Reaction Center Shifting in Partially Fluorinated Electrolytes for Robust Lithium Metal Battery.

The strategic formulation of a compatible electrolyte plays a pivotal role in extending the longevity of lithium-metal batteries (LMBs). Here, we present findings on a partially fluorinated electrolyte distinguished by a subdued solvation affinity towards Li+ ions and a concentrated anion presence within the primary solvation layer. This distinctive solvation arrangement redirects the focal points of reactions from solvent molecules to anions, facilitating the predominant involvement of anions in the creation of a LiF-enriched solid-electrolyte interphase (SEI). Electrochemical assessments showcase effective Li+ transport kinetics, diminished overpotential polarization for Li nucleation, and prolonged cycling durability in Li||Li cells employing the partially fluorinated electrolyte. When tested in Li||NCM811 cells, the designed electrolyte delivers a capacity retention of 89.30% and exhibits a high average Coulombic efficiency of 99.80% over 100 cycles with a charge-potential cut-off of 4.6 V vs. Li/Li+ under the current density of 0.4 C. Furthermore, even at a current density of 1C, the cells maintain 81.90% capacity retention and a high average Coulombic efficiency of 99.40% after 180 cycles. This work underscores the significance of weak-solvation interaction in partially fluorinated electrolytes and highlights the crucial role of solvent structure in enabling the long-term stability and high-energy density of LMBs.

Seeding Atomic Silver into Internal Lattice Sites of Transition Metal Oxide for Advanced Electrocatalysis.

Transition metal oxides (TMOs) are widely studied for loading of various catalysts due to their low cost and high structure flexibility. However, the prevailing close-packed nature of most TMOs crystals has restricted the available loading sites to surface only, while their internal bulk lattice remains unactuated due to the inaccessible narrow space that blocks out most key reactants and/or particulate catalysts. Herein, using tunnel-structured MnO2, this study demonstrates how TMO's internal lattice space can be activated as extra loading sites for atomic Ag in addition to the conventional surface-only loading, via which a dual-form Ag catalyst within MnO2 skeleton is established. In this design, not only faceted Ag nanoparticles are confined onto MnO2 surface by coherent lattice-sharing, Ag atomic strings are also seeded deep into the sub-nanoscale MnO2 tunnel lattice, enriching the catalytically active sites. Tested for electrochemical CO2 reduction reaction (eCO2RR), such dual-form catalyst exhibits a high Faradaic efficiency (94%), yield (67.3 mol g-1 h-1) and durability (≈48 h) for CO production, exceeding commercial Ag nanoparticles and most Ag-based electrocatalysts. Theoretical calculations further reveal the concurrent effect of such dual-form catalyst featuring facet-dependent eCO2RR for Ag nanoparticles and lattice-confined eCO2RR for Ag atomic strings, inspiring the future design of catalyst-substrate configuration.

Genetic analysis of isolated methylmalonic acidemia in Henan, China: c.1663G>A variant of MMUT prevalent in the Henan population.

BACKGROUND: Methylmalonic acidemia (MMA) is the most common organic acidemia in China, and isolated MMA accounts for approximately 30 % of all types of MMA. Common variants of the MMUT gene vary greatly around the world. The present study aims to determine the high-frequency and novel genetic variants of the MMUT gene in the Henan population of China and evaluate the prognosis of patients carrying the c.1663G>A (p.Ala555Thr) variant. METHODS: We performed next-generation sequencing for 41 patients with isolated MMA screened by tandem mass spectrometry (MS/MS) and analysed the genetic results. We also evaluated the prognosis of patients with the c.1663G>A variant. We used Jalview software for multispecies sequence alignment and Missense3D and DynaMut to predict the protein function of the detected novel variants. RESULTS: A total of 43 variants from 41 patients with isolated MMA were detected, of which c.1663G>A (14.63 %), c.729_730insTT (10.98 %), and c.1106G>A (8.53 %) are high-frequency variants of the MMUT gene in the Henan population. The patients carrying the c.1663G>A variant tended to be responsive to vitamin B12, have a low mortality rate. We also identified 5 novel variants (c.479C>T, c.811G>C, c.965T>A, c.1142G>A and c.1667C>T). CONCLUSION: The rare variant c.1663G>A is prevalent in the Henan population, and infants with this variant tend to have good prognosis. Our findings, especially novel variants, will help broaden the spectrum of genetic variants and facilitate clinical diagnosis and genetic counselling for affected families.

Metabolomic insights into the effect of chickpea protein hydrolysate on the freeze-thaw tolerance of industrial yeasts.

The use of frozen dough is an intensive food-processing practice that contributes to the development of chain operations in the bakery industry. However, the fermentation activity of yeasts in frozen dough can be severely damaged by freeze-thaw stress, thereby degrading the final bread quality. In this study, chickpea protein hydrolysate significantly improved the quality of steamed bread made from frozen dough while enhancing the yeast survival rate and maintaining yeast cell structural integrity under freeze-thaw stress. The mechanism underlying this protective role of chickpea protein hydrolysate was further investigated by untargeted metabolomics analysis, which suggested that chickpea protein hydrolysate altered the intracellular metabolites associated with central carbon metabolism, amino acid synthesis, and lipid metabolism to improve yeast cell freeze-thaw tolerance. Therefore, chickpea protein hydrolysate is a promising natural antifreeze component for yeast cryopreservation in the frozen dough industry.

Toxicity risk assessment of flupyradifurone for the predatory pirate bug, Orius strigicollis (Poppius) (Heteroptera: Anthocoridae), a biological control agent of Diaphorina citri Kuwayama (Hemiptera: Liviidae).

Diaphorina citri Kuwayama (Hemiptera: Liviidae), commonly known as the Asian citrus psyllid, is a prominent citrus tree pest that serves as a vector for Asian huanglongbing (HLB). The substantial costs incurred by the citrus industry as a consequence of this disease have spurred considerable interest in the combined control of D. citri using insecticides and natural enemies. However, the successful implementation of such integrated pest management strategies is dependent on ensuring the compatibility of using natural enemies in the presence of insecticides. In this regard, we evaluated the lethal and sublethal effects of flupyradifurone on Orius strigicollis (Poppius) (Heteroptera: Anthocoridae), an important predatory biological control agent, in which we assessed the risk of exposure to flupyradifurone under both in- and off-field scenario. The median lethal rate (LR50) value of flupyradifurone against O. strigicollis (9.089 g a.i. ha-1), was found to be significantly lower than the maximum field recommended rate (MFRR, 170 g a.i. ha-1). Additionally, at 0.254 g a.i. ha-1, flupyradifurone was established to significantly prolong the developmental duration of O. strigicollis from the first to third instar nymphs. Although we detected no significant difference in the survival of immature O. strigicollis subjected to 0.064 g a.i. ha-1 and control treatments, survival was significantly lower in 0.127 and 0.254 g a.i. ha-1 treatments. Moreover, whereas there were no significant differences in adult longevity between the 0.127 g a.i. ha-1 and control treatments, we recorded a significant reduction in fecundity. Furthermore, there were reductions in peak life expectancy, reproductive value, finite rate of increase, intrinsic rate of increase, and net reproduction rate in response to exposure to increasing flupyradifurone rate. Additionally, at 0.127 g a.i. ha-1, the mean generation time was significantly longer than that under control conditions. Following simulated exposure to flupyradifurone for 100 days, population of O. strigicollis in the 0.064 g a.i. ha-1 and control treatments were found to be significantly larger than those exposed to 0.127 g a.i. ha-1. On the basis on LR50 evaluations, whereas the risk of exposure risk was unacceptable for O. strigicollis under in-field scenario, it remained acceptable off-field. Nonetheless, the sublethal effect of prolonged exposure to residual flupyradifurone could pose an unacceptable off-field risk to O. strigicollis (e.g., in adjacent habitats). Consequently, the effects of different flupyradifurone exposure scenarios on O. strigicollis should be thoroughly assessed, and reducing the dosage of flupyradifurone could be advantageous for the control of D. citri when combine with augmentative release of O. strigicollis.

Monodispersed Sub-1 nm Inorganic Cluster Chains in Polymers for Solid Electrolytes with Enhanced Li-Ion Transport.

The organic-inorganic interfaces can enhance Li+ transport in composite solid-state electrolytes (CSEs) due to the strong interface interactions. However, Li+ non-conductive areas in CSEs with inert fillers will hinder the construction of efficient Li+ transport channels. Herein, CSEs with fully active Li+ conductive networks are proposed to improve Li+ transport by composing sub-1 nm inorganic cluster chains and organic polymer chains. The inorganic cluster chains are monodispersed in polymer matrix by a brief mixed-solvent strategy, their sub-1 nm diameter and ultrafine dispersion state eliminate Li+ non-conductive areas in the interior of inert fillers and filler-agglomeration, respectively, providing rich surface areas for interface interactions. Therefore, the 3D networks connected by the monodispersed cluster chains finally construct homogeneous, large-scale, continuous Li+ fast transport channels. Furthermore, a conjecture about 1D oriented distribution of organic polymer chains along the inorganic cluster chains is proposed to optimize Li+ pathways. Consequently, the as-obtained CSEs possess high ionic conductivity at room temperature (0.52 mS cm-1 ), high Li+ transference number (0.62), and more mobile Li+ (50.7%). The assembled LiFePO4 /Li cell delivers excellent stability of 1000 cycles at 0.5 C and 700 cycles at 1 C. This research provides a new strategy for enhancing Li+ transport by efficient interfaces.

Fluorinated Nonflammable In Situ Gel Polymer Electrolyte for High-Voltage Lithium Metal Batteries.

Rechargeable lithium metal batteries (LMBs) offer excellent opportunities for applications requiring high-energy-density battery systems. So far, it has received a lot of interest in pairing higher-energy-density high-voltage nickel-rich cathodes. Here, fluorinated solvents were used instead of the usual carbonate solvents to prepare gel polymer electrolytes (FGPE) by in situ polymerization of polymers introducing the fluorine-containing groups. Theoretically and experimentally, FGPE has proven to be ultra-compatible with the lithium metal anode and LiNi0.8Co0.1Mn0.1O2 cathode. A stable plating/stripping process of over 2000 h can be achieved for symmetrical lithium cells using FGPE. The Li||FGPE||NCM811 cell has a longer cycle life at a high voltage (4.5 V). In addition, the zero self-extinguishing time indicates that the FGPE has sufficient safety. In summary, the design of this electrolyte provides ideas to improve the safety and energy density of LMBs.

Identification and characterization of forced degradation products of 5-hydroxymethyl-2-furaldehyde (5-HMF) by HPLC, LC-LTQ/Orbitrap and NMR studies.

5-Hydroxymethyl-2-furaldehyde (5-HMF) is a kind of aldehyde compound with highly active furan ring, which is generated by dehydration of glucose, fructose, and other monosaccharides. It widely exists in drugs, foods, health products, cosmetics, and traditional Chinese medicine preparations with high sugar content. Due to the toxicity, the concentration of 5-HMF was always monitored to identify non-conformities and adulteration, as well as ensure the process efficiency, traceability and safety in foods or drugs in the pharmacopoeias of various countries. Herein, a comprehensive forced degradation study was performed to characterize the degradation products (DPs) of 5-HMF under hydrolytic (neutral, acidic, and alkaline) degradation, oxidative, thermal, humidity, and photolytic degradation conditions. A total of five degradants were identified, and two of them (DP-3 and DP-5) were novel DPs first reported in our study. Major DPs (i.e., DP-1 and DP-2) with relatively high peak areas were isolated using semi-preparative HPLC and characterized by LC-LTQ/Orbitrap and NMR. 5-HMF was only stable in alkaline hydrolysis condition. In addition, the degradation pathways and mechanism of these DPs were also explained using LC-LTQ/Orbitrap. In silico toxicity and metabolism behavior of the DPs were evaluated using Derek Nexus and Meteor Nexus software, respectively. The predicted toxicity data indicated that both the drug 5-HMF and its DPs bear the potential of hepatotoxicity, mutagenicity, chromosome damage, and skin sensitisation. Our research may be beneficial for the quality control and suitable storage conditions of 5-HMF.

Allelic phenotype prediction of phenylketonuria based on the machine learning method.

BACKGROUND: Phenylketonuria (PKU) is caused by mutations in the phenylalanine hydroxylase (PAH) gene. Our study aimed to predict the phenotype using the allelic genotype. METHODS: A total of 1291 PKU patients with 623 various variants were used as the training dataset for predicting allelic phenotypes. We designed a common machine learning framework to predict allelic genotypes associated with the phenotype. RESULTS: We identified 235 different mutations and 623 various allelic genotypes. The features extracted from the structure of mutations and graph properties of the PKU network to predict the phenotype of PKU were named PPML (PKU phenotype predicted by machine learning). The phenotype of PKU was classified into three different categories: classical PKU (cPKU), mild PKU (mPKU) and mild hyperphenylalaninemia (MHP). Three hub nodes (c.728G>A for cPKU, c.721 for mPKU and c.158G>A for HPA) were used as each classification center, and 5 node attributes were extracted from the network graph for machine learning training features. The area under the ROC curve was AUC = 0.832 for cPKU, AUC = 0.678 for mPKU and AUC = 0.874 for MHP. This suggests that PPML is a powerful method to predict allelic phenotypes in PKU and can be used for genetic counseling of PKU families. CONCLUSIONS: The web version of PPML predicts PKU allele classification supported by applicable real cases and prediction results. It is an online database that can be used for PKU phenotype prediction http://www.bioinfogenetics.info/PPML/ .

[Analysis of GCH1 gene variant in a consanguineous Chinese pedigree affected with tetrahydrobiopterin deficiency].

OBJECTIVE: To explore the genetic basis for a child featuring tetrahydrobiopterin deficiency and global developmental delay. METHODS: Clinical and laboratory examinations were carried out for the child. Genomic DNA of the patient was subjected to high-throughput sequencing to identify genetic variants associated with hyperphenylalaninemia. Candidate variants were verified by Sanger sequencing. RESULTS: The result of blood tandem mass spectrometry showed that the Phenylalanine in the blood was 642.7 µmol/l, and the ratio of Phenylalanine/Tyrosine was 5.42. Analysis of urinary pterin: neopterin 0.09 mmol/mol Cr, biopterin 0.04 mmol/mol Cr, biopterin% 77%, which suggested tetrahydrobiopterin deficiency. The parents of the proband were first cousins. DNA sequencing revealed that the proband has harbored homozygous c.353A>T variants in exon 2 of the GCH1 gene, for which his great grandmother, grandfather, mother, uncle, father and elder brother were heterozygous carriers with normal phenotype and no clinical symptoms associated with dopa responsive dystonia. CONCLUSION: The homozygous c.353A>T variant of the GCH1 gene probably underlay the tetrahydrobiopterin deficiency in this pedigree of consanguineous marriage.

Identification of phenylketonuria patient genotypes using single-gene full-length sequencing.

BACKGROUND: Phenylketonuria (PKU) is a common, autosomal recessive inborn error of metabolism caused by PAH gene variants. After routine genetic analysis methods were applied, approximately 5% of PKU patients were still not diagnosed with a definite genotype. METHODS: In this study, for the first time, we identified PKU patients with unknown genotypes via single-gene full-length sequencing. RESULTS: The detection rate of PKU genotype increased from 94.6 to 99.4%, an increase of approximately 5%. The variants c.1199 + 502A > T and 1065 + 241C > A were found at a high frequency in Chinese PKU patients. CONCLUSION: Our study suggest that single-gene full-length sequencing is a rapid, efficient and cost-effective tool to improve the genotype detection rate of PKU patients. Moreover, we provides additional case data to support pathogenicity of deep intronic variants in PAH.

Clinical effect of rigid gas permeable (RGP) contact lens in improving vision and controlling myopia progression of unilateral high myopic children.

BACKGROUND: The aim of this study was to explore the clinical effect of the RGP contact lens in improving vision and controlling myopia progression of the unilateral high myopic children. METHODS: In this retrospective analysis case series study, we analyzed the clinical data for 23 subjects with unilateral high myopic children under 6 years old, with the spherical equivalent refractive error of the myopic eye from -5.0 D to -12.0 D, who were enrolled from the outpatient clinic at Beijing Tongren Hospital, China. Fourteen subjects could successfully fit the RGP contact lens, and nine subjects used the spectacle lens. Complete ocular examination was performed at the first visit at the clinic and every three months during the follow-up period. RESULTS: In the RGP group, the change of axial length (AL) of the high myopic eye was from 25.62 ± 1.31 mm to 25.69 ± 1.31 mm after 12 months. The change of spherical equivalent (SE) was from -8.73 ± 2.54 D to -8.48 ± 2.77 D. The best corrected visual acuity (BCVA) improved from 0.24 ± 0.18 to 0.78 ± 0.26. In the spectacle group, the change of AL was from 24.76 ± 0.56 mm to 24.94 ± 0.71 mm. The change of SE was from -6.16 ± 2.86 D to -9.45 ± 2.06 D. The improvement of BCVA was from 0.52 ± 0.15 to 0.72 ± 0.23. CONCLUSIONS: Wearing RGP lens in the children with unilateral high myopia is a safe, convenient and effective method to improve the best corrected vision and controlling myopia progression.

An integrated strategy for the systematic chemical characterization of Salvianolate lyophilized injection using four scan modes based on the ultra-high performance liquid chromatography-triple quadrupole-linear ion trap mass spectrometry.

Salvianolate lyophilized injection (SLI), a freeze-dried powder injection derived from aqueous extract of S. miltiorrhiza, is therapeutically used to treat the syndrome of blood stasis and collateral blockage during the recovery period after stroke. To date, it has remained a significant challenge to comprehensively characterize the compounds of SLI, particularly the minor components with potential bioactivities, in one sample injection analysis. Using an integrative four scan modes approach coupled with ultra-high performance liquid chromatography-triple quadrupole-linear ion trap mass spectrometry (UHPLC-QTRAP-MS/MS), we propose a novel, sensitive, and simple strategy for systematic and rapid profiling of the chemical components of SLI. First, an in-house database of constituents from the water-soluble extract of Danshen was created. Second, the fragmentation behaviors of the representative components in SLI were obtained using the untargeted scan mode enhanced MS (EMS)-information dependent acquisition (IDA)-enhanced product ion (EPI). The specific fragments acquired were then utilized to conduct precursor ion (Prec) and neutral loss (NL)-IDA-EPI scans. Following that, a sensitive predictive multiple reaction monitoring (pMRM)-IDA-EPI scan method with 454 transitions was developed based on the prominent fragment ions and plausible predictions. A total of 171 compounds were tentatively identified from SLI. Among them, 27 minor components have not been previously reported. This strategy allows most isomeric compounds at trace levels to be readily distinguished and annotated. Finally, 15 batches of 13 representative components in SLI selected by the qualitative results were accurately quantified. Salvianolic acid A (Sal A), Sal B, Sal D, lithospermic acid (LA), and rosmarinic acid (RA) were proved to be the predominant constituents. Sal B had the highest amount (195.08-350.46 µg·mg-1), followed by LA, Sal A, Sal D, and RA. Moreover, these 15 batches of samples showed good uniformity, and no abnormal batches existed. These results suggest that this novel strategy can accelerate the identification of undiscovered chemical components and serve as an alternative method for in-depth profiling of compounds in other traditional Chinese medicines (TCMs).

In vitro and in vivo inhibition of Helicobacter pylori by Lactobacillus plantarum pH3A, monolaurin, and grapefruit seed extract.

Helicobacter pylori infection is the most common cause of gastritis and gastric ulcers. Considering the severe side effects of current antibiotic therapies, it is crucial to find an alternate treatment for H. pylori infection. In this study, we investigated the anti-H. pylori effects of a newly isolated strain of Lactobacillus plantarum (pH3A), monolaurin, grapefruit seed extract (GSE), and their synergies in vitro and in vivo. Monolaurin and GSE suppressed H. pylori growth and urease activity at a minimal inhibitory concentration (MIC) of 62.5 ppm. Live cells and cell-free culture supernatant (CFCS) of L. plantarum pH3A with or without pH adjustment also significantly inhibited H. pylori growth. Although synergy was not observed between monolaurin and GSE, the addition of CFCS significantly enhanced their anti-H. pylori activities. Moreover, L. plantarum pH3A significantly decreased the ability of H. pylori to adhere to AGS cells and interleukin (IL)-8 production in the H. pylori-stimulated AGS cell line. The addition of GSE or monolaurin strengthened these effects. In the in vivo study, H. pylori colonization of the mouse stomach and total serum IgG production were significantly reduced by L. plantarum pH3A treatment, but the addition of monolaurin or GSE did not contribute to these anti-H. pylori activities. Therefore, the L. plantarum pH3A strain can potentially be applied as an alternative anti-H. pylori therapy, but evidence of its synergy with monolaurin or GSE in vivo is still lacking.

Sub-Nanometer Confined Ions and Solvent Molecules Intercalation Capacitance in Microslits of 2D Materials.

The ion intercalation behavior in 2D materials is widely applied in energy storage, electrocatalysis, and desalination. However, the detailed effect of ions on the performance, combining the influence of interlayer force and the change of solvent shell, is far less well understood. Here the solvated alkali metal ions with different sizes are intercalated into the lattice of 2D materials with different spacings (Ti3 C2 Tx , δ-MnO2 , and reduced graphene oxide) to construct the intercalation model related with sub-nanometer confined ions and solvent molecules to further understand the intercalation capacitance. Based on electrochemical methods and density functional theory calculation, the ions lose the electrostatic shielding solvent shell or shorten the distance between the layers, resulting in a significant increase in capacitance. It is found that the intercalation capacitance arises from the diffusion of solvated ions and is controlled by quantum and electrochemical capacitance for desolvated ions. This effect of solvation structure on performance can be applied in a variety of electrochemical interface studies and provides a new research view for energy storage mechanisms.

Effect of Cold Storage on the Quality of Psyttalia incisi (Hymenoptera: Braconidae), a Larval Parasitoid of Bactrocera dorsalis (Diptera: Tephritidae).

Psyttalia incisi (Silvestri) is the dominant parasitoid against Bactrocera dorsalis (Hendel) in fruit-producing regions of southern China. Prior to a large-scale release, it is important to generate a sufficient stockpile of P. incisi whilst considering how best to maintain their quality and performance; cold storage is an ideal method to achieve these aims. In this study, the impacts of temperature and storage duration on the developmental parameters of P. incisi pupae at different age intervals were assessed. Then, four of the cold storage protocols were chosen for further evaluating their impacts on the quality parameters of post-storage adults. Results showed that the emergence rate of P. incisi was significantly affected by storage temperature, storage duration, and pupal age interval and their interactions. However, when late-age P. incisi pupae developed at a temperature of 13 °C for 10 or 15 d, no undesirable impacts on dry weight, flight ability, longevity, reproduction parameters of post-storage adults, emergence rate, or the female proportion of progeny were recorded. Our findings demonstrate that cold storage has the potential for enhancing the flexibility and effectiveness of the large-scale production and application of P. incisi.

Host-Seeking Behavior of Aphidius gifuensis (Hymenoptera: Braconidae) Modulated by Chemical Cues Within a Tritrophic Context.

Aphidius gifuensis Ashmaed is a generalist endoparasitoid that parasitizes a variety of aphid species. In China, it is widely used as a biological control agent to protect vegetables and tobaccos in open fields; control efficiency is largely dependent on its host-seeking ability. In this study, a six-choice olfactometer was used to investigate the olfactory responses of A. gifuensis to tobacco plants that had suffered damage (either varying degrees of mechanical damage or from aphid-feeding at different time intervals) and tobacco volatiles with different dosages. Furthermore, the regularity of A. gifuensis females' response toward an aphid/tobacco complex was monitored using a Y-tube olfactometer. Our findings suggest that tobacco plants are significantly attractive to A. gifuensis after they have been punctured with 50 holes, or housed with Myzus persicae (Sulzer) at a density of 400 aphids, except at an infestation time of 12 h. Moreover, aphid density had a more significant effect on the response than the time interval since aphid application. Aphidius gifuensis was found to be active during the daytime and preferred to search for their aphid hosts at 14:00 h. Five EAG-active tobacco volatiles (trans-2-hexenal, methyl salicylate, benzaldehyde, cis-3-hexen-1-ol, and 1-hexanal) were found to significantly attract A. gifuensis females at different concentration ranges. The practical implications of these results are discussed in the framework of the sustainable biological control of pest aphids in agricultural production systems.

Thirteen bisbenzylisoquinoline alkaloids in five Chinese medicinal plants: Botany, traditional uses, phytochemistry, pharmacokinetic and toxicity studies.

RELEVANCE: Bisbenzylisoquinoline (BBIQ) alkaloids are generally present in plants of Berberidaceae, Monimiaceae and Ranunculaceae families in tropical and subtropical regions. Some species of these families are used in traditional Chinese medicine, with the effects of clearing away heat and detoxification, promoting dampness and defecation, and eliminating sores and swelling. This article offers essential data focusing on 13 representative BBIQ compounds, which are mainly extracted from five plants. The respective botany, traditional uses, phytochemistry, pharmacokinetics, and toxicity are summarized comprehensively. In addition, the ADME prediction of the 13 BBIQ alkaloids is compared and analyzed with the data obtained. MATERIALS AND METHODS: We have conducted a systematic review of the botanical characteristics, traditional uses, phytochemistry, pharmacokinetics and toxicity of BBIQ alkaloids based on literatures collected from PubMed, Web of Science and Elsevier during 1999-2020. ACD/Percepta software was utilized to predict the pharmacokinetic parameters of BBIQ alkaloids and their affinity with enzymes and transporters. RESULTS: Botany, traditional uses, phytochemistry, pharmacokinetic and toxicity of 13 alkaloids, namely, tetrandrine, dauricine, curine, trilobine, isotrilobine, cepharanthine, daurisoline, thalicarpine, thalidasine, isotetrandrine, liensinine, neferine and isoliensinine, have been summarized in this paper. It can't be denied that these alkaloids are important material basis of pharmacological effects of family Menispermaceae and others, and for traditional and local uses which has been basically reproduced in the current studies. The 13 BBIQ alkaloids in this paper showed strong affinity and inhibitory effect on P-glycoprotein (P-gp), with poor oral absorption and potent binding ability with plasma protein. BBIQ alkaloids represented by tetrandrine play a key role in regulating P-gp or reversing multidrug resistance (MDR) in a variety of tumors. The irrationality of their usage could pose a risk of poisoning in vivo, including renal and liver toxicity, which are related to the formation of quinone methide during metabolism. CONCLUSION: Although there is no further clinical evaluation of BBIQ alkaloids as MDR reversal agents, their effects on P-gp should not be ignored. Considering their diverse distribution, pharmacokinetic characteristics and toxicity reported during clinical therapy, the quality standards in different plant species and the drug dosage remain unresolved problems.

Pathogenic variants identified by whole-exome sequencing in 43 patients with epilepsy.

BACKGROUND: Epilepsy is a group of neurological disorders characterized by recurrent epileptic seizures. Epilepsy is affected by many factors, approximately 20-30% of cases are caused by acquired conditions, but in the remaining cases, genetic factors play an important role. Early establishment of a specific diagnosis is important to treat and manage this disease. METHODS: In this study, we have recruited 43 epileptic encephalopathy patients and the molecular genetic analysis of those children was performed by whole-exome sequencing (WES). RESULTS: Fourteen patients (32.6%, 14/43) had positive genetic diagnoses, including fifteen mutations in fourteen genes. The overall diagnostic yield was 32.6%. A total of 9 patients were diagnosed as pathogenic mutations, including 4 variants had been reported as pathogenic previously and 6 novel variants that had not been reported previously. Therefore, WES heralds promise as a tool for clinical diagnosis of patients with genetic disease. CONCLUSION: Early establishment of a specific diagnosis, on the one hand, is necessary for providing an accurate prognosis and recurrence risk as well as optimizing management and treatment options. On the other hand, to unveil the genetic architecture of epilepsy, it is of vital importance to investigate the phenotypic and genetic complexity of epilepsy.