Delayed diagnosis in inflammatory bowel disease: Time to consider solutions.

In this editorial, we discuss a recently published manuscript by Blüthner et al in the World Journal of Gastroenterology, with a specific focus on the delayed diagnosis of inflammatory bowel disease (IBD). IBD, which includes Crohn's disease and ulcerative colitis, is a chronic intestinal disorder. A time lag may exist between the onset of inflammation and the appearance of signs and symptoms, potentially leading to an incorrect or delayed diagnosis, a situation referred to as the delayed diagnosis of IBD. Early diagnosis is crucial for effective patient treatment and prognosis, yet delayed diagnosis remains common. The reasons for delayed diagnosis of IBD are numerous and not yet fully understood. One key factor is the nonspecific nature of IBD symptoms, which can easily be mistaken for other conditions. Additionally, the lack of specific diagnostic methods for IBD contributes to these delays. Delayed diagnosis of IBD can result in numerous adverse consequences, including increased intestinal damage, fibrosis, a higher risk of colorectal cancer, and a decrease in the quality of life of the patient. Therefore, it is essential to diagnose IBD promptly by raising physician awareness, enhancing patient education, and developing new diagnostic methods.

Circulating fatty acids and risk of severe non-alcoholic fatty liver disease in the UK biobank: a prospective cohort of 116 223 individuals.

Fatty acid (FA) metabolism plays an important role in the development of nonalcoholic fatty liver disease (NAFLD). However, data on the relationship between circulating FAs and NAFLD risk are limited. This study aims to assess the associations between specific circulating FAs and severe NAFLD risk among the general population. Overall 116 223 participants without NAFLD and other liver diseases from the UK Biobank were enrolled between 2006 and 2010 and were followed up until the end of 2021. Plasma concentrations of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) were analyzed using an NMR-based biomarker profiling platform. Hazard ratios (HRs) and 95% confidence intervals (CIs) of NAFLD risk were estimated using Cox proportional-hazard models adjusted for other potential confounders. During a mean follow-up of 12.3 years, we documented 1394 cases of severe NAFLD. After multivariate adjustment, plasma SFAs and MUFAs were associated with a higher risk of severe NAFLD, whereas plasma n-3 PUFAs, n-6 PUFAs, and linoleic acid (LA) were associated with a lower risk. As compared with the lowest quartile, HRs (95% CIs) of severe NAFLD risk in the highest quartiles were 1.85 (1.45-2.36) for SFAs, 1.74 (1.23-2.44) for MUFAs, 0.79 (0.65-0.97) for n-3 PUFAs, 0.68 (0.48-0.96) for n-6 PUFAs, and 0.73 (0.54-0.99) for LA. The significant relationships were mainly mediated by serum TG for SFAs, HDL-C for MUFAs and n-6 PUFAs, and C-reactive protein for n-3 PUFAs. Plasma SFAs were associated with a more pronounced increase in the risk of severe NAFLD among participants with fewer SFA-associated alleles (P interaction = 0.032). Dietary recommendations for reducing plasma SFAs and MUFAs while increasing n-3 and n-6 PUFAs may be protective for severe NAFLD, which could be mediated by lipid metabolism and inflammation.

Self-inspired learning for denoising live-cell super-resolution microscopy.

Every collected photon is precious in live-cell super-resolution (SR) microscopy. Here, we describe a data-efficient, deep learning-based denoising solution to improve diverse SR imaging modalities. The method, SN2N, is a Self-inspired Noise2Noise module with self-supervised data generation and self-constrained learning process. SN2N is fully competitive with supervised learning methods and circumvents the need for large training set and clean ground truth, requiring only a single noisy frame for training. We show that SN2N improves photon efficiency by one-to-two orders of magnitude and is compatible with multiple imaging modalities for volumetric, multicolor, time-lapse SR microscopy. We further integrated SN2N into different SR reconstruction algorithms to effectively mitigate image artifacts. We anticipate SN2N will enable improved live-SR imaging and inspire further advances.

Zotarolimus alleviates post-trabeculectomy fibrosis via dual functions of anti-inflammation and regulating AMPK/mTOR axis.

OBJECTIVE: Postoperative scar formation is the primary cause of uncontrolled intraocular pressure following trabeculectomy failure. This study aimed to evaluate the efficacy of zotarolimus as an adjuvant anti-scarring agent in the experimental trabeculectomy. METHODS: We performed differential gene and Gene Ontology enrichment analysis on rabbit follicular transcriptome sequencing data (GSE156781). New Zealand white Rabbits were randomly assigned into three groups: Surgery only, Surgery with mitomycin-C treatment, Surgery with zotarolimus treatment. Rabbits were euthanized 3 days or 28 days post-trabeculectomy. Pathological sections were analyzed using immunohistochemistry, immunofluorescence, and Masson staining. In vitro, primary human tenon's capsule fibroblasts (HTFs) were stimulated by transforming growth factor-ß1 (TGF-ß1) and treated with either mitomycin-C or zotarolimus. Cell proliferation and migration were evaluated using cell counting kit-8, cell cycle, and scratch assays. Mitochondrial membrane potential was detected with the JC-1 probe, and reactive oxygen species were detected using the DCFH-DA probe. RNA and protein expressions were quantified using RT-qPCR and immunofluorescence. RESULTS: Transcriptome sequencing analysis revealed the involvement of complex immune factors and metabolic disorders in trabeculectomy outcomes. Zotarolimus effectively inhibited fibrosis, reduced proinflammatory factor release and immune cell infiltration, and improved the surgical outcomes of trabeculectomy. In TGF-ß1-induced HTFs, zotarolimus reduced fibrosis, proliferation, and migration without cytotoxicity via the dual regulation of the TGF-ß1/Smad2/3 and AMPK/AKT/mTOR pathways. CONCLUSION: Our study demonstrates that zotarolimus mitigates fibrosis by reducing immune infiltration and correcting metabolic imbalances, offering a potential treatment for improving trabeculectomy surgical outcomes.

Effects of changing spatial scale on debris-flow hazard assessment: A case study in the Dadu River basin, China.

Debris flows are a prevalent mountain hazard that poses severe risks to human life and property. Debris-flow hazard assessments at the regional scale are vital for risk management, which establish spatial associations between debris flows and their influencing factors based on specific evaluation units. Different spatial scales of evaluation units can influence the spatial attributes and associations obtained by statistics, and further affect the accuracy of hazard assessments. However, there is limited consensus regarding the optimal spatial scale of evaluation units for debris-flow hazard assessment. To address this issue, six different scales of grid cells and forty influencing factors related to topography, material sources, hydrology, and human activities are analyzed by the geographical detector model to assess the debris-flow hazards in the Dadu River basin, China. The results reveal that over 92 % of debris-flow points fall within hazardous zones across all spatial scales, confirming the effectiveness of the assessment model. Topography, particularly local gully topography, dominates the debris-flow occurrence in the study area, while human activities also significantly contribute. As the spatial scale of evaluation units increases, the explanatory power of the influencing factors improves, with the 90 % quantile ranging from 0.23 to 0.46. This result suggests that larger spatial scales weaken the spatial characteristics of the factors. The finer and more informative the factors are, the more sensitive to spatial scale effects. The 10 km × 10 km is identified as the optimal spatial scale, which effectively preserves the local spatial characteristics while avoiding information loss or overload. These findings provide valuable insights for enhancing the accuracy of hazard assessments and improving the efficiency of risk management.

Retrocorneal membrane interception enhanced penetrating canaloplasty for patients with open angle glaucoma secondary to ICE syndrome.

INTRODUCTION: To assess the efficacy and safety of retrocorneal membrane interception (RMI)-enhanced penetrating canaloplasty in glaucoma secondary to iridocorneal endothelial syndrome (GS-ICE) with open angle or small peripheral anterior synechiae (PAS). METHODS: A series of 13 patients (13 eyes) with GS-ICE and uncontrolled intraocular pressure (IOP) underwent RMI-enhanced penetrating canaloplasty from March 2019 to October 2020. The patients were followed up at one week, 1 month, 3 months, 6 months, and 12 months, postoperatively. The main outcome measure was surgical success, which was defined as an IOP ≤ 18 mmHg or ≤ 21 mmHg, with glaucoma medications (qualified success), or without glaucoma medications (complete success). Secondary outcome measures were IOP, medication usage, and surgical complications. RESULTS: Among the 13 GS-ICE eyes, 12 (92%) achieved qualified success and 10 (77%) achieved complete success at 12 months postoperatively. The mean IOP decreased from 36.41 ± 8.92 mmHg on 3.0 (IQR 0.5) medications before surgery to 17.09 ± 7.71 mmHg (p = 0.0004) on 0.0 (IQR 0.5) medications (p = 0.0004) at 12 months after surgery. Transient hypotony (38%) and hyphema (38%) were the most common complications. CONCLUSIONS: RMI-enhanced penetrating canaloplasty appears effective and safe in treating GS-ICE with open angle or small PAS up to one year of follow up.

DJ-1 regulates mitochondrial function and promotes retinal ganglion cell survival under high glucose-induced oxidative stress.

Purpose: This study aimed to investigate the antioxidative and neuroprotective effects of DJ-1 in mitigating retinal ganglion cell (RGC) damage induced by high glucose (HG). Methods: A diabetic mouse model and an HG-induced R28 cell model were employed for loss- and gain-of-function experiments. The expression levels of apoptosis and oxidative stress-related factors, including Bax, Bcl-2, caspase3, Catalase, MnSOD, GCLC, Cyto c, and GPx-1/2, were assessed in both animal and cell models using Western blotting. Retinal structure and function were evaluated through HE staining, electroretinogram, and RGC counting. Mitochondrial function and apoptosis were determined using JC-1 and TUNEL staining, and reactive oxygen species (ROS) measurement. Results: In the mouse model, hyperglycemia resulted in reduced retinal DJ-1 expression, retinal structural and functional damage, disrupted redox protein profiles, and mitochondrial dysfunction. Elevated glucose levels induced mitochondrial impairment, ROS generation, abnormal protein expression, and apoptosis in R28 cells. Augmenting DJ-1 expression demonstrated a restoration of mitochondrial homeostasis and alleviated diabetes-induced morphological and functional impairments both in vivo and in vitro. Conclusion: This study provides novel insights into the regulatory role of DJ-1 in mitochondrial dynamics, suggesting a potential avenue for enhancing RGC survival in diabetic retinopathy.

Fueling the fight against cancer: Exploring the impact of branched-chain amino acid catalyzation on cancer and cancer immune microenvironment.

Metabolism of Branched-chain amino acids (BCAAs) is essential for the nutrient necessities in mammals. Catalytic enzymes serve to direct the whole-body BCAAs oxidation which involve in the development of various metabolic disorders. The reprogrammed metabolic elements are also responsible for malignant oncogenic processes, and favor the formation of distinctive immunosuppressive microenvironment surrounding different cancers. The impotent immune surveillance related to BCAAs dysfunction is a novel topic to investigate. Here we focus on the BCAA catalysts that contribute to metabolic changes and dysregulated immune reactions in cancer progression. We summarize the current knowledge of BCAA catalyzation, highlighting the interesting roles of BCAA metabolism in the treatment of cancers.

Endophytic Bacillus velezensis XS142 is an efficient antagonist for Verticillium wilt of potato.

Potato Verticillium wilt (PVW) caused by Verticillium dahliae is a vascular disease, that seriously affects potato (Solanum tuberosum L.) yield and quality worldwide. V. dahliae occupies the vascular bundle and therefore it cannot efficiently be treated with fungicides. Further, the application of these pesticides causes serious environmental problems. Therefore, it is of great importance to find environmentally friendly biological control methods. In this study, bacterial strains were isolated from agricultural lands on which potato had been cultured for 5 years. Five strains with a broad-spectrum antagonistic activity were selected. Among these five strains, Bacillus velezensis XS142 showed the highest antagonistic activity. To study the mechanism of XS142, by which this strain might confer tolerance to V. dahliae in potato, the genome of strain XS142 was sequenced. This showed that its genome has a high level of sequence identity with the model strain B. velezensis FZB42 as the OrthoANI (Average Nucleotide Identity by Orthology) value is 98%. The fungal suppressing mechanisms of this model strain are well studied. Based on the genome comparison it can be predicted that XS142 has the potential to suppress the growth of V. dahliae by production of bacillomycin D, fengycin, and chitinase. Further, the transcriptomes of potatoes treated with XS142 were analyzed and this showed that XS142 does not induce ISR, but the expression of genes encoding peptides with antifungal activity. Here we showed that XS142 is an endophyte. Further, it is isolated from a field where potato had been cultured for several years. These properties give it a high potential to be used, in the future, as a biocontrol agent of PVW in agriculture.

Identification of SPP1+ macrophages in promoting cancer stemness via vitronectin and CCL15 signals crosstalk in liver cancer.

Macrophages play a multifaceted role in cancer biology, with both pro-tumorigenic and anti-tumorigenic functions. Understanding the mechanisms underlying macrophage involvement in cancer progression is essential for the development of therapeutic strategies. Our study analyzed single-cell RNA sequencing data from 12 patients with liver cancer and identified a subpopulation of macrophages characterized by elevated expression of SPP1, which correlates with poor prognosis in liver cancer patients. These SPP1+ macrophages induce upregulation of tumor stemness through a vitronectin (VTN)-dependent paracrine mechanism. Mechanistically, VTN derived from SPP1+ macrophages promote integrin αvß5/adenosine 5'-monophosphate-activated protein kinase (AMPK)/Yes-associated protein 1 (YAP1)/SYR-box transcription factor 4 (SOX4) signaling, mediating liver tumor stemness and progression. Conversely, CCL15 produced by liver cancer cells drives polarization of M0 macrophages toward an SPP1+ macrophage phenotype, establishing a positive feedback loop of macrophage-tumor stemness. Furthermore, the presence of SPP1+ macrophages confers chemoresistance in liver cancer, and inhibition of the macrophage-tumor feedback loop through targeting integrin αvß5/YAP1 signaling sensitizes liver cancer cells to chemotherapy. Our study highlights the crucial role of SPP1+ macrophages in liver cancer progression, providing novel insights for clinical liver cancer therapy.

Multieffect Preoxidation Strategy to Convert Bituminous Coal into Hard Carbon for Enhancing Sodium Storage Performance.

Preoxidation is an effective strategy to inhibit the graphitization of coals during carbonization. However, the single effect of the traditional preoxidation strategy could barely increase surface-active sites, hindering further enhancement of sodium storage. Herein, a multieffect preoxidation strategy was proposed to suppress structural rearrangement and create abundant surface-active sites. Mg(NO3)2·6H2O helps to introduce oxygen-containing functional groups into bituminous coal at 450 °C, which acted as a cross-linking agent to inhibit the rearrangement of carbon layers and promote structural cross-linking during the subsequent thermal carbonization process. Besides, the residue solid decomposition product MgO would react with carbon to create surface-active sites. The obtained coal-based hard carbon contained more pseudographitic domains and sodium storage active sites. The optimized sample could deliver an excellent capacity of 287.1 mAh g-1 at 20 mA g-1, as well as remarkable cycling stability of capacity retention of 96.1% after 200 cycles at 50 mA g-1, and notable capacity retention of 88.9% after 1000 cycles at 300 mA g-1. This work provides an effective and practical strategy to convert low-cost bituminous coal into advanced hard carbon anodes for sodium-ion batteries (SIBs).

Analysis of the Mitochondrial COI Gene and Genetic Diversity of Endangered Goose Breeds.

The mitochondrial cytochrome c oxidase subunit I (COI) genes of six endangered goose breeds (Xupu, Yangjiang, Yan, Wuzong, Baizi, and Lingxian) were sequenced and compared to assess the genetic diversity of endangered goose breeds. By constructing phylogenetic trees and evolutionary maps of genetic relationships, the affinities and degrees of genetic variations among the six different breeds were revealed. A total of 92 polymorphic sites were detected in the 741 bp sequence of the mtDNA COI gene after shear correction, and the GC content of the processed sequence (51.11%) was higher than that of the AT content (48.89%). The polymorphic loci within the populations of five of the six breeds (Xupu, Yangjiang, Yan, Baizi, and Lingxian) were more than 10, the haplotype diversity > 0.5, and the nucleotide diversity (Pi) > 0.005, with the Baizi geese being the exception. A total of 35 haplotypes were detected based on nucleotide variation among sequences, and the goose breed haplotypes showed a central star-shaped dispersion; the FST values were -0.03781 to 0.02645, The greatest genetic differentiation (FST = 0.02645) was observed in Yan and Wuzong breeds. The most frequent genetic exchange (Nm > 15.00) was between the Wuzong and Yangjiang geese. An analysis of molecular variance showed that the population genetic variation mainly came from within the population; the base mismatch differential distribution analysis of the goose breeds and the Tajima's D and Fu's Fs neutral detection of the historical occurrence dynamics of their populations were negative (p > 0.10). The distribution curve of the base mismatches showed a multimodal peak, which indicated that the population tended to be stabilised. These results provide important genetic information for the conservation and management of endangered goose breeds and a scientific basis for the development of effective conservation strategies.

Intercepting Dendrite Growth With a Heterogeneous Solid Electrolyte for Long-Life All-Solid-State Lithium Metal Batteries.

The application of lithium metal anode in all-solid-state batteries has the potential to achieve both high energy density and safety performance. However, the presence of serious dendrite issues hinders this potential. Here, the ion transport pathways and orientation of dendrite growth are regulated by utilizing the differences of ionic conductivity in heterogeneous electrolytes. The in situ formed Li-Ge alloy phases from the spontaneous reaction between Li10GeP2S12 and the attracted dendrites greatly enhance the ability to resist dendrite growth. As an outcome, the heterogeneous electrolyte achieves a high critical current density of 2.1 mA cm-2 and long-term stable symmetrical battery operation (0.3 mA cm-2 for 17 000 h and 1.0 mA cm-2 for 2000 h). Besides, due to the superior interfacial stability and low interface impedance between the heterogeneous electrolyte and lithium anode, the Li||LiNi0.8Co0.1Mn0.1O2 full battery exhibits great cycling stability (80.5% after 500 cycles at 1.0 mA cm-2) and rate performance (125.4 mAh g at 2.0 mA cm-2). This work provides a unique strategy of interface regulation via heterogeneous electrolytes design, offering insights into the development of state-of the-art all-solid-state batteries.

Cutting-Based Manufacturing and Surface Wettability of Microtextures on Pure Titanium.

Pure titanium is a preferred material for medical applications due to its outstanding properties, and the fabrication of its surface microtexture proves to be an effective method for further improving its surface-related functional properties, albeit imposing high demands on the processing accuracy of surface microtexture. Currently, we investigate the fabrication of precise microtextures on pure titanium surfaces with different grid depths using precision-cutting methods, as well as assess its impact on surface wettability through a combination of experiments and finite element simulations. Specifically, a finite element model is established for pure titanium precision cutting, which can predict the surface formation behavior during the cutting process and further reveal its dependence on cutting parameters. Based on this, precision-cutting experiments were performed to explore the effect of cutting parameters on the morphology of microtextured pure titanium with which optimized cutting parameters for high-precision microtextures and uniform feature size were obtained. Subsequent surface wettability measurement experiments demonstrated from a macroscopic perspective that the increase in the grid depth of the microtexture increases the surface roughness, thereby enhancing the hydrophilicity. Corresponding fluid-solid coupling finite-element simulation is carried out to demonstrate from a microscopic perspective that the increase in the grid depth of the microtexture decreases the cohesive force inside the droplet, thereby enhancing the hydrophilicity.

A New Technique of Sterile Polyethylene Instrument Cover as Temporary Corneal Patch to Reconstruct Anterior Chamber in Penetrating Keratoplasty Combined with Intraocular Surgery.

PURPOSE: Complications such as explosive choroidal hemorrhage, residual cortex, and capsule rupture often occur during intraocular surgery combined with penetrating keratoplasty (PKP) due to poor maintenance of the anterior chamber. To address these challenges, we have innovatively utilized a sterile polyethylene instrument cover to temporarily reconstruct the anterior chamber. METHODS: In this report, we describe a technique where a 'temporary corneal patch' was created from a sterile instrument cover, using a trephine to ensure a diameter approximately 1-2 mm wider than the corneal bed or perforation. This patch was then sutured into the host corneal bed or the perforation with 10-0 nylon sutures during intraocular surgery combined with PKP. Each case was evaluated for surgical efficacy and complications. RESULTS: We successfully applied this technique in three cases of combined corneal transplantation surgery. In two cases, PKP, phacoemulsification, and intraocular lens implantation were successfully performed. In the third case, PKP, vitrectomy, and other intraocular procedures were performed. No intraoperative or postoperative complications were observed. CONCLUSION: The use of a sterile polyethylene material as a temporary corneal patch for anterior chamber reconstruction represents a safe, effective, and cost-efficient approach for intraocular surgery combined with PKP or posterior segment surgery as a keratoprosthesis.

Attachment Style Modifies the Effect of Spousal Support on Postpartum Depression in Women.

Objective: This study aims to examine the impact of spousal support on postpartum depression in women with different attachment styles and assessing if attachment style influences this effect. Methods: From March to May 2022, 96 couples with late-stage pregnant women were randomly selected from tertiary maternity hospitals in Shandong and Guangdong provinces for a prepartum survey. Psychological assessments were conducted using the Adult Attachment Scale, Dyadic Coping Inventory, and the Patient Health Questionnaire-9 (PHQ-9) Depression Scale. To examine the relationship between each variable and postpartum depression, univariate and multiple logistic regression analyses were employed. Additionally, interaction analysis was used to analyze the interplay between different attachment styles and how spousal support influences women's postpartum depression. Results: The findings revealed that even after accounting for confounding variables, prepartum spousal support was an independent predictor of postpartum depression (adjusted odds ratio (OR) = 0.82, 95% CI: 0.69-0.96, P = .015). Women with a secure attachment style showed a significantly lower incidence of postpartum depression compared to those with insecure attachment styles (24.2% vs. 46%, P = .037). In the secure attachment group, spousal support had a protective effect against postpartum depression (adjusted OR = 0.57, 95% CI: 0.36-0.91, P = .018), and attachment style emerged as a potential interactive factor influencing the impact of spousal support on postpartum depression (P for interaction = .029). Conclusion: The provision of spousal support, especially to individuals with secure attachment styles, plays a preventive role in postpartum depression. This underscores the importance of considering attachment styles in interventions targeting postpartum depression prevention.

Constructing Targeted Strong Nb4d-O2p-Li2s Configurations to Obtain Excellent Energy Density and Long Life for Li-rich Cathodes.

The Li-rich Mn-based cathode materials (LMRs) deliver excellent energy density and exhibit low cost, which are considered as the most promising cathode materials for the next generation lithium-ion batteries. However, the irreversible redox reaction of the oxygen atoms directly leads to release oxygen and intensifies phase transformation. Besides, the local stress and strain will be generated due to the unit-cell volume difference between R-3m and C2/m phases, which continuously aggravates the collapse of secondary particles. Herein, the strong Nb4d-O2p-Li2s configurations at the Li1 sites of the TM-layer in the C2/m phase and secondary particles with the radial arrangement of refined primary particles are designed to inhibit oxygen release and relieve lattice stress by Nb2O5 treatment. Meanwhile, the preferential growth of the active {010} planes is presented to obtain an excellent transmission rate of Li+. As a result, the designed LMR delivers remarkable electrochemical properties with high discharge capacity and initial coulomb efficiency of 276 mA h g-1 and 85% at 0.1 C, outstanding cycling retention rate of 81% after 300 cycles. This novel crystal structure combining oxygen coordination regulation and micro-nano scale design provides inspiration for the design of high-performance LMRs.

Efficacy and safety of efdamrofusp alfa versus aflibercept in participants with neovascular age-related macular degeneration: a randomized, double-masked, active-controlled, non-inferiority, phase 2 trial.

PURPOSE: To evaluate efficacy and safety of efdamrofusp alfa compared with aflibercept in neovascular age-related macular degeneration (nAMD). DESIGN: Randomized, double-masked, multicenter, active-controlled, non-inferiority phase 2 study PARTICIPANTS: A total of 231 treatment-naïve and previously treated participants with active choroidal neovascularization secondary to nAMD were enrolled. METHODS: Eligible participants were randomized (1:1:1) to 2 mg efdamrofusp alfa, 4 mg efdamrofusp alfa or 2 mg aflibercept groups. Participants in all groups received three initial monthly loading doses, followed by treatment every 8 weeks with assessment every 4 weeks up to week 52. MAIN OUTCOME MEASURES: The primary endpoint was the mean BCVA change from baseline to week 36. The pre-specified noninferiority margin was set as -5 letters (80% CI). RESULTS: Each treatment group included 77 participants. The mean BCVA changes from baseline to week 36 for 2 mg efdamrofusp alfa, 4 mg efdamrofusp alfa and aflibercept groups were +10.6, +11.4, +12.0 letters, respectively; Least Squares (LS) mean difference were -1.4 (80% CI: -3.5 to 0.7) between 2 mg efdamrofusp alfa and aflibercept, and -0.6 (80% CI: -2.7 to 1.6) between 4 mg efdamrofusp alfa and aflibercept. Mean central retinal thickness changes were consistent across groups. Adverse event rate was comparable among the groups. CONCLUSIONS: Efdamrofusp alfa demonstrated noninferiority to aflibercept in BCVA improvement, accompanied by a similar safety profile.

Downregulation of Splicing Factor PTBP1 Curtails FBXO5 Expression to Promote Cellular Senescence in Lung Adenocarcinoma.

Polypyrimidine tract-binding protein 1 (PTBP1) plays an essential role in splicing and post-transcriptional regulation. Moreover, PTBP1 has been implicated as a causal factor in tumorigenesis. However, the involvement of PTBP1 in cellular senescence, a key biological process in aging and cancer suppression, remains to be clarified. Here, it is shown that PTBP1 is associated with the facilitation of tumor growth and the prognosis in lung adenocarcinoma (LUAD). PTBP1 exhibited significantly increased expression in various cancer types including LUAD and showed consistently decreased expression in multiple cellular senescence models. Suppression of PTBP1 induced cellular senescence in LUAD cells. In terms of molecular mechanisms, the silencing of PTBP1 enhanced the skipping of exon 3 in F-box protein 5 (FBXO5), resulting in the generation of a less stable RNA splice variant, FBXO5-S, which subsequently reduces the overall FBXO5 expression. Additionally, downregulation of FBXO5 was found to induce senescence in LUAD. Collectively, these findings illustrate that PTBP1 possesses an oncogenic function in LUAD through inhibiting senescence, and that targeting aberrant splicing mediated by PTBP1 has therapeutic potential in cancer treatment.

Thyroid-associated ophthalmopathy: the role of oxidative stress.

Thyroid-associated ophthalmopathy (TAO) is an autoimmune condition affecting the eyes, characterized by proptosis, extraocular muscle involvement, and in severe cases, vision impairment including diplopia, optic neuropathy, and potential blindness. The exact etiology of TAO remains elusive; however, increased oxidative stress and decreased antioxidant capacity are pivotal in its pathogenesis. Elevated oxidative stress not only directly damages orbital tissues but also influences thyroid function and autoimmune responses, exacerbating tissue destruction. This review explores the role of oxidative stress in TAO, elucidates its mechanisms, and evaluates the efficacy and limitations of antioxidant therapies in managing TAO. The findings aim to enhance understanding of oxidative stress mechanisms in TAO and propose potential antioxidant strategies for future therapeutic development.