PEO-Based Solid Composite Polymer Electrolyte for High Capacity Retention All-Solid-State Lithium Metal Battery.

The limited ionic conductivity at room temperature and the constrained electrochemical window of poly(ethylene oxide) (PEO) pose significant obstacles that hinder its broader utilization in high-energy-density lithium metal batteries. The garnet-type material Li6.4 La3 Zr1.4 Ta0.6 O12 (LLZTO) is recognized as a highly promising active filler for enhancing the performance of PEO-based solid polymer electrolytes (SPEs). However, its performance is still limited by its high interfacial resistance. In this study, a novel hybrid filler-designed SPE is employed to achieve excellent electrochemical performance for both the lithium metal anode and the LiFePO4 cathode. The solid composite membrane containing hybrid fillers achieves a maximum ionic conductivity of 1.9 × 10-4 S cm-1 and a Li+ transference number of 0.67 at 40 °C, respectively. Additionally, the Li/Li symmetric cells demonstrate a smooth and stable process for 2000 h at a current density of 0.1 mA cm-2 . Furthermore, the LiFePO4 /Li battery delivers a high-rate capacity of 159.2 mAh g-1 at 1 C, along with a capacity retention of 95.2% after 400 cycles. These results validate that employing a composite of both active and inactive fillers is an effective strategy for achieving superior performance in all-solid-state lithium metal batteries (ASSLMBs).

Association of anhedonia and suicidal ideation in patients with treatment-refractory depression after intravenous ketamine infusions.

OBJECTIVES: Accumulating evidence suggests that the effects of ketamine administered intravenously at subanaesthetic doses on both anhedonic symptoms and suicidal ideation occur independently of depressive symptoms in major depressive disorder (MDD) and bipolar disorder (BD). This study sought to determine the relationship between anhedonia and suicidal ideation after serial ketamine infusions. METHODS: A total of 79 subjects with either treatment-refractory MDD (n = 60) or BD (n = 19) were included in a clinical ketamine study. The Montgomery-Åsberg Depression Rating Scale (MADRS) anhedonia factor and the first five items of the Scale for Suicidal Ideations (SSI-Part I) were used to assess anhedonia symptoms and suicidal ideation, respectively. RESULTS: At baseline, anhedonia, as measured by the MADRS, was not significantly associated with suicidal ideation or specific suicide-related ideation as measured by SSI-Part I (all p's > 0.05). Only the 'wish to die' and 'desire to make a suicide attempt' items were positively associated with anhedonia at two weeks after the sixth ketamine infusion, which was independent of the reductions in depressive symptoms (all p's < 0.05). CONCLUSION: Anhedonia as measured by the MADRS appeared to not be positively related to suicidal ideation after serial ketamine infusions.KEY POINTSSerial ketamine (0.5 mg/kg) infusions have shown quick and dramatic antisuicidal and antianhedonic effects in patients with depression.The association between anhedonia and suicidal ideation after serial ketamine infusions is unclear.Anhedonia appeared to not be positively related to suicidal ideation after serial ketamine infusions.

Development and validation of a stability-indicating HPLC method to determine the impurity profile of fosaprepitant dimeglumine in the injection formulation.

Fosaprepitant dimeglumine, an injectable phosphorylated prodrug of aprepitant, has been approved for preventing chemotherapy-induced nausea and vomiting. A novel stability-indicating HPLC method was designed and validated to determine process- and degradation-related impurities of fosaprepitant dimeglumine in an injection formulation. Chromatographic separation was done on a NanoChrom C18 (250 mm×4.6 mm, 5µm) column at a column oven temperature of 35°C. Mobile phase A had 0.5 M ammonium dihydrogen phosphate solution (pH fixed to 2.2 with orthophosphoric acid) and acetonitrile at 80:20 ratio and mobile phase B had methanol and acetonitrile at 70:30 ratio. The formulations underwent forced degradation conditions, like acidic, basic, thermal oxidation and photolytic conditions. The designed HPLC approach was validated per International Conference of Harmonization (ICH) guidelines, including limit of detection (LOD), specificity, limit of quantitation (LOQ), accuracy, linearity, precision and robustness. The results showed that this method is specific, sensitive, precise, accurate and robust.

Development of spirocyclic phosphoramidite-based hybrid diphosphorus ligands for enantioselective iridium-catalyzed hydrogenation of imines.

Unsymmetrical hybrid chiral diphosphorus ligands bearing a spirocyclic phosphoramidite scaffold have been developed and successfully applied in the iridium-catalyzed asymmetric hydrogenation of imines. With this newly developed chiral iridium catalytic system, a wide range of imines including sterically hindered ones could be hydrogenated to give the corresponding optically active amines in high yields (up to >99%) and with excellent enantioselectivities (up to >99% ee). The utility of this hydrogenation has been demonstrated by the preparation of the chiral fungicide (S)-benalaxyl.

Ligand-Induced GPR110 Activation Facilitates Axon Growth after Injury.

Recovery from axonal injury is extremely difficult, especially for adult neurons. Here, we demonstrate that the activation of G-protein coupled receptor 110 (GPR110, ADGRF1) is a mechanism to stimulate axon growth after injury. N-docosahexaenoylethanolamine (synaptamide), an endogenous ligand of GPR110 that promotes neurite outgrowth and synaptogenesis in developing neurons, and a synthetic GPR110 ligand stimulated neurite growth in axotomized cortical neurons and in retinal explant cultures. Intravitreal injection of GPR110 ligands following optic nerve crush injury promoted axon extension in adult wild-type, but not in gpr110 knockout, mice. In vitro axotomy or in vivo optic nerve injury rapidly induced the neuronal expression of gpr110. Activating the developmental mechanism of neurite outgrowth by specifically targeting GPR110 that is upregulated upon injury may provide a novel strategy for stimulating axon growth after nerve injury in adults.

Adjunctive Fluvoxamine for Schizophrenia: A Meta-analysis of Randomized Double-Blind, Placebo-Controlled Trials.

BACKGROUND: This was a meta-analysis of double-blind, randomized controlled trials that examined the therapeutic effects and tolerability of adjunctive fluvoxamine versus placebo for schizophrenia. METHODS: The Review Manager, Version 5.3, was used to analyze data. RESULTS: Five double-blind randomized controlled trials (N = 284) covering 145 patients on adjunctive fluvoxamine and 139 patients on placebo were included in the analyses. Meta-analyses of total psychopathology, and negative, positive, and depressive symptoms did not show significant differences between the fluvoxamine and placebo groups. Two studies examined the effects of adjunctive fluvoxamine on cognitive functioning with mixed findings. Fluvoxamine was superior over placebo in lessening weight gain and metabolic abnormalities. Although fluvoxamine led to more discontinuation, no significant group differences were found regarding adverse drug reactions. CONCLUSIONS: There was inconsistent evidence for the therapeutic effect of adjunctive fluvoxamine on cognitive functions and preliminary evidence for alleviating metabolic syndrome caused by clozapine. More studies are needed to explore further the effectiveness of adjunctive fluvoxamine for schizophrenia.

Adjunctive Reboxetine for Schizophrenia: Meta-analysis of Randomized Double-blind, Placebo-controlled Trials.

BACKGROUND: Results of previous studies on the safety and efficacy of adjunctive reboxetine for schizophrenia have been inconsistent. AIM: The aim of this study was to examine the efficacy and tolerability of reboxetine as an adjunct medication to antipsychotic treatment in a meta-analysis of randomized controlled trials (RCTs). METHODS: Two independent investigators extracted data for a random effects meta-analysis and assessed the quality of studies using risk of bias and the Jadad scale. Weighted and standardized mean differences (WMDs/SMDs) and risk ratio (RR)±95% confidence intervals (CIs) were calculated. RESULTS: Nine RCTs (n=630) with double-blind design were identified. Reboxetine outperformed placebo in improving negative (9 RCTs, n=602, SMD: -0.47 [95% CI: -0.87, -0.07], p=0.02; I2=82%), but not the overall, positive, and general psychopathology scores. The significant therapeutic effect on negative symptoms disappeared in the sensitivity analysis after removing an outlying study and in 50% (6/12) of the subgroup analyses. Reboxetine outperformed placebo in reducing weight (3 RCTs, n=186, WMD: -3.83 kg, p=0.04; I2=92%) and body mass index (WMD: -2.23 kg/m2, p=0.04; I2=95%). Reboxetine caused dry mouth but was associated with less weight gain overall and weight gain of ≥7% of the initial weight. All-cause discontinuation and other adverse events were similar between reboxetine and placebo. CONCLUSION: Adjunctive reboxetine could be useful for attenuating antipsychotic-induced weight gain, but it was not effective in treating psychopathology including negative symptoms in schizophrenia.

Genome-wide screening of hexokinase gene family and functional elucidation of HXK2 response to cold stress in Jatropha curcas.

Hexokinase, the key rate-limiting enzyme of plant respiration and glycolysis metabolism, has been found to play a vital role in plant sugar sensing and sugar signal transduction. Using Jatropha curcas genome database and bioinformatics method, J. curcas HXK gene family (JcHXK) was identified and its phylogenetic evolution, functional domain, signal peptide at the N-terminal, and expression analysis were conducted. The results showed that a total of 4 HXK genes (JcHXK1, JcHXK2, JcHXK3, and JcHKL1) with 9 exons were systematically identified from J. curcas. JcHXK1, JcHXK3, and JcHKL1 with putative transmembrane domain at the N-terminal belonged to the type of secretory pathway protein, and JcHXK2 contained putative chloroplast targeting peptide. Quantitative real-time PCR (qRT-PCR) analysis revealed that all the four JcHXKs were expressed in different tissues of the leaves, roots, and seeds; however, JcHXK1 and JcHKL1 expression were higher in the roots, whereas JcHXK2 and JcHXK3 showed over-expression in the leaves and seeds, respectively. Furthermore, all the four JcHXKs were up-regulated in the leaves after cold stress at 12 °C; however, only JcHXK3 remarkably demonstrated cold-induced expression in the roots, which reached the highest expression level at 12 h (2.28-fold). According to the cis-acting element analysis results, JcHXK2 contained the most low temperature responsive elements, which was closely related to the cold resistance in J. curcas. A pET-28a-JcHXK2 prokaryotic recombinant expression vector was successfully constructed and a 57.0 kDa protein was obtained, JcHXK2 revealed catalytic activity towards glucose and fructose, with a higher affinity for glucose than fructose. The subcellular localization assays revealed that JcHXK2 was localized in the chloroplast. The results of this study might provide theoretical foundation for further studies on gene cloning and functional verification of HXK family in J. curcas.

Combination of Metformin and Lifestyle Intervention for Antipsychotic-Related Weight Gain: A Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Weight gain is a common antipsychotic (AP)-related adverse drug reaction (ADR) that can increase the risk of cardiovascular diseases and premature mortality. This meta-analysis examined the efficacy and tolerability of combining metformin and lifestyle intervention for AP-related weight gain in schizophrenia. METHODS: Randomized controlled trials (RCTs) with meta-analyzable data were searched and retrieved by 2 independent investigators. RevMan software (version 5.3) was used to synthesize data, and to calculate the standardized or weighted mean differences and risk ratio with their 95% confidence intervals. RESULTS: Six RCTs (n=732) were included and meta-analyzed. The metformin and lifestyle combination (MLC) group had significant reduction in weight and body mass index compared with the metformin group, lifestyle group, and placebo group. There was less frequent weight gain of≥7% in the MLC group over placebo. No other group differences in ADRs, total psychopathology, and all-cause discontinuation were found. In terms of study quality, 5 RCTs were open-labelled, 1 RCT had low risk allocation concealment, and 3 RCTs specifically described randomization methods. CONCLUSION: Combining metformin and lifestyle intervention shows significant effect in reducing AP-related weight gain. Higher quality and larger RCTs are needed to confirm these findings.Review registration: CRD42017059198.

CYP2E1 Rsa Ι/Pst Ι polymorphism and lung cancer susceptibility: A meta-analysis involving 10,947 subjects.

The above article, published in the Journal of Cellular and Molecular Medicine on 14 September 2016 in Wiley Online Library (wileyonlinelibrary.com), and in Volume 19, pp. 2136-2142, has been retracted by agreement between the authors, the journal Editor in Chief, Stefan Constantinescu, and John Wiley & Sons Ltd. The retraction has been agreed due to unattributed overlap of the language used in the "Materials and method" and "Discussion" sections of this study and the following article published in Lung Cancer: "CYP2E1 Rsa I/Pst I polymorphism is associated with lung cancer risk among Asians" by Ping Zhan, Jing Wang, Yu Zhang, Li-Xin Qiu, Su-feng Zhao, Qian Qian, Shu-Zhen Wei, Li-Ke Yu and Yong Song, Volume 69, 2010, pages 19-25. REFERENCE Shen Z-T, Wu X-H, Li B, Shen J-S, Wang Z, Li J, Zhu X-X. CYP2E1 Rsa Ι/Pst Ι polymorphism and lung cancer susceptibility: a meta-analysis involving 10,947 subjects. J Cell Mol Med. 2015;19:2136-2142. https://doi.org/10.1111/jcmm.12579.

Erythropoietin for Cognitive Deficits Associated with Schizophrenia, Bipolar Disorder, and Major Depression: A Systematic Review.

INTRODUCTION: The purpose of this study is to systematically review the efficacy and safety of adjunctive erythropoietin (EPO) in treating cognitive deficits associated with schizophrenia, bipolar disorder, and major depression based on randomized controlled trials (RCTs). METHODS: Two evaluators independently and systematically searched and selected studies, extracted data, and conducted quality assessment. RESULTS: Four RCTs with 144 patients (71 in the EPO group and 73 in the placebo group) met the study entry criteria. Adjunctive EPO could improve schizophrenia-related cognitive performance. In patients with bipolar disorder, EPO could also enhance sustained attention, recognition of happy faces, and speed of complex information processing across learning, attention, and executive function when compared with placebo. In addition, EPO could enhance verbal recall, recognition, and memory in patients with major depression. DISCUSSION: This preliminary study found that adjunctive EPO appears to be effective in treating cognitive deficits associated with schizophrenia, bipolar disorder, and major depression without major adverse effects observed. Further higher quality RCTs with larger samples are needed to confirm the findings. REVIEW REGISTRATION: CRD42017058094.

Effects of chilling stress on the accumulation of soluble sugars and their key enzymes in Jatropha curcas seedlings.

As osmolytes and signaling molecules, soluble sugars participate in the response and adaptation of plants to environmental stresses. In the present study, we measured the effect of chilling (12 °C) stress on the contents of eight soluble sugars in the leaves, cotyledons, stems, and roots of Jatropha curcas seedlings, as well as on the activities of eight rate-limiting enzymes that are critical to the metabolism of those soluble sugars. Chilling stress promoted both starch hydrolysis and soluble sugar accumulation. The soluble sugar contents of the leaves and cotyledons were affected more than that of the stems and roots. Meanwhile, the activities of the corresponding metabolic enzymes (e.g., ß-amylase, uridine diphosphate glucose phosphorylase, and sucrose phosphate synthase) also increased in some organs. The gradual increase of soluble neutral alkaline invertase activity in the four studied organs suggested that sucrose catabolic production, such as glucose and fructose, was especially important in determining resistance to chilling stress and hexose signal transduction pathway. In addition, the substantial accumulation of raffinose family oligosaccharides and increase in corresponding metabolic enzyme activity suggested that galactinol and raffinose play an important role in determining the chilling resistance of J. curcas. Together, these findings establish a foundation for determining the relationship between the chilling resistance and soluble sugar accumulation of J. curcas and for investigating the mechanisms underlying sugar signaling transduction and stress responses.

Amantadine for Antipsychotic-Related Weight Gain: Meta-Analysis of Randomized Placebo-Controlled Trials.

PURPOSE: Weight gain associated with antipsychotics in schizophrenia has been an ongoing concern. This meta-analysis examined the efficacy and safety of amantadine as an adjunctive treatment of weight gain in schizophrenia by systematically searching and analyzing randomized controlled trials (RCTs). RCTs comparing adjunctive amantadine with placebo in adult patients with schizophrenia were included in the meta-analysis. METHODS: Two independent investigators searched the literature and extracted data. Weighted and standardized mean differences (WMDs/SMDs) and risk ratio ± 95% confidence intervals were calculated. RESULTS: Five RCTs (n = 265) with double-blinded design lasting 8.2 ± 5.9 weeks were included in the analysis. Amantadine outperformed placebo regarding weight reduction with moderate effect size (trials, 3; n = 205; WMD -2.22 kg; P = 0.001, I = 45%). Amantadine also outperformed placebo at endpoint in the negative symptom (the Positive and Negative Syndrome Scale [PANSS] [1 trial] and the Scale for the Assessment of Negative Symptoms [1 trial]) scores (trials, 2; n = 84; SMD, -0.56; P = 0.01, I = 12%), but not in the PANSS total scores (trials, 2) (SMD, -0.31; P = 0.16, I = 0%) and the positive symptom (PANSS [1 trial] and the Scale for the Assessment of Positive Symptoms [1 trial]) scores (SMD, 0.13; P = 0.54, I = 0%). Except for insomnia (P = 0.007; number needed to harm, 6; 95% confidence interval, 4-16), all-cause discontinuation (risk ratio, 1.12; P = 0.54, I = 0%) and other adverse events were similar between the amantadine and placebo groups. CONCLUSIONS: According to this meta-analysis of 5 RCTs, adjunctive amantadine seems to be an effective option for attenuating antipsychotic-related weight gain in patients with schizophrenia. More RCTs are needed to inform clinical recommendations.

Borinic Acid Polymer: Simplified Synthesis and Enzymatic Biofuel Cell Application.

A simplified one-pot and less harmful method has been introduced for the synthesis of borinic acid monomer. The corresponding borinic acid polymer (PBA) has been prepared by reversible addition-fragmentation chain transfer polymerization. Property investigations confirm the characteristics of PBA as a new type of "smart material" in the field of thermo-responsive polymer. The potential application of PBA in the field of enzymatic biofuel cell has been illustrated with a wide open circuit potential of 0.92 V.

RAFT-Polymerization-Induced Self-Assembly and Reorganizations: Ultrahigh-Molecular-Weight Polymer and Morphology-Tunable Micro-/Nanoparticles in One Pot.

A one-pot method is introduced for the successful synthesis of narrow-distributed (D = 1.22) vinyl polymer with both ultrahigh molecular weight (UHMW) (M w = 1.31 × 106 g mol-1 ) and micro-/nanomorphology under mild conditions. The method involves the following four stages: homogeneous polymerization, polymerization-induced self-assembly (PISA), PISA and reorganization, and PISA and multiple reorganizations. The key points to the production of UHMW polystyrene are to minimize radical termination by segregating radicals in different nanoreactors and to ensure sufficient chain propagation by promoting further reorganizations of these reactors in situ. This method therefore endows polymeric materials with the outstanding properties of both UHMW and tunable micro-/nanoparticles under mild conditions in one pot.

BMDREDD REGULATES THE APOPTOSIS COORDINATING WITH BMDAXX, BMCIDE-B, BMFADD, AND BMCREB IN BMN CELLS.

The apoptosis mechanisms in mammals were investigated relatively clearly. However, little is known about how apoptosis is achieved at a molecular level in silkworm cells. We cloned a caspase homologous gene named BmDredd (where Bm is Bombyx mori and Dredd is death-related ced-3/Nedd2-like caspase) in BmN cells from the ovary of Bm and analyzed its biological information. We constructed the N-terminal, C-terminal, and overexpression vector of BmDredd, respectively. Our results showed that the transcriptional expression level of BmDredd was increased in the apoptotic BmN cells. Furthermore, overexpression of BmDredd increased the caspase-3/7 activity. Simultaneously, RNAi of BmDredd could save BmN cells from apoptosis. The immunofluorescence study showed that BmDredd located at the cytoplasm in normal cell otherwise is found at the nucleus when cells undergo apoptosis. Moreover, we quantified the transcriptional expressions of apoptosis-related genes including BmDredd, BmDaxx (where Daxx is death-domain associated protein), BmCide-b (where Cide-b is cell death inducing DFF45-like effector), BmFadd (Fadd is fas-associated via death domain), and BmCreb (where Creb is cAMP-response element binding protein) in BmN cells with dsRNA interferences to detect the molecular mechanism of apoptosis. In conclusion, BmDredd may function for promoting apoptosis and there are various regulatory interactions among these apoptosis-related genes.

CYP2E1 Rsa Ι/Pst Ι polymorphism and lung cancer susceptibility: a meta-analysis involving 10,947 subjects.

Many studies have examined the association between the CYP2E1 Rsa Ι/Pst Ι (rs3813867) polymorphism gene polymorphisms and lung cancer risk in various populations, but their results have been inconsistent. The PubMed and CNKI database was searched for case-control studies published up to October 2013. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. In this meta-analysis, we assessed 23 published studies involving comprising 4727 lung cancer cases and 6220 controls of the association between CYP2E1 Rsa Ι/Pst Ι polymorphism and lung cancer risk. For the homozygote c2/c2 and c2 allele carriers (c1/c2 + c2/c2), the pooled ORs for all studies were 0.73(95% CI = 0.62-0.84; P = 0.005 for heterogeneity) and 0.84 (95% CI = 0.77-0.92; P = 0.001 for heterogeneity) when compared with the homozygous wild-type genotype (c1/c1). In the stratified analysis by ethnicity, the same significantly risks were found among Asians and mixed population for both the c2 allele carriers and homozygote c2/c2. However, no significant associations were found in Caucasian population all genetic models. This updated meta-analysis suggests that CYP2E1 Rsa Ι/Pst Ι c2 allele is a decreased risk factor for the developing lung cancer among Asians and mixed population.

Thermo-responsive behavior of borinic acid polymers: experimental and molecular dynamics studies.

The thermo-responsive properties of borinic acid polymers were investigated by experimental and molecular dynamics simulation studies. The homopolymer poly(styrylphenyl(tri-iso-propylphenyl)borinic acid) (PBA) exhibits an upper critical solution temperature (UCST) in polar organic solvents that is tunable over a wide temperature range by addition of small amounts of H2O. The UCST of a 1 mg mL(-1) PBA solution in DMSO can be adjusted from 20 to 100 °C by varying the H2O content from ∼0-2.5%, in DMF from 0 to 100 °C (∼3-17% H2O content), and in THF from 0 to 60 °C (∼4-19% H2O). The UCST increases almost linearly from the freezing point of the solvent with higher freezing point to the boiling point of the solvent with the lower boiling point. The mechanistic aspects of this process were investigated by molecular dynamics simulations. The latter indicate rapid and strong hydrogen-bond formation between BOH moieties and H2O molecules, which serve as crosslinkers to form an insoluble network. Our results suggest that borinic acid-containing polymers are promising as new "smart" materials, which display thermo-responsive properties that are tunable over a wide temperature range.

RNAi KNOCKDOWN OF BmRab3 LED TO LARVA AND PUPA LETHALITY IN SILKWORM Bombyx mori L.

Rab3 GTPases are known to play key a role in vesicular trafficking, and express highest in brain and endocrine tissues. In mammals, Rab3 GTPases are paralogs unlike in insect. In this study, we cloned Rab3 from the silk gland tissue of silkworm Bombyx mori, and identified it as BmRab3. Our in silico analysis indicated that BmRab3 is an isoform with a theoretical isoelectric point and molecular weight of 5.52 and 24.3 kDa, respectively. Further, BmRab3 showed the C-terminal hypervariability for GGT2 site but having two other putative guanine nucleotide exchange factor/GDP dissociation inhibitor interaction sites. Multiple alignment sequence indicated high similarities of BmRab3 with Rab3 isoforms of other species. The phylogeny tree showed BmRab3 clustered between the species of Tribolium castaneum and Aedes aegypti. Meanwhile, the expression analysis of BmRab3 showed the highest expression in middle silk glands (MSGs) than all other tissues in the third day of fifth-instar larva. Simultaneously, we showed the differential expression of BmRab3 in the early instar larva development, followed by higher expression in male than female pupae. In vivo dsRNA interference of BmRab3 reduced the expression of BmRab3 by 75% compared to the control in the MSGs in the first day. But as the worm grew to the third day, the difference of BmRab3 between knockdown and control was only about 10%. The knockdown later witnessed underdevelopment of the larvae and pharate pupae lethality in the overall development of silkworm B. mori L.

TRANSCRIPTION FACTOR Bmsage PLAYS A CRUCIAL ROLE IN SILK GLAND GENERATION IN SILKWORM, Bombyx mori.

Salivary gland secretion is altered in Drosophila embryos with loss of function of the sage gene. Saliva has a reduced volume and an increased electron density according to transmission electron microscopy, resulting in regions of tube dilation and constriction with intermittent tube closure. However, the precise functions of Bmsage in silkworm (Bombyx mori) are unknown, although its sequence had been deposited in SilkDB. From this, Bmsage is inferred to be a transcription factor that regulates the synthesis of silk fibroin and interacts with another silk gland-specific transcription factor, namely, silk gland factor-1. In this study, we introduced a germline mutation of Bmsage using the Cas9/sgRNA system, a genome-editing technology, resulting in deletion of Bmsage from the genome of B. mori. Of the 15 tested samples, seven displayed alterations at the target site. The mutagenesis efficiency was about 46.7% and there were no obvious off-target effects. In the screened homozygous mutants, silk glands developed poorly and the middle and posterior silk glands (MSG and PSG) were absent, which was significantly different from the wild type. The offspring of G0 mosaic silkworms had indel mutations causing 2- or 9-bp deletions at the target site, but exhibited the same abnormal silk gland structure. Mutant larvae containing different open-reading frames of Bmsage had the same silk gland phenotype. This illustrated that the mutant phenotype was due to Bmsage knockout. We conclude that Bmsage participates in embryonic development of the silk gland.