Uncovering the complexity of structural variants in four individuals with autism spectrum disorder.

Autism spectrum disorder (ASD) is an increasingly recognized childhood developmental disorder. Despite extensive study, causal variants and molecular diagnosis remain elusive. There is both heterogeneity of the phenotype, as well as the genetic landscape associated with phenotype, which includes both inherited and de novo mutations.

Green synthesis of nanoparticles using medicinal plants as an eco-friendly and therapeutic potential approach for neurodegenerative diseases: a comprehensive review.

Central nervous system disorders impact over 1.5 billion individuals globally, with neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases being particularly prominent. These conditions, often associated with aging, present debilitating symptoms including memory loss and movement difficulties.

Rearrangements of viral and human genomes at human papillomavirus integration events and their allele-specific impacts on cancer genome regulation.

Human papillomavirus (HPV) integration has been implicated in transforming HPV infection into cancer. To resolve genome dysregulation associated with HPV integration, we performed Oxford Nanopore long-read sequencing on 72 cervical cancer genomes from an Ugandan dataset that was previously characterized using short-read sequencing. We found recurrent structural rearrangement patterns at HPV integration events, which we categorized as: del(etion)-like, dup(lication)-like, translocation, multibreakpoint, or repeat region integrations.

Long-read sequencing for detection and subtyping of Prader-Willi and Angelman syndromes.

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are imprinting disorders caused by genetic or epigenetic aberrations of 15q11.2-q13. Their clinical testing is often multitiered; diagnostic testing begins with methylation-specific multiplex ligation-dependent probe amplification or methylation-sensitive PCR and then proceeds to molecular subtyping to determine the mechanism and recurrence risk.

Cloning and Optimization of Intracellular Expression of Human Interferon β-1a in GS115.

Background: Interferon-beta (IFN-β) is a cytokine with a wide range of biological and pharmaceutical applications, including multiple sclerosis (MS), cancer, some autoimmune disorders, and viral infectious diseases. Thus, many studies have been performed to develop novel strategies for the high-yield production of functional IFN-β in a cost-effective approach. Here, we aimed to improve the intracellular expression of IFN-β-1a in .

Integrated bioprocessing and genetic strategies to enhance soluble expression of anti-HER2 immunotoxin in E. Coli.

Immunotoxins are widely applied for cancer therapy. However, bacterial expression of immunotoxins usually leads to the formation of insoluble and non-functional recombinant proteins. This study was aimed to improve soluble expression of a novel anti-HER2 immunotoxin under the regulation of the trc promoter in Escherichia coli by optimization of the cultivation conditions using response surface methodology (RSM).

More balance toward activating receptors and cytotoxic activity of NK cells ex vivo differentiated from human umbilical cord blood-derived CD34 stem cells in comparison with peripheral blood NK cells.

Adoptive immunotherapies that use functional NK cells depend on the availability of sufficient numbers of these cells. We expanded umbilical cord blood (UCB)-CD34 HSCs for 2 weeks and then differentiated them into NK cells and compared their function to peripheral blood (PB) NK cells. We assessed NKG2D, NKG2A, NKp30, NKp44, NKp46, and the expression of CD107a, CD57, CD69, FasL, PD-1, and IFN-γ level in two groups after co-culture with K562 cell line.

"Cyclophilin A" Enzymatic Effect on the Aggregation Behavior of 1N4R Tau Protein: An Overlooked Crucial Determinant that should be Re-considered in Alzheimer's Disease Pathogenesis.

Background: Neurodegenerative disorders like Alzheimer's disease (AD) involve the abnormal aggregation of tau protein, which forms toxic oligomers and amyloid deposits. The structure of tau protein is influenced by the conformational states of distinct proline residues, which are regulated by peptidyl-prolyl isomerases (PPIases). However, there has been no research on the impact of human cyclophilin A (CypA) as a PPIase on (non-phosphorylated) tau protein aggregation.

Strong capacity of differentiated PD-L1 CAR-modified UCB-CD34 cells and PD-L1 CAR-modified UCB-CD34-derived NK cells in killing target cells and restoration of the anti-tumor function of PD-1-high exhausted T Cells.

Background: Using natural killer (NK) cells to treat hematopoietic and solid tumors has great promise. Despite their availability from peripheral blood and cord blood, stem cell-derived NK cells provide an "off-the-shelf" solution.

Methods: In this study, we developed two CAR-NK cells targeting PD-L1 derived from lentiviral transduction of human umbilical cord blood (UCB)-CD34 cells and UCB-CD34-derived NK cells.

Computational design of newly engineered DARPins as HER2 receptor inhibitors for breast cancer treatment.

Background And Purpose: Human epidermal growth factor receptor 2 (HER2) is overexpressed in approximately 25% of breast cancer patients; therefore, its inhibition is a therapeutic target in cancer treatment.

Experimental Approach: In this study, two new variants of designed ankyrin repeat proteins (DARPins), designated EG3-1 and EG3-2, were designed to increase their affinity for HER2 receptors. To this end, DARPin G3 was selected as a template, and six-point mutations comprising Q26E, I32V, T49A, L53H, K101R, and G124V were created on its structure.

Effects of Implantable Cardioverter-Defibrillator Leads on the Tricuspid Valve and Right Ventricle: A Randomized Trial.

Background: There are no randomized data to inform the extent to which transvenous cardiac leads cause tricuspid regurgitation (TR).

Objectives: This study sought to determine the effect of a transvenous implantable cardioverter-defibrillator (TV-ICD) on TR severity, and secondarily, on right ventricular (RV) size and function.

Methods: We evaluated TR severity before and 6 months after implantable cardioverter-defibrillator insertion in a post hoc analysis of adults randomized to receive a transvenous (n = 252) or subcutaneous implantable cardioverter-defibrillator (S-ICD) (n = 251) device.

Co-delivery of carboplatin and doxorubicin using ZIF-8 coated chitosan-poly(N-isopropyl acrylamide) nanoparticles through a dual pH/thermo responsive strategy to breast cancer cells.

A dual pH/temperature sensitive core-shell nanoformulation has been developed based on ZIF-8 coated with chitosan-poly(N-isopropyl acrylamide) (CS-PNIPAAm) for co-delivery of doxorubicin (DOX) and carboplatin (CBP) in breast cancer cells. The resulting nanoparticles (NPs) had particle sizes around 200 nm and a zeta potential of about +30 mV. The CBP and DOX loading contents in the final NPs were 11.

Evaluation of the effect of phenylpropanoids on the binding of heparin to human serum albumin and glycosylated human serum albumin concerning anticoagulant activity: A comparison study.

The nonenzymatic advanced glycation end products (AGEs) and the accumulation of AGEs are the two main factors associated with the long-term pathogenesis of diabetes. Human serum albumin (HSA) as the most abundant serum protein has a higher fortuity to be modified by nonenzymatic glycation. In this study, the interaction of three phenylpropanoids (caffeic acid (Caf), p-coumaric acid (Cou), and cinnamic acid (Cin)) toward HSA and glycosylated HSA (gHSA) was analyzed by multiple spectroscopic techniques combined with molecular docking.

The induction of tau aggregation is restricted by sulfamethoxazole and provides new information regarding the use of the drug.

The aggregation of tau protein in the form of paired helical filament (PHF) leads to the breakdown of microtubule structure and the development of neurodegenerative disorders, such as Alzheimer's disease. Therefore, inhibiting tau protein aggregation is a potential strategy for preventing the progression of these disorders. In this study, sulfamethoxazole (SMZ), an antibiotic that easily crosses the blood-brain barrier and interacts with tau protein, was tested for its ability to inhibit tau aggregation .

Probiotic and the potential risk of spreading antibiotic resistance: a systematic review.

Background And Purpose: , the most popular probiotic, has recently gained more attention because it is a potential reservoir of antibiotic resistance. This review summarized and discussed the phenotypic-genotypic characteristics of antibiotic resistance.

Experimental Approach: Google Scholar, PubMed, Web of Science, and Scopus were searched up to February 2022.

Anti HER-2 aptamer functionalized gold nanoparticles of dasatinib for targeted chemo-radiotherapy in breast cancer cells.

In the present study, gold nanoparticles functionalized with anti HER-2 aptamer were designed for effective targeted delivery of dasatinib (DSB) to breast cancer cells. Anti HER-2 aptamer attached to porous or plain gold nanoparticles were compared for dasatinib delivery. Activated drug with succinic anhydride and L-cysteine linker was used for conjugation of DSB to gold nanoparticles.

Corrigendum to "Introducing an interesting and novel strategy based on exploiting first-order advantage from spectrofluorimetric data for monitoring three toxic metals in living cells" [Toxicol. Rep. 9 (2022) 647-655].

[This corrects the article DOI: 10.1016/j.toxrep.

Minimizing total weighted latency in home healthcare routing and scheduling with patient prioritization.

We study a home healthcare routing and scheduling problem, where multiple healthcare service provider teams should visit a given set of patients at their homes. The problem involves assigning each patient to a team and generating the routes of the teams such that each patient is visited once. When patients are prioritized according to the severity of their condition or their service urgency, the problem minimizes the total weighted waiting time of the patients, where the weights represent the triage levels.

Effective Reduction of Tau Amyloid Aggregates in the Presence of Cyclophilin from Pollens; An Alternative Mechanism of Action of the Allergen.

Background: A hallmark pathology of Alzheimer's disease (AD) is the construction of neurofibrillary tangles, which are made of hyperphosphorylated Tau. The cis-proline isomer of the pThr/Ser-Pro sequence has been suggested to act as an aggregation precursor according to the 'Cistauosis' hypothesis; however, this aggregation scheme is not yet completely approved. Various peptidyl-prolyl isomerases (PPIases) may specifically isomerize cis/trans-proline bonds and restitute Tau's ability to attach microtubules and may control Tau amyloid aggregation in AD.

Construction and Periplasmic Expression of a Bispecific Tandem scFv for Dual Targeting of Immune Checkpoints.

Background: Immune checkpoints are molecules that act as regulators of immune system pathways. However, some tumor cells can express the ligands of immune checkpoints to escape from antitumor immune responses. Some agents, such as antibodies, can inhibit these checkpoints that prevent the immune system from targeting and killing cancer cells.

Design and construction of scFv-PE35KDEL as a novel immunotoxin against human epidermal growth factor receptor 2 for cancer therapy.

Propose: Human epidermal growth factor receptor 2 (HER2) is overexpressed on the surface of some kinds of cancer cells including breast cancer. In this study, we designed and produced a novel immunotoxin consisting anti-HER2 single-chain Fv (scFv) from pertuzumab and a modified form of Pseudomonas exotoxin (PE35KDEL).

Methods: The three-dimensional (3D) structure of the fusion protein (anti-HER IT) was predicted by MODELLER 9.

Co-Expression of Chaperones for Improvement of Soluble Expression and Purification of An Anti-HER2 scFv in .

Background: Single-chain fragment variable (scFv) is one of the most commonly used antibody fragments. They offer some advantages over full-length antibodies, including better penetration to target tissues. However, their functional production has been a challenge for manufacturers due to the potential misfolding and formation of inclusion bodies.

Parent-of-origin detection and chromosome-scale haplotyping using long-read DNA methylation sequencing and Strand-seq.

Hundreds of loci in human genomes have alleles that are methylated differentially according to their parent of origin. These imprinted loci generally show little variation across tissues, individuals, and populations. We show that such loci can be used to distinguish the maternal and paternal homologs for all human autosomes without the need for the parental DNA.