A toe-inspired rigid-flexible coupling wheel design method for improving the terrain adaptability of a sewer robot.

The human toe, characterized by its rigid-flexible structure comprising hard bones and flexible joints, facilitates adaptive and stable movement across varied terrains. In this paper, we utilized a motion capture system to study the adaptive adjustments of toe joints when encountering obstacles. Inspired by the mechanics of toe joints, we proposed a novel design method for a rigid-flexible coupled wheel. The wheel comprises multiple elements: a rigid skeleton, supporting toes, connecting shafts, torsion springs, soft tendons, and damping pads. The torsion springs connect the rigid frame to the supporting toes, enabling them to adapt to uneven terrains and pipes with different diameters. The design was validated through kinematic and dynamic modeling, rigid-flexible coupled dynamics simulation, and stress analysis. Different stiffness coefficients of torsion springs were compared for optimal wheel design. Then, the wheel was applied to a sewer robot, and its performance was evaluated and compared with a pneumatic rubber tire in various experiments, including movement on flat surfaces, overcoming small obstacles, adaptability tests in different terrains, and active driving force tests in dry and wet pipelines. The results prove that the designed wheel showed better stability and anti-slip properties than conventional tires, making it suitable for diverse applications such as pipeline robots, desert vehicles, and lunar rovers.

Association between triglyceride-glucose index trajectories and radiofrequency ablation outcomes in patients with stage 3D atrial fibrillation.

BACKGROUND: This study investigates the relationship between triglyceride-glucose (TyG) index trajectories and the results of ablation in patients with stage 3D atrial fibrillation (AF). METHODS: A retrospective cohort study was carried out on patients who underwent AF Radiofrequency Catheter Ablation (RFCA) at the Cardiology Department of the Fourth Affiliated Hospital of Zhejiang University and Taizhou Hospital of Zhejiang Province from January 2016 to December 2022. The main clinical endpoint was determined as the occurrence of atrial arrhythmia for at least 30 s following a 3-month period after ablation. Using a latent class trajectory model, different trajectory groups were identified based on TyG levels. The relationship between TyG trajectory and the outcome of AF recurrence in patients was assessed through Kaplan-Meier survival curve analysis and multivariable Cox proportional hazards regression model. RESULTS: The study included 997 participants, with an average age of 63.21 ± 9.84 years, of whom 630 were males (63.19%). The mean follow-up period for the participants was 30.43 ± 17.75 months, during which 200 individuals experienced AF recurrence. Utilizing the minimum Bayesian Information Criterion (BIC) and the maximum Entropy principle, TyG levels post-AF RFCA were divided into three groups: Locus 1 low-low group (n = 791), Locus 2 low-high-low group (n = 14), and Locus 3 high-high group (n = 192). Significant differences in survival rates among the different trajectories were observed through the Kaplan-Meier curve (P < 0.001). Multivariate Cox regression analysis showed a significant association between baseline TyG level and AF recurrence outcomes (HR = 1.255, 95% CI: 1.087-1.448). Patients with TyG levels above 9.37 had a higher risk of adverse outcomes compared to those with levels below 8.67 (HR = 2.056, 95% CI: 1.335-3.166). Furthermore, individuals in Locus 3 had a higher incidence of outcomes compared to those in Locus 1 (HR = 1.580, 95% CI: 1.146-2). CONCLUSION: The TyG trajectories in patients with stage 3D AF are significantly linked to the outcomes of AF recurrence. Continuous monitoring of TyG levels during follow-up may help in identifying patients at high risk of AF recurrence, enabling the early application of effective interventions.

Self-Assembly of Sulfate-Containing Peptides Sequesters VEGF for Inhibiting Cancer Cell Invasion.

Heparan sulfate proteoglycans (HSPGs) play a crucial role in regulating cancer growth and migration by mediating interactions with growth factors. In this study, we developed a self-assembling peptide (S1) containing a sulfate group to simulate the contiguous sulfated regions (S-domains) in heparan sulfate for growth factor binding, aiming to sequester growth factors like VEGF. Spectral and structural studies as well as simulation studies suggested that S1 self-assembled into nanostructures similar to the heparan sulfate chains and effectively bound to VEGF. On cancer cell surfaces, S1 self-assemblies sequestered VEGF, leading to a reduction in VEGF levels in the medium, consequently inhibiting cancer cell growth, invasion, and angiogenesis. This study highlights the potential of self-assembling peptides to emulate extracellular matrix functions, offering insights for future cancer therapeutic strategies.

TDDFT Study on the ESIPT Properties of 2-(2'-Hydroxyphenyl)-Benzothiazole and Sensing Mechanism of a Derived Fluorescent Probe for Fluoride Ion.

The level of fluoride ions (F-) in the human body is closely related to various pathological and physiological states, and the rapid detection of F- is important for studying physiological processes and the early diagnosis of diseases. In this study, the detailed sensing mechanism of a novel high-efficiency probe (PBT) based on 2-(2'-hydroxyphenyl)-benzothiazole derivatives towards F- has been fully investigated based on density functional theory (DFT) and time-dependent density functional theory (TDDFT) methods. F- attacks the O-P bond of PBT to cleavage the dimethylphosphinothionyl group, and the potential products were evaluated by Gibbs free energy and spectroscopic analyses, which ultimately identified the product as HBT-Enol1 with an intramolecular hydrogen bond. Bond parameters, infrared vibrational spectroscopy and charge analysis indicate that the hydrogen bond is enhanced at the excited state (S1), favoring excited state intramolecular proton transfer (ESIPT). The mild energy barrier further evidences the occurrence of ESIPT. Combined with frontier molecular orbital (FMO) analysis, the fluorescence quenching of PBT was attributed to the photoinduced electron transfer (PET) mechanism and the fluorescence turn-on mechanism of the product was attributed to the ESIPT process of HBT-Enol1.

Smoking Behavior and its Effect on Psychiatric Symptoms of Patients with Stable Schizophrenia.

Context: Schizophrenia is a common and clinically disabling mental disorder. Many patients with schizophrenia smoke. Research on the effects of smoking on schizophrenia's symptoms are inconsistent. Objective: The study intended to investigate the smoking status of patients with stable schizophrenia to determine the effects of smoking on schizophrenia-related symptoms. Design: The research team performed an case-control study. Setting: The study took place at Beijing Huilongguan Hospital in Beijing, Changping District, China. Participants: Participants were 160 patients at the hospital who had been diagnosed with stable schizophrenia between April 2018 and March 2020. Groups: The research team divided participants into two groups based on their current smoking status: (1) a smoking group with 72 participants and (2) a nonsmoking group with 88 participants. Outcome Measures: The research team: (1) examined the types of antipsychotic drugs that participants received; (2) used a schizophrenia-related scale, the Positive and Negative Syndrome Scale (PANSS), to examine participants' status; (3) examined the smoking habits of the smoking group; and (4) analyzed the correlation between the PANSS score and the smoking group's smoking index. Results: No significant difference existed between the groups in the type of medicine used (P > .05). The smoking group's PANSS total (P = .014), positive symptom (P = .039), and negative symptom (P = .003) scores were significantly lower than those of the nonsmoking group (P < .05). No significant difference existed between the groups in the general psychopathological symptom score (P > .05). The smoking group started smoking between 13 and 24 years of age, with an mean age of 19.11 ± 4.10 years. The group smoked 10-30 cigarettes/d, with a mean smoking amount of 18.4 ± 3.1 cigarettes/d, and the smoking index was 344.7 ± 48.0. The smoking group's smoking index was significantly negatively correlated with the positive symptom, negative symptom, and total PANSS scores (all P = .000). No correlation existed between the smoking index and the general psychopathological symptom score (P > .05). Conclusions: Smoking patients with stable schizophrenia generally exhibit fewer symptoms than nonsmoking patients, which relate to the alleviation of mental tension that smoking can provide.

Discovery of 6-Acylamino/Sulfonamido Benzoxazolone with IL-6 Inhibitory Activity as Promising Therapeutic Agents for Ulcerative Colitis.

Ulcerative colitis has been widely concerned for its persistent upward trend, and the sustained overproduction of pro-inflammatory cytokines such as IL-6 remains a crucial factor in the development of UC. Therefore, the identification of new effective drugs to block inflammatory responses is an urgent and viable therapeutic strategy for UC. In our research, twenty-three 6-acylamino/sulfonamido benzoxazolone derivatives were synthesized, characterized, and evaluated for anti-inflammatory activity against NO and IL-6 production in LPS-induced RAW264.7 cells. The results demonstrated that most of the target compounds were capable of reducing the overexpression of NO and IL-6 to a certain degree. For the most active compounds 3i, 3j and 3 l, the inhibitory activities were superior or equivalent to those of the positive drug celecoxib with a dose-dependent relationship. Furthermore, animal experiments revealed that active derivatives 3i, 3j and 3 l exhibited definitive therapeutical effect on DSS induced ulcerative colitis in mice by mitigating weight loss and DAI score while decreasing levels of pro-inflammatory cytokines such as IL-6 and IFN-γ, simultaneously increasing production of anti-inflammatory cytokines IL-10. In addition, compounds 3i, 3j and 3 l could also inhibit the oxidative stress to alleviate ulcerative colitis by decreasing MDA and MPO levels. These finding demonstrated that compounds 3i, 3j and 3 l hold significant potential as novel therapeutic agents for ulcerative colitis.

New sesquiterpenoids with neuroprotective effects in vitro and in vivo from the Picrasma chinensis.

Three undescribed sesquiterpenes, designed as pichinenoid A-C (1-3), along with nine known ones (4-12) were isolated from the stems and leaves of Picrasma chinensis. The new isolates including their absolute configurations were elucidated based on extensive spectroscopic methods, single crystal X-ray diffraction, and electronic circular dichroism (ECD) experiments, as well as comparison with literature data. Structurally, compounds 1 and 2 are descending sesquiterpenes, while pichinenoid C (3) is a rare sesquiterpene bearing a 2-methylenebut-3-enoic acid moiety at the C-6 side chain. All the isolated compounds were tested for their neuroprotective effects against the H2O2-induced damage on human neuroblastoma SH-SY5Y cells, and most of them showed moderate neuroprotective activity. Especially, compounds 1, 3-5, and 7 showed a potent neuroprotective effect at 25 or 50 µM. Moreover, the neuroprotective effects of compounds 1 and 4 were tested on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. Results of western blot and immunofluorescence indicated that compound 4 significantly counteract the toxicity of MPTP, and reversed the expression of tyrosine hydroxylase (TH) in substantia nigra (SN) and striatum (ST) of the mouse brain. Interestingly, western blot data suggested compound 4 also enhanced B-cell lymphoma-2 (Bcl-2) and heme oxygenase 1 (HO-1) expressions in the brain tissues from MPTP damaged mouse.

Comparative efficacy of non-invasive brain stimulation for post-stroke cognitive impairment: a network meta-analysis.

BACKGROUND: Non-invasive brain stimulation (NIBS) is a burgeoning approach with the potential to significantly enhance cognition and functional abilities in individuals who have undergone a stroke. However, the current evidence lacks robust comparisons and rankings of various NIBS methods concerning the specific stimulation sites and parameters used. To address this knowledge gap, this systematic review and meta-analysis seek to offer conclusive evidence on the efficacy and safety of NIBS in treating post-stroke cognitive impairment. METHODS: A systematic review of randomized control trials (RCT) was performed using Bayesian network meta-analysis. We searched RCT in the following databases until June 2022: Cochrane Central Register of Controlled Trials (CENTRAL), PUBMED, and EMBASE. We compared any active NIBS to control in terms of improving cognition function and activities of daily living (ADL) capacity following stroke. RESULTS: After reviewing 1577 retrieved citations, a total of 26 RCTs were included. High-frequency (HF)-repetitive transcranial magnetic stimulation (rTMS) (mean difference 2.25 [95% credible interval 0.77, 3.66]) was identified as a recommended approach for alleviating the global severity of cognition. Dual-rTMS (27.61 [25.66, 29.57]) emerged as a favorable technique for enhancing ADL function. In terms of stimulation targets, the dorsolateral prefrontal cortex exhibited a higher ranking in relation to the global severity of cognition. CONCLUSIONS: Among various NIBS techniques, HF-rTMS stands out as the most promising intervention for enhancing cognitive function. Meanwhile, Dual-rTMS is highly recommended for improving ADL capacity.

A Fully Automated Mini-Mental State Examination Assessment Model Using Computer Algorithms for Cognitive Screening.

Background: Rapidly growing healthcare demand associated with global population aging has spurred the development of new digital tools for the assessment of cognitive performance in older adults. Objective: To develop a fully automated Mini-Mental State Examination (MMSE) assessment model and validate the model's rating consistency. Methods: The Automated Assessment Model for MMSE (AAM-MMSE) was an about 10-min computerized cognitive screening tool containing the same questions as the traditional paper-based Chinese MMSE. The validity of the AAM-MMSE was assessed in term of the consistency between the AAM-MMSE rating and physician rating. Results: A total of 427 participants were recruited for this study. The average age of these participants was 60.6 years old (ranging from 19 to 104 years old). According to the intraclass correlation coefficient (ICC), the interrater reliability between physicians and the AAM-MMSE for the full MMSE scale AAM-MMSE was high [ICC (2,1)=0.952; with its 95% CI of (0.883,0.974)]. According to the weighted kappa coefficients results the interrater agreement level for audio-related items showed high, but for items "Reading and obey", "Three-stage command", and "Writing complete sentence" were slight to fair. The AAM-MMSE rating accuracy was 87%. A Bland-Altman plot showed that the bias between the two total scores was 1.48 points with the upper and lower limits of agreement equal to 6.23 points and -3.26 points. Conclusions: Our work offers a promising fully automated MMSE assessment system for cognitive screening with pretty good accuracy.

The role of NLRP6 in the development and progression of neurological diseases.

The nervous system possesses the remarkable ability to undergo changes in order to store information; however, it is also susceptible to damage caused by invading pathogens or neurodegenerative processes. As a member of nucleotide-binding oligomerization domain-like receptor (NLR) family, the NLRP6 inflammasome serves as a cytoplasmic innate immune sensor responsible for detecting microbe-associated molecular patterns. Upon activation, NLRP6 can recruit the adapter protein apoptosis-associated speck-like protein (ASC) and the inflammatory factors caspase-1 or caspase-11. Consequently, inflammasomes are formed, facilitating the maturation and secretion of pro-inflammatory cytokines such as inflammatory factors-18 (IL-18) and inflammatory factors-1ß (IL-1ß). Precise regulation of NLRP6 is crucial for maintaining tissue homeostasis, as dysregulated inflammasome activation can contribute to the development of various diseases. Furthermore, NLRP6 may also play a role in the regulation of extraintestinal diseases. In cells of the brain, such as astrocytes and neurons, NLRP6 inflammasome are also present. Here, the assembly and subsequent activation of caspase-1 mediated by NLRP6 contribute to disease progression. This review aims to discuss the structure and function of NLRP6, explain clearly the mechanisms that induce and activate NLRP6, and explore its role within the central and peripheral nervous system.

Enzyme Catalysis Causes Fluid Flow, Motility, and Directional Transport on Supported Lipid Bilayers.

The dynamic interplay between the composition of lipid membranes and the behavior of membrane-bound enzymes is critical to the understanding of cellular function and viability, and the design of membrane-based biosensing platforms. While there is a significant body of knowledge about how lipid composition and dynamics affect membrane-bound enzymes, little is known about how enzyme catalysis influences the motility and lateral transport on lipid membranes. Using enzyme-attached lipids in supported bilayers (SLBs), we provide direct evidence of catalysis-induced fluid flow that underlies the observed motility on SLBs. Additionally, by using active enzyme patches, we demonstrate the directional transport of tracer particles on SLBs. As expected, enhancing the membrane viscosity by incorporating cholesterol into the bilayer suppresses the overall movement. These are the first steps in understanding diffusion and transport on lipid membranes due to active, out-of-equilibrium processes that are the hallmark of living systems. In general, our study demonstrates how active enzymes can be used to control diffusion and transport in confined 2-D environments.

Clerodane diterpenoids with in-vitro anti-neuroinflammatory activity from the tuberous root of Tinospora sagittata (Menispermaceae).

Twenty-six clerodane diterpenoids have been isolated from T. sagittata, a plant species of traditional Chinese medicine Radix Tinosporae, also named as "Jin Guo Lan". Among them, there are eight previously undescribed clerodane diterpenoids (tinotanoids A-H: 1-8), and 18 known diterpenoids (9-26). The absolute configurations of compounds 1, 2, 5, 8, 13, 17 and 20 were determined by single-crystal X-ray diffraction. Compound 1 is the first example of rotameric clerodane diterpenoid with a γ-lactone ring which is constructed between C-11 and C-17; meanwhile, compounds 3 and 4 are two pairs of inseparable epimers. Compounds 2, 12 and 17 demonstrated excellent inhibitory activity on NO production against LPS-stimulated BV-2 cells with IC50 values of 9.56 ± 0.69, 9.11 ± 0.53 and 11.12 ± 0.70 µM, respectively. These activities were significantly higher than that of the positive control minocycline (IC50 = 23.57 ± 0.92 µM). Moreover, compounds 2, 12 and 17 dramatically reduced the LPS-induced upregulation of iNOS and COX-2 expression. Compounds 2 and 12 significantly inhibited the levels of pro-inflammatory cytokines TNF-α, IL-1ß and IL-6 that were increased by LPS stimulation.

Dynamic Oscillation and Motion of Oil-in-Water Emulsion Droplets.

The interplay of interfacial tensions on droplets results in a range of self-powered motions that mimic those of living systems and serve as a tunable model to understand their complex non-equilibrium behavior. Spontaneous shape deformations and oscillations are crucial features observed in nature but difficult to incorporate in synthetic artificial systems. Here, we report sessile oil-in-water emulsions that exhibit rapid oscillating behavior. The oscillations depend on the nature and concentration of the surfactant, the chemical composition of the oil, and the wettability of the solid substrate. The rapid changes in the contact angle per oscillation are observed using side-view optical microscopy. We propose that the changes in the interfacial tension of the oil droplets is due to the partitioning of the surfactant into the oil phase and the movement of self-emulsified oil out of the parent droplets giving rise to the rhythmic variation in droplet contact-line. The ability to control and understand droplet oscillation can help model similar oscillations in out-of-equilibrium systems in nature and reproduce biomimetic behavior in artificial systems for various applications, such as microfluidic lab-on-a-chip and adaptive materials.

Self-Propelling Macroscale Sheets Powered by Enzyme Pumps.

Nanoscale enzymes anchored to surfaces act as chemical pumps by converting chemical energy released from enzymatic reactions into spontaneous fluid flow that propels entrained nano- and microparticles. Enzymatic pumps are biocompatible, highly selective, and display unique substrate specificity. Utilizing these pumps to trigger self-propelled motion on the macroscale has, however, constituted a significant challenge and thus prevented their adaptation in macroscopic fluidic devices and soft robotics. Using experiments and simulations, we herein show that enzymatic pumps can drive centimeter-scale polymer sheets along directed linear paths and rotational trajectories. In these studies, the sheets are confined to the air/water interface. With the addition of appropriate substrate, the asymmetric enzymatic coating on the sheets induces chemically driven, buoyancy flows that controllably propel the sheet's motion on the air/water interface. The directionality and speed of the motion can be tailored by changing the pattern of the enzymatic coating, type of enzyme, and nature and concentration of the substrate. This work highlights the utility of biocompatible enzymes for generating motion in macroscale fluidic devices and robotics and indicates their potential utility for in vivo applications.

Mechanism of Intestinal Epithelial Absorption and Electrophysiological Regulation of the Shrimp Peptide QMDDQ.

We investigated the absorption mechanism of the shrimp peptide QMDDQ in small intestines, explored its physiological function in inhibiting neuronal hyperactivity, and verified its entry into the brain in vivo to display functional activity. The everted rat sac model and a Caco-2 paracellular absorption monolayer model were used, indicating that QMDDQ has a good absorption capacity with an apparent permeability coefficient (Papp) > 1 × 10-6 cm/s and the absorption of QMDDQ was concentration-dependent. When the concentration of QMDDQ was 1 mM and the transport time was 180 min, the highest absorption concentration of QMDDQ was 41.17 ± 3.48 µM (P < 0.05). The myosin light-chain kinase (MLCK)-specific inhibitor ML-7 and activator MPA, Western blotting, and immunofluorescence results showed that QMDDQ absorption takes place by mediating the MLCK-p-MLCK-MLC signaling pathway, reversibly opening the zonula occludens-1 (ZO-1), occludin in tight junctions (TJs), upregulating claudin-2 expression, and reaching targets through blood to inhibit neuronal overactivity. Results of fluorescence imaging in vivo verified that QMDDQ could enter the brain 4 h after oral administration. The results provide a theoretical foundation for the mechanism of paracellular absorption of active peptides and a starting point for the development of functional foods for Alzheimer's disease intervention.

Chemical Profiling, Quantitation, and Bioactivities of Ginseng Residue.

Ginseng residue is a by-product stemming from the commercial extraction of ginsenosides. To assess the disparities between ginseng residue and ginseng tablet, we employed the ultra-high-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry (UPLC-Q-TOF/MS) technique for sample analysis. The analyses revealed the presence of 39 compounds in both ginseng residue and ginseng tablets. Subsequently, the contents of total ginsenosides and total ginseng polysaccharides in the ginseng residue and ginseng tablet were determined. The results indicate that while only a small fraction of ginsenosides remained in the ginseng residue, a significant amount of polysaccharides was retained. Furthermore, our evaluation encompassed the antioxidant activities of both ginseng residue and ginseng tablets. Notably, ginseng residue exhibited robust antioxidant effects, thereby showcasing its potential for recycling as a functional food raw material.

Relationship between serum 25-hydroxyvitamin D concentrations and blood pressure among US adults without a previous diagnosis of hypertension: evidence from NHANES 2005-2018.

Background: There are various cross-sectional studies that concluded that vitamin D is associated with blood pressure, but randomized controlled studies have not yielded consistent conclusions. Considering many limitations indeed, our study aimed to examine whether concentrations of 25(OH)D are inversely associated with blood pressure in people without a previous diagnosis of hypertension. Method: We analyzed data from the 2005-2018 National Health and Nutrition Examination Survey. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by applying multivariable logistic regression models. The dose-response relationship was assessed by means of restricted cubic spline regression, and stratification analyses were employed to test the consistency between the subgroups. Results: Of 17,467 participants aged ≥ 20 years without a previous diagnosis of hypertension, 4,769 had higher blood pressure. Compared with individuals whose 25(OH)D levels were in the bottom quartile (<44.3 nnol/L), adjusting for multiple confounders, the ORs for higher blood pressure were 0.90(95%CI 0.78, 1.05), 0.85(95%CI 0.72, 0.99), and 0.86(95%CI 0.72, 1.02), respectively (P for trend = 0.096). Furthermore, as a continuous variable, 25(OH)D concentrations were non-linearly associated with an increased risk of hypertension (P < 0.001). The interaction between the sleeplessness subgroup and higher blood pressure was significant (P = 0.042). Conclusion: In adults without a previous diagnosis of hypertension in the United States, concentrations of 25(OH)D were inversely associated with higher blood pressure when it was <84 nmol/L.

Pressure and temperature dual-parameter optical sensor based on the MIM waveguide structure coupled with two T-shaped cavities.

This paper elaborates on the design and simulation of a multifunctional optical sensor that features simultaneous detection of pressure and temperature, which is based on the metal-insulator-metal waveguide structure with two T-shaped resonant cavities. Depending on the simulation findings, pressure and temperature can be measured separately by two T-shaped cavities at different Fano resonance wavelengths. As the pressure applied to the upper T-shaped cavity increases, the resonance wavelength first shifts linearly due to the slight deformation of the cavity, and the maximum pressure sensitivity reaches 12.48 nm/MPa. After the pressure exceeds a threshold, the relationship between pressure and resonance wavelength transforms into a quadratic polynomial. In the lower T-shaped cavity, solid polydimethylsiloxane is sealed as a thermal-sensitive material, effectively preventing material overflow brought on by structural micro-vibration under pressure, and its high thermo-optical coefficient prompts a temperature sensitivity of 0.36 nm/°C. Furthermore, by optimizing the choice of Fano resonances, pressure and temperature can be sensed independently without mutual interference. The designed sensor provides extensive application possibilities for scenarios where multiparameter monitoring is required.

High-average-power single-longitudinal-mode pulse laser based on a pulse saturation seed-injection locking OPO.

A high-average-power and narrow-linewidth nanosecond (ns) pulse 824 nm laser is a crucial source for the generation of deep-ultraviolet (DUV) 248 nm laser by means of the sum-frequency process with the 354.5 nm laser. To this purpose, in this Letter, we present a seed-injection-locked high-average-power ns pulse single-longitudinal-mode (SLM) 824 nm laser. By developing a novel, to the best of our knowledge, pulse-saturated seed-injection locking method, disturbance of the pulse laser on the locking of the injected seed laser is successfully eliminated. As a result, the output power of 824 nm laser is up to 21.2 W at the incident pump power of 48.1 W, and the pulse width is 15 ns. Especially, the signal-to-noise ratio of the detected modulated sideband signal exceeds 28 dB, which ensures that the achieved linewidth of the 824 nm laser is as narrow as 38.8 MHz. These results demonstrate the potential of the proposed pulse saturation seed-injection locking OPO cavity for high-power and narrow-linewidth laser applications.

Tinopanoids K-T, clerodane diterpenoids with anti-inflammatory activity from Tinospora crispa.

A total of 17 structurally diverse clerodane diterpenoids, including ten undescribed clerodane diterpenoids (tinopanoids K-T, 1-10) and seven known compounds (11-17), were isolated from the vines and leaves of Tinospora crispa. Compound 3 has not only bear the dominant substituents of γ-hydroxy-α, ß-unsaturated-γ-lactone with anti-inflammatory activity, but also a ternary epoxy structure at C-3/C-4. The planar structures and relative configurations of the clerodane diterpenoids were elucidated by spectroscopic data interpretation. The absolute configurations of compounds 1, 4, 8 and 13 were determined by single-crystal X-ray crystallographic, while that of compound 3 was determined using computed ECD data and single crystal X-ray diffraction of related p-bromobenzoate ester (3a). Subsequently, all compounds were evaluated for their inhibitory effect on nitric oxide (NO) production of LPS-activated BV-2 cells, and compounds 3 and 8 exhibited better NO inhibitory potency, with IC50 values of 5.6 and 13.8 µM than the positive control minocycline (Mino, IC50 = 22.9 µM). The corresponding results of western blot analysis and qRT-PCR revealed that compound 3 can significantly inhibit the inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) protein expressions, mRNA levels of pro-inflammatory cytokins of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6) and interleukin 1ß (IL-1ß). The underlying mechanism by which compound 3 exerted anti-neuroinflammatory effects was investigated by western blot and immunofluorescence assay, which suggested compound 3 inhibited LPS induced neuroinflammation via the suppression of toll-like receptor 4 (TLR4) dependent Signal Transducer and Activator of Transcription 3 (Stat3) and mitogen-activated protein kinase (MAPK) signaling pathways, and the activation of Heme Oxygenase-1 (HO-1) mediated signals.