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Cardiovascular diseases (CVDs) have emerged as a common health problem. However, despite their prevalence, little progress has been made in their treatment. In recent years, neurotrophic factors (NTFs) have been discovered to exert cardioprotective functions for CVDs. NTFs can modulate vascular integrity, myocardial remodeling, angiogenesis, and autonomic regulation, playing the roles of maintaining cardiovascular homeostasis and influencing disease progression. Under pathological conditions, the supplement of NTFs can induce substantial adaptations to mitigate adverse cardiac responses. Several NTFs have been investigated in this regard. This review briefly elaborates on present insights into the expression, signaling pathways, and regulatory effects of NTFs on the development of CVDs, and also discusses emerging therapeutic strategies based on NTFs, ranging from exercise to advanced modalities including stem cell therapy, gene transfer, recombinant protein therapy and NTF mimetics, among which the mimetics and exercise interventions emerge as the most promising avenues for clinical translation.

Androgen insensitivity syndrome (AIS) is a genetic disorder affecting 46 XY individuals, leading to varied degrees of incomplete development of sexual characteristics. In patients with vaginal agenesis who wish to engage in sexual activity, surgical interventions, such as neovaginoplasty, may be required. While traditional approaches pose drawbacks, the emergence of Nile tilapia fish skin (NTFS) for vaginal agenesis management offers a promising, cost-effective alternative. This study aims to evaluate morphofunctional outcomes in AIS patients who underwent neovaginoplasty using NTFS. In this case series, five patients diagnosed with AIS underwent modified McIndoe vaginoplasty using NTFS. Outpatient consultations at 30, 90, and 180 days assessed neovagina aesthetics and functionality. Sexual function was evaluated using the Female Sexual Function Index (FSFI), and genital self-image was assessed with the Female Genital Self-Image Scale (FGSIS). Tissue sampling at 30 and 180 days post-surgery involved histopathological analysis of the vaginal wall. Surgeries were conducted to form vaginal canals measuring 9-10 cm, with no intraoperative complications. Three patients experienced difficulties during sexual intercourse within the six months following surgery, while one reported successful sexual activity. An average FSFI score of 18.7 and an FGSIS score of 14.6 were observed. Histopathological analysis of vaginal wall samples at 1 and 6 months post-surgery indicated the presence of fibrovascular connective tissue and inflammatory response. Neovaginoplasty with NTFS emerges as a cost-efficient approach with minimal complications. Epithelial tissue formation was not observed at 6 months post-surgery. The study underscores challenges in achieving morphofunctional outcomes in AIS individuals, emphasizing the need for hormonal considerations and psychological factors.

This research aimed to overcome challenges posed by cefepime excessive elimination rate and poor patient compliance by developing transdermal delivery system using nano-transfersomes based chitosan gel. Rotary evaporation-sonication method and the Box-Behnken model were used to prepare cefepime loaded nano-transfersomes (CPE-NTFs). The physiochemical characterization of CPE-NTFs were analyzed including DLS, deformability index, DSC and antimicrobial study. Optimized CPE-NTFs loaded into chitosan gel and appropriately characterized. In vitro release, ex vivo and in vivo studies were performed. The CPE-NTFs were physically stable with particle size 222.6 ± 1.8 nm, polydispersity index 0.163 ± 0.02, zeta potential -20.8 ± 0.1 mv, entrapment efficiency 81.4 ± 1.1% and deformability index 71 ± 0.2. DSC analysis confirmed successful drug loading and thermal stability. FTIR analysis showed no chemical interaction among the excipients of CPE-NTFs gel. The antibacterial activity demonstrated a remarkable reduction in the minimum inhibitory concentration of cefepime when incorporated into nano-transfersomes. CPE-NTFs based chitosan gel (CPE-NTFs gel) showed significant physicochemical properties. In vitro release studies exhibited sustained release behavior over 24 h, and ex vivo studies indicated enhanced permeation and retention compared to conventional cefepime gel. In vivo skin irritation studies confirmed CPE-NTFs gel was nonirritating and biocompatible for transdermal delivery. This research showed nano-transfersomes based chitosan gel is a promising approach for cefepime transdermal delivery and provides sustained release of cefepime.

Meloidogyne incognita is the most damaging nematode pest globally causing root-knot diseases in crops. Nematode trapping fungi (NTFs) is a group of microfungi that form traps to capture and parasitize the nematodes, including M. incognita. The easiest way to use NTFs is introduction of nematophagous and soil-adoptive strains in nematode-infested soil. This study mainly focused on efficacy test of five species of NTFs against M. incognita on tomato under pot and microplot field conditions. In vitro nematophagous potential assays of NTFs showed 99.3% and 97.9% killing of M. incognita (J2s) by Drechslerella dactyloides and D. brochopaga, respectively, within 120 h. Pea bran substrate supported maximum sporulation, particularly in D. dactyloides. A bio-efficacy test of D. dactyloides showed reduction in numbers of root-knots and eggs/J2s per plant by 70.8% and 74.1% in pot conditions, and by 66.0% and 70.3% in microplot conditions, respectively, whereas D. brochopaga reduced the number of root-knots and eggs/J2s per plant by 68.3% and 72% in pots, and 64.6% and 68.1.% in microplots. Athrobotrys oligospora, A. musiformis and A. conoides showed moderate-to-low efficacy against M. incognita in pot and microplot conditions. This study demonstrates better bio-eficacy of D. dactyloides and D. brochopaga against M. incognita on tomato under pot and microplot conditions, in comparison to A. oligospora, A. musiformis and A. conoides. Our results also advocate that soil application of D. dactyloides and D. brochopaga individually or in consortia could be environmentally safe and effective strategies for biocontrol of M. incognita. © 2026 Society of Chemical Industry.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized primarily by the irreversible loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) of the midbrain. Although its etiology is complex, mitochondrial dysfunction has been widely recognized as a central hub in the pathogenesis of PD. Concurrently, neurotrophic factors (NTFs), particularly glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) and cerebral dopamine neurotrophic factor (CDNF), which exhibit specific trophic effects on dopaminergic neurons, play a crucial role in the endogenous neuroprotective system. This review aims to move beyond simple mechanistic descriptions and critically analyze the interaction of the “NTFs-mitochondria axis” in PD. We will systematically examine experimental evidence supporting the role of this axis (from in vitro to in vivo models) and clarify its strengths and limitations. Emphasis is placed on the fundamental translational challenges revealed by GFLs-based clinical trials (such as GDNF and neurturin [NRTN]), including delivery bottlenecks, treatment timing, and limitations of disease models. Finally, we evaluate the potential and obstacles of novel strategies targeting this axis (such as new viral vectors, small molecule agonists, mitochondria-targeted drugs, and combination therapies). A deep understanding and addressing the dysregulation of the NTFs-mitochondrial network holds promise for opening new avenues in the development of disease-modifying therapies, but it is essential to remain keenly aware of existing challenges.

Under low-nutrient conditions, nematode-trapping fungi (NTFs) can differentiate their mycelia into specialized trapping devices for capturing prey. Using energy-dispersive X-ray spectroscopy in conjunction with transmission electron microscopy, together with a series of bioassay, we identified that the characteristic electron-dense bodies in trapping devices contained more iron than vacuoles and mitochondria, functioning as an unrecognized iron storage organelle. Genomic analysis revealed that all NTFs lack the Ccc1-mediated vacuolar iron detoxification mechanism conserved in most fungi. Heterogenous expression of yeast-derived Ccc1 gene in Arthrobotrys oligospora significantly reduced trapping device formation and nematicidal activity. Mapping key factor fluctuations onto Bayesian relaxed molecular clock analysis indicated that the loss of Ccc1-mediated vacuolar iron storage occurred during Late Paleozoic Ice Age, whereas the emergence of trapping devices and the acquisition of desferriferrichrome were closely associated with elevated temperatures. Temperature bioassays showed that trap formation is highly temperature-dependent, with free iron levels inversely correlated with temperature, consistent with the temperature sensitivity of A. oligospora, which cannot grow above 30°C. Our findings demonstrated that global temperature fluctuations serve as a critical driver of the evolution of NTFs and act as a catalyst for the emergence of trapping devices, novel phenotypic indicator of eukaryotic iron overload.

The aim of this study was to develop paroxetine (PXT) loaded nanotransferosomal gel (PXT-NTFG) for intranasal brain delivery. The process involved fabricating PXT-NTFs (paroxetine-loaded nanotransferosomes) through a thin film hydration method and optimizing them based on parameters such as particle size (PS), zeta potential (ZP), polydispersity index (PDI), and entrapment efficiency (EE). The optimized PXT-NTFs exhibited uniform morphology with a PS of 158.30 ± 2.73 nm, low PDI (0.142 ± 0.072), high ZP (21.00 ± 0.75 mV), and excellent EE (88.09 ± 3.40 %). Characterization through various techniques confirmed the incorporation of PXT into the nanotransferosomes and its conversion to amorphous state. Moreover, PXT-NTFG was formulated with suitable viscosity and mucoadhesive properties. In vitro release studies demonstrated sustained drug release from PXT-NTFG at different pH levels as compared to PXT-NTFs and NTF dispersion. Similarly, ex vivo experiments showed 4 folds enhanced drug permeation from PXT-NTFG when compared with PXT conventional gel. Stability studies indicated that the optimized PXT-NTFs remained stable for four months at 4°C and 25°C. Additionally, improved behavioral outcomes, increased neuronal survival rates, and upregulated brain-derived neurotrophic factor (BDNF) expression was observed in lipopolysaccharide (LPS) induced depressed Sprague-Dawley rats after treatment with PXT-NTFG as compared to PXT-dispersion treated and untreated LPS-control groups. Notably, the formulation led to a significant reduction in brain and plasma TNF-α levels. In conclusion, intranasal PXT-NTFG is a promising formulation with sustained drug release, improved brain targeting and enhanced antidepressant activity.

Neurotrophic factors (NTFs) are secreted proteins that are crucial in neuronal growth, survival, and function. Individuals with neurodegenerative diseases, characterized by neuronal loss and various functional disorders, have been reported to exhibit altered levels of NTFs. This suggests that modulating NTF levels may offer a promising therapeutic strategy to alter the progression of neurodegenerative diseases. Although numerous efforts have been made to deliver NTFs to target regions, their clinical application remains challenging due to their inability to cross the blood-brain barrier (BBB) and the adverse side effects observed in clinical trials. Consequently, various delivery methods have been explored to overcome these limitations. In this review, we discuss recent therapeutic approaches utilizing NTFs and their signaling pathways as interventions against neurodegenerative diseases.

Nuchal-type fibromas (NTFs) are rare, benign tumors that predominantly originate in the posterior neck and often arise due to repetitive mechanical use. They are more common in males than females. Clinically, NTFs present as slow-growing, painless masses that are firm to the touch and immobile. The masses are typically not accompanied by other symptoms of erythema, warmth, or ulcerations as they are non-inflammatory in nature, with the possibility of tenderness in later stages of growth as nerves become entrapped in the tumor. Patients may present with cosmetic concerns and focal discomfort depending on the location and size of the mass. Extra-nuchal sites are uncommon, with locations reported in the literature including the upper back, shoulder, and face, with only one case reported where an NTF was found unilaterally on the ankle. We present a rare case of a 48-year-old male with bilateral masses in the ankle extensor retinacula, consistent with nuchal-type fibromas determined by histopathology. To our knowledge, our patient's presentation of bilateral extra-nuchal NTFs of the lower extremity is among the first to be reported in the literature.

The "Alzheimer's disease and related dementias (AD/ADRD) Focused Administrative Supplements for National Institutes of Health (NIH) Grants that are not focused on Alzheimer's disease (AD Supplements to Non-AD awards)" program provides funded investigators from scientific areas other than AD/ADRD with administrative supplements to parent NIH grant awards to expand their current work into AD/ADRD. This analysis reviewed awardees of the supplement from fiscal years 2018 to 2022 using data obtained from NIH's internal grants administration data. The goal was to identify awardees who were New-to-the-Field (NTF) of AD/ADRD and assess outcome measures of success (subsequent applications, awards, and publications). In total, 1,555 AD Supplements to Non-AD awards were awarded (16% awarded to National Institute on Aging [NIA] grants; 84% to all other NIH Institutes and Centers [ICs]). Seventy-two percent of all awards went to awardees considered NTF. At the time of this analysis, administrative supplements to NTFs were awarded, on average, 3.42 years ago, so some projects have had little time to have substantial outcomes. The total awardee subsequent funding rate for all ICs was 60% (62% for NIA only). Regarding subsequent publications across all IC NTFs, 2.8% of NIH grants led by an NTF investigator had associated publications on an AD/ADRD-relevant topic after the supplement. For NIA-only administrative supplements, 5.4% of parent grants led by NTFs had associated subsequent AD/ADRD publications. The findings suggest that AD Supplements to Non-AD awards have stimulated scientific interest among investigators who were new to AD/ADRD research at the time of application and may facilitate interdisciplinary research by bringing investigators into new and/or growing areas of research.

HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) shows distinct biological and clinical behaviour when compared to HPV-negative OPSCC. The overall role of the tumour microenvironment (TME) in head and neck cancer progression and metastasis has been studied intensively, but differences in HPV-negative and HPV-positive OPSCCs are less understood. To investigate the role of cancer-associated fibroblasts (CAFs) and the functional interactions of normal tonsil fibroblasts (NTFs) and OP CAFs with HPV+ and HPV- OPSCC cells and explore novel candidates in tumour-fibroblast crosstalk. A retrospective cohort of 143 primary OPSCCs was characterised using HPV16/18 RNAScope assay, p16 IHC and ɑ-SMA. Four OPSCC, three NTF and 2 new OPSCC CAF cultures were used to assess the cytokine-based interactions using cytokine arrays on conditioned media (CM), followed by co-culture approaches to identify the role of individual cell types and the role of OPN (SPP1) and IL-6 in SCC/fibroblast communication. HPV status was associated with better overall survival. Although ɑ-SMA expression was observed in both OPSCC subtypes, it provided survival stratification only in the HPV-positive group (Log-Rank p = 0.02). Three normal tonsillar fibroblast cultures (NTFs) were characterised by induction of myofibroblastic and senescent phenotypes with similar reactivity to our published NOF phenotype. The OPSCC-derived CAF cultures were characterised and their baseline myofibroblastic and senescence phenotypes varied. Cytokine array analysis of CM to identify novel candidates in the crosstalk between OPSCC tumour cells and NTFs/CAFs identified differences in the cytokine profiles on comparison of HPV+ and HPV- OPSCC cells. Osteopontin (OPN/SPP1) was identified, particularly in HPV-negative OPSCC cell analyses. We have demonstrated that OPN was produced by the OPSCC cells and revealed an associated upregulation of IL-6 in fibroblasts. Treatment of NTFs with rOPN showed alteration in phenotype, including increased contraction and IL-6 production. Antibody-mediated inhibition of CD44v6 attenuated the production of IL-6 by OPN in NTFs. This investigation with OPSCC fibroblasts provides novel insights into the role of CAFs in OPSCC mediated by IL-6 stimulated release of OPN from HPV negative OPSCC cells. The details of HPV-positive SCC cell/fibroblast cytokine crosstalk remain elusive.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterised by the degeneration of dopaminergic neurons in the substantia nigra pars compacta, resulting in motor symptoms such as tremor, rigidity and bradykinesia, along with cognitive impairments. While conventional research has largely focused on pathological degeneration, recent advances highlight the role of neuroplasticity-the brain's ability to reorganise and adapt neural circuits-as a potential mechanism for functional recovery and disease modification. This review examines therapeutic strategies that enhance neuroplasticity in chronic Parkinson's disease mouse models. Key approaches discussed include neurotrophic factor (NTF) administration, deep brain stimulation (DBS), stem cell-based therapies and physical exercise. Evidence from experimental studies suggests that NTFs support dopaminergic neuron survival and synaptic repair, DBS modulates dysfunctional neural circuits and promotes adaptive plasticity, stem cell therapies offer both neuronal replacement and neurotrophic support, and physical exercise stimulates endogenous neuroplastic processes such as neurogenesis and synaptic reorganisation. Despite promising findings, variations in experimental design, disease severity and outcome measures across studies limit direct comparison and translation of results. Neuroplasticity-based interventions represent a promising avenue for slowing disease progression and improving functional outcomes in Parkinson's disease. Integrating pharmacological, neuromodulatory and behavioural approaches may enhance therapeutic efficacy, though further research is required to standardise protocols and facilitate clinical translation.

Iron homeostasis is critical for the survival of almost all organisms, yet its dysregulation is often caused by a synergistic effect of genetic and environmental factors. Previous studies have shown that trapping devices of the predominant nematode-trapping fungus (NTF) Arthrobotrys oligospora serve as an unprecedented iron sequestration system compensatory for lack of the crucial fungal vacuolar iron detoxification mechanism. Here, we found that among the Ascomycota phylum, only NTFs lacked gene coq7, which encodes COQ7 responsible for ubiquinol (UQ) biosynthesis and efficient iron chelation. Addition of exogenous UQ10 or heterologous expression of yeast gene coq7 in A. oligospora inhibited the formation of fungal trapping devices. Interestingly, mutant nematodes with disruption of gene coq7 can greatly reduce nematode-capturing ability of fungal trapping devices. Exogenous COQ7s exhibit significant adsorption effects on fungal trapping devices both in vitro and in vivo. Transcriptional, metabolic, mutational, and phenotypic analyses indicated that A. oligospora utilized a chemotaxonomic class of highly oxygenated arthrobotrisins with similar characteristics to UQ₃, instead of UQs, in response to elevated oxygen levels. Loss of arthrobotrisin biosynthesis led to a delayed growth of the mutant Δart but enhanced UQ₈ biosynthesis, trapping device formation, and nematicidal activity. Time-calibrated evolutionary analyses, combined with geological data, indicated that the NTF ancestor lost the coq7 gene after acquiring the art gene cluster during the cold "superoligotrophy" period, characterized by dramatic shifts in global oxygen levels and temperature changes. Our findings indicated that the trapping devices of NTF capture nematodes primarily for iron chelation therapy, rather than solely for food, which addresses the long-standing issue regarding the limited carnivorous ability of trapping devices.

Gonadal dysgenesis, a genetic condition characterized by incomplete of defective formation of the gonads, can present with vaginal agenesis in individuals with 46, XY karyotype. We report an innovative intervention in the management of vaginal agenesis in a 19-year-old female with gonadal dysgenesis. Despite initial attempts with vaginal dilators, the patient presented unresponsive, leading to the adoption of a neovaginoplasty using Nile Tilapia Fish Skin (NTFS) as graft. The procedure, based on the McIndoe technique, involved the creation of a 10 cm x 3 cm vaginal canal with an NTFS-wrapped acrylic mold without complications. The use of NTFS as a graft for neovaginoplasty in gonadal dysgenesis, a novel approach not previously reported in medical literature for this diagnosis, demonstrated favorable outcomes in terms of functionality and patient well-being.

Abnormal cytoplasmic aggregates containing the TDP-43 protein and its fragments are present in the central nervous system of the majority of patients with amyotrophic lateral sclerosis (ALS) and in patients with frontotemporal lobar degeneration (FTLD). Many studies have focused on the C-terminal cleavage products of TDP-43 (CTFs), but few have focused on the N-terminal products (NTFs), yet several works and their protein domain composition support the involvement of NTFs in pathophysiology. In the present study, we expressed six NTFs of TDP-43, normally generated in vivo by proteases or following the presence of pathogenic genetic truncating variants, in HEK-293T cells. The N-terminal domain (NTD) alone was not sufficient to produce aggregates. Fragments containing the NTD and all or part of the RRM1 domain produced nuclear aggregates without affecting cell viability. Only large fragments also containing the RRM2 domain, with or without the glycine-rich domain, produced cytoplasmic aggregates. Of these, only NTFs containing even a very short portion of the glycine-rich domain caused a reduction in cell viability. Our results provide insights into the involvement of different TDP-43 domains in the formation of nuclear or cytoplasmic aggregates and support the idea that work on the development of therapeutic molecules targeting TDP-43 must also take into account NTFs and, in particular, those containing even a small part of the glycine-rich domain.

Iron acquisition plays a crucial role in fungal pathogenicity. Nematode-trapping fungi (NTFs) serve as important biocontrol agents that can develop traps to capture and kill nematodes. Here, we characterize a non-ribosomal peptide synthase-independent siderophore biosynthetic gene, DhSip1, in NTF Dactylellina haptotyla, which modulates trap (adhesive knob) development and pathogenicity by regulating siderophore-dependent iron acquisition. The deletion of DhSip1 severely impaired adhesive knob formation and reduced nematode mortality. A chrome azurol S assay confirmed that the gene deletion impaired siderophore biosynthesis. Conversely, overexpression of DhSip1 enhanced these phenotypes. Notably, the pathogenicity defects of ΔDhSip1 were fully rescued by exogenous iron rescue assay, supporting a functional link between iron acquisition and adhesive knob-mediated infection. Fluorescence localization revealed specific enrichment of DhSip1 in adhesive knobs during late infection, suggesting that its localization provides a mechanism for local iron enrichment, thereby potentially supporting the formation of adhesive knobs. Collectively, DhSip1 optimizes predatory efficiency by coordinating iron acquisition with adhesive knob development in D. haptotyla. Our work provides new insights into the pathogenicity mechanism of D. haptotyla and establishes a theoretical foundation for biocontrol product development.IMPORTANCEFungal pathogens require iron for pathogenicity, but the role of iron acquisition in Dactylellina haptotyla remains unclear. This study identifies a novel non-ribosomal peptide synthase-independent siderophore synthetase gene, DhSip1, in D. haptotyla, which is essential for siderophore production, iron acquisition, and adhesive knob formation. We demonstrate that iron acquisition critically governs both the adhesive knob development and the pathogenicity of D. haptotyla. Furthermore, DhSip1 mediates local iron enrichment within adhesive knobs, revealing a unique pathogenic mechanism that directly links iron homeostasis to nematode predation. Our findings not only advance our understanding of the pathogenic mechanisms in D. haptotyla but also pave the way for designing effective biocontrol products.

Neurodegenerative disorders are characterised by the chronic progressive degeneration of specific neuronal subtypes, neuroinflammation, myelin damage and synaptic loss. Despite their growing incidence, advancements in effective treatments remain limited, because of lack of knowledge for the aetiology of the diverse pathophysiology to design systematic therapies. Several studies highlight the role of neurotrophic factors (NTFs) as potential neuroprotective, regenerative therapies for these disorders. Although NTFs hold protective and regenerative potential for chronic neuroinflammatory and neurodegenerative conditions, major hurdles impair their clinical use, such as optimising the dosage of NTFs, minimising the invasiveness of delivery methods, overcoming blood-brain-barrier (BBB) impermeability and managing side effects. In the last two decades our group have synthesised and screened a large chemical library of steroidal analogues of dehydroepiandrosterone (DHEA), an endogenous steroid hormone, for their ability to mimic neurotrophin neuroprotective and neurogenic actions. Interestingly, DHEA was shown to interact with all neurotrophin receptors, acting most probably as an ancestral neurotrophin early in evolution. However, its chronic pharmacological use is questioned by its action as a major precursor of steroidogenesis. This review highlights the findings of numerous preclinical studies on these synthetic, non-toxic, BBB permeable DHEA derivatives, named microneurotrophins (MNTs), deprived of endocrine actions, activators of specific neurotrophin receptors. The multimodal actions of MNTs against neuronal death and activation of microglia, in addition to their beneficial effects in synaptogenesis and neurogenesis, place them as interesting lead molecules in the armamentarium of therapeutics for neurodegeneration.

Ischemic stroke (IS), a multifactorial disease resulting from the complex interplay of various environmental and genetic risk factors. Neurotrophic factors (NTFs) have a potential role in IS, but the exact mechanisms are unknown. The aim of this study was to identify biomarkers associated with the occurrence and development of NTFs and to analyze their potential mechanisms of action. In this study, we selected the intersection of neurotrophic factor genes, differentially expressed genes (DEGs) and key genes in the IS module based on IS-related datasets (GSE16561 and GSE58294). Machine learning screened out 5 biomarkers for IS diagnosis (MMP9, MARCKS, IGF2R, HECW2 and CYBRD1). GSEA results showed that different signaling pathways were activated in IS samples with high expression of different diagnostic genes. Furthermore, an immunological analysis was carried out, which demonstrated significant differences in the levels of activated B cells, neutrophils, and activated CD8 T cells between IS patients and normal samples. RT-qPCR results showed that there were significant differences in the expression of CYBRD1, MARCKS and MMP9 between IS and control patients. In conclusion, we identified 5 diagnostic markers that may be involved in the progression of IS, including MMP9, MARCKS, IGF2R, HECW2 and CYBRD1. Finally, differential expression of MMP9, MARCKS, and CYBRD1 was detected in peripheral blood samples from 15 IS and 5 normal cases. Our analysis could serve as a foundation for enhancing comprehension of the underlying molecular mechanisms governing the pathogenesis and progression of IS. The identified biomarkers might serve as targets for the development of novel diagnostic assays, enabling earlier detection of IS and potentially leading to more timely and effective treatment interventions.

Objective: To evaluate the efficacy and safety of a novel tip-flexible suction ureteral access sheath (NTFS-UAS) combined with flexible ureteroscopic lithotripsy (FURS) for treating kidney stones ≥30 mm in a large cohort. Methods: The clinical data of 206 patients with renal calculi ≥30 mm treated by NTFS-UAS combined with FURS from June 2021 to September 2023 were analyzed retrospectively. The outcomes under investigation encompassed demographic information, stone-related characteristics, operative time, stone-free rates (SFRs), and postoperative complications. Results: The median operation duration was 110 minutes (interquartile 84.00-146.25 minutes). Immediate and 1-month SFRs were 83.98% and 85.44%, respectively. Multivariate analysis revealed five risk factors independently affecting stone clearance rate: stone size (≥50 mm, odds ratio [OR] = 3.826, p = 0.039), stone number (multiple: OR = 8.745, p = 0.015), stone location (multiple calyces: OR = 10.371, p = 0.045; lower calyx: OR = 9.615, p = 0.047), severe hydronephrosis (OR = 8.338, p = 0.002), and the Resorlu-Unsal scoring system (RUSS) score (6-7: OR = 10.829, p = 0.009; 4-5: OR = 4.223, p = 0.008). The incidence of Clavien-Dindo grade II-III complication was 5.82%. Positive preoperative urine culture (OR = 9.533, p = 0.012) and RUSS score (6-7: OR = 25.678, p = 0.026; 4-5: OR = 11.444, p = 0.038) were identified as the most important variables that may contribute to the development of high-grade postoperative complications. Conclusion: NFTS-UAS combined with FURS achieved satisfactory outcomes with good efficacy and safety for treating large renal stones ≥30 mm, and it can be utilized as an effective treatment option for patients having contraindications or preference against percutaneous nephrolithotomy. In addition, clinical factors, such as stone size, severe hydronephrosis, positive preoperative urine culture, and RUSS stone score that likely affected the outcomes of NFTS-UAS, should be fully taken into account when the surgeon performing FURS using NFTS-UAS.