Current ectopic implantation has shown limited efficacy in promoting reinnervation of the nigrostriatal pathway, which is critically affected in Parkinson's disease (PD). Homotopic transplantation, on the other hand, may facilitate physiological cell rewiring of the basal ganglia, potentially improving PD symptoms. This study aimed to evaluate the efficacy and safety of homotopically engrafting human induced pluripotent stem cells (hiPSCs)‐derived midbrain organoids into the substantia nigra of PD rats. A rat model of PD was induced using 6‐hydroxydopamine (6‐OHDA) and homotopically transplanted into the lesioned SN with hiPSC‐derived hMOs. The engrafted hMOs survived and continually mature in host brains, and were mainly differentiated into dopaminergic lineage neurons, part of which presented TH+ fibers. Behavioral evaluation demonstrated that transplantation of hMOs gradually reverse the motor disorder caused by 6‐OHDA lesioning by 22% at week 5 and 35% by week 10 post‐transplantation, respectively. No tumor formation or migration was detected in either subcutaneous space or vital organs following 10 weeks implantation. These findings support the efficacy and safety of homotopical hMOs transplantation, offering a promising cell‐based strategy for treating Parkinson's disease.

Hypertrophic scar (HS) is one of the most common complications of skin injuries, with a lack of effective therapeutic approaches to date. Most current research has focused on the dysfunction of hypertrophic scar fibroblasts (HSFBs) and dermal vascular endothelial cells (HDVECs), neglecting the crucial role of the inflammatory microenvironment that causes them to be abnormal. In this study, we first discovered and validated that the S100A8/9 specific inhibitor Paquinimod could inhibit macrophage polarization toward M1, and further suppress the proliferation, migration, collagen formation, and angiogenesis of HSFBs and HDVECs in vitro. This mechanism has also been validated in a rat model of HS. Then, we developed a good biocompatibility and penetrability Paquinimod‐Hydrogel Hybrid Microneedle Array Patch (PHMAP) for HS treatment. With the advantages of excellent penetrability, surface sealing, sustained release, and precise uniform distribution, PHMAP exhibited superior therapeutic efficacy over intravenous and intradermal injections. These results suggest that PHMAP can be a promising and advanced solution for HS prevention and therapies.

Volumetric muscle loss is the significant loss of skeletal muscle volume beyond the innate regenerative capacity, resulting in functional impairment. The current standard of care combines muscle autografting with physical therapy but is often insufficient to reach full recovery. Decellularized skeletal muscle (DSM) provides an interesting alternative to repair volumetric muscle loss. The native structure and composition of the extracellular matrix in these acellular implants provide a blueprint for muscle regeneration. Moreover, DSM can be combined with cells to facilitate the regeneration of the skeletal muscle defect. This systematic review provides a complete and thorough overview of the state‐of‐the‐art applications and efficacy of DSM matrices in skeletal muscle repair in vivo, selected according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. Technical information on the different methods to create DSM implants and the implantation studies is provided. Moreover, details on the evaluation of the structural and functional regeneration of the muscle defect after implantation of the DSM are described. Results reveal a large heterogeneity in the analysis of regeneration upon DSM implantation. This heterogeneity makes it difficult to fully assess the efficiency of DSM to regenerate skeletal muscle, hampering further translation of this technique. Therefore, we suggest a multi‐level evaluation method to assess (i) muscle regeneration, (ii) vascularization, (iii) innervation of the regenerated muscle, and (iv) functional regeneration in a quantitative way.

State the PurposeObtaining high‐quality samples to diagnose streptococcal pharyngitis in pediatric patients is challenging due to discomfort associated with traditional pharyngeal swabs. This may cause reluctance to go to the clinic, inaccurate diagnosis, or inappropriate treatment for children with sore throats. Here, we determined the efficacy of CandyCollect, a lollipop‐inspired open‐microfluidic pathogen collection device, to capture Group A Streptococcus (GAS) and compare user preference for CandyCollect, conventional pharyngeal swabs, or mouth swabs in children with pharyngitis and their caregivers.ResultsAll child participants (30/30) were positive for GAS by qPCR on both the mouth swab and CandyCollect. Caregivers ranked CandyCollect as a good sampling method overall (27/30), and all caregivers (30/30) would recommend CandyCollect for children 5 years and older. Twenty‐three of 30 children “really like” the taste and 24/30 would prefer to use CandyCollect if a future test were needed. All caregivers (30/30) and most children (28/30) would be willing to use CandyCollect at home.ConclusionAll participants tested positive for GAS on all three collection methods (pharyngeal swab, mouth swab, and CandyCollect). While both caregivers and children like CandyCollect, some caregivers would prefer a shorter collection time. Future work includes additional studies with larger cohorts presenting with pharyngitis of unknown etiology and shortening collection time while maintaining the attractive form of the device.

Urothelial carcinomas (UCs) are the fourth most common male malignancies. However, currently implemented detection methods for UC are usually invasive and/or show passable sensitivity and specificity. An accurate, practical, and effective approach is urgently needed for UC clinical detection. Based on the observation that PCDHGB7 was hypermethylated in UC, we developed a bisulfite‐free quantitative polymerase chain reaction (qPCR)‐based PCDHGB7 evaluation to enable urine for UC noninvasive detection. A total of 887 urine samples from UC/benign diseases of the urinary system (BUD) patients between 2022 and 2023 were included. All collected samples were divided into training and validation sets in a 2:1 ratio based on the order of patient enrollment. Results showed that hypermethylated PCDHGB7 exhibited excellent sensitivity of 87.3% (95% CI: 80.7%–92.3%) and specificity of 91.0% (95% CI: 84.8%–95.3%) in efficiently distinguishing UC from BUD patients in the validation set, which is highly consistent with its performance in the training set. Moreover, PCDHGB7 hypermethylation showed promising potential in identifying sessile UC tumors or cases that might be missed in clinical detection and outperformed standard urine cytology in detecting bladder cancer (82.1% vs. 34.5%), ureter cancer (78.1% vs. 34.4%), and renal pelvis cancer (90.9% vs. 22.7%). Overall, bisulfite‐free qPCR‐based PCDHGB7 evaluation in urine provided a noninvasive, easy‐to‐perform, and effective way for UC early detection.

Gastrointestinal cancers, a major global cause of cancer‐related mortality and disease burden, are a heterogeneous group of malignant aliments involving different organs of the digestive system. The late clinical diagnosis, genomic tumor heterogeneity, high complexity of the gastrointestinal tumor microenvironment, along with increasing treatment resistance have been recognized as the main contributing factors to the current inadequacy of the clinical interventions and poor prognosis of the gastrointestinal cancer patients. In the coming years, gastrointestinal cancer‐related global mortality is unfortunately predicted to increase due to the absence of early detection and effective therapeutic options. Biomembrane‐coated biomimetic nanoparticles (NPs) have recently been appointed as advanced nanotechnological tools for the clinical management of gastrointestinal cancers. These comprise not only cell‐mimicking nanodevices (the pioneers of this top‐down coating technology), but also exosome and bacterial mimetics. Due to their enhanced bio‐interfacing features, biocompatibility, immune evasion, and specific targetability to tumorous tissues, these biomimetic nanostructures have been successfully exploited to provide safer, effective, and targeted gastrointestinal cancer applications. This review highlights the latest research on biomembrane‐coated nanosystems for the clinical therapy and diagnosis of the most common and deadliest subtypes of gastrointestinal cancers, namely colorectal cancer, gastric cancer, liver cancer, esophageal cancer, and pancreatic cancer. The current challenges toward their clinical translation are also mentioned.

Stem cell therapies have emerged as a transformative approach in modern medicine, with the potential to address and possibly cure a broad spectrum of diseases. These therapies utilize living stem cells that can perform complex biological functions not replicable by traditional drugs. Stem cell therapies have an expanding therapeutic landscape, with several products already approved and numerous clinical trials underway. Among the various stem cell types, hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) are most widely studied. In this review, we provide a detailed analysis of the current clinical landscape of stem cell therapies. We review 27 stem cell products that have received regulatory approvals and discuss 800 ongoing clinical trials, with a focus on HSCs and MSCs. We also discuss the critical challenges to be addressed to facilitate the clinical translation of stem cell therapies.

Cardiovascular diseases (CVDs) continue to drive global mortality rates, underscoring an urgent need for advancements in healthcare solutions. The development of point‐of‐care (POC) devices that provide rapid diagnostic services near patients has garnered substantial attention, especially as traditional healthcare systems face challenges such as delayed diagnoses, inadequate care, and rising medical costs. The advancement of machine learning techniques has sparked considerable interest in medical research and engineering, offering ways to enhance diagnostic accuracy and relevance. Improved data interoperability and seamless connectivity could enable real‐time, continuous monitoring of cardiovascular health. Recent breakthroughs in computing power and algorithmic design, particularly deep learning frameworks that emulate neural processes, have revolutionized POC devices for CVDs, enabling more frequent detection of abnormalities and automated, expert‐level diagnosis. However, challenges such as data privacy concerns and biases in dataset representation continue to hinder clinical integration. Despite these barriers, the translational potential of machine learning‐assisted POC devices presents significant opportunities for advancement in CVDs healthcare.

Monoclonal antibodies (mAbs) are commonly used biologic therapeutics with a wide variety of clinical applications. During the development process, manufacturers consider different production parameters to improve protein yield and achieve appropriate quality of the product. Synonymous gene recoding is one of such attributes that is often considered and implemented to enhance protein expression. However, it has to be used with caution, as it may lead to protein misfolding and ER stress, which complicates efforts to manufacture the desired mAb. To investigate how changing mRNA sequence composition under different protein production parameters might affect the quality of recombinantly produced mAbs, we performed a comprehensive and systematic study assessing impact of synonymous gene recoding (commonly referred to as codon optimization) strategies in the context of varied cell culture parameters on product quality, biochemical and functional characteristics. We report the impact of these parameters on mAb glycosylation profiles, charge variant profile, aggregation, fragmentation, and mAb functional response from combinations of different production parameters. These results uncovered a complex interplay of sequence composition and manufacturing parameters and emphasize the importance of assessing changes to key quality attributes when optimizing mAb manufacturing, including the use of synonymous gene recoding.

Human Mpox disease (MPX) is an endemic zoonotic disease that develops when patients are infected with the Mpox virus (MPXV). MPXV shares a high level of genetic similarity to other poxviruses and the clinical presentation of MPX is similar to other poxvirus infections which can result in a delay in diagnosis. In addition, the MPXV virus is phylogenetically divided into two different clades which affects the severity of disease. In recent years, there has been an unusual worldwide spread of MPXV, leading to a global public health problem. The most important step in the fight against MPX is rapid, highly specific, and accurate diagnosis. Following the rapid spread of disease in recent years, efforts to develop diagnostic tests have gained momentum. Here, MPX, MPX epidemiology, and MPX diagnostic tests are discussed. Furthermore, biochemical diagnostic tests, molecular diagnostic tests and their development, and point-of-care (PoC) diagnostic applications are reviewed. Molecular diagnostic technologies such as polymerase chain reaction, recombinase polymerase amplification, and loop-mediated isothermal amplification methods that detect MPX are evaluated. Additionally, next-generation combined molecular techniques and their importance in PoC transition are explored.