The use of proteins and peptides-based therapy in managing and preventing pathogenic viruses.

Therapeutic proteins have been employed for centuries and reached approximately 50 % of all drugs investigated. By 2023, they represented one of the top 10 largest-selling pharma products ($387.03 billion) and are anticipated to reach around $653.35 billion by 2030. Growth hormones, insulin, and interferon (IFN α, γ, and ß) are among the leading applied therapeutic proteins with a higher market share. Protein-based therapies have opened new opportunities to control various diseases, including metabolic disorders, tumors, and viral outbreaks. Advanced recombinant DNA biotechnology has offered the production of therapeutic proteins and peptides for vaccination, drugs, and diagnostic tools. Prokaryotic and eukaryotic expression host systems, including bacterial, fungal, animal, mammalian, and plant cells usually applied for recombinant therapeutic proteins large-scale production. However, several limitations face therapeutic protein production and applications at the commercial level, including immunogenicity, integrity concerns, protein stability, and protein degradation under different circumstances. In this regard, protein-engineering strategies such as PEGylation, glycol-engineering, Fc-fusion, albumin conjugation, and fusion, assist in increasing targeting, product purity, production yield, functionality, and the half-life of therapeutic protein circulation. Therefore, a comprehensive insight into therapeutic protein research and findings pave the way for their successful implementation, which will be discussed in the current review.

Corneal myxoma following micro-pulse cyclophotocoagulation in a young female: A case report.

INTRODUCTION: Corneal myxoma is a rare benign tumor that can occur in the cornea where the exact cause remains unknown. However, it is thought to be a reactive process that can be caused by corneal infections, ectasia, ocular trauma, or surgery. PRESENTATION OF CASE: In this case report, we describe a 35-year-old-woman who presented with corneal myxoma after micro-pulse cyclophotocoagulation (MPCPC). The patient presented with decreased vision due to a large pedunculated white corneal mass after being treated with MPCPC as a non-surgical management of her pre-existing glaucoma. The corneal mass was localized to the sub-epithelial space and was excised successfully by a minimal invasive procedure without recurrence over a 1-year period. DISCUSSION: Corneal myxomas are unusual benign tumors typically seen in adults as whitish gelatinous lesion. Only a few individual cases and case series have been reported in the literature. The exact pathogenesis is yet to be known. The lesion is thought to be due to an inflammatory process. We are reporting a case of corneal myxoma that has occurred after MPCPC which is a non-surgical cyclodestructive procedure. The procedure has not been mentioned previously as a risk factor for corneal myxoma. Our case is the first corneal myxoma developing after MPCPC. CONCLUSION: We report a corneal myxoma noted in a young female after a non-surgical laser procedure. Though the lesion is rare, it should be considered in physicians' differential of a corneal mass especially in the presence of chronic ocular.

Modern Internet Search Analytics: Is There a Difference in What Patients are Searching Regarding the Operative and Nonoperative Management of Scoliosis?

STUDY DESIGN: Observational Study. OBJECTIVES: This study aimed to investigate the most searched types of questions and online resources implicated in the operative and nonoperative management of scoliosis. METHODS: Six terms related to operative and nonoperative scoliosis treatment were searched on Google's People Also Ask section on October 12, 2023. The Rothwell classification was used to sort questions into fact, policy, or value categories, and associated websites were classified by type. Fischer's exact tests compared question type and websites encountered between operative and nonoperative questions. Statistical significance was set at the .05 level. RESULTS: The most common questions concerning operative and nonoperative management were fact (53.4%) and value (35.5%) questions, respectively. The most common subcategory pertaining to operative and nonoperative questions were specific activities/restrictions (21.7%) and evaluation of treatment (33.3%), respectively. Questions on indications/management (13.2% vs 31.2%, P < .001) and evaluation of treatment (10.1% vs 33.3%, P < .001) were associated with nonoperative scoliosis management. Medical practice websites were the most common website to which questions concerning operative (31.9%) and nonoperative (51.4%) management were directed to. Operative questions were more likely to be directed to academic websites (21.7% vs 10.0%, P = .037) and less likely to be directed to medical practice websites (31.9% vs 51.4%, P = .007) than nonoperative questions. CONCLUSIONS: During scoliosis consultations, spine surgeons should emphasize the postoperative recovery process and efficacy of conservative treatment modalities for the operative and nonoperative management of scoliosis, respectively. Future research should assess the impact of website encounters on patients' decision-making.

Biomineralization of Polyelectrolyte-Functionalized Electrospun Fibers: Optimization and In Vitro Validation for Bone Applications.

In recent years, polyelectrolytes have been successfully used as an alternative to non-collagenous proteins to promote interfibrillar biomineralization, to reproduce the spatial intercalation of mineral phases among collagen fibrils, and to design bioinspired scaffolds for hard tissue regeneration. Herein, hybrid nanofibers were fabricated via electrospinning, by using a mixture of Poly ɛ-caprolactone (PCL) and cationic cellulose derivatives, i.e., cellulose-bearing imidazolium tosylate (CIMD). The obtained fibers were self-assembled with Sodium Alginate (SA) by polyelectrolyte interactions with CIMD onto the fiber surface and, then, treated with simulated body fluid (SBF) to promote the precipitation of calcium phosphate (CaP) deposits. FTIR analysis confirmed the presence of SA and CaP, while SEM equipped with EDX analysis mapped the calcium phosphate constituent elements, estimating an average Ca/P ratio of about 1.33-falling in the range of biological apatites. Moreover, in vitro studies have confirmed the good response of mesenchymal cells (hMSCs) on biomineralized samples, since day 3, with a significant improvement in the presence of SA, due to the interaction of SA with CaP deposits. More interestingly, after a decay of metabolic activity on day 7, a relevant increase in cell proliferation can be recognized, in agreement with the beginning of the differentiation phase, confirmed by ALP results. Antibacterial tests performed by using different bacteria populations confirmed that nanofibers with an SA-CIMD complex show an optimal inhibitory response against S. mutans, S. aureus, and E. coli, with no significant decay due to the effect of CaP, in comparison with non-biomineralized controls. All these data suggest a promising use of these biomineralized fibers as bioinspired membranes with efficient antimicrobial and osteoconductive cues suitable to support bone healing/regeneration.

Conformational changes induced by selected flavor compounds from spices regulate the binding ability of myofibrillar proteins to aldehyde compounds.

Interactions among flavor compounds from spices (FCS) and myofibrillar proteins (MP) were investigated. Fluorescence and Fourier transform infrared spectroscopy showed that hydrogen bonding and hydrophobic interactions were the main binding forces between FCS and MP. The FCS increased the particle size and SH content of MP and caused a reduction of zeta potential from -5.23 to -6.50 mV. Furthermore, FCS could modify the binding ability of MP and aldehydes. Eugenol reduced the ability of MP to bond with aldehydes by 22.70-47.87 %. Molecular dynamics simulations demonstrated that eugenol may combat nonanal to attain binding site of amino acid residue (PHE165) and induce protein conformational changes. Electrostatic interactions and van der Waals forces within myosin-nonanal may be disrupted by these alterations, which could reduce stability of complex and cause release of nonanal. This study could provide new insights into regulating the ability of proteins to release and hold flavors.

Influence of Dietary Probiotic and Alpha-Monolaurin on Performance, Egg Quality, Blood Constituents, and Egg Fatty Acids' Profile in Laying Hens.

This work was designed to evaluate the advantages of using multi-strain probiotics feed (Bacillus subtilis, Bacillus licheniformis and Clostridium butyricum) (PRO) and alpha-monolaurin (AML) on laying performance, criteria of egg quality, blood parameters, and yolk fatty acids' profile in laying hens. One hundred forty of Bovans brown laying hens at 45 weeks old (25th week of egg production) were randomly allocated into four groups, with seven replicates of five birds each in a complete randomized design. The first group was fed a basal diet without feed additives (0 g/kg diet), and the second, third, and fourth groups received diets containing 1 g PRO, 1 g AML, and 1 g PRO + 1 g AML/kg diet, respectively. No significant impacts of PRO, AML, or their mixture on body weight (BW), body weight gain (BWG), feed intake (FI), or egg weight. Egg production, egg mass, and feed conversion ratio (FCR) were enhanced by 1 g PRO/kg and /or 1 g AML/kg supplementation in laying hen diets. Furthermore, egg shape index, eggshell thickness, and yolk color were statistically higher by PRO and AML supplementation at 55 weeks. However, oviduct, infundibulum, and uterus weights were significantly decreased by 1 g PRO or/and 1 g AML. Additionally, total cholesterol, triglycerides, low density lipoprotein (LDL), glucose, and glutamate pyruvate transaminase (GPT) levels were decreased by PRO and AML supplementation. In conclusion, it seems that dietary inclusion with 1 g PRO/kg, 1 g of AML/kg, and 1 g PRO + 1 g AML improved egg production, egg mass, FCR, and yolk fatty acids profile and lowered total cholesterol and malondialdehyde (MDA) contents in laying hens.

Risk Factors for Undergoing Surgical Intervention for Vertebral Compression Fractures: An Analysis of 703,499 Patients.

STUDY DESIGN: Retrospective Cohort OBJECTIVES: Vertebral compression fractures (VCFs) are typically treated nonoperatively, but can be treated with either kyphoplasty or vertebroplasty when indicated. The decision to treat patients with/without surgical intervention is dependent on the severity of deformity and patient risk profile. The aims of this study were to: 1) compare baseline patient demographics, 2) identify risk factors of patients undergoing operative versus nonoperative management, and 3) identify patient-specific risk factors associated with post-operative re-admissions. METHODS: This retrospective database study used patient information from January 1st, 2010, to October 31st, 2021. Cohorts were identified by patients diagnosed with VCFs through International Classification of Disease, Ninth Revision (ICD-9), ICD-10 codes, identifying those undergoing kyphoplasty/vertebroplasty via Current Procedural Terminology (CPT) codes. The two research domains utilized in this investigation were baseline demographic profiles of patients who underwent kyphoplasty or vertebroplasty for treatment of VCFs, and those who underwent nonoperative management served as the control cohort. RESULTS: Of the 703,499 patients diagnosed with VCFs, 76,126 patients (10.8%) underwent kyphoplasty or vertebroplasty within 90 days of diagnosis of a VCF. Univariate analysis demonstrated female sex was associated with increased risk of undergoing surgical management for VCF (p<0.0001). Several co-morbidities were significantly associated with increased rates of readmission including hypertension, tobacco use, coronary artery disease, and COPD (p <0.0001 for all). CONCLUSIONS: This study highlights specific comorbidities that are significantly associated with higher rates of kyphoplasty or vertebroplasty for the treatment of thoracolumbar wedge compression fractures and increased risk for 90-day post-operative hospital readmission.

Trifluoperazine mitigates cyclophosphamide-induced hepatic oxidative stress, inflammation, and apoptosis in mice by modulating the AKT/mTOR-driven autophagy and Nrf2/HO-1 signaling cascades.

AIM: This study aims to investigate the hepatoprotective effect of the antipsychotic drug trifluoperazine (TFP) against cyclophosphamide (CPA)-induced hepatic injury by exploring its effect on autophagy and the Nrf2/HO-1 signaling pathway. MAIN METHODS: The hepatotoxicity of CPA was assessed by biochemical analysis of the serum hepatotoxicity markers (ALT, AST, and direct bilirubin), histopathological examination, and ultrastructure analysis by transmission electron microscopy (TEM). The ELISA technique was used to assess the hepatic content of oxidative stress (MDA and SOD) and inflammatory markers (IL-1ß and TNF-α). Immunohistochemical assessment was used to investigate the hepatic expression of NF-κB, Nrf2, caspase-3, as well as autophagy flux markers (p62 and LC3B). The mRNA expression of HO-1 was assessed using RT-qPCR. Western blot assay was used to determine the expression of p-AKT and p-mTOR. KEY FINDINGS: TFP improved CPA-induced hepatotoxicity by reducing the elevated hepatotoxicity markers, and alleviating the histopathological changes with improving ultrastructure alterations. It also reduced oxidative stress by reducing MDA content and upregulating SOD activity. In addition, it exhibited anti-inflammatory and anti-apoptotic effects by decreasing NF-κB expression, IL-1ß, TNF-α levels, and caspase-3 expression. Furthermore, TFP-induced hepatoprotection was mediated by favoring Nrf2 expression and increasing the mRNA level of HO-1. As well, it improved autophagy by increasing LC3B expression concurrently with reducing p62 expression. Moreover, TFP modulated the AKT/mTOR pathway by reducing the expression of p-AKT and p-mTOR. SIGNIFICANCE: TFP significantly protected against CPA-induced hepatotoxicity by upregulating Nrf2/HO-1 signaling along with enhancement of protective autophagy via inhibition of the AKT/mTOR signaling pathway.

Risk Factors for Readmission Following Surgical Decompression for Spinal Epidural Abscesses: An Analysis of 4595 Patients.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: The study aimed to (1) compare baseline demographics of patients undergoing surgery for SEA who were/were not readmitted; (2) identify risk factors for 90-day readmissions; and (3) quantify 90-day episode-of-care health care costs. BACKGROUND: Spinal epidural abscess (SEA), while rare, occurring ~2.5-5.1/10,000 admissions, may lead to permanent neurologic deficits and mortality. Definitive treatment often involves surgical intervention via decompression. METHODS: A search of the PearlDiver database from 2010 to 2021 for patients undergoing decompression for SEA identified 4595 patients. Cohorts were identified through the International Classification of Disease, Ninth Revision (ICD-9), ICD-10, and Current Procedural Terminology codes. Baseline demographics of patients who were/were not readmitted within 90 days following decompression were aggregated/compared, identifying factors associated with readmission. Using Bonferroni correction, a P-value<0.001 was considered statistically significant. RESULTS: Readmission within 90 days of surgical decompression occurred in 36.1% (1659/4595) of patients. While age/gender were not associated with readmission rate, alcohol use disorder, arrhythmia, chronic kidney disease, ischemic heart disease, and obesity were associated with readmission. Readmission risk factors included fluid/electrolyte abnormalities, obesity, paralysis, tobacco use, and pathologic weight loss (P<0.0001). Mean same-day total costs ($17,920 vs. $8204, P<0.001) and mean 90-day costs ($46,050 vs. $15,200, P<0.001) were significantly higher in the readmission group. CONCLUSION: A substantial proportion of patients (36.1%) are readmitted within 90 days following surgical decompression for SEA. The top 5 risk factors in descending order are fluid/electrolyte abnormalities, pathologic weight loss, tobacco use, pre-existing paralysis, and obesity. This study highlights areas for perioperative medical optimization that may reduce health care utilization.

GPT-4 as a Source of Patient Information for Anterior Cervical Discectomy and Fusion: A Comparative Analysis Against Google Web Search.

STUDY DESIGN: Comparative study. OBJECTIVES: This study aims to compare Google and GPT-4 in terms of (1) question types, (2) response readability, (3) source quality, and (4) numerical response accuracy for the top 10 most frequently asked questions (FAQs) about anterior cervical discectomy and fusion (ACDF). METHODS: "Anterior cervical discectomy and fusion" was searched on Google and GPT-4 on December 18, 2023. Top 10 FAQs were classified according to the Rothwell system. Source quality was evaluated using JAMA benchmark criteria and readability was assessed using Flesch Reading Ease and Flesch-Kincaid grade level. Differences in JAMA scores, Flesch-Kincaid grade level, Flesch Reading Ease, and word count between platforms were analyzed using Student's t-tests. Statistical significance was set at the .05 level. RESULTS: Frequently asked questions from Google were varied, while GPT-4 focused on technical details and indications/management. GPT-4 showed a higher Flesch-Kincaid grade level (12.96 vs 9.28, P = .003), lower Flesch Reading Ease score (37.07 vs 54.85, P = .005), and higher JAMA scores for source quality (3.333 vs 1.800, P = .016). Numerically, 6 out of 10 responses varied between platforms, with GPT-4 providing broader recovery timelines for ACDF. CONCLUSIONS: This study demonstrates GPT-4's ability to elevate patient education by providing high-quality, diverse information tailored to those with advanced literacy levels. As AI technology evolves, refining these tools for accuracy and user-friendliness remains crucial, catering to patients' varying literacy levels and information needs in spine surgery.

Derivation of a novel antimicrobial peptide from the Red Sea Brine Pools modified to enhance its anticancer activity against U2OS cells.

Cancer associated drug resistance is a major cause for cancer aggravation, particularly as conventional therapies have presented limited efficiency, low specificity, resulting in long term deleterious side effects. Peptide based drugs have emerged as potential alternative cancer treatment tools due to their selectivity, ease of design and synthesis, safety profile, and low cost of manufacturing. In this study, we utilized the Red Sea metagenomics database, generated during AUC/KAUST Red Sea microbiome project, to derive a viable anticancer peptide (ACP). We generated a set of peptide hits from our library that shared similar composition to ACPs. A peptide with a homeodomain was selected, modified to improve its anticancer properties, verified to maintain high anticancer properties, and processed for further in-silico prediction of structure and function. The peptide's anticancer properties were then assessed in vitro on osteosarcoma U2OS cells, through cytotoxicity assay (MTT assay), scratch-wound healing assay, apoptosis/necrosis detection assay (Annexin/PI assay), RNA expression analysis of Caspase 3, KI67 and Survivin, and protein expression of PARP1. L929 mouse fibroblasts were also assessed for cytotoxicity treatment. In addition, the antimicrobial activity of the peptide was also examined on E coli and S. aureus, as sample representative species of the human bacterial microbiome, by examining viability, disk diffusion, morphological assessment, and hemolytic analysis. We observed a dose dependent cytotoxic response from peptide treatment of U2OS, with a higher tolerance in L929s. Wound closure was debilitated in cells exposed to the peptide, while annexin fluorescent imaging suggested peptide treatment caused apoptosis as a major mode of cell death. Caspase 3 gene expression was not altered, while KI67 and Survivin were both downregulated in peptide treated cells. Additionally, PARP-1 protein analysis showed a decrease in expression with peptide exposure. The peptide exhibited minimal antimicrobial activity on critical human microbiome species E. coli and S. aureus, with a low inhibition rate, maintenance of structural morphology and minimal hemolytic impact. These findings suggest our novel peptide displayed preliminary ACP properties against U2OS cells, through limited specificity, while triggering apoptosis as a primary mode of cell death and while having minimal impact on the microbiological species E. coli and S. aureus.

Insights into flavor formation of braised chicken: Based on E-nose, GC-MS, GC-IMS, and UPLC-Q-Exactive-MS/MS.

Effects of braising duration on volatile organic compounds (VOCs) and lipids in chicken were investigated. Aroma profiles identified by an electronic nose were effective in differentiating braising stages. During braising process, a total of 25 key VOCs were detected in braised chicken, and sample braised for 210 min exhibited the highest level of key VOCs. Additionally, a gas chromatography mass spectrometry fingerprint was established to evaluate the distribution of VOCs throughout the braising process. Partial least square discriminant analysis indicated that 2-heptanone, 3-methyl-2-butanone, octanal, nonanal, butanal, (E)-2-pentenal, 1-octen-3-ol, 1-hexanol, pentanal, hexanal, and 1-pentanol significantly affected flavor characteristics of braised chicken. Furthermore, 88 differential lipids were screened, and glycerolipids metabolic was found to be main metabolic pathway during braising process. Triglycerides (TG) and phosphatidyl ethanolamine (PE), such as TG (16:0/18:1/18:2), TG (18:0/18:1/18:2), TG (18:1/18:2/18:3), TG (18:1/18:1/18:2), PE (O-18:2/18:2), PE(O-18:2/18:1), and TG (16:0/16:1/18:2), played a vital role in the generation of VOCs.

Evolution of Endogenous Retroviruses in the Subfamily of Caprinae.

The interest in endogenous retroviruses (ERVs) has been fueled by their impact on the evolution of the host genome. In this study, we used multiple pipelines to conduct a de novo exploration and annotation of ERVs in 13 species of the Caprinae subfamily. Through analyses of sequence identity, structural organization, and phylogeny, we defined 28 ERV groups within Caprinae, including 19 gamma retrovirus groups and 9 beta retrovirus groups. Notably, we identified four recent and potentially active groups prevalent in the Caprinae genomes. Additionally, our investigation revealed that most long noncoding genes (lncRNA) and protein-coding genes (PC) contain ERV-derived sequences. Specifically, we observed that ERV-derived sequences were present in approximately 75% of protein-coding genes and 81% of lncRNA genes in sheep. Similarly, in goats, ERV-derived sequences were found in approximately 74% of protein-coding genes and 75% of lncRNA genes. Our findings lead to the conclusion that the majority of ERVs in the Caprinae genomes can be categorized as fossils, representing remnants of past retroviral infections that have become permanently integrated into the genomes. Nevertheless, the identification of the Cap_ERV_20, Cap_ERV_21, Cap_ERV_24, and Cap_ERV_25 groups indicates the presence of relatively recent and potentially active ERVs in these genomes. These particular groups may contribute to the ongoing evolution of the Caprinae genome. The identification of putatively active ERVs in the Caprinae genomes raises the possibility of harnessing them for future genetic marker development.

Physio-molecular responses of tomato cultivars to biotic stress: Exploring the interplay between Alternaria alternata OP881811 infection and plant defence mechanisms.

Plant fungal diseases impose a formidable challenge for global agricultural productivity, a meticulous examination of host-pathogen interactions. In this intricate study, an exhaustive investigation was conducted on infected tomatoes obtained from Egyptian fields, leading to the precise molecular identification of the fungal isolate as Alternaria alternata (OP881811), and the isolate showed high identity with Chinese isolates (ON973896 and ON790502). Subsequently, fourteen diverse tomato cultivars; Cv Ferment, Cv 103, Cv Damber, Cv 186, Cv 4094, Cv Angham, Cv N 17, Cv Gesma, Cv 010, Cv branch, cv 2020, Cv 023, Cv Gana and Cv 380 were meticulously assessed to discern their susceptibility levels upon inoculation with Alternaria alternata. Thorough scrutiny of disease symptom manifestation and the extent of tomato leaf damage ensued, enabling a comprehensive evaluation of cultivar responses. Results unveiled a spectrum of plant susceptibility, with three cultivars exhibiting heightened vulnerability (Cv Ferment, Cv 103 and Cv Damber), five cultivars displaying moderate susceptibility (Cv 186, Cv 4094, Cv Angham, Cv N 17 and Cv Gesma), and six cultivars demonstrating remarkable resilience to the pathogen (Cv 010, Cv branch, cv, 2020; Cv 023, Cv Gana and Cv 380). In order to gain a thorough understanding of the underlying physiological patterns indicative of plant resistance against A. alternata, an in-depth exploration of polyphenols, flavonoids, and antioxidant enzymes ensued. These key indicators were closely examined, offering valuable insights into the interplay between plant physiology and pathogen response. Robust correlations emerged, with higher contents of these compounds correlating with heightened susceptibility, while lower levels were indicative of enhanced plant tolerance. In tandem with the physiological assessment, a thorough investigation of four pivotal defensive genes (PR5, PPO, PR3, and POX) was undertaken, employing cutting-edge Real-Time PCR technology. Gene expression profiles displayed intriguing variations across the evaluated tomato cultivars, ultimately facilitating the classification of cultivars into distinct groups based on their levels of resistance, moderate susceptibility, or heightened sensitivity. By unravelling the intricate dynamics of plant susceptibility, physiological responses, and patterns of gene expression, this comprehensive study paves the way for targeted strategies to combat plant fungal diseases. The findings contribute valuable insights into host-pathogen interactions and empower agricultural stakeholders with the knowledge required to fortify crop resilience and safeguard global food security.

Functionalization of bacterial cellulose: Exploring diverse applications and biomedical innovations: A review.

The demand for the functionalization of additive materials based on bacterial cellulose (BC) is currently high due to their potential applications across various sectors. The preparation of BC-based additive materials typically involves two approaches: in situ and ex situ. In situ modifications entail the incorporation of additive materials, such as soluble and dispersed substances, which are non-toxic and not essential for bacterial cell growth during the production process. However, these materials can impact the yield and self-assembly of BC. In contrast, ex situ modification occurs subsequent to the formation of BC, where the additive materials are not only adsorbed on the surface but also impregnated into the BC pellicle, while the BC slurry was homogenized with other additive materials and gelling agents to create composite films using the casting method. This review will primarily focus on the in situ and ex situ functionalization of BC then sheds light on the pivotal role of functionalized BC in advancing biomedical technologies, wound healing, tissue engineering, drug delivery, bone regeneration, and biosensors.

Peptide nucleic acid-assisted generation of targeted double-stranded DNA breaks with T7 endonuclease I.

Gene-editing technologies have revolutionized biotechnology, but current gene editors suffer from several limitations. Here, we harnessed the power of gamma-modified peptide nucleic acids (γPNAs) to facilitate targeted, specific DNA invasion and used T7 endonuclease I (T7EI) to recognize and cleave the γPNA-invaded DNA. Our data show that T7EI can specifically target PNA-invaded linear and circular DNA to introduce double-strand breaks (DSBs). Our PNA-Guided T7EI (PG-T7EI) technology demonstrates that T7EI can be used as a programmable nuclease capable of generating single or multiple specific DSBs in vitro under a broad range of conditions and could be potentially applied for large-scale genomic manipulation. With no protospacer adjacent motif (PAM) constraints and featuring a compact protein size, our PG-T7EI system will facilitate and expand DNA manipulations both in vitro and in vivo, including cloning, large-fragment DNA assembly, and gene editing, with exciting applications in biotechnology, medicine, agriculture, and synthetic biology.

Ticagrelor Versus Clopidogrel in Endovascular Therapy for Cerebral Aneurysms: A Systematic Review and Meta-Analysis.

BACKGROUND: Antiplatelet therapy is pivotal in endovascular treatment for intracranial aneurysms. However, there is a lack of studies comparing ticagrelor to clopidogrel in patients with aneurysms undergoing endovascular therapy. Additionally, the existing literature lacks adequate sample size, significant subgrouping, and follow-up, making our study important to cover these gaps. METHODS: We searched 5 databases to collect all relevant studies. Categorical outcomes were pooled as relative risk (R.R.) with a 95% confidence interval (CI). In the single-arm meta-analysis, outcomes were pooled as proportions and their corresponding 95% CI. RESULTS: This comprehensive analysis of 18 studies involving 2,427 patients. For thromboembolic events, the pooled (R.R.) did not show significant differences, whether considering overall events. A similar pattern was observed for thromboembolic events stratified by aneurysmal rupture status, with no significant differences in overall events. Hemorrhagic events did not also exhibit significant differences in previously mentioned stratifications. Furthermore, there were no substantial differences in death and mRS (0-2) on discharge between Ticagrelor and Clopidogrel. Single-arm meta-analyses for Ticagrelor demonstrated low rates of thromboembolic events, hemorrhage, death, and favorable mRS scores, with associated confidence intervals (CIs). Main line of endovascular treatment did not significantly affect either thromboembolic or hemorrhagic outcomes with Ticagrelor and Clopidogrel. CONCLUSIONS: We found no significant differences in key outcomes like thromboembolic events, hemorrhagic events, mortality rates, and favorable mRS (0-2) upon discharge in the studied patients between Ticagrelor and Clopidogrel. Moreover, the single-arm meta-analysis for Ticagrelor revealed low rates of thromboembolic events, hemorrhage, mortality, and high rates of favorable mRS scores.

Harnessing Peptide Nucleic Acids and the Eukaryotic Resolvase MOC1 for Programmable, Precise Generation of Double-Strand DNA Breaks.

Programmable site-specific nucleases (SSNs) hold extraordinary promise to unlock myriad gene editing applications in medicine and agriculture. However, developing small and specific SSNs is needed to overcome the delivery and specificity translational challenges of current genome engineering technologies. Structure-guided nucleases have been harnessed to generate double-strand DNA breaks but with limited success and translational potential. Here, we harnessed the power of peptide nucleic acids (PNAs) for site-specific DNA invasion and the generation of localized DNA structures that are recognized and cleaved by the eukaryotic resolvase AtMOC1 from Arabidopsis thaliana. We named this technology PNA-assisted Resolvase-mediated (PNR) editing. We tested the PNR editing concept in vitro and demonstrated its precise target specificity, examined the nucleotide requirement around the PNA invasion for the AtMOC1-mediated cleavage, mapped the AtMOC1-mediated cleavage sites, tested the role of different types and lengths of PNA molecules invasion into dsDNA for the AtMOC1-mediated cleavage, optimized the in vitro PNA invasion and AtMOC1 cleavage conditions such as temperature, buffer conditions, and cleavage time points, and demonstrated the multiplex cleavage for precise fragment release. We discuss the best design parameters for efficient, site-specific in vitro cleavage using PNR editors.