Water decoction of Pericarpium citri reticulatae and Amomi fructus ameliorates alcohol-induced liver disease involved in the modulation of gut microbiota and TLR4/NF-κB pathway.

Introduction: Alcohol consumption alters the diversity and metabolic activities of gut microbiota, leading to intestinal barrier dysfunction and contributing to the development of alcoholic liver disease (ALD), which is the most prevalent cause of advanced liver diseases. In this study, we investigated the protective effects and action mechanism of an aqueous extraction of Pericarpium citri reticulatae and Amomi fructus (PFE) on alcoholic liver injury. Methods: C57BL/6 mice were used to establish the mouse model of alcoholic liver injury and orally administered 500 and 1,000 mg/kg/d of PFE for 2 weeks. Histopathology, immunohistochemistry, immunofluorescence, Western blotting, qRT-PCR, and 16S rDNA amplicon sequencing were used to analyze the mechanism of action of PFE in the treatment of alcohol-induced liver injury. Results: Treatment with PFE significantly improved alcohol-induced liver injury, as illustrated by the normalization of serum alanine aminotransferase, aspartate aminotransferase, total triglyceride, and cholesterol levels in ALD mice in a dose-dependent manner. Administration of PFE not only maintained the intestinal barrier integrity prominently by upregulating mucous production and tight junction protein expressions but also sensibly reversed the dysregulation of intestinal microecology in alcohol-treated mice. Furthermore, PFE treatment significantly reduced hepatic lipopolysaccharide (LPS) and attenuated oxidative stress as well as inflammation related to the TLR4/NF-κB signaling pathway. The PFE supplementation also significantly promoted the production of short-chain fatty acids (SCFAs) in the ALD mice. Conclusion: Administration of PFE effectively prevents alcohol-induced liver injury and may also regulate the LPS-involved gut-liver axis; this could provide valuable insights for the development of drugs to prevent and treat ALD.

[Therapeutic effect of ß-tricalcium phosphate in mastoid cavity obliterationunder endoscope].

Objective:To investigate the therapeutic effect of ß-tricalcium phosphate in mastoid cavity obliteration for middle ear cholesteatoma under endoscope. Methods:Sixty patients with middle ear cholesteatoma admitted to our department from September 2021 to March 2022 were included in this study. The observation group（n=30） received ß-tricalcium phosphate during mastoid cavity obliteration. The control group（n=30） received autologous tissue during mastoid cavity obliteration. Pure tone audiometry was performed before surgery and after surgery in both groups, and the air conduction thresholds of 500, 1 000, 2 000 and 4 000 Hz were recorded. The external acoustic meatus cross-sectional area within 1 cm of the external acoustic meatus opening was measured during the operation and after the operation. The differences of postoperative ear drying time, hearing change and mastoid cavity healing were compared between the two groups. Results:The duration of postoperative dry ear in the observation group was 2-14 weeks, with an average of （9.4±2.7） weeks, while that in the control group was 4-26 weeks, with an average of（16.0±5.7） weeks. The difference in dry ear time between the two groups was statistically significant（P<0.05）. In the observation group, the threshold change was -19-27 dB, with an average of（6.4±10.7） dB, and in the control group, the threshold change was -9-17 dB, with an average of （4.7±7.1） dB. There was no significant difference in hearing change between the two groups（P>0.05）. In the observation group, the cross-sectional area of 1 cm inside the ear canal opening was -5.9-8.2 mm², with an average of （-0.6±2.6） mm², and in the control group, the cross-sectional area of 1 cm inside the ear canal opening was -5.5-5.2 mm², with an average of （-0.4±2.3） mm². There was no significant difference in intraoperative cavity changes between the two groups（P>0.05）. Conclusion:The application of ß-tricalcium phosphate to fill the mastoid cavity during the operation of endoscopic middle ear cholesteatoma has no adverse effect on the hearing of patients, can shorten the postoperative dry ear time, and results in good postoperative healing, which is worth promoting.

Neuroimmune interactions and their roles in neurodegenerative diseases.

The nervous system possesses bidirectional, sophisticated and delicate communications with the immune system. These neuroimmune interactions play a vitally important role in the initiation and development of many disorders, especially neurodegenerative diseases. Although scientific advancements have made tremendous progress in this field during the last few years, neuroimmune communications are still far from being elucidated. By organizing recent research, in this review, we discuss the local and intersystem neuroimmune interactions and their roles in Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Unveiling these will help us gain a better understanding of the process of interplay inside the body and how the organism maintains homeostasis. It will also facilitate a view of the diseases from a holistic, pluralistic and interconnected perspective, thus providing a basis of developing novel and effective methods to diagnose, intervene and treat diseases.

Cordyceps militaris: A novel mushroom platform for metabolic engineering.

Cordyceps militaris, widely recognized as a medicinal and edible mushroom in East Asia, contains a variety of bioactive compounds, including cordycepin (COR), pentostatin (PTN) and other high-value compounds. This review explores the potential of developing C. militaris as a cell factory for the production of high-value chemicals and nutrients. This review comprehensively summarizes the fermentation advantages, metabolic networks, expression elements, and genome editing tools specific to C. militaris and discusses the challenges and barriers to further research on C. militaris across various fields, including computational biology, existing DNA elements, and genome editing approaches. This review aims to describe specific and promising opportunities for the in-depth study and development of C. militaris as a new chassis cell. Additionally, to increase the practicability of this review, examples of the construction of cell factories are provided, and promising strategies for synthetic biology development are illustrated.

Backstepping control based on adaptive neural network and disturbance observer for reconfigurable variable stiffness actuator.

Reconfigurable variable stiffness actuator (RVSA) has attracted increasing attention in robotics due to its safety, compliance, and robustness. However, the control of the RVSA is challenging due to nonlinear factors such as high-order nonlinear dynamic, model uncertainties, time-varying model parameters, and disturbances. In this paper, firstly, a lightweight RVSA structure with both passive and active nonlinear variable stiffness characteristic is developed. Secondly, a dynamic surface backstepping control method based on a radial basis neural network and disturbance observer (DSBC-RBFNN-DOB) is proposed to achieve position control of the lightweight RVSA with matched and unmatched uncertainties. To address solve the "complexity explosion" and noise problems in traditional backstepping control, the dynamic surface backstepping control (DSBC) method is used to design the controller. Then, a method based on radial basis neural network (RBFNN) and disturbance observer (DOB) are used to compensate for the matched and unmatched uncertainties in the link and motor. In this method, the matched uncertainties are compensated using RBFNN, and the DOB is integrated to compensate RBFNN approximation errors and unmatched uncertainties. Through Lyapunov stability analysis, the semi-global boundedness of the controller is proven. Finally, the proposed method is simulated and actually implemented, verifying the effectiveness of the method. Simulation and experimental results show that the root mean square error (RMSE) of the proposed method is only 0.97277° and 0.6418°, respectively. Compared with PID, DSBC, and DSBC-RBFNN, the error reduction percentages in simulation (experiment) are 85.6 % (88.9 %), 49.4 % (88.4 %) and 36.1 % (80.0 %) respectively.

Regulatory mechanism of GA3 application on grape (Vitis vinifera L.) berry size.

Gibberellin A3 (GA3) is often used as a principal growth regulator to increase plant size. Here, we applied Tween-20 (2%)-formulated GA3 (T1:40 mg/L; T2:70 mg/L) by dipping the clusters at the initial expansion phase of 'Red Globe' grape (Vitis vinifera L.) in 2018 and 2019. Tween-20 (2%) was used as a control. The results showed that GA3 significantly increased fruit cell length, cell size, diameter, and volume. The hormone levels of auxin (IAA) and zeatin (ZT) were significantly increased at 2 h (0 d) -1 d after application (DAA0-1) and remained significantly higher at DAA1 until maturity. Conversely, ABA exhibited an opposite trend. The mRNA and non-coding sequencing results yielded 436 differentially expressed mRNA (DE_mRNAs), 79 DE_lncRNAs and 17 DE_miRNAs. These genes are linked to hormone pathways like cysteine and methionine metabolism (ko00270), glutathione metabolism (ko00480) and plant hormone signal transduction (ko04075). GA3 application reduced expression of insensitive dwarf 2 (GID2, VIT_07s0129g01000), small auxin-upregulated RNA (SAUR, VIT_08s0007g03120) and 1-aminocyclopropane-1-carboxylate synthase (ACS, VIT_18s0001g08520), but increased SAUR (VIT_04s0023g00560) expression. These four genes were predicted to be negatively regulated by vvi-miR156, vvi-miR172, vvi-miR396, and vvi-miR159, corresponding to specific lncRNAs. Therefore, miRNAs could affect grape size by regulating key genes GID2, ACS and SAUR. The R2R3 MYB family member VvRAX2 (VIT_08s0007g05030) was upregulated in response to GA3 application. Overexpression of VvRAX2 in tomato transgenic lines increased fruit size in contrast to the wild type. This study provides a basis and genetic resources for elucidating the novel role of ncRNAs in fruit development.

Arthroscopic Linear Chain Fixation for the Treatment of Medial Meniscus Posterior Root Tear: A Case Study.

BACKGROUND: The repair and reconstruction of medial meniscus posterior root tears (MMPRTs) is an important issue in the field of orthopedic sports medicine. This study reports the first application of arthroscopic linear chain fixation for the treatment of MMPRTs. CASE PRESENTATION: A 78-year-old female patient presented with a 1.5-month history of right knee pain accompanied by a locked facet joint. The patient underwent surgery with the new linear chain fixation method. In this method, the suture and the loop part of the buckle-strap titanium plate were combined into a linear chain mechanical complex, and the tension of the posterior root stump was gradually increased by pulling on the two attachment lines at the external mouth of the tibial tunnel. The postoperative Lysholm score was 89, and the visual analogue scale score was 0.9, indicating a significant improvement in knee joint function. At the 7-month and 1-year post-surgery follow-up, physical and MRI examinations confirmed satisfactory healing of the MMPRTs. CONCLUSION: This surgical approach offers several benefits, including a simplified instrumentation setup, preservation of natural anatomical structures, and reliable residual stump fixation. It has the potential for clinical implementation.

Bowel Stiffness Assessed by Shear-Wave Ultrasound Elastography Predicts Disease Behavior Progression in Patients With Crohn's Disease.

INTRODUCTION: There is a lack of reliable predictors of disease behavior progression in patients with Crohn's disease (CD). Real-time shear-wave elastography (SWE) is a novel method for evaluating tissue stiffness. However, its value for assessing CD has not yet been investigated. We aimed to explore the value of SWE and other ultrasound parameters at diagnosis in predicting CD behavior progression. METHODS: We retrospectively collected data from patients with CD with the nonstenotic nonpenetrating disease (B1 phenotype based on the Montreal classification). All patients underwent intestinal ultrasound at baseline and were followed up. The end point was defined as disease behavior progression to stricturing (B2) or penetrating (B3) disease. Cox regression analysis was performed for the association between baseline characteristics and subsequent end points. In addition, a multivariate nomogram was established to predict the risk of disease behavior progression quantitatively. RESULTS: A total of 130 patients with CD with B1 phenotype were enrolled. Twenty-seven patients (20.8%) developed B2 or B3 disease, with a median follow-up of 33 months. Multivariate analysis identified that SWE was the only independent predictor of disease behavior progression (hazard ratio 1.08, 95% confidence interval 1.03-1.12, P = 0.001). A reverse of the HR appeared at the cutoff 12.75 kPa. The nomogram incorporating SWE and other clinical characteristics showed a good prediction performance (area under the curve = 0.792). DISCUSSION: Intestinal stiffness assessed using SWE is an independent predictor of disease behavior progression in patients with CD. Patients with CD with SWE >12.75 kPa at diagnosis are prone to progress toward stricturing or penetrating diseases.

LRP4-related signalling pathways and their regulatory role in neurological diseases.

The mechanism of action of low-density lipoprotein receptor related protein 4 (LRP4) is mediated largely via the Agrin-LRP4-MuSK signalling pathway in the nervous system. LRP4 contributes to the development of synapses in the peripheral nervous system (PNS). It interacts with signalling molecules such as the amyloid beta-protein precursor (APP) and the wingless type protein (Wnt). Its mechanisms of action are complex and mediated via interaction between the pre-synaptic motor neuron and post-synaptic muscle cell in the PNS, which enhances the development of the neuromuscular junction (NMJ). LRP4 may function differently in the central nervous system (CNS) than in the PNS, where it regulates ATP and glutamate release via astrocytes. It mayaffect the growth and development of the CNS by controlling the energy metabolism. LRP4 interacts with Agrin to maintain dendrite growth and density in the CNS. The goal of this article is to review the current studies involving relevant LRP4 signaling pathways in the nervous system. The review also discusses the clinical and etiological roles of LRP4 in neurological illnesses, such as myasthenia gravis, Alzheimer's disease and epilepsy. In this review, we provide a theoretical foundation for the pathogenesis and therapeutic application of LRP4 in neurologic diseases.

Muscle Strength Decline Caused by Eperisone Hydrochloride: A Case Report.

A 65-year-old female with thoracic spinal stenosis and incomplete paraplegia underwent T11-T12 posterior thoracic interbody fusion. During postoperative rehabilitation, she experienced thigh pain, involuntary lower limb convulsions, and muscle fatigue. Despite being prescribed eperisone hydrochloride for relief, her muscle strength decreased after 14 doses. This adverse effect, not listed in the latest Chinese medication instructions, subsided 4 days after discontinuation. This case suggests eperisone hydrochloride potentially caused reversible muscle strength decline, highlighting its potential unsuitability for incomplete paraplegia patients due to possible further muscle strength reduction. We propose updating the medication instructions to alert clinicians to this risk.

Time-delay control scheme with adaptive fixed-time convergent super-twisting fractional-order nonsingular terminal sliding mode for piezoelectric displacement amplifier.

Piezoelectric displacement amplifiers (PDAs) have been widely used in precision positioning fields. However, the inherent hysteresis and creep nonlinear effect of piezoelectric actuators (PEAs) and time-varying lumped disturbances bring extreme challenges to the precise motion control of PDAs. Although various control schemes based on PEAs have been developed and have shown significant results. However, due to the high sensitivity of precision positioning to environmental variations, the development and identification of accurate models and the control timeliness often become obstacles in engineering. To realize precise motion control of PDAs under complex lumped disturbances, a new time-delay control scheme (AFSTA-FONTSM) using an adaptive fixed-time convergent super-twisting algorithm (AFSTA) and a fractional-order nonsingular terminal sliding mode (FONTSM) is proposed. Specifically, the time-delay information obtained by time-delay estimation technology is used to estimate the lumped dynamic characteristic of the system, thus establishing a simple control framework without a system dynamic model. FONSTM is constructed as a sliding mode manifold, and satisfactory error dynamic characteristic is obtained. A new AFSTA is designed as the reaching law in the sliding mode phase. AFSTA has fixed-time convergence when the upper bound of lumped disturbances exists, which ensures the control timeliness. Benefiting from the newly designed adaptive algorithm, the upper bound value of lumped disturbances is no longer needed to determine the control gains, which effectively prevents overestimation of the control gains. Correspondingly, the convergence time of AFSTA is estimated, and the stability of the closed-loop system is analyzed by the Lyapunov theory. Three existing time-delay control schemes, namely MSTA-FONTSM, AMSTA-FONTSM, and ASTA-FONTSM are selected, and four scenes are designed for comparative experiments. The experimental results show that MSTA-FONTSM has the worst control performance among the four control schemes. For the step, and continuous cosine trajectories with periods of T = 1 s and T = 2 s, the root-mean-square error of the proposed AFSTA-FONTSM is reduced by 56.86%, 54.03%, and 50.24% compared with MSTA-FONTSM. For disturbance experiments under different loads, the control performance of the proposed AFSTA-FONTSM is still superior to the other three control schemes without load.

ULK1 confers neuroprotection by regulating microglial/macrophages activation after ischemic stroke.

Microglial activation and autophagy play a critical role in the progression of ischemic stroke and contribute to the regulation of neuroinflammation. Unc-51-like kinase 1 (ULK1) is the primary autophagy kinase involved in autophagosome formation. However, the impact of ULK1 on neuroprotection and microglial activation after ischemic stroke remains unclear. In this study, we established a photothrombotic stroke model, and administered SBI-0206965 (SBI), an ULK1 inhibitor, and LYN-1604 hydrochloride (LYN), an ULK1 agonist, to modulate ULK1 activity in vivo. We assessed sensorimotor deficits, neuronal apoptosis, and microglial/macrophage activation to evaluate the neurofunctional outcome. Immunofluorescence results revealed ULK1 was primarily localized in the microglia of the infarct area following ischemia. Upregulating ULK1 through LYN treatment significantly reduced infarct volume, improved motor function, promoted the increase of anti-inflammatory microglia. In conclusion, ULK1 facilitated neuronal repair and promoted the formation of anti-inflammatory microglia pathway after ischemic injury.

Enhanced oxidative stress is associated with tissue neutrophilia and poor steroid response in chronic rhinosinusitis with nasal polyps.

Objective: To analyze the oxidative stress status and its association with tissue neutrophilia and oral steroid response in chronic rhinosinusitis with nasal polyps (CRSwNP) patients. Methods: The levels of total oxidant status (TOS) were detected in the sinonasal tissues by using specific assay kits. Tissue neutrophil was examined by immunohistochemical staining, and oxidant status index (OSI) was evaluated in polyps tissues, and the messenger RNA (mRNA) levels of superoxide dismutase 2 (SOD2), aldehyde dehydrogenase 1 (ALDH1A1), and microsomal glutathione S-transferase 1 (MGST1) were examined using quantitative real-time polymerase chain reaction in the sinonasal tissues. The receiver operating characteristics (ROCs) curve of ALDH1A1, MGST1, and SOD2 mRNA levels were evaluated to determine the steroid response of CRSwNP patients. Results: The levels of TOS and OSI were significantly higher in CRSwNP and CRSsNP than in normal controls, and OSI in polyps tissues was positively associated with tissue neutrophilia and poor steroid response. The ALDH1A1, MGST1, and SOD2 mRNA levels showed comparable accuracy as predictors of poor steroid response indicated by the area under the curve. Conclusion: These findings provided evidence that the increased level of oxidative stress contributes to enhanced tissue neutrophilia and poor steroid response in CRSwNP patients.

Subchondral fatigue fracture of the femoral head in young military recruits: Potential risk factors.

BACKGROUND: Subchondral fatigue fracture of the femoral head (SFFFH) mainly occurs in young military recruits and might be confused with osteonecrosis of the femoral head. However, less research focuses on the risk factor for SFFFH. AIM: To evaluate the intrinsic risk factors for SFFFH in young military recruits. METHODS: X-ray and magnetic resonance imaging data were used for analysis. Acetabular anteversion of the superior acetabulum, acetabular anteversion of the center of the acetabulum (AVcen), anterior acetabular sector angle (AASA), posterior acetabular sector angle, superior acetabular sector angle, neck-shaft angle (NSA), inferior iliac angle (IIA), and ischiopubic angle were calculated. Then, logistic regression, receiver operating characteristic curve analysis, and independent samples t-test were performed to identify the risk factors for SFFFH. RESULTS: Based on the results of logistic regression, age [odds ratio (OR): 1.33; 95% confidence interval (95%CI): 1.12-1.65; P = 0.0031] and treatment timing (OR: 0.86; 95%CI: 0.75-0.96; P = 0.015) could be considered as the indicators for SFFFH. AVcen (P = 0.0334), AASA (P = 0.0002), NSA (P = 0.0007), and IIA (P = 0.0316) were considered to have statistical significance. Further, AVcen (OR: 1.41; 95%CI: 1.04-1.95) and AASA (OR: 1.44; 95%CI: 1.21-1.77), especially AASA (area under curve: 66.6%), should be paid much more attention due to the higher OR than other indicators. CONCLUSION: We have for the first time unveiled that AASA and age could be key risk factors for SFFFH, which further verifies that deficient anterior coverage of the acetabulum might be the main cause of SFFFH.

Dihydro-Resveratrol Attenuates Oxidative Stress, Adipogenesis and Insulin Resistance in In Vitro Models and High-Fat Diet-Induced Mouse Model via AMPK Activation.

Management of obesity has become a prevalent strategy for preventing the diseases closely integrated with excess body weight such as diabetes over the last half century. Searching for therapeutic agents acting on oxidative stress, adipogenesis and insulin resistance is considered as an efficient approach to control obesity-related diseases. The present study was designed to examine the in vitro and in vivo effects of dihydro-resveratrol (DR2), a naturally occurring compound from Dendrobium medicinal plants, on oxidative stress aggravation, adipogenesis, lipogenesis and insulin sensitivity. We utilized an in vitro 3T3-L1 adipocyte differentiation model to show that DR2 could reduce pre-adipocyte maturation by activation of AMPK/SIRT1 signaling proteins to inhibit p38MAPK proteins. With the use of in vitro oxidative-stress-induced hepatocytes and myoblasts models, DR2 was also shown to be able to reduce oxidative stress aggravation through mediation of Nrf2-related antioxidative cascade, reduce intracellular lipid accumulation through phosphorylation of ACC protein, reduce lipid peroxidation in hepatocytes and promote insulin sensitivity via activation of AKT protein in the insulin-resistant HepG2 cells and C2C12 cells. The effects of DR2 on adipogenesis, lipid accumulation, insulin resistance and blood glucose clearance were further demonstrated in the high-fat diet-induced obesity mouse model. Our in vitro and in vivo studies determined that DR2 could contain therapeutic potential for the treatment of obesity and type 2 diabetes.

Efficacy of image-enhanced endoscopy for colorectal adenoma detection: A multicenter, randomized trial.

BACKGROUND: Improved adenoma detection at colonoscopy has decreased the risk of developing colorectal cancer. However, whether image-enhanced endoscopy (IEE) further improves the adenoma detection rate (ADR) is controversial. AIM: To compare IEE with white-light imaging (WLI) endoscopy for the detection and identification of colorectal adenoma. METHODS: This was a multicenter, randomized, controlled trial. Participants were enrolled between September 2019 to April 2021 from 4 hospital in China. Patients were randomly assigned to an IEE group with WLI on entry and IEE on withdrawal (n = 2113) or a WLI group with WLI on both entry and withdrawal (n = 2098). The primary outcome was the ADR. The secondary endpoints were the polyp detection rate (PDR), adenomas per colonoscopy, adenomas per positive colonoscopy, and factors related to adenoma detection. RESULTS: A total of 4211 patients (966 adenomas) were included in the analysis (mean age, 56.7 years, 47.1% male). There were 2113 patients (508 adenomas) in the IEE group and 2098 patients (458 adenomas) in the WLI group. The ADR in two group were not significantly different [24.0% vs 21.8%, 1.10, 95% confidence interval (CI): 0.99-1.23, P = 0.09]. The PDR was higher with IEE group (41.7%) than with WLI group (36.1%, 1.16, 95%CI: 1.07-1.25, P = 0.01). Differences in mean withdrawal time (7.90 ± 3.42 min vs 7.85 ± 3.47 min, P = 0.30) and adenomas per colonoscopy (0.33 ± 0.68 vs 0.28 ± 0.62, P = 0.06) were not significant. Subgroup analysis found that with narrow-band imaging (NBI), between-group differences in the ADR, were not significant (23.7% vs 21.8%, 1.09, 95%CI: 0.97-1.22, P = 0.15), but were greater with linked color imaging (30.9% vs 21.8%, 1.42, 95%CI: 1.04-1.93, P = 0.04). the second-generation NBI (2G-NBI) had an advantage of ADR than both WLI and the first-generation NBI (27.0% vs 21.8%, P = 0.01; 27.0% vs 21.2.0%, P = 0.01). CONCLUSION: This prospective study confirmed that, among Chinese, IEE didn't increase the ADR compared with WLI, but 2G-NBI increase the ADR.

A novel water-soluble Cu(II) gluconate complex inhibits cancer cell growth by triggering apoptosis and ferroptosis related mechanisms.

Metal copper complexes have attracted extensive attention as potential alternatives to platinum-based anticancer drugs due to their possible different modes of action. Herein, a new copper(II) gluconate complex, namely [Cu(DPQ)(Gluc)]·2H2O (CuGluc, DPQ = pyrazino[2,3-f][1,10]phenanthroline), with good water-solubility and high anticancer activity was synthesized by using D-gluconic acid (Gluc-2H) as an auxiliary ligand. The complex was well characterized by single-crystal X-ray diffraction analysis, elemental analysis, molar conductivity, and Fourier transform infrared spectroscopy (FTIR). The DNA-binding experiments revealed that CuGluc was bound to DNA by intercalation with end-stacking binding. CuGluc could oxidatively cleave DNA, in which 1O2 and H2O2 were involved. In addition, CuGluc was bound to the IIA subdomain of human serum albumin (HSA) through hydrophobic interaction and hydrogen bonding, showing a good affinity for HSA. The complex showed superior anticancer activity toward several cancer cells than cisplatin in vitro. Further studies indicated that CuGluc caused apoptotic cell death in human liver cancer (HepG2) cells through elevated intracellular reactive oxygen species (ROS) levels, mitochondrial dysfunction, cell cycle arrest, and caspase activation. Interestingly, CuGluc also triggered the ferroptosis mechanism through lipid peroxide accumulation and inhibition of glutathione peroxidase 4 (GPX4) activity. More importantly, CuGluc significantly inhibited tumor growth in vivo, which may benefit from the combined effects of apoptosis and ferroptosis. This work provides a promising strategy to develop highly effective antitumor copper complexes by coordinating with the glucose metabolite D-gluconic acid and exploiting the synergistic effects of apoptosis and ferroptosis mechanisms.

Laquinimod Inhibits Microglial Activation, Astrogliosis, BBB Damage, and Infarction and Improves Neurological Damage after Ischemic Stroke.

Glial activation is involved in neuroinflammation and blood-brain barrier (BBB) damage, which plays a key role in ischemic stroke-induced neuronal damage; therefore, regulating glial activation is an important way to inhibit ischemic brain injury. Effects of laquinimod (LAQ) include inhibiting axonal damage and neuroinflammation in multiple neuronal injury diseases. However, whether laquinimod can exert neuroprotective effects after ischemic stroke remains unknown. In this study, we investigated the effect of LAQ on glial activation, BBB damage, and neuronal damage in an ischemic stroke model. Adult ICR mice were used to create a photothrombotic stroke (PT) model. LAQ was administered orally at 30 min after ischemic injury. Neurobehavioral tests, Evans Blue, immunofluorescence, TUNEL, Nissl staining, and western blot were performed to evaluate the neurofunctional outcome. Quantification of immunofluorescence was evaluated by unbiased stereology. LAQ post-treatment significantly reduced infarction and improved forepaw function at 5 days after PT. Interestingly, LAQ treatment significantly promoted anti-inflammatory microglial activation. Moreover, LAQ treatment reduced astrocyte activation, glial scar formation, and BBB breakdown in ischemic brains. Therefore, this study demonstrated that LAQ post-treatment restricted microglial polarization, astrogliosis, and glial scar and improved BBB damage and behavioral function. LAQ may serve as a novel target to develop new therapeutic agents for ischemic stroke.

Sub-pm linewidth, high pulse energy, high beam quality microsecond-pulse Ti:sapphire laser at 766.699†nm.

In this letter, a sub-pm linewidth, high pulse energy and high beam quality microsecond-pulse 766.699 nm Ti:sapphire laser pumped by a frequency-doubled Nd:YAG laser is demonstrated. At an incident pump energy of 824 mJ, the maximum output energy of 132.5 mJ at 766.699 nm with linewidth of 0.66 pm and a pulse width of 100 µs is achieved at a repetition rate of 5 Hz. To the best of our knowledge, this is the highest pulse energy at 766.699 nm with pulse width of hundred micro-seconds for a Ti:sapphire laser. The beam quality factor M2 is measured to be 1.21. It could be precisely tuned from 766.623 to 766.755 nm with a tuning resolution of 0.8 pm. The wavelength stability is measured to be less than ±0.7 pm over 30 min. The sub-pm linewidth, high pulse energy and high beam quality Ti:sapphire laser at 766.699 nm can be used to create a polychromatic laser guide star together with a home-made 589 nm laser in the mesospheric sodium and potassium layer for the tip-tilt correction resulting in the near-diffraction limited imagery on a large telescope.

Synthesis, characterization and biological activity of novel copper complexes containing a ß-carboline derivative and amino acids.

Copper complexes have long been considered as a promising class of anticancer or antibacterial therapeutics. In this paper, two novel copper(II) complexes containing a ß-carboline derivative and amino acids, namely [Cu(1-Im-ßc)(L-Val)]ClO4·0.5H2O (Cu1) and [Cu(1-Im-ßc)(L-Phe)]ClO4·0.5H2O (Cu2), where 1-Im-ßc = 1-(2-imidazolyl)-ß-carboline, L-Val = L-valine, and L-Phe = L-phenylalanine, were designed and synthesized. The complexes were characterized by elemental analysis, infrared spectroscopy, molar conductivity measurements, and mass spectrometry to determine their spatial structures and compositions. Both complexes bind to DNA by insertion. The complexes also show a good affinity for human serum albumin (HSA). In addition, the antitumor activity of the two complexes against lung cancer cells (A549), cervical cancer cells (HeLa), and breast cancer cells (MBA-MD-231) is significantly superior to that of the traditional antitumor drug, cisplatin. Finally, the anticancer mechanism results show that the complexes can induce apoptosis in HeLa cells, which is associated with mitochondrial damage, oxidative stress caused by reactive oxygen species (ROS) production, and activation of the caspase protein family. This study demonstrates that the introduction of aromatic heterocyclic alkaloid ligands with a broad spectrum of biological activities and water-soluble amino acid ligands into copper complexes can regulate their amphiphilic properties and biological activity, so as to obtain highly efficient copper-based therapeutics.