Infant and adult human intestinal enteroids are morphologically and functionally distinct.

Human intestinal enteroids (HIEs) are gaining recognition as physiologically relevant models of the intestinal epithelium. While HIEs from adults are used extensively in biomedical research, few studies have used HIEs from infants. Considering the dramatic developmental changes that occur during infancy, it is important to establish models that represent infant intestinal characteristics and physiological responses. We established jejunal HIEs from infant surgical samples and performed comparisons to jejunal HIEs from adults using RNA sequencing (RNA-Seq) and morphologic analyses. We then validated differences in key pathways through functional studies and determined whether these cultures recapitulate known features of the infant intestinal epithelium. RNA-Seq analysis showed significant differences in the transcriptome of infant and adult HIEs, including differences in genes and pathways associated with cell differentiation and proliferation, tissue development, lipid metabolism, innate immunity, and biological adhesion. Validating these results, we observed a higher abundance of cells expressing specific enterocyte, goblet cell, and enteroendocrine cell markers in differentiated infant HIE monolayers, and greater numbers of proliferative cells in undifferentiated 3D cultures. Compared to adult HIEs, infant HIEs portray characteristics of an immature gastrointestinal epithelium including significantly shorter cell height, lower epithelial barrier integrity, and lower innate immune responses to infection with an oral poliovirus vaccine. HIEs established from infant intestinal tissues reflect characteristics of the infant gut and are distinct from adult cultures. Our data support the use of infant HIEs as an ex vivo model to advance studies of infant-specific diseases and drug discovery for this population. IMPORTANCE: Tissue or biopsy stem cell-derived human intestinal enteroids are increasingly recognized as physiologically relevant models of the human gastrointestinal epithelium. While enteroids from adults and fetal tissues have been extensively used for studying many infectious and non-infectious diseases, there are few reports on enteroids from infants. We show that infant enteroids exhibit both transcriptomic and morphological differences compared to adult cultures. They also differ in functional responses to barrier disruption and innate immune responses to infection, suggesting that infant and adult enteroids are distinct model systems. Considering the dramatic changes in body composition and physiology that begin during infancy, tools that appropriately reflect intestinal development and diseases are critical. Infant enteroids exhibit key features of the infant gastrointestinal epithelium. This study is significant in establishing infant enteroids as age-appropriate models for infant intestinal physiology, infant-specific diseases, and responses to pathogens.

Association between IGF-1 levels and MDD: a case-control and meta-analysis.

Purpose: Insulin-like growth factor-1 (IGF-1) has a variety of neurotrophic effects, including neurogenesis, remyelination and synaptogenesis, and is an effective regulator of neuronal plasticity. Although multiple studies have investigated IGF-1 in depression-related disorders, few studies have focused on patients with a first episode of clearly diagnosed depression who had never used antidepressants before. Therefore, this study investigated first-episode and drug-naïve patients with depression to supplement the current evidence around IGF-1 levels in depressive disorders. Patients and methods: This study consisted of two parts. In the first part, 60 patients with first-episode and drug-naïve depression and 60 controls matched for age, sex, and BMI were recruited from the outpatient department of the Fourth Hospital of Wuhu City, and the community. The case-control method was used to compare differences in serum IGF-1 levels between the two groups. In the second part, 13 case-control studies were screened through the database for meta-analysis to verify the reliability of the results. Results: Results of the case-control study demonstrated that serum IGF-1 levels are significantly higher in patients with first-episode and drug-naïve depression compared to healthy controls (p<0.05), although there was no significant difference between men and women with diagnosed MDD, there was no significant correlation between serum IGF-1 level and age in patients with depression and no significant correlation between IGF-1 level and the severity of depression. The meta-analysis corroborates these findings and demonstrated that IGF-1 levels are significantly higher in MDD patients than in healthy controls. Conclusion: Patients with first-episode and drug-naïve depression have higher IGF-1 levels, but the exclusion of confounding factors in studies of IGF-1 as it relates to depressive disorders must be taken into consideration strictly, and additional research is needed to fully understand the critical role of IGF-1 in depression. Systematic review registration: PROSPERO, identifier CRD42023482222.

Advancements in Human Norovirus Cultivation in Human Intestinal Enteroids.

Human noroviruses (HuNoVs) are a significant cause of both epidemic and sporadic acute gastroenteritis worldwide. The lack of a reproducible culture system for HuNoVs was a major obstacle in studying virus replication and pathogenesis for almost a half-century. This barrier was overcome with our successful cultivation of multiple HuNoV strains in human intestinal enteroids (HIEs), which has significantly advanced HuNoV research. We previously optimized culture media conditions and generated genetically-modified HIE cultures to enhance HuNoV replication in HIEs. Building upon these achievements, we now present additional advancements to this culture system, which involve testing different media, unique HIE lines, and additional virus strains. HuNoV infectivity was evaluated and compared in new HIE models, including HIEs generated from different intestinal segments of individual adult organ donors, HIEs made from human embryonic stem cell-derived human intestinal organoids that were transplanted into mice (H9tHIEs), genetically-engineered (J4 FUT2 knock-in [ KI ], J2 STAT1 knock-out [ KO ]) HIEs, as well as HIEs derived from a patient with common variable immunodeficiency (CVID) and from infants. Our findings reveal that small intestinal HIEs, but not colonoids, from adults, H9tHIEs, HIEs from a CVID patient, and HIEs from infants support HuNoV replication with segment and strain-specific differences in viral infection. J4 FUT2-KI HIEs exhibit the highest susceptibility to HuNoV infection, allowing the cultivation of a broader range of GI and GII HuNoV strains than previously reported. Overall, these results contribute to a deeper understanding of HuNoVs and highlight the transformative potential of HIE cultures in HuNoV research. Importance: Human noroviruses (HuNoVs) are very contagious and cause significant acute gastroenteritis globally, but studying them has been hindered by the lack of a reproducible culture system for nearly 50 years. This barrier was overcome by successfully cultivating multiple HuNoV strains in human intestinal enteroids (HIEs), advancing HuNoV research. We previously optimized culture conditions and developed genetically modified HIEs to enhance HuNoV replication. In this study, we tested different media, unique HIE lines, and additional virus strains, evaluating HuNoV infectivity in new HIE models. These models include HIEs from various intestinal segments of adult donors, human embryonic stem cell-derived HIEs transplanted into mice (H9tHIEs), genetically-engineered HIEs (J4 FUT2 knock-in [ KI ], J2 STAT1 knock-out [ KO ]), HIEs from a common variable immunodeficiency (CVID) patient, and from infants. Our findings show that adult small intestinal HIEs, H9tHIEs, CVID patient HIEs, and infant HIEs support HuNoV replication with segment and strain-specific differences. J4 FUT2-KI HIEs exhibited the highest susceptibility, allowing cultivation of a broader range of HuNoV strains. These results enhance the understanding of HuNoVs and highlight the transformative potential of HIE cultures in HuNoV research.

Silencing of ZNF610 suppresses cell proliferation and migration in lung adenocarcinoma.

Zinc finger proteins (ZNFs) play a significant role in the initiation and progression of tumors. Nevertheless, the specific contribution of ZNF610 to lung adenocarcinoma (LUAD) remains poorly understood. This study sought is to elucidate the role of ZNF610 in LUAD. Transcript data of LUAD were obtained from The Cancer Genome Atlas Program (TCGA) database and processed via R program. The expression of ZNF610 was assessed in various cell lines. To compare the proliferative capacity of cells with or without ZNF610 silencing, CCK8, cell colony formation assay, and Celigo label-free cell counting assay were employed. Furthermore, transwell migration and invasion assays were conducted to evaluate the migratory and invasive abilities of the cells. The expression levels of genes and proteins were assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot techniques. In different LUAD cells, the expression level of ZNF610 was found to be significantly higher in LUAD cells compared to MRC-5 and BASE-2B cells. Moreover, the silencing of ZNF610 resulted in a decrease in cell proliferation and migration abilities. Additionally, the apoptosis rate of cells increased upon silencing ZNF610. Notably, the proportion of cells in the G0/G1 phase increased, while the proportion of cells in the S phase decreased following ZNF610 silencing. Finally, ß-catenin and snail were identified as downstream targets of ZNF610 in cells. Our findings suggest that silencing ZNF610 could inhibit LUAD cell proliferation and migration, possibly through the downregulation of ß-catenin and snail.

Genetic relatedness, antibiotic resistance, and virulence of Klebsiella pneumoniae isolated from health care and food sources in Wuhan, China.

BACKGROUND: To investigate genetic relatedness and antibiotic resistance of Klebsiella pneumoniae from retail meat samples, clinical source samples, and hospital environmental samples in Wuhan, China. METHODS: Hypermucoviscosity and biofilm formation of K. pneumoniae were assessed by string test and crystal violet staining. MICs of 18 antimicrobials were determined by broth microdilution. PCR detected 14 antibiotic resistance genes. Genetic relatedness and clonal dissemination were analyzed by PFGE. RESULTS: Among 5,730 samples, 46 were tested positive for K pneumoniae, with higher rates observed in meat (23.4%) than in clinical samples (0.6%) and hospital environmental samples (8.0%). Meat-derived isolates showed high resistance to tetracycline (36.4%, 4/11), sulfonamide (27.3%, 3/11), and gentamicin (27.3%, 3/11), whereas clinical isolates exhibited significant resistance to ampicillin-sulbactam (32.3%, 10/31). Multidrug resistance was observed in 17.4% (8/46) of the isolates, particularly in hospital environmental samples (3/4). Biofilm production was observed in 88.1% (37/42) of K pneumoniae. Pulsed-field gel electrophoresis analysis revealed patient-to-patient K pneumoniae transmission, transmission between patients and hospital environment, as well as cross-contamination between markets. CONCLUSIONS: The findings underscore the importance of comprehensive surveillance, infection control, and judicious antibiotic use in mitigating the impact of K pneumoniae on public health, especially in the food chain and health care settings.

Joint extraction of wheat germplasm information entity relationship based on deep character and word fusion.

The verified text data of wheat varieties is an important component of wheat germplasm information. To automatically obtain a structured description of the phenotypic and genetic characteristics of wheat varieties, the aim at solve the issues of fuzzy entity boundaries and overlapping relationships in unstructured wheat variety approval data, WGIE-DCWF (joint extraction model of wheat germplasm information entity relationship based on deep character and word fusion) was proposed. The encoding layer of the model deeply fused word semantic information and character information using the Transformer encoder of BERT. This allowed for the cascading fusion of contextual semantic feature information to achieve rich character vector representation and improve the recognition ability of entity features. The triple extraction layer of the model established a cascading pointer network, extracted the head entity, extracted the tail entity according to the relationship category, and decoded the output triplet. This approach improved the model's capability to extract overlapping relationships. The experimental results demonstrated that the WGIE-DCWF model performed exceptionally well on both the WGD (wheat germplasm dataset) and the public dataset DuIE. The WGIE-DCWF model not only achieved high performance on the evaluation datasets but also demonstrated good generalization. This provided valuable technical support for the construction of a wheat germplasm information knowledge base and is of great significance for wheat breeding, genetic research, cultivation management, and agricultural production.

Non-telecentric photoacoustic microscopy for multi-scale imaging.

Optical-resolution photoacoustic microscopy (OR-PAM) excels in precisely imaging a biological tissue based on absorption contrast. However, existing OR-PAMs are confined by fixed compromises between spatial resolution and field of view (FOV), preventing the integration of large FOV and local high-resolution within one system. Here, we present a non-telecentric OR-PAM (nTC-PAM) that empowers efficient adaptation of FOV and spatial resolution to match the multi-scale requirement of diverse biological imaging. Our method allows for a large-scale transformation in FOV and even surpassing the nominal FOV of the objective with minimal marginal degradation of the lateral resolution. We demonstrate the advantage of nTC-PAM through multi-scale imaging of the leaf phantom, mouse ear, and cortex. The results reveal that nTC-PAM can switch the FOV and spatial resolution to meet the requirements of different biological tissues, such as large-scale imaging of the whole cerebral cortex and high-resolution imaging of microvascular structures in local brain regions.

RETRACTED: Serebrovska et al. Intermittent Hypoxia-Hyperoxia Training Improves Cognitive Function and Decreases Circulating Biomarkers of Alzheimer's Disease in Patients with Mild Cognitive Impairment: A Pilot Study. Int. J. Mol. Sci. 2019, 20, 5405.

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Influence factors of metagenomic next-generation sequencing negative results in diagnosed patients with spinal infection.

The aim of this study was to evaluate the influence factors of metagenomic next-generation sequencing (mNGS) negative results in the diagnosed patients with spinal infection. mNGS test was applied in a cohort of 114 patients with suspected spinal infection, among which 56 patients had a final diagnosis of spinal infection. mNGS achieved a sensitivity of 75.0% (95% CI, 61.6% to 85.6%) and a specificity of 84.5% (95% CI, 72.6% to 92.7%), using histopathology and culture results as reference. Diagnosed patients with a negative culture result had lower white blood cell account, percentage of neutrophilic granulocyte, C-reactive protein (all P<0.05) and relatively higher rate of prior antimicrobial treatment history (P=0.059). However, diagnosed patients with a negative mNGS result did not have such difference with mNGS-positive patients, suggesting that mNGS was not strictly limited by the above indicators, which presented the advantages of this technique from another point of view.

Antibiotic-Resistance Profiles and Genetic Diversity of Shigella Isolates in China: Implications for Control Strategies.

The urgent need for comprehensive and systematic analyses of Shigella as the key pathogen led us to meticulously explore the epidemiology and molecular attributes of Shigella isolates. Accordingly, we procured 24 isolates (10 from Xinjiang and 14 from Wuhan, China) and performed serotype identification and antimicrobial susceptibility testing. Resistance gene detection and homology analysis by polymerase chain reaction and pulsed-field gel electrophoresis (PFGE), respectively, were performed for genetic diversity analysis. All isolates were identified as Shigella flexneri, with 70% (35.4-91.9%) and 30% (8.1-64.6%) of the Xinjiang isolates and 85.7% (56.2-97.5%) and 14.3% (2/14, 2.5-43.9%) of the Wuhan isolates belonging to serotype 2a and serotype 2b, respectively. All isolates displayed resistance to at least two antibiotics and complete resistance to ampicillin. Multidrug resistance (MDR) was recorded in 70.8% (48.8-86.6%) of isolates, with Xinjiang isolates exhibiting relatively higher resistance to ampicillin-sulbactam, piperacillin, ceftriaxone, and aztreonam. Conversely, Wuhan isolates displayed higher MDR and resistance to tetracycline, ciprofloxacin, levofloxacin, and cefepime relative to Xinjiang isolates. Molecular scrutiny of antibiotic-resistance determinants revealed that blaTEM was the main mechanism of ampicillin resistance, blaCTX-M was the main gene for resistance to third- and fourth-generation cephalosporins, and tetB was the predominant gene associated with tetracycline resistance. Four Xinjiang and seven Wuhan isolates shared T1-clone types (>85%), and two Xinjiang and one Wuhan isolates were derived from the T6 clone with a high similarity of 87%. Six PFGE patterns (T1, T2, T5, T6-3, T8, and T10) of S. flexneri were associated with MDR. Thus, there is a critical need for robust surveillance and control strategies in managing Shigella infections, along with the development of targeted interventions and antimicrobial stewardship programs tailored to the distinct characteristics of Shigella isolates in different regions of China.

YOLOv8s-CGF: a lightweight model for wheat ear Fusarium head blight detection.

Fusarium head blight (FHB) is a destructive disease that affects wheat production. Detecting FHB accurately and rapidly is crucial for improving wheat yield. Traditional models are difficult to apply to mobile devices due to large parameters, high computation, and resource requirements. Therefore, this article proposes a lightweight detection method based on an improved YOLOv8s to facilitate the rapid deployment of the model on mobile terminals and improve the detection efficiency of wheat FHB. The proposed method introduced a C-FasterNet module, which replaced the C2f module in the backbone network. It helps reduce the number of parameters and the computational volume of the model. Additionally, the Conv in the backbone network is replaced with GhostConv, further reducing parameters and computation without significantly affecting detection accuracy. Thirdly, the introduction of the Focal CIoU loss function reduces the impact of sample imbalance on the detection results and accelerates the model convergence. Lastly, the large target detection head was removed from the model for lightweight. The experimental results show that the size of the improved model (YOLOv8s-CGF) is only 11.7 M, which accounts for 52.0% of the original model (YOLOv8s). The number of parameters is only 5.7 × 106 M, equivalent to 51.4% of the original model. The computational volume is only 21.1 GFLOPs, representing 74.3% of the original model. Moreover, the mean average precision (mAP@0.5) of the model is 99.492%, which is 0.003% higher than the original model, and the mAP@0.5:0.95 is 0.269% higher than the original model. Compared to other YOLO models, the improved lightweight model not only achieved the highest detection precision but also significantly reduced the number of parameters and model size. This provides a valuable reference for FHB detection in wheat ears and deployment on mobile terminals in field environments.

High spatiotemporal mapping of cortical blood flow velocity with an enhanced accuracy.

Cerebral blood flow velocity is one of the most essential parameters related to brain functions and diseases. However, most existing mapping methods suffer from either inaccuracy or lengthy sampling time. In this study, we propose a particle-size-related calibration method to improve the measurement accuracy and a random-access strategy to suppress the sampling time. Based on the proposed methods, we study the long-term progress of cortical vasculopathy and abnormal blood flow caused by glioma, short-term variations of blood flow velocity under different anesthetic depths, and cortex-wide connectivity of the rapid fluctuation of blood flow velocities during seizure onset. The experimental results demonstrate that the proposed calibration method and the random-access strategy can improve both the qualitative and quantitative performance of velocimetry techniques and are also beneficial for understanding brain functions and diseases from the perspective of cerebral blood flow.

Wearable photoacoustic watch for humans.

Longitudinal detection of hemodynamic changes based on wearable devices is imperative for monitoring human healthcare. Photoacoustic effect is extremely sensitive to variations in hemoglobin. Therefore, wearable photoacoustic devices are apt to monitor human healthcare via the observation of hemodynamics. However, the bulky system and difficulties in miniaturizing and optimizing the imaging interface restrict the development of wearable photoacoustic devices for human use. In this study, we developed a wearable photoacoustic watch with a fully integrated system in a backpack that has a size of 450 mm × 300 mm × 200 mm and an affordable weight of 7 kg for an adult to wear. The watch has a size of 43 mm × 30 mm × 24 mm, weighs 40 g, and features a lateral resolution of 8.7 µm, a field of view (FOV) of 3 mm in diameter, and a motorized adjustable focus for optimizing the imaging plane for different individuals. We recruited volunteers to wear the watch and the backpack and performed in vivo imaging of the vasculatures inside human wrists under the conditions of walking and human cuff occlusion to observe hemodynamic variations during different physiological states. The results suggest that the focus shifting capability of the watch makes it suitable for different individuals, and the compact and stable design of the entire system allows free movements of humans.

Photoacoustic expansion microscopy of melanosomes.

Optical resolution photoacoustic microscopy (OR-PAM) is a hybrid imaging method for visualizing organelles due to the high spatial resolution and abundant optical contrast. Usually, OR-PAM employs high numerical aperture (NA) objectives and high-frequency ultrasonic detectors to resolve three-dimensional (3D) microstructures of cells. Expansion microscopy (ExM) provides a nanoscale resolution by isotropically enlarging cells instead of utilizing ultrahigh NA objectives. In this Letter, we report the development of photoacoustic expansion microscopy (PA-ExM) that combines the advantages of OR-PAM and ExM for 3D organelle imaging using near-infrared light. We evaluate the performance of PA-ExM using label-free melanoma cells, where the image quality of melanosome distributions in expanded cells using a 40× objective is comparable to that of unexpanded cells using an oil-immersed 100× objective. The results suggest that PA-ExM possesses the great potential to study organelles.

Grafting a Polymer Coating Layer onto Li1.2 Ni0.13 Co0.13 Mn0.54 O2 Cathode by Benzene Diazonium Salts to Facilitate the Cycling Performance and High-Voltage Stability.

Li-rich Mn-based cathodes have been regarded as promising cathodes for lithium-ion batteries because of their low cost of raw materials (compared with Ni-rich layer structure and LiCoO2 cathodes) and high energy density. However, for practical application, it needs to solve the great drawbacks of Li-rich Mn-based cathodes like capacity degradation and operating voltage decline. Herein, an effective method of surface modification by benzene diazonium salts to build a stable interface between the cathode materials and the electrolyte is proposed. The cathodes after modification exhibit excellent cycling performance (the retention of specific capacity is 84.2% after 350 cycles at the current density of 1 C), which is mainly attributed to the better stability of the structure and interface. This work provides a novel way to design the coating layer with benzene diazonium salts for enhancing the structural stability under high voltage condition during cycling.

Infant and Adult Human Intestinal Enteroids are Morphologically and Functionally Distinct.

Background & Aims: Human intestinal enteroids (HIEs) are gaining recognition as physiologically relevant models of the intestinal epithelium. While HIEs from adults are used extensively in biomedical research, few studies have used HIEs from infants. Considering the dramatic developmental changes that occur during infancy, it is important to establish models that represent infant intestinal characteristics and physiological responses. Methods: We established jejunal HIEs from infant surgical samples and performed comparisons to jejunal HIEs from adults using RNA sequencing (RNA-Seq) and morphologic analyses. We validated differences in key pathways through functional studies and determined if these cultures recapitulate known features of the infant intestinal epithelium. Results: RNA-Seq analysis showed significant differences in the transcriptome of infant and adult HIEs, including differences in genes and pathways associated with cell differentiation and proliferation, tissue development, lipid metabolism, innate immunity, and biological adhesion. Validating these results, we observed a higher abundance of cells expressing specific enterocyte, goblet cell and enteroendocrine cell markers in differentiated infant HIE monolayers, and greater numbers of proliferative cells in undifferentiated 3D cultures. Compared to adult HIEs, infant HIEs portray characteristics of an immature gastrointestinal epithelium including significantly shorter cell height, lower epithelial barrier integrity, and lower innate immune responses to infection with an oral poliovirus vaccine. Conclusions: HIEs established from infant intestinal tissues reflect characteristics of the infant gut and are distinct from adult cultures. Our data support the use of infant HIEs as an ex-vivo model to advance studies of infant-specific diseases and drug discovery for this population.

Rotavirus-mediated DGAT1 degradation: A pathophysiological mechanism of viral-induced malabsorptive diarrhea.

Gastroenteritis is among the leading causes of mortality globally in infants and young children, with rotavirus (RV) causing ~258 million episodes of diarrhea and ~128,000 deaths annually in infants and children. RV-induced mechanisms that result in diarrhea are not completely understood, but malabsorption is a contributing factor. RV alters cellular lipid metabolism by inducing lipid droplet (LD) formation as a platform for replication factories named viroplasms. A link between LD formation and gastroenteritis has not been identified. We found that diacylglycerol O-acyltransferase 1 (DGAT1), the terminal step in triacylglycerol synthesis required for LD biogenesis, is degraded in RV-infected cells by a proteasome-mediated mechanism. RV-infected DGAT1-silenced cells show earlier and increased numbers of LD-associated viroplasms per cell that translate into a fourfold-to-fivefold increase in viral yield (P < 0.05). Interestingly, DGAT1 deficiency in children is associated with diarrhea due to altered trafficking of key ion transporters to the apical brush border of enterocytes. Confocal microscopy and immunoblot analyses of RV-infected cells and DGAT1-/- human intestinal enteroids (HIEs) show a decrease in expression of nutrient transporters, ion transporters, tight junctional proteins, and cytoskeletal proteins. Increased phospho-eIF2α (eukaryotic initiation factor 2 alpha) in DGAT1-/- HIEs, and RV-infected cells, indicates a mechanism for malabsorptive diarrhea, namely inhibition of translation of cellular proteins critical for nutrient digestion and intestinal absorption. Our study elucidates a pathophysiological mechanism of RV-induced DGAT1 deficiency by protein degradation that mediates malabsorptive diarrhea, as well as a role for lipid metabolism, in the pathogenesis of gastroenteritis.

The Role of OCTA in Evaluating Diabetic Retinopathy Progression: A Meta-Analysis.

Background: Diabetic retinopathy (DR) substantially threatens ocular health, necessitating the accurate and prompt assessment of its onset and progression. Optical coherence tomography angiography (OCTA) is a valuable tool for evaluating periocular microvascular indicators, offering insights crucial for diagnosing and treating DR. Objective: This meta-analysis aims to evaluate the progression of diabetic retinopathy (DR) by examining periocular microvascular indicators using optical coherence tomography angiography (OCTA). The objective is to provide substantive evidence for the future diagnosis and treatment of DR. Methods: We analyzed the relevant research retrieved from PubMed and Web of Science until January 2023. The inclusion and exclusion criteria were carefully applied to select eligible studies. Quality assessment was performed using the Newcastle-Ottawa Scale, with studies scoring 4 or less excluded. Meta-analysis was conducted using Revman 5.3 software and focused on key indicators, including peripapillary vascular length density (pVLD) and peripapillary vascular density (pVD). Heterogeneity was assessed using I2 and P values, with effect sizes determined via fixed-effect or random-effects models based on heterogeneity levels. Results: Six studies involving 839 DR-afflicted eyes and 3209 non-DR eyes were included after screening. All selected articles exhibited high reference value, with quality scores ranging from 5 to 8 points. The meta-analysis demonstrated that DR patients displayed significantly lower pVD and pVLD in the superficial (SCP) and deep capillary plexus (DCP) compared to non-DR patients (P < .05). These findings remained consistent across different effect models, reaffirming their validity. Conclusions: Patients with DR exhibit reduced levels of pVD and pVLD in the SCP and DCP compared to non-DR individuals. OCTA examination of periocular microvascular indicators emerges as an effective tool for assessing the onset and progression of DR.

Human intestinal organoids from Cronkhite-Canada syndrome patients reveal link between serotonin and proliferation.

Cronkhite-Canada Syndrome (CCS) is a rare, noninherited polyposis syndrome affecting 1 in every million individuals. Despite over 50 years of CCS cases, the etiopathogenesis and optimal treatment for CCS remains unknown due to the rarity of the disease and lack of model systems. To better understand the etiology of CCS, we generated human intestinal organoids (HIOs) from intestinal stem cells isolated from 2 patients. We discovered that CCS HIOs are highly proliferative and have increased numbers of enteroendocrine cells producing serotonin (also known as 5-hydroxytryptamine or 5HT). These features were also confirmed in patient tissue biopsies. Recombinant 5HT increased proliferation of non-CCS donor HIOs and inhibition of 5HT production in the CCS HIOs resulted in decreased proliferation, suggesting a link between local epithelial 5HT production and control of epithelial stem cell proliferation. This link was confirmed in genetically engineered HIOs with an increased number of enteroendocrine cells. This work provides a new mechanism to explain the pathogenesis of CCS and illustrates the important contribution of HIO cultures to understanding disease etiology and in the identification of novel therapies. Our work demonstrates the principle of using organoids for personalized medicine and sheds light on how intestinal hormones can play a role in intestinal epithelial proliferation.

Long-term assessment of cutaneous inflammation and treatment using optical resolution photoacoustic microscopy.

Cutaneous inflammation is an acute skin disease characterized by edema and vascular hyperplasia. Longitudinal monitoring of vasculature is crucial for studying the development of inflammation and evaluating the therapeutic efficacy of drugs. Optical-resolution photoacoustic microscopy (OR-PAM) is a hybrid imaging tool for non-invasive and label-free visualization of microcirculations with a capillary-scale spatial resolution. In this study, we assess the feasibility of OR-PAM for long-term monitoring of vascular changes in 12-O-Tetradecanoylphorbol-13-Acetate (TPA)-induced mouse models, as well as the corresponding treatment process. Quantitative vascular evaluation is conducted based on derived key parameters, including vessel length, branchpoint number, vessel area fraction, vessel diameter, fractal dimension, vessel tortuosity and ear thickness, which reveal that vascular morphological changes are highly dependent on the concentration of TPA and existence of therapeutic drugs. Furthermore, the results show the potential of OR-PAM in the clinical management of inflammation and as an effective tool to evaluate vascular responses to pharmacological interventions in vivo.