Late-onset traumatic corneal flap dislocation and secondary epithelial ingrowth 24 years after LASIK.

Purpose: To analyze the diagnostic process, treatment, and post-operative outcomes of a unique case involving a late-onset (24 years post) traumatic corneal flap displacement after Laser-assisted in situ keratomileusis (LASIK) surgery due to a plant-related trauma. with an emphasis on the accompanying extensive epithelial ingrowth beneath the flap. Observations: A 59-year-old male patient experienced corneal flap displacement 24 years post-LASIK due to a minor plant-related trauma. This case was complicated by extensive epithelial ingrowth beneath the flap, which was initially misdiagnosed with fungal keratitis. Upon identification of the actual cause, corneal flap repair surgery was performed, leading to partial vision recovery. Conclusions and importance: This case signifies the potential for LASIK flap displacement even decades post-surgery due to minor traumas and highlights the need for vigilance in diagnosing associated complications like epithelial ingrowth. It indicates the importance of ophthalmologists and clinicians being vigilant for such complications and necessitates their familiarity with basic management techniques or quick referral to a corneal refractive surgery specialist. This report of a 24-year interval between LASIK and traumatic flap displacement with epithelial ingrowth is one of the longest known. The case also demonstrates that patients with late flap displacement can regain significant visual acuity with timely and appropriate management.

Exenatide-Modified Deferoxamine-Based Nanoparticles Ameliorates Neurological Deficits in Parkinson's Disease Mice.

Purpose: To avoid the biotoxicity and poor bioavailability of deferoxamine mesylate (DFO), an iron chelation for the treatment of Parkinson's disease (PD), a self-oriented DFO nanoparticle functionalized with Exendin-4 was developed, which can be targeted delivered into the lesion brain area to achieve synergistic effects against PD by iron chelation and inflammatory suppression. Methods: The self-oriented DFO nanoparticles (Ex-4@DFO NPs) were synthesized by double emulsion technique, and characterized in terms of the particle size, morphology and DFO encapsulation efficiency. The cellular internalization, biocompatibility and cytoprotection of NPs were assessed on BV-2 and SH-SY5Y cells. The brain targeting and therapeutic effect of NPs were investigated in MPTP-induced PD mice by near-infrared II fluorescence imaging and immunofluorescence staining, as well as mobility behavioral tests. Results: Ex-4@DFO NPs with a particle size of about 100 nm, showed great biocompatibility and cytoprotection in vitro, which inhibited the decrease of mitochondrial membrane potential of SH-SY5Y cells and the release of inflammatory factors of BV-2 cells. In MPTP-induced PD mice, Ex-4@DFO NPs could penetrate the BBB into brain, and significantly mitigate the loss of dopaminergic neurons and inflammation in the substantia nigra, finally alleviate the mobility deficits. Conclusion: This self-oriented nanosystem not only improved the biocompatibility of DFO, but also enhanced therapeutic effects synergistically by ameliorating neuronal damage and neuroinflammation, showing a potential therapeutic strategy for PD.

Research progress on ferroptosis in colorectal cancer.

Ferroptosis is a new form of cell death that differs from traditional forms of death. It is ferroptosis-dependent lipid peroxidation death. Colorectal cancer(CRC) is the most common tumor in the gastrointestinal tract with a long occultation period and a poor five-year prognosis. Exploring effective systemic treatments for CRC remains a great challenge worldwide. Numerous studies have demonstrated that ferroptosis can participate in the biological malignant process of various tumor, including CRC, so understanding the role and regulatory mechanisms of ferroptosis in CRC plays a crucial role in the treatment of CRC. In this paper, we reviews the mechanisms of ferroptosis in CRC, the associated regulatory factors and their interactions with various immune cells in the immune microenvironment. In addition, targeting ferroptosis has emerged as an encouraging strategy for CRC treatment. Finally, to inform subsequent research and clinical diagnosis and treatment, we review therapeutic approaches to CRC radiotherapy, immunotherapy, and herbal therapy targeting ferroptosis.

Distinct roles of the two BRCA2 DNA binding domains in DNA damage repair and replication fork preservation.

Homologous recombination (HR) is a highly conserved tool for the removal of DNA double-strand breaks (DSBs) and the preservation of stalled and damaged DNA replication forks. Successful completion of HR requires the tumor suppressor BRCA2. Germline mutations in BRCA2 lead to familial breast, ovarian, and other cancers, underscoring the importance of this protein for maintaining genome stability. BRCA2 harbors two distinct DNA binding domains, one that possesses three oligonucleotide/oligosaccharide binding (OB) folds (known as the OB-DBD), and with the other residing in the C-terminal recombinase binding domain (termed the CTRB-DBD) encoded by the last gene exon. Here, we employ a combination of genetic, biochemical, and cellular approaches to delineate contributions of these two DNA binding domains toward HR and the maintenance of stressed DNA replication forks. We show that OB-DBD and CTRB-DBD confer ssDNA and dsDNA binding capabilities to BRCA2, respectively, and that BRCA2 variants mutated in either DNA binding domain are impaired in the ability to load the recombinase RAD51 onto ssDNA pre-occupied by RPA. While the CTRB-DBD mutant is modestly affected for HR, it exhibits a strong defect in the protection of stressed replication forks. In contrast, the OB-DBD is indispensable for both BRCA2 functions. Our study thus defines the unique contributions of the two BRCA2 DNA binding domains in genome maintenance.

Functional Analysis of BARD1 Missense Variants on Homology-Directed Repair in Ovarian and Breast Cancers.

Women with germline BRCA1 mutations face an increased risk of developing breast and ovarian cancers. BARD1 (BRCA1 associated RING domain 1) is an essential heterodimeric partner of BRCA1, and mutations in BARD1 are also associated with these cancers. While BARD1 mutations are recognized for their cancer susceptibility, the exact roles of numerous BARD1 missense mutations remain unclear. In this study, we conducted functional assays to assess the homology-directed DNA repair (HDR) activity of all BARD1 missense substitutions identified in 55 breast and ovarian cancer samples, using the real-world data from the COSMIC and cBioPortal databases. Seven BARD1 variants (V85M, P187A, G491R, R565C, P669L, T719R, and Q730L) were confirmed to impair DNA damage repair. Furthermore, cells harboring these BARD1 variants exhibited increased sensitivity to the chemotherapeutic drugs, cisplatin, and olaparib, compared to cells expressing wild-type BARD1. These findings collectively suggest that these seven missense BARD1 variants are likely pathogenic and may respond well to cisplatin-olaparib combination therapy. This study not only enhances our understanding of BARD1's role in DNA damage repair but also offers valuable insights into predicting therapy responses in patients with specific BARD1 missense mutations.

Halogen substitution strategy for exploiting high-performance molecular ferroelectrics.

Molecular ferroelectrics are emerging as a robust family of electric-ordered materials due to their distinct structural flexibility, molecular tunability, and versatility. In recent years, diverse chemical design approaches have significantly contributed to discovering and optimizing ferroelectric performances of molecule-based ferroelectric systems. Notably, halogen substitution is one of the most effective strategies for inducing symmetry breaking and optimizing the dipole moments and potential energy barriers. In this minireview, we have summarized recent significant advances of halogen substitution strategy in molecule-based ferroelectrics, including organic-inorganic hybrids and metal-free molecular systems. Subsequently, we discuss the underlying mechanism of halogen substitution to improve ferroelectric performances, including the generation of spontaneous polarization, enhancement of Curie temperature, and bandgap engineering. Finally, the future directions in designing and modulating molecular ferroelectrics by halogen substitution strategy are also highlighted.

Achieving functional recovery without anatomical repositioning: A case of corneal flap inversion trauma post femtosecond laser-assisted in situ keratomileusis surgery.

Post femtosecond laser-assisted in situ keratomileusis corneal flap inversion trauma is an exceptionally rare and challenging complication in ophthalmology, highlighted by a case involving a 29-year-old woman who suffered an eye injury from ice chips 10 months after undergoing bilateral femtosecond laser-assisted in situ keratomileusis surgery. The injury led to a corneal flap inversion and melting, exacerbated by a delay in seeking treatment due to the pandemic. When she finally presented for medical attention, her vision was severely compromised, with dense epithelial ingrowth obstructing the visual axis or blocking the pupillary entrance. Despite these complications, medical interventions to remove the epithelial cells and attempts to reposition the corneal flap were carried out. Although the flap could not be fully anatomically restored due to scarring and stromal melt, the patient experienced a remarkable recovery in vision, achieving 20/17 visual acuity 6 months post-surgery. This case illustrates that satisfactory visual outcomes can be achieved even when perfect anatomical restoration is not possible. It challenges the traditional focus on anatomical perfection in corneal surgery and highlights the potential for functional recovery to take precedence over anatomical correction, reducing the need for further risky procedures. The outcome stresses the importance of tailored patient management and careful assessment of the risks and benefits in complex surgical cases.

The role and mechanism of NRG1/ErbB4 in inducing the differentiation of induced pluripotent stem cells into cardiomyocytes.

BACKGROUND: We aimed to investigate the effect and potential mechanism of enhancing Neuregulin1 (NRG1)/v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4 (ErbB4) expression on the differentiation of induced pluripotent stem cells (iPSCs) into cardiomyocytes. METHODS: We utilized CRISPR-CAS9 technology to knock in ErbB4 and obtained a single-cell clone IPSN-AAVS1-CMV-ErbB4 (iPSCs-ErbB4). Subsequently, we induced the differentiation of iPSCs into cardiomyocytes and quantified the number of beating embryoid bodies. Furthermore, quantitative real-time PCR assessed the expression of cardiomyocyte markers, including ANP (atrial natriuretic peptide), Nkx2.5 (NK2 transcription factor related locus 5), and GATA4 (GATA binding protein 4). On the 14th day of differentiation, we observed the α-MHC (α-myosin heavy chain)-positive area using immunofluorescent staining and conducted western blotting to detect the expression of cTnT (cardiac troponin) protein and PI3K/Akt signaling pathway-related proteins. Additionally, we intervened the iPSCs-ErbB4 + NRG1 group with the PI3K/Akt inhibitor LY294002 and observed alterations in the expression of cardiomyocyte differentiation-related genes. RESULTS: The number of beating embryoid bodies increased after promoting the expression of NRG1/ErbB4 compared to the iPSCs control group. Cardiomyocyte markers ANP, Nkx2.5, and GATA4 significantly increased on day 14 of differentiation, and the positive area of α-MHC was three times that of the iPSCs control group. Moreover, there was a marked increase in cTnT protein expression. However, there was no significant difference in cardiomyocyte differentiation between the iPSCs-ErbB4 group and the iPSCs control group. Akt phosphorylation was significantly increased in the iPSCs-ErbB4 + NRG1 group. LY294002 significantly reversed the enhancing effect of NRG1/ErbB4 overexpression on Akt phosphorylation as well as the increase in α-MHC and cTnT expression. CONCLUSIONS: In conclusion, promoting the expression of NRG1/ErbB4 induced the differentiation of iPSC into cardiomyocytes, possibly through modulation of the PI3K/Akt signaling pathway.

Advances in the transport of oral nanoparticles in gastrointestinal tract.

Biological barriers in the gastrointestinal tract (GIT) prevent oral absorption of insoluble drugs. Recently, significant progress has been made in the development of various nanoparticles (NPs) designed to enhance the efficacy of oral drugs. However, the mechanism underlying the intracellular transport of NPs remains unclear, and there are still limitations to improving the oral bioavailability of drugs. This article reviews the challenges faced in the absorption of oral NPs, proposes strategies to overcome these barriers, and discusses the future prospects.

Zipper-Like Dynamic Switching of Coordination Bonds Gives a Polar Bimetallic Halide toward Self-Driven X-ray Detection.

Polar molecular crystals hold a promise for controlling bulk physical properties originated in their unique switchable polarity via structural transformation. However, the mechanisms for switching polarization are mainly limited to displacive and disorder-order phase transitions, which rarely involve the reconstruction of chemical bonds. Here, we have switched and tuned electric polarization in a bimetallic halide, (Neopentylammonium)4AgBiBr8 (1), as verified by light-excited pyroelectric effect. Most notably, its Ag-Br coordination bonds show a zipper-like dynamic switching behavior from the 'locked' to 'unlocked' state, namely, reconstruction of chemical bonds. Coupling with the dynamic ordering of organic cations, this bond-switching transition makes a contribution to switchable polarization of 1. As expected, its polarity creates pyroelectric effect for self-driven X-ray detection with high sensitivity (3.8×103 µC Gy-1 cm-2) and low limit of detection (4.8 nGy s-1). This work on the bond-switching mechanism provides an avenue to design polar molecular candidate for smart optoelectronic devices.

Dual metal centers within a water-stable Co/Ni bimetallic metal-triazolate framework contribute to durable photocatalysis for water treatment.

Bimetallic metal-organic frameworks (MOFs) have been studied extensively in various fields, including photocatalytic and electrocatalytic applications. The enhanced catalytic activity is typically attributed to the synergistic effect of the two metals, often without further explanation. Here, we demonstrate a CoNi-bimetallic triazolate MOF with fixed metal occupancy within the MOF's secondary building unit. Due to the difference in electronegativity and so on, the charge redistribution between the two metal centers could be responsible for the enhanced photocatalytic activity. In addition, the metal(II)-triazolate MOFs we synthesized exhibit unique metal-N coordination and a strong bond between the metal center and triazole ring. Therefore, their crystal structure and high porosity are highly retained even after exposure to humid environments for several months or stirring in water for several days. Overall, the CoNi-bimetallic triazolate MOF combines the excellent water stability and high surface area of its two monometallic counterparts. It can be further tailored to yield the highest colloidal stability during photocatalytic water treatment. As a result, the dual metal centers within the bimetallic MOF, combined with boosted colloidal stability, demonstrate the highest reactive oxygen species generation and promising antibacterial performance compared to their Ni- or Co-based counterparts. These findings shed light on the future design of robust MOF-based photocatalysts, particularly bimetallic ones.

Root exudates facilitate the regulation of soil microbial community function in the genus Haloxylon.

Introduction: Root exudates act as the "language" of plant-soil communication, facilitating crucial interactions, information exchange, and energy transfer between plants and soil. The interactions facilitated by root exudates between plants and microorganisms in the rhizosphere are crucial for nutrient uptake and stress resilience in plants. However, the mechanism underlying the interaction between root exudates and rhizosphere microorganisms in desert plants under drought conditions remains unclear, especially among closely related species. Methods: To reveal the ecological strategies employed by the genus Haloxylon in different habitats. Using DNA extraction and sequencing and UPLC-Q-Tof/MS methods, we studied root exudates and soil microorganisms from two closely related species, Haloxylon ammodendron (HA) and Haloxylon persicum (HP), to assess differences in their root exudates, soil microbial composition, and interactions. Results: Significant differences were found in soil properties and root traits between the two species, among which soil water content (SWC) and soil organic carbon (SOC) in rhizosphere and bulk soils (P < 0.05). While the metabolite classification of root exudates was similar, their components varied, with terpenoids being the main differential metabolites. Soil microbial structure and diversity also exhibited significant differences, with distinct key species in the network and differential functional processes mainly related to nitrogen and carbon cycles. Strong correlations were observed between root exudate-mediated root traits, soil microorganisms, and soil properties, although the complex interactions differed between the two closely relative species. The primary metabolites found in the network of HA include sugars and fatty acids, while HP relies on secondary metabolites, steroids and terpenoids. Discussion: These findings suggest that root exudates are key in shaping rhizosphere microbial communities, increasing microbial functionality, fostering symbiotic relationships with hosts, and bolstering the resilience of plants to environmental stress.

Clinical characteristics and toxicological spectrum analysis of 493 cases of acute poisoning in children.

OBJECTIVE: This retrospective study aimed to analyze the clinical characteristics and toxicological spectrum of acute poisoning in children treated at our pediatric intensive care unit. The findings provide a basis for the treatment and prevention of acute poisoning in children. METHODS: Clinical data of hospitalized children aged 0 to14 years with acute poisoning, treated between January 2015 and December 2023, were collected and analyzed. The analysis included the types of poisoning, sex and age distribution of children, routes and causes of poisoning, time from poisoning to medical consultation, length of hospital stays, and treatment outcomes. RESULTS: Among the 493 cases of acute poisoning in children, pesticide poisoning (n = 252, 51.1%) was the most common type, followed by medication poisoning (n = 182, 36.9%). Chemical poisoning accounted for 7.7% (n = 38), while food poisoning and inhalation of harmful gases accounted for 3.0% (n = 15) and 1.2% (n = 6), respectively. The main route of poisoning was oral ingestion (n = 477, 96.8%), while accidental ingestion accounted for a large proportion (n = 379, 79.4%), and adolescents aged 11 to 14 years accounted for 20.6% (n = 98).Apart from the predominance of girls attempting suicide by self-administering antipsychotic medications (n = 88, 75.9%) due to depression, there was no significant difference in sex distribution among other types of poisoning children. The highest incidence of poisoning except children who self-administer antipsychotic drugs occurred in children aged 1-3 years (n = 267, 54.2%) and 8-14 years (n = 135, 27.4%), with the highest proportion in the preschool age group. The average time from poisoning to medical consultation was 33.4 ± 54.9 h, and majority of children received treatment within 48 h after poisoning (n = 423, 85.8%). The overall effective treatment rate was 96.8%. CONCLUSION: Acute poisoning in children has complex and diverse causes, with accidental ingestion being the main route. Prevention should be emphasized, including strengthening child safety education and improving parental supervision. Moreover, psychological health education is crucial for adolescents during their puberty. In the event of acute poisoning, prompt medical consultation and appropriate treatment are necessary to mitigate adverse outcomes.

Rodent models in sensorineural hearing loss research: A comprehensive review.

Sensorineural hearing loss (SNHL) constitutes a major global health challenge, affecting millions of individuals and substantially impairing social integration and quality of life. The complexity of the auditory system and the multifaceted nature of SNHL necessitate advanced methodologies to understand its etiology, progression, and potential therapeutic interventions. This review provides a comprehensive overview of the current animal models used in SNHL research, focusing on their selection based on specific characteristics and their contributions to elucidating pathophysiological mechanisms and evaluating novel treatment strategies. It discusses the most commonly used rodent models in hearing research, including mice, rats, guinea pigs, Mongolian gerbils, and chinchillas. Through a comparative analysis, this review underscores the importance of selecting models that align with specific research objectives in SNHL studies, discussing the advantages and limitations of each model. By advocating for a multidisciplinary approach that leverages the strengths of various animal models with technological advancements, this review aims to facilitate significant advancements in the prevention, diagnosis, and treatment of sensorineural hearing loss.

Characterization of Bacillus pacificus G124 and Its Promoting Role in Plant Growth and Drought Tolerance.

Drought represents a major environmental threat to global agricultural productivity. Employing plant growth-promoting rhizobacteria (PGPR) offers a promising strategy to enhance plant growth and resilience under drought stress. In this study, the strain G124, isolated from the arid region of Qinghai, was characterized at the molecular level, and its ability to enhance plant drought tolerance was validated through pot experiments. The findings revealed that the strain G124 belongs to Bacillus pacificus, with a 99.93% sequence similarity with B. pacificus EB422 and clustered within the same clade. Further analysis indicated that the strain G124 demonstrated a variety of growth-promoting characteristics, including siderophore production, phosphate solubilization, and the synthesis of indole-3-acetic acid (IAA), among others. Moreover, inoculation with B. pacificus G124 resulted in significant enhancements in plant height, leaf area, chlorophyll content, relative water content, and root development in both Arabidopsis thaliana and Medicago sativa seedlings under drought conditions. Additionally, G124 boosted antioxidant enzyme activities and osmolyte accumulation, while reducing malondialdehyde (MDA) and reactive oxygen species (ROS) levels in M. sativa seedlings exposed to drought. These findings suggest that B. pacificus G124 holds significant promise for enhancing plant drought tolerance and could be effectively utilized in crop management strategies under arid conditions.

Accurate segmentation of intracellular organelle networks using low-level features and topological self-similarity.

MOTIVATION: Intracellular organelle networks (IONs) such as the endoplasmic reticulum (ER) network and the mitochondrial (MITO) network serve crucial physiological functions. The morphology of these networks plays a critical role in mediating their functions. Accurate image segmentation is required for analyzing the morphology and topology of these networks for applications such as molecular mechanism analysis and drug target screening. So far, however, progress has been hindered by their structural complexity and density. RESULTS: In this study, we first establish a rigorous performance baseline for accurate segmentation of these organelle networks from fluorescence microscopy images by optimizing a baseline U-Net model. We then develop the multi-resolution encoder (MRE) and the hierarchical fusion loss (Lhf) based on two inductive components, namely low-level features and topological self-similarity, to assist the model in better adapting to the task of segmenting IONs. Empowered by MRE and Lhf, both U-Net and Pyramid Vision Transformer (PVT) outperform competing state-of-the-art models such as U-Net++, HR-Net, nnU-Net, and TransUNet on custom datasets of the ER network and the MITO network, as well as on public datasets of another biological network, the retinal blood vessel network. In addition, integrating MRE and Lhf with models such as HR-Net and TransUNet also enhances their segmentation performance. These experimental results confirm the generalization capability and potential of our approach. Furthermore, accurate segmentation of the ER network enables analysis that provides novel insights into its dynamic morphological and topological properties. AVAILABILITY AND IMPLEMENTATION: Code and data are openly accessible at https://github.com/cbmi-group/MRE.

Unusual Triple-State Switching of Thermally Induced Birefringence in a Two-Dimensional Perovskite Ferroelectric.

Birefringent crystals hold a significant position in optical and optoelectronic fields due to their capability to control polarized light. Despite various chemical strategies devoted to designing birefringent crystals, it remains a challenge to switch and manipulate birefringence under physical stimuli. Here we present an unusual triple-state switching of birefringence in a 2D perovskite ferroelectric, (N-methylcyclohexylammonium)2PbCl4 (1), which exhibits two reversible phase transitions at 361 and 373 K. The in-plane birefringence of 1 (Δnbc) shows three distinctive states inside the bc plane, namely, the low-, high-, and zero-Δnbc states. Strikingly, a huge augmentation of Δnbc is solidly confirmed up to ∼400% between its low and high states, far beyond other birefringent materials. The origin of this triple-state switching of birefringence involves the variation of the ferroelastic strain and domain in the vicinity of the phase transition. As an entirely new mode of switching birefringence, this work facilitates the further development of new intelligent nonlinear optics.

Promotion of DNA end resection by BRCA1-BARD1 in homologous recombination.

The licensing step of DNA double-strand break repair by homologous recombination entails resection of DNA ends to generate a single-stranded DNA template for assembly of the repair machinery consisting of the RAD51 recombinase and ancillary factors1. DNA end resection is mechanistically intricate and reliant on the tumour suppressor complex BRCA1-BARD1 (ref. 2). Specifically, three distinct nuclease entities-the 5'-3' exonuclease EXO1 and heterodimeric complexes of the DNA endonuclease DNA2, with either the BLM or WRN helicase-act in synergy to execute the end resection process3. A major question concerns whether BRCA1-BARD1 directly regulates end resection. Here, using highly purified protein factors, we provide evidence that BRCA1-BARD1 physically interacts with EXO1, BLM and WRN. Importantly, with reconstituted biochemical systems and a single-molecule analytical tool, we show that BRCA1-BARD1 upregulates the activity of all three resection pathways. We also demonstrate that BRCA1 and BARD1 harbour stand-alone modules that contribute to the overall functionality of BRCA1-BARD1. Moreover, analysis of a BARD1 mutant impaired in DNA binding shows the importance of this BARD1 attribute in end resection, both in vitro and in cells. Thus, BRCA1-BARD1 enhances the efficiency of all three long-range DNA end resection pathways during homologous recombination in human cells.