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Chitosan is widely employed in gene carriers due to its excellent gene loading capacity, ease of modification, and exceptional biodegradability. However, low gene delivery efficiency, high cytotoxicity, and lack of tracer biomimetic properties limit its clinical use. To address these issues, a novel biomimetic tracking gene delivery carrier, RBCm-C50kQT, was constructed by using the design scheme of cell membrane coated carbon quantum dots/chitosan. This carrier improves stability and tracking performance while embedding the cell membrane enhances biosafety. RBCm-C50kQT effectively carries and protects DNA, improving uptake and transfection efficiency with reduced cytotoxicity. It maintains strong fluorescence tracking and shows high uptake efficiencies of 83.62 % and 77.45 % in 293 T and HeLa cells, respectively, with maximum transfection efficiencies of 68.80 % and 45.47 %. This advancement supports gene therapy improvements and paves the way for future clinical applications.

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Plasmonic excitations decay within femtoseconds, leaving nonthermal (often referred to as "hot") charge carriers behind that can be injected into molecular structures to trigger chemical reactions that are otherwise out of reach─a process known as plasmonic catalysis. In this Letter, we demonstrate that strong coupling between resonator structures and plasmonic nanoparticles can be used to control the spectral overlap between the plasmonic excitation energy and the charge injection energy into nearby molecules. Our atomistic description couples real-time density-functional theory self-consistently to an electromagnetic resonator structure via the radiation-reaction potential. Control over the resonator provides then an additional knob for nonintrusively enhancing plasmonic catalysis, here more than 6-fold, and dynamically reacting to deterioration of the catalyst─a new facet of modern catalysis.

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Micro- and nanoplastics (MPs/NPs) constitute emerging and widely-distributed environmental contaminants to which humans are highly exposed. They possibly represent a threat for human health. In order to identify cellular/molecular targets for these plastic particles, we have analysed the effects of exposure to manufactured polystyrene (PS) MPs and NPs on in vitro activity and expression of human membrane drug transporters, known to interact with chemical pollutants. PS MPs and NPs, used at various concentrations (1, 10 or 100 µg/mL), failed to inhibit efflux activities of the ATP-binding cassette (ABC) transporters P-glycoprotein, MRPs and BCRP in ABC transporter-expressing cells. Furthermore, PS particles did not impair the transport of P-glycoprotein or BCRP substrates across intestinal Caco-2 cell monolayers. Uptake activities of solute carriers (SLCs) such as OCT1 and OCT2 (handling organic cations) or OATP1B1, OATP1B3, OATP2B1, OAT1 and OAT3 (handling organic anions) were additionally not altered by PS MPs/NPs in HEK-293 cells overexpressing these SLCs. mRNA expression of ABC transporters and of the SLCs OCT1 and OATP2B1 in Caco-2 cells and human hepatic HepaRG cells were finally not impaired by a 48-h exposure to MPs/NPs. Altogether, these data indicate that human drug transporters are unlikely to be direct and univocal targets for synthetic PS MPs/NPs.

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OBJECTIVE: To investigate whether Molybdenum blood level is a marker of cancer risk on BRCA1 carriers. METHODS: A prospective cohort study was conducted among 989 initially unaffected women with a BRCA1 mutation. Blood samples were collected to measure molybdenum levels, and participants were followed for an average of 7.5 years. Cox proportional hazards models were used to assess the association between blood molybdenum levels and cancer incidence, adjusting for potential confounders. RESULTS: High blood molybdenum levels (> 0.70 µg/L) were significantly associated with an increased risk of developing ovarian cancer (HR = 5.55; 95%CI: 1.59-19.4; p = 0.007) and any cancer (HR = 1.74; 95%CI: 1.17-2.61; p = 0.007) but not breast cancer (HR = 1.46, CI = 0.91-2.33; p = 0.12). The cumulative incidence of ovarian cancer at ten years was 1.2% for the lowest molybdenum tertile, 4.2% for the middle tertile, and 8.7% for the highest tertile. CONCLUSION: Elevated blood molybdenum levels are associated with an increased risk of ovarian cancer on BRCA1 mutation carriers. Lowering molybdenum levels may potentially reduce cancer risk in this population, and high molybdenum levels could serve as a marker for considering preventive oophorectomy in BRCA1 carriers. Further research is warranted to confirm these findings and explore interventions targeting molybdenum levels as a preventive measure for ovarian cancer in BRCA1 mutation carriers.

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Utilizing hot carriers for efficient plasmonic-mediated chemical reactions (PMCRs) to convert solar energy into secondary energy is one of the most feasible solutions to the global environmental and energy crisis. Finding a plasmonic heterogeneous nanostructure with a more efficient and reasonable hot carrier transport path without affecting the intrinsic plasmonic properties is still a major challenge that urgently needs to be solved in this field. Herein, the mechanism by which plasmonic-promoted interatomic hot electron redistribution on the surface of Au3Cu alloy nanoparticles promotes the electrocatalytic nitrogen reduction reaction (ENRR) is successfully clarified. The localized surface plasmon resonance (LSPR) effect can boost the transfer of plasmonic hot electrons from Au atoms to Cu atoms, trigger the interatomic electron regulation of Au3Cu alloy nanoparticles, enhance the desorption of ammonia molecules, and increase the ammonia yield by approximately 93.9%. This work provides an important reference for rationally designing and utilizing the LSPR effect to efficiently regulate the distribution and mechanism of plasmonic hot carriers on the surface of heterogeneous alloy nanostructures.

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The use of nanotechnology can reduce the challenges facing the use of herbal compounds in the fight against infectious agents. The aim of the present research is to produce nano niosomes containing Bunium persicum essential oil with high efficiency in the temperature and acidity of the living environment of Trichomonas vaginalis parasite and to investigate its toxicity on this parasite. First, Essential oil compounds were identified using GC-Mass. Then six niosomal formulations were made using Tween 40, 60, and 80 and cholesterol by thin film method. Three formulations that have more suitable particle size, zeta potential, and essential oil release and encapsulation efficiency were selected by MTT method to investigate the toxicity on HFF (Human foreskin fibroblasts) cell line. The formulation with lower toxicity was optimized using DSPE-mPEG(2000) polymer. Encapsulation efficiency, particle size, zeta potential, release of essential oil (in temperature and acidity similar to Trichomonas vaginalis living environment), particle morphology and toxicity of optimal formulation (on HFF and Trichomonas vaginalis) were investigated. At the end, the stability of the optimized nanoparticles was studied for 120 days. 12 chemical compounds including γ-Terpinene, Cuminic aldehyde and Para-cymene were identified Bunium persicum essential oil. The optimized formulation has a particle size of 159.73 nm, a zeta potential of -25.1 mV and an encapsulation efficiency of 63.11 %, which has a slow and continuous release at the similar temperature and acidity as Trichomonas vaginalis. Niosomal nanoparticles have a spherical shape and a smooth surface and have little toxicity on the HFF cell line. Also, the toxicity of nano niosomes containing essential oil on Trichomonas vaginalis is higher than free essential oil in all concentrations. The optimized niosomal nanoparticles have good stability because their physicochemical properties have changed very little during 120 days. In conclusion optimized Niosomal formulation containing Bunium persicum essential oil compared to free essential oil can have a higher efficiency to deal with Trichomonas parasite in laboratory conditions.

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Silk proteins, viz., sericin, fibroin and their modified forms etc., have been thoroughly researched as natural biopolymers for the development of varied nanomaterials exhibiting diverse biomedical applications. The silk proteins are extracted from the cocoons by degumming and treatment with soaps, followed by dissolution and dialysis against water. These proteins exhibit distinct mechanical and physicochemical characteristics including biocompatibility, controlled biodegradability, self-assembling traits, chemical modifiability, and adaptability, thus making it an ideal drug delivery vehicle. In this regard, silk protein-derived drug delivery systems have been reported as efficient carrier to encapsulate and stabilize the wide variety of pharmacological molecules, enzymes, proteins, vaccines, and even DNA, allowing them to remain active for a longer period of time. Further, different delivery carriers researched employing these proteins for multitude of applications include hydrogels, sponges, fibres, scaffolds and particulate delivery systems. Additionally, the chemical modification of silk proteins has further opened avenues for development of other modified silk proteins with improved physicochemical traits and hence exhibiting enormous potential in development of varied bioenhanced carrier systems. The current article thus provides the holistic information of characteristics, types of silk protein-based delivery carriers, and their fabrication techniques, while emphasizing the applications of different silk proteins in biomedicine and drug delivery.

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Objectives: Psoriasis is a chronic inflammatory, T-lymphocyte immune-mediated skin disease. In this study, skin-permeating nanolipid carriers (NLCs) of Methotrexate (MTX) and Baicalin (BL) were formulated. This further gave formulation of nano-lipid encapsulated carriers for dual-drug delivery of the hydrophilic and hydrophobic drugs through the liposomal gel. Materials and Methods: Optimization of the formulation of NLCs was performed and characterized by determining their particle size, drug permeation, skin irritation, drug loading capacity, stability, in vitro drug release behavior, and in vitro cellular viability. Ex vivo skin permeation and in vivo psoriatic efficiency were also evaluated and compared. Results: Results revealed that the amount of MTX permeating the skin was 2.4 to 4.4 fold greater for dual-drug s than for single NLCs. The optimized dual-drug loaded NLCs had an average particle size (150.20 ± 3.57 nm) and polydispersity index (0.301 ± 0.01) and high entrapment (86.32 ± 2.78% w/w). The MTX nanoparticles exhibit a positive Zeta potential of 38.6 mV. The psoriasis area and severity index scoring showed the lowest skin erythema, skin thickness and scaling. MTX-BL NLCs were inhibited the expression of inflammatory cytokines (tumor necrosis factor-alpha, and interleukin-17) . Conclusion: It can be concluded that newer targeting strategies for NLCs for dual-drug delivery of nano-lipid carriers could be administered topically for the treatment of psoriasis.

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Exosomes, extracellular vesicles secreted by various cells, actively participate in intercellular communication by facilitating the exchange of crucial molecular information such as DNA, RNA, and lipids. Within this intricate network, microRNAs, endogenous non-coding small RNAs, emerge as pivotal regulators of post-transcriptional gene expression, significantly influencing the development of neurodegenerative diseases. The historical prominence of traditional Chinese medicine (TCM) in clinical practice in China underscores its enduring significance. Notably, TCM monomers, serving as active constituents within herbal medicine, assume a critical role in the treatment of neurodegenerative diseases, particularly in mitigating oxidative stress, inhibiting apoptosis, and reducing inflammation. This comprehensive review aims to delineate the specific involvement of exosomal microRNAs in various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, stroke, and amyotrophic lateral sclerosis. Furthermore, the exploration extends to the application of TCM monomers, elucidating their efficacy as therapeutic agents in these conditions. Additionally, the review examines the utilization of exosomes as drug delivery carriers in the context of neurodegenerative diseases, providing a nuanced understanding of the potential synergies between TCM and modern therapeutic approaches. This synthesis of knowledge aims to contribute to the advancement of our comprehension of the intricate molecular mechanisms underlying neurodegeneration and the potential therapeutic avenues offered by TCcom interventions.

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In the field of photocatalytic treatment of dye wastewater, zinc oxide (ZnO) is a typical semiconductor photocatalyst, but it has some disadvantages such as wide band gap, low carrier yield and easy recombination. In this study, Cr-ZnO/N-CQDs catalyst was synthesised using the strategy of p-type doping and construction of Z-scheme heterojunction. The results showed that the removal rate of Cr-ZnO/N-CQDs for MB dye was 97.42 %, which was 70.56 % higher than that of ZnO, and was still 92.16 % after 5 cycles, and the TOC removal rate of methylene blue wastewater was 88.60 %. The reason for the enhanced photocatalytic activity of Cr-ZnO/N-CQDs is that the π* electron (e-) in the N-CQDs interact with the 3d orbitals of Cr-ZnO, so that e- is more easily transferred from the valence band of Cr-ZnO to the conduction band of N-CQDs. The band gap of p-type Cr-ZnO is narrowed, which makes its photogenerated carrier yield increase, hole concentration raise, and the adsorption capacity of H2O molecules reduce by 1.04 eV. The density functional theory calculation shows that the maximum Gibbs free energy of Cr-ZnO for the production of hydroxyl radical is 0.05 eV lower than that of ZnO. This study lays theoretical and practical foundation for the photocatalytic treatment of dye wastewater with ZnO.

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Glioblastoma (GB) is the most common and lethal primary form of malignant brain cancers. Its intrinsic aggressiveness and the blood-brain barrier (BBB) are two major factors that limit the efficacy of standard therapies. In recent years, nanostructured lipid carriers (NLCs) have established themselves as a promising avenue for improving drug delivery to the brain, overcoming the challenges associated with the low drug permeability of the BBB. This work delves into the systematic development of a novel carrier for pitavastatin delivery by establishing a "get it right at the first time" quality by design perspective, supported by multivariate analysis, computational modelling, and molecular docking. The manufacturing process was comprehensively evaluated at each step, from raw material selection to NLC purification, thus leading to a carrier with optimal colloidal, encapsulation and stability properties. The cytotoxic behaviour of the carrier was assessed in a panel of GB cell lines, which includes a low, a medium and a highly sensitive cell line to pitavastatin, providing a better discriminatory power and addressing the different potential in the therapeutic responses. The results obtained reflect a strong antiglioblastoma activity in concentrations where the standard of care lacks activity, as well as a swift and prominent internalization by GB cells. Overall, this work positions these long-term stable parenteral systems in line with the hypothesis of providing more effective surrogate therapeutics in the field of GB.

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Recent progress in therapeutics for amyotrophic lateral sclerosis (ALS) has spurred development and imbued the field of ALS with hope for more breakthroughs, yet substantial scientific gaps persist. This unmet need remains a stark reminder that innovative paradigms are needed to invigorate ALS research. To move toward more informative, targeted, and personalized drug development, the National Institutes of Health (NIH) established a national ALS clinical research consortium called Access for ALL in ALS (ALL ALS). This new consortium is a multi-institutional effort that aims to organize the ALS clinical research landscape in the United States. ALL ALS is operating in partnership with several stakeholders to operationalize the recommendations of the Accelerating Access to Critical Therapies for ALS Act (ACT for ALS) Public Private Partnership. ALL ALS will provide a large-scale, centralized, and readily accessible infrastructure for the collection and storage of a wide range of data from people living with ALS (symptomatic cohort) or who may be at risk of developing ALS (asymptomatic ALS gene carriers). Importantly, ALL ALS is designed to encourage community engagement, equity, and inclusion. The consortium is prioritizing the enrollment of geographically, ethnoculturally, and socioeconomically diverse participants. Collected data include longitudinal clinical data and biofluids, genomic, and digital biomarkers that will be harmonized and linked to the central Accelerating Medicines Partnership for ALS (AMP ALS) portal for sharing with the research community. The aim of ALL ALS is to deliver a comprehensive, inclusive, open-science dataset to help researchers answer important scientific questions of clinical relevance in ALS.

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Purpose: Osteoprotegerin (OPG) plays an important role in the inhibition of osteoclast formation and bone resorption. Studies have reported lower OPG levels among women with a pathogenic variant (mutation) in the BRCA1 gene, and thus, may be at greater risk for skeletal bone loss. Thus, we investigated the association between circulating OPG and two validated markers of bone health: 1) bone fracture risk score (FRAX) and 2) bone mineral density (BMD), among BRCA mutation carriers. Methods: Women with a blood sample and clinical data were included in this analysis. An enzyme-linked immunosorbent assay (ELISA) was used to quantify serum OPG (pg/mL) and the 10-year risk of major osteoporotic fracture (FRAXmajor) and hip fracture (FRAXhip) (%) was estimated using a web-based algorithm. For a subset of women, lumbar spine BMD was previously assessed by dual x-ray absorptiometry (DXA)(T-score). A Mann-Whitney U test was used to evaluate the association between OPG and FRAX score, while linear regression was used to assess the association of OPG and BMD. Results: Among 701 women with a BRCA1 mutation, there was a significant (and unexpected) positive association between OPG levels and FRAX score (FRAXmajor: 2.12 (low OPG) vs. 2.53 (high OPG) P < 0.0001; FRAXhip: 0.27 (low OPG) vs. 0.44 (high OPG) P < 0.0001). In a subset with BMD measurement (n = 50), low serum OPG was associated with a significantly lower BMD T-score (-1.069 vs. -0.318; P = 0.04). Conclusion: Our findings suggest that women with inherently lower OPG may be at risk of lower BMD, the gold standard marker of bone disease. Due to the young age of our cohort, on-going studies are warranted to re-evaluate the association between OPG and FRAX in BRCA mutation carriers.

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Oral conditions, such as recurrent aphthous stomatitis, are chronic inflammatory disorders that significantly affect the life quality. This study aims to develop a novel buccal mucoadhesive based on methacrylate hydroxypropyl methylcellulose (M-HPMC) and methacrylate lignin (M-SLS) encapsulated with nanostructured lipid carriers (NLCs) for controlled release of alpha-pinene (α-pinene). NLCs with particle sizes of 152 ± 3 nm were prepared by using stearic acid and oleic acid as solid and liquid lipids, respectively. Following the successful synthesis of M-HPMC and M-SLS, various concentrations of α-pinene loaded NLCs (0, 18, 38, and 50 wt%) were encapsulated in M-HPMC/M-SLS hydrogel. It was demonstrated that the physiological and mechanical performances of hydrogels were changed, depending on the NLC content. Remarkably, the incorporation of 18 wt% NLC improved the compressive strength (143 ± 14 kPa) and toughness (17 ± 1 kJ/m3) of M-HPMC/M-SLS hydrogel. This nanocomposite hydrogel considerably decreased dissipated energy from 1.64 kJ/m3 to 0.99 kJ/m3, after a five-cycle compression test. The nanocomposite hydrogel exhibited controlled α-pinene release for up to 96 h which could significantly improve the antioxidant activity of M-HPMC/M-SLS matrix. Moreover, the reinforcing M-HPMC/M-SLS hydrogel with α-pinene-loaded NLCs resulted in increased adhesive strength (113.5 ± 7.5 kPa) to bovine buccal mucosa and cytocompatibility in contact with fibroblasts.

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BACKGROUND: Variant transthyretin amyloidosis (ATTRv) is a rare multisystemic disorder caused by mutations in the transthyretin (TTR) gene. The aim of the present work was to describe the clinical profile of asymptomatic carriers (AC) and Coutinho stage 1 ATTRv patients in Spain. METHODS: National, multicentre, cross-sectional study that included 86 AC and 19 patients diagnosed in the previous 12 months to enrolment. Clinical and demographical data, TTR gene mutations, red flags anamnesis, neurological and cardiological assessments were collected. RESULTS: The mean age of patients was 56.8 years at onset and 58.6 years at diagnosis; 53% of patients and 51% of AC were from non-endemic areas. Val50Met was the most frequent mutation in both groups. Neuropathy impairment score data (mean 17.7 ± 20.5) and small-fibre function in lower limbs assessed with SUDOSCAN revealed that patients were diagnosed at early stages of neurological impairment. Peripheral polyneuropathy (84.2%), autonomic neuropathy (73.7%), cardiac (63.2%) and gastrointestinal (47.4%) alterations were the most common symptoms in patients. Autonomic neuropathy, gastrointestinal impairment, carpal tunnel syndrome, cardiac and ocular alterations were potentially related to ATTRv in the AC group. CONCLUSIONS: The EMPATIa study provides a detailed description of AC and Coutinho stage 1 ATTRv patients across Spain, confirming the multisystemic clinical profile of the disease. This study reveals a diagnosis delay around 1.8 years, highlighting the importance of a profound disease awareness to reach a diagnose in earlier stages of neurological impairment.

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Heat treatment and pH are crucial factors in the formulation and processing of food and beverages; thus, a thorough understanding of the impact of these factors on the interactions between bioactive constituents and proteins is essential to developing effective protein-based delivery systems. This study explores the influences of pH (ranged from 1.5 to 7.5) and preheating treatment on the characteristics of caseinates-lutein (LU)/zeaxanthin (ZX) complexes and evaluates the potential application of caseinates as protective carriers in xanthophyll-fortified beverages. The properties and interactions of caseinates and two xanthophylls were systematically investigated utilizing a range of spectroscopic techniques, including ultraviolet-visible (UV-Vis) spectroscopy, dynamic light scattering (DLS), fluorescence spectroscopy, and Fourier transform infrared (FTIR) spectroscopy. Caseinates were bound to LU/ZX with a binding constant of the order 105 M-1. Furthermore, ZX exhibited a higher affinity for caseinates than LU. In particular, the decreased pH level of complex formulation and the preheating of caseinates at 85 °C strengthened the binding affinity between LU/ZX and caseinates. The caseinate-LU/ZX complexes effectively improved the chemical stability of LU/ZX and achieved a bioaccessibility rate of over 70 %. This study provides a guide for developing commercially available xanthophyll-fortified beverages and further expanding the application of caseinates as encapsulation carriers for extremely hydrophobic nutrients in the food industry.

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Deuterium labeling is a highly valuable yet challenging subject of research in various scientific fields. Conventional deuteration methods often involve harsh reaction conditions and suffer from limited reactivity and selectivity. Herein, we report a visible light-driven C-X (X = halogen) to C-D (D = deuterium) exchange strategy over copper-doped cadmium sulfide quantum dots (Cu-CdS QDs) under mild conditions, eliminating the need for noble metal catalysts and expensive deuterium sources. The conversion of aryl halides into deuterated products using Cu-CdS QDs reaches up to 99%, which is four times higher than that achieved using pristine CdS QDs. The substantial enhancement in the photocatalytic activity of the QDs can be primarily attributed to the generation of long-lived charge carriers (approximately 6 µs) induced by Cu doping. Mechanistic studies reveal that the Cu dopants considerably retard the recombination of photoinduced carriers by creating intermediate energy levels that serve as hole trapping centers in CdS QDs, thereby improving the electron utilization efficiency in energetically demanding photoreduction reactions. Additionally, the introduction of Cu increases the energy offset between the conduction band of CdS QDs and molecular acceptors, facilitating the electron transfer process. Upon visible light irradiation, a series of aryl halides can be efficiently converted into the desired deuterated compounds using D2O as the deuterium source. This work demonstrates that regulating charge carrier dynamics in ultrasmall QD-based photocatalysts is a promising strategy for promoting organic transformations.

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This study focuses on the development of environmentally friendly Au-Cu2-xS/CuInS2 heteronanotrimers. The chosen strategy relies on the laser photodeposition of a single gold nanodot (ND) onto Janus Cu2- xS/CuInS2 heteronanocrystals (HNCs). This method offers precise control over the number, location, and size (5 to 8 nm) of the Au NDs by adjusting laser power for the career production, concentration of hole scavenger for charge equilibration in redox reactions, and gold precursor concentration, and exposure time for the final ND size. The photoreduction of gold ions onto HNCs starts systematically at the Cu2- xS tip. The Au deposition then depends on the CuInS2 segment length. For short HNCs, stable Au-Cu2- xS/CuInS2 heteronanotrimers form, while long HNCs undergo a secondary photo-induced step: the initial Au ND is progressively oxidized, with concomitant deposition of a second gold ND on the CuInS2 side, to yield Au2S-Cu2- xS/CuInS2-Au heteronanotrimers. Results are rationalized by quantitative comparison with a model that describes the growth kinetics of NDs and Au-Cu2- xS transformation and emphasizes the importance of charge separation in predicting selective deposition in heteronanotrimer production. The key parameter controlling Au-Cu2‒ xS/CuInS2 HNCs is the photoinduced electric field gradient generated by charge separation, which is tailored by controlling the CuInS2 segment size.

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Exosomes are small vesicles that form when multivesicular bodies fuse with the plasma membrane and are released into body fluids. They play a vital role in facilitating communication between cells by transferring different biomolecules, including DNA, RNA, proteins, and lipids, over both short and long distances. They also function as vital mediators in both states of health and disease, exerting an impact on several physiological processes. Exosomes have been modified to overcome the limitations of natural exosomes to enhance their potential as carriers for drug delivery systems, and these modifications aim to improve the drug delivery efficiency, enhance tissue and organ targeting, and prolong the circulating half-life of exosomes. This review discussed recent advancements in exosome nanotechnology, as well as the progression and use of exosomes for drug delivery. The potential commercialisation and challenges associated with the use of exosome-based drug delivery systems were also discussed, aiming to motivate the development of exosome-based theranostic nanoplatforms and nanotechnology for improved healthcare treatments.

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BACKGROUND: Hereditary transthyretin amyloidosis (ATTR) is an autosomal dominant disease characterized by amyloid fibril deposition. The TTR c.148G > T mutation (V30L) in ATTR is rarely reported, and its biochemical properties are unknown. METHODS: Seven patients and two asymptomatic carriers from two unrelated families diagnosed with V30L variant of ATTR were included. Data on clinical manifestations, laboratory examination, electrophysiology, ophthalmological corneal confocal microscopy (CCM), pathology and molecular biological experiments was collected and analyzed. RESULTS: Most patients initially experienced paresthesia, with varying degrees of peripheral neuropathy, autonomic dysfunction, and cardiac involvement. Nerve conduction studies showed extensive motor and sensory nerve involvement in upper and lower limbs. CCM revealed reduced corneal nerve density and fiber length. Sural nerve biopsies indicated loss of myelinated nerve fibers, with neurogenic patterns in gastrocnemius muscle biopsies. Asymptomatic carriers had nearly normal electrophysiology but mild reductions in corneal nerve fiber density and length. Sural nerve biopsies in carriers showed mild reductions in small myelinated nerve fibers. V30L mutation impaired thermodynamic and kinetic stability of the mutant protein. Plasma TTR tetramer concentration was lower in ATTR V30L patients compared to healthy donors. Small molecule stabilizers failed to exhibit satisfactory inhibition on fibril formation of V30L mutation in vitro. CONCLUSION: This study highlights the multisystem involvement in ATTR V30L patients, including neuropathy and cardiac issues. Both patients and carriers showed abnormalities in nerve conduction, corneal microscopy, and pathology. The V30L mutation impaired protein stability and reduced plasma TTR tetramer levels. Small molecule stabilizers were ineffective, indicating a need for alternative treatments.