force data reveal erythrocyte deformational capacity. To further characterize the deformability of diseased erythrocytes, the experiments used glutaraldehyde-fixed erythrocytes to simulate diseased cells. OTs detect increased shear modulus, while image recognition indicates decreased deformation. The integration of OTs and image recognition presents a comprehensive approach to deformation analysis, introducing novel ideas and methodologies for investigating erythrocytic lesions.

Organic nano carbon source inducing 3D silica nanoparticles-graphene nanosheet layer on Cu current collector for high-performance anode-free lithium metal batteries.

Anode-free lithium metal batteries (AFLBs) have attracted considerable attention due to their high theoretical specific capacity and absence of Li. However, the heterogeneous Li deposition and stripping on the lithiophobic Cu collector hamper AFLBs in practice. To achieve a uniform and reversible Li deposition, a carbon-based layer on the Cu collector has attracted intense interest due to its high conductivity. However, the 2D single-component carbon-based interface is inadequate lithiophilic for obtaining the homogeneous Li deposition and preventing the lithium dendrite from piercing the separator. Herein, we present a 3D embedded lithiophilic SiO2 nanoparticles-graphene nanosheet matrix (SiO2@G-M) on the Cu collector by organic nano carbon source. In this structure, the lithiophilic SiO2 nanoparticles as active points promote the homogeneous lithium nucleation and the 3D graphene nanosheet matrix offers homogenous electron distribution and voids to prevent the piercing. Finally, SiO2@G-M/Li cell shows a high coulombic efficiency of 98.62 % after 100 cycles at a high current density of 2 mA cm-2 with an areal capacity of 1 mAh cm-2.

Combinational zimberelimab plus lenvatinib and chemotherapy for alpha-fetoprotein elevated, advanced gastric cancer patients (AFPGC): a phase 1 dose-escalation study.

BACKGROUND: Alpha-fetoprotein elevated gastric cancer (AFPGC) got growing interests for its aggressive nature and unfavorable prognosis. Here, a phase 1 dose escalation study was conducted to evaluate safety and efficacy of zimberelimab (GLS-010, anti-PD-1) plus lenvatinib and chemotherapy (XELOX) as the first-line treatment for AFPGC. METHODS: Histologically confirmed HER2-negative, advanced GC patients with elevated serum AFP level (≥ 20 ng/ml) were screened. Using a 3 + 3 dose escalation design, patients were administered varying doses of lenvatinib (12, 16, 20 mg) with GLS-010 and XELOX. The primary endpoints were safety and determination of recommended phase II dose (RP2D). Secondary endpoints included overall response rate (ORR), progression-free survival (PFS) and disease control rate. RESULTS: Nine patients were enrolled with no dose-limiting toxicities observed. Most frequent treatment-related AEs were fatigue (55.6%), hand-foot syndrome (55.6%) and rash (55.6%), and no grade ≥ 4 AEs were reported. All patients exhibited disease control with ORR reaching 33.3%. The median PFS and OS reached 7.67 months (95% CI 4.07-11.27) and 13.17 months (95% CI 2.78-23.56), respectively. Serum AFP level was found correlated with therapeutic responses. Further 16s rRNA sequencing analysis demonstrated altered gut microbiota with elevated abundance of Lachnospiraceae bacterium-GAM79 and Roseburia hominis A2-183. CONCLUSIONS: GLS-010 plus lenvatinib and XELOX demonstrated a manageable safety profile with promising efficacy for AFPGC. With RP2D of lenvatinib determined as 16 mg, further expansion cohort is now ongoing. Translational investigation suggested that serum AFP can be indictive for therapeutic responses and certain microbiota species indicating favorable responses to immunotherapy was elevated after the combinational treatment.

Peripheral blood eosinophils: an important reference for radiologists to distinguish between pulmonary paragonimiasis and tuberculous pleurisy in children.

OBJECTIVE: In this study, we examined the value of chest CT signs combined with peripheral blood eosinophil percentage in differentiating between pulmonary paragonimiasis and tuberculous pleurisy in children. METHODS: Patients with pulmonary paragonimiasis and tuberculous pleurisy were retrospectively enrolled from January 2019 to April 2023 at the Kunming Third People's Hospital and Lincang People's Hospital. There were 69 patients with pulmonary paragonimiasis (paragonimiasis group) and 89 patients with tuberculous pleurisy (tuberculosis group). Clinical symptoms, chest CT imaging findings, and laboratory test results were analyzed. Using binary logistic regression, an imaging model of CT signs and a combined model of CT signs and eosinophils were developed to calculate and compare the differential diagnostic performance of the two models. RESULTS: CT signs were used to establish the imaging model, and the receiver operating characteristic (ROC) curve was plotted. The area under the curve (AUC) was 0.856 (95% CI: 0.799-0.913), the sensitivity was 66.7%, and the specificity was 88.9%. The combined model was established using the CT signs and eosinophil percentage, and the ROC was plotted. The AUC curve was 0.950 (95% CI: 0.919-0.980), the sensitivity was 89.9%, and the specificity was 90.1%. The differential diagnostic efficiency of the combined model was higher than that of the imaging model, and the difference in AUC was statistically significant. CONCLUSION: The combined model has a higher differential diagnosis efficiency than the imaging model in the differentiation of pulmonary paragonimiasis and tuberculous pleurisy in children. The presence of a tunnel sign on chest CT, the absence of pulmonary nodules, and an elevated percentage of peripheral blood eosinophils are indicative of pulmonary paragonimiasis in children.

Dipeptidyl peptidase 4 interacts with porcine coronavirus PHEV spikes and mediates host range expansion.

Porcine hemagglutinating encephalomyelitis virus (PHEV), a neurotropic betacoronavirus, is prevalent in natural reservoir pigs and infects mice. This raises concerns about host jumping or spillover, but little is known about the cause of occurrence. Here, we revealed that dipeptidyl peptidase 4 (DPP4) is a candidate binding target of PHEV spikes and works as a broad barrier to overcome. Investigations of the host breadth of PHEV confirmed that cells derived from pigs and mice are permissive to virus propagation. Both porcine DPP4 and murine DPP4 have high affinity for the viral spike receptor-binding domain (RBD), independent of their catalytic activity. Loss of DPP4 expression results in limited PHEV infection. Structurally, PHEV spike protein binds to the outer surface of blades IV and V of the DPP4 ß-propeller domain, and the DPP4 residues N229 and N321 (relative to human DPP4 numbering) participate in RBD binding via its linked carbohydrate entities. Removal of these N-glycosylations profoundly enhanced the RBD-DPP4 interaction and viral invasion, suggesting they act as shielding in PHEV infection. Furthermore, we found that glycosylation, rather than structural differences or surface charges, is more responsible for DPP4 recognition and species barrier formation. Overall, our findings shed light on virus-receptor interactions and highlight that PHEV tolerance to DPP4 orthologs is a putative determinant of its cross-species transmission or host range expansion.IMPORTANCEPHEV is a neurotropic betacoronavirus that is circulating worldwide and has raised veterinary and economic concerns. In addition to being a reservoir species of pigs, PHEV can also infect wild-type mice, suggesting a "host jump" event. Understanding cross-species transmission is crucial for disease prevention and control but remains to be addressed. Herein, we show that the multifunctional receptor DPP4 plays a pivotal role in the host tropism of PHEV and identifies the conserved glycosylation sites in DPP4 responsible for this restriction. These findings highlight that the ability of PHEV to utilize DPP4 orthologs potentially affects its natural host expansion.

Identification of O-Methyltransferases Potentially Contributing to the Structural Diversity of 2-(2-Phenylethyl)chromones in Agarwood.

2-(2-Phenylethyl)chromones (PECs) are the primary constituents responsible for the promising pharmacological activities and unique fragrance of agarwood. However, the O-methyltransferases (OMTs) involved in the formation of diverse methylated PECs have not been reported. In this study, we identified one Mg2+-dependent caffeoyl-CoA-OMT subfamily enzyme (AsOMT1) and three caffeic acid-OMT subfamily enzymes (AsOMT2-4) from NaCl-treated Aquilaria sinensis calli. AsOMT1 not only converts caffeoyl-CoA to feruloyl-CoA but also performs nonregioselective methylation at either the 6-OH or 7-OH position of 6,7-dihydroxy-PEC. On the other hand, AsOMT2-4 preferentially utilizes PECs as substrates to produce structurally diverse methylated PECs. Additionally, AsOMT2-4 also accepts nonPEC-type substrates such as caffeic acid and apigenin to generate methylated products. Protein structure prediction and site-directed mutagenesis revealed that residues of L313 and I318 in AsOMT3, as well as S292 and F313 in AsOMT4 determine the distinct regioselectivity of these two OMTs toward apigenin. These findings provide important biochemical evidence of the remarkable structural diversity of PECs in agarwood.

High nutrient utilization and resorption efficiency promote bamboo expansion and invasion.

Bamboos are fast-growing, aggressively-spreading, and invasive woody clonal species that often encroach upon adjacent tree plantations, forming bamboo-tree mixed plantations. However, the effects of bamboo invasion on leaf carbon (C) assimilation, and nitrogen (N) and phosphorus (P) utilization characteristics remains unclear. We selected four different stands of Pleioblastus amarus invading Chinese fir (Cunninghamia lanceolata) plantations to investigate the concentrations, stoichiometry, and allometric growth relationships of mature and withered leaves of young and old bamboos, analyzing N and P utilization and resorption patterns. The stand type, bamboo age, and their interaction affected the concentrations, stoichiometry and allometric growth patterns of leaf C, N, and P in both old and young bamboos, as well as the N and P resorption efficiency. Bamboo invasion into Chinese fir plantations decreased leaf C, N, and P concentrations, C:N and C:P ratios, N and P resorption efficiency, and allometric growth exponents among leaf C, N, and P, while it only slightly altered N:P ratios. PLS-PM analysis revealed that bamboo invasion negatively impacted leaf C, N, and P concentrations, as well as N and P utilization and resorption. The results indicate that high N and P utilization and resorption efficiency, along with the mutual sharing of C, N, and P among bamboos in interface zones, promote continuous bamboo expansion and invasion. Collectively, these findings highlight the significance of N and P utilization and resorption in bamboo expansion and invasion and provide valuable guidance for the establishment of mixed stands and the ecological management of bamboo forests.

An optimized EEGNet decoder for decoding motor image of four class fingers flexion.

As a cutting-edge technology of connecting biological brain and external devices, brain-computer interface (BCI) exhibits promising applications on extensive fields such as medical and military. As for the disable individuals with four limbs losing the motor functions, it is a potential treatment way to drive mechanical equipments by the means of non-invasive BCI, which is badly depended on the accuracy of the decoded electroencephalogram (EEG) singles. In this study, an explanatory convolutional neural network namely EEGNet based on SimAM attention module was proposed to enhance the accuracy of decoding the EEG singles of index and thumb fingers for both left and right hand using sensory motor rhythm (SMR). An average classification accuracy of 72.91% the data of eight healthy subjects was obtained, which were captured from the one second before finger movement to two seconds after action. Furthermore, the character of event-related desynchronization (ERD) and event related synchronization (ERS) of index and thumb fingers was also studied in this study. These findings have significant importance for controlling external devices or other rehabilitation equipment using BCI in a fine way.

The single-cell opioid responses in the context of HIV (SCORCH) consortium.

Substance use disorders (SUD) and drug addiction are major threats to public health, impacting not only the millions of individuals struggling with SUD, but also surrounding families and communities. One of the seminal challenges in treating and studying addiction in human populations is the high prevalence of co-morbid conditions, including an increased risk of contracting a human immunodeficiency virus (HIV) infection. Of the ~15 million people who inject drugs globally, 17% are persons with HIV. Conversely, HIV is a risk factor for SUD because chronic pain syndromes, often encountered in persons with HIV, can lead to an increased use of opioid pain medications that in turn can increase the risk for opioid addiction. We hypothesize that SUD and HIV exert shared effects on brain cell types, including adaptations related to neuroplasticity, neurodegeneration, and neuroinflammation. Basic research is needed to refine our understanding of these affected cell types and adaptations. Studying the effects of SUD in the context of HIV at the single-cell level represents a compelling strategy to understand the reciprocal interactions among both conditions, made feasible by the availability of large, extensively-phenotyped human brain tissue collections that have been amassed by the Neuro-HIV research community. In addition, sophisticated animal models that have been developed for both conditions provide a means to precisely evaluate specific exposures and stages of disease. We propose that single-cell genomics is a uniquely powerful technology to characterize the effects of SUD and HIV in the brain, integrating data from human cohorts and animal models. We have formed the Single-Cell Opioid Responses in the Context of HIV (SCORCH) consortium to carry out this strategy.

Effects of Ultrasound-Guided Thoracic Paravertebral Nerve Block Combined with Perineural or IV Dexmedetomidine on Acute and Chronic Pain After Thoracoscopic Resection of Lung Lesions: A Double-Blind Randomized Trial.

Background: Thoracic paravertebral block (TPVB) analgesia can be prolonged by local anesthetic adjuvants such as dexmedetomidine. This study aimed to evaluate the two administration routes of dexmedetomidine on acute pain and chronic neuropathic pain (NeuP) prevention compared with no dexmedetomidine. Methods: A total of 216 patients were randomized to receive TPVB using 0.4% ropivacaine alone (R Group), with perineural dexmedetomidine 0.5 µg·kg-1 (RD0.5 Group) or 1.0 µg·kg-1 (RD1.0 Group), or intravenous (IV) dexmedetomidine 0.5 µg·kg-1·h-1 (RDiv Group). The primary outcome was the incidence of chronic NeuP, defined as a Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain score > 12 points at 3-month after surgery. Results: (1) For the primary outcome, RD0.5 Group and RD1.0 Group demonstrated a decreased incidence of chronic NeuP at 3-month after surgery; (2) Compared with R Group, RDiv Group, RD0.5 Group, and RD1.0 Group can reduce VAS scores at rest and movement and Prince-Henry Pain scores at 12 and 24-h after surgery, the consumption of oral morphine equivalent (OME) and improve QOD-15 at POD1; (3) Compared with RDiv Group, RD0.5 Group and RD1.0 Group can reduce VAS scores at rest and movement and Prince-Henry Pain scores at 12 and 24-h after surgery, the consumption of postoperative OME and improve QOD-15 at POD1; (4) Compared with RD0.5 Group, RD1.0 Group effectively reduced VAS scores at rest at 12 and 24-h after surgery, VAS scores in movement and Prince-Henry Pain scores at 12-h after surgery. However, RD1.0 Group showed an increased incidence of drowsiness. Conclusion: Perineural or IV dexmedetomidine are similarly effective in reducing acute pain, but only perineural dexmedetomidine reduced chronic NeuP. Moreover, considering postoperative complications such as drowsiness, perineural dexmedetomidine (0.5 µg·kg-1) may be a more appropriate choice. Clinical Trial Registration: Chinese Clinical Trial Registry (ChiCTR2200058982).

Transcutaneous electrical acupoint stimulation for rehabilitation after total knee arthroplasty: a systematic review and meta-analysis.

BACKGROUND: Rehabilitation after total knee arthroplasty (TKA) has become an indispensable part of the treatment strategy for degenerative joint disease. Despite some current research demonstrating efficacy of transcutaneous electrical acupoint stimulation (TEAS) for post-TKA rehabilitation, the evidence is not conclusive. OBJECTIVE: To systematically assess the evidence supporting TEAS for rehabilitation after TKA. METHODS: A literature search of the PubMed, Embase, The Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wanfang, and Chinese Scientific Journal Data databases for relevant studies published up to October 16, 2023, was performed. Main indicators included visual analog scale (VAS) and functional scores; secondary indicators included range of motion (ROM), interleukin-6 (IL-6) and C-reactive protein (CRP) levels, and analgesia-related adverse events. Risk of bias was evaluated using the Cochrane Tool, and meta-analysis was performed using Review Manager version 5.4. RESULTS: Twenty RCTs with 1295 participants were included. TEAS improved several outcomes compared to control groups. The TEAS group had significantly greater pain reduction at postoperative 6 h, 12 h, 24 h, 48 h, 72 h, 7 days, and 14 days. Moreover, TEAS significantly improved the Hospital for Special Surgery Knee Score, Knee Society Score, and ROM. Patients who underwent TEAS exhibited a lower incidence of analgesia-related adverse events and lower IL-6 and CRP levels. CONCLUSIONS: Available evidence indicates that the application of TEAS in patients undergoing TKA is related to postoperative pain alleviation, functional improvement, and fewer adverse events associated with analgesia.

Basement membrane-associated gene expression as a predictor of survival in oral cancer.

BACKGROUND: This study sought to investigate the prognostic value of basement membrane (BM)-associated gene expressions in oral cancer. METHODS: We harvested and integrated data on BM-associated genes (BMGs), the oral cancer transcriptome, and clinical information from public repositories. After identifying differentially expressed BMGs, we used Cox and Lasso regression analyses to create a BMG-based risk score for overall survival at various intervals. We then validated this score using the GSE42743 cohort as a validation set. The prognostic potential of the risk scores and their relations to clinical features were assessed. Further, we conducted functional pathway enrichment, immune cell infiltration, and immune checkpoint analyses to elucidate the immunological implications and therapeutic potential of the BMG-based risk score and constituent genes. To confirm the expression levels of the BMG LAMA3 in clinical samples of oral cancer tissue, we performed quantitative real-time PCR (qRT-PCR) and immunohistochemical staining. RESULTS: The BMGs LAMA3, MMP14, and GPC2 demonstrated notable prognostic significance, facilitating the construction of a BMG-based risk score. A higher risk score derived from BMGs correlated with a poorer survival prognosis for oral cancer patients. Moreover, the risk-associated BMGs exhibited a significant relationship with immune function variability (P < 0.05), discrepancies in infiltrating immune cell fractions, and immune checkpoint expressions (P < 0.05). The upregulated expression levels of LAMA3 in oral cancer tissues were substantiated through qRT-PCR and immunohistochemical staining. CONCLUSION: The BMG-based risk score emerged as a reliable prognostic tool for oral cancer, meriting further research for validation and potential clinical application.

Application of multimodal standardized analgesia under the concept of enhanced recovery after surgery in laparoscopic radical colorectal cancer surgery.

Aims: To observe the efficacy and safety of multimodal standardized analgesia in patients undergoing laparoscopic radical colorectal cancer surgery. Methods: A prospective, double-blind, randomized study of patients who were admitted to our hospital between December 2020 and March 2022 with a diagnosis of colorectal cancer and who intended to undergo elective laparoscopic radical colorectal cancer surgery was conducted. The participants were randomly divided into two intervention groups, namely, a multimodal standardized analgesia group and a routine analgesia group. In both groups, the visual analogue scale (VAS) pain scores while resting at 6 h, 24 h, 48 h and 72 h and during movement at 24 h, 48 h and 72 h; the number of patient controlled intravenous analgesia (PCIA) pump button presses and postoperative recovery indicators within 3 days after surgery; the interleukin-6 (IL-6) and C-reactive protein (CRP) levels on the 1st and 4th days after surgery; and the incidence of postoperative adverse reactions and complications were recorded. Results: Compared with the control group, the multimodal standardized analgesia group had significantly lower VAS pain scores at different time points while resting and during movement (P<0.05), significantly fewer PCIA pump button presses during the first 3 postoperative days (P<0.05), and significantly lower IL-6 and CRP levels on the 1st postoperative day (P<0.05). There was no statistically significant difference in the time to out-of-bed activity, the time to first flatus, the IL-6 and CRP levels on the 4th postoperative day or the incidence of postoperative adverse reactions and complications between the two groups (P >0.05). Conclusion: For patients undergoing laparoscopic radical colorectal cancer surgery, multimodal standardized analgesia with ropivacaine combined with parecoxib sodium and a PCIA pump had a better analgesic effect, as it effectively inhibited early postoperative inflammatory reactions and promoted postoperative recovery and did not increase the incidence of adverse reactions and complications. Therefore, it is worthy of widespread clinical practice.

Association between physical frailty and cortical structure in middle-aged and elderly people: a Mendelian randomization study.

Introduction: Physical weakness is associated with cortical structures, but the exact causes remain to be investigated. Therefore, we utilized Mendelian randomization (MR) analysis to uncover the underlying connection between frailty and cortical structures. Methods: The Genome-Wide Association Study (GWAS) on frailty pooled data from publicly available sources such as the UK Biobank and included five indicators of frailty: weakness, walking speed, weight loss, physical activity, and exhaustion. GWAS data on cerebral cortical structure were obtained from the ENIGMA consortium, and we assessed the causal relationship between hereditary frailty and cortical surface area (SA) or cortical thickness (TH). Inverse variance weighting (IVW) was used as the primary estimate, and heterogeneity and multidimensionality were monitored by MR-PRESSO to detect outliers. Additionally, MR-Egger, Cochran's Q test, and weighted median were employed. Results: At the aggregate level, there was no causal relationship between frailty and cortical thickness or surface area. At the regional level, frailty was associated with the thickness of the middle temporal lobe, parahippocampus, rostral middle frontal lobe, lower parietal lobe, anterior cingulate gyrus, upper temporal lobe, lateral orbital frontal cortex, pericardial surface area, rostral middle frontal lobe, upper temporal lobe, rostral anterior cingulate gyrus, lower parietal lobe, and upper parietal lobe. These results were nominally significant, and sensitivity analyses did not detect any multidirectionality or heterogeneity, suggesting that the results of our analyses are reliable. Discussion: The results of our analyses suggest a potential causal relationship between somatic weakness and multiple regions of cortical structure. However, the specific mechanisms of influence remain to be investigated. Preliminary results from our analysis suggest that the effects of physical frailty on cortical structures are influenced by various factors related to frailty exposure. This relationship has been documented, and it is therefore both feasible and meaningful to build on existing research to explore the clinical significance of the relationship.

Procatechuic acid and protocatechuic aldehyde increase survival of Caenorhabditis elegans after fungal infection and inhibit fungal virulence.

Protocatechuic acid (PCA) and protocatechuic aldehyde (PAL) are important phenolic compounds in plants. We here investigated their possible beneficial effect against fungal infection and the underlying mechanism. The model animal of Caenorhabditis elegans was used as host, and Candida albicans was used as fungal pathogen. The nematodes were first infected with C. albicans, and the PCA and PAL treatment were then performed. Post-treatment with 10-100 µM PCA and PAL suppressed toxicity of C. albicans infection in reducing lifespan. Accompanied with this beneficial effect, treatment with 10-100 µM PCA and PAL inhibited C. albicans accumulation in intestinal lumen. In addition, treatment with 10-100 µM PCA and PAL suppressed the increase in expressions of antimicrobial genes caused by C. albicans infection. The beneficial effect of PCA and PAL against C. albicans infection depended on p38 MAPK and insulin signals. Moreover, although treatment with 10-100 µM PCA and PAL could not exhibit noticeable antifungal activity, PCA and PAL treatment obviously suppressed biofilm formation, inhibited hyphal growth, and reduced expressions of virulence genes (ALS3, CaVps34, Vma7, Vac1, and/or HWP1) related to biofilm formation and hyphal growth in C. albicans. Therefore, our data demonstrated the potential of PCA and PAL post-treatment against fungal infection and fungal virulence.

Ion Current Rectification Activity Induced by Boron Hydride Nanosheets to Enhance Magnesium Analgesia.

The low analgesic efficiency has limited magnesium used in analgesia. Here, we report boron hydride (BH) with ion current rectification activity can significantly improve the analgesic efficiency of magnesium, even higher than morphine. The synthesized injectable MgB2 composes of hexagonal boron sheets alternating with Mg2+. In pathological environment, while the intercalated Mg2+ will be exchanged by H+, the 2-dimensional borophene-analogue BH sheets will be formed to interact with the charged cations via the cation-pi interaction, synergistically leading to a sort of two-way dynamic modulation of sodium and potassium ion currents in neurons. By coordinating with the released Mg2+ to compete Ca2+, the threshold potential remarkably increases from the normal -35.9 mV to -5.9 mV, which significantly suppresses neuronal excitability, providing a potent analgesic effect. In three typical pain models , including CFA-induced inflammatory pain, PINP- or CCI-induced neuropathic pain, MgB2 demonstrates its analgesic efficiency approximately 2.23, 3.20, and 2.0 times higher than the clinical MgSO4, respectively. The development of MgB2 as analgesic drugs addresses the unmet medical need of pain relief without the risks of drug tolerance or addiction to opioids.

Highly transparent Ce:Nd:YAG ceramic with good light conversion capacity for solar-pumped solid-state lasers.

Developing a high quality ceramic laser gain medium for solar directly pumped solid state lasers is essential, and yet the light conversion efficiency of the gain media for solar pumping remains a challenge. In this study, Ce and Nd ions, co-doped YAG transparent ceramics with theoretical transmittance and stable Ce3+ valent state were developed, and revealed that the absorbed visible light and light conversion efficiency in Ce,Nd:YAG ceramics were 3.98 times and 1.34 times higher than those in widely reported Cr,Nd:YAG ceramics, respectively. A concentration matching principle between Ce3+ and Nd3+ ions in YAG was established, and a higher Nd3+ ion doping concentration with a relatively low Ce3+ concentration was favorable to improve both the light conversion efficiency and emission intensity at 1064 nm of Ce,Nd:YAG ceramics. Energy transfer efficiency from Ce3+ to Nd3+ of the 0.3 at.%Ce,1.5at.%Nd:YAG ceramic reached as high as 61.71% at room temperature. Surprisingly, it was further promoted to 64.31% at a higher temperature of 473 K. More excited electrons at the upper energy level of Ce3+ ion under the high temperature accounted for this novel phenomenon. This study proposes a new design strategy of gain materials for solar directly pumped solid state lasers.

Imaging Neurotransmitters with Small-Molecule Fluorescent Probes.

Neurotransmitters play a crucial role in regulating communication between neurons within the brain and central nervous system. Thus, imaging neurotransmitters has become a high priority in neuroscience. This minireview focuses on recent advancements in the development of fluorescent small-molecule fluorescent probes for neurotransmitter imaging and applications of these probes in neuroscience. Innovative approaches for probe design are highlighted as well as attributes which are necessary for practical utility, with a view to inspiring new probe development capable of visualizing neurotransmitters.

Polyphenols as Potential Antioxidants for the Treatment of Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IDD) is a common musculoskeletal system disease, which is one of the most important causes of low back pain. Despite the high prevalence of IDD, current treatments are limited to relieving symptoms, and there are no effective therapeutic agents that can block or reverse the progression of IDD. Oxidative stress, the result of an imbalance between the production of reactive oxygen species (ROS) and clearance by the antioxidant defense system, plays an important role in the progression of IDD. Polyphenols are antioxidant compounds that can inhibit ROS production, which can scavenge free radicals, reduce hydrogen peroxide production, and inhibit lipid oxidation in nucleus pulposus (NP) cells and IDD animal models. In this review, we discussed the antioxidant effects of polyphenols and their regulatory role in different molecular pathways associated with the pathogenesis of IDD, as well as the limitations and future prospects of polyphenols as a potential treatment of IDD.

Single-Cell Transcriptomic Analyses of Brain Parenchyma in Patients With New-Onset Refractory Status Epilepticus (NORSE).

BACKGROUND AND OBJECTIVES: New-onset refractory status epilepticus (NORSE) occurs in previously healthy children or adults, often followed by refractory epilepsy and poor outcomes. The mechanisms that transform a normal brain into an epileptic one capable of seizing for prolonged periods despite treatment remain unclear. Nonetheless, several pieces of evidence suggest that immune dysregulation could contribute to hyperexcitability and modulate NORSE sequelae. METHODS: We used single-nucleus RNA sequencing to delineate the composition and phenotypic states of the CNS of 4 patients with NORSE, to better understand the relationship between hyperexcitability and immune disturbances. We compared them with 4 patients with chronic temporal lobe epilepsy (TLE) and 2 controls with no known neurologic disorder. RESULTS: Patients with NORSE and TLE exhibited a significantly higher proportion of excitatory neurons compared with controls, with no discernible difference in inhibitory GABAergic neurons. When examining the ratio between excitatory neurons and GABAergic neurons for each patient individually, we observed a higher ratio in patients with acute NORSE or TLE compared with controls. Furthermore, a negative correlation was found between the ratio of excitatory to GABAergic neurons and the proportion of GABAergic neurons. The ratio between excitatory neurons and GABAergic neurons correlated with the proportion of resident or infiltrating macrophages, suggesting the influence of microglial reactivity on neuronal excitability. Both patients with NORSE and TLE exhibited increased expression of genes associated with microglia activation, phagocytic activity, and NLRP3 inflammasome activation. However, patients with NORSE had decreased expression of genes related to the downregulation of the inflammatory response, potentially explaining the severity of their presentation. Microglial activation in patients with NORSE also correlated with astrocyte reactivity, possibly leading to higher degrees of demyelination. DISCUSSION: Our study sheds light on the complex cellular dynamics in NORSE, revealing the potential roles of microglia, infiltrating macrophages, and astrocytes in hyperexcitability and demyelination, offering potential avenues for future research targeting the identified pathways.