Prognostic relevance of immune-related adverse events in lung cancer patients undergoing immune checkpoint inhibitor therapy: a systematic review and meta-analysis.

Background: Immune checkpoint inhibitors (ICIs) work by activating the immune system, a mechanism that may also cause immune-related adverse events (irAEs). This study seeks to investigate on how different irAEs impact prognosis of advanced lung cancer (LC) patients and identify useful approaches to manage irAEs. Methods: A thorough literature search of PubMed, Embase, the Cochrane Library and manual searches up to January 2024 were undertaken. Treatment outcomes including progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR) were obtained. Meta-analysis was conducted using R software (version 4.3.1). Results: There were 106 studies with 41,050 advanced or recurrent LC patients included. The occurrence of irAEs was correlated with better PFS [hazard ratio (HR) =0.54; 95% confidence interval (CI): 0.49-0.59], OS (HR =0.57; 0.51-0.63), ORR [risk ratio (RR) =2.03; 95% CI: 1.81-2.28] and DCR (RR =1.55; 95% CI: 1.40-1.72) and remained significant after adjusting programmed death-ligand 1 (PD-L1) level. IrAEs affecting skin (OS: HR =0.45; 95% CI: 0.38-0.53) and endocrine system (OS: HR =0.51; 95% CI: 0.41-0.62), of mild severity (OS: HR =0.52; 95% CI: 0.35-0.79), arising in multiple sites (OS: HR =0.47; 95% CI: 0.38-0.59), induced by monotherapy (OS: HR =0.58; 95% CI: 0.52-0.65), with a delayed onset (cutoff: 3 months; OS: HR =0.37; 95% CI: 0.19-0.71) were identified as positive prognostic markers. In contrast, though pulmonary irAEs were found to be corelated with enhanced treatment response (ORR: RR =1.75; 95% CI: 1.37-2.25), they may harm survival, especially those with grade ≥3 (OS: HR =2.40; 95% CI: 1.39-4.14). Treatment resumption tended to improve PFS but might not reduce the risk of death compared to permanent discontinuation. Conclusions: IrAEs suggest better treatment outcomes generally, yet severe pneumonia could increase mortality risk. Close supervision and appropriate handling protocols are warranted to weigh treatment benefit against risk.

Removal of antibiotic resistant bacteria and antibiotic resistance genes by an electrochemically driven UV/chlorine process for decentralized water treatment.

The UV/chlorine (UV/Cl2) process is a developing advanced oxidation process and can efficiently remove antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs). However, the transportation and storage of chlorine solutions limit the application of the UV/Cl2 process, especially for decentralized water treatment. To overcome the limitation, an electrochemically driven UV/Cl2 process (E-UV/Cl2) where Cl2 can be electrochemically produced in situ from anodic oxidation of chloride (Cl-) ubiquitously present in various water matrices was evaluated in this study. >5-log inactivation of the ARB (E. coli) was achieved within 5 s of the E-UV/Cl2 process, and no photoreactivation of the ARB was observed after the treatment. In addition to the ARB, intracellular and extracellular ARGs (tetA, sul1, sul2, and ermB) could be effectively degraded (e.g., log(C0/C) > 4 for i-ARGs) within 5 min of the E-UV/Cl2 process. Atomic force microscopy showed that the most of the i-ARGs were interrupted into short fragments (< 30 nm) during the E-UV/Cl2 process, which can thus effectively prevent the self-repair of i-ARGs and the horizontal gene transfer. Modelling results showed that the abatement efficiencies of i-ARG correlated positively with the exposures of •OH, Cl2-•, and ClO• during the E-UV/Cl2 process. Due to the short treatment time (5 min) required for ARB and ARG removal, insignificant concentrations of trihalomethanes (THMs) were generated during of the E-UV/Cl2 process, and the energy consumption (EEO) of ARG removal was ∼0.20‒0.27 kWh/m3-log, which is generally comparable to that of the UV/Cl2 process (0.18-0.23 kWh/m3-log). These results demonstrate that the E-UV/Cl2 process can provide a feasible and attractive alternative to the UV/Cl2 process for ARB and ARG removal in decentralized water treatment system.

Dynamical analysis of a novel 2D Lyapunov exponent controllable memristive chaotic map.

The proposal of discrete memristors has made memristive chaotic maps based on them an important research topic. In this study, a new two-dimensional chaotic map without fixed points is constructed, and numerical simulation results display its rich dynamical behaviors. The analysis reveals the map's center inversion symmetry and Lyapunov exponent controller. The map exhibits complex dynamical behaviors, including memristor initial-boosting and single-parameter-offset boosting. Embedding the absolute value function within the memristor results in the emergence of localized boosting-free regions. Moreover, a class of multicavity transients is captured that greatly enhances the system's complexity. Ultimately, this map is implemented on the STM32 platform, demonstrating its practical applicability in potential practical application scenarios.

CTC-derived pancreatic cancer models serve as research tools and are suitable for precision medicine approaches.

Pancreatic ductal adenocarcinoma (PDAC) poses significant clinical challenges, often presenting as unresectable with limited biopsy options. Here, we show that circulating tumor cells (CTCs) offer a promising alternative, serving as a "liquid biopsy" that enables the generation of in vitro 3D models and highly aggressive in vivo models for functional and molecular studies in advanced PDAC. Within the retrieved CTC pool (median 65 CTCs/5 mL), we identify a subset (median content 8.9%) of CXCR4+ CTCs displaying heightened stemness and metabolic traits, reminiscent of circulating cancer stem cells. Through comprehensive analysis, we elucidate the importance of CTC-derived models for identifying potential targets and guiding treatment strategies. Screening of stemness-targeting compounds identified stearoyl-coenzyme A desaturase (SCD1) as a promising target for advanced PDAC. These results underscore the pivotal role of CTC-derived models in uncovering therapeutic avenues and ultimately advancing personalized care in PDAC.

Memory B cell responses induced by pneumococcal conjugate vaccine schedules with fewer doses: analysis of a randomised-controlled trial in Viet Nam.

The use of pneumococcal conjugate vaccine (PCV) schedules with fewer doses are being considered to reduce costs and improve access, particularly in low- and middle-income countries. While several studies have assessed their immunogenicity, there are limited data on their potential for long-term immune protection, as assessed by pneumococcal serotype-specific memory B cell (Bmem) responses. This current study reports secondary outcome data that aims to compare Bmem responses following reduced-dose (0 + 1 and 1 + 1) schedules of PCV10 and PCV13 in Vietnamese infants from our randomised-controlled trial (trial registration number NCT03098628). Following vaccination at 12 months of age, Bmem levels for most serotypes peaked seven days post-vaccination and were higher in magnitude for the 1 + 1 than 0 + 1 schedules and for PCV13 than PCV10. Furthermore, Bmem did not wane as rapidly as IgG levels by 24 months of age. Further studies are needed to assess the use of Bmem as markers of long-term protection against pneumococcal carriage and disease, which is crucial to generate data for immunisation program decision-making.

CaF2 nanoparticles enabling LiF-dominated solid electrolyte interphase for dendrite-free and ultra-stable lithium metal batteries.

The uncontrollable growth of Li dendrites and severe interfacial parasitic reactions on the Li anode are the primary obstacles to the practical application of lithium (Li) metal batteries. Effective artificial solid electrolyte interphase is capable of regulating uniform Li deposition and isolateing Li from electrolyte, thereby eliminating parasitic reactions. Herein, we rationally design a uniform LiF-dominated solid electrolyte interphase through an in-situ reaction between CaF2 nanoparticles and the Li anode, which allows dendrite-free Li deposition and restrains interfacial deterioration. Accordingly, the protective Li electrode demonstrated exceptional stability, sustaining over 6000 h at a current density of 2 mA cm-2 in symmetric cells and attaining over 1000 cycles with a low capacity decay rate of 0.015 % per cycle in coupling with LiFePO4 cathodes.

Deep ultraviolet laser at 223.8†nm with adjustable repetition rate and narrow pulse width.

We presented the first, to our knowledge, demonstration of an ultraviolet (UV) laser at 223.8 nm by six-harmonic generation of an electro-optic Q-switched cavity dumping 1342 nm Nd:YVO4 laser. It offers high power, constant short pulse duration, and adjustable pulse repetition rate. The pulse duration is independent of the pump power and repetition rate compared to classical Q-switched oscillators. The output efficiency of the UV laser is optimized by adjusting the focusing lens. With the incident pump power of 30 W, an maximum average output power of 249 mW was obtained at 13 kHz. The pulse width maintained 3.4-3.5 ns from 5 to 20 kHz. The maximum pulse energy of 28.1 µJ was obtained at 5 kHz, and the corresponding peak power was up to 8.1 kW.

Targeted small molecule therapy and inhibitors for lymphoma.

Lymphoma, a blood tumor, has become the ninth most common cancer in the world in 2020. Targeted inhibition is one of the important treatments for lymphoma. At present, there are many kinds of targeted drugs for the treatment of lymphoma. Studies have shown that Histone deacetylase, Bruton's tyrosine kinase and phosphoinositide 3-kinase all play an important role in the occurrence and development of tumors and become important and promising inhibitory targets. This article mainly expounds the important role of these target protein in tumors, and introduces the mechanism of action, structure-activity relationship and clinical research of listed small molecule inhibitors of these targets, hoping to provide new ideas for the treatment of lymphoma.

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Immunogenicity of BNT162b2 as a first booster after a ChAdOx1 primary series in a Thai geriatric population living with frailty.

OBJECTIVES: Impact of frailty towards immunogenicity and reactogenicity of BNT162b2 boosters administered via intramuscular or intradermal routes in a Thai geriatric population DESIGN: Prospective, randomized, open-labeled. SETTING: Siriraj Hospital, Thailand. PARTICIPANTS: Geriatric adults aged ≥65 years. INTERVENTION: 10 µg intradermal or 30 µg intramuscular BNT162b2 (Pfizer-BioNTech). MEASUREMENTS: Anti-SARS-CoV-2 receptor binding domain IgG, neutralizing antibodies (NAb), and interferon-gamma producing cells against Wuhan and Omicron BA.4/5. Analyses were stratified based on participants' Clinical Frailty Scale. RESULTS: A total of 139 participants were included in the analysis. Two-four weeks post-booster administration, NAb titers against Wuhan but not Omicron BA.4/5 were significantly lower among frail participants than non-frail participants who received intramuscular administration. Spike-specific T cell responses were similar for frail and non-frail participants, regardless of administration route. Frail participants who received intradermal BNT162b2 had fewer local adverse events (AEs), but higher systemic AEs than non-frail participants. CONCLUSION: Similar immune responses across vaccine routes warrants further evaluation of intradermal BNT162b2 in frail geriatric populations. Frail participants may be more sensitive to reporting systemic AEs. REGISTRATION OF CLINICAL TRIALS: The parent study was registered under the Thai Clinical Trials Registry (TCTR20220112002).

Ni-B-PTFE Nanocomposite Co-Deposition on the Surface of 2A12 Aluminum Alloy.

The spinning cup, a crucial component of textile equipment, relies heavily on 2A12 aluminum alloy as its primary raw material. Commonly, electroplating and chemical nickel-phosphorus (Ni-P) plating are employed to improve the surface characteristics of the object. Nevertheless, due to the growing expectations for the performance of aluminum alloys, the hardness and wear resistance of Ni-P coatings are no longer sufficient to fulfill industry standards. This study primarily focuses on the synthesis of Ni-B-PTFE nanocomposite chemical plating and its effectiveness when applied to the surface of 2A12 aluminum alloy. We examine the impact of the composition of the plating solution, process parameters, and various other factors on the pace at which the coating is deposited, the hardness of the surface, and other indicators of the coating. The research findings indicate that the composite co-deposited coating achieves its optimal surface morphology when the following conditions are met: a nickel chloride concentration of 30 g/L, an ethylenediamine concentration of 70 mL, a sodium borohydride concentration of 0.6 g/L, a sodium hydroxide concentration of 90 g/L, a lead nitrate concentration of 30 mL, a pH value of 12, a temperature of 90 °C, and a PTFE concentration of 10 mL/L. The coating exhibits consistency, density, a smooth surface, and an absence of noticeable pores or fissures. The composite co-deposited coating exhibits a surface hardness of 1109 HV0.1, which significantly surpasses the substrate's hardness of 232.38 HV0.1. The Ni-B-PTFE composite coating exhibits an average friction coefficient of around 0.12. It has a scratch width of 855.18 µm and a wear mass of 0.05 mg. This coating demonstrates superior wear resistance when compared to Ni-B coatings. The Ni-B-PTFE composite coating specimen exhibits a self-corrosion potential of -6.195 V and a corrosion current density of 7.81 × 10-7 A/cm2, which is the lowest recorded. This enhances its corrosion resistance compared to Ni-B coatings.

Suppressing SENP1 inhibits esophageal squamous carcinoma cell growth via SIRT6 SUMOylation.

PURPOSE: Esophageal squamous cell carcinoma (ESCC) is a prevalent tumor in the gastrointestinal tract, but our understanding of the molecular mechanisms underlying ESCC remains incomplete. Existing studies indicate that SUMO specific peptidase 1 (SENP1) plays a crucial role in the development and progression of various malignant tumors through diverse molecular mechanisms. However, the functional mechanism and clinical implications of SENP1 in the progression of ESCC remain unclear. METHODS: Bulk RNA-Sequencing (RNA-seq) was used to compare potential genes in the esophageal tissues of mice with ESCC to the control group. The up-regulated SENP1 was selected. The protein level of SENP1 in ESCC patient samples was analyzed by immunohistochemistry and western blot. The potential prognostic value of SENP1 on overall survival of ESCC patients was examined using tissue microarray analysis and the Kaplan-Meier method. The biological function was confirmed through in vitro and in vivo knockdown approaches of SENP1. The role of SENP1 in cell cycle progression and apoptosis of ESCC cells was analyzed by flow cytometry and western blot. The downstream signaling pathways regulated by SENP1 were investigated via using RNA-Seq. SENP1-associated proteins were identified through immunoprecipitation. Overexpression of Sirtuin 6 (SIRT6) wildtype and mutant was performed to investigate the regulatory role of SENP1 in ESCC progression in vitro. RESULTS: Our study discovered that SENP1 was upregulated in ESCC tissues and served as a novel prognostic factor. Moreover, SENP1 enhanced cell proliferation and migration of ESCC cell lines in vitro, as well as promoted tumor growth in vivo. Thymidine kinase 1 (TK1), Geminin (GMNN), cyclin dependent kinase 1(CDK1), and cyclin A2 (CCNA2) were identified as downstream genes of SENP1. Mechanistically, SENP1 deSUMOylated SIRT6 and subsequently inhibited SIRT6-mediated histone 3 lysine 56 (H3K56) deacetylation on those downstream genes. SIRT6 SUMOylation mutant (4KR) rescued the growth inhibition upon SENP1 depletion. CONCLUSIONS: SENP1 promotes the malignant progression of ESCC by inhibiting the deacetylase activity of SIRT6 pathway through deSUMOylation. Our findings suggest that SENP1 may serve as a valuable biomarker for prognosis and a target for therapeutic intervention in ESCC.

Development of a predictive model to predict postoperative bone metastasis in pathological I-II non-small cell lung cancer.

Background: Bone is a common metastatic site in postoperative metastasis, but related risk factors for early-stage non-small cell lung cancer (NSCLC) remain insufficiently investigated. Thus, the study aimed to identify risk factors for postoperative bone metastasis in early-stage NSCLC and construct a nomogram to identify high-risk individuals. Methods: Between January 2015 and January 2021, we included patients with resected stage I-II NSCLC at the Department of Thoracic Surgery, West China Hospital. Univariable and multivariable Cox regression analyses were used to identify related risk factors. Additionally, we developed a visual nomogram to forecast the likelihood of bone metastasis. Evaluation of the model involved metrics such as the area under the curve (AUC), C-index, and calibration curves. To ensure reliability, internal validation was performed through bootstrap resampling. Results: Our analyses included 2,106 eligible patients, with 54 (2.56%) developing bone metastasis. Multivariable Cox analyses showed that tumor nodules with solid component, higher pT stage, higher pN stage, and histologic subtypes especially solid/micropapillary predominant types were considered as independent risk factors of bone metastasis. In the training set, the developed model demonstrated AUCs of 0.807, 0.769, and 0.761 for 1-, 3-, and 5-year follow-ups, respectively. The C-index, derived from 1,000 bootstrap resampling, showed values of 0.820, 0.793, and 0.777 for 1-, 3-, and 5-year follow-ups. The calibration curve showed that the model was well calibrated. Conclusions: The predictive model is proven to be valuable in estimating the probability of bone metastasis in early-stage NSCLC following surgery. Leveraging four easy-to-acquire clinical parameters, this model effectively identifies high-risk patients and enables individualized surveillance strategies for better patient care.

"Nutrient-fungi-host" tripartite interaction in cancer progression.

The human microbiome exhibits a profound connection with the cancer development, progression, and therapeutic response, with particular emphasis on its components of the mycobiome, which are still in the early stages of research. In this review, we comprehensively summarize cancer-related symbiotic and pathogenic fungal genera. The intricate mechanisms through which fungi impact cancer as an integral member of both gut and tissue-resident microbiomes are further discussed. In addition, we shed light on the pivotal physiological roles of various nutrients, including cholesterol, carbohydrates, proteins and minerals, in facilitating the growth, reproduction, and invasive pathogenesis of the fungi. While our exploration of the interplay between nutrients and cancer, mediated by the mycobiome, is ongoing, the current findings have yet to yield conclusive results. Thus, delving into the relationship between nutrients and fungal pathogenesis in cancer development and progression would provide valuable insights into anticancer therapy and foster precision nutrition and individualized treatments that target fungi from bench to bedside.

Modified arthroscopic repair of a posterior cruciate ligament tibial avulsion fracture improves IKDC and Lysholm score compared to open reduction.

PURPOSE: The purpose of this study was to analyse the difference between arthroscopic fixation and open reduction internal fixation (ORIF) of posterior cruciate ligament (PCL) tibial avulsion fractures. METHODS: This retrospective study analysed patients with an acute PCL tibial avulsion fracture who underwent surgical treatment at our hospital and follow-up for at least 24 months. Variables based on sex, age, Meyers-McKeever type, surgical method, meniscus tear, external fixation, labour or sports, Lysholm knee score, IKDC score, and KT-1000 value were also recorded. Multifactor unconditional logistic regression and Student's t test with 1:1 propensity score matching (PSM) to remove confounding factors were used for analysis. RESULTS: Sixty-five cases achieved knee function graded as "good" or better, and 9 cases not. Single-factor analysis indicated that Meyers-McKeever type (χ2 = 4.669, P = 0.031) and surgical approach (χ2 = 9.428, P = 0.002) are related to functional outcomes. Multifactorial logistic regression analysis further confirmed that Meyers-McKeever typing (OR = 10.763, P = 0.036, [95% CI 1.174-98.693]) and surgical approach (OR = 9.274, P = 0.008, [95% CI 1.794-47.934]) are independent risk factors affecting prognosis. In addition, PSM verified significant differences in the Lysholm score (t = 3.195, P = 0.006), IKDC score (t = 4.703, P = 0.000) and A-KT/H-KT (t = 2.859, P = 0.012). However, the affected-side KT-1000 value (A-KT, mm, t = 1.225, P = 0.239) and healthy-side KT-1000 value (H-KT, mm, t = 1.436, P = 0.172) did not significantly differ between the two groups. The proportions of cases in which the Lysholm score, IKDC and A-KT/H-KT exceeded the minimal clinically important difference (MCID) were 62.5% (20/32), 62.5% (20/32) and 93.75% (30/32), respectively. CONCLUSION: Compared with ORIF, an arthroscopic approach for PCL tibial avulsion fractures achieves better results. LEVEL OF EVIDENCE: Retrospective cohort study; Level II.

Cetuximab combined with chemotherapy for simultaneous esophageal squamous cell carcinoma and colon adenocarcinoma: A case report.

BACKGROUND: Multiple primary carcinomas (MPCs) are defined as two or more independent primary cancers that occur simultaneously or sequentially in the same individual. Synchronous MPCs are rarer than solitary cancers or metachronous MPCs. Accurate diagnoses of synchronous MPCs and the choice of treatment are critical for successful outcomes in these cases. CASE SUMMARY: A 64-year-old patient presented with dysphagia, without obvious cause. A diagnosis of synchronous esophageal squamous cell carcinoma and colon adenocarcinoma with liver metastasis was confirmed based on examination and laboratory results. After multi-disciplinary consultations, combination chemotherapy (a 3-wk cycle with oxaliplatin 212 mg administered on day 1 and capecitabine 1.5 g twice daily on days 1-14) and esophageal cancer radiotherapy were initiated. Based on the results of genetic testing, we switched to a regimen of leucovorin + fluorouracil + oxaliplatin and cetuximab regimen for 8 cycles. Subsequently, capecitabine and bevacizumab were administered until the most recent follow-up, at which the tumor remained stable. CONCLUSION: Successful cetuximab chemotherapy treatment provides a reference for the non-operative and homogeneous treatment of different pathological types of synchronous MCPs.

Research Progress in the Use of Small Molecule Smac Mimetics in Combination Therapy of Cancer.

Inhibitors of Apoptosis Proteins (IAP) are inhibitors that can block programmed cell death, are expressed at high levels in various cancers, and are recognized as a therapeutic target for cancer therapy. In the past few years, several small molecule IAP protein inhibitors have been designed to mimic the endogenous IAP antagonist, but no IAP inhibitors have been approved for marketing worldwide. Previously, xevinapant has been awarded a breakthrough therapy designation by the FDA. In addition, a combination of Smac-mimetics and chemotherapeutic compounds has been reported to improve anticancer efficacy. According to the phase II clinical data, xevinapant has the potential to significantly enhance the standard therapy for patients with head and neck cancer, which is expected to be approved as an innovative therapy for cancer patients. Therefore, this paper briefly describes the mechanism of IAPs (AT-406, APG-1387, GDC- 0152, TL32711, and LCL161) as single or in combination for cancer treatment, their application status as well as the synthetic pathway, and explores the research prospects and challenges of IAPs antagonists in the tumor combination therapy, with the hope of providing strong insights into the further development of Smac mimics in tumor therapy.

Suction versus non-suction drainage strategy after uniportal thoracoscopic lung surgery: a prospective cohort study.

Background: The postoperative outcomes of suction drainage versus non-suction drainage after uniportal video-assisted thoracoscopic surgery (UniVATS) come with little consensus. This study aimed to prospectively compare the postoperative outcomes of suction drainage versus non-suction drainage in patients who underwent UniVATS. Methods: Between October 2022 and January 2023, patients undergoing UniVATS were prospectively enrolled. The choice of drainage strategy (suction or non-suction) was at the surgeon's discretion. The primary outcome was chest tube duration, with secondary outcomes including postoperative drainage volume, pain scores, postoperative complications, length of hospital stay, and hospitalization cost. Baseline characteristics and postoperative outcomes were compared. Univariable and multivariable analyses were used to identify risk factors for postoperative outcomes. Results: A total of 206 patients were enrolled in this study, with 103 patients in each group. Baseline characteristics were well-balanced. The chest tube duration did not significantly differ between the two groups. However, suction drainage exhibited a significantly lower total drainage volume compared to non-suction drainage (280.00 vs. 400.00 mL, P=0.03). Suction drainage was associated with a significantly shorter postoperative hospital stay (3.00 vs. 4.00 days, P<0.001) and lower pain score on the second postoperative day (POD). Multivariable analyses also confirmed that suction drainage was significantly correlated with a lower total drainage volume and a shorter postoperative hospital stay. Conclusions: These findings suggested that the suction drainage was superior to non-suction drainage in terms of postoperative drainage volume and length of hospital stay in patients undergoing UniVATS.

Danshensu reduces neuronal excitability by enhancing potassium currents in bushy cells in the mouse cochlear nucleus.

Danshensu, also known as salvianic acid A, is a primary active compound extracted from a traditional Chinese herb Danshen (Salvia miltiorrhiza). While its antioxidative and neuroprotective effects are well-documented, the underlying mechanisms are poorly understood. In this study, we sought out to investigate if and how Danshensu modulates neuronal excitability and voltage-gated ionic currents in the central nervous system. We prepared brain slices of the mouse brainstem and performed patch-clamp recording in bushy cells in the anteroventral cochlear nucleus, with or without Danshensu incubation for 1 h. QX-314 was used internally to block Na+ current, while tetraethylammonium and 4-aminopyridine were used to isolate different subtypes of K+ current. We found that Danshensu of 100 µm decreased the input resistance of bushy cells by approximately 60% and shifted the voltage threshold of spiking positively by approximately 7 mV, resulting in significantly reduced excitability. Furthermore, we found this reduced excitability by Danshensu was caused by enhanced voltage-gated K+ currents in these neurons, including both low voltage-activated IK,A, by approximately 100%, and high voltage-activated IK,dr, by approximately 30%. Lastly, we found that the effect of Danshensu on K+ currents was dose-dependent in that no enhancement was found for Danshensu of 50 µm and Danshensu of 200 µm failed to cause significantly more enhancement on K+ currents when compared to that of 100 µm. We found that Danshensu reduced neuronal excitability in the central nervous system by enhancing voltage-gated K+ currents, providing mechanistic support for its neuroprotective effect widely seen in vivo.