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Summary Societal Impact Statement Climate change continues to intensify the challenges of food production as agricultural systems face more variable and extreme weather. Coupled with increasing human population, growers must balance increasing crop yields with nutrient content to prevent global malnutrition. Photosynthetic diversity may permit some crops to tolerate climate change and elevated CO2 whilst maintaining both crop yield quantity and quality. This review examines how photosynthetic diversity interacts with crop production and nutritional stability under elevated CO2 and climate change, and highlights opportunities for photosynthetic diversity to inspire agricultural solutions. Summary Innovative agricultural solutions are desperately needed to achieve food security for a growing human population amidst the imminent pressures of climate change that threaten more variable and extreme weather, placing additional pressures on already precarious agricultural systems. Not only are crop yields at risk under climate change but rising global atmospheric CO2 concentrations are concurrently driving a carbon dilution effect that threatens to reduce the nutritional quality of our crops to further global malnutrition. Plants using different photosynthetic metabolisms, however, experience these negative impacts to yield and nutrition to different degrees. Thus, photosynthetic diversity may offer solutions to combat malnutrition under climate change and elevated CO2 concentrations, whether that be through targeting existing resilient species for agricultural programmes or applying agricultural biotechnology to engineer photosynthetic diversity into existing crops. Here, we discuss how each major photosynthetic type is predicted to fare under elevated CO2 concentrations and climate change and explore agricultural opportunities to maintain both yield and nutrient stability.

Abstract This study investigates the spray combustion characteristics of waste cooking oil (WCO) in comparison between a swirl nozzle (SN) and a conventional nozzle (CN) of equal cross‐section. n‐Heptane, methyl decanoate, and methyl‐9‐decenoate were used as WCO substitutes in the simulation. The research primarily focuses on multiphase flow using the Lagrangian‐drop Eulerian‐fluid (LDEF) method, employing an equilibrium phase spray model (EP) for droplet behaviour analysis. The model's efficacy was validated through comparisons with experimental works by other engine researchers. At varying injection pressures, the study found that SN slightly reduced evaporative spray tip penetration but increased the cone angle compared to CN. This suggests early fuel jet disintegration and improved air entrainment due to SN. SN also showed a higher heat release rate and temperature, with soot reduction between 3.20 to 6.72% as injection pressure increased from 100 to 300 MPa. This indicates that SN achieves better air‐fuel mixture than CN. Further, the study discovered that the influence of SN becomes more significant as the rheological properties of WCO lessen under ultra‐high injection pressures.

Abstract Improving energy efficiency and cost reduction is a perennial challenge in engineering. Natural biological systems have evolved unique functional surfaces or special physiological functions over centuries to adapt to their complex environments. Among these biological wonders, fish, one of the oldest vertebrate groups, has garnered significant attention due to its exceptional fluid dynamics capabilities. Researchers are actively exploring the potential of fish skin's distinctive structural and material characteristics in reducing resistance. In this study, models of biomimetic imbricated fish scale are established, and the evolution characteristics of the flow field and drag reduction performance on these bionic surfaces are investigated. The results showed a close relationship between the high–low velocity stripes generated and the fluid motion by the imbricated fish scale surface. The stripes' prominence increases with the spacing of the adjacent scales and tilt angle of the fish scale, and the velocity amplitude of the stripes decreases as the exposed length of the imbricated fish scale surface increases. Moreover, the biomimetic imbricated fish scale surface can decrease the velocity gradient and thereby reduce the wall shear stress. The insights gained from the fish skin‐inspired imbricated fish surface provide valuable perspectives for an in‐depth analysis of fish hydrodynamics and offer fresh inspiration for drag reduction and antifouling strategies in engineering applications.

Abstract Hydrogels, characterised as highly hydrophilic three‐dimensional polymer networks, have gained increasing attention due to their unique physicochemical properties, finding applications in various fields. Natural polymer hydrogels exhibit higher biocompatibility and biodegradability compared to traditional synthetic polymer hydrogels. Proteins, being the principal materials of natural polymer hydrogels, bear numerous modifiable functional groups. The resultant hydrogel possesses responsiveness, adjustable degradability, and underway as an excellent biomaterial. Seven common raw materials used to construct protein hydrogels are introduced. In terms of comparing natural polymer hydrogels with traditional synthetic polymer hydrogels, the authors conduct a detailed analysis and comparison, highlighting the advantages of natural polymer hydrogels in terms of biocompatibility and biodegradability, and summarising their characteristics. The authors also address the limitations of various protein hydrogels and list existing strengthening cross‐linking strategies, proposing new insights to overcome the application limits of protein hydrogels. Additionally, the applications of protein hydrogels in drug delivery, biosensing, bio‐inks and tissue engineering are discussed. The authors conclude by summarising the current challenges faced by protein hydrogels and prospecting its future development.

Abstract Bionic lubricant materials are a class of materials inspired by natural organisms and offer excellent lubrication properties and biocompatibility. In the field of sports medicine, their application opens up new possibilities for the prevention and treatment of sports‐related diseases. The authors will introduce the existing theoretical models of friction in the locomotor system, the characteristics and advantages of biomimetic lubrication materials and discuss in depth their applications in the field of sports medicine. The development of bionic lubrication materials opens up unprecedented opportunities for sports medicine to provide more effective and long‐lasting treatment options for patients.

Abstract Biomaterials with exceptional performance are crucial for addressing the challenges of complex bone regeneration. Compared with traditional three‐dimensional scaffolds, injectable microspheres enable new strategies for the treatment of irregular bone defects. Biodegradable poly (lactic‐co‐glycolic acid) has found widespread applications as microcarriers of drugs, proteins, and other active macromolecules. Applied to the surface of poly (lactic‐co‐glycolic acid) cage‐like structures (PLGA‐CAS), hydroxyapatite (HA) effectively reduces inflammation while enhancing biological effects. In this study, we loaded the surface of PLGA‐CAS with micro‐ and nano‐hydroxyapatite particles, referred to as μHA/PLGA‐CAS and nHA/PLGA‐CAS, respectively. Subsequently, their material characteristics and biological effects were assessed. The incorporation of hydroxyapatite onto PLGA‐CAS resulted in enhanced surface roughness and hydrophilicity, coupled with improved thermal stability and delayed degradation. Furthermore, μHA/PLGA‐CAS induced osteogenic differentiation of osteoblast precursor cells, while nHA/PLGA‐CAS improved endothelial cell adhesion and stimulated angiogenic differentiation in vitro. Collectively, these findings suggest that μHA/PLGA‐CAS and nHA/PLGA‐CAS, each with distinct characteristics, hold significant potential for application as microcarriers in various biomedical contexts.

Abstract Bone implantation surgery is often accompanied by bacterial infection, resulting in infectious bone non‐union, pathological fracture and other serious consequences, which will aggravate the pain of patients. A non‐antibiotic coating consisting of sodium dodecyl sulphate (SDS) and levulinic acid (LA) with different concentrations was prepared by the authors on the zinc–aluminium alloy (ZA6‐1) using a wet chemistry treatment for orthopaedic application. The influence of SDS/LA concentrations on the surface morphology, composition and performance of the developed coating was investigated. The results showed that as‐prepared coating on a zinc alloy surface could improve the substrate's corrosion resistance and increase the degradation rate from 0.82 to 19.70 μm/year upon raising the SDS/LA concentration. Furthermore, higher hydrophilicity (100%) and morphology, as well as good cell adhesion and differentiation (ALP >95% for 7 days) were observed on coated zinc alloys. The increased SDS/LA concentration slightly weakens the biocompatibility and enhances the antibacterial performance of coated zinc alloys due to the synergistic effect of SDS/LA. Overall, the coating comprising 6 wt.% SDS and 9 wt.% LA showed excellent antibacterial action with a high level of biocompatibility, confirming its potential application for orthopaedic implants.

Abstract Due to trauma and disease, bone defects endanger the healthy life of human beings. At present, the gold standard for bone defect repair is still autologous bone transplantation and allogeneic bone transplantation. However, its insufficient source, potential disease transmission and immune rejection limit its clinical application. Therefore, the development of bone repair materials plays an important role in promoting bone repair. As the interface between material and tissue, the surface of the material plays an important role in the reaction after implantation, which determines the effectiveness of defect repair treatment. With the development of surface engineering and technology, bone repair materials have developed from biological inertia to biological activity by endowing various biological functions by controlling the composition, topological morphology and structure of the material surface etc. The inspired biofunctionalisation of material surface includes the capacities of inducing osteogenesis, promoting angiogenesis, antibacterial, immune regulation etc., as well as integration of postoperative repair and treatment. The authors review the biofunctionalisation of biomaterial surface and the inspired biological effects for bone repair, mainly including physical and chemical properties of material surface to regulate osteogenesis, and functional strategy of bone repair material surface.

Abstract It is a developed photosynthetic co‐culture system to alleviate the hypoxia and hypoxia/reoxygenation (H/R)‐injured human umbilical vein endothelial cells (HUVECs). The algae, Chlorella vulgaris, were encapsulated to slow their growth while not affecting the photosynthetic oxygen‐producing capacity by Layer‐by‐layer (LbL) using gelatin and sodium alginate as the positive and negative charges materials, respectively. Then, the photosynthetic co‐culture system of HUVECs and self‐oxygenating alginate hydrogel (Algae‐gel) was constructed in which the optimal ratios between algae and HUVECs were 5:1 and 20:1 for a 2D or 3D co‐cultured manner, respectively. It indicated that the 3D co‐cultured manner of HUVECs needed more O2 by the production of algae than it did in a 2D co‐cultured manner. The co‐cultured Algae‐gel could alleviate hypoxia and the oxidative stress injury of hypoxia and hypoxia/reoxygenation (H/R)‐treated HUVECs in the proliferation, intracellular ROS and cellular migratory ability. In addition, the Algae‐gel could downregulate the expression of hypoxia‐inducible factors 1α (HIF‐1α) and vascular endothelial growth factor (VEGF) of hypoxia and H/R‐injured HUVECs due to the improvement of hypoxia and H/R injury. This photosynthetic co‐culture system could offer a promising approach for repairing hypoxia and H/R‐injured cells or tissue by providing safe and stable O2.

Abstract Titanium (Ti) dental scaffolds are widely used in dental prosthetics due to their excellent mechanical properties and biocompatibility. However, conventional Ti scaffolds manufactured through machining often do not fit perfectly with the bone defect site. Laser powder bed fusion (LPBF) technology enables the personalised manufacturing of custom‐made Ti scaffolds. A custom‐made Ti scaffold was prepared using LPBF and its surface roughness was improved through chemical polishing. To enhance the surface roughness, a nitric acid mixed solution with a specific composition of HF: HNO3:C3H6O3 = 2:2:3 was used. The polishing mechanism was investigated by adjusting the F/Ti ratio to control the formation and dissolution of the oxide film. As a result, the surface of the Ti scaffold after polishing exhibited a smooth and flat appearance compared to the LPBF part, with a reduced surface roughness (Ra) of 1.23 ± 0.19 μm. The custom‐made Ti scaffold also demonstrated favourable mechanical properties, with a bending strength of 335.18 ± 33.62 MPa and stiffness of 2.13 ± 0.21 GPa. Furthermore, in vitro cell tests confirmed the excellent biocompatibility of the custom‐made Ti scaffold. The authors present a feasible strategy for the further clinical application of custom‐made Ti scaffolds, offering enhanced surface properties and addressing the limitations of conventional machining methods.

Abstract Engineered stone silicosis (ESS), primarily caused by inhaling respirable crystalline silica, poses a significant occupational health risk globally. ESS has no effective treatment and presents a rapid progression from simple silicosis (SS) to progressive massive fibrosis (PMF), with respiratory failure and death. Despite the use of diagnostic methods like chest x‐rays and high‐resolution computed tomography, early detection of silicosis remains challenging. Since routine blood tests have shown promise in detecting inflammatory markers associated with the disease, this study aims to assess whether routine blood biomarkers, coupled with machine learning techniques, can effectively differentiate between healthy individuals, subjects with SS, and PMF. To this end, 107 men diagnosed with silicosis, ex‐workers in the engineered stone (ES) sector, and 22 healthy male volunteers as controls not exposed to ES dust were recruited. Twenty‐one primary biochemical markers derived from peripheral blood extraction were obtained retrospectively from clinical hospital records. Relief‐F features selection technique was applied, and the resulting subset of 11 biomarkers was used to build five machine learning models, demonstrating high performance with sensitivities and specificities in the best case greater than 82% and 89%, respectively. The percentage of lymphocytes, the angiotensin‐converting enzyme, and lactate dehydrogenase indexes were revealed, among others, as blood biomarkers with significant cumulative importance for the machine learning models. Our study reveals that these biomarkers could detect a chronic inflammatory status and potentially serve as a supportive tool for the diagnosis, monitoring, and early detection of the progression of silicosis.

Abstract While surgical resection is a mainstay of cancer treatment, many tumors are unresectable due to stage, location, or comorbidities. Ablative therapies, which cause local destruction of tumors, are effective alternatives to surgical excision in several settings. Ethanol ablation is one such ablative treatment modality in which ethanol is directly injected into tumor nodules. Ethanol, however, tends to leak out of the tumor and into adjacent tissue structures, and its biodistribution is difficult to monitor in vivo. To address these challenges, this study presents a cutting‐edge technology known as Light‐Activatable Sustained‐Exposure Ethanol Injection Technology (LASEIT). LASEIT comprises a three‐part formulation: (1) ethanol, (2) benzoporphyrin derivative, which enables fluorescence‐based tracking of drug distribution and the potential application of photodynamic therapy, and (3) ethyl cellulose, which forms a gel upon injection into tissue to facilitate drug retention. In vitro drug release studies showed that ethyl cellulose slowed the rate of release in LASEIT by 7×. Injections in liver tissues demonstrated a 6× improvement in volume distribution when using LASEIT compared to controls. In vivo experiments in a mouse pancreatic cancer xenograft model showed LASEIT exhibited significantly stronger average radiant efficiency than controls and persisted in tumors for up to 7 days compared to controls, which only persisted for less than 24 h. In summary, this study introduced LASEIT as a novel technology that enabled real‐time fluorescence monitoring of drug distribution both ex vivo and in vivo. Further research exploring the efficacy of LASEIT is strongly warranted.

Abstract Cowpea mosaic virus (CPMV) has demonstrated superior immune stimulation and efficacy as an intratumoral immunotherapy, providing a strong argument for its clinical translation. One important consideration for any new drug candidate is the long‐term stability of the drug and its formulation. Therefore, our lab has evaluated the physical stability and biological activity, that is, anti‐tumor potency, of formulations of CPMV in buffer (with and without a sucrose preservative) in multiple temperature conditions ranging from ultralow freezers to a heated incubator over a period of 9 months. We found that non‐refrigerated temperatures 37°C and room temperature quickly led to CPMV destabilization, as evidenced by significant protein and RNA degradation after just 1 week. Refrigerated storage at 4°C extended physical stability, though signs of particle breakage and RNA escape appeared after 6 and 9 months. CPMV stored in frozen conditions, including −20°C, −80°C, and liquid N2, remained intact and matched the characteristics of fresh CPMV throughout the duration of the study. The biological activity was evaluated using a murine dermal melanoma model, and efficacy followed the observed trends in physical stability: CPMV stored in refrigerated and warmer conditions exhibited decreased anti‐tumor efficacy compared to freshly prepared formulations. Meanwhile, frozen‐stored CPMV performed similarly to freshly purified CPMV, resulting in reduced tumor growth and extended survival. Data, therefore, indicates that CPMV stored long‐term in cold or frozen conditions remains stable and efficacious, providing additional support to advance this powerful plant virus to translation.

Abstract Confounding results of engineered mesenchymal stem cells (MSCs) used as cellular vehicles has plagued technologies whereby success or failure of novel approaches may be dismissed or inaccurately ascribed solely to the biotechnology platform rather than suitability of the human donor. Polymeric materials were screened for non‐viral engineering of MSCs from multiple human donors to deliver bone morphogenic protein‐4 (BMP4), a protein previously investigated in clinical trials for glioblastoma (GBM) to combat a subpopulation of highly invasive and tumorigenic clones. A “smart technology” that target the migratory and stem‐like nature of GBM will require: (1) a cellular vehicle (MSC) which can scavenge and target residual cells left behind after surgical debulking and deliver; (2) anti‐glioma cargo (BMP4). Multiple MSC donors are safely engineered, though varied in susceptibility to accept BMP4 due to intrinsic characteristics revealed by their molecular signatures. Efficiency is compared via secretion, downstream signaling, differentiation, and anti‐proliferative properties across all donors. In a clinically relevant resection and recurrence model of patient‐derived human GBM, we demonstrate that nanoengineered MSCs are not “donor agnostic” and efficacy is influenced by the inherent suitability of the MSC to the cargo. Therefore, donor profiles hold greater influence in determining downstream outcomes than the technical capabilities of the engineering technology.

Abstract Mesenchymal stem cell (MSC)‐derived extracellular vesicles (EVs) are a promising treatment for myocardial infarction (MI), but their therapeutic efficacy is limited by inefficient accumulation at the target site. A minimally invasive MSC EV therapy that enhances EV accumulation at the disease site and extends EV retention could significantly improve post‐infarct cardiac regeneration. Here, we show that EVs decorated with the next‐generation of high‐affinity (HiA) heterodimerizing leucine zippers, termed HiA Zippersomes, amplify targetable surface areas through in situ crosslinking and exhibited ~7‐fold enhanced accumulation within the infarcted myocardium in mice after 3 days and continued to be retained up to Day 21, surpassing the performance of unmodified EVs. After MI in mice, HiA Zippersomes increase the ejection fraction by 53% and 100% compared with unmodified EVs and phosphate‐buffered saline (PBS), respectively. This notable improvement in cardiac function played a crucial role in restoring healthy heart performance. HiA Zippersomes also robustly decrease infarct size by 52% and 60% compared with unmodified EVs and PBS, respectively, thus representing a promising platform for minimally invasive vesicle delivery to the infarcted heart compared to intramyocardial injections.

Abstract Self‐organizing brain organoids provide a promising tool for studying human development and disease. Here we created human forebrain organoids with stable and homogeneous expression of channelrhodopsin‐2 (ChR2) by generating AAVS1 safe harbor locus‐targeted, ChR2 knocked‐in human pluripotent stem cells (hPSCs), followed by the differentiation of these genetically engineered hPSCs into forebrain organoids. The resulting ChR2‐expressing human forebrain organoids showed homogeneous cellular expression of ChR2 throughout entire regions without any structural and functional perturbations and displayed consistent and robust neural activation upon light stimulation, allowing for the non‐virus mediated, spatiotemporal optogenetic control of neural activities. Furthermore, in the hybrid platform in which brain organoids are connected with spinal cord organoids and skeletal muscle spheroids, ChR2 knocked‐in forebrain organoids induced strong and consistent muscle contraction upon brain‐specific optogenetic stimulation. Our study thus provides a novel, non‐virus mediated, preclinical human organoid system for light‐inducible, consistent control of neural activities to study neural circuits and dynamics in normal and disease‐specific human brains as well as neural connections between brain and other peripheral tissues.

Abstract Hydrogels have been used in the clinic since the late 1980s with broad applications in drug delivery, cosmetics, tissue regeneration, among many other areas. The past three decades have witnessed rapid advances in the fields of polymer chemistry, crosslinking approaches, and hydrogel fabrication methods, which have collectively brought many new hydrogel products, either injectable or non‐injectable, to clinical studies. In an article published in 2020 entitled “Hydrogels in the clinic”, we reviewed the clinical landscape and translational challenges of injectable hydrogels. Here, we provide an update on the advances in the field and also extend the scope to include non‐injectable hydrogels. We highlight recently approved hydrogel products, provide an update on the clinical trials of injectable hydrogels, and discuss active clinical trials of topically applied and implantable hydrogels.

Abstract The hollow fiber membrane bundle is the functional component of artificial lungs, transferring oxygen to and carbon dioxide from the blood. It is also the primary location of blood clot formation and propagation in these devices. The geometric design of fiber bundles is defined by a narrow set of parameters that determine gas exchange efficiency and blood flow resistance, principally: fiber packing density, path length, and frontal area. These same parameters also affect thrombosis. This study investigated the effect of these parameters on clot formation using 3D printed flow chambers that mimic the geometry and blood flow patterns of fiber bundles. Hollow fibers were represented by an array of vertical micro‐rods (380 μm diameter) arranged with three packing densities (40%, 50%, and 60%) and two path lengths (2 and 4 cm). Blood was pumped through these devices corresponding to three mean blood flow velocities (16, 20, and 25 cm/min). Results showed that (1) clot formation decreases dramatically with decreasing packing density and increasing blood flow velocity, (2) clot formation at the outlet of the fiber bundle enhances deposition upstream, and consequently (3) greater path length provides greater clot‐free fiber surface area for gas exchange than a shorter path length. These results can help guide the design of less thrombogenic, more efficient artificial lung designs.

Abstract Given the prevalence of hematological conditions, surgeries, and trauma incidents, hemostats—therapeutics designed to control and arrest bleeding—are an important tool in patient care. The prophylactic and therapeutic use of hemostats markedly enhances survival rates and improves the overall quality of life of patients suffering from these conditions. Since their inception in the 1960s, hemostats have witnessed remarkable progress in terms of the active ingredients utilized, therapeutic outcomes, demonstrated efficacy, and the storage stability. In this review, we provide a comprehensive analysis of commercially available hemostats approved by the FDA, along with newer investigative hemostats currently in active clinical trials. We delve into the modality of active ingredients, route of administration, formulation type, and disease indications of these approved and investigative hemostats. Further, we analyze the trends observed in the hemostat actives for Hemophilia A and B, concluding with insights into the emerging patterns and noteworthy developments to watch for in this dynamic field.

Abstract Gestational diabetes mellitus (GDM) is a pregnancy disorder associated with short‐ and long‐term adverse outcomes in both mothers and infants. The current clinical test of blood glucose levels late in the second trimester is inadequate for early detection of GDM. Here we show the utility of Raman spectroscopy (RS) for rapid and highly sensitive maternal metabolome screening for GDM in the first trimester. Key metabolites, including phospholipids, carbohydrates, and major amino acids, were identified with RS and validated with mass spectrometry, enabling insights into associated metabolic pathway enrichment. Using classical machine learning (ML) approaches, we showed the performance of the RS metabolic model (cross‐validation AUC 0.97) surpassed that achieved with patients' clinical data alone (cross‐validation AUC 0.59) or prior studies with single biomarkers. Further, we analyzed novel proteins and identified fetuin‐A as a promising candidate for early GDM prediction. A correlation analysis showed a moderate to strong correlation between multiple metabolites and proteins, suggesting a combined protein‐metabolic analysis integrated with ML would enable a powerful screening platform for first trimester diagnosis. Our study underscores RS metabolic profiling as a cost‐effective tool that can be integrated into the current clinical workflow for accurate risk stratification of GDM and to improve both maternal and neonatal outcomes.

Abstract Sperm quality analysis plays an important role in diagnosing infertility, which is widely implemented by computer‐assisted sperm analysis (CASA) of sperm‐swimming imaging from commercial phase‐contrast microscopy. A well‐equipped microscope comes with a high cost, increasing the burden of assessment, and it also occupies a large volume. For point‐of‐care testing (POCT) of sperm quality, these factors are confronted with the challenges of low‐cost and portable instruments. In this study, an encoded light‐emitting diode (LED) array illumination is employed to achieve a portable microscope with multicontrast imaging for sperm quality analysis. This microscopy has dimensions of 16.5 × 14.0 × 25.0 cm, and its dark‐field (DF) imaging provides high‐contrast sperm image data which is suitable for CASA. According to DF imaging, we developed a software of LabCASA, which can used to assess the motility characteristics of sperm. Compared with TrackMate, the difference in motility parameters from our software was less than 10% in the coefficient of variation (CV). The sperm motility parameters vary with the chamber temperature, which further confirms the reliability of our system with DF imaging. The DF imaging provides strong robustness for tracking sperm's motion under different microscopes. For assessment of the motility parameters, our system can work at a lower cost with a plastic structure. This system with DF imaging is suitable for portable POCT of sperm quality analysis, which is highly cost‐effective in resource‐constrained circumstances.

Abstract Biobanks hold a pivotal role in facilitating translational and clinical research endeavors. However, the effects of prolonged storage on frozen blood samples analytes are not well defined yet. The aim of this study was to investigate the long‐term stability of the quality of DNA, RNA, and endocrine markers within blood samples amassed from the biobank over the past 11 years. The results show that the overall quality and integrity of DNA remained not significantly influenced. However, RNA integrity and purity displayed substantial deterioration as storage duration increased, to ensure high‐quality RNA for downstream analyses, advised to prioritize using blood samples stored within 3 years. Furthermore, the study examined the influence of storage time on endocrine markers. Through repeated measures ANOVA and linear regression analyses, it was evident that storage duration significantly influenced the levels of endocrine markers. This insight aids researchers in selecting appropriate markers for their investigations and augments the precision and dependability of results when dealing with long‐term stored samples.

Abstract Postoperative critical care management of congenital heart disease patients requires prompt intervention when the patient deviates significantly from clinician‐determined vital sign and hemodynamic goals. Current monitoring systems only allow for static thresholds to be set on individual variables, despite the expectations that these signals change as the patient recovers and that variables interact. To address this incongruency, we have employed statistical process monitoring (SPM) techniques originally developed to monitor batch industrial processes to monitor high‐frequency vital sign and hemodynamic data to establish multivariate trajectory maps for patients with d‐transposition of the great arteries following the arterial switch operation. In addition to providing multivariate trajectory maps, the multivariate control charts produced by the SPM framework allow for assessment of adherence to the desired trajectory at each time point as the data is collected. Control charts based on slow feature analysis were compared with those based on principal component analysis. Alarms generated by the multivariate control charts are discussed in the context of the available clinical documentation.

Abstract Tissue engineering has emerged as a promising avenue for reconstructive urology, though only a limited number of tissue‐engineered urethral constructs have advanced to clinical testing. Presently, there exists a dearth of agreement regarding the most promising constructs deserving of implementation in clinical practice. The objective of this review was to provide a comprehensive analysis of preclinical trials findings of a tissue‐engineered urethra and to identify the most promising constructs for future translation into clinical practice. A systematic search of the Pubmed, Scopus, and PMC databases was conducted in accordance with the PRISMA statement. Manuscripts published in English between 2015 and 2022, reporting on the methodology for creating a tissue‐engineered urethra, assessing the regenerative potential of the scaffold in a male animal model, and evaluating the clinical and histological outcomes of treatment, were included. A total of 48 manuscripts met the inclusion criteria, with 12 being eligible for meta‐analysis. Meta‐analysis revealed no significant benefit of any matrix type in terms of complication rates. However, acellular matrices demonstrated significant advantage over cellular matrices in case of no postoperative stricture formation (odds ratio = 0.06 [95% CI 0.01; 0.23], p

Abstract Spinal cord injury (SCI) is a cause of profound and irreversible damage, with no effective therapy to promote functional recovery. Photobiomodulation (PBM) may provide a viable therapeutic approach using red or near‐infrared light to promote recovery after SCI by mitigating neuroinflammation and preventing neuronal apoptosis. Our current study aimed to optimize PBM dose regimens and develop and validate the efficacy of an invasive PBM delivery paradigm for SCI. Dose optimization studies were performed using a serum withdrawal model of injury in cultures of primary adult rat dorsal root ganglion neurons (DRGN). Implantable and transcutaneous PBM delivery protocols were developed and validated using cadaveric modeling. The efficacy of PBM in promoting recovery after SCI in vivo was studied in a dorsal column crush injury model of SCI in adult rats. Optimal neuroprotection in vitro was achieved between 4 and 22 mW/cm2. 11 mW/cm2 for 1 min per day (0.66 J/cm2) increased cell viability by 45% over 5 days (p

Abstract Heart valve replacement surgeries are performed on patients suffering from abnormal heart valve function. In these operations, the problematic tissue is replaced with mechanical valves or with bioprosthetics that are being developed. The thrombotic effect of mechanical valves, reflecting the need for lifelong use of anticoagulation drugs, and the short‐lived nature of biological valves make these two types of valves problematic. In addition, they cannot adapt to the somatic growth of young patients. Although decellularized scaffolds have shown some promise, a successful translation has so far evaded. Although decellularized porcine xenografts have been extensively studied in the literature, they have several disadvantages, such as a propensity for calcification in the implant model, a risk of porcine endogenous retrovirus (PERV) infection, and a high xenoantigen density. As seen in clinical data, it is clear that there are biocompatibility problems in almost all studies. However, since decellularized sheep heart valves have not been tried in the clinic, a large data pool could not be established. This review compares and contrasts decellularized porcine and sheep xenografts for heart valve tissue engineering. It reveals that decellularized sheep heart valves can be an alternative to pigs in terms of biocompatibility. In addition, it highlights the potential advantages of bioinks derived from the decellularized extracellular matrix in 3D bioprinting technology, emphasizing that they can be a new alternative for the application. We also outline the future prospects of using sheep xenografts for heart valve tissue engineering.

Abstract Glioblastoma (GBM) is the most common primary malignant brain tumor diagnosed in adults, carrying with it an extremely poor prognosis and limited options for effective treatment. Various cell therapies have emerged as promising candidates for GBM treatment but fail in the clinic due to poor tumor trafficking, poor transplantation efficiency, and high systemic toxicity. In this study, we design, characterize, and test a 3D‐printed cell delivery platform that can enhance the survival of therapeutic cells implanted in the GBM resection cavity. Using continuous liquid interface production (CLIP) to generate a biocompatible 3D hydrogel, we demonstrate that we can effectively seed neural stem cells (NSCs) onto the surface of the hydrogel, and that the cells can proliferate to high densities when cultured for 14 days in vitro. We show that NSCs seeded on CLIP scaffolds persist longer than freely injected cells in vivo, proliferating to 20% higher than their original density in 6 days after implantation. Finally, we demonstrate that therapeutic fibroblasts seeded on CLIP more effectively suppress tumor growth and extend survival in a mouse model of LN229 GBM resection compared to the scaffold or therapeutic cells alone. These promising results demonstrate the potential to leverage CLIP to design hydrogels with various features to control the delivery of different types of cell therapies. Future work will include a more thorough evaluation of the immunological response to the material and improvement of the printing resolution for biocompatible aqueous resins.

Abstract Antibody‐drug conjugates (ADCs), chemotherapeutic agents conjugated to an antibody to enhance their targeted delivery to tumors, represent a significant advancement in cancer therapy. ADCs combine the precise targeting capabilities of antibodies and the potent cell‐killing effects of chemotherapy, allowing for enhanced cytotoxicity to tumors while minimizing damage to healthy tissues. Here, we provide an overview of the current clinical landscape of ADCs, highlighting 11 U.S. Food and Drug Administration (FDA)‐approved products and discussing over 500 active clinical trials investigating newer ADCs. We also discuss some key challenges associated with the clinical translation of ADCs and highlight emerging strategies to overcome these hurdles. Our discussions will provide useful guidelines for the future development of safer and more effective ADCs for a broader range of indications.

Abstract Conventional chemotherapeutic agents are limited by their lack of targeting and penetration and their short retention time, and chemotherapy might induce an immune suppressive environment. Peptide self‐assembly can result in a specific morphology, and the resulting morphological changes are stimuli responsive to the external environment, which is important for drug permeation and retention of encapsulated chemotherapeutic agents. In this study, a polypeptide (Pep1) containing the peptide sequences PLGLAG and RGD that is responsive to matrix metalloproteinase 2 (MMP‐2) was successfully developed. Pep1 underwent a morphological transformation from a spherical structure to aggregates with a high aspect ratio in response to MMP‐2 induction. This drug delivery system (DI/Pep1) can transport doxorubicin (DOX) and indomethacin (IND) simultaneously to target tumor cells for subsequent drug release while extending drug retention within tumor cells, which increases immunogenic cell death and facilitates the immunotherapeutic effect of CD4+ T cells. Ultimately, DI/Pep1 attenuated tumor‐associated inflammation, enhanced the body's immune response, and inhibited breast cancer growth by combining the actions of DOX and IND. Our research offers an approach to hopefully enhance the effectiveness of cancer treatment.

Abstract Lymph node (LN)‐resident dendritic cells (DCs) are a promising target for vaccination given their professional antigen‐presenting capabilities and proximity to a high concentration of immune cells. Direct intra‐LN injection has been shown to greatly enhance the immune response to vaccine antigens compared to traditional intramuscular injection, but it is infeasible to implement clinically in a vaccination campaign context. Employing the passive lymphatic flow of antigens to target LNs has been shown to increase total antigen uptake by DCs more than inflammatory adjuvants, which recruit peripheral DCs. Herein, we describe a novel vaccination platform in which two complementary multi‐arm poly(ethylene glycol) (PEG) polymers—one covalently bound to the model antigen ovalbumin (OVA)—are injected subcutaneously into two distinct sites. These materials then drain to the same LN through different lymphatic vessels and, upon meeting in the LN, rapidly crosslink. This system improves OVA delivery to, and residence time within, the draining LN compared to all control groups. The crosslinking of the two PEG components also improves humoral immunity without the need for any pathogen‐mimicking adjuvants. Further, we observed a significant increase in non‐B/T lymphocytes in LNs cross‐presenting the OVA peptide SIINFEKL on MHC I over a dose‐matched control containing alum, the most common clinical adjuvant, as well as an increase in DC activation in the LN. These data suggest that this platform can be used to deliver antigens to LN‐resident immune cells to produce a stronger humoral and cellular immune response over materials‐matched controls without the use of traditional adjuvants.

Abstract Streptomyces genus produces a large number of antibiotics, which are always synthesized by specific biosynthetic gene clusters (BGCs). To resist autotoxicity, transporters encoded by genes located within BGC occasionally pump antibiotic along with transporter encoded by gene located outside BGC. Daunorubicin is an anthracycline antibiotic biosynthesized by Streptomyces species, playing a crucial role in the treatment of leukaemia. In existing studies, only one two‐component ATP‐binding cassette (ABC) transporter, encoded by drrA1‐drrB1 (abbreviated as drrAB1) and located within the daunorubicin BGC, has been proven to extrude daunorubicin. In this work, two other two‐component ABC transporters, encoded by drrAB2 and drrAB3 and located outside the cluster, were found to play the complementary role in daunorubicin efflux in S. coeruleorubidus. Disruption of three drrABs resulted in a 94% decrease in daunorubicin production. Furthermore, drrAB2 is regulated by the TetR family regulator DrrR1, responding to the intracellular accumulation of daunorubicin and suggesting its role in stress response and self‐resistance. Although the homologues of DrrAB1 are only found in three anthracycline BGCs, the homologues of DrrAB2 and DrrAB3 are spread in many Streptomyces strains which do not contain any known anthracycline BGC. This indicates that DrrAB2 and DrrAB3 may recognize and extrude a broader range of substrates besides daunorubicin, thus playing a more extensive role in cellular detoxification.

Abstract Infected wounds can result in complex clinical complications and delayed healing, presenting a significant global public health challenge. This study explored the effects of topical application of two probiotics, Lactobacillus rhamnosus GG (LGG) and Bifidobacterium animalis subsp. lactis BB‐12, on the microenvironment of infected wounds and their impact on wound healing. LGG and BB‐12 were applied separately and topically on the Staphylococcus aureus (S. aureus)‐infected skin wounds of the rat model on a daily basis. Both probiotics significantly accelerated wound healing, demonstrated by enhanced granulation tissue formation and increased collagen deposition, with BB‐12 showing superior efficacy. LGG and BB‐12 both effectively inhibited neutrophil infiltration and decreased the expression of pro‐inflammatory cytokines tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6). Notably, BB‐12 markedly reduced IL‐6 levels, while LGG significantly lowered TNF‐α, transforming growth factor‐β (TGF‐β) and vascular endothelial growth factor (VEGF). Additionally, both probiotics promoted macrophage polarization towards the anti‐inflammatory M2 phenotype. Microbiota analysis revealed that LGG and BB‐12 significantly decreased the abundance of pathogenic bacteria (e.g. Staphylococcus and Proteus) and increased the proportion of beneficial bacteria (e.g. Corynebacterium). Particularly, BB‐12 was more effective in reducing Staphylococcus abundance, whereas LGG excelled in promoting Corynebacterium growth. These findings suggest the ability of LGG and BB‐12 to modulate the wound microenvironment, enhance wound healing and provide valuable insights for the management of infected wounds.

Abstract In this research, biogenic selenium nanoparticles were produced by the fungi Yarrowia lipolytica, and the biological activity of its nanoparticles was studied for the first time. The electron microscopy analyses showed the production of nanoparticles were intracellular and the resulting particles were extracted and characterized by XRD, zeta potential, FESEM, EDX, FTIR spectroscopy and DLS. These analyses showed amorphous spherical nanoparticles with an average size of 110 nm and a Zeta potential of −34.51 ± 2.41 mV. Signatures of lipids and proteins were present in the capping layer of biogenic selenium nanoparticles based on FTIR spectra. The antimicrobial properties of test strains showed that Serratia marcescens, Klebsiella pneumonia, Escherichia coli, Pseudomonas aeruginosa and Bacillus subtilis were inhibited at concentrations between 160 and 640 μg/mL, while the growth of Candida albicans was hindered by 80 μg/mL of biogenic selenium nanoparticles. At concentrations between 0.5 and 1.5 mg/mL of biogenic selenium nanoparticles inhibited up to 50% of biofilm formation of Klebsiella pneumonia, Acinetobacter baumannii, Staphylococcus aureus and Pseudomonas aeruginosa. Additionally, the concentration of 20–640 μg/mL of these bioSeNPs showed antioxidant activity. Evaluating the cytotoxicity of these nanoparticles on the HUVEC and HepG2 cell lines did not show any significant toxicity within MIC concentrations of SeNPs. This defines that Y. lipolytica synthesized SeNPs have strong potential to be exploited as antimicrobial agents against pathogens of WHO concern.

Abstract The widespread use of opioids for chronic pain management not only poses a significant public health issue but also contributes to the risk of tolerance, dependence, and addiction, leading to opioid use disorder (OUD), which affects millions globally each year. Recent research has highlighted a potential bidirectional relationship between the gut microbiome and OUD. This emerging perspective is critical, especially as the opioid epidemic intensifies, emphasizing the need to investigate how OUD may alter gut microbiome dynamics and vice versa. Understanding these interactions could reveal new insights into the mechanisms of addiction and tolerance, as well as provide novel approaches for managing and potentially mitigating OUD impacts. This comprehensive review explores the intricate bidirectional link through the gut–brain axis, focusing on how opiates influence microbial composition, functional changes, and gut mucosal integrity. By synthesizing current findings, the review aims to inspire new strategies to combat the opioid crisis and leverage microbiome‐centred interventions for preventing and treating OUD.

Abstract Previous reports have demonstrated that alcohol consumption significantly reduces the abundance of Lactobacillus in the gut. In this study, we selected five species of the genus Lactobacillus, commonly found in fermented foods, and acknowledged them as safe, edible, and effective in preventing or treating certain diseases, to evaluate their effects on alcoholic liver disease (ALD). By comparing the liver damage indices in each group, we found that the type strain of Lactobacillus helveticus (LH, ATCC 15009) had the most marked alleviating effect on ALD‐induced liver injury. Furthermore, experiments combining microbiomics and metabolomics were conducted to explore the mechanisms underlying the hepatoprotective effects of LH. Finally, we discovered that LH mitigated ethanol‐induced liver steatosis and inflammation in ALD mice by altering the structure and function of the gut microbiome, increasing intestinal levels of short‐chain fatty acids (SCFAs), and enhancing gut barrier integrity. These findings suggest a potential strategy for the clinical management of patients with ALD.

Abstract Escherichia coli (E. coli) is a ubiquitous symbiotic bacterium in the gut, and the diversity of E. coli genes determines the diversity of its functions. In this review, the two‐edged sword theory was innovatively proposed. For the question ‘how can we harness the ambivalent nature of E. coli to screen and treat CRC?’, in terms of CRC screening, the variations in the abundance and subtypes of E. coli across different populations present an opportunity to utilise it as a biomarker, while in terms of CRC treatment, the natural beneficial effect of E. coli on CRC may be limited, and engineered E. coli, particularly certain subtypes with probiotic potential, can indeed play a significant role in CRC treatment. It seems that the favourable role of E. coli as a genetic tool lies not in its direct impact on CRC but its potential as a research platform that can be integrated with various technologies such as nanoparticles, imaging methods, and synthetic biology modification. The relationship between gut microflora and CRC remains unclear due to the complex diversity and interaction of gut microflora. Therefore, the application of E. coli should be based on the ‘One Health’ view and take the interactions between E. coli and other microorganisms, host, and environmental factors, as well as its own changes into account. In this paper, the two‐edged sword role of E. coli in CRC is emphasised to realise the great potential of E. coli in CRC screening and treatment.

Abstract Polycystic ovary syndrome (PCOS) is one of the most widespread endocrinopathy affecting women of reproductive age with detrimental effects on life quality and health. Among several mechanisms involved in its aetiopathogenesis, recent studies have also postulated the involvement of the vaginal and intestinal microbiota in the development of this disorder. In this study, an accurate insight into the microbial changes associated with PCOS was performed through a pooled‐analysis highlighting that this syndrome is characterized by intestinal and vaginal dysbiosis with a reduction of beneficial microorganisms and a higher proportion of potential pathogens. Based on this observation, we evaluated the ability of a milk‐derived protein exerting positive outcomes in the management of PCOS, that is, α‐lactalbumin (α‐LA), to recover PCOS‐related dysbiosis. In vitro experiments revealed that this protein improved the growth performances of members of two health‐promoting bacterial genera, that is, Bifidobacterium and Lactobacillus, depleted in both intestinal and vaginal microbiota of PCOS‐affected women. In addition, α‐LA modulated the taxonomic composition and growth performances of the microbial players of the complex intestinal and vaginal microbiota. Finally, an in vivo pilot study further corroborated these observations. The oral administration of α‐LA for 30 days to women with PCOS revealed that this protein may have a role in favouring the growth of health‐promoting bacteria yet limiting the proliferation of potential pathogens. Overall, our results could pave the way to the use of α‐LA as a valid compound with ‘prebiotic effects’ to limit/restore the PCOS‐related intestinal and vaginal dysbiosis.

Abstract A healthy mucus is essential for maintaining intestinal homeostasis and overall well‐being. In recent years, extensive research focused on understanding the intricate interactions between mucus and the gut microbiota. Mucus‐adhering bacteria play crucial roles in preserving barrier integrity, epithelial permeability and mucus architecture, as well as in the colonization resistance against pathogens. Unravelling the significance of these microorganisms in human health and disease is challenging, primarily because most of the studies on the human gut microbiota rely on faecal samples, which do not fully represent the microecological complexity found in the intestinal mucosa. This review discusses novel strategies to specifically target and evaluate the mucosal microbiota, such as culturomics applied to mucosal biopsies or brushings, intestinal organoids and artificial in vitro models incorporating mucus.

Abstract The interrelationship between climate change, pollution and the aerobiome (the microbiome of the air) is a complex ecological dynamic with profound implications for human and ecosystem health. This mini‐review explores the multifaceted relationships among these factors. By synthesising existing research and integrating interdisciplinary perspectives, we examine the mechanisms driving interactions within the climate change–pollution–aerobiome nexus. We also explore synergistic and cascading effects and potential impacts on human health (including both communicable and non‐communicable diseases) and that of wider ecosystems. Based on our mini‐review results, climate change influences air pollution and, independently, air pollution affects the composition, diversity and activity of the aerobiome. However, we apply a ‘systems thinking’ approach and create a set of systems diagrams to show that climate change likely influences the aerobiome (including bacteria and fungi) via climate change–pollution interactions in complex ways. Due to the inherent complexity of these systems, we emphasise the importance of holistic and/or interdisciplinary approaches and collaborative efforts in understanding this nexus to safeguard planetary health in an era of rapid environmental change.

Abstract Merkel cell polyomavirus (MCPyV) is the foremost causative factor of Merkel cell carcinoma (MCC), a rare yet highly aggressive skin cancer. Although the evaluation of circulating IgG antibodies against Merkel cell polyomavirus (MCPyV) LT/sT oncoproteins is clinically useful for MCC diagnosis/prognosis, a limited number of assays for identifying such antibodies have been developed. Herein, a novel indirect immunoassay with synthetic epitopes/mimotopes of MCPyV oncoproteins was computationally designed and experimentally validated on control sera and sera from healthy individuals and MCC patients. Upon computational design of five synthetic peptides, the performance of the immunoassay in detecting anti‐oncoprotein IgGs in MCPyV‐positive and ‐negative control sera was evaluated. The immunoassay was afterwards extended on sera from healthy individuals, and, for longitudinal analysis, MCC patients. Performance properties such as sensitivity and specificity and positive/negative predictive values were adequate. Receiver‐operating characteristic (ROC) curves indicated that the areas under the curves (AUCs) were within the low/moderately accurate ranges. Immunoassay was repeatable, reproducible and accurate. As expected, the serum anti‐oncoprotein IgG prevalence in healthy individuals was low (2%–5%). Anti‐oncoprotein IgGs slightly increased when MCC patients experienced partial tumour remission and/or stable disease, compared to baseline. Our data indicate that the newly developed immunoassay is reliable for detecting circulating anti‐oncoprotein IgGs both in healthy individuals and MCC patients.

Abstract In Komagataella phaffii (Pichia pastoris), formate is a recognized alternative inducer to methanol for expression systems based on the AOX1 promoter (pAOX1). By disrupting the formate dehydrogenase encoding FDH1 gene, we converted such a system into a self‐induced one, as adding any inducer in the culture medium is no longer requested for pAOX1 induction. In cells, formate is generated from serine through the THF‐C1 metabolism, and it cannot be converted into carbon dioxide in a FdhKO strain. Under non‐repressive culture conditions, such as on sorbitol, the intracellular formate generated from the THF‐C1 metabolism is sufficient to induce pAOX1 and initiate protein synthesis. This was evidenced for two model proteins, namely intracellular eGFP and secreted CalB lipase from C. antarctica. Similar protein productivities were obtained for a FdhKO strain on sorbitol and a non‐disrupted strain on sorbitol‐methanol. Considering a K. Phaffii FdhKO strain as a workhorse for recombinant protein synthesis paves the way for the further development of methanol‐free processes in K. phaffii.

Abstract Plant health is crucial for maintaining the well‐being of humans, animals and the environment. Plant pathogens pose significant challenges to agricultural production, global food security and ecosystem biodiversity. This problem is exacerbated by the impact of climate change, which is expected to alter the emergence and evolution of plant pathogens and their interaction with their plant hosts. Traditional approaches to managing phytopathogens involved the use of chemical pesticides, but alternative strategies are needed to address their ongoing decline in performance as well as their negative impact on the environment and public health. Here, we highlight the advancement and effectiveness of biocontrol strategies based on the use of antimicrobial‐producing plant‐associated bacteria, anti‐virulence therapy (e.g. quorum quenching) and microbiome engineering as sustainable biotechnological approaches to promote plant health and foster sustainable agriculture. Notably, Enterobacterales are emerging as important biocontrol agents and as a source of new antimicrobials for potential agricultural use. We analysed here the genomes of over 250 plant‐associated enterobacteria to examine their potential to synthesize secondary metabolites. Exploration of the plant microbiome is of major interest in the search for eco‐friendly alternatives for reducing the use of chemical pesticides.

Abstract Fusarium wilt is one of the major constraints on global watermelon production, and Fusarium oxysporum f. sp. niveum (Fon) is the causative agent of Fusarium wilt in watermelon and results in severe yield and quality losses worldwide. The enhancement of antifungal activity from antagonistic bacteria against Fon is highly practical for managing Fusarium wilt in watermelon. The aim of this study was to maximize the antifungal activity of Bacillus velezensis LZN01 by optimizing fermentation conditions and analysing its regulatory mechanism via transcriptome sequencing. The culture and fermentation conditions for strain LZN01 were optimized by single‐factor and response surface experiments. The optimum culture conditions for this strain were as follows: the addition of D‐fructose at 35 g/L and NH4Cl at 5 g/L in LB medium, pH 7, and incubation at 30°C for 72 h. The fungal inhibition rate for strain LZN01 reached 71.1%. The improvement of inhibition rate for strain LZN01 in optimization fermentation was supported by transcriptomic analysis; a total of 491 genes were upregulated, while 736 genes were downregulated. Transcriptome analysis revealed that some differentially expressed genes involved in carbon and nitrogen metabolism, oxidation–reduction, fatty acid and secondary metabolism; This optimization process could potentially lead to significant alterations in the production levels and types of antimicrobial compounds by the strain. Metabolomics and UPLC/Q‐Exactive Orbitrap MS analysis revealed that the production yields of antimicrobial compounds, such as surfactin, fengycin, shikimic acid, and myriocin, increased or were detected in the cell‐free supernatant (CFS) after the fermentation optimization process. Our results indicate that fermentation optimization enhances the antifungal activity of the LZN01 strain by influencing the expression of genes responsible for the synthesis of antimicrobial compounds.

Abstract In situ vaccination is a therapeutic approach aimed at exploiting tumour antigens available at a tumour site to induce tumour‐specific adaptive immune responses. Antigens released from dying tumour cells are assumed to be taken up by activated dendritic cells and presented to T cells that seek out and destroy tumour cells. This process is significantly impeded in the immunosuppressive microenvironment of tumours. There is a growing trend in in situ vaccine strategies that utilize bacteria as natural adjuvants or as factories for cytokines, aiming to enhance the presentation of in situ antigens by antigen‐presenting cells. Recently, a novel approach using flagellate bacteria‐mediated antigen delivery to activate dendritic cells has been proposed. This method actively facilitates the delivery of intratumoral antigens, improving their presentation for in situ cancer vaccination. Here, we highlight how flagellate bacteria‐mediated antigen delivery enhances the immune activation capabilities of in situ vaccines. Meanwhile, we provide perspectives and outlooks on these promising antigen delivery technologies.

Abstract Phthalic acid esters (PAEs) are synthetic diesters derived from o‐phthalic acid, commonly used as plasticizers. These compounds pose significant environmental and health risks due to their ability to leach into the environment and act as endocrine disruptors, carcinogens, and mutagens. Consequently, PAEs are now considered major emerging contaminants and priority pollutants. Microbial degradation, primarily by bacteria and fungi, offers a promising method for PAEs bioremediation. This article highlights the current state of microbial PAEs degradation, focusing on the major bottlenecks and associated challenges. These include the identification of novel and more efficient PAE hydrolases to address the complexity of PAE mixtures in the environment, understanding PAEs uptake mechanisms, characterizing novel o‐phthalate degradation pathways, and studying the regulatory network that controls the expression of PAE degradation genes. Future research directions include mitigating the impact of PAEs on health and ecosystems, developing biosensors for monitoring and measuring bioavailable PAEs concentrations, and valorizing these residues into other products of industrial interest, among others.

Abstract The emergence of new techniques in both microbial biotechnology and artificial intelligence (AI) is opening up a completely new field for monitoring and sometimes even controlling the evolution of pathogens. However, the now famous generative AI extracts and reorganizes prior knowledge from large datasets, making it poorly suited to making predictions in an unreliable future. In contrast, an unfamiliar perspective can help us identify key issues related to the emergence of new technologies, such as those arising from synthetic biology, whilst revisiting old views of AI or including generative AI as a generator of abduction as a resource. This could enable us to identify dangerous situations that are bound to emerge in the not‐too‐distant future, and prepare ourselves to anticipate when and where they will occur. Here, we emphasize the fact that amongst the many causes of pathogen outbreaks, often driven by the explosion of the human population, laboratory accidents are a major cause of epidemics. This review, limited to animal pathogens, concludes with a discussion of potential epidemic origins based on unusual organisms or associations of organisms that have rarely been highlighted or studied.

Abstract Bacterial infections represent a significant global threat to human health, leading to considerable economic losses through increased healthcare costs and reduced productivity. One major challenge in treating these infections is the presence of biofilms ‐ structured bacterial communities that form protective barriers, making traditional treatments less effective. Additionally, the rise of antibiotic‐resistant bacteria has exacerbated treatment difficulties. To address these challenges, researchers are developing and exploring innovative approaches to combat biofilm‐related infections. This mini‐review highlights recent advancements in the following key areas: surface anti‐adhesion technologies, electricity, photo/acoustic‐active materials, endogenous mimicking agents, and innovative drug delivery systems. These strategies aim to prevent biofilm formation, disrupt existing biofilms, and enhance the efficacy of antimicrobial treatments. Currently, these approaches show great potential for applications in medical fields such as medical device and wound – associated biofilm infections. By summarizing these developments, this mini‐review provides a comprehensive resource for researchers seeking to advance the management and treatment of biofilm‐associated infections.

Abstract Bacterial surface display in combination with fluorescence‐activated cell sorting is a versatile and robust system and an interesting alternative approach to phage display for the generation of therapeutic affinity proteins. The system enables real‐time monitoring and sorting of cell populations, which presents unique possibilities for drug development. It has been used to develop several affibody molecules currently being evaluated preclinically for the treatment and diagnosis of, for example, cancer and neurodegenerative diseases. Additionally, it can be implemented in other areas of drug design, such as for mapping epitopes and evolving enzyme specificities.

Abstract Classical epidemiology relies on incidence, mortality rates, and clinical data from individual testing, which can be challenging for many countries. Therefore, innovative, flexible, cost‐effective, and scalable surveillance techniques are needed. Wastewater‐based epidemiology (WBE) has emerged as a highly powerful tool in this regard. WBE analyses substances excreted in human fluids and faeces that enter the sewer system. This approach provides insights into community health status and lifestyle habits. WBE serves as an early warning system for viral surveillance, detecting the emergence of new pathogens, changes in incidence rates, identifying future trends, studying outbreaks, and informing the performance of action plans. While WBE has long been used to study different viruses such as poliovirus and norovirus, its implementation has surged due to the pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2. This has led to the establishment of wastewater surveillance programmes at international, national, and community levels, many of which remain operational. Furthermore, WBE is increasingly applied to study other pathogens, including antibiotic resistance bacteria, parasites, fungi, and emerging viruses, with new methodologies being developed. Consequently, the primary focus now is on creating international frameworks to enhance states' preparedness against future health risks. However, there remains considerable work to be done, particularly in integrating the principles of One Health into epidemiological surveillance to acknowledge the interconnectedness of humans, animals, and the environment in pathogen transmission. Thus, a broader approach to analysing the three pillars of One Health must be developed, transitioning from WBE to wastewater and environmental surveillance, and establishing this approach as a routine practice in public health.

Abstract The efficiency of global crop production is under threat from microbial pathogens which is likely to be worsened by climate change. Major contributors to plant disease are Pseudomonas syringae (P. syringae) pathovars which affect a variety of important crops. This opinion piece focuses on P. syringae pathovars actinidiae and syringae, which affect kiwifruit and stone fruits, respectively. We discuss some of the current control strategies for these pathogens and highlight recent research developments in combined biocontrol agents such as bacteriophages and combinations of bacteriophages with known anti‐microbials such as antibiotics and bacteriocins.