Endolysosomal channel TMEM175 mediates antitoxin activity of DABMA.

DABMA is a chemical molecule optimized from the parent compound ABMA and exhibits broad-spectrum antipathogenic activity by modulating the host's endolysosomal and autophagic pathways. Both DABMA and ABMA inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a cellular assay, which further expands their anti-pathogen spectrum in vitro. However, their precise mechanism of action has not yet been resolved. TMEM175 is a newly characterized endolysosomal channel which plays an essential role in the homeostasis of endosomes and lysosomes as well as organelle fusion. Here, we show that DABMA increases the endosomal TMEM175 current through organelle patch clamping with an EC50 of 17.9 µm. Depletion of TMEM175 protein significantly decreases the antitoxin activity of DABMA and affects its action on acidic- and Rab7-positive endosomes as well as on endolysosomal trafficking. Thus, TMEM175 is necessary for DABMA's activity and may represent a druggable target for the development of anti-infective drugs. Moreover, DABMA, as an activator of the TMEM175 channel, may be useful for the in-depth characterization of the physiological and pathological roles of this endolysosomal channel.

Endoscopic polidocanol foam sclerobanding for the treatment of grade II-III internal hemorrhoids: A prospective, multi-center, randomized study.

BACKGROUND: Endoscopic rubber band ligation (ERBL) is a nonsurgical technique for the treatment of symptomatic internal hemorrhoids but is limited by recurrence and post-procedural pain. AIM: To evaluate satisfaction, long-term recurrence, and post-procedural pain in managing internal hemorrhoids using a combination of polidocanol foam sclerotherapy and ERBL. METHODS: This was a prospective, multicenter, randomized study. A total of 195 consecutive patients diagnosed with grade II-III internal hemorrhoids were enrolled from four tertiary hospitals and randomly divided into a cap-assisted endoscopic polidocanol foam sclerobanding (EFSB) or an ERBL group. All patients were followed-up for 12 months. Symptom-based severity and post-procedural pain were assessed using a hemorrhoid severity score (HSS) and a visual analog scale (VAS). Continuous variables were reported as medians and interquartile range. RESULTS: One hundred and ninety-five patients were enrolled, with 98 in the EFSB group. HSS was lower in the EFSB group than in the ERBL group at 8 weeks [4.0 (3.0-5.0) vs 5.0 (4.0-6.0), P = 0.003] and 12-month [2.0 (1.0-3.0) vs 3.0 (2.0-3.0), P < 0.001] of follow-up. The prolapse recurrence rate was lower in the EFSB group at 12 months (11.2% vs 21.6%, P = 0.038). Multiple linear regression analysis demonstrated that EFSB treatment [B = -0.915, 95% confidence interval (CI): -1.301 to -0.530, P = 0.001] and rubber band number (B = 0.843, 95%CI: 0.595-1.092, P < 0.001) were negatively and independently associated with the VAS score 24 hours post-procedure. The median VAS was lower in the EFSB group than in the ERBL [2.0 (1.0-3.0) vs 3.0 (2.0-4.0), P < 0.001]. CONCLUSION: Cap-assisted EFSB provided long-term satisfaction and effective relief from the recurrence of prolapse and pain 24 hours post-procedure.

Comparison of selective laser melting and stereolithography etching templates for guided endodontics.

Background: With the increasing application of guided endodontics to treat complex root canal treatment, the entire process of root canal treatment has become more precise, reducing damage to tooth structure and improving success rates. However, due to the limitations of the operating space, the use of guided endodontic templates in posterior root canal treatment is less common. This study aims to compare the accuracy and reliability of selective laser melting (SLM) and traditional stereolithography etching (SLA) guided endodontic templates for posterior root canals, providing better treatment strategies for posterior root canal treatment. Methods: The teeth were randomly assigned to either SLM or SLA group. Preoperative cone-beam computed tomography (CBCT) and a three-dimensional (3D) scanner were used to establish the 3D root canal system and the accurate occlusal models of the teeth. The virtual access to the canal access was designed using Mimics 19.0 and 3-Matic 11.0. The endodontic access was performed based on either SLM or SLA templates. The accuracy of endodontic preparation was measured in three-dimensions by calculating deviations from planned accesses. The template height and tooth substance loss rates in each group were measured. Results: SLM-guided templates have a low average deviation at the entry point and apical portion of the bur of total posterior teeth (including premolars and molars) and individual molars (P < 0.05). Moreover, there was a significant difference in angular deviations and height of template in total posterior teeth and individual molars (P < 0.05). The mean substance loss rate of the SLA group was slightly greater than that of the SLM group, but the difference was not statistically (P > 0.05). Conclusions: SLM-guided endodontics provides a more predictable and precise location of root canal orifice for the treatment of posterior teeth.

Hyperactivation of mTOR/eIF4E Signaling Pathway Promotes the Production of Tryptophan-To-Phenylalanine Substitutants in EBV-Positive Gastric Cancer.

Although messenger RNA translation is tightly regulated to preserve protein synthesis and cellular homeostasis, chronic exposure to interferon-γ (IFN-γ) in several cancers can lead to tryptophan (Trp) shortage via the indoleamine-2,3-dioxygenase (IDO)- kynurenine pathway and therefore promotes the production of aberrant peptides by ribosomal frameshifting and tryptophan-to-phenylalanine (W>F) codon reassignment events (substitutants) specifically at Trp codons. However, the effect of Trp depletion on the generation of aberrant peptides by ribosomal mistranslation in gastric cancer (GC) is still obscure. Here, it is shows that the abundant infiltrating lymphocytes in EBV-positive GC continuously secreted IFN-γ, upregulated IDO1 expression, leading to Trp shortage and the induction of W>F substitutants. Intriguingly, the production of W>F substitutants in EBV-positive GC is linked to antigen presentation and the activation of the mTOR/eIF4E signaling pathway. Inhibiting either the mTOR/eIF4E pathway or EIF4E expression counteracted the production and antigen presentation of W>F substitutants. Thus, the mTOR/eIF4E pathway exposed the vulnerability of gastric cancer by accelerating the production of aberrant peptides and boosting immune activation through W>F substitutant events. This work proposes that EBV-positive GC patients with mTOR/eIF4E hyperactivation may benefit from anti-tumor immunotherapy.

Overall and subgroup prevalence of self-reported asthma in US adults: a nationally representative cross-sectional study.

BACKGROUND: The purpose of this study is to determine the variations in the prevalence of self-reported asthma among the adult population in the United States of America (USA), analyzing demographic characteristics, physical indicators, living habits, and sarcopenia. METHODS: 10,566 participants from the 2009 to 2018 National Health and Nutrition Examination Survey (NHANES) of the USA who were 20 years of age or older and not pregnant were included in the study. RESULTS: The prevalence of patients with asthma varies by age, gender, and race. The weighted prevalence is 15.5%, estimated to represent 19.36 million people in the USA (95% CI, 14.5% to 16.6%). The prevalence of self-reported asthma decreases with age, with the highest prevalence among young adults aged 20-25 for both males and females. Females were also more susceptible to asthma compared to males. The increase in asthma prevalence attributed to smoking was most pronounced among African American and Caucasian participants (p < 0.05), while its effect on Mexican American and Asian participants was relatively minor. Notably, the prevalence of asthma was significantly higher in African American and Caucasian participants with sarcopenia compared to those without sarcopenia. CONCLUSIONS: The prevalence of asthma is associated to varying degrees with factors such as age, gender, smoking, and the presence of sarcopenia. The elevated prevalence of asthma among young people and females warrants attention. Intensifying efforts toward smoking cessation and the scientific management of sarcopenia could be instrumental in reducing the incidence of asthma.

Label-free electrochemical biosensor based on dual amplification of gold nanoparticles and polycaprolactones for CEA detection.

Carcinoembryonic Antigen (CEA), an acidic glycoprotein with human embryonic antigen properties, is found on the surface of cancer cells that have differentiated from endodermal cells. This paper presents a label-free electrochemical immunoassay for the dual amplification detection of CEA using gold nanoparticles loaded with polypyrrole polydopamine (Au/PPy-PDA) and polymerized polycaprolactone (Ng-PCL) prepared by ring-opening polymerization (ROP). First, the composite Au/PPy-PDA was adhered to the electrode surface. Then, gold nanoparticles form a Au-S bond with the sulfhydryl group in Apt1 to secure it on the electrode surface. Subsequently, the non-specific binding sites on the electrodes surface are closed by bovine serum albumin (BSA). Next, CEA is dropped onto the electrode surface, which is immobilized by antigen-antibody specific recognition, and the carboxyl-functionalized Apt2 forms a "sandwich structure" of antibody-antigen-antibody by specific recognition. Polymeric Ng-PCL is adhered to the electrode surface, leading to an increase in the electrochemical impedance signal, resulting in a complete chain of signal analysis. Finally, the response signal is detected by electrochemical impedance spectroscopy (EIS). Under optimal experimental conditions, the method has the advantages of high sensitivity and wide linear range (1 pg mL-1∼100 ng mL-1), and the lower limit of detection (LOD) is 0.234 pg mL-1. And it has the same high sensitivity, selectivity and interference resistance for the real samples detection. Thus, it provides a new way of thinking about biomedical and clinical diagnosis.

Comparison of different hydroxyapatite composites for bone tissue repair: In vitro and in vivo analyses.

Objectives: The material used for bone tissue repair needs to be simultaneously osteoconductive, osteoinductive, and osteogenic. To overcome this problem, researchers combine hydroxyapatite (HA) with natural materials to improve properties. This paper compares the effects of angiogenesis and osteogenesis with different composites through in vivo experiments and characterization analysis. Materials and Methods: Chitosan/nHA (CS/nHA) and sodium alginate/nHA (SA/nHA) microspheres were synthesized via reverse-phase emulsification crosslinking and analyzed using scanning electron microscopy (SEM), energy dispersion spectroscopy (EDS), and X-ray diffraction (XRD). Implanted into mouse thigh muscles, their angiogenic and osteogenic potentials were assessed after 8 and 12 weeks through various staining methods and immunohistochemistry. Results: The mean vascular density (MVD) of CS/nHA, CaP/nHA, and SA/nHA groups was (134.92±35.30) n/mm2, (159.09±22.14) n/mm2, (160.31±42.23) n/mm2 at 12 weeks, respectively. The MVD of the CaP/nHA and SA/nHA groups were significantly higher than that of the CS/nHA group. The collagen volume fractions (CVF) were 34.13%, 51.53%, and 54.96% in the CS/nHA, CaP/nHA, and SA/nHA groups, respectively. In addition, the positive expression area ratios of OPN and CD31 in the CaP/nHA and SA/nHA groups were also significantly higher than those in the CS/nHA group. Conclusion: The ability of SA/nHA composite microspheres in osteogenesis and angiogenesis is clearly superior to that of the CS/nHA group and is comparable to that of CaP/nHA, which has superior osteogenesis ability, indicating that SA/nHA composite microspheres have greater application prospects in bone tissue engineering.

Inositol 1,4,5-Trisphosphate Receptors Regulate Vascular Smooth Muscle Cell Proliferation and Neointima Formation in Mice.

BACKGROUND: Vascular smooth muscle cell (VSMC) proliferation is involved in many types of arterial diseases, including neointima hyperplasia, in which Ca2+ has been recognized as a key player. However, the physiological role of Ca2+ release via inositol 1,4,5-trisphosphate receptors (IP3Rs) from endoplasmic reticulum in regulating VSMC proliferation has not been well determined. METHODS AND RESULTS: Both in vitro cell culture models and in vivo mouse models were generated to investigate the role of IP3Rs in regulating VSMC proliferation. Expression of all 3 IP3R subtypes was increased in cultured VSMCs upon platelet-derived growth factor-BB and FBS stimulation as well as in the left carotid artery undergoing intimal thickening after vascular occlusion. Genetic ablation of all 3 IP3R subtypes abolished endoplasmic reticulum Ca2+ release in cultured VSMCs, significantly reduced cell proliferation induced by platelet-derived growth factor-BB and FBS stimulation, and also decreased cell migration of VSMCs. Furthermore, smooth muscle-specific deletion of all IP3R subtypes in adult mice dramatically attenuated neointima formation induced by left carotid artery ligation, accompanied by significant decreases in cell proliferation and matrix metalloproteinase-9 expression in injured vessels. Mechanistically, IP3R-mediated Ca2+ release may activate cAMP response element-binding protein, a key player in controlling VSMC proliferation, via Ca2+/calmodulin-dependent protein kinase II and Akt. Loss of IP3Rs suppressed cAMP response element-binding protein phosphorylation at Ser133 in both cultured VSMCs and injured vessels, whereas application of Ca2+ permeable ionophore, ionomycin, can reverse cAMP response element-binding protein phosphorylation in IP3R triple knockout VSMCs. CONCLUSIONS: Our results demonstrated an essential role of IP3R-mediated Ca2+ release from endoplasmic reticulum in regulating cAMP response element-binding protein activation, VSMC proliferation, and neointima formation in mouse arteries.

Interaction between CAFs and apoptotic cancer cells promotes OSCC proliferation via STING signaling.

BACKGROUND: Apoptosis can fuel oncogenesis by the education of surrounding stromal cells. However, the function of cancer-associated fibroblasts (CAFs), which interacted with apoptotic cancer cells, in oral squamous cell carcinoma (OSCC) progression is still unknown. OBJECTIVES: This study aimed to explore the prognostic value of apoptosis and the biological effects of CAFs, interacted with apoptotic cancer cells, on OSCC. METHODS: A total of 166 samples from OSCC patients were stained via TUNEL reaction to evaluate the correlation between apoptosis and clinical characteristics. Cell viability and proliferation were assessed through flow cytometry and CCK-8 assays, respectively. Levels of mRNA and protein were examined through qRT-PCR, western blot and immunofluorescence. RESULTS: Higher percentage of apoptotic cancer cells in OSCC positively correlated with more Ki67+ cells and predicted poor clinical outcomes. Conditioned medium from CAFs exposed to apoptotic cancer cells significantly facilitated cell proliferation. Co-culture CAFs with apoptotic cancer cells dampened the phosphorylation of STING/IRF3 signaling, as well as the production of type I interferon, which was required for the inhibition of OSCC cell proliferation. CONCLUSION: These results demonstrate the interplay between apoptotic cancer cells and CAFs promotes OSCC proliferation via STING signaling, identifying a potential therapy targeted CAFs surrounded with apoptotic cancer cells for OSCC.

Plant Leaf Functional Adaptions along Urban-Rural Gradients of Jinhua City.

Environmental changes induced by urbanization may significantly alter plant survival strategies, thereby introducing uncertainties in their ability to withstand extreme heat. This study, centered on Jinhua City, distinguished urban, suburban, and rural areas to represent the various intensities of urbanization. It examined the leaf function properties of evergreen and deciduous trees common in these regions, focusing on leaf and branch characteristics. Employing an analysis of variance (ANOVA), principal component analysis (PCA), and path analysis (PA) of the plant functional traits and the climatic factors of each region, this study assessed the impact of urbanization on plant survival strategies. By tracking changes in plant functional traits from June to August, it explored the capacity of plants to acclimate to urban-warming-related heat stress across different urbanization gradients. The findings revealed that leaf thickness (LT) and stomatal size (SS) initially decreased and then increased, whereas specific leaf area (SLA) and leaf tissue density (LTD) first rose and then declined, from rural to urban regions. From June to August, branch wood density (WD), chlorophyll (Chl) content, LTD, and leaf dry matter content (LDMC) increased, whereas SLA and leaf water content (LWC) diminished, in all regions. PCA suggested that there was no significant change in the resource allocation strategy of plants (p > 0.05), with drought tolerance significantly reduced in the suburbs on the gradient of urbanization (p < 0.05). During the summer, with high temperature, plants were predominantly biased towards slow-return, conservative strategies, particularly among evergreen species. Compared to precipitation, PA revealed a significant urban warming effect. During summer, temperature was the main factor influencing resource investment strategy and drought resistance, with a notably stronger impact on the former. The high temperature in summer promoted a conservative survival strategy in plants, and the urbanization effect increased their tolerance to high temperatures.

Single-cell transcriptome analysis of macrophage subpopulations contributing to chemotherapy resistance in ovarian cancer.

BACKGROUND: Ovarian cancer, a fatal gynecological malignancy, is primarily managed through surgery and chemotherapy. However, a significant challenge arises as patients frequently experience relapse due to chemotherapy resistance. This study delves into the complex functions and underlying mechanisms of macrophages in chemotherapy resistance in ovarian cancer. METHOD: The single-cell transcriptome sequencing data of ovarian cancer with or without chemotherapy were analyzed. Then, corresponding cell types were identified, and macrophages were extracted from all cells. Following the standardized single-cell analysis using the Seurat package, 15 distinct macrophage clusters were found and differentially expressed genes among them were analyzed. Moreover, their association with chemotherapy resistance was explored through cell proportions and gene expression. RESULT: In the single-cell transcriptomic analysis of ovarian cancer tissues before and after chemotherapy, the cellular proportion of CXCL5+ macrophages, THBS1+ macrophages, and MMP9+ macrophages were significantly increased following chemotherapy. Further investigation revealed that these macrophage subpopulations upregulated the expression of multiple pro-tumorigenic angiogenic or invasive factors, in addition to CXCL5, THBS1, and MMP9, including CTSL, CXCL1, and CCL18. Finally, pathway enrichment analysis revealed the significant activation of signaling pathways, such as NOD-like receptor, MAPK, and TNF in these macrophage subpopulations, which provides direction for studying the mechanism of these subpopulations. CONCLUSION: CXCL5+, THBS1+, and MMP9+ macrophage subpopulations exhibit an increased cellular prevalence post-chemotherapy and pro-tumorigenic molecular expression profiles, suggesting a close association with chemoresistance in ovarian cancer. These findings contribute to our understanding of the roles and mechanisms of macrophages in ovarian cancer chemoresistance, providing a theoretical basis and direction for the development of therapies targeting macrophages in overcoming ovarian cancer chemoresistance.

Harmine inhibits pulmonary fibrosis through regulating DNA damage repair-related genes and activation of TP53-Gadd45α pathway.

BACKGROUND: Harmine has many pharmacological activities and has been found to significantly inhibit the fibrosis of keloid fibroblasts. DNA damage repair (DDR) is essential to prevent fibrosis. This study aimed to investigate the effects of harmine on pulmonary fibrosis and its underlying mechanisms. METHODS: Bleomycin and TGF-ß1 were used to construct pulmonary fibrosis models in vivo and in vitro, then treated with harmine to explore harmine's effects in treating experimental pulmonary fibrosis and its related mechanisms. Then, RNA sequencing was applied to investigate further the crucial DDR-related genes and drug targets of harmine against pulmonary fibrosis. Finally, the expression levels of DDR-related genes were verified by real-time quantitative PCR (RT-qPCR) and western blot. RESULTS: Our in vivo experiments showed that harmine treatment could improve weight loss and lung function and reduce tissue fibrosis in mice with pulmonary fibrosis. The results confirmed that harmine could inhibit the viability and migration of TGF-ß1-induced MRC-5 cells, induce their apoptosis, and suppress the F-actin expression, suggesting that harmine could suppress the phenotypic transition from lung fibroblasts to lung myoblasts. In addition, RNA sequencing identified 1692 differential expressed genes (DEGs), and 10 DDR-related genes were screened as critical DDR-related genes. RT-qPCR and western blotting showed that harmine could down-regulate the expression of CHEK1, ERCC1, ERCC4, POLD1, RAD51, RPA1, TOP1, and TP53, while up-regulate FEN1, H2AX and GADD45α expression. CONCLUSIONS: Harmine may inhibit pulmonary fibrosis by regulating DDR-related genes and activating the TP53-Gadd45α pathway.

Influence of ABC stroke score on late recurrence of paroxysmal atrial fibrillation following radiofrequency catheter ablation.

BACKGROUND: In this study we investigated the impact of ABC stroke score on the recurrence of paroxysmal atrial fibrillation (PAF) following radiofrequency catheter ablation (RFCA). METHODS: A total of 132 patients with PAF who underwent RFCA from October 2018 to September 2019 were included in this study. During the first phase of this study the patients were categorized into two groups based on late recurrence of atrial fibrillation after RFCA. In the second phase, the patients were further divided into two groups based on whether their ABC stroke score was ≥ 6.5. RESULT: The univariate analysis indicated that the risk factors for late recurrence of PAF included early recurrence, ABC stroke score, CHA2DS2-VASc score, and NT-proBNP (P < 0.05). Cox multivariate regression analysis revealed that ABC stroke score (P = 0.006) and early recurrence (P = 0.000) were independent predictors of late recurrence, and ABC stroke score ≥ 6.5 was a risk for predicting recurrence of PAF after RFCA with a sensitivity of 66.7% and specificity of 65.7%. After the completion of the 1:1 matching, the univariate Cox analysis indicated that an elevated score of ABC stroke (≥ 6.5) was an independent predictor of late recurrence of PAF (HR = 2.687, 95% CI: 1.036-6.971, P = 0.042). However, using an ABC stroke score cut off at 6.4 predicted the recurrence of atrial tachyarrhythmia with 85% sensitivity and 58.5% specificity. CONCLUSION: An ABC stroke score ≥ 6.4 is a predictor for late recurrence of PAF after RFCA.

[The Identification Idea of Antibodies Against Ku and Other High-Frequency Antigens].

OBJECTIVE: This study was aimed to provide ideas for identifying the antibodies to high-frequency antigens by analyzing a female case of high-frequency antigen antibody (anti-Ku) using serological and sequencing method. METHODS: The methods for identification of blood group, erythrocyte antigen, screening and identification of antibody were used to detect the blood type and antibody in the proband. The proband's serum and reagent screening cells treated with Sulfhydryl reagent were applied to judge the type and characteristics of this antibodies when reacted with the regaent screening cells or proband's serum respectively. Gene sequencing was used to determine the genotype of the proband's blood group. RESULTS: The proband's red blood cells were determined as O type RhD positive, whose serum showed strong positive reaction to antibody-screening cells and antibody identification cells with the same intensity in saline and IAT medium, however, the self-cells showed negative effect. The Direct Antihuman Globulin of proband's red blood cells also showed weak positive reaction, and the other blood types were CcEe, Jk(a+b-), P1-, Le(a-b -), Lu (a-b +), K-, k-, Kp(a-b-). Serum of the proband treated with 2-ME still react with three groups of screening cells in IAT medium. The reaction intensity of proband's serum was also unchanged with the cells modified with papain and bromelain, but showed negative effect when the cells were treated with sulfhydryl agents including DTT and 2-ME. Gene sequencing revealed that the KEL genotype of the patient was KEL*02N.24 . This patient had a rare K0 phenotype. CONCLUSION: The rare Kell-null blood group (also known as K0) were identified by serological and molecular tests in the proband who produced both IgG and IgM type of antibody to high-frequency antigen (anti-Ku). These two methods are of great significance in the identification of this rare blood group as well as the antibody to high frequency antigen.

Correction: Preventing lead leakage in perovskite solar cells and modules with a low-cost and stable chemisorption coating.

Correction for 'Preventing lead leakage in perovskite solar cells and modules with a low-cost and stable chemisorption coating' by Zongxu Zhang et al., Mater. Horiz., 2024, 11, 2449-2456, https://doi.org/10.1039/D4MH00033A.

Simultaneous Circular Dichroism and Wavefront Manipulation with Generalized Pancharatnam-Berry Phase Metasurfaces.

Simultaneous circular dichroism and wavefront manipulation have gained considerable attention in various applications, such as chiroptical spectroscopy, chiral imaging, sorting and detection of enantiomers, and quantum optics, which can improve the miniaturization and integration of the optical system. Typically, structures with n-fold rotational symmetry (n ≥ 3) are used to improve circular dichroism, as they induce stronger interactions between the electric and magnetic fields. However, manipulating the wavefront with these structures remains challenging because they are commonly considered isotropic and lack a geometric phase response in linear optics. Here, we propose and experimentally demonstrate an approach to achieve simultaneous circular dichroism (with a maximum value of ∼0.62) and wavefront manipulation using a plasmonic metasurface made up of C3 Archimedes spiral nanostructures. The circular dichroism arises from the magnetic dipole-dipole resonance and strong interactions between adjacent meta-atoms. As a proof of concept, two metadevices are fabricated and characterized in the near-infrared regime. This configuration possesses the potential for future applications in photodetection, chiroptical spectroscopy, and the customization of linear and nonlinear optical responses.

Adventitious embryonic causal gene FhRWP regulates multiple developmental phenotypes in citrus reproduction.

Citrus is a model plant for studying adventitious embryos, a form of asexual reproduction controlled by a single dominant gene, RWP. This gene has been identified as the causal gene for nucellar embryogenesis, but its function has not yet been fully understood. In this study, we used the fast-growing Fortunella hindsii as a system to explore chromatin accessibility during the nucellar embryony initiation, emphasizing elevated chromatin accessibility in polyembryonic (PO) genotypes compared to monoembryonic ones (MO). Notably, a higher level of accessible chromatin was observed in one allele of the promoter region of FhRWP, consistent with increased expression of the allele carrying the causal structural variant. By independently performing RNAi and gene editing experiments on PO genotypes, we found the downregulation of FhRWP expression could reduce the number of nucellar embryos, while its knockout resulted in abnormal axillary bud development. In overexpression experiments, FhRWP was identified as having the unique capability of inducing the embryogenic callus formation in MO stem segments, possibly through the regulation of the WUS-CLV signaling network and the ABA and cytokinin pathway, marking the inaugural demonstration of FhRWP's potential to reignite somatic cells' embryogenic fate. This study reveals the pleiotropic function of RWP in citrus and constructs a regulatory network during adventitious embryo formation, providing a new tool for bioengineering applications in plant regeneration.

Effect of different ulnar osteotomies on loading of the distal radioulnar joint: a finite element analysis.

BACKGROUND: Ulnar impingement syndrome is a prevalent source of ulnar carpal pain; however, there is ongoing debate regarding the specific location of shortening, the method of osteotomy, the extent of shortening, and the resulting biomechanical alterations. METHOD: To investigate the biomechanical changes in the distal radioulnar joint (DRUJ) resulting from different osteotomy methods, a cadaveric specimen was dissected, and the presence of a stable DRUJ structure was confirmed. Subsequently, three-dimensional data of the specimen were obtained using a CT scan, and finite element analysis was conducted after additional processing. RESULTS: The DRUJ stress did not change significantly at the metaphyseal osteotomy of 2-3 mm but increased significantly when the osteotomy length reached 5 mm. When the osteotomy was performed at the diaphysis, the DRUJ stress increased with the osteotomy length, and the increase was greater than that of metaphyseal osteotomy. Stress on the DRUJ significantly increases when the position is changed to pronation dorsi-extension. Similarly, the increase in stress in diaphyseal osteotomy was greater than that in metaphyseal osteotomy. When the model was subjected to a longitudinal load of 100 N, neither osteotomy showed a significant change in DRUJ stress at the neutral position. However, the 100 N load significantly increased stress on the DRUJ when the position was changed to pronation dorsi-extension, and the diaphyseal osteotomy significantly increased stress on the DRUJ. CONCLUSIONS: For patients with distal oblique bundle, metaphyseal osteotomy result in a lower increase in intra-articular pressure in the DRUJ compared to diaphyseal osteotomy. However, it is crucial to note that regardless of the specific type of osteotomy employed, it is advisable to avoid a shortening length exceeding 5 mm.