Detection of calcitonin gene-related peptide based on increased antigen-driven interaction with antibody variable regions.

Introduction: Calcitonin gene-related peptide (CGRP) is involved in trigeminal neuralgia and migraine, and measuring the CGRP concentration in the serum is crucial for the early prediction of these conditions. Current methods for CGRP detection are primarily radioimmunoassay, which needs radioactive substances and enzyme-linked immunosorbent assays (ELISAs) which need long detection time and some have a narrow detection range. Methods: The genes of anti-CGRP antibody variable regions were cloned into pDong1 vector to obtain pDong1/Fab-CGRP, with which phage-Fab was prepared, and the concentration of CGRP was detected by competitive ELISA. The pDong1/Fab-CGRP was modified to obtain pDong1/OS-CGRP, with which the co-expression solution containing phage-displayed heavy chain variable fragments (phage-VH) and light chain was obtained. CGRP was detected by OS-ELISA based on phage-VH, antibody light chain, and anti-light chain antibody. The VL gene was cloned into the pMAL vector to obtain pMAL-VL (CGRP), with which maltose binding protein fused with VL (MBP-VL) was prepared. CGRP was detected by OS-ELISA employing MBP-VL and phage-VH. Results: OS-ELISAs that measure the CGRP concentration by quantifying the interaction between variable regions were investigated. OS-ELISA using phage-VH and secreted light chains in the same culture system exhibited a limit of detection (LOD) of 0.05 nM, offering higher sensitivity than competitive assay with an LOD of 0.75 nM, whereas using phage-VH and separately prepared MBP-VL exhibited an LOD of 0.15 nM and a broader detection range of 0.15-500 nM than competitive ELISA, whose detection range was 0.75-10 nM. Discussion: The combination of the two OS assays achieved high sensitivity and a broad detection range for CGRP, which may have significance in clinical applications.

Accuracy and patient-centered results of marker-based and marker-free registrations for dynamic computer-assisted implant surgery: A randomized controlled trial.

OBJECTIVES: To compare implant placement accuracy and patient-centered results between the dynamic computer-assisted implant surgeries (d-CAISs) using marker-based and marker-free registration methods. MATERIALS AND METHODS: A double-armed, single-blinded randomized controlled trial was conducted, in which 34 patients requiring single implant placement at the esthetic zone were randomly assigned to the marker-based (n = 17) or marker-free (n = 17) groups. The marker-based registration was performed using a splint containing radiopaque markers, while the marker-free registration used natural teeth. The primary outcome assessed implant positioning accuracy via angular and linear deviations between preoperative and postoperative implant positions in CBCT. Patients were also surveyed about the intraoperative experience and oral health impact profile (OHIP). RESULTS: The global linear deviations at the implant platform (0.82 ± 0.28 and 0.85 ± 0.41 mm) and apex (1.28 ± 0.34 and 0.85 (IQR: 0.64-1.50) mm) for the marker-based and marker-free groups respectively showed no significant difference. However, the angular deviation of the marker-free group (2.77 ± 0.92 ° ) was significantly lower than the marker-based group (4.28 ± 1.58 ° ). There was no significant difference in the mean postoperative OHIP scores between the two groups (p = .758), with scores of 2.74 ± 1.21 for marker-based and 2.93 ± 2.18 for marker-free groups, indicating mild oral health-related impairment in both. Notably, patients in the marker-free group showed significantly higher satisfaction (p = .031) with the treatment procedures. CONCLUSIONS: D-CAIS with a marker-free registration method for single implantation in the anterior maxilla has advantages in improving implant placement accuracy and patients' satisfaction, without generating a significant increase in clinical time and expenses.

Fluorescence quenching-based immunological probe for ticagrelor monitoring.

Introduction: Ticagrelor is extensively utilized for the treatment of acute coronary syndromes (ACS), but its platelet aggregation inhibitory effects can potentially result in tissue bleeding, posing a serious risk to patients' lives. Methods: In this study, we developed highly sensitive full length anti-ticagrelor Quenchbodies (Q-bodies) for fast monitoring of ticagrelor both in solution and serum for the first time. Ticagrelor coupled with N- hydroxysuccinimide (Ticagrelor-NHS) ester was also designed and synthesized for interaction and biological activity detection. Results: Both ATTO-labeled MEDI2452 (2452A) Q-body and TAMRA-labeled IgG 152 (152T) Q-body demonstrated efficient detection of ticagrelor and its active metabolite (TAM). The 2452A Q-body exhibited a broader detection range, while the 152T Q-body displayed a lower limit of detection (LOD). Under physiological conditions (Ticagrelor:TAM, 3:1), the concentration of ticagrelor was further measured, yielding LOD values of 4.65 pg/mL and 2.75 pg/mL for the two Q-bodies, with half-maximal effect concentrations of 8.15 ng/mL and 3.0 ng/mL, respectively. Discussion: Compared with traditional liquid chromatography-mass spectrometry (LC-MS) methods, anti-ticagrelor Q-bodies have higher sensitivity and detection speed. It enabled the completion of analysis within 3 min, facilitating rapid preoperative detection of blood drug concentration in ACS to determine the feasibility of surgery and mitigate the risk of intraoperative and postoperative hemorrhage. The swift detection of ticagrelor holds promise for enhancing individualized drug administration, preventing adverse reactions, and providing preoperative guidance.

Fine particulate matter and its constituent on ovarian reserve: Identifying susceptible windows of exposure.

BACKGROUND: Little is known about the associations of exposure to fine particulate matter (PM2.5) and its constituents with ovarian reserve, and the potential susceptible window of exposure remains unclear. METHODS: We performed a retrospective cohort study of 5189 women who attended a fertility center in Hubei, China, during 2019-2022, and estimated concentrations of PM2.5 and its major constituents during the development of follicles (4th-6th month [W1], 0-4th month [W2], 0-6th month [W3]) and 1-year before measurement (W4) based on Tracking Air Pollution in China database. We used multivariable linear regression and logistic regression models to examine the associations of PM2.5 and its constituent exposures with anti-Müllerian hormone (AMH), the preferred indicator of ovarian reserve. RESULTS: We observed significantly decreased AMH levels associated with increasing PM2.5 concentrations, with the percent changes (95 % confidence intervals [CIs]) of 1.99 % (0.24 %-3.71 %) during W1 and 3.99 % (0.74 %-7.15 %) during W4 for per 10 µg/m3 increases in PM2.5.When PM2.5 exposure levels were equal to 50th percentile (32.6-42.3 µg/m3) or more, monotonically decreased AMH levels and increased risks of low AMH were seen with increasing PM2.5 concentrations during W1 and W4 (P < 0.05). Black carbon (BC), ammonium (NH4+), nitrate (NO3-), and organic matter (OM) during W1, and NH4+, NO3-, as well as sulfate (SO42-) during W4 were significantly associated with decreased AMH. Moreover, PM2.5 and SO42- exposures during W4 were positively associated with low AMH. Additionally, the associations were stronger among women aged <35 years, lived in urban regions, or measured AMH in cold-season (P for interaction <0.05). CONCLUSION: PM2.5 and specific chemical components (particularly NH4+, NO3-, and SO42-) exposure during the secondary to antral follicle stage and 1-year before measurement were associated with diminished ovarian reserve (DOR), indicating the adverse impact of PM2.5 and its constituent exposures on female reproductive potential.

Nontargeted metabolomics analysis of follicular fluid in patients with endometriosis provides a new direction for the study of oocyte quality.

Endometriosis is a common, estrogen-dependent chronic gynecological disease that endangers the reproductive system and systemic metabolism of patients. We aimed to investigate the differences in metabolic profiles in the follicular fluid between infertile patients with endometriosis and controls. A total of 25 infertile patients with endometriosis and 25 infertile controls who were similar in age, BMI, fertilization method and ovulation induction treatment were recruited in this study. Metabolomics analysis of follicular fluid was performed by two methods of high-performance liquid chromatography tandem mass spectrometry. There were 36 upregulated and 17 downregulated metabolites in the follicular fluid of patients in the endometriosis group. KEGG pathway analysis revealed that these metabolites were enriched in phenylalanine, tyrosine and tryptophan biosynthesis, aminoacyl-tRNA biosynthesis, phenylalanine metabolism and pyrimidine metabolism pathways. A biomarker panel consisting of 20 metabolites was constructed by random forest, with an accuracy of 0.946 and an AUC of 0.988. This study characterizes differences in follicular fluid metabolites and associated pathway profiles in infertile patients with endometriosis. These findings can provide a better comprehensive understanding of the disease and a new direction for the study of oocyte quality, as well as potential metabolic markers for the prognosis of endometriosis.

High-Resolution Single-Shot Fast Spin-Echo MR Imaging with Deep Learning Reconstruction Algorithm Can Improve Repeatability and Reproducibility of Follicle Counting.

OBJECTIVE: To investigate the diagnostic performance of high-resolution single-shot fast spin-echo (SSFSE) imaging with deep learning (DL) reconstruction algorithm on follicle counting and compare it with original SSFSE images and conventional fast spin-echo (FSE) images. METHODS: This study included 20 participants (40 ovaries) with clinically confirmed polycystic ovary syndrome (PCOS) who underwent high-resolution ovary MRI, including three-plane T2-weighted FSE sequences and slice-matched T2-weighted SSFSE sequences. A DL reconstruction algorithm was applied to the SSFSE sequences to generate SSFSE-DL images, and the original SSFSE images were also saved. Subjective evaluations such as the blurring artifacts, subjective noise, and clarity of the follicles on the SSFSE-DL, SSFSE, and conventional FSE images were independently conducted by two observers. Intra-class correlation coefficients and Bland-Altman plots were used to present the repeatability and reproducibility of the follicle number per ovary (FNPO) based on the three types of images. RESULTS: SSFSE-DL images showed less blurring artifact, subjective noise, and better clarity of the follicles than SSFSE and FSE (p < 0.05). For the repeatability of the FNPO, SSFSE-DL showed the highest intra-observer (ICC = 0.930; 95% CI: 0.878-0.962) and inter-observer (ICC = 0.914; 95% CI: 0.843-0.953) agreements. The inter-observer 95% limits of agreement (LOA) for SSFSE-DL, SSFSE, and FSE ranged from -3.7 to 4.5, -4.4 to 7.0, and -7.1 to 7.6, respectively. The intra-observer 95% LOA for SSFSE-DL, SSFSE, and FSE ranged from -3.5 to 4.0, -5.1 to 6.1, and -5.7 to 4.2, respectively. The absolute values of intra-observer and inter-observer differences for SSFSE-DL were significantly lower than those for SSFSE and FSE (p < 0.05). CONCLUSIONS: Compared with the original SSFSE images and the conventional FSE images, high-resolution SSFSE images with DL reconstruction algorithm can better display follicles, thus improving FNPO assessment.

Low dosage of prednisone acetate combined with doxycycline in the treatment of chronic endometritis in patients with repeated implantation failure.

OBJECTIVE: To retrospectively investigate whether the oral administration of prednisone acetate with doxycycline increases the cure rate of chronic endometritis (CE) and improves in vitro fertilization (IVF) outcomes in patients with repeated implantation failure (RIF) with CE. METHODS: In total, 352 patients with RIF were investigated, 128 of whom were diagnosed with CE by hysteroscopy and endometrial immunohistochemical analysis. The patients with CE were divided into CD138-positive high-power field (HPF) counts of 1-2 and ≥3. Forty-five patients were orally administered prednisone acetate tablet 5 mg daily and doxycycline 100 mg twice daily for 14 consecutive days (group A), and 55 patients were administered doxycycline 100 mg orally twice daily for 14 days (group B) and underwent repeated endometrial sampling and histological assessment. Twenty-eight patients (group C) did not receive any treatment. The cure rate of CE and final reproductive outcomes of the frozen-thawed embryo transfer cycle were compared. RESULTS: The total cure rate, cure rate of patients with CE(CD138+ HPF counts: 1-2), and cure rate of patients with CE(CD138+ HPF counts: ≥3) showed no significant difference between groups A and B. Logistics regression analysis indicated that the implantation rate, human chorionic gonadotropin (hCG)-positive rate, clinical pregnancy rate, clinical pregnancy rate with fetal heartbeat on day 30 (D30), and ongoing pregnancy rate was significantly higher in group A than in group C. For CE-cured patients after the treatment, the implantation rate, hCG-positive rate, clinical pregnancy rate, clinical pregnancy rate with fetal heartbeat on D30, and ongoing pregnancy rate were significantly higher in group A than in group B. CONCLUSION: CE is closely related to RIF occurrence, and the combined oral administration of prednisone acetate and doxycycline can be a treatment option for patients with RIF with CE and improves reproductive outcomes, although it does not improve the CE cure rate compared with doxycycline treatment alone.

Blocking Caspase-1/Gsdmd and Caspase-3/-8/Gsdme pyroptotic pathways rescues silicosis in mice.

Millions of patients suffer from silicosis, but it remains an uncurable disease due to its unclear pathogenic mechanisms. Though the Nlrp3 inflammasome is involved in silicosis pathogenesis, inhibition of its classic downstream factors, Caspase-1 and Gsdmd, fails to block pyroptosis and cytokine release. To clarify the molecular mechanism of silicosis pathogenesis for new therapy, we examined samples from silicosis patients and genetic mouse models. We discovered an alternative pyroptotic pathway which requires cleavage of Gsdme by Caspases-3/8 in addition to Caspase-1/Gsdmd. Consistently, Gsdmd-/-Gsdme-/- mice showed markedly attenuated silicosis pathology, and Gsdmd-/-Gsdme-/- macrophages were resistant to silica-induced pyroptosis. Furthermore, we found that in addition to Caspase 1, Caspase-8 cleaved IL-1ß in silicosis, explaining why Caspase-1-/- mice also suffered from silicosis. Finally, we found that inhibitors of Caspase-1, -3, -8 or an FDA approved drug, dimethyl fumarate, could dramatically alleviate silicosis pathology through blocking cleavage of Gsdmd and Gsdme. This study highlights that Caspase-1/Gsdmd and Caspase-3/8/Gsdme-dependent pyroptosis is essential for the development of silicosis, implicating new potential targets and drug for silicosis treatment.

The Deficiency of SCARB2/LIMP-2 Impairs Metabolism via Disrupted mTORC1-Dependent Mitochondrial OXPHOS.

Deficiency in scavenger receptor class B, member 2 (SCARB2) is related to both Gaucher disease (GD) and Parkinson's disease (PD), which are both neurodegenerative-related diseases without cure. Although both diseases lead to weight loss, which affects the quality of life and the progress of diseases, the underlying molecular mechanism is still unclear. In this study, we found that Scarb2-/- mice showed significantly reduced lipid storage in white fat tissues (WAT) compared to WT mice on a regular chow diet. However, the phenotype is independent of heat production, activity, food intake or energy absorption. Furthermore, adipocyte differentiation and cholesterol homeostasis were unaffected. We found that the impaired lipid accumulation of Adiponectin-cre; Scarb2fl/fl mice was due to the imbalance between glycolysis and oxidative phosphorylation (OXPHOS). Mechanistically, the mechanistic target of rapamycin complex 1 (mTORC1)/ eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) pathway was down-regulated in Scarb2 deficient adipocytes, leading to impaired mitochondrial respiration and enhanced glycolysis. Altogether, we reveal the role of SCARB2 in metabolism regulation besides the nervous system, which provides a theoretical basis for weight loss treatment of patients with neurodegenerative diseases.

Epithelial STAT6 O-GlcNAcylation drives a concerted anti-helminth alarmin response dependent on tuft cell hyperplasia and Gasdermin C.

The epithelium is an integral component of mucosal barrier and host immunity. Following helminth infection, the intestinal epithelial cells secrete "alarmin" cytokines, such as interleukin-25 (IL-25) and IL-33, to initiate the type 2 immune responses for helminth expulsion and tolerance. However, it is unknown how helminth infection and the resulting cytokine milieu drive epithelial remodeling and orchestrate alarmin secretion. Here, we report that epithelial O-linked N-Acetylglucosamine (O-GlcNAc) protein modification was induced upon helminth infections. By modifying and activating the transcription factor STAT6, O-GlcNAc transferase promoted the transcription of lineage-defining Pou2f3 in tuft cell differentiation and IL-25 production. Meanwhile, STAT6 O-GlcNAcylation activated the expression of Gsdmc family genes. The membrane pore formed by GSDMC facilitated the unconventional secretion of IL-33. GSDMC-mediated IL-33 secretion was indispensable for effective anti-helminth immunity and contributed to induced intestinal inflammation. Protein O-GlcNAcylation can be harnessed for future treatment of type 2 inflammation-associated human diseases.

The Correlation between Chronic Endometritis and Tubal-Factor Infertility.

OBJECTIVE: To identify the prevalence and risk factors for chronic endometritis (CE) with tubal factors and the correlation between chronic endometritis and tubal factors among infertile populations. METHOD: A total of 52 patients with chronic endometritis (CE group) who underwent laparoscopy and hysteroscopic surgery were recruited between July 2020 and December 2021. A total of 38 patients without chronic endometritis (non-CE group) were included as a control. Patients with endometriosis and intra-uterine abnormalities were excluded. Endometrial samples were collected during surgery for CD138 immunohistochemistry staining for the diagnosis of CE. Preoperative information (including age, reproductive health characteristics, previous medical and surgical history), intra-operative information (including the patency of the fallopian tube, the presence of hydrosalpinx, score and the grade of tubal lesion condition) and post-operative information (counts of CD138-positive HPF in the endometrial specimen) were collected. RESULT: A multivariate analysis revealed that tubal factors with unilateral or bilateral occlusion were significantly higher in the CE group (OR 3.066, 95% CI 1.020-9.213, p = 0.046). The bilateral occlusion of fallopian tubes (OR 8.785, 95% CI 1.408-54.818, p = 0.020) rather than unilateral occlusion (OR 2.860, 95% CI 0.893-9.162, p = 0.077) was significantly associated with chronic endometritis. The presence of a hydrosalpinx on one side (OR 7.842, 95% CI 1.279-48.086, p = 0.026) or both sides (OR 9.450, 95% CI 1.037-86.148, p = 0.046) was significantly associated with chronic endometritis. The comparison of CD138-positive HPF counts among the tubal occlusion patients without hydrosalpinx, patients with unilateral hydrosalpinx and patients with bilateral hydrosalpinx were as follows: 1 HPF (50.00% vs. 12.50% vs. 11.11%, p = 0.051), 2 HPF (38.89% vs. 25.00% vs. 22.22%, p = 0.615), ≥3 HPF (11.11% vs. 62.50% vs. 66.67%, p = 0.005). The stage of tubal condition was positively correlated with CD138-positive HPF counts in women with chronic endometritis (r = 0.460, p = 0.001). CONCLUSION: CE was closely related to the blockage of fallopian tubes and hydrosalpinx. The severity degree of the fallopian lesion condition was associated with inflammation of the endometrium.

Enhanced Electroplasticity through Room-Temperature Dynamic Recrystallization in a Mg-3Al-1Sn-1Zn Alloy.

It has been well known that electric pulse can be utilized to enhance the plasticity of metals, which is attributed to the change of dislocation dynamics, e.g., localized planar slip to homogeneous wavy slip. Here, we show another effect of pulse current, which facilitates texture weakening through room-temperature dynamic recrystallization and additionally improve the plasticity of a polycrystalline Mg-3Al-1Sn-1Zn alloy. By conducting a tensile test under electrical pulse, we found that the peak flow stress and fracture strain depend strongly on current density. As peak current densities increases, the flow stress drops and the fracture strain increases. Our Electron Backscatter Diffraction results suggest that dynamic recrystallization occurs at room temperature, which develops a weakened texture. Our work provides a new insight into electroplasticity mechanism in Mg alloys.

Lactobacillus fermentum CQPC08 protects rats from lead-induced oxidative damage by regulating the Keap1/Nrf2/ARE pathway.

In this experiment, Lactobacillus fermentum CQPC08 (LF-CQPC08) isolated from traditionally fermented pickles was used to study its mitigation effect on lead acetate-induced oxidative stress and lead ion adsorption capacity in rats. In vitro experiments showed that the survival rate in artificial gastric juice and the growth efficiency in artificial bile salt of LF-CQPC08 was 93.6% ± 2.2% and 77.2% ± 0.8%, and the surface hydrophobicity rate was 45.5% ± 0.3%. The scavenging rates of hydroxyl radical, superoxide anion, and 1,1-diphenyl-2-picrylhydrazyl (DPPH) were 47.8% ± 0.9%, 63.9% ± 1.2%, and 83.6% ± 1.5%, respectively, and the reduction power was 107.3 ± 2.8 µmol L-1. LF-CQPC08 could not only adsorb 76.9% ± 1.0% lead ions in aqueous solution but also reduce the lead content in serum, liver, kidneys, and brain tissue of Sprague-Dawley (SD) rats, as well as maintain the cell structure and tissue state of the liver and kidneys. In addition, by examining the indicators of inflammation and oxidation in the serum, liver, and kidneys of SD rats, we found that LF-CQPC08 can reduce the proinflammatory factors interleukin (IL)-1 beta (1ß), IL-6, tumor necrosis factor alpha, and interferon gamma in the body, increase the level of anti-inflammatory factor IL-10, enhance the activity of antioxidant enzymes such as superoxide dismutase and catalase and glutathione levels in serum and organ tissues, and reduce the production of reactive oxygen species and accumulation of lipid peroxide malondialdehyde. LF-CQPC08 can also activate the Keap1/Nrf2/ARE signaling pathway to promote high-level expression of the downstream antioxidants heme oxygenase 1 (HO-1), NAD(P)H : quinone oxidoreductase 1 (NQO1), and γ-glutamylcysteine synthetase (γ-GCS). As food-grade lactic acid bacteria, LF-CQPC08 has great potential and research value in removing heavy metals from food and alleviating the toxicity of heavy metals in the future.

Lactobacillus plantarum HFY09 alleviates alcohol-induced gastric ulcers in mice via an anti-oxidative mechanism.

The protective effect of Lactobacillus plantarum HFY09 (LP-HFY09) on alcohol-induced gastric ulcers was investigated. Gastric morphology observation and pathological tissue sections showed that LP-HFY09 effectively relieved gastric tissue injury. The biochemical indicator detection showed that LP-HFY09 increased superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione (GSH), prostaglandin E2 (PGE2), and somatostatin (SS) levels, and decreased malondialdehyde (MDA) levels. Moreover, LP-HFY09 inhibited the levels of inflammatory cytokines interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α), and elevated the level of anti-inflammatory cytokine IL-10. The quantitative polymerase chain reaction (q-PCR) examination revealed that LP-HFY09 enhanced the mRNA expression of nuclear factor E2-related factor 2 (Nrf2) and downstream genes, including copper/zinc superoxide dismutase (SOD1), heme oxygenase-1 (HO-1), gamma-glutamylcysteine synthetase (GSH1), manganese superoxide dismutase (SOD2), catalase (CAT), and GSH-Px. This study indicated that LP-HFY09 alleviated alcohol-induced gastric ulcers by increasing gastric mucosa defense factor, and inhibiting oxidative stress and the inflammatory response. PRACTICAL APPLICATIONS: LP-HFY09 has the potential to be investigated as a treatment for gastric injury induced by alcohol.

Effect of Pulsed Current on the Tensile Deformation Behavior and Microstructure Evolution of AZ80 Magnesium Alloy.

In this work, the tensile deformation behavior of an as-extruded AZ80 magnesium alloy under pulsed current (PC) was investigated based on microstructure observations. We found that compared with the tensile tests at room temperature (RT) and given temperature (GT), the flow stress is reduced due to both thermal and athermal effects of pulsed current. A quasi-in-situ electron backscatter diffraction (EBSD) analysis reveals that at the same strain, the geometrically necessary dislocation (GND) density of the RT sample is the highest, followed by the GT sample and the PC sample. This proves that the athermal effect can promote the annihilation of dislocations and slow down dislocation pileup, which reduces the flow stress. In addition, the twinning behavior under different deformation conditions was studied; the twins are {10-12} tension twins, which are activated with the assistance of local stress. We found that the twin fraction in the PC sample is lower than that in the RT and GT samples, due to the least accumulation of GNDs at grain boundaries, which decreases the nucleation of {10-12} tension twins.

Human embryo gene editing: God's scalpel or Pandora's box?

Gene editing refers to the site-specific modification of the genome, which mainly focuses on basic research, model organism construction and treatment and prevention of disease. Since the first application of CRISPR/Cas9 on the human embryo genome in 2015, the controversy over embryo gene editing (abbreviated as EGE in the following text) has never stopped. At present, the main contradictions focus on (1) ideal application prospects and immature technologies; (2) scientific progress and ethical supervision; and (3) definition of reasonable application scope. In fact, whether the EGE is 'God's scalpel' or 'Pandora's box' depends on the maturity of the technology and ethical supervision. This non-systematic review included English articles in NCBI, technical documents from the Human Fertilization and Embryology Authority as well as reports in the media, which performed from 1980 to 2018 with the following search terms: 'gene editing, human embryo, sequence-specific nuclease (SSN) (CRISPR/Cas, TALENT, ZFN), ethical consideration, gene therapy.' Based on the research status of EGE, this paper summarizes the technical defects and ethical controversies, enumerates the optimization measures and looks forward to the application prospect, aimed at providing some suggestions for the development trend. We should regard the research and development of EGE optimistically, improve and innovate the technology boldly and apply its clinical practice carefully.

A SNP of bacterial blc disturbs gut lysophospholipid homeostasis and induces inflammation through epithelial barrier disruption.

BACKGROUND: Alteration of commensal bacterial composition is associated with many inflammatory diseases. However, few studies have pinpointed the specific bacterial genes that may suppress host immune responses against microbes and maintain homeostasis in the host intestine. METHODS: High-throughput screening was performed in Caenorhabditis elegans with a single gene knockout ut screening was performed in Caenorhabditis elegans with a single gene knockout Escherichia coli (E. coli) library and identified the immune suppression gene blc. The coding sequences of blc among different kinds of E. coli strains were aligned to identify the single nucleotide polymorphisms (SNPs). Physiological and biochemical experiments were performed in C. elegans and mice to explore the function of the blc variant. FINDINGS: By screening 3983 E. coli mutants, we discovered that 9 bacterial genes, when deleted, activate innate immunity in the host C. elegans. Among these 9 genes, the gene encoding blc showed a distinctive SNP in many clinically pathogenic bacteria. We found that bacteria with this SNP, which converts Blc G84 to Blc E84, are highly enriched in the faeces of patients with inflammatory bowel disease (IBD). Exposure to BlcE84-encoding bacteria resulted in epithelial barrier disruption and immune activation in both worms and mice. Detailed analysis indicated that infection with BlcE84-encoding bacteria causes a significant decrease in LPE levels in the intestine and subsequently disrupts gut epithelial integrity in mice. Consistently, the levels of LPE in patients with IBD are significantly lower than those in healthy people. Finally, supplementation with LPE, which activates LPA1/PLCß/PKC signaling, reversed the defects induced by BlcE84-encoding bacteria. INTERPRETATION: Our results identified a novel bacterial gene, blc, in E. coli that regulates host gut integrity and immunity. FUND: The Ministry of Science and Technology of China; the National Natural Science Foundation of China; and the Natural Science Foundation of Jiangsu Province.

N-Doped carbon coated bismuth nanorods with a hollow structure as an anode for superior-performance potassium-ion batteries.

Bismuth (Bi) is a promising anode material for potassium-ion batteries due to its high energy density. However, the large volume change limits its applications. Herein, N-doped carbon coated Bi nanorods with a hollow structure are fabricated and they exhibit excellent long-term cycling performance (88% capacity retention over 1000 cycles) and high-rate ability (297 mA h g-1 at 20C, 94% capacity of that at 1C). Furthermore, the mechanism was expounded by in situ XRD, indicating a multi-phase reaction for the initial discharge process and three two-phase reactions for the subsequent charge/discharge processes.