Direct Activation Research Articles

Novel Indirect Antioxidant Activity Independent of Nrf2 Exerted by Lactic Acid Bacteria.

In recent years, the health benefits of lactic acid bacteria have garnered attention, but their antioxidant activity remains relatively underexplored. We have been analyzing the antioxidant activities of various dietary phytochemicals by assessing their ability to mitigate oxidative stressor-induced toxicity in zebrafish larvae through pretreatment. In this study, the antioxidant activities of 24 strains of heat-killed lactic acid bacteria from various origins were examined using this zebrafish assay system. The results revealed that all 24 strains possessed antioxidant activity that reduces hydrogen peroxide toxicity. Further detailed analysis using the H61 strain, which exhibited the strongest activity, showed that no direct antioxidant activity was observed in the assay system, suggesting that the detected antioxidant activity was entirely indirect. Moreover, it was found that pretreatment of zebrafish larvae with the H61 strain for more than 6 h was required to exert its antioxidant activity. This duration was similar to that required by dietary antioxidants that activate the Keap1-Nrf2 pathway, suggesting potential involvement of this pathway. However, analysis using Nrf2-knockout zebrafish revealed that the antioxidant activity of strain H61 is independent of Nrf2, indicating that it represents a novel indirect antioxidant activity that does not involve the Keap1-Nrf2 pathway. To further characterize this activity, the ability to mitigate the toxicity of oxidative stressors other than hydrogen peroxide was examined. The results indicated that while the toxicity of tert-butyl hydroperoxide was reduced, unlike with the Keap1-Nrf2 pathway, it was not effective in counteracting the toxicity of paraquat or arsenite, which generate superoxide radicals. In conclusion, we have identified a novel indirect antioxidant activity in lactic acid bacteria.

A regulatory module mediating temperature control of cell-cell communication facilitates tree bud dormancy release.

The control of cell-cell communication via plasmodesmata (PD) plays a key role in plant development. In tree buds, low-temperature conditions (LT) induce a switch in plasmodesmata from a closed to an open state, which restores cell-to-cell communication in the shoot apex and releases dormancy. Using genetic and cell-biological approaches, we have identified a previously uncharacterized transcription factor, Low-temperature-Induced MADS-box 1 (LIM1), as an LT-induced, direct upstream activator of the gibberellic acid (GA) pathway. The LIM1-GA module mediates low temperature-induced plasmodesmata opening, by negatively regulating callose accumulation to promote dormancy release. LIM1 also activates expression of FT1 (FLOWERING LOCUS T), another LT-induced factor, with LIM1-FT1 forming a coherent feedforward loop converging on low-temperature regulation of gibberellin signaling in dormancy release. Mathematical modeling and experimental validation suggest that negative feedback regulation of LIM1 by gibberellin could play a crucial role in maintaining the robust temporal regulation of bud responses to low temperature. These results reveal genetic factors linking temperature control of cell-cell communication with regulation of seasonally-aligned growth crucial for adaptation of trees.

New rhodol-sulforaphane conjugates as innovative isothiocyanate-based cytotoxic agents for cancer cells

In search of semisynthetic derivatives with increased antitumor activity, we condensed sulforaphane (SFR) with rhodol, a fluorophore platform capable of modifying the intracellular trafficking and pharmacokinetics of the linked molecules. The two tested derivatives, namely MG28 and MG46, showed a far higher, as compared to SFR, cytotoxicity toward cancer cells. Apoptotic cell death was preceded by the extensive generation of DNA lesions, which were repaired relatively slowly and caused formation of micronuclei. Unlike SFR, rhodol-SFR conjugates’ DNA lesions resulted from direct interactions with nuclear DNA. Overall, MG28 and MG46 exhibit a remarkable cytotoxic effect, which is the likely consequence of their direct and intense DNA damaging activity, i.e., a novel and peculiar mechanism arising from the conjugation of the parental rhodol and SFR. Considering that a wide number of clinically used drugs kill cancer cells by inducing DNA damage, MG could represent a new and promising chance in antitumor chemotherapy.

Selective photocatalytic oxidative coupling of methane via directional activation of oxygen over Au-loaded ZnSn-LDH with defect structure

The selective photocatalytic oxidative coupling of methane (OCM) holds great potential in converting low-cost feedstock into C2 products. However, the challenge lies in improving the photocatalytic OCM activity through catalyst design and gaining a deeper understanding of reactant activation in the OCM process. Here, we synthesized Au-ZnSn-LDH with oxygen vacancies to achieve efficient selective oxidation of methane using O2. The optimal hybrid exhibits a C2H6 yield of 2666 μmol g−1 h−1 and 76.8 % selectivity. Our findings showed that the oxygen within the surface of ZnSn-LDH (possibly from adsorption at Ov vacancy sites) provides sites for the evolution of O2 to O2− with assistance from Au cocatalyst. More O2− could be generated from O2 provides a desired reactivity to selectively promote selective C−H activation of CH4 under photoexcitation. The Au cocatalyst plays crucial roles in facilitating the methyl transfer and promoting C−C coupling to produce C2H6 as the main product while avoiding undesirable overoxidation.

Impact of ICT diffusion and opportunity entrepreneurship on environmental sustainability in Saudi Arabia

The need to prioritize sustainable development is expanding in light of the world's environmental concerns. To address these concerns, entrepreneurship is essential as a catalyst for inventions, economic expansion, and social change. Entrepreneurship activities have direct and indirect effects in the face of environmental risks and uncertainties. This study addresses gaps in understanding entrepreneurship's non-linear and complementarity effects, particularly opportunity-driven entrepreneurship and information and communication technologies (ICT), on the quality of the environment in Saudi Arabia. The dynamic ordinary least squares (DOLS) method is used to estimate long-run relationships. Saudi Arabia will be the perfect context for sustainability because the country has prioritized sustainability through its Vision 2030, and the Saudi government has substantially supported entrepreneurship. The main contribution of this paper to the existing literature is evident in its examination of the quadratic relationships between both opportunity-driven entrepreneurship and ICT diffusion, including ICT access, use, and skills, on environmental quality. In addition, the study delves into the ICT diffusion's modulating effects on the nexus of opportunity entrepreneurship with environmental quality, providing insights into how these factors can effectively improve environmental quality. The findings show that opportunity entrepreneurship and ICT diffusion initially deteriorate environmental quality before leading to improvements as their levels mature in the economy. Moreover, interactions between ICT proxies and opportunity entrepreneurship yield mixed effects, with negative net effects on CO2 emissions and ecological footprint countered by positive net effects on the environmental performance index. These findings highlight the dual role of ICT diffusion as a contributor to environmental challenges and a potential solution, depending on the level of its diffusion and interaction with entrepreneurial activities. Therefore, policymakers should create plans that encourage and direct business activity toward more environmentally friendly methods. They should also consider the short- and long-term effects of growing digital technologies on environmental sustainability and how they might revolutionize how entrepreneurship and sustainability goals are aligned.

Analysis of Spatial and Temporal Variation of Water Quality: A Case Study of Kotagala Wetland, Nuwara Eliya, Sri Lanka

Water quality of wetland ecosystems is a critical concern due to its implications on human health and aquatic life. This study was conducted to assess the spatial and temporal variation of water quality in Kotagala wetland to understand its impact on water safety for domestic uses and ecosystem health. Water samples were collected (n = 70) from six inlets and the wetland outlet from November 2021 to August 2022, and analyzed for pH, electrical conductivity (EC), salinity, total dissolved solids (TDS), total suspended solids (TSS), nitrate, and phosphate. The pH, EC, and nitrate showed significant correlations. Spatial clustering divided the monitoring sites into two clusters, as areas of higher and lower pollution levels. Discriminant analysis highlighted the significance of EC, pH, and nitrate concentrations in differentiating these clusters. Principal According to principal component analysis (PCA) 88.8% of the total variance of spatial variation in water quality was explained by the first two components. Temporal clustering following seasonal variations revealed the influence of rainfall pattern on water quality. EC, TDS, TSS, and nitrate concentrations emerged as the most important factors in this temporal categorization. In PCA, 76.8% of the total variance of temporal variation in water quality was explained by the first two components. Findings highlight the urgent need for sustainable strategies and policies to mitigate the impacts of human activities on wetland water quality, since water quality variations in the wetland was significantly impacted by direct human activities, and variations in rainfall trends in the area.

Synthesis, Molecular Docking Studies and Biological Evaluation of Thiazolyl Hydrazone Derivatives of Chromone-3-carbaldehyde as Potent Anti-Oxidant and Anti-Inflammatory Agents.

A series of 15 thiazolyl hydrazone derivatives of chromone-3- carbaldehyde have been designed and synthesized by the cyclization of thiosemicarbazone derivatives of chromone-3-carbaldehydes with 4'-substituted-2-bromo acetophenones. All these derivatives were evaluated for antioxidant activity by their direct scavenging activity objects to reactive oxygen species such as DPPH, and nitric oxide, as well as in vitro antiinflammatory activity by a protein denaturation method. Most of these synthesized compounds have shown significant antioxidant activity, among which the compounds 5b, 5c, 5e, 5g, and 5j showed very good antioxidant activities in comparison with the standard ascorbic acid. The in vitro anti-inflammatory activity revealed that the compounds 5b, 5g, and 5h possessed significant activity compared to standard diclofenac sodium. Additionally, molecular docking studies of these molecules using ovalbumin as the protein showed remarkable interactions with its active site residues, and the results indicated that the binding mode of these compounds closely resembled that of the reference compound, diclofenac sodium. Thus, these compounds represent an attractive template for the evaluation of new antiinflammatory and antioxidant agents and might be useful for exploring new therapeutic tools.

Thymosin α1 reverses oncolytic adenovirus-induced M2 polarization of macrophages to improve antitumor immunity and therapeutic efficacy

Although oncolytic adenoviruses are widely studied for their direct oncolytic activity and immunomodulatory role in cancer immunotherapy, the immunosuppressive feedback loop induced by oncolytic adenoviruses remains to be studied. Here, we demonstrate that type V adenovirus (ADV) induces the polarization of tumor-associated macrophages (TAMs) to the M2 phenotype and increases the infiltration of regulatory Tcells (Tregs) in the tumor microenvironment (TME). By selectively compensating for these deficiencies, thymosin alpha 1 (Tα1) reprograms "M2-like" TAMs toward an antitumoral phenotype, thereby reprogramming the TME into a state more beneficial for antitumor immunity. Moreover, ADVTα1 is constructed by harnessing the merits of all the components for the aforementioned combinatorial therapy. Both exogenously supplied and adenovirus-produced Tα1 orchestrate TAM reprogramming and enhance the antitumor efficacy of ADV via CD8+ Tcells, showing promising prospects for clinical translation. Our findings provide inspiration for improving oncolytic adenovirus combination therapy and designing oncolytic engineered adenoviruses.

Novel Catalyst-free Activation of Chlorine by Visible Light for Micropollutant Abatement

This study systematically investigated the direct activation of chlorine by visible light emitting diode (Vis-LED). Vis-LED could effectively activate chlorine to degrade micropollutants with degradation efficiency and pseudo-first-order degradation rate constant range of 64.3%-100% and 0.0340-0.195min-1, respectively. Quenching experiments and modeling results suggested that reactive chlorine species (RCS, including ClO•, Cl2•-, and Cl•) and hydroxyl radical (•OH) were involved in the degradation of atenolol (ATL). The contribution ratio of ClO•, free available chlorine, Cl•, Cl2•-, and •OH to ATL degradation were 58.7%, 17.4%, 15.6%, 1.8%, and 5.9%, respectively, in Vis-LED448/chlorine process. Moreover, the innate quantum yields of HClO and ClO- decreased from 0.229 and 0.0206 to 0.0489 and 0.0109mol·Einstein-1, respectively, as the wavelength increased from 448 to 513nm, leading to a decrease in ATL degradation, which was consistent with the model results. Experimental and modeling results have confirmed that ATL degradation decreased when pH increased from 4.0 to 9.0. Cl- had little effect on the degradation of ATL, while HA and HCO3- affected ATL degradation by scavenging reactive species and/or shielding effect. The concentration of disinfection by-products decreased with the increase of wavelength and pH. In summary, Vis-LED/chlorine is an efficient water treatment process even without a catalyst.

Direct activation of toll-like receptor 4 signaling in group 2 innate lymphoid cells contributes to inflammatory responses of allergic diseases

Direct activation of toll-like receptor 4 signaling in group 2 innate lymphoid cells contributes to inflammatory responses of allergic diseases

Space- and frequency-division multiplexing in photonic second-order topological insulators

Higher-order topological insulators, originally proposed in quantum condensed matters, have provided a new avenue for localizing and transmitting light in photonic devices. Nontrivial band topology in crystals with certain symmetries can host robust topological edge states and lower dimensional topological corner states (TCS), making them a promising platform for photonics applications. Here, we have designed several types of TCS with only two specific C6v-symmetric photonic crystals with various seamless splicing boundaries, where all the supposed TCS with diverse electromagnetic characteristics are visualized via numerical simulations and experimental measurements. More interestingly, we have observed that those TCS overlapping in spectral and spatial space tend to interweaved, inducing spectrum division. Meanwhile, the equivalent corners appear to have TCS with a phase difference, which is critical for directional activation of pseudospin dependence. Our findings demonstrate that coupled TCS with phase difference at different nanocavities can be selectively excited by a chiral source, which indicates that the TCS at this time have pseudospin-dependent properties. We further design a specific splicing structure to prevent coupling between adjacent TCS. This work provides a flexible approach for space- and frequency-division multiplexing in photonic devices.

Effective activation of PMS by encapsulating monodispersed Fe3O4 within N, S heteroatoms co-doped carbon chamber for ROX removal dominated by the non-radical pathway

Developing the eco-friendly catalyst-adsorption iron-based materials with improved catalytic activity and minimal Fe leaching is fascinating for roxarsone (ROX) removal. Herein, Fe3O4 nanoparticles were encapsulated in flexible N, S-modified carbon chamber (Fe3O4@NS4C) through the “hydrothermal + pyrolysis” process to form a catalyst with multi-active sites. ROX could be degraded nearly 100 % at pH 5.0 − 11.0 and secondary inorganic As species concentration is lower than 0.09 mg/L by efficient adsorption. Especially, the Fe ion leaching concentration in Fe3O4@NS4C/PMS after ROX removal is decreased to 0.08 mg/L. Combined with quenching experiment, EPR, Raman spectroscopy and electrochemical analysis, the non-radical activation mechanism dominated by 1O2 and electron transfer was determined. The synergistic interaction between the N doped sites and the S anchored sites within the carbon matrix not only improves the adsorption of PMS on the catalyst but also facilitates the direct activation of PMS to 1O2, while the surface electron transfer improves the Fe2+/Fe3+ redox cycling in PMS activation. The active sites of ROX attacked by 1O2 were examined through Fukui function computations. Combined with HPLC-MS, the ROX degradation pathway was determined, and the toxicity of intermediates was evaluated. Furthermore, the removal performance of ROX in Fe3O4@NS4C/PMS system was also assessed in different environment for practical application, indicating that the advantages in the synergy between N, S co-doping carbon chamber and encapsulated iron oxide for water purification.

Tucaresol: A Clinical Stage Oral Candidate Drug with Two Distinct Antiviral Mechanisms

Globally, approximately 39 million people are living with Human Immunodeficiency Virus, HIV, arising from approximately 86 million infections since this epidemic began in 1981. However, the number of HIV infections is unevenly distributed with two thirds of global infections confined to Sub-Saharan Africa. Due to viral drug resistance, the most effective treatment requires a triple drug combination thereby adding to the complexity and cost of therapy. As such, many people living with HIV or at risk of infection do not have access to prevention or treatment of this potentially fatal disease. There is no cure for HIV [1]. Tucaresol is an orally active clinical stage drug which functions as a host targeted antiviral agent by protection or reconstitution of CD4+ T helper immune cells. We report herein that Tucaresol also displays in-vitro activity against HIV in infected human peripheral blood mononuclear cells. Although this in-vitro antiviral activity is not potent, the excellent safety profile and bioavailability of Tucaresol, along with its low Molecular Weight, support attainment of relevant drug concentrations in man to achieve significant in-vivo activity. This is demonstrated by previously reported stabilization of viremia in a prior proof of concept phase 1b/2a HIV clinical trial [2]. It is possible that the significant in-vivo activity of Tucaresol arises from synergy between co-stimulation of CD4+ T helper cells and the direct activity against virally infected cells. A pan in-vitro viral screen of Tucaresol further revealed a weak, direct antiviral activity against human herpes virus 6B, human papillomavirus 11, measles virus and hepatitis B virus.

SELECTED TASKS OF THE PROVINCIAL COMMANDER OF THE STATE FIRE SERVICE IN TERMS OF ENSURING SAFETY DURING MASS SPORTS EVENTS IN POLAND

This article discusses the rights and obligations of the provincial commander of the State Fire Service, who has been equipped with the tasks of this entity in the field of safety of mass sports events. In accordance with the regulations of the Act of March 20, 2009, on the safety of mass events adopted by the legislator, the provincial commander of the State Fire Service plays a key role, among others, in assessing the safety status of the facility or area where a mass sports event is to be held. The commander also undertakes a number of direct activities aimed at preventing the occurrence of various types of threats during the events in question.

Phenylephrine Enhances the Mitogenic Effect of S-Allyl-L-cysteine on Primary Cultured Hepatocytes through Protein Kinase C-Induced B-Raf Phosphorylation.

The co-mitogenic effects of the α1-adrenoceptor agonist phenylephrine on S-allyl-L-cysteine (SAC)-induced hepatocyte proliferation were examined in primary cultures of adult rat hepatocytes. The combination of phenylephrine (10-10-10-6 M) and SAC (10-6 M) exhibited a significant dose-dependent increase in the number of hepatocyte nuclei and viable cells compared to SAC alone. This combination also increased the progression of hepatocyte nuclei into the S-phase. The potentiating effect of phenylephrine on SAC-induced cell proliferation was counteracted by prazosin (an α1-adrenergic receptor antagonist) and GF109203X (selective protein kinase C (PKC) inhibitor). In addition, PMA (direct PKC activator) potentiated the proliferative effects of SAC similarly to phenylephrine. In essence, these findings suggest that PKC activity plays a crucial role in enhancing SAC-induced cell proliferation. Moreover, the effects of phenylephrine on SAC-induced Ras activity, Raf phosphorylation, and extracellular signal-regulated kinase 2 (ERK2) phosphorylation were investigated. Phenylephrine (or PMA) in combination with SAC did not augment Ras activity, but further increased ERK2 phosphorylation and its upstream B-Raf phosphorylation. These results indicate that PKC activation, triggered by stimulating adrenergic α1 receptors, further amplifies SAC-induced cell proliferation through enhanced ERK2 phosphorylation via increased B-Raf-specific phosphorylation in primary cultured hepatocytes.

The Activation of Muscarinic Acetylcholine Receptors Protects against Neuroinflammation in a Mouse Model through Attenuating Microglial Inflammation.

Neuroinflammation is a critical factor that contributes to neurological impairment and is closely associated with the onset and progression of neurodegenerative diseases. In the central nervous system (CNS), microglia play a pivotal role in the regulation of inflammation through various signaling pathways. Therefore, mitigating microglial inflammation is considered a promising strategy for restraining neuroinflammation. Muscarinic acetylcholine receptors (mAChRs) are widely expressed in the CNS and exhibit clear neuroprotective effects in various disease models. However, whether the activation of mAChRs can harness benefits in neuroinflammation remains largely unexplored. In this study, the anti-inflammatory effects of mAChRs were found in a neuroinflammation mouse model. The expression of various cytokines and chemokines was regulated in the brains and spinal cords after the administration of mAChR agonists. Microglia were the primary target cells through which mAChRs exerted their anti-inflammatory effects. The results showed that the activation of mAChRs decreased the pro-inflammatory phenotypes of microglia, including the expression of inflammatory cytokines, morphological characteristics, and distribution density. Such anti-inflammatory modulation further exerted neuroprotection, which was found to be even more significant by the direct activation of neuronal mAChRs. This study elucidates the dual mechanisms through which mAChRs exert neuroprotective effects in central inflammatory responses, providing evidence for their application in inflammation-related neurological disorders.

Rapid Emergence of Resistance to Broad-Spectrum Direct Antimicrobial Activity of Avibactam.

Avibactam (AVI) is a diazabicyclooctane (DBO) β-lactamase inhibitor used clinically in combination with ceftazidime. At concentrations higher than those typically achieved in vivo , it also has broad-spectrum direct antibacterial activity against Enterobacterales strains, including metallo-β-lactamase-producing isolates, mediated by inhibition of penicillin-binding protein 2 (PBP2). This activity is mechanistically similar to that of more potent novel DBOs (zidebactam, nacubactam) in late clinical development. We found that resistance to AVI emerged readily, with a mutation frequency of 2×10 -6 to 8×10 -5 . Whole genome sequencing of resistant isolates revealed a heterogeneous mutational target that permitted bacterial survival and replication despite PBP2 inhibition, in line with prior studies of PBP2-targeting drugs. While such mutations are believed to act by upregulating the bacterial stringent response, we found a similarly high mutation frequency in bacteria deficient in components of the stringent response, although we observed a different set of mutations in these strains. Although avibactam-resistant strains had increased lag time, suggesting a fitness cost that might render them less problematic in clinical infections, there was no statistically significant difference in growth rates between susceptible and resistant strains. The finding of rapid emergence of resistance to avibactam as the result of a large mutational target has important implications for novel DBOs with potent direct antibacterial activity, which are being developed with the goal of expanding cell wall-active treatment options for multidrug-resistant gram-negative infections but may be vulnerable to treatment-emergent resistance.

Antibacterial effects of human mesenchymal stem cells and their derivatives: a systematic review.

The growing problem of antimicrobial resistance (AMR) poses a significant challenge to public health; This is partly due to the lack of advancements in the development of novel antibiotics and the pressing need for alternative treatment options. Mesenchymal stem cells (MSC) possess secretory components that enhance the immune response and peptides that disrupt the bacteria constitution. The isolation of various human tissues has facilitated the investigation of the diverse potentials of MSC and their components. Further research is needed to fully understand the spectrum and efficacy of these elements and their differences. The primary aim of this study was to perform a thorough review of the current literature related to the antimicrobial properties of MSC and their associated components. The objective was to establish an insight into the results and effects of utilizing MSC in relation to bacterial colonization, and to present an overview of previously documented findings. This systematic literature review was conducted using the PubMed, Embase, and Web of Science databases. Data on the effect of MSC or their derivatives were measured by calculating the percentage of bacterial counts reduction after treatment with MSC in comparison to the control. A total of 3,911 articles were screened, and 31 eligible publications were selected for inclusion in the analysis. In the current systematic review, the majority of the experimental designs showed positive outcomes in terms of bacterial load reduction when MSC or their derivatives were used, with bone marrow being the most effective tissue. The rest of the findings exhibited heterogeneity in the spectrum of outcomes that could be attributed to the effects of using various tissues derived MSC in both in vivo and in vitro studies. The findings of our study indicate the potential antibacterial characteristics of MSC. The direct antimicrobial activity of these cells was demonstrated by our results, which quantitatively showed a decrease in bacterial growth after treatment with MSC. However, additional research is required to clarify the factors that determine the efficacy of their antimicrobial activity and their various components.

Электрохимический синтез замещенных 2-амино-4Н-хромен-3-карбонитрилов на основе кросс-сопряженных диеноновых производных циклогексана и малононитрила

The relevance of research in the field of chemistry of compounds of a number of 2-aminochromen(pyran)-3-carbonitrile is due to their practical significance and numerous transformation possibilities. Over the past two decades, there has been a dynamic development of the electrochemical synthesis of compounds of this series, which is determined by the possibility of eliminating expensive or toxic reagents, conducting reactions at normal temperatures and pressure in electrolyzers of a fairly simple design and other advantages. Based on the efficiency and environmental friendliness of this method, we have for the first time synthesized 2-aminotetrahydro-4H-chromene-3-carbonitriles based on available cross-conjugated dienone derivatives of cyclohexane series and malononitrile under electrolysis conditions (platinum cathode, graphite anode, KBr electrolyte, 80% EtOH). The control over the course of the reaction and the electrochemical behavior of all components has been carried out using cyclic voltammetry. The analysis of the voltammograms made it possible to establish the direct activation of the methylene component at the cathode with the formation of the anion -CH(CN)2. A comparison of the electrochemical synthesis of chromencarbonitriles with the chemical one indicates a significant advantage of electrosynthesis due to the exclusion of a toxic organic catalyst, reduction of reaction time with good yields of products, as well as the possibility of monitoring reactions using cyclic voltammetry, dispersion of products.

The Impact of the COVID‐19 Pandemic on Nurses' and Junior Doctors' Workloads

ABSTRACTAimsTo explore the impact of the COVID‐19 pandemic on nurses' and junior doctors' workload, changes to direct care and the impact of workload on resource allocation.DesignMixed‐method design was used.MethodsData were collected from direct observation, hospital administrative database and a survey. Nurses and junior doctors were observed on two COVID‐19 wards and one non‐COVID‐19 ward using a semi‐structured observation schedule. Survey data were collected from nurses and junior doctors that had worked on the COVID‐19 ward during the pandemic. Patient data were collected from Web Patient Administration System during the period of March–August 2021 and compared to March–August 2022.ResultsThe results of this study indicated that the workloads of nurses and junior doctors changed on the COVID‐19 wards. Nurses on the COVID‐19 ward spent less time on administration, communication and documentation compared to nurses working on the non‐COVID‐19 ward. For junior doctors, less time was being spent on direct care activities and administrative work compared to the non‐COVID ward. On the COVID‐19 wards, patients were older and had a shorter length of stay compared to the year before. Five themes were identified from the surveys, staffing shortages resulting in higher workloads and the need for overtime, unforeseen time to undertake tasks, lack of support and physical health and patient care compromised.ConclusionThe study highlights the need for systemic changes to staffing shortages and elevated workloads to improve the compromised mental and physical health caused during the pandemic and to retain the workforce for future sustainability.ImplicationsAs we collectively reflect on the lessons learned from this unprecedented period, it is imperative to address the challenges experienced proactively, fostering a healthcare environment that prioritises the well‐being of its front line heroes and, by extension, the quality of patient care.Reporting MethodSTROBE.Patient or Public ContributionNo patient or public contribution.