Vision Screening Research Articles

Mobile assessment of visual function helps to prevent Re-Injury in elderly patients with recent hip fractures

IntroductionPatients undergoing surgery due to hip fracture face an elevated risk of a subsequent fall during rehabilitation. An important contributing factor to this risk is deteriorated visual function, often responsive to intervention. This study aims to explore differences in visual acuity (VA) and stereovision (SV) between individuals with a history of fall-related hip injuries (study group) and age-matched controls, utilizing a mobile application (EuvisionTab, ET) to distinguish age-related visual decline from pathological vision. Materials & MethodsA total of 32 and 71 participants were enrolled in the study and control groups, respectively (mean age: 74.9 years, range: 60–96). Monocular logMAR VA was measured using a tablet by means of an adaptive threshold-search algorithm. SV was assessed using low-dot density static and dynamic random dot stereograms. An age-dependent reference limit for VA was established. For ET stereotests, the number of correctly identified optotypes out of 10 random presentations served as the measure for further comparisons. Visually impaired status in the study group was determined if patients failed either the VA threshold or the SV criteria. ResultsIn the control group, an apparent but statistically nonsignificant decline in VA was observed, while stereovision remained stable and did not exhibit significant age-related variations based on ET stereotests. Conversely, the study group demonstrated significantly worse results in monocular VA (p = 0.0032) and for both stereotests (p = 0.018 for static, p = 0.036 for dynamic) according to paired samples t-test and chi-square test, respectively. Hip injuries were significantly associated with visual impairment (OR = 4.88, p = 0.0012). DiscussionThis study focuses on one possible risk factor of elderly falls, namely, vision impairment. Patients with visual decay present a higher incidence of hip injuries compared to age-matched controls. This data suggest that vision screening and, when feasible, restoration of visual function may contribute to the prevention of secondary falls, refractures, or contralateral fractures. A mobile-based screening protocol, executable as part of a postoperative bedside examination and independent of specialized eye care, can be proposed.

Drupacine as a potent SARS-CoV-2 replication inhibitor in vitro

Despite the availability of vaccines and antiviral treatments, the continued emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and breakthrough infections underscores the need for new, potent antiviral therapies. In a previous study, we established a transcription and replication-competent SARS-CoV-2 virus-like particle (trVLP) system that recapitulates the complete viral life cycle. In this study, we combined high-content screening (HCS) with the SARS-CoV-2 trVLP cell culture system, providing a powerful phenotype-oriented approach to assess the antiviral potential of compounds on a large scale. We screened a library of 3,200 natural compounds and identified drupacine as a potential candidate against SARS-CoV-2 infection. Furthermore, we utilized a SARS-CoV-2 replicon system to demonstrate that drupacine could inhibit viral genome transcription and replication. However, in vitro, enzymatic assays revealed that the inhibition could not be attributed to conventional antiviral targets, such as the viral non-structural proteins nsp5 (MPro) or nsp12 (RdRp). In conclusion, our findings position drupacine as a promising antiviral candidate against SARS-CoV-2, providing a novel scaffold for developing anti-coronavirus disease 2019 (COVID-19) therapeutics. Further investigation is required to pinpoint its precise target and mechanism of action.

Anticancer agent 5-fluorouracil reverses meropenem resistance in carbapenem-resistant Gram-negative pathogens

The global increasing incidence of clinical infections caused by carbapenem-resistant Gram-negative pathogens requires urgent and effective treatment strategies. Antibiotic adjuvants represent a promising approach to enhance the efficacy of meropenem against carbapenem-resistant bacteria. This study shows that the anticancer agent 5-fluorouracil (5-FU, 50 µM) significantly reduced the minimum inhibitory concentration of meropenem against blaNDM-5 positive Escherichia coli by 32-fold through cell-based high-throughput screening. Further pharmacological studies indicated that 5-FU exhibited potentiation effects on carbapenem antibiotics against 42 Gram-negative bacteria producing either metallo-β-lactamases (MBLs), such as NDM and IMP, or serine β-lactamases (Ser-BLs), like KPC and OXA. These bacteria included E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter spp., 32 of which were obtained from human clinical samples. Mechanistic investigations revealed that 5-FU inhibited the transcription and expression of the blaNDM-5 gene. In addition, 5-FU combined with meropenem enhanced bacterial metabolism, and stimulated the production of reactive oxygen species (ROS), thereby rendering bacteria more susceptible to meropenem. In a mouse systemic infection model, 5-FU combined with meropenem reduced bacterial loads and effectively elevated the survival rate of 83.3%, compared with 16.7% with meropenem monotherapy. Collectively, these findings indicate the potential of 5-FU as a novel meropenem adjuvant to improve treatment outcomes against infections caused by carbapenem-resistant bacteria.

P02-44 Robotic device for fully automated high-content screening on C. elegans as a novel NAMs platform for DART assessment

P02-44 Robotic device for fully automated high-content screening on C. elegans as a novel NAMs platform for DART assessment

LP-35 Use of high-content screening technology for toxicological testing

LP-35 Use of high-content screening technology for toxicological testing

Disparities in Amblyopia Treatment Outcomes: The Impact of Sociodemographic Factors, Treatment Compliance, and Age of Diagnosis

ObjectiveTo identify clinical and sociodemographic factors associated with disparities in amblyopia treatment outcomes. DesignRetrospective chart review. SubjectsChildren ≤8 years old diagnosed and treated for unilateral refractive or strabismic amblyopia at our institution from 2012-2022. MethodsChildren with amblyopia were categorized by outcome: resolved amblyopia (<0.2 logMAR interocular difference [IOD] in visual acuity, or no fixation preference in non-verbal patients) or persistent amblyopia. Demographic and clinical data were recorded from the medical record. Zip codes were used to calculate Childhood Opportunity Index (COI) scores, estimated annual household income, and distance to hospital. Main Outcome MeasuresSociodemographic and clinical factors were compared between children with resolved and persistent amblyopia. Factors significant at p<0.10 on univariate analysis were included in a multivariable regression model. Results168 patients met inclusion criteria, and 131 (78%) had resolved amblyopia. Demographic factors associated with resolution of amblyopia were younger age at diagnosis (3.3±1.7 vs. 4.5±1.9 years, p=0.0009), English as the primary language (79.4% vs. 62.2%, p=0.04), higher estimated annual income ($83,315.93±29,276.64 vs. $71,623.00±26,842.56, p=0.03), higher COI scores (50.9±27.3 vs. 40.0±26.4, p=0.03), and living further from our institution (28.6±37.6 vs. 14.9±12.7 miles, p=0.003). Patients with resolved amblyopia also had higher rates of treatment compliance (83.2±25.0% vs. 75.6±24.4%, p=0.009) and shorter delays in follow-up (40.1±76.8 vs. 61.1±90.4 days, p=0.02). Amblyopia persistence was borderline associated with governmental insurance and higher presenting IOD in visual acuity (both p=0.06). On multivariate analysis, only younger age at amblyopia diagnosis (p=0.0010) remained significantly associated with amblyopia resolution. ConclusionsOur findings suggest that disparities in amblyopia outcomes are related to differences in age at diagnosis. Interventions to lower the age at which amblyopia is diagnosed, such as programs to improve vision screening rates and access to pediatric eye care in at-risk groups, may directly address inequities in rates of amblyopia resolution.

Geographic Patterns of Ocular Oncologist Supply and Patient Demand for Uveal Melanoma Treatment in the United States: A Supply and Demand Analysis.

To study geographic patterns of supply and demand for uveal melanoma and other ocular oncology healthcare by ocular oncology physicians in the United States. Google search interest data was obtained through trends.google.com. The combined-state density of ocular oncology physicians was calculated by dividing the number of practicing ocular oncologists in each state and its surrounding states by the state population. Relative search volume (RSV) values were divided by ocular oncology physician density to calculate the Google relative demand index (gRDI) for each state.Medicare (mRDI) and IRIS® Registry (iRDI) relative demand indices were calculated using prevalence data obtained through the Vision and Eye Health Surveillance System (VEHSS). Data from the US Census Bureau and Centers for Disease Control (CDC) databases were also utilized to analyze associations with poverty rates, percent living in urban or rural areas, vision screening rates, and ocular neoplasm rates. Alabama showed the highest RSV (100), while the lowest was reported in New Mexico (20). Vermont had the highest density of combined-state ocular oncology ophthalmologists (1.85 per 100,000 residents). New Mexico had the lowest RDI (0.013 gRDI, 0.015 mRDI, 0.018 iRDI) with 32 combined-state ocular oncologists and a population of 2,114,371. Ocular neoplasm prevalence rates ranged between 1.32% and 5.40% and significantly correlated with RSV. Single-state gRDI correlated with rural status and negatively correlated with urban areas (≥50,000 individuals). Single-state ophthalmologist density correlated positively with percent living in urban areas and vision screening rates, and negatively with rural status. This study uncovered significant heterogeneity in the geographical distribution of ocular oncology physicians and RDI throughout the United States, highlighting potential undersupply scenarios. This may guide efforts to increase ocular oncology physician and surgeon availability in areas of need.

Longitudinal assessment of the progression of severe keratoconus based on corneal topography

We aimed to assess long-term disease progression in patients with severe keratoconus (KC). Clinical records of 125 patients (201 eyes) with severe KC followed-up for > 12 months were retrospectively analyzed. From these, 28 patients (31 eyes) were included. Corneal topography parameters evaluated included thinnest corneal thickness (TCT), maximum keratometry (Kmax), anterior and posterior mean corneal radii of 3 mm (aKM, pKM), steep keratometry, and KC screening indices. All patients wore rigid gas permeable contact lenses (RGPCLs) for an extended period. The median patient age and follow-up period were 20 (interquartile range [IQR] 17–22) years and 25 (15–38) months, respectively. Compared to baseline, the aKM, Kmax, and KC screening indices on the anterior corneal surface were reduced at the final follow-up (P < 0.05). No changes were observed in RGP-corrected visual acuity, TCT, pKM, or KC screening indices on the posterior corneal surface. The higher the baseline value, the greater the reduction in aKM and Kmax. Five patients (16%) experienced disease progression during follow-up. Patients with severe KC showed reduced anterior corneal surface curvature and no change in corneal thickness during an average follow-up period of 2–3 years while wearing RGPCLs.

Knowledge, Attitude, Practice and Associated Factors Regarding Vision Screening among Preschool Teachers in Malaysia

Knowledge, Attitude, Practice and Associated Factors Regarding Vision Screening among Preschool Teachers in Malaysia

Gelsemium low doses protect against serum deprivation-induced stress on mitochondria in neuronal cells

Gelsemium dynamized dilutions (GDD) are known as a remedy for a wide range of behavioral and psychological symptoms of depression and anxiety at ultra-low doses, yet the underlying mechanisms of the mode of action of G. sempervirens itself are not well understood. The present study was designed to examine the neuroprotective effects of Gelsemium preparations in counteracting stress-related mitochondrial dysfunctions in neuronal cells. We started by studying how serum deprivation affects the mitochondrial functions of human neuroblastoma (SH-SY5Y) cells. Next, we looked into the potential of various Gelsemium dilutions to improve cell survival and ATP levels. After identifying the most effective dilutions, 3C and 5C, we tested their ability to protect SH-SY5Y cells from stress-induced mitochondrial deficits. We measured total and mitochondrial superoxide anion radicals using fluorescent dyes dihydroethidium (DHE) and the red mitochondrial superoxide indicator (MitoSOX). Additionally, we assessed total nitric oxide levels with 4,5-diaminofluorescein diacetate (DAF-2DA), examined the redox state using pRA305cells stably transfected with a plasmid encoding a redox-sensitive green fluorescent protein, and analyzed mitochondrial network morphology using an automated high-content analysis device, Cytation3. Furthermore, we investigated bioenergetics by measuring ATP production with a bioluminescence assay (ViaLighTM HT) and evaluated mitochondrial respiration (OCR) and glycolysis (ECAR) using the Seahorse Bioscience XF24 Analyzer. Finally, we determined cell survival using an MTT reduction assay. Our research indicates that Gelsemium dilutions (3C and 5C) exhibited neuroprotective effects by: - Normalizing total and mitochondrial superoxide anion radicals and total nitric oxide levels. - Regulating the mitochondrial redox environment and mitochondrial networks morphology. - Increasing ATP generation as well as OCR and ECAR levels, thereby reducing the viability loss induced by serum withdrawal stress. These findings highlight that dynamized Gelsemium preparations may have neuroprotective effects against stress-induced cellular changes in the brain by regulating mitochondrial functions, essential for the survival, plasticity, and function of neurons in depression.

A highly sensitive reporter system to monitor endogenous YAP1/TAZ activity and its application in various human cells.

The activation of yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ) has been implicated in both regeneration and tumorigenesis, thus representing a double-edged sword in tissue homeostasis. However, how the activity of YAP1/TAZ is regulated or what leads to its dysregulation in these processes remains unknown. To explore the upstream stimuli modulating the cellular activity of YAP1/TAZ, we developed a highly sensitive YAP1/TAZ/TEAD-responsive DNA element (YRE) and incorporated it into a lentivirus-based reporter cell system to allow for sensitive and specific monitoring of the endogenous activity of YAP1/TAZ in terms of luciferase activity invitro and Venus fluorescence invivo. Furthermore, by replacing YRE with TCF- and NF-κB-binding DNA elements, we demonstrated the applicability of this reporter system to other pathways such as Wnt/β-catenin/TCF- and IL-1β/NF-κB-mediated signaling, respectively. The practicality of this system was evaluated by performing cell-based reporter screening of a chemical compound library consisting of 364 known inhibitors, using reporter-introduced cells capable of quantifying YAP1/TAZ- and β-catenin-mediated transcription activities, which led to the identification of multiple inhibitors, including previously known as well as novel modulators of these signaling pathways. We further confirmed that novel YAP1/TAZ modulators, such as potassium ionophores, Janus kinase inhibitors, platelet-derived growth factor receptor inhibitors, and genotoxic stress inducers, alter the protein level or phosphorylation of endogenous YAP1/TAZ and the expression of their target genes. Thus, this reporter system provides a powerful tool to monitor endogenous signaling activities of interest (even in living cells) and search for modulators in various cellular contexts.

Vaginal cytomorphological profile in correlating suicidal deaths in medicolegal autopsy cases

Objectives: Vaginal cytology is a sensitive method for assessing women’s hormonal status, showing variations in menstrual cycle phases. Studies suggest a higher rate of female suicides during the luteal phase. This study aimed to link vaginal cytomorphological profiles with the manner of death and age of the deceased. Materials and Methods: Vaginal smears from 64 autopsy cases were microscopically examined for maturation index (MI) and value, reflecting hormonal profiles. Statistical Analysis: ANOVA between the mean of maturation value with manner of death was found to be significant. Results: Among the 48 suicides, 54.2% showed predominantly intermediate cells in the luteal phase, indicating a mid-zone shift in the MI. The remaining 16 non-suicidal cases showed fewer intermediate cells. Suicides shared a similar cytological profile and MI, especially in the reproductive age group. Conclusions: While vaginal smears are typically used in sexual assault cases to detect sperm, they also offer insights into women’s hormonal profiles. Understanding these profiles could provide clues about psychological status and its relation to the manner of death beyond sexual assault.

Explore the safety and efficiency of mild myopia retention in patients with myopia and presbyopia

Objective: To explore the corrective effects of a personalized corneal refractive surgery design that retains mild myopia in patients over 40 years old with refractive errors and presbyopia. Methods: A retrospective case series study was conducted, including 60 patients (120 eyes) over 40 years old who underwent corneal refractive surgery at Peking Union Medical College Hospital l from January 2023 to December 2023. The patients were divided into two groups based on their preference: Group A (retained mild myopia) and Group B (fully corrected), with 30 patients (60 eyes) in each group. Preoperative and postoperative visual acuity, subjective refraction, slit-lamp examination, corneal topography, and intraocular pressure were assessed at 1 day, 1 week, 1 month, 3 months, 6 months, and 12 months after surgery. The effectiveness and safety indices were calculated based on visual acuity before and after surgery. The National Eye Institute Refractive Quality of Life questionnaire was used to evaluate patient satisfaction and postoperative visual symptoms. Results: There were no significant differences in preoperative uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), spherical equivalent (SE), corneal thickness, and intraocular pressure between the two groups (all P>0.05). At the final follow-up, the proportions of eyes with UDVA≥0.8 and≥1.0 were 93.3% (56/60) and 60.0% (36/60) in Group A, and 100% (60/60) and 83.3% (50/60) in Group B, respectively. The SE was significantly different between Group A [(-0.35±0.52) D] and Group B [(-0.07±0.55) D] (P<0.05). Near visual acuity was better in Group A than in Group B (P<0.05). The effectiveness indices were 0.96±0.23 and 0.99±0.12, and the safety indices were 1.02±0.11 and 1.02±0.07 for Groups A and B, respectively. Both groups had high overall satisfaction, but Group A had higher scores for near vision, reading, and computer screen viewing. Conclusion: The personalized corneal refractive surgery design that retains mild myopia provides good corrective effects for patients over 40 years old with refractive errors, improving patient satisfaction and quality of life.

A nucleic acid binding protein map of germline regulation in Caenorhabditis elegans

Fertility requires the faithful proliferation of germ cells and their differentiation into gametes. Controlling these cellular states demands precise timing and expression of gene networks. Nucleic acid binding proteins (NBPs) play critical roles in gene expression networks that influence germ cell development. There has, however, been no functional analysis of the entire NBP repertoire in controlling in vivo germ cell development. Here, we analyzed germ cell states and germline architecture to systematically investigate the function of 364 germline-expressed NBPs in the Caenorhabditis elegans germ line. Using germline-specific knockdown, automated germ cell counting, and high-content analysis of germ cell nuclei and plasma membrane organization, we identify 156 NBPs with discrete autonomous germline functions. By identifying NBPs that control the germ cell cycle, proliferation, differentiation, germline structure and fertility, we have created an atlas for mechanistic dissection of germ cell behavior and gamete production.

Screen Time Soars and Vision Suffers: How School Closures During the Pandemic Affected Children and Adolescents' Eyesight.

This study aimed to determine the impact of school closures on visual acuity and screen time among students in Qatar. An analytical cross-sectional study was conducted, targeting governmental school students. Data were collected via telephone interviews with parents, and visual acuity measurements were extracted from the electronic health records. We interviewed 1546 parents of selected students, about 24% reported their children's history of visual disturbances, primarily refractive errors. The mean screen time across the week increased significantly by 11.5 ± 11.6h during school closures. We observed a significant decline of visual acuity during the closure compared to the pre-closure period across the entire sample, both sexes, and the younger age group. Furthermore, logistic regression analysis showed that local students and those with a history of visual disturbances were 1.7 times (AOR: 1.73, 95%CI 1.18-2.54, p = 0.005) and 2.5 times (AOR: 2.52, 95%CI 1.69-3.76, p < 0.001) more likely to experience decline of visual acuity respectively. School closures in Qatar were associated with a significant increase in screen time among students and a notable decline in their visual acuity. This deterioration highlights the need to monitor children's screen time and implement cost-effective measures to reduce screen exposure and enhance overall eye health among students.

Integrating Physiology, Cytology, and Transcriptome to Reveal the Leaf Variegation Mechanism in Phalaenopsis Chia E Yenlin Variegata Leaves.

Phalaenopsis orchids, with their unique appearance and extended flowering period, are among the most commercially valuable Orchidaceae worldwide. Particularly, the variegation in leaf color of Phalaenopsis significantly enhances the ornamental and economic value and knowledge of the molecular mechanism of leaf-color variegation in Phalaenopsis is lacking. In this study, an integrative analysis of the physiology, cytology, and transcriptome profiles was performed on Phalaenopsis Chia E Yenlin Variegata leaves between the green region (GR) and yellow region (YR) within the same leaf. The total chlorophyll and carotenoid contents in the YR exhibited a marked decrease of 72.18% and 90.21%, respectively, relative to the GR. Examination of the ultrastructure showed that the chloroplasts of the YR were fewer and smaller and exhibited indistinct stromal lamellae, ruptured thylakoids, and irregularly arranged plastoglobuli. The transcriptome sequencing between the GR and YR led to a total of 3793 differentially expressed genes, consisting of 1769 upregulated genes and 2024 downregulated genes. Among these, the chlorophyll-biosynthesis-related genes HEMA, CHLH, CRD, and CAO showed downregulation, while the chlorophyll-degradation-related gene SGR had an upregulated expression in the YR. Plant-hormone-related genes and transcription factors MYBs (37), NACs (21), ERFs (20), bHLH (13), and GLK (2), with a significant difference, were also analyzed. Furthermore, qRT-PCR experiments validated the above results. The present work establishes a genetic foundation for future studies of leaf-pigment mutations and may help to improve the economic and breeding values of Phalaenopsis.

TFEB activator tanshinone IIA and derivatives derived from Salvia miltiorrhiza Bge. Attenuate hepatic steatosis and insulin resistance

Ethnopharmacological relevanceSalvia miltiorrhiza Bge. (SMB) is an herbal medicine extensively used for improving metabolic disorders, including Nonalcoholic fatty liver disease (NAFLD). However, the potential material basis and working mechanism still remained to be elucidated. Aim of the studyTo find potential ingredients for therapy of NAFLD by high content screening and further verify the efficacy on restoring hepatic steatosis and insulin resistance, and clarify the potential working mechanism. Materials and methodsThe mouse transcription factor EB (Tfeb) in preadipocytes was knocked out by CRISPR-Cas9 gene editing. High content screening of TFEB nuclear translocation was performed to identify TFEB activators. The effect of candidate compounds on reducing lipid accumulation was evaluated using Caenorhabditis elegans (C. elegans). Then the role of Salvia miltiorrhiza extract (SMB) containing Tanshinone IIA and the derivatives were further investigated on high-fat diet (HFD) fed mice. RNA-seq was performed to explore potential molecular mechanism of SMB. Finally, the gut microbiota diversity was evaluated using 16S rRNA sequencing to investigate the protective role of SMB on regulating gut microbiota homeostasis. ResultsKnockout of Tfeb led to excessive lipid accumulation in adipocytes while expression of TFEB homolog HLH-30 in C. elegans (MAH240) attenuated lipid deposition. Screening of TFEB activators identified multiple candidates from Salvia miltiorrhiza, all of them markedly induced lysosome biogenesis in HepG2 cells. One of the candidate compounds Tanshinone IIA significantly decreased lipid droplet deposition in HFD fed C. elegans. Administration of SMB on C57BL/6J mice via gastric irrigation at the dose of 15 g/kg/d markedly alleviated hepatic steatosis, restored serum lipid profile, and glucose tolerance. RNA-seq showed that gene expression profile was altered and the genes related to lipid metabolism were restored. The disordered microbiome was remodeled by SMB, Firmicutes and Actinobacteriotawere notably reduced, Bacteroidota and Verrucomicrobiota were significantly increased. ConclusionTaken together, the observations presented here help address the question concerning what were the main active ingredients in SMB for alleviating NAFLD, and established that targeting TFEB was key molecular basis for the efficacy of SMB.

Assessing The Relationship Between Demand And Accessibility For Pediatric Ophthalmology Services By State In The United States.

To investigate the relationship between public demand for pediatric ophthalmology services and the accessibility of such services on a statewide basis in the United States, focusing on strabismus care. Using Google Trends data, search volumes for "strabismus" were analyzed from January 2014 to December 2023. Pediatric ophthalmologist availability was assessed via the American Academy of Ophthalmology directory, normalized for state population size to create a relative demand index. Additional metrics from the United States Census Bureau and Centers for Disease Control and Prevention provided socioeconomic and health data. Correlation coefficients were used to explore relationships between search volumes, specialist availability, vision screening, socioeconomics, and demographic factors. The data revealed variability in public interest in pediatric ophthalmology across states, with Alaska showing the highest relative search volume for strabismus. The data also indicated notable disparities in pediatric ophthalmologist density, with North Dakota, Vermont, and Wyoming having no pediatric ophthalmologists. A significant correlation was identified between pediatric ophthalmologist availability and vision screening (R = 0.486, p < 0.001). Negative correlations were observed between the relative demand index and urbanization (R = -0.388, p = 0.007), as well as the strabismus prevalence (R = -0.455, p = 0.001), indicating that urbanization and specialist distribution influence eyecare demand and access. The findings highlight disparities in accessibility and demand for pediatric ophthalmology services across the US, influenced by urbanization and distribution of healthcare professionals. The study underscores the need for targeted interventions to improve access to care and bridge gaps in pediatric ophthalmology service provision.

A natural small molecule alleviates liver fibrosis by targeting apolipoprotein L2.

Liver fibrosis is an urgent clinical problem without effective therapies. Here we conducted a high-content screening on a natural Euphorbiaceae diterpenoid library to identify a potent anti-liver fibrosis lead, 12-deoxyphorbol 13-palmitate (DP). Leveraging a photo-affinity labeling approach, apolipoprotein L2 (APOL2), an endoplasmic reticulum (ER)-rich protein, was identified as the direct target of DP. Mechanistically, APOL2 is induced in activated hepatic stellate cells upon transforming growth factor-β1 (TGF-β1) stimulation, which then binds to sarcoplasmic/ER calcium ATPase 2 (SERCA2) to trigger ER stress and elevate its downstream protein kinase R-like ER kinase (PERK)-hairy and enhancer of split 1 (HES1) axis, ultimately promoting liver fibrosis. As a result, targeting APOL2 by DP or ablation of APOL2 significantly impairs APOL2-SERCA2-PERK-HES1 signaling and mitigates fibrosis progression. Our findings not only define APOL2 as a novel therapeutic target for liver fibrosis but also highlight DP as a promising lead for treatment of this symptom.

Automatic Detection of Quasi-Periodic Emissions from Satellite Observations by Using DETR Method

The ionospheric quasi-periodic wave is a type of typical and common electromagnetic wave phenomenon occurring in extremely low-frequency (ELF) and very low-frequency ranges (VLF). These emissions propagate in a distinct whistler-wave mode, with varying periodic modulations of the wave intensity over time scales from several seconds to a few minutes. We developed an automatic detection model for the QP waves in the ELF band recorded by the China Seismo-Electromagnetic Satellite. Based on the 827 QP wave events, which were collected through visual screening from the electromagnetic field observations, an automatic detection model based on the Transformer architecture was built. This model, comprising 34.27 million parameters, was trained and evaluated. It achieved mean average precision of 92.3% on the validation dataset, operating at a frame rate of 39.3 frames per second. Notably, after incorporating the proton cyclotron frequency constraint, the model displayed promising performance. Its lightweight design facilitates easy deployment on satellite equipment, significantly enhancing the feasibility of on-board detection.