HPV16 E6-induced M2 macrophage polarization in the cervical microenvironment via exosomal miR-204-5p.

The persistent infection of high-risk human papillomavirus (HPV) and the progression of cervical cancer necessitate the involvement of microenvironmental immunity. As cervical lesions advance, there is an observed increase in the infiltration of type 2 (M2) macrophages. However, the precise mechanism driving this increased infiltration of M2 macrophages remains unclear. In this study, we investigated the role of exosomes in polarising M2 macrophages in cervical lesions associated with HPV E6. Through the analysis of bioinformatics data and clinical specimens, we discovered a positive correlation between HPV E6/E7 mRNA copy number and the level of M2 macrophage infiltration. Exosomes derived from HPV E6 overexpressed (HPV E6+) cervical squamous cell carcinoma (CESC) cells were found to induce the polarisation of macrophages towards M2 type. Specifically, miR-204-5p, enriched in HPV E6 + CESC exosomes, was transported into macrophages and triggered M2 macrophage polarisation by inhibiting JAK2. The clinical relevance of exosomal miR-204-5p in the progression of cervical lesions was validated through serum samples from 35 cases. Exosomal miR-204-5p emerges as a critical factor influencing M2 macrophage polarisation and is correlated with the severity of cervical lesions. Consequently, miR-204-5p could be used as a potential treatment and a candidate biomarker for cervical lesions.

Hoxc10-mediated 'positional memory' regulates cartilage formation subsequent to femoral heterotopic grafting.

The Hox gene plays a crucial role in the bone development, determining their structure and morphology. Limb bone grafts expressing Hox positive genes are commonly used for free transplantation to repair Hox negative mandibular critical bone defects. However, the specific role of original Hox genes in newly formed bone during the cross-layer bone grafting healing process remains unexplored. Our findings demonstrate that femurs ectopically grafted into the mandibular environment retained a significant ability to differentiate into cartilage and form cartilaginous callus, which may be a key factor contributing to differences in bone graft healing. Hoxc10, an embryonic layer-specific genes, regulates cartilage formation during bone healing. Mechanistically, we observed Hoxc10 retention in co-cultured femoral BMSCs. Knocking out Hoxc10 narrows the bone gap and reduces cartilage formation. In summary, we reveal Hoxc10's 'positional memory' after adult cross-layer bone graft, influencing the outcomes of autologous bone graft.

Prenatal diagnosis, ultrasound findings, and pregnancy outcome of 17q12 deletion and duplication syndromes: a retrospective case series.

OBJECTIVE: Analyze the ultrasound findings, single-nucleotide polymorphism array (SNP-array) results, and pregnancy outcomes of fetuses with 17q12 deletions and duplications in the second and third trimesters. Explore the prenatal ultrasound characteristics and pregnancy outcomes of these fetuses. METHODS: Retrospective data were collected for 16 fetuses diagnosed with 17q12 deletion and seven fetuses with 17q12 duplication through SNP-array during prenatal diagnosis at a single Chinese tertiary medical center from January 2017 to December 2023. Maternal demographics, ultrasound findings of the fetuses, SNP-array results, pregnancy outcomes, and follow-up information were reviewed and analyzed. Peripheral blood from the parents was extracted to determine whether the CNVs in the fetuses were inherited or de novo. RESULTS: The copy-number variation (CNV) sizes ranged from 1.39 to 1.94 Mb in cases of 17q12 deletion and from 1.42 to 1.91 Mb in cases of 17q12 duplication. These CNVs included 15 OMIM genes, such as HNF1B, LHX1, and ACACA. In fetuses with a 17q12 deletion, the primary manifestation was renal abnormalities (93.8%, 15/16). Of these, 13 cases (81.3%, 13/16) exhibited bilateral or unilateral hyperechogenic kidneys, and 12 cases (75%, 12/16) had multicystic hyperechogenic kidneys. Two cases (12.5%, 2/16) showed multiple organ structural abnormalities. In fetuses with a 17q12 duplication, four cases (57.1%, 4/7) revealed cardiovascular system abnormalities, including tetralogy of fallot, pulmonary artery stenosis, ventricular septal defect, and tricuspid regurgitation. Two cases (28.6%, 2/7) presented with upper gastrointestinal obstruction. Additionally, one case was particularly unique, characterized by multiple structural malformations, such as ventricular septal defect, microcephaly, cleft lip, and palate. Nine cases opted for pregnancy termination, and 14 chose to continue the pregnancy. Two cases underwent surgical treatment after birth for upper gastrointestinal obstruction, and the prognosis was good. Among the 10 cases of 17q12 deletion, six cases showed consistent prenatal ultrasound findings and postnatal clinical features. Four cases were found to have discrepancies with prenatal ultrasound findings; while the renal ultrasound phenotype appeared normal during the last follow-up, two of these cases were subsequently diagnosed with neuropsychiatric phenotypes. CONCLUSION: Our study expanded the clinical phenotype spectrum of fetuses with 17q12 deletion and duplication, and conducted a preliminary evaluation of prenatal ultrasound findings and postnatal clinical phenotypes in follow-up cases. We further demonstrated a high correlation between fetuses with 17q12 deletion and hyperechogenic, multicystic kidneys. The primary manifestations in fetuses with 17q12 duplication are likely cardiovascular system malformations, which also exhibit a broad spectrum of phenotypic features.

Comprehensive Mapping of Cyclotides from Viola philippica by Using Mass Spectrometry-Based Strategy.

Cyclotides are plant cyclic peptides with exceptional stability and diverse bioactivity, making them promising candidates for biomedical applications. Therefore, the study of cyclotides has attracted increasing attention in recent years. However, the existing cyclotide detection methods face limitations in sensitivity, accuracy, and reliability. To address these challenges, we developed an integrated strategy using a combination of strong cation exchange chromatography techniques for removing interfering small molecules, Orbitrap Exploris 480 mass spectrometry (OEMS); this is a detection and database searching-based method for cyclotide verification, which greatly improved the sensitivity, accuracy, and reliability of cyclotide identification. This strategy was subsequently employed for cyclotide mapping in Viola with a minute amount of starting tissue, resulting the identification of 65 known and 18 potentially novel cyclotides, which is the largest dataset of cyclotides for Viola philippica. This strategy provided valuable insights into the cyclotide diversity and distribution in V. philippica, with potential applications in drug discovery and other biomedical fields.

Evaluating stability and bioactivity of Rehmannia-derived nanovesicles during storage.

Plant-derived nanovesicles (PDNVs) have garnered growing attention in the biomedical field owing to their abundance in plant-derived ribonucleic acids (RNA), proteins, lipids and metabolites. The question about the preservation of PDNVs is a crucial and unavoidable concern in both experiments' settings and their potential clinical application. The objective of this research was to examine the impact of varying storage temperatures on the stability and bioactivity of Rehmannia-derived nanovesicles (RDNVs). The results showed that RDNVs aggregated after 2 weeks of storage period at 4 °C, and the particle size of some RDNVs gradually increased with time, along with the increase of solution potential. After 2 months of storage, all RDNVs exhibited varying levels of aggregation irrespective of storage temperature. The bioactivities of nanovesicles under different temperature storage conditions revealed a gradual decline in cell proliferation inhibition bioactivity over time, significantly lower than that of freshly prepared RDNVs. In contrast, the preservation of anti-migratory activity in RDNVs was found to be more effective when subjected to rapid freezing in liquid nitrogen followed by storage at - 80 °C, as opposed to direct storage at - 80 °C. These findings suggest that temperature alone may not be sufficient in safeguarding the activity and stability of RDNVs, highlighting the necessity for the development of novel protective agents for PDNVs.

Comparison of nanovesicles derived from Panax notoginseng at different size: physical properties, composition, and bioactivity.

Aim: Plant-derived nanovesicles have emerged as potential agents for combating tumors. In this study, we investigated the inhibitory effects of Panax notoginseng-derived nanovesicles (PnNVs) on the proliferation and migration of squamous cell carcinoma. Additionally, we explored the relationship between plant tuber size and the physical properties, composition and bioactivity of these nanovesicles. Methods: We isolated PnNVs from Panax notoginseng tubers of varying sizes: small-sized (s_PnNVs), medium-sized (m_PnNVs) and large-sized (l_PnNVs), and evaluated for size, potential, and morphology. Cellular uptake efficiency was assessed using confocal microscopy and flow cytometry. The ability of different PnNVs to inhibit oral squamous cell carcinoma cells was evaluated using plate cloning, CCK8 assay, and scratch healing assay. Off-target metabolomics was used to compare metabolic compounds of different PnNVs. Results: Our findings revealed that s_PnNVs exhibited lower potential but had the highest cellular uptake efficiency, whereas m_PnNVs were characterized by the smallest size and lowest cellular uptake efficiency. Notably, m_PnNVs demonstrated the most effective inhibition of squamous cell carcinoma growth and migration. Compositional analyses showed that PnNVs were rich in proteins and contained lower levels of RNA, with l_PnNVs having the highest protein content. Furthermore, untargeted metabolomics analysis revealed a significant increase in the expression of specific antitumour-related metabolites in m_PnNVs compared to s_PnNVs and l_PnNVs. Conclusion: Overall, our results underscore the influence of plant tuber size on the bioactivity of the nanovesicles from which they are derived, emphasizing its importance for experimental design and study reproducibility.

Effect of impacted mandibular third molar extraction on periodontal microbiota and clinical parameters of adjacent teeth: A randomized clinical trial.

It is urgently necessary to clarify the effect of extraction of impacted mandibular third molar (IMTM) on the periodontal tissue of adjacent second molars (ASMs). In this study, the ASM periodontal condition and pathogenic microbes were assessed before IMTM extraction and at 1, 4, 8 and 12 weeks postoperatively. Based on the inclusion and exclusion criteria, our study revealed that IMTM extractions adversely affected distal － periodontal probing depth (dPPD), attachment loss (dAL), plaque index (dPLI) and bleeding on probing (dBOP) within 8 weeks, but these indices gradually normalize after 12 weeks. The subgingival pathogens near the ASMs distal surface, Porphyromonas and Pseudomonas, were significantly increased postoperatively. Moreover, relevance of ASMs clinical indices and subgingival microbes after IMTM extractions was found. In contrast to the situation in chronic periodontitis, the effects of IMTM extraction on dPPD, dAL, dPLI and dBOP of ASMs were mainly correlated with Pseudomonas. Additionally, while the IMTM extractions have adverse distal periodontal indices of ASMs within 8 weeks and increase subgingival pathogens, the modified triangular flap (MTF) had fewer distal periodontal indices and less Pseudomonas. Compared to the traditional envelope flap and triangular flap, the MTF benefits the periodontal health, which could be considered as the priority option for IMTM extractions.

O-carboxymethyl chitosan in biomedicine: A review.

O-carboxymethyl chitosan (O-CMC) is a chitosan derivative produced through the substitution of hydroxyl (-OH) functional groups in glucosamine units with carboxymethyl (-CH2COOH) substituents, effectively addressing the inherent solubility issues of chitosan in aqueous solutions. O-CMC has garnered significant interest due to its enhanced solubility, elevated viscosity, minimal toxicity, and advantageous biocompatibility properties. Furthermore, O-CMC demonstrates antibacterial, antifungal, and antioxidant characteristics, rendering it a promising candidate for various biomedical uses such as wound healing, tissue engineering, anti-tumor therapies, biosensors, and bioimaging. Additionally, O-CMC is well-suited for the fabrication of nanoparticles, hydrogels, films, microcapsules, and tablets, offering opportunities for effective drug delivery systems. This review outlines the distinctive features of O-CMC, offers analyses of advancements and future potential based on current research, examines significant obstacles for clinical implementation, and foresees its ongoing significant impacts in the realm of biomedicine.

Exploring new avenues of health protection: plant-derived nanovesicles reshape microbial communities.

Symbiotic microbial communities are crucial for human health, and dysbiosis is associated with various diseases. Plant-derived nanovesicles (PDNVs) have a lipid bilayer structure and contain lipids, metabolites, proteins, and RNA. They offer unique advantages in regulating microbial community homeostasis and treating diseases related to dysbiosis compared to traditional drugs. On the one hand, lipids on PDNVs serve as the primary substances that mediate specific recognition and uptake by bacteria. On the other hand, due to the multifactorial nature of PDNVs, they have the potential to enhance growth and survival of beneficial bacterial while simultaneously reducing the pathogenicity of harmful bacteria. In addition, PDNVs have the capacity to modulate bacterial metabolism, thus facilitating the establishment of a harmonious microbial equilibrium and promoting stability within the microbiota. These remarkable attributes make PDNVs a promising therapeutic approach for various conditions, including periodontitis, inflammatory bowel disease, and skin infection diseases. However, challenges such as consistency, isolation methods, and storage need to be addressed before clinical application. This review aims to explore the value of PDNVs in regulating microbial community homeostasis and provide recommendations for their use as novel therapeutic agents for health protection.

Mediating effects of attitude on the relationship between knowledge and willingness to organ donation among nursing students.

Background: The current rate of organ donation in China falls significantly below the global average and the actual demand. Nursing students play a crucial role in supporting and promoting social and public welfare activities. This study primary aims to analyze the levels of knowledge, attitudes, willingness toward organ donation, and attitudes toward death among nursing students, and investigate the mediating role of attitude in the relationship between knowledge and willingness. The secondary aims to identify factors that may influence the willingness. Methods: A convenience sample of nursing students completed online-administered questionnaires measuring the level of knowledge, attitudes, and willingness toward organ donation before and after clinical internship. Spearman correlation and mediation analyses were used for data analyses. Results: Before the clinical internship, there were 435 nursing students who had not yet obtained their degrees and were completing their clinical internships. After the internship, this number decreased to 323. The mean score for knowledge before and after the clinical internship (7.17 before and 7.22 after, with no significant difference), the attitude (4.58 before and 4.36 after, with significant difference), the willingness (12.41% before and 8.67% after, with significant difference), the Death Attitude Profile-Revised (DAP-R) score (94.41 before and 92.56 after, with significant difference). The knowledge indirectly affected nursing students' willingness to organ donation through attitude. Knowledge had a direct and positive impact on attitudes (ß = 1.564). Additionally, nursing students' attitudes positively affected their willingness (ß = 0.023). Attitudes played a mediating role in the relationship between knowledge and willingness (ß = 0.035). Additionally, attitude toward death, fear of death, and acceptance of the concept of escape were found to be correlated with their willingness. Conclusion: Organ donation willingness was found to be low among nursing students. Positive attitudes were identified as a mediating factor between knowledge and willingness. Additionally, DAP-R was a related factor. Therefore, it is recommended to focus on improving knowledge and attitude, as well as providing death education to help nursing students establish a positive attitude toward death. These efforts can contribute to the promotion of organ donation.

The temporal protein signature analyses of developing human deciduous molar tooth germ.

The tooth serves as an exemplary model for developmental studies, encompassing epithelial-mesenchymal transition and cell differentiation. The essential factors and pathways identified in tooth development will help understand the natural development process and the malformations of mineralized tissues such as skeleton. The time-dependent proteomic changes were investigated through the proteomics of healthy human molars during embryonic stages, ranging from the cap-to-early bell stage. A comprehensive analysis revealed 713 differentially expressed proteins (DEPs) exhibiting five distinct temporal expression patterns. Through the application of weighted gene co-expression network analysis (WGCNA), 24 potential driver proteins of tooth development were screened, including CHID1, RAP1GDS1, HAPLN3, AKAP12, WLS, GSS, DDAH1, CLSTN1, AFM, RBP1, AGO1, SET, HMGB2, HMGB1, ANP32A, SPON1, FREM1, C8B, PRPS2, FCHO2, PPP1R12A, GPALPP1, U2AF2, and RCC2. Then, the proteomics and transcriptomics expression patterns of these proteins were further compared, complemented by single-cell RNA-sequencing (scRNA-seq). In summary, this study not only offers a wealth of information regarding the molecular intricacies of human embryonic epithelial and mesenchymal cell differentiation but also serves as an invaluable resource for future mechanistic inquiries into tooth development.

Photochemical Mechanisms of Hydroxyquinoline Benzimidazole: Insights from Electronic Structure Calculations and Nonadiabatic Dynamics Simulations.

Excited-state intramolecular double proton transfer (ESIDPT) has received much attention because of its widespread existence in the life reactions of living organisms, and materials with this property are significant for their special luminescent properties. In this work, the complete active space self-consistent field (CASSCF) and OM2/multireference configuration interaction (OM2/MRCI) methods have been employed to study the static electronic structure calculations of the photochemistry and the possibility of ESIDPT process of hydroxyquinoline benzimidazole (HQB) molecule, along with the nonadiabatic dynamics simulations. The computational results show that the HQB molecule is relaxed to the S1-ENOL minimum after being excited to the Franck-Condon point in the S1 state. Subsequently, during the nonadiabatic deactivation process, the OH···N proton transfer and the twisting of benzimidazole occur before arriving at the single proton transfer conical intersection S1S0-KETO. Finally, the system can either return to the initial ground-state structure S0-ENOL or to the single proton transfer ground-state structure S0-KETO, both of which have almost the same probability. The dynamics simulations also show that no double proton transfer occurs. The excited-state lifetime of HQB is fitted to 1.1 ps, and only 64% of the dynamic trajectories return to the ground state within the 2.0 ps simulation time. We hope the detailed reaction mechanism of the HQB molecule will provide new insights into similar systems.

Temperature-sensitive hydrogel releasing pectolinarin facilitate scarless wound healing.

The dressing that promotes scarless healing is essential for both normal function and aesthetics after a wound. With a deeper understanding of the mechanisms involved in scar formation during the wound healing process, the ideal dressing becomes clearer and more promising. For instance, the yes-associated transcriptional regulator (YAP) has been extensively studied as a key gene involved in regulating scar formation. However, there has been limited attention given to pectolinarin, a natural flavonoid that may exhibit strong binding affinity to YAP, in the context of scarless healing. In this study, we successfully developed a temperature-sensitive Pluronic@F-127 hydrogel as a platform for delivering pectolinarin to promote scarless wound healing. The bioactive pectolinarin was released from the hydrogel, effectively enhancing endothelial cell migration, proliferation and the expression of angiogenesis-related genes. Additionally, a concentration of 20 µg/mL of pectolinarin demonstrated remarkable antioxidant ability, capable of counteracting the detrimental effects of reactive oxygen species (ROS). Our results from rat wound healing models demonstrated that the hydrogel accelerated wound healing, promoting re-epithelialization and facilitating skin appendage regeneration. Furthermore, we discovered that a concentration of 50 µg/mL of pectolinarin incorporated to the hydrogel exhibited the most favourable outcomes in terms of promoting wound healing and minimizing scar formation. Overall, our study highlights that the significant potential of locally released pectolinarin might substantially inhibit YAP and promoting scarless wound healing.

The Association Between Vitamin D and Early Childhood Caries: A Systematic Review and Meta-Analysis.

PURPOSE: Previous surveys have reported that children with vitamin D deficiency were likely to suffer from early childhood caries (ECC). The aim of this systematic review and meta-analysis was to determine 1. whether the status of vitamin D is intrinsically related to the occurrence of ECC and 2. the optimal level of vitamin D for the prevention of ECC. MATERIALS AND METHODS: The database of PubMed, Web of Science, Cochrane, Embase and Google scholar were searched for targeted literature. The eligibility criteria were observational studies in which children with ECC were compared to children without ECC in terms of their vitamin D status. Applying the Newcastle-Ottawa tool, study selection, data extraction, and risk of bias assessment were performed by 2 reviewers independently. Meta-analysis was performed using the Cochrane Collaboration's Review Manager 5.4 software. RESULTS: 501 articles were retrieved from the electronic databases; 11 studies were finally included in systematic review, 10 studies of which were submitted to meta-analysis. The 25(OH)D levels in the ECC group were statistically significantly lower compared with that in the caries-free group (WMD = -13.96, 95% CI: [-19.88,-8.03], p < 0.001), especially in regard to the association between S-ECC and vitamin D (WMD = -18.64, 95% CI: [-20.06,-17.22], p < 0.001). The subgroup analyses in terms of geographical region demonstrated that children with a level of 25(OH)D of 50-75 nmol/l were more likely to have ECC than those with over 75 nmol/l (OR = 1.42, 95% CI: [1.26,1.60], p < 0.001), with data from Asia and Europe combined for analysis Conclusions: The level of vitamin D was lower in children with ECC than in caries-free children, and the correlation between S-ECC and vitamin D was even stronger. The optimal 25(OH)D level for preventing occurrence and development of ECC was ≥ 75 nmol/l. Thus, clinicians should view the development of early caries also from a systemic perspective.

Cellular Uptake of Engineered Extracellular Vesicles: Biomechanisms, Engineered Strategies, and Disease Treatment.

Extracellular vesicles (EVs), lipid-enclosed nanosized membrane vesicles, are regarded as new vehicles and therapeutic agents in intercellular communication. During internal circulation, if EVs are not effectively taken up by recipient cells, they will be cleared as "cellular waste" and unable to deliver therapeutic components. It can be seen that cells uptake EVs are the prerequisite premise for sharing intercellular biological information. However, natural EVs have a low rate of absorption by their recipient cells, off-target delivery, and rapid clearance from circulation, which seriously reduces the utilization rate. Affecting the uptake rate of EVs through engineering technologies is essential for therapeutic applications. Engineering strategies for customizing EV uptake can potentially overcome these limitations and enable desirable therapeutic uses of EVs. In this review, the mechanism and influencing factors of natural EV uptake will be described in detail. Targeting each EV uptake mechanism, the strategies of engineered EVs and their application in diseases will be emphatically discussed. Finally, the future challenges and perspectives of engineered EVs are presented multidimensionally.

Plant-derived nanovesicles: harnessing nature's power for tissue protection and repair.

Tissue damage and aging lead to dysfunction, disfigurement, and trauma, posing significant global challenges. Creating a regenerative microenvironment to resist external stimuli and induce stem cell differentiation is essential. Plant-derived nanovesicles (PDNVs) are naturally bioactive lipid bilayer nanovesicles that contain proteins, lipids, ribonucleic acid, and metabolites. They have shown potential in promoting cell growth, migration, and differentiation into various types of tissues. With immunomodulatory, microbiota regulatory, antioxidant, and anti-aging bioactivities, PDNVs are valuable in resisting external stimuli and facilitating tissue repair. The unique structure of PDNVs provides an optimal platform for drug encapsulation, and surface modifications enhance their stability and specificity. Moreover, by employing synergistic administration strategies, PDNVs can maximize their therapeutic potential. This review summarized the progress and prospects of PDNVs as regenerative tools, provided insights into their selection for repair activities based on existing studies, considered the key challenge for clinical application, and anticipated their continued prominent role in the field of biomedicine.

Excited-state relaxation mechanisms of 2,2'-(1-phenyl-1H-1,2,4-triazole-3,5-diyl)diphenol: single- or double-proton transfer?

Triazole compounds are important organic systems with excellent electronic properties, which have diagnostic potential in the fields of organic electronics and organic photovoltaics. The important photophysical nature of these systems is the transformation between the enol and keto forms after excited-state proton transfer. In this study, the IR vibrational spectrum, ESIPT mechanism, and excited-state decay dynamics of 2,2'-(1-phenyl-1H-1,2,4-triazole-3,5-diyl)diphenol (ExPh) were explored using electronic structure calculations and non-adiabatic dynamics simulations. Two S1/S0 conical intersections with distinct proton transfer (ESIPT-I and ESIPT-II) involved were obtained. The associated two-dimensional S1 minimum-energy potential energy surface indicated that the dynamical roles of these two S1/S0 conical intersections in the S1 excited-state decay were quite different. The ESIPT-I reaction was more favorable to occur than the ESIPT-II process. Our dynamics simulations supported this hypothesis with the whole trajectories decaying to the ground state via the S1S0-1 conical intersection, which involved the ESIPT-I process. The ESIPT-Involved efficient deactivation pathway could be partially responsible for the decrease in fluorescence emission. These results and ESIPT mechanisms are helpful for understanding the decay pathways of similar systems.

The alterations in ocular biometric parameters following short-term discontinuation of long-term orthokeratology and prior to subsequent lens fitting: a preliminary study.

PURPOSE: To investigate the alterations in biometric parameters among Chinese adolescents over an extended period of wearing orthokeratology lenses, as well as the subsequent changes after a one-month cessation of lens usage prior to the secondary lens fitting. METHODS: Twenty-four myopic patients aged 7-14 were enrolled in this 37-month prospective observational study. Ocular biometric parameters were measured in the study. Ocular biometric parameters were assessed, and the utilization of Generalized Estimating Equations (GEE) was employed in the analysis to address the correlation between the two eyes of each participant. RESULTS: The axial length (AL) increased by 0.55 mm after 36 months of lens wearing and further increased to 0.62 mm at the 37-month follow-up compared to the initial measurement. The differences in AL elongation per month between the 37-month time point and the 12-, 24-, and 36-month marks of lens wearing were found to be statistically significant (p12-month = 0.001; p24-month = 0.003; p36-month = 0.001). Following the cessation of lens wear for 1 month, there was no significant complete recovery observed in the flat and steep keratometry values. However, the intraocular pressure and anterior chamber depth returned to their baseline levels. CONCLUSIONS: The AL elongation undergoes alterations during temporary discontinuation of lenses, with the flat and steep keratometry measurements remaining significantly flatter compared to the baseline. However, the intraocular pressure and anterior chamber depth return to their initial levels after one month of lens cessation.

Engineered Plant-Derived Nanovesicles Facilitate Tumor Therapy: Natural Bioactivity Plus Drug Controlled Release Platform.

Tumors are the second-most common disease in the world, killing people at an alarming rate. As issues with drug resistance, lack of targeting, and severe side effects are revealed, there is a growing demand for precision-targeted drug delivery systems. Plant-derived nanovesicles (PDNVs), which arecomposed of proteins, lipids, RNA, and metabolites, are widely distributed and readily accessible. The potential for anti-proliferative, pro-apoptotic, and drug-resistant-reversing effects on tumor cells, as well as the ability to alter the tumor microenvironment (TME) by modulating tumor-specific immune cells, make PDNVs promising anti-tumor therapeutics. With a lipid bilayer structure that allows drug loading and a transmembrane capacity readily endocytosed by cells, PDNVs are also expected to become a new drug delivery platform. Exogenous modifications of PDNVs enhance their circulating stability, tumor targeting ability, high cell endocytosis rate, and controlled-release capacity. In this review, we summarize PDNVs' natural antitumor activity, as well as engineered PDNVs as efficient precision-targeted drug delivery tools that enhance therapeutic effects. Additionally, we discuss critical considerations related to the issues raised in this area, which will encourage researchers to improve PDNVs as better anti-tumor therapeutics for clinic applications.

Non-adiabatic dynamics simulations of the S1 excited-state relaxation of diacetyl phenylenediamine.

The small molecule built around the benzene ring, diacetyl phenylenediamine (DAPA), has attracted much attention due to its synthesis accessibility, large Stokes shift, etc. However, its meta structure m-DAPA does not fluoresce. In a previous investigation, it was found that such a property is due to the fact that it undergoes an energy-reasonable double proton transfer conical intersection during the deactivation of the S1 excited-state, then returns to the ground state by a nonradiative relaxation process eventually. However, our static electronic structure calculations and non-adiabatic dynamics analysis results indicate that only one reasonable non-adiabatic deactivation channel exists: after being excited to the S1 state, m-DAPA undergoes an ultrafast and barrierless ESIPT process and reaches the single-proton-transfer conical intersection. Subsequently, the system either returns to the keto-form S0 state minimum with proton reversion or returns to the single-proton-transfer S0 minimum after undergoing a slight twist of the acetyl group. The dynamics results show that the S1 excited-state lifetime of m-DAPA is 139 fs. In other words, we propose an efficient single-proton-transfer non-adiabatic deactivation channel of m-DAPA that is different from previous work, which can provide important mechanistic information of similar fluorescent materials.