Schisandrin B, a dual positive allosteric modulator of GABAA and glycine receptors, alleviates seizures in multiple mouse models.

Epilepsy is a prevalent and severe neurological disorder and approximately 30% of patients are resistant to existing medications. It is of utmost importance to develop alternative therapies to treat epilepsy. Schisandrin B (SchB) is a major bioactive constituent of Schisandra chinensis (Turcz.) Baill and has multiple neuroprotective effects, sedative and hypnotic activities. In this study, we investigated the antiseizure effect of SchB in various mouse models of seizure and explored the underlying mechanisms. Pentylenetetrazole (PTZ), strychnine (STR), and pilocarpine-induced mouse seizure models were established. We showed that injection of SchB (10, 30, 60 mg/kg, i.p.) dose-dependently delayed the onset of generalized tonic-clonic seizures (GTCS), reduced the incidence of GTCS and mortality in PTZ and STR models. Meanwhile, injection of SchB (30 mg/kg, i.p.) exhibited therapeutic potential in pilocarpine-induced status epilepticus model, which was considered as a drug-resistant model. In whole-cell recording from CHO/HEK-239 cells stably expressing recombinant human GABAA receptors (GABAARs) and glycine receptors (GlyRs) and cultured hippocampal neurons, co-application of SchB dose-dependently enhanced GABA or glycine-induced current with EC50 values at around 5 µM, and application of SchB (10 µM) alone did not activate the channels in the absence of GABA or glycine. Furthermore, SchB (10 µM) eliminated both PTZ-induced inhibition on GABA-induced current (IGABA) and strychnine (STR)-induced inhibition on glycine-induced current (Iglycine). Moreover, SchB (10 µM) efficiently rescued the impaired GABAARs associated with genetic epilepsies. In addition, the homologous mutants in both GlyRs-α1(S267Q) and GABAARs-α1(S297Q)ß2(N289S)γ2L receptors by site-directed mutagenesis tests abolished SchB-induced potentiation of IGABA and Iglycine. In conclusion, we have identified SchB as a natural positive allosteric modulator of GABAARs and GlyRs, supporting its potential as alternative therapies for epilepsy.

Tetraanionic arachno-Carboranyl Ligand Imparts Strong Axiality to Terbium(III) Single-Molecule Magnets.

A family of fully sandwiched arachno-lanthanacarborane complexes formulated as {η6 -[µ-1,2-[o-C6 H4 (CH2 )2 ]-1,2-C2 B10 H10 ]2 Ln}{Li5 (THF)10 } (Ln=Tb, Dy, Ho, Er, Y) is successfully synthesized, where the "carbons-adjacent" carboranyl ligand (arachno-R2 -C2 B10 H10 4- ) bears four negative charges and coordinates to the central lanthanide ions using the hexagonal η6 C2 B4 face. Thus, the central lanthanide cations are pseudo-twelve-coordinate and have an approximate pseudo-D6h symmetry or hexagonal-prismatic geometry. As the crystal field effect imparted by this geometry is still unknown, we thoroughly investigated the magnetic properties of this series of complexes and found that the crystal field imposed by this ligand causes a relation of Tb>Dy>Ho>Er for the energy gaps between the ground and the first excited states, which is of striking resemblance to the ferrocenophane and phthalocyanine ligands although the latter two ligands give disparate local coordination geometries. Moreover, the effective energy barrier to magnetization reversal of 445(10) K, the observable hysteresis loop up to 4 K and the relaxation time of the yttrium-diluted sample reaching 193(17) seconds at 2 K under an optimized field for the Tb analogue of this family of arachno-lanthanacarborane complexes, render a new benchmark for Tb3+ -based single-molecule magnets.

Dysprosiacarboranes as Organometallic Single-Molecule Magnets.

The dicarbollide ion, nido-C2 B9 H11 2- is isoelectronic with cyclopentadienyl. Herein, we make dysprosiacarboranes, namely [(C2 B9 H11 )2 Ln(THF)2 ][Na(THF)5 ] (Ln=Dy, 1Dy) and [(THF)3 (µ-H)3 Li]2 [{η5 -C6 H4 (CH2 )2 C2 B9 H9 }Dy{η2 :η5 -C6 H4 (CH2 )2 C2 B9 H9 }2 Li] 3Dy and show that dicarbollide ligands impose strong magnetic axiality on the central DyIII ion. The effective energy barrier (Ueff ) for the loss of magnetization can be varied by the substitution pattern on the dicarbollide. This finding is demonstrated by comparing complexes of nido-C2 B9 H11 2- and nido-[o-xylylene-C2 B9 H9 ]2- , which show a Ueff of 430(5) K and 804(7) K, respectively. The blocking temperature defined by the open hysteresis temperature of 3Dy reaches 6.8 K. Moreover, the linear complex [Dy(C2 B9 H11 )2 ]- is predicted to have comparable properties with the linear [Dy(CpMe3 )2 ]+ complex. As such, carboranyl ligands and their derivatives may provide a new type of organometallic ligand for high-performance single-molecule magnets.

Mosquitocidal and Oviposition Repellent Activities of the Extracts of Seaweed Bryopsis pennata on Aedes aegypti and Aedes albopictus.

The ever-increasing threat from infectious diseases and the development of insecticide resistance in mosquito populations drive the global search for new natural insecticides. The aims of this study were to evaluate the mosquitocidal activity of the extracts of seaweed Bryopsis pennata against dengue vectors Aedes aegypti and Aedes albopictus, and determine the seaweed's toxic effect on brine shrimp nauplii (as a non-target organism). In addition, the chemical compositions of the active larvicidal extract and fraction were analyzed by using liquid chromatography-mass spectrometry (LC-MS). Chloroform extract exhibited strong ovicidal activity (with LC50 values of 229.3 and 250.5 µg/mL) and larvicidal activity against Ae. aegypti and Ae. albopictus. The larvicidal potential of chloroform extract was further ascertained when its A7 fraction exhibited strong toxic effect against Ae. aegypti (LC50 = 4.7 µg/mL) and Ae. albopictus (LC50 = 5.3 µg/mL). LC-MS analysis of the chloroform extract gave a tentative identification of 13 compounds; Bis-(3-oxoundecyl) tetrasulfide was identified as the major compound in A7 fraction. Methanol extract showed strong repellent effect against female oviposition, along with weak adulticidal activity against mosquito and weak toxicity against brine shrimp nauplii. The mosquitocidal results of B. pennata suggest further investigation for the development of effective insecticide.

The major bioactive components of seaweeds and their mosquitocidal potential.

Seaweeds are one of the most widely studied natural resources for their biological activities. Novel seaweed compounds with unique chemical structures have been reported for their pharmacological properties. The urge to search for novel insecticidal compound with a new mode of action for development of botanical insecticides supports the relevant scientific research on discovering the bioactive compounds in seaweeds. The mosquitocidal potential of seaweed extracts and their isolated compounds are documented in this review paper, along with the discussion on bioactivities of the major components of seaweeds such as polysaccharides, phenolics, proteins, terpenes, lipids, and halogenated compounds. The effects of seaweed extracts and compounds toward different life stages of mosquito (egg, larva, pupa, and adult), its growth, development, and reproduction are elaborated. The structure-activity relationships of mosquitocidal compounds are discussed to extrapolate the possible chemical characteristics of seaweed compounds responsible for insecticidal properties. Furthermore, the possible target sites and mode of actions of the mosquitocidal seaweed compounds are included in this paper. The potential synergistic effects between seaweeds and commercial insecticides as well as the toxic effects of seaweed extracts and compounds toward other insects and non-target organisms in the same habitat are also described. On top of that, various factors that influence the mosquitocidal potential of seaweeds, such as abiotic and biotic variables, sample preparation, test procedures, and considerations for a precise experimental design are discussed. The potential of active seaweed extracts and compounds in the development of effective bioinsecticide are also discussed.

Development of prediction model of low anterior resection syndrome for colorectal cancer patients after surgery based on machine-learning technique.

BACKGROUND: Low anterior resection syndrome (LARS) is a common postoperative complication in patients with colorectal cancer, which seriously affects their postoperative quality of life. At present, the aetiology of LARS is still unclear, but some risk factors have been studied. Accurate prediction and early management of medical intervention are keys to improving the quality of life of such high-risk patients. OBJECTIVES: Based on machine-learning methods, this study used the follow-up results of postoperative patients with colorectal cancer to develop prediction models for LARS and conducted a comparative analysis between the different models. METHODS: A total of 382 patients diagnosed with colorectal cancer and undergoing surgery at West China Hospital from April 2017 to December 2020 were retrospectively selected as the development cohort. Logistic regression, support vector machine, decision tree, random forest and artificial neural network algorithms were used to construct the prediction models of the obtained dataset. The models were internally validated using cross-validation. The area under the curve and Brier score measures were used to evaluate and compare the differentiation and calibration degrees of the models. The sensitivity, specificity, positive predictive value and negative predictive value of the different models were described for clinical use. RESULTS: A total of 342 patients were included, the incidence of LARS being 47.4% (162/342) during the six-month follow-up. After feature selection, the factors influencing the occurrence of LARS were found to be location, distance, diverting stoma, exsufflation and surgical type. The prediction models based on five machine-learning methods all showed acceptable performance. CONCLUSIONS: The five models developed based on the machine-learning methods showed good prediction performance. However, considering the simplicity of clinical use of the model results, the logistic regression model is most recommended. The clinical applicability of these models will also need to be evaluated with external cohort data.

Intelligent cyclic fire warning sensor based on hybrid PBO nanofiber and montmorillonite nanocomposite papers decorated with phenyltriethoxysilane.

An abundance of early warning graphene-based nano-materials and sensors have been developed to avoid and prevent the critical fire risk of combustible materials. However, there are still some limitations that should be addressed, such as the black color, high-cost and single fire warning response of graphene-based fire warning materials. Herein, we report an unexpected montmorillonite (MMT)-based intelligent fire warning materials that have excellent fire cyclic warning performance and reliable flame retardancy. Combining phenyltriethoxysilane (PTES) molecules, poly(p-phenylene benzobisoxazole) nanofiber (PBONF), and layers of MMT to form a silane crosslinked 3D nanonetwork system, the homologous PTES decorated MMT-PBONF nanocomposites are designed and fabricated via a sol-gel process and low temperature self-assembly method. The optimized nanocomposite paper shows good mechanical flexibility (good recovery after kneading or bending process), high tensile strength of âˆ¼81 MPa and good water resistance. Furthermore, the nanocomposite paper exhibits high-temperature flame resistance (almost unchanged structure and size after 120 s combustion), sensitive flame alarm response (∼0.3 s response once exposure onto a flame), cyclic fire warning performance (>40 cycles), and adaptability to complex fire situations (several fire attack and evacuation scenarios), showing promising applications for monitoring the critical fire risk of combustible materials. Therefore, this work paves a rational way for design and fabrication of MMT-based smart fire warning materials that combine excellent flame shielding and sensitive fire alarm functions.

Equatorial coordination optimization for enhanced axiality of mononuclear Dy(iii) single-molecule magnets.

We present a controlled synthetic route to optimize the equatorial coordination environment of three Dy(iii) borohydride complexes: Dy(BH4)3(THF)3 (1), [Dy(BH4)2(THF)5][BPh4] (2) and [Dy(BH4)2(18-C-6)][Na(THF)2(18-C-6)][BPh4]2 (3) (THF = tetrahydrofuran, BPh4- = tetraphenyl borate, 18-C-6 = 18-crown-6-ether), which have the same axial coordination environment, while different equatorial sites. Alteration of the coordination environment on the equatorial sites leads to a significant change in their magnetic properties. In the absence of the dc field, complex 1 with three THF molecules and one BH4- ligand in the equatorial plane shows no single-molecule magnet (SMM) behaviour, complex 2 having five THF molecules at equatorial sites displays small tails of out-of-phase (χ'') signals, and complex 3 containing one 18-C-6 with six O atoms in the equatorial plane exhibits χ'' signals at higher temperatures. These results show the optimization of the equatorial coordination environment of Dy(iii) mononuclear single-molecule magnets.

A dichlorido-bridged dinuclear Dy(iii) single-molecule magnet with an effective energy barrier larger than 600 K.

We report a dichlorido-bridged dinuclear dysprosium(iii) single-molecule magnet [Dy(Cy2N)2(µ-Cl)(THF)]2 which shows an effective energy barrier for magnetization reversal (Ueff) of ca. 623 K. This is by far the largest Ueff barrier for any chlorido-bridged lanthanide single-molecule magnet. We observe two relaxation processes with near-identical temperature dependencies, one of which disappears upon magnetic dilution. We suspect that these two processes are the isolated and coupled relaxation processes.

Field- and temperature-dependent quantum tunnelling of the magnetisation in a large barrier single-molecule magnet.

Understanding quantum tunnelling of the magnetisation (QTM) in single-molecule magnets (SMMs) is crucial for improving performance and achieving molecule-based information storage above liquid nitrogen temperatures. Here, through a field- and temperature-dependent study of the magnetisation dynamics of [Dy(tBuO)Cl(THF)5][BPh4]·2THF, we elucidate the different relaxation processes: field-independent Orbach and Raman mechanisms dominate at high temperatures, a single-phonon direct process dominates at low temperatures and fields >1 kOe, and a field- and temperature-dependent QTM process operates near zero field. Accounting for the exponential temperature dependence of the phonon collision rate in the QTM process, we model the magnetisation dynamics over 11 orders of magnitude and find a QTM tunnelling gap on the order of 10-4 to 10-5 cm-1. We show that removal of Dy nuclear spins does not suppress QTM, and argue that while internal dipolar fields and hyperfine coupling support QTM, it is the dynamic crystal field that drives efficient QTM.

Larvicidal activity, inhibition effect on development, histopathological alteration and morphological aberration induced by seaweed extracts in Aedes aegypti (Diptera: Culicidae).

OBJECTIVE: To investigate the larvicidal activity, inhibition effect on development, histopathological alteration and morphological aberration induced by the extracts derived from seaweeds Bryopsis pennata (B. pennata), Sargassum binderi (S. binderi) and Padina australis in Aedes aegypti (Ae. aegypti) larvae and to characterize the phytochemical components of the three seaweeds. METHODS: Larvicidal activity of the seaweeds towards the larvae of Ae. aegypti was determined according to WHO. The inhibition effect of seaweeds was assessed by determining the mortality, adult emergence rate, larval and pupa duration of the treated larvae. Histopathological effect on midgut epithelium of larvae and morphological aberration induced by the methanol extracts were examined. Phytochemical analysis was done to determine the presence of alkaloids, saponins, steroids and terpenoids in the seaweeds. RESULTS: Chloroform partition of B. pennata extract exhibited the strongest larvicidal activity (LC50 = 82.55 µg/mL), followed by methanol extract of B. pennata (LC50 = 160.07 µg/mL) and chloroform partition of S. binderi extract (LC50 = 192.43 µg/mL). The methanol extract of S. binderi exhibited the strongest effect on prolongation of larval period (1.5-fold longer as compared to control) and resulted in strongest inhibition effect in adult emergence (98.67%). The histopathological study showed that larvae treated with seaweed extracts had cytopathological alteration of the midgut epithelium. The morphological observation revealed that the anal papillae and terminal spiracles of larvae were the common sites of aberrations. CONCLUSIONS: The study provided information on various effects of seaweed extracts on Ae. aegypti. Further investigation on identifying the active compounds and their mechanisms of action is recommended.