The interaction between KIF21A and KANK1 regulates dendritic morphology and synapse plasticity in neurons.

JOURNAL/nrgr/04.03/01300535-202501000-00029/figure1/v/2024-05-14T021156Z/r/image-tiff Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory. Kinesin-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1; however, whether KIF21A modulates dendritic structure and function in neurons remains unknown. In this study, we found that KIF21A was distributed in a subset of dendritic spines, and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative spines. Furthermore, the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic plasticity. Knockdown of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching, and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1, but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and talin1. Knocking down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals' cognitive abilities. Taken together, our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.

A phase II clinical trial of toripalimab in advanced solid tumors with polymerase epsilon/polymerase delta (POLE/POLD1) mutation.

Patients carrying mutations in polymerase epsilon/polymerase delta have shown positive responses to immune checkpoint inhibitors. Yet, prospective trials exploring the efficacy in those with polymerase epsilon/polymerase delta mutations are still lacking. A phase II clinical trial was initiated to evaluate the efficacy of toripalimab, a humanized IgG4K monoclonal antibody to human PD-1, in patients with advanced solid tumors with unselected polymerase epsilon/polymerase delta mutations but without microsatellite instability-high. A total of 15 patients were enrolled, 14 of whom were assessed for treatment efficacy. There was a 21.4% overall response rate, with a disease control rate of 57.1%. The median overall survival and median progression-free survival were 17.9 (95% CI 13.5-not reach) months and 2.5 (95% CI 1.4-not reach) months, respectively. For patients with exonuclease domain mutations, the objective response rate was 66.7% (2/3), with a disease control rate of 66.7% (2/3). For those with non-exonuclease domain mutations, the rates were 9.1% (1/11) and 54.5% (6/11), respectively. Notably, patients with PBRM1 gene mutations exhibited a high response rate to toripalimab at 75.0% (3/4). This study showed that neither the exonuclease domain mutations nor non-exonuclease domain mutations could fully predict the efficacy of immunotherapy, urging the need for more investigations to clarify potential immune sensitization differences within polymerase epsilon/polymerase delta mutation variants.

Matrine-loaded self-adhesive swelling microneedle for inflammation regulation to improve eczema treatment.

Eczema is a common chronic dermatological disease. Conventional treatments exhibit limited efficacy due to fast drug release resulting in short-term relief. Development of a new treatment strategy that enables sustained drug release and long-term maintenance on the skin surface is necessary. A self-adhesive swelling microneedle patch (SDSMNs) was designed and constructed using a two-step casting method. The adhesive substrate was prepared by blending gelatin and dopamine via oxidation of NaIO4, so it could adhere onto the skin surface as well as withstand repeated bending movement without detachment. The swelling needles were fabricated using polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP), which could swell by absorbing interstitial fluid and release the drug in a controlled manner. SDSMNs also showed desirable antibacterial activities toward E. coli and S. aureus. The adhesive microneedles loaded with matrine (MAT-SDSMNs), an anti-inflammatory Chinese medicine, dramatically relieved eczema symptoms through IL-17 mediated inflammation responses. The use of MAT-SDSMNs significantly decreased the infiltration of inflammation cells and level of inflammatory cytokines, reduced the skin thickness, and increased collagen deposition fraction compared with conventional ointment or subcutaneous injection. The results suggested that MAT-SDSMNs can improve eczema treatment by regulating the local inflammatory microenvironment, providing a simple, self-administered sustainable strategy for eczema treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-024-00235-z.

Particulate matter 2.5 accelerates aging: Exploring cellular senescence and age-related diseases.

Exposure to Particulate matter 2.5 (PM2.5) accelerates aging, causing declines in tissue and organ function, and leading to diseases such as cardiovascular, neurodegenerative, and musculoskeletal disorders. PM2.5 is a major environmental pollutant and an exogenous pathogen in air pollution that is now recognized as an accelerator of human aging and a predisposing factor for several age-related diseases. In this paper, we seek to elucidate the mechanisms by which PM2.5 induces cellular senescence, such as genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, and mitochondrial dysfunction, and age-related diseases. Our goal is to increase awareness among researchers within the field of the toxicity of environmental pollutants and to advocate for personal and public health initiatives to curb their production and enhance population protection. Through these endeavors, we aim to promote longevity and health in older adults.

How to trace etomidate in illegal E-cigarettes from authentic human hair: identification, quantification and multiple-factor analysis.

PURPOSE: The abusive consumption of illegal E-cigarettes containing etomidate (ET) can have a significant impact on public mental and physical well-being. The purpose of this study is to establish a rapid quantitative method using ultra-high-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) for the targeted screening of etomidate (ET) and its metabolite etomidate acid (ETA) in hair samples. METHODS: A 1 mL methanol solution containing the internal standard ET-d5 at a concentration of 50 pg/mg was added to 20 mg of hair and milled below 4 °C. After centrifugation, 5 µL of the supernatant was injected into a UHPLC-MS/MS system. RESULTS: The limit of detection (LOD) and limit of quantification (LOQ) were determined to be 1 pg/mg and 10 pg/mg, respectively, for ET, and 10 pg/mg and 25 pg/mg, respectively, for ETA. Calibration curves for all analytes showed good linearity (r > 0.997), indicating a reliable method. Accuracies were between 92.12% and 110.72%. Intra-day and inter-day precision for all analytes at all concentration levels were below 10.13%. Analyte recoveries ranged from 86.90% to 101.43%, with a matrix effect ranging from -18.55% to -14.93%. CONCLUSIONS: The validated method was successfully used to analyze 105 hair samples from suspected ET users. Of these, 50 tested positive for ET and 43 tested positive for ETA above the LOQ. This demonstrates the effectiveness of the developed UHPLC-MS/MS method in detecting ET and ETA in hair samples, which could be instrumental in addressing the issue of illegal E-cigarette abuse and its impact on public health.

Comprehensive spatial distribution profiling of bioactive emodin in mouse organs using mass spectrometry imaging.

Emodin is an important anthraquinone compound with good anti-inflammatory activity in Chinese traditional medicine rhubarb. Detailed spatial distribution information in bio-tissues plays an important role in revealing the pharmacodynamics, toxicology and chemical mechanism of emodin. Herein, the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry imaging (MALDI-TOF-MSI) analytical method was established to obtain information on the spatial and temporal changes of emodin in multiple mouse tissue sections (heart, liver, spleen, lung, kidney, and brain) after intraperitoneal injection of emodin in mice. The measurements were accomplished in the negative ion mode in the range of m/z 250-285 Da with a spatial resolution on 40 µm. It was found that emodin was predominantly distributed in the arteriolar vascular region of the heart, the capsule region of the spleen, and the cortex of the kidney. Moreover, the MALDI-TOF-MSI result implied that emodin might be distributed in the brain. These more detailed spatial distribution information provides the significant reference for investigating the action mechanism of emodin, which cannot be obtained from conventional LC-MS analysis. The distribution trend of emodin in the results of MALDI-TOF-MSI analysis agreed with the ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) results well, demonstrating the complementarity and reliability of the established MALDI-TOF-MSI method. Our work provided a label-free molecular imaging method to investigate the precise spatial distribution of emodin in various organs, which prove great potential in studying the effective substances and mechanism of rhubarb.

Clinical and Imaging Features of Pulmonary Nodular Lymphoid Hyperplasia.

PURPOSE: To investigate the clinical and radiographic features of PNLH and the relationship with pathologic features. MATERIALS AND METHODS: A total of 11 patients in whom PNLH was confirmed in our department were retrospectively studied. The clinical and radiographic features were extracted and analyzed, and we also discussed the relationship between radiologic and pathologic features. RESULTS: Of the 11 patients with PNLH, 5 were discovered incidentally, while 4 presented with chest symptoms. Laboratory tests showed no specificity and the lesions were located under the pleura with an adjacent pleural indentation. Most lesions were solid, with some showing signs of spiculation or spiculate protuberance. In some cases, hypodense areas and vocules were visible. The enhanced scan showed marked enhancement, but most had no lymph node enlargement, and there was no pleural effusion. CONCLUSIONS: The clinical manifestations of PNLH are nonspecific and the imaging features overlap with those of malignant lung tumors, and the diagnosis depends on pathologic examination.

Terphenyllin induces CASP3-dependent apoptosis and pyroptosis in A375 cells through upregulation of p53.

BACKGROUND: Melanoma, one of the most lethal forms of skin cancer, has the potential to develop in any area where melanocytes are present. Currently, postoperative recurrence due to the emergence of systemic drug resistance represents a significant challenge in the treatment of melanoma. In this study, terphenyllin (TER), a distinctive inhibitory impact on melanoma cells was identified from the natural p-terphenyl metabolite. This study aimed to elucidate the intrinsic mechanism of this inhibitory effect, which may facilitate the discovery of novel chemotherapeutic agents. METHODS: A transcriptome sequencing and metabolomic analysis of TER-treated A375 cells was conducted to identify potential pathways of action. The key proteins were knocked out and backfilled using CRISPR-Cas9 technology and molecular cloning. Subsequently, the results of cytosolic viability, LDH release, immunofluorescence and flow cytometry were employed to demonstrate the cell death status of the drug-treated cells. RESULTS: The p53 signalling pathway was markedly upregulated following TER treatment, leading to the activation of CASP3 via the intrinsic apoptotic pathway. The activated CASP3 initiated apoptosis, while simultaneously continuing to cleave the GSDME, thereby triggering pyroptosis. The knockout of p53, a key protein situated upstream of this pathway, resulted in a significant rescue of TER-induced cell death, as well as an alleviation of the decrease in cell viability. However, the knockout of key proteins situated downstream of the pathway (CASP3 and GSDME) did not result in a rescue of TER-induced cell death, but rather a transformation of the cells from apoptosis and pyroptosis. CONCLUSIONS: The induction of apoptosis and pyroptosis in A375 cells by TER is mediated via the p53-BAX/FAS-CASP3-GSDME signalling pathway. This lays the foundation for TER as a potential anti-melanoma drug in the future. It should be noted that CASP3 and GSDME in this pathway solely regulate the mode of cell death, rather than determine whether cell death occurs. This distinction may prove valuable in future studies of apoptosis and pyroptosis.

Comparison of effect and safety of phacoemulsification surgery performed by resident and attending physicians.

Aim: The objective of this study is to compare the effect and safety of phacoemulsification surgery performed by resident and attending physicians. Methods: This was a retrospective study. Eyes with cataract who underwent phacoemulsification surgery at the First Affiliated Hospital of Ningbo University between January 2021 and December 2023 were reviewed. All the patients were followed up for at least 12 months and were divided into two groups according to the surgery performer. SPSS was used to analyze data, considering p < 0.05 significant. Results: Overall, 316 patients with cataract in group 1 (surgery performed by resident physician, n = 181) and group 2 (surgery performed by attending physician, n = 135) were reviewed. There were no statistically significant differences in patient demographics variables and cataract grade between the groups. The resident surgeon used more cumulative dissipate energy (15.00 ± 7.25 vs. 10.83 ± 6.52, p < 0.001) and operation time (20.46 ± 5.69 vs. 12.59 ± 4.61 min, p < 0.001) to complete the surgery. Also, the ECL in group 1 was higher (14.87 ± 5.00 vs. 10.77 ± 4.46, p < 0.001). The eyes had significant visual improvement in both groups postoperatively (p < 0.05), but at the 12-month follow-up, eyes in group 2 had better best-corrected visual acuity [0.10 (0.00, 0.22) vs. 0.10 (0.10, 0.22) logMAR, p = 0.039]. Except for month 1, the intraocular pressure was no statistical difference in group 1 and group 2 (14.65 ± 2.52 vs. 15.30 ± 2.34 mmHg, p = 0.019). Cases in group 1 were more likely to undergo intraoperative and postoperative complications (37 vs. 14, p = 0.031), including cornea edema (p = 0.025), capsule tear (p = 0.044), and posterior capsular opacification (p = 0.027). Conclusion: The effect of phacoemulsification surgery performed by the resident physician is satisfying, but compared to the attending physician, the higher probability of complications should be paid more attention.

Mycobacterium marinum hand infection: a case report and literature review.

Mycobacterium marinum, a photochromogenic, slow-growing mycobacterium, thrives in both marine and freshwater environments. Optimal growth occurs between 25°C and 35°C, with survival becoming challenging above 37°C. Typically, M. marinum enters the body via skin abrasions, often leading to infections of the upper extremities. Diagnosis of M. marinum infection is frequently challenging and delayed due to the difficult pathogen identification. At present, a standardized treatment protocol has yet to be established. Presented herein is a case study detailing an infection of the right hand's middle finger caused by M. marinum. Notably, his occupation as a chef, handling fish and seafood post-injury, was a significant factor. Histological examination of the skin biopsy and positive acid-fast staining were consistent with a diagnosis of mycobacterial infection. Pathological examination confirmed a skin infection with infectious granuloma, and tissue section acid-fast staining revealed acid-fast bacill. Cultures on Columbia blood agar yielded rough, flattened, yellow-fleshy colonies after 10 days, which was identified as M. marinum through 16S rRNA sequencing. The patient responded well to a 3-month regimen of oral moxifloxacin (0.4 qd) and linezolid (0.6 qd), resulting in rash resolution and pain relief, with no recurrence observed for 1-year follow-up. This report presents the first documented acid-fast staining images of M. marinum tissue sections and colony morphology photographs, offering an in-depth view of M. marinum's morphological characteristics. It aims to enhance awareness of M. marinum infections, underscore the necessity for clinicians to delve into patient histories, and provide a review of the clinical manifestations, diagnostic techniques, therapeutic approaches, and pathogenic mechanisms associated with M. marinum.

Microvascular structural changes in esophageal squamous cell carcinoma pathology according to intrapapillary capillary loop types under magnifying endoscopy.

BACKGROUND: The intrapapillary capillary loop (IPCL) characteristics, visualized using magnifying endoscopy, are commonly assessed for preoperative evaluation of the infiltration depth of esophageal squamous cell carcinoma (ESCC). Japan Esophageal Society (JES) classification is the most widely used classification. Microvascular structural changes are evaluated by magnifying endoscopy for the presence or absence of each morphological factor: tortuosity, dilatation, irregular caliber, and different shapes. However, the pathological characteristics of IPCLs have not been thoroughly investigated, especially the microvascular structures corresponding to the deepest parts of the lesions' infiltration. AIM: To investigate differences in pathological microvascular structures of ESCC, which correspond to the deepest parts of the lesions' infiltration. METHODS: Patients with ESCC and precancerous lesions diagnosed at Peking University Third Hospital were enrolled between January 2019 and April 2023. Patients first underwent magnified endoscopic examination, followed by endoscopic submucosal dissection or surgical treatment. Pathological images were scanned using a three-dimensional slice scanner, and the pathological structural differences in different types, according to the JES classification, were analyzed using nonparametric tests and t-tests. RESULTS: The 35 lesions were divided into four groups according to the JES classification: A, B1, B2, and B3. Statistical analyses revealed significant differences (a P < 0.05) in the short and long calibers, area, location, and density between types A and B. Notably, there were no significant differences in these parameters between types B1 and B2 and between types B2 and B3 (P > 0.05). However, significant differences in the short calibers, long calibers, and area of IPCL were observed between types B1 and B3 (a P < 0.05); no significant differences were found in the density or location (P > 0.05). CONCLUSION: Pathological structures of IPCLs in the deepest infiltrating regions differ among various IPCL types classified by the JES classification under magnifying endoscopy, especially between the types A and B.

Long-term Autotrophic Growth and Solar-to-chemical Conversion in Shewanella Oneidensis MR-1 through Light-driven Electron Transfer.

Members of the genus Shewanella are known for their versatile electron accepting routes, which allow them to couple decomposition of organic matter to reduction of various terminal electron acceptors for heterotrophic growth in diverse environments. Here, we report autotrophic growth of Shewanella oneidensis MR-1 with photoelectrons provided by illuminated biogenic CdS nanoparticles. This hybrid system enables photosynthetic oscillatory acetate production from CO2 for over five months, far exceeding other inorganic-biological hybrid system that can only sustain for hours or days. Biochemical, electrochemical and transcriptomic analyses reveal that the efficient electron uptake of S. oneidensis MR-1 from illuminated CdS nanoparticles supplies sufficient energy to stimulate the previously overlooked reductive glycine pathway for CO2 fixation. The continuous solar-to-chemical conversion is achieved by photon induced electric recycling in sulfur species. Overall, our findings demonstrate that this mineral-assisted photosynthesis, as a widely existing and unique model of light energy conversion, could support the sustained photoautotrophic growth of non-photosynthetic microorganisms in nutrient-lean environments and mediate the reversal of coupled carbon and sulfur cycling, consequently resulting in previously unknown environmental effects. In addition, the hybrid system provides a sustainable and flexible platform to develop a variety of solar products for carbon neutrality.

Modulation of Kondo Behavior in a Two-Dimensional Epitaxial Bilayer Bi(111)/Fe3GeTe2 Moiré Heterostructure.

Artificial two-dimensional (2D) moiré superlattices provide a platform for generating exotic quantum matter or phenomena. Here, an epitaxial heterostructure composed of bilayer Bi(111) and an Fe3GeTe2 substrate with a zero-twist angle is acquired by molecular beam epitaxy. Scanning tunneling microscopy and spectroscopy studies reveal the spatially tailored Kondo resonance and interfacial magnetism within this moiré superlattice. Combined with first-principles calculations, it is found that the modulation effect of the moiré superlattice originates from the interfacial orbital hybridization between Bi and Fe atoms. Our work provides a tunable platform for strong electron correlation studies to explore 2D artificial heavy Fermion systems and interface magnetism.

Association between textbook outcome and long-term survival among patients undergoing curative-intent resection of gastric cancer.

BACKGROUND: A single metric does not sufficiently capture the multidimensional and complex perioperative nature of treatment for patients with gastric cancer. There is a newly developed composite indicator, called textbook outcome, that reflects the "ideal" surgical outcome. However, limited evidence exists for the long-term prognosis of textbook outcome in patients with gastric cancer. Thus, this study was aimed at assessing the association between textbook outcome and long-term oncologic prognosis after gastrectomy. METHODS: In total, 2,658 consecutive patients who underwent gastrectomy between January 2004 and December 2017 were included. The primary endpoint was 5-year conditional survival (if the patient survived the first 30 days after surgery). Textbook outcome was defined as retrieved ≥15 lymph nodes, pR0 resection, complete-potentially curative resection during operation, hospitalization ≤21 days, no reinterventions, no severe postoperative complications, no hospital readmission ≤30 days after discharge, no unplanned intensive care unit treatment, and no 30-day postoperative mortality. Multivariable analysis was performed to evaluate the adjusted predictors of textbook outcome. A Cox regression analysis was used to analyze the relationship between achieving textbook outcome parameters and long-term oncologic prognosis. RESULTS: A total of 1,770 (66.6%) of the 2,658 patients achieved all textbook outcome metrics in this study. The textbook outcome group displayed a greater 5-year conditional overall survival than the nontextbook outcome group (64.7% vs 40.2%, P < .001). The 5-year conditional disease-free survival of the patients with textbook outcomes was strongly superior to that of the patients without textbook outcomes (63.1% vs 37.6%, P < .001). Textbook outcome was independently associated with longer 5-year conditional overall survival and disease-free survival (hazard ratio 0.494 [0.439-0.557] and hazard ratio 0.487 [0.433-0.547], respectively). CONCLUSIONS: Attaining textbook outcome is strongly related to an improved long-term oncologic prognosis for patients with gastric cancer, underscoring the need for continued efforts to enhance surgical care quality.

Pilot Study of Intelligent Office Blood Pressure Measurement Model in Shanghai, China, 2022.

Introduction: An intelligent office blood pressure measurement (IOBPM) model for community-based hypertension management was piloted in Shanghai, China, to overcome the conventional blood pressure management (CBPM) model's deficiencies. Methods: We selected adults aged 35-89 years who were being treated and managed for hypertension in two community health centers for the IOBPM and CBPM models. The IOBPM model consisted of two or three consecutive blood pressure (BP) measurements using a pre-programmed and validated automatic device. The BP data for the CBPM model were obtained from the routine follow-up records of hypertensive patients and derived from the Shanghai Non-communicable Diseases Management Information System. Subjects in the IOBPM model were selected by a simple random sampling method, and propensity score matching was used to select a comparable control population from the CBPM model based on important covariables. The BP levels, end-digit preferences, frequency distribution, and BP control were compared between the two models. Results: We selected 2,909 patients for the IOBPM model and 5,744 for the CBPM model. The systolic BP in the CBPM model was 12.3 mmHg lower than in the IOBPM model. In the CBPM model, there were statistically significant end-digit preferences (P < 0.001), with zero being the most reported end-digit (23.3% for systolic BP and 27.7% for diastolic BP). There was no significant end-digit preference in the IOBPM model. Certain BP values below 140/90 mmHg in the CBPM model were more frequent, while the IOBPM model showed a normal distribution. The BP control in the CBPM model was significantly higher than the IOBPM model (P < 0.001). Conclusion: The IOBPM model appears to overcome the deficiencies of the CBPM model, leading to more accurate and reliable BP measurements.

[Clinical anatomy of the free latissimus dorsi myocutaneous flap and its application in the restoration of giant defects of the head and neck].

PURPOSE: To investigate the feasibility and effect of free latissimus dorsi myocutaneous flap in the reconstruction of giant head and neck defects. METHODS: Free latissimus dorsi myocutaneous flap on the cadaver was simulated dissected, and measured by Image-Pro Plus 6.0 to assess the feasibility of repairing giant head and neck defects. Between May 2011 and September 2022, seven patients with giant head and neck defects of different causes repaired with the latissimus dorsi myocutaneous flap were retrospectively analyzed. RESULTS: The diameter of the initiating thoracodorsal artery was (4.03±0.56) mm, and the mean lengths of the arteriolar and venous pedicles of the latissimus dorsi myocutaneous flaps obtained from human specimens were (85.5±10.5) mm and (104±4.2) mm, respectively. Among 7 patients, 5 cases had scalp defects, the remaining 2 cases had neck defects. There were no substantial postoperative problems in the donor site, and all seven latissimus dorsi myocutaneous flaps were successfully transplanted. CONCLUSIONS: For the treatment of considerable head and neck deformities, the latissimus dorsi myocutaneous flap is an optimal muscle flap due to its abundance of tissue, enough length of vascular pedicles, and sufficient venous drainage.

Bacterial infection-biased abundance of proteins in the skin mucus of obscure puffer (Takifugu Obscurus).

The skin mucus of fish is equipped with immunological and antimicrobial peptides that confer protection against invading pathogens. The skin mucus has been studied in fish however information regarding its immunological roles in bacterial infection is rare. This study highlighted the proteins and peptides in the skin mucus of Obscure puffer Takifugu obscurus that quantitatively altered against Aeromonas hydrophila infection. We infected the fish through bath immersion, intraperitonially, and treated with PBS (control) then compared the level of proteins in the skin mucus among the groups using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The Tandem Mass Tag (TMT) based quantification showed that 4896 proteins were Deferentially Quantified Proteins (DQPs), based on 19,751 unique peptides. Of which 170 were depleted (decreased in abundance) and 69 were abundant in comparison of Bath Treated (BT) vs Control (C) groups. Similarly, 76 DQPs were depleted and 70 were abundant in comparison of Treated (T) vs BT groups. Further, 126 DQPs were depleted, and 34 were abundant in comparison to T vs C groups. The DQPs we report were mostly immunological and were involved in unique biological functions and pathways. The interesting protein we report, where some of the proteins are for the first time in fish, shows the protein-rich structure of the mucus of fish, which may act as a biomarker to be targeted for bacterial disease therapy in fish and ultimately hint to the way of making resistance in fish against bacterial pathogens.

Formation mechanism and regulation analysis of trumpet leaf in Ginkgo biloba L.

Introduction: The research on plant leaf morphology is of great significance for understanding the development and evolution of plant organ morphology. As a relict plant, the G. biloba leaf morphology typically exhibits bifoliate and peltate forms. However, throughout its long evolutionary history, Ginkgo leaves have undergone diverse changes. Methods: This study focuses on the distinct "trumpet" leaves and normal fan-shaped leaves of G. biloba for analysis of their phenotypes, photosynthetic activity, anatomical observations, as well as transcriptomic and metabolomic analyses. Results: The results showed that trumpet-shaped G. biloba leaves have fewer cells, significant morphological differences between dorsal and abaxial epidermal cells, leading to a significantly lower net photosynthetic rate. Additionally, this study found that endogenous plant hormones such as GA, auxin, and JA as well as metabolites such as flavonoids and phenolic acids play roles in the formation of trumpet-shaped G. biloba leaves. Moreover, the experiments revealed the regulatory mechanisms of various key biological processes and gene expressions in the trumpet-shaped leaves of G. biloba. Discussion: Differences in the dorsal and abdominal cells of G. biloba leaves can cause the leaf to curl, thus reducing the overall photosynthetic efficiency of the leaves. However, the morphology of plant leaves is determined during the primordia leaf stage. In the early stages of leaf development, the shoot apical meristem (SAM) determines the developmental morphology of dicotyledonous plant leaves. This process involves the activity of multiple gene families and small RNAs. The establishment of leaf morphology is complexly regulated by various endogenous hormones, including the effect of auxin on cell walls. Additionally, changes in intracellular ion concentrations, such as fluctuations in Ca2+ concentration, also affect cell wall rigidity, thereby influencing leaf growth morphology.

Female-specific association between the APOE E4 allele and age at diagnosis of glaucoma in UK Biobank.

OBJECTIVE: To explore the impact of the apolipoprotein E (APOE) E4 allele in the gender-specific aging process in glaucoma by illustrating the interaction between risk factors, including the APOE E4 allele, gender and intraocular pressure (IOP), for age at diagnosis (AAD) of glaucoma. DESIGN: A cross-sectional study included UK Biobank participants with complete data (2006-2010) for analysis. Data were analyzed in December 2023. PARTICIPANTS: 2,236 glaucoma patients and 103,232 controls. METHODS: We evaluated multivariable-adjusted associations of AAD of glaucoma, APOE E4 allele (0: absence; 1: presence), and IOP using linear mixed model (LMM) analyses across groups stratified by AAD of mean age of menopause (50 years) and gender. MAIN OUTCOMES MEASURES: AAD of glaucoma, APOE E4 allele and IOP. RESULTS: Glaucoma patients were older and had a higher percentage of males and a higher mean IOP compared to controls (all P < 0.001). Further stratifying the glaucoma patients by AAD of 50 and gender, lower IOP (Model 1 adjusted by age, ßIOP=-0.096±0.041, P=0.019) and positive APOE E4 allele (Model 2 adjusted by age and IOP, ße4=1.093±0.488, P=0.026) were associated with an older AAD in females with an AAD < 50 years under univariate LMM. In multivariate LMM adjusted by age (Model 3), the effect size of both factors increased in the multivariate model as the beta-value increased. (ßIOP=-0.111±0.040, P=0.007; ße4=1.235±0.485, P=0.012) (Model 1 vs Model 3: P=0.011). In females with an AAD ≥50 years, only positive APOE E4 allele (adjusted by age and IOP, ße4=-1.121±0.412, P=0.007) was associated with a younger AAD. In males, only higher IOP was associated with an older AAD in those with an AAD ≥50 years (ßIOP=0.088±0.032, P=0.006). CONCLUSIONS: APOE E4 allele may initially delay and later accelerate the development of glaucoma in females around the transition period of 50 years, which is the mean age of menopause, and importantly, this is independent of IOP. Understanding the specific transition states and modifiable factors within each age phase is crucial for developing interventions or strategies that promote healthy aging.