Golden Hour Intravenous Thrombolysis for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

OBJECTIVES: The benefits of intravenous thrombolysis are time-dependent, with maximum efficacy when administered within the first "golden" hour after onset. Nevertheless, the impact of golden hour thrombolysis has not been well quantified. METHODS: Medline, Embase, and Web of Science databases were systematically searched from inception to August 27, 2023. We included studies that reported safety and efficacy outcomes of ischemic stroke patients treated with intravenous thrombolysis in the golden hour versus later treatment window. The primary outcome was an excellent functional outcome, defined as a modified Rankin Scale score of 0-1 at 90 days. The secondary efficacy outcome was a good functional outcome (defined as modified Rankin Scale score of 0-2). The main safety outcome was symptomatic intracerebral hemorrhage. RESULTS: Seven studies involving 78,826 patients met the selection criteria. Golden hour thrombolysis was associated with higher odds of 90-day excellent functional outcomes (OR 1.40, 95% CI 1.16-1.67) and 90-day good functional outcomes (OR 1.38, 95% CI 1.13-1.69) compared with thrombolysis outside the golden hour. The number needed to treat to benefit for golden hour thrombolysis to reduce disability by at least 1 level on the modified Rankin Scale per patient was 2.6. Rates of symptomatic intracerebral hemorrhage and mortality were similar between groups. INTERPRETATION: Golden hour thrombolysis significantly improved acute ischemic stroke outcomes. The findings provide rationale for intensive efforts aimed at expediting thrombolytic therapy within the golden hour window following the onset of acute ischemic stroke. ANN NEUROL 2024;96:582-590.

Integer factorization using stochastic magnetic tunnel junctions.

Conventional computers operate deterministically using strings of zeros and ones called bits to represent information in binary code. Despite the evolution of conventional computers into sophisticated machines, there are many classes of problems that they cannot efficiently address, including inference, invertible logic, sampling and optimization, leading to considerable interest in alternative computing schemes. Quantum computing, which uses qubits to represent a superposition of 0 and 1, is expected to perform these tasks efficiently1-3. However, decoherence and the current requirement for cryogenic operation4, as well as the limited many-body interactions that can be implemented, pose considerable challenges. Probabilistic computing1,5-7 is another unconventional computation scheme that shares similar concepts with quantum computing but is not limited by the above challenges. The key role is played by a probabilistic bit (a p-bit)-a robust, classical entity fluctuating in time between 0 and 1, which interacts with other p-bits in the same system using principles inspired by neural networks8. Here we present a proof-of-concept experiment for probabilistic computing using spintronics technology, and demonstrate integer factorization, an illustrative example of the optimization class of problems addressed by adiabatic9 and gated2 quantum computing. Nanoscale magnetic tunnel junctions showing stochastic behaviour are developed by modifying market-ready magnetoresistive random-access memory technology10,11 and are used to implement three-terminal p-bits that operate at room temperature. The p-bits are electrically connected to form a functional asynchronous network, to which a modified adiabatic quantum computing algorithm that implements three- and four-body interactions is applied. Factorization of integers up to 945 is demonstrated with this rudimentary asynchronous probabilistic computer using eight correlated p-bits, and the results show good agreement with theoretical predictions, thus providing a potentially scalable hardware approach to the difficult problems of optimization and sampling.

Retraction Note: A homing system targets therapeutic T cells to brain cancer.

This Article has been retracted; see accompanying Retraction.

Mechanisms of DNA Damage Response in Mammalian Oocytes.

DNA damage poses a significant challenge to all eukaryotic cells, leading to mutagenesis, genome instability and senescence. In somatic cells, the failure to repair damaged DNA can lead to cancer development, whereas, in oocytes, it can lead to ovarian dysfunction and infertility. The response of the cell to DNA damage entails a series of sequential and orchestrated events including sensing the DNA damage, activating DNA damage checkpoint, chromatin-related conformational changes, activating the DNA damage repair machinery and/or initiating the apoptotic cascade. This chapter focuses on how somatic cells and mammalian oocytes respond to DNA damage. Specifically, we will discuss how and why fully grown mammalian oocytes differ drastically from somatic cells and growing oocytes in their response to DNA damage.

First Measurement Using Elliptically Polarized Photons of the Double-Polarization Observable E for γp→pπ

We report the measurement of the helicity asymmetry E for the pπ^{0} and nπ^{+} final states using, for the first time, an elliptically polarized photon beam in combination with a longitudinally polarized target at the Crystal Ball experiment at MAMI. The results agree very well with data that were taken with a circularly polarized photon beam, showing that it is possible to simultaneously measure polarization observables that require linearly (e.g., G) and circularly polarized photons (e.g., E) and a longitudinally polarized target. The new data cover a photon energy range 270-1400 MeV for the pπ^{0} final state (230-842 MeV for the nπ^{+} final state) and the full range of pion polar angles, θ, providing the most precise measurement of the observable E. A moment analysis gives a clear observation of the pη cusp in the pπ^{0} final state.

A homing system targets therapeutic T cells to brain cancer.

Successful T cell immunotherapy for brain cancer requires that the T cells can access tumour tissues, but this has been difficult to achieve. Here we show that, in contrast to inflammatory brain diseases such as multiple sclerosis, where endothelial cells upregulate ICAM1 and VCAM1 to guide the extravasation of pro-inflammatory cells, cancer endothelium downregulates these molecules to evade immune recognition. By contrast, we found that cancer endothelium upregulates activated leukocyte cell adhesion molecule (ALCAM), which allowed us to overcome this immune-evasion mechanism by creating an ALCAM-restricted homing system (HS). We re-engineered the natural ligand of ALCAM, CD6, in a manner that triggers initial anchorage of T cells to ALCAM and conditionally mediates a secondary wave of adhesion by sensitizing T cells to low-level ICAM1 on the cancer endothelium, thereby creating the adhesion forces necessary to capture T cells from the bloodstream. Cytotoxic HS T cells robustly infiltrated brain cancers after intravenous injection and exhibited potent antitumour activity. We have therefore developed a molecule that targets the delivery of T cells to brain cancer.

The ruminant gut microbiome vs enteric methane emission: The essential microbes may help to mitigate the global methane crisis.

Ruminants release enteric methane into the atmosphere, significantly increasing greenhouse gas emissions and degrading the environment. A common focus of traditional mitigation efforts is on dietary management and manipulation, which may have limits in sustainability and efficacy, exploring the potential of essential microorganisms as a novel way to reduce intestinal methane emissions in ruminants; a topic that has garnered increased attention in recent years. Fermentation and feed digestion are significantly aided by essential microbes found in the rumen, such as bacteria, fungi, and archaea. The practical implications of the findings reported in various studies conducted on rumen gut concerning methane emissions may pave the way to understanding the mechanisms of CH4 production in the rumen to enhance cattle feed efficiency and mitigate CH4 emissions from livestock. This review discussed using essential bacteria to reduce intestinal methane emissions in ruminants. It investigates how particular microbial strains or consortia can alter rumen fermentation pathways to lower methane output while preserving the health and productivity of animals. We also describe the role of probiotics and prebiotics in managing methane emissions using microbial feed additives. Further, recent studies involving microbial interventions have been discussed. The use of new methods involving functional metagenomics and meta-transcriptomics for exploring the rumen microbiome structure has been highlighted. This review also emphasizes the challenges faced in altering the gut microbiome and future directions in this area.

A potent formula against triple-negative breast cancer-sorafenib-carbon nanotubes-folic acid: Targeting, apoptosis triggering, and bioavailability enhancing.

Triple-negative breast cancer (TNBC) has short survival rates. This study aimed to prepare a novel formula of sorafenib, carbon nanotubes (CNTs), and folic acid to be tested as a drug delivery system targeting versus TNBC compared with free sorafenib and to evaluate the formula stability, in vitro pharmacodynamic, and in vivo pharmacokinetic properties. The formula preparation was done by the synthesis of polyethylene glycol bis amine linker, CNT PEGylation, folic acid attachment, and sorafenib loading. The prepared formula has been characterized using X-ray diffraction, Flourier-transform infrared, 1HNMR, UV, high resolution-transmission electron microscope, field emission scanning electron microscopy, and Zeta potential. In vitro studies included drug release determination, MTT assay, flow cytometry to determine the apoptotic stage with percent, cell cycle analysis, and apoptotic marker assays for caspase-3, 8, 9, cytochrome c, and BCL-2. The in vivo study was performed to determine bioavailability and half-life in rats. The in vitro MTT antiproliferative assay revealed that the formula was threefold more cytotoxic toward TNBC cells than free sorafenib, and the flow cytometry showed a significant increase in apoptosis and necrosis. The formula has a greater inhibitory effect on BCL-2 and a lessening effect on cytochrome c and caspases 3, 8, and 9 than free sorafenib. In vivo experiments proved that our novel formula was superior to free sorafenib by increasing bioavailability by eight times and prolonging the half-life by three times. These results confirmed the successful preparation of the desired formula with better pharmacodynamic and pharmacokinetic properties. These promising results may show a novel therapeutic strategy for TNBC patients.

Progressive multifocal leukoencephalopathy in patients with chronic kidney disease.

Progressive multifocal leukoencephalopathy (PML) is an opportunistic central nervous system infection caused by the human polyomavirus 2, leading to demyelination from oligodendrocyte death and rapid neurologic decline. Most commonly, PML affects patients in immunocompromised states. However, rare reports of PML in an immunocompetent host exist. Here, we report two cases of PML in older individuals with chronic kidney disease (CKD). CKD can ultimately lead to immune system dysfunction and place patients in a relatively immunosuppressed state. Testing for JC virus should remain a consideration for rapid, unexplained neurologic decline even without known immunocompromised status in the appropriate clinical setting.

Capture and metabolomic analysis of the human endometrial epithelial organoid secretome.

Suboptimal uterine fluid (UF) composition can lead to pregnancy loss and likely contributes to offspring susceptibility to chronic adult-onset disorders. However, our understanding of the biochemical composition and mechanisms underpinning UF formation and regulation remain elusive, particularly in humans. To address this challenge, we developed a high-throughput method for intraorganoid fluid (IOF) isolation from human endometrial epithelial organoids. The IOF is biochemically distinct to the extraorganoid fluid (EOF) and cell culture medium as evidenced by the exclusive presence of 17 metabolites in IOF. Similarly, 69 metabolites were unique to EOF, showing asymmetrical apical and basolateral secretion by the in vitro endometrial epithelium, in a manner resembling that observed in vivo. Contrasting the quantitative metabolomic profiles of IOF and EOF revealed donor-specific biochemical signatures of organoids. Subsequent RNA sequencing of these organoids from which IOF and EOF were derived established the capacity to readily perform organoid multiomics in tandem, and suggests that transcriptomic regulation underpins the observed secretory asymmetry. In summary, these data provided by modeling uterine luminal and basolateral fluid formation in vitro offer scope to better understand UF composition and regulation with potential impacts on female fertility and offspring well-being.

Periostin's role in uterine leiomyoma development: a mini-review on the potential periostin poses as a pharmacological intervention for uterine leiomyoma.

Uterine leiomyomas, also known as fibroids or myomas, occur in an estimated 70-80% of reproductive aged women. Many experience debilitating symptoms including pelvic pain, abnormal uterine bleeding (AUB), dyspareunia, dysmenorrhea, and infertility. Current treatment options are limited in preserving fertility, with many opting for sterilizing hysterectomy as a form of treatment. Currently, surgical interventions include hysterectomy, myomectomy, and uterine artery embolization in addition to endometrial ablation to control AUB. Non-surgical hormonal interventions, including GnRH agonists, are connotated with negative side effects and are unacceptable for women desiring fertility. Periostin, a regulatory extra cellular matrix (ECM) protein, has been found to be expressed in various gynecological diseases including leiomyomas. We previously determined that periostin over-expression in immortalized myometrial cells led to the development of a leiomyoma-like cellular phenotype. Periostin is induced by TGF-ß, signals through the PI3K/AKT pathway, induces collagen production, and mediates wound repair and fibrosis, all of which are implicated in leiomyoma pathology. Periostin has been linked to other gynecological diseases including ovarian cancer and endometriosis and is being investigated as pharmacological target for treating ovarian cancer, post-surgical scarring, and numerous other fibrotic conditions. In this review, we provide discussion linking pathological inflammation and wound repair, with a TGF-ß-periostin-collagen signaling in the pathogenesis of leiomyomas, and ultimately the potential of periostin as a druggable target to treat leiomyomas.

A novel urease-assisted ratiometric fluorescence sensing platform based on pH-modulated copper-quenched near-infrared carbon dots and methyl red-quenched red carbon dots for selective urea monitoring.

A novel and sensitive fluorescence ratiometric method is developed for urea detection based  on the pH-sensitive response of two fluorescent carbon dot (CD) systems: R-CDs/methyl red (MR) and NIR-CDs/Cu2+. The sensing mechanism involves breaking down urea using the enzyme urease, releasing ammonia and increasing pH. At higher pH, the fluorescence of NIR-CDs is quenched due to the enhanced interaction with Cu2+, while the fluorescence of R-CDs is restored as the acidic MR converts to its basic form, removing the inner filter effect. The ratiometric signal (F608/F750) of the R-CDs/MR and NIR-CDs/Cu2+ intensities changed in response to the pH induced by urea hydrolysis, enabling selective and sensitive urea detection. Detailed spectroscopic and morphological investigations confirmed the fluorescence probe design and elucidated the sensing mechanism. The method exhibited excellent sensitivity (0.00028 mM LOD) and linearity range (0.001 - 8.0 mM) for urea detection, with successful application in milk samples for monitoring adulteration, demonstrating negligible interference and high recovery levels (96.5% to 101.0%). This ratiometric fluorescence approach offers a robust strategy for selective urea sensing in complicated matrices.

Effect of Salvadora persica on resin-dentin bond stability.

BACKGROUND: The stability of resin-dentin interfaces is still highly questionable. The aim of this study was to evaluate the effect of Salvadora persica on resin-dentin bond durability. MATERIALS AND METHODS: Extracted human third molars were used to provide mid-coronal dentin, which was treated with 20% Salvadora persica extract for 1 min after acid-etching. Microtensile bond strength and interfacial nanoleakage were evaluated after 24 h and 6 months. A three-point flexure test was used to measure the stiffness of completely demineralized dentin sticks before and after treatment with Salvadora persica extract. The hydroxyproline release test was also used to measure collagen degradation by endogenous dentin proteases. Statistical analysis was performed using two-way ANOVA followed by post hoc Bonferroni test and unpaired t-test. P-values < 0.05 were considered statistically significant. RESULTS: The use of Salvadora persica as an additional primer with etch-and-rinse adhesive did not affect the immediate bond strengths and nanoleakage (p > 0.05). After 6 months, the bond strength of the control group decreased (p = 0.007), and nanoleakage increased (p = 0.006), while Salvadora persica group showed no significant difference in bond strength and nanoleakage compared to their 24 h groups (p > 0.05). Salvadora persica increased dentin stiffness and decreased collagen degradation (p < 0.001) compared to their controls. CONCLUSION: Salvadora persica extract pretreatment of acid-etched dentin preserved resin-dentin bonded interface for 6 months. CLINICAL SIGNIFICANCE: Durability of resin-dentin bonded interfaces is still highly questionable. Endogenous dentinal matrix metalloproteinases play an important role in degradation of dentinal collagen within such interfaces. Salvadora persica may preserve resin-dentin interfaces for longer periods of time contributing to greater clinical success and longevity of resin composite restorations.

Detecting white spot lesions on post-orthodontic oral photographs using deep learning based on the YOLOv5x algorithm: a pilot study.

BACKGROUND: Deep learning model trained on a large image dataset, can be used to detect and discriminate targets with similar but not identical appearances. The aim of this study is to evaluate the post-training performance of the CNN-based YOLOv5x algorithm in the detection of white spot lesions in post-orthodontic oral photographs using the limited data available and to make a preliminary study for fully automated models that can be clinically integrated in the future. METHODS: A total of 435 images in JPG format were uploaded into the CranioCatch labeling software and labeled white spot lesions. The labeled images were resized to 640 × 320 while maintaining their aspect ratio before model training. The labeled images were randomly divided into three groups (Training:349 images (1589 labels), Validation:43 images (181 labels), Test:43 images (215 labels)). YOLOv5x algorithm was used to perform deep learning. The segmentation performance of the tested model was visualized and analyzed using ROC analysis and a confusion matrix. True Positive (TP), False Positive (FP), and False Negative (FN) values were determined. RESULTS: Among the test group images, there were 133 TPs, 36 FPs, and 82 FNs. The model's performance metrics include precision, recall, and F1 score values of detecting white spot lesions were 0.786, 0.618, and 0.692. The AUC value obtained from the ROC analysis was 0.712. The mAP value obtained from the Precision-Recall curve graph was 0.425. CONCLUSIONS: The model's accuracy and sensitivity in detecting white spot lesions remained lower than expected for practical application, but is a promising and acceptable detection rate compared to previous study. The current study provides a preliminary insight to further improved by increasing the dataset for training, and applying modifications to the deep learning algorithm. CLINICAL REVELANCE: Deep learning systems can help clinicians to distinguish white spot lesions that may be missed during visual inspection.

Treatment with onion bulb extract both prevents and reverses allergic inflammation in a murine model of asthma.

CONTEXT: Asthma presents a global health challenge. The main pharmacotherapy is synthetic chemicals and biological-based drugs that are costly, and have significant side effects. In contrast, use of natural products, such as onion (Allium cepa L., Amaryllidaceae) in the treatment of airway diseases has increased world-wide because of their perceived efficacy and little safety concerns. However, their pharmacological actions remain largely uncharacterized. OBJECTIVE: We investigated whether onion bulb extract (OBE) can (1) reverse established asthma phenotype (therapeutic treatment) and/or (2) prevent the development of the asthma phenotype, if given before the immunization process (preventative treatment). MATERIALS AND METHODS: Six groups of male Balb/c mice were established for the therapeutic (21 days) and five groups for the preventative (19 days) treatment protocols; including PBS and house dust mite (HDM)-challenged mice treated with vehicle or OBE (30, 60, and 100 mg/kg/i.p.). Airways inflammation was determined using cytology, histology, immunofluorescence, Western blot, and serum IgE. RESULTS: Therapeutic (60 mg/kg/i.p.) and preventative (100 mg/kg/i.p.) OBE treatment resulted in down-regulation of HDM-induced airway cellular influx, histopathological changes and the increase in expression of pro-inflammatory signaling pathway EGFR, ERK1/2, AKT, pro-inflammatory cytokines and serum IgE. DISCUSSION AND CONCLUSION: Our data show that OBE is an effective anti-inflammatory agent with both therapeutic and preventative anti-asthma effects. These findings imply that onion/OBE may be used as an adjunct therapeutic agent in established asthma and/or to prevent development of allergic asthma. However, further studies to identify the active constituents, and demonstrate proof-of-concept in humans are needed.

Closing the loop: Strengthening course quality of Pharm.D. program via applying a comprehensive four-step review approach.

This study explores the course review process implemented by the College of Pharmacy at King Saud University for its Pharm.D. program. Through a qualitative research design, a dedicated course review committee was established to oversee the evaluation process. The committee gathered and analyzed data from various sources, including course reports, student evaluations, and exam center reports, to achieve a holistic understanding of each course's effectiveness. The evaluation process was structured into a Four-Step Course Evaluation Approach: data collection, data review and recommendations, taking appropriate action, and communicating the outcomes. The "closing the loop" stage ensured that recommendations were effectively implemented, and course evaluation data were systematically archived for future reference. The results of this study, based on the evaluation of 25 courses, revealed significant improvements in course quality, alignment with program learning outcomes, and adherence to accreditation standards. Key findings included the identification of gaps and discrepancies, leading to targeted interventions and enhanced course content. Overall, this study highlights the effectiveness of a structured course review process in enhancing the quality of education and ensuring continuous improvement within the college. The committee focuses on refining evaluation criteria, conducting workshops, and providing training to stay current with emerging accreditation standards and best practices. This systematic course review process demonstrates the College's commitment to providing high-quality education and preparing students for successful careers in pharmacy, with significant implications for the improvement of pharmacy education and the overall student learning experience.

The effect of inhibiting hindbrain A2 noradrenergic neurons by 6-Hydroxydopamine on lipopolysaccharide-treated male rats autistic animal model.

Autism spectrum disorder (ASD) is a complex neurodevelopmental illness that often emerges in early childhood. The incidence of ASD has shown a notable rise in recent years. ASD is defined by deficits in social communication, and presence of rigid and repetitive behaviors and interests. The underlying mechanisms of ASD remain elusive. Multiple studies have documented the presence of neuroinflammation and increased levels of inflammatory cytokines, specifically, IL-6, TNF, and NF-κB, in various brain regions, including the prefrontal cortex (PFC) and hippocampus in individuals with ASD. Noradrenergic neurons play a crucial role in brain development and the regulation of motor, behavioral, and memory functions. This study sought to examine the impact of intracerebroventricular (icv.) injection of the neurotoxin, 6-hydroxydopamine (6-OHDA), in the caudal dorsal vagal complex A2 neurons on various neuroinflammatory pathways at the hippocampus and PFC in valproic acid (VPA) autistic animal model. This was done in conjunction with an intraperitoneal (i.p.) injection of Lipopolysaccharides (LPS) in animal models with VPA-induced autism. We specifically examined the impact of the caudal fourth ventricle 6-OHDA icv. injection and LPS (i.p.) injection on self-grooming behavior. We measured the mRNA expression of IL-6, TNF-a, and NF-κB using qRT-PCR, and the protein expression of COX-2, GPX-1, p-AMPK, and AMPK using western blot analysis. The self-grooming activity was considerably higher in the combined treatment group (6-OHDA icv. + LPS i.p.) compared to the control group. A substantial increase observed in the expression of IL-6, TNF-α, and NF-κB genes in the PFC of the treatment group that received icv. Administration of 6-OHDA, compared to the control group. The VPA-autism rats that received the combo treatment exhibited a slight increase in the expression level of NF-κB gene in the hippocampus, compared to the control group. At the PFC, we noticed a substantial drop in the expression of the antioxidant protein GPX-1 in the group that received the combo treatment compared to the control group. Our data investigates a novel aspect that the 6-OHDA-induced inhibition of hindbrain A2 neurons could be influencing the neuroinflammatory pathways in the PFC and hippocampus of autistic animal models.

Light-Activated Assembly of Connexon Nanopores in Synthetic Cells.

During developmental processes and wound healing, activation of living cells occurs with spatiotemporal precision and leads to rapid release of soluble molecular signals, allowing communication and coordination between neighbors. Nonliving systems capable of similar responsive release hold great promise for information transfer in materials and site-specific drug delivery. One nonliving system that offers a tunable platform for programming release is synthetic cells. Encased in a lipid bilayer structure, synthetic cells can be outfitted with molecular conduits that span the bilayer and lead to material exchange. While previous work expressing membrane pore proteins in synthetic cells demonstrated content exchange, user-defined control over release has remained elusive. In mammalian cells, connexon nanopore structures drive content release and have garnered significant interest since they can direct material exchange through intercellular contacts. Here, we focus on connexon nanopores and present activated release of material from synthetic cells in a light-sensitive fashion. To do this, we re-engineer connexon nanopores to assemble after post-translational processing by a protease. By encapsulating proteases in light-sensitive liposomes, we show that assembly of nanopores can be triggered by illumination, resulting in rapid release of molecules encapsulated within synthetic cells. Controlling connexon nanopore activity provides an opportunity for initiating communication with extracellular signals and for transferring molecular agents to the cytoplasm of living cells in a rapid, light-guided manner.

Sire modulates developmental kinetics and transcriptome of the bovine embryo.

In brief: The first week of gestation is a period of major pregnancy loss in cattle, this study reveals that the male plays a key role in regulating embryonic development during this time. Abstract: The impact of sire on preimplantation embryonic development in cattle remains poorly understood. This study evaluated differences in embryos produced in vitro from sires with varying capacities to produce blastocysts. Sires classified as high (HP) and low performing (LP) based on their ability to produce embryos were used to better understand how sire regulates embryonic development. By monitoring development, it was determined that the most common arrest stage was the five- to six-cell stage. Embryos (four to six cells) from HP and LP sires were then analyzed for autophagic activity, where embryos for LP sires exhibited increased autophagy than HP-derived embryos. Transcriptome analysis of four-cell embryos found that embryos from LP sires might have issues in sperm mitochondrial clearance, histone retention, and DNA damage, while HP sires had increased expression of genes involved in transcription, chromosome segregation, and cell division. In conclusion, LP sires had an increased proportion of embryos arresting at the five- to six-cell stage, and these embryos had higher rates of cellular stress due to paternal contributions from the spermatozoon.

First Evidence of Axial Shape Asymmetry and Configuration Coexistence in

The excited states of N=44 ^{74}Zn were investigated via γ-ray spectroscopy following ^{74}Cu ß decay. By exploiting γ-γ angular correlation analysis, the 2_{2}^{+}, 3_{1}^{+}, 0_{2}^{+}, and 2_{3}^{+} states in ^{74}Zn were firmly established. The γ-ray branching and E2/M1 mixing ratios for transitions deexciting the 2_{2}^{+}, 3_{1}^{+}, and 2_{3}^{+} states were measured, allowing for the extraction of relative B(E2) values. In particular, the 2_{3}^{+}→0_{2}^{+} and 2_{3}^{+}→4_{1}^{+} transitions were observed for the first time. The results show excellent agreement with new microscopic large-scale shell-model calculations, and are discussed in terms of underlying shapes, as well as the role of neutron excitations across the N=40 gap. Enhanced axial shape asymmetry (triaxiality) is suggested to characterize ^{74}Zn in its ground state. Furthermore, an excited K=0 band with a significantly larger softness in its shape is identified. A shore of the N=40 "island of inversion" appears to manifest above Z=26, previously thought as its northern limit in the chart of the nuclides.