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Purpose: The purpose of this study was to assess the use of resected condyle thickness measurement, obtained with caliper, when verifying the accuracy of distal femoral bone resection in total knee arthroplasty.Methods: Fifty-two total knee arthroplasties were performed to treat osteoarthritis with varus knee. The difference of caliper-measured thickness of resected medial and lateral femoral condyles after removal of cartilage from the lateral condyle was compared with radiographically measured values. The preoperative planned valgus cut angles and the postoperative femoral component valgus angles were compared.Results: The difference of radiograph-measured thickness averaged 2.4 ± 2.2 mm and the difference of caliper-measured thickness averaged 2.0 ± 2.1 mm (r = 0.735, P < 0.001). The postoperative femoral component valgus angle averaged 4.8° ± 1.6° (range, 2.0°-7.6°). The difference between the valgus cut angle and femoral component valgus angle averaged -0.3° ± 1.5°.Conclusions: The confirmation of correspondence between the caliper-measured and radiographically measured thickness of resected condyles could verify the accuracy of distal femoral bone resection in total knee arthroplasty.Level Of Evidence: III. [ABSTRACT FROM AUTHOR]

The purpose of this study is to evaluate results after total knee arthroplasty using a medial pivot prosthesis with the posterior cruciate ligament (PCL)-retaining and PCL-sacrificing techniques. The PCL was retained in 67 knees and sacrificed in 70 knees. The mean Knee Society knee score increased from 59.6 before surgery to 91.5 at the last follow-up, and the mean function score increased from 53.6 to 85.4. The mean preoperative femorotibial angle was varus 4.1°, which corrected to valgus 5.8° after surgery. The increased knee and function score did not vary significantly between the cruciate-retaining and cruciate-sacrificing groups (P > .108), nor did the mean preoperative and postoperative femorotibial angle (P > .140). The clinical results of total knee arthroplasty with a medial pivot prosthesis were satisfactory, whether the PCL was retained or sacrificed. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the results of total knee arthroplasty (TKA) following a closed wedge high tibial osteotomy (HTO). A total of 16 TKAs were performed in 13 patients who had previously undergone a closed wedge HTO. The clinical results were reviewed using the Hospital for Special Surgery (HSS) score. The radiographic results were evaluated with respect to the femorotibial angle (FTA), joint line height (JLH) and tibial bone resection. The average HSS score before TKA was 63.6, which improved to 92.8 at the last follow-up. The FTA averaged varus 0.9 preoperatively and valgus 5.7 at the last follow-up. The JLH averaged 13.9 mm preoperatively and 15.6 mm at the last follow-up. The amount of tibial bone resection averaged 4.8 mm. A meticulous surgical technique can produce satisfactory results in TKA after HTO, considering the correction of the deformity, JLH and the amount of the tibial bone resection. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate whether hydrosalpingeal fluid (HSF) is toxic to the mouse embryo as assessed by the blastocyst development rate (BDR) and by cell counting in vitro. HSF was collected from nine patients undergoing salpingoneostomy to correct hydrosalpinx. Two-cell embryos were obtained from superovulated ICR mice. T6 medium and T6 + 0.4% bovine serum albumin (BSA) were used as control media. T6 medium containing 10% or 50% HSF and 100% HSF from each patient were used as test media. Nine to 15 embryos were cultured in microdrops prepared from each of these media. The BDR was examined after 72 h of culture in these media. To assess the total cell number within each blastocyst, the blastocysts were fixed and stained with Hoechst 33342 to facilitate cell counting. The BDR was affected adversely only by 100% HSF and not in media containing 10% or 50% HSF. The mean BDR using T6 medium and T6 + BSA were 88.7% and 85.3%, respectively. The mean BDR using media containing 10% HSF or 50% HSF were 90.0% and 89.4%, respectively. Mean BDR using 100% HSF was 75.2% (P < 0.05). The overall mean cell counts (± SEM) using T6 medium and T6 + BSA were 86.9 ± 3.2 and 91.0 ± 3.8 respectively. Mean cell counts were decreased significantly only in blastocysts cultured in 100% HSF (63.3 ± 4.6; P < 0.01) but not in blastocysts cultured in 10% or 50% HSF (90.8 ± 4.2 and 81.9 ± 6.1 respectively). Thus, it is concluded that HSF has no embryotoxic effect but has a mildly negative effect on embryonic growth and development. [ABSTRACT FROM PUBLISHER]

Large-scale studies are essential to answer questions about complex microbial communities that can be extremely dynamic across hosts, environments, and time points. However, managing acquisition, processing, and analysis of large numbers of samples poses many challenges, with cross-contamination being the biggest obstacle. Contamination complicates analysis and results in sample loss, leading to higher costs and constraints on mixed sample type study designs. While many researchers opt for 96-well plates for their workflows, these plates present a significant issue: the shared seal and weak separation between wells leads to well-to-well contamination. To address this concern, we propose an innovative high-throughput approach, termed as the Matrix method, which employs barcoded Matrix Tubes for sample acquisition. This method is complemented by a paired nucleic acid and metabolite extraction, utilizing 95% (vol/vol) ethanol to stabilize microbial communities and as a solvent for extracting metabolites. Comparative analysis between conventional 96-well plate extractions and the Matrix method, measuring 16S rRNA gene levels via quantitative polymerase chain reaction, demonstrates a notable decrease in well-to-well contamination with the Matrix method. Metagenomics, 16S rRNA gene amplicon sequencing (16S), and untargeted metabolomics analysis via liquid chromatography-tandem mass spectrometry (LC-MS/MS) confirmed that the Matrix method recovers reproducible microbial and metabolite compositions that can distinguish between subjects. This advancement is critical for large-scale study design as it minimizes well-to-well contamination and technical variation, shortens processing times, and integrates with automated infrastructure for enhancing sample randomization and metadata generation., Importance: Understanding dynamic microbial communities typically requires large-scale studies. However, handling large numbers of samples introduces many challenges, with cross-contamination being a major issue. It not only complicates analysis but also leads to sample loss and increased costs and restricts diverse study designs. The prevalent use of 96-well plates for nucleic acid and metabolite extractions exacerbates this problem due to their wells having little separation and being connected by a single plate seal. To address this, we propose a new strategy using barcoded Matrix Tubes, showing a significant reduction in cross-contamination compared to conventional plate-based approaches. Additionally, this method facilitates the extraction of both nucleic acids and metabolites from a single tubed sample, eliminating the need to collect separate aliquots for each extraction. This innovation improves large-scale study design by shortening processing times, simplifying analysis, facilitating metadata curation, and producing more reliable results., Competing Interests: R.K. is a scientific advisory board member and consultant for BiomeSense, Inc., has equity, and receives income. He is a scientific advisory board member and has equity in GenCirq. He is a consultant and scientific advisory board member for DayTwo and receives income. He has equity in and acts as a consultant for Cybele. He is a co-founder of Biota, Inc., and has equity. He is a cofounder of Micronoma, has equity, and is a scientific advisory board member. D.M. is a consultant for, and has stock in, BiomeSense, Inc. P.C.D. is an advisor and holds equity in Cybele, Sirenas, and BileOmix and is a scientific co-founder and advisor for and holds equity in Ometa, Enveda, and Arome with prior approval by University of California San Diego. P.C.D. also consulted for DSM animal health in 2023. The terms of these arrangements have been reviewed and approved by the University of California San Diego, in accordance with its conflict of interest policies.

High levels of social connectivity among group-living animals have been hypothesized to benefit individuals by creating opportunities to rapidly reseed the microbiome and maintain stability against disruption. We tested this hypothesis by perturbing the microbiome of a wild population of Grant's gazelles with an antibiotic and asking whether microbiome recovery differs between individuals with high versus low levels of social connectivity. We found that after treatment, individuals with high social connectivity experienced a faster increase in microbiome richness than less socially connected individuals. Unexpectedly, the rapid increase in microbiome richness of highly connected individuals that received treatment led to their microbiomes becoming more distinct relative to the background population. Our results suggest that the microbiome of individuals with high social connectivity can be rapidly recolonized after a perturbation event, but this leads to a microbiome that is more distinct from, rather than more similar to the unperturbed state. This work provides new insight into the role of social interactions in shaping the microbiome.

Ingenane-type diterpenoids (ITDs) are distinct components of plants belonging to the genus Euphorbia . These compounds have significant cytotoxic effects on non-small cell lung cancer (NSCLC) cells. However, the underlying molecular mechanism has yet to be reported. To explore the mechanism of the anticancer effect of ITDs, we carried out a network pharmacology prediction study. PPI network suggested that SRC and PI3K had high levels of interaction. In addition, KEGG analysis revealed that these common targets were significantly enriched in the PI3K/Akt signalling pathway. 13-oxyingenol-dodecanoate (13OD) was used for validation after the biological evaluation of some ITDs against NSCLC cells. It demonstrated that 13OD could significantly inhibit the growth of NSCLC cells by inducing apoptosis. The results from molecular docking and Western blotting showed that 13OD interacted with SRC and PI3K and down-regulated the SRC/PI3K/Akt signalling pathway in NSCLC cells. This study provided the underlying mechanism of ITDs against NSCLC.

Background/aims: To compare the performance of generative versus retrieval-based chatbots in answering patient inquiries regarding age-related macular degeneration (AMD) and diabetic retinopathy (DR)., Methods: We evaluated four chatbots: generative models (ChatGPT-4, ChatGPT-3.5 and Google Bard) and a retrieval-based model (OcularBERT) in a cross-sectional study. Their response accuracy to 45 questions (15 AMD, 15 DR and 15 others) was evaluated and compared. Three masked retinal specialists graded the responses using a three-point Likert scale: either 2 (good, error-free), 1 (borderline) or 0 (poor with significant inaccuracies). The scores were aggregated, ranging from 0 to 6. Based on majority consensus among the graders, the responses were also classified as 'Good', 'Borderline' or 'Poor' quality., Results: Overall, ChatGPT-4 and ChatGPT-3.5 outperformed the other chatbots, both achieving median scores (IQR) of 6 (1), compared with 4.5 (2) in Google Bard, and 2 (1) in OcularBERT (all p ≤8.4×10 -3 ). Based on the consensus approach, 83.3% of ChatGPT-4's responses and 86.7% of ChatGPT-3.5's were rated as 'Good', surpassing Google Bard (50%) and OcularBERT (10%) (all p ≤1.4×10 -2 ). ChatGPT-4 and ChatGPT-3.5 had no 'Poor' rated responses. Google Bard produced 6.7% Poor responses, and OcularBERT produced 20%. Across question types, ChatGPT-4 outperformed Google Bard only for AMD, and ChatGPT-3.5 outperformed Google Bard for DR and others., Conclusion: ChatGPT-4 and ChatGPT-3.5 demonstrated superior performance, followed by Google Bard and OcularBERT. Generative chatbots are potentially capable of answering domain-specific questions outside their original training. Further validation studies are still required prior to real-world implementation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Autonomous micro/nanorobots capable of performing programmed missions are at the forefront of next-generation micromachinery. These small robotic systems are predominantly constructed using functional components sourced from micro- and nanoscale materials; therefore, combining them with various advanced materials represents a pivotal direction toward achieving a higher level of intelligence and multifunctionality. This review provides a comprehensive overview of advanced materials for innovative micro/nanorobotics, focusing on the five families of materials that have witnessed the most rapid advancements over the last decade: two-dimensional materials, metal-organic frameworks, semiconductors, polymers, and biological cells. Their unique physicochemical, mechanical, optical, and biological properties have been integrated into micro/nanorobots to achieve greater maneuverability, programmability, intelligence, and multifunctionality in collective behaviors. The design and fabrication methods for hybrid robotic systems are discussed based on the material categories. In addition, their promising potential for powering motion and/or (multi-)functionality is described and the fundamental principles underlying them are explained. Finally, their extensive use in a variety of applications, including environmental remediation, (bio)sensing, therapeutics, etc. , and remaining challenges and perspectives for future research are discussed.

Ischaemic stroke (IS) is the second leading cause of death and a major cause of disability worldwide. Currently, the clinical management of IS still depends on restoring blood flow via pharmacological thrombolysis or mechanical thrombectomy, with accompanying disadvantages of narrow therapeutic time window and risk of haemorrhagic transformation. Thus, novel pathophysiological mechanisms and targeted therapeutic candidates are urgently needed. The autophagy-lysosomal pathway (ALP), as a dynamic cellular lysosome-based degradative process, has been comprehensively studied in recent decades, including its upstream regulatory mechanisms and its role in mediating neuronal fate after IS. Importantly, increasing evidence has shown that IS can lead to lysosomal dysfunction, such as lysosomal membrane permeabilization, impaired lysosomal acidity, lysosomal storage disorder, and dysfunctional lysosomal ion homeostasis, which are involved in the IS-mediated defects in ALP function. There is tightly regulated crosstalk between transcription factor EB (TFEB), mammalian target of rapamycin (mTOR) and lysosomal function, but their relationship remains to be systematically summarized. Notably, a growing body of evidence emphasizes the benefits of naturally derived compounds in the treatment of IS via modulation of ALP function. However, little is known about the roles of natural compounds as modulators of lysosomes in the treatment of IS. Therefore, in this context, we provide an overview of the current understanding of the mechanisms underlying IS-mediated ALP dysfunction, from a lysosomal perspective. We also provide an update on the effect of natural compounds on IS, according to their chemical structural types, in different experimental stroke models, cerebral regions and cell types, with a primary focus on lysosomes and autophagy initiation. This review aims to highlight the therapeutic potential of natural compounds that target lysosomal and ALP function for IS treatment., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Pepper ( Piper nigrum L.) is a widely used spice plant known for its fruits and roots, which serve as flavor enhancers in culinary applications and hold significant economic value. Despite the popularity of pepper fruits, their roots remain relatively understudied, with limited research conducted on their bioactive components. This study focused on discovering and separating the primary bioactive amide alkaloids found in pepper roots. The process involved using the antioxidant activity of crude fractions and the Global Natural Products Social Molecular Networking analysis platform. The process led to the discovery of 23 previously unknown hydroxyl-amide alkaloids. Notably, compounds 11 , 12 , and 14 showed excellent antioxidant activity, while compound 11 exhibited significant inhibitory effects on mushroom tyrosinase. Theoretical exploration of enzyme-ligand interactions was conducted through molecular docking and molecular dynamics simulation. The findings of this study highlight the potential of hydroxyl-amide alkaloids as antioxidant products and natural food preservatives in the pharmaceutical and food cosmetic industries.

Plastics are one of the most pervasive materials on Earth, to which humans are exposed daily. Polystyrene (PS) is a common plastic packaging material. However, the impact of PS on human health remains poorly understood. Therefore, this study aimed to identify intestinal damage induced by PS nanoplastics (PS-NPs) in zebrafish larvae which have a high homology with humans. Four days post fertilization (dpf), zebrafish larvae were exposed to 0-, 10-, and 50-ppm PS-NPs for 48 h Initially, to ascertain if 100 nm PS-NPs could accumulate in the gastrointestinal (GI) tract of zebrafish larvae, the larvae were exposed to red fluorescence-labeled PS-NPs, and at 6 dpf, the larvae were examined using a fluorescence microscope. Analysis of the fluorescence intensity revealed that the GI tract of larvae exposed to 50-ppm exhibited a significantly stronger fluorescence intensity than the other groups. Nonfluorescent PS-NPs were then used in further studies. Scanning electron microscopy (SEM) confirmed the spherical shape of the PS-NPs. Fourier-transform infrared spectroscopy (FT-IR) analysis revealed chemical alterations in the PS-NPs before and after exposure to larvae. The polydispersity index (PDI) value derived using a Zetasizer indicated a stable dispersion of PS-NPs in egg water. Whole-mount apoptotic signal analysis via TUNEL assay showed increased apoptosis in zebrafish larval intestines exposed to 50-ppm PS-NPs. Damage to the intestinal tissue was assessed by Alcian blue (AB) and hematoxylin and eosin (H&E) staining. AB staining revealed increased mucin levels in the zebrafish larval intestines. Thin larval intestinal walls with a decrease in the density of intestinal epithelial cells were revealed by H&E staining. The differentially expressed genes (DEGs) induced by PS-NPs were identified and analyzed. In conclusion, exposure to PS-NPs may damage the intestinal barrier of zebrafish larvae due to increased intestinal permeability, and the in vivo gene network may change in larvae exposed to PS-NPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Context.—: Pathology training programs generally prepare graduates well for the workforce, but there may be other aspects to navigating a job that make the transition from being a trainee to a practicing pathologist challenging., Objective.—: To identify perceived challenges of independent practice for early career pathologists and assess how these impressions evolve throughout their first year., Design.—: A survey was distributed to 12 anatomic pathology fellows from 4 institutions near the end of their final training year, and 6 months and 1 year after starting their first job. The surveys queried participants' comfort level with signing out cases independently and interacting with colleagues/trainees via Likert attitude scale questions, with free-text segments to elaborate on challenges experienced., Results.—: The response rate to all 3 surveys was 100%. Confidence and comfort level with different aspects of independent sign-out increased incrementally over time. Main challenges encountered at 6 months included a high case load, signing out cases in areas outside of their subspecialty, time management, balancing teaching while signing out, laboratory issues, and developing relationships with clinicians. At 12 months, main challenges included time management, high case load, understaffing, laboratory issues, and signing out cases in areas outside of their subspecialty., Conclusions.—: This study identified real-time challenges faced by those adjusting to their first year of independent practice. By gaining a better understanding of the factors that make this transition challenging, we can find tailored ways to support our early career pathologists., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

Purpose: This study assessed the use of liver stiffness (LS) and dispersion slope (DS) in classifying patients with chronic hepatitis B (CHB) by the necessity of antiviral treatment., Methods: A retrospective review examined 249 patients with CHB (male:female, 107:142; mean age, 53±14 years) between April 2018 and March 2022. Patients for whom treatment was indicated, termed group 1, exhibited either serum alanine transaminase (ALT) and aspartate aminotransferase levels not exceeding five times the upper limit of normal and LS &gt;13 kPa, or hepatitis B virus DNA &gt;2,000 IU/mL and ALT &gt;40 IU/L. The remaining patients comprised group 2 (treatment not required). In subgroup analysis, patients with LS &lt;13 kPa were further examined., Results: Overall, group 1 exhibited significantly higher LS (12.64±6.76 vs. 6.31±1.67 kPa, P&lt;0.001) and DS (15.52±4.95 vs. 11.04±1.93 [m/s]/kHz, P&lt;0.001) than group 2. In subgroup analysis, group 1 also demonstrated significantly higher values (LS: 8.05±2.12 vs 6.31±1.67 kPa, P&lt;0.001, DS: 13.06±2.75 vs. 11.04±1.93 [m/s]/kHz, P&lt;0.001). The areas under the curve (AUCs) for LS and DS in group 1 were 0.855 (95% confidence interval [CI], 0.80 to 0.90; P&lt;0.001) and 0.810 (95% CI, 0.75 to 0.86; P&lt;0.001), respectively. In subgroup analysis, the AUCs for LS and DS in group 1 were 0.751 (95% CI, 0.69 to 0.81; P&lt;0.001) and 0.711 (95% CI, 0.64 to 0.77; P&lt;0.001), respectively. Within group 1, the AUCs for LS and DS did not differ significantly (P&gt;0.05)., Conclusion: LS and DS assist in classifying patients with CHB by their need for antiviral treatment.

Plants and their use as bioreactors for the generation of recombinant proteins have become one of the hottest topics in the field of Plant Biotechnology and Plant Synthetic Biology. Plant bioreactors offer superior engineering potential compared to other types, particularly in the realm of subcellular accumulation strategies for increasing production yield and quality. This review explores established and emerging strategies for subcellular accumulation of recombinant proteins in tobacco bioreactors, highlighting recent advancements in the field. Additionally, the review provides reference to the crucial initial step of selecting an optimal subcellular localization for the target protein, a design that substantially impacts production outcomes., Competing Interests: Competing interests: The authors have no relevant relationships to disclose., (Copyright © 2024 Shi-Jian Song et al.)

Extrachromosomal circular DNA (eccDNA), a pervasive yet enigmatic component of the eukaryotic genome, exists autonomously from its chromosomal counterparts. Ubiquitous in eukaryotes, eccDNA plays a critical role in the orchestration of cellular processes and the etiology of diseases, particularly cancers. However, the full scope of its influence on health and disease remains elusive, presenting a rich vein of research yet to be mined. Unraveling the complexities of eccDNA necessitates a distillation of methodologies - from biogenesis to functional analysis - a landscape we overview in this study with precision and clarity. Here, we systematically outline cutting-edge methodologies from high-throughput sequencing and bioinformatics to experimental validations, showcasing the intricate world of eccDNAs. We combed through a treasure trove of auxiliary research resources and analytical tools. Moreover, we chart a course for future inquiry, illuminating the horizon with potential groundbreaking strategies for designing eccDNA research projects and pioneering new methodological frontiers., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: Human milk is unquestionably beneficial for preterm infants. We investigated how the transition from tube to oral/breastfeeding impacts the preterm infants' oral and gut microbiome and metabolome., Methods: We analyzed stool, saliva, and milk samples collected from a cohort of preterm infants enrolled in the MAP Study, a prospective observational trial. The microbiome and metabolome of the samples were analyzed from 4 longitudinal sample time points, 2 during tube feeds only and 2 after the initiation of oral/breastfeeding., Results: We enrolled 11 mother-infant dyads (gestational age = 27.9 (23.4-32.2)) and analyzed a total of 39 stool, 44 saliva, and 43 milk samples over 4 timepoints. In saliva samples, there was a shift towards increased Streptococcus and decreased Staphylococcus after oral feeding/breastfeeding initiation (p < 0.05). Milk sample metabolites were strongly influenced by the route of feeding and milk type (p < 0.05) and represented the pathways of Vitamin E metabolism, Vitamin B12 metabolism, and Tryptophan metabolism., Conclusion: Our analysis demonstrated that the milk and preterm infant's saliva microbiome and metabolome changed over the course of the first four to 5 months of life, coinciding with the initiation of oral/breastfeeds., Impact: The microbiome and metabolome is altered in the infant's saliva but not their stool, and in mother's milk when feeds are transitioned from tube to oral/breastfeeding. We assessed the relationship between the gut and oral microbiome/metabolome with the milk microbiome/metabolome over a longitudinal period of time in preterm babies. Metabolites that changed in the infants saliva after the initiation of oral feeds have the potential to be used as biomarkers for disease risk., (© 2024. The Author(s).)

Objective: To understand the effect of collagen peptides on the function of mouse lymphocytes under simulated microgravity., Methods: The splenocytes of mice were isolated, and the rotary cell culture system was used to simulate the microgravity. The T lymphocytes were stimulated with mitotic agents, concanavalin A (ConA), and the cells were treated with different concentrations of collagen peptides. The proliferation of lymphocytes and the levels of cytokines in the supernatant were detected., Results: Simulated microgravity could inhibit the proliferation of spleen T lymphocytes and decrease the level of cytokines in the supernatant. Collagen peptides could promote the lymphocyte proliferation and cytokine production in cells cultured under simulated microgravity., Conclusion: Collagen peptides may attenuate the inhibitory effect of simulated microgravity on T lymphocytes by regulating the cell proliferation and the secretion of cytokines.

Purpose: To evaluate the association between three allergic diseases (allergic dermatitis, allergic rhinitis, and asthma) and the development of retinal vein occlusion (RVO), a major retinal disease that causes visual impairment., Method: This study used data obtained from the Korean National Health Insurance Claims database between 2009 and 2018. The association between the three atopic triads (allergic dermatitis, allergic rhinitis, and asthma) and the occurrence of sight-threatening RVO, as determined by diagnostic and treatment codes, were analyzed. Multivariate adjusted Cox regression analysis was used to determine the hazard ratios (HRs) and 95% confidence intervals for RVO development in the presence of allergic disease., Results: In this population-based study, 2,160,195 (54.6%) individuals were male, 1,794,968 (45.4%) were female, and 620,938 (15.7%) were diagnosed with allergic diseases. Patients with either asthma or allergic rhinitis had a greater risk of RVO (adjusted hazard ratio (aHR) = 1.101, 95% confidence interval [CI] = 1.029-1.178 for asthma; aHR = 1.181, 95% CI = 1.147-1.215 for allergic rhinitis) compared to those without asthma or allergic rhinitis; however, patients with atopic dermatitis did not show a significant association with RVO (aHR = 1.071, 95% CI = 0.889-1.290), after adjusting for other risk factors., Conclusion: Our study revealed that allergic rhinitis, asthma, and coexisting multiple allergic conditions were associated with an increased risk of RVO. Thus, it may be advisable to suggest an ophthalmological examination for patients with allergies due to the increased possibility of the occurrence of retinal vascular disease.

Demyelinating diseases are often caused by a variety of triggers, including immune responses, viral infections, malnutrition, hypoxia, or genetic factors, all of which result in the loss of myelin in the nervous system. The accumulation of myelin debris at the lesion site leads to neuroinflammation and inhibits remyelination; therefore, it is crucial to promptly remove the myelin debris. Initially, Fc and complement receptors on cellular surfaces were the primary clearance receptors responsible for removing myelin debris. However, subsequent studies have unveiled the involvement of additional receptors, including Mac-2, TAM receptors, and the low-density lipoprotein receptor-related protein 1, in facilitating the removal process. In addition to microglia and macrophages, which serve as the primary effector cells in the disease phase, a variety of other cell types such as astrocytes, Schwann cells, and vascular endothelial cells have been demonstrated to engage in the phagocytosis of myelin debris. Furthermore, we have concluded that oligodendrocyte precursor cells, as myelination precursor cells, also exhibit this phagocytic capability. Moreover, our research group has innovatively identified the low-density lipoprotein receptor as a potential phagocytic receptor for myelin debris. In this article, we discuss the functional processes of various phagocytes in demyelinating diseases. We also highlight the alterations in signaling pathways triggered by phagocytosis, and provide a comprehensive overview of the various phagocytic receptors involved. Such insights are invaluable for pinpointing potential therapeutic strategies for the treatment of demyelinating diseases by targeting phagocytosis., (© 2024 Wiley Periodicals LLC.)

Importance: Feasibility of home urogenital microbiome specimen collection is unknown., Objectives: This study aimed to evaluate successful sample collection rates from home and clinical research centers., Study Design: Adult women participants enrolled in a multicentered cohort study were recruited to an in-person research center evaluation, including self-collected urogenital samples. A nested feasibility substudy evaluated home biospecimen collection prior to the scheduled in-person evaluation using a home collection kit with written instructions, sample collection supplies, and a Peezy™ urine collection device. Participants self-collected samples at home and shipped them to a central laboratory 1 day prior to and the day of the in-person evaluation. We defined successful collection as receipt of at least one urine specimen that was visibly viable for sequencing., Results: Of 156 participants invited to the feasibility substudy, 134 were enrolled and sent collection kits with 89% (119/134) returning at least 1 home urine specimen; the laboratory determined that 79% (106/134) of these urine samples were visually viable for analysis. The laboratory received self-collected urine from the research center visit in 97% (115/119); 76% (91/119) were visually viable for sequencing. Among 401 women who did not participate in the feasibility home collection substudy, 98% (394/401) self-collected urine at the research center with 80% (321/401) returned and visibly viable for sequencing., Conclusions: Home collection of urogenital microbiome samples for research is feasible, with comparable success to clinical research center collection. Sample size adjustment should plan for technical and logistical difficulties, regardless of specimen collection site., Competing Interests: Emily S. Lukacz is a scientific advisory board member and consultant for Pathnostics (2021 to present), receives royalties from UpToDate (2015 to present), is an advisory board member for Emmi Solutions (patient education material, 2023 to present), and works for Tegus.com (2023 to present). Furthermore, she is a consultant (study section) for NIDDK and received research funding from NIDDK, NICHD, and PCORI. Cynthia S. Fok received author royalty from UptoDate and is a consultant for UroCure and Medtronic. Melanie R. Meister is an advisory board member for AbbVie Inc. Margaret G. Mueller provides expert testimony for Butler Snow and received educational honoraria from Axonics and NIH funding (NIDDK and NICHD). Ariana L. Smith received research funding from Convatec and PA Department of State, is an associate editor for NAU, and is on the board of directors and a treasurer for SUFU. Ann Stapleton is a consultant for GSK. Daniel McDonald is a consultant for, and has equity in, BiomeSense, Inc. The terms of these arrangements have been reviewed and approved by the University of California, San Diego, in accordance with its conflict of interest policies. Rob Knight is a scientific advisory board member and consultant for BiomeSense, Inc., has equity, and receives income. He is a scientific advisory board member and has equity in GenCirq. He is a consultant and scientific advisory board member for DayTwo and receives income. He has equity in and acts as a consultant for Cybele. He is a cofounder of Biota, Inc. and has equity. He is a cofounder of Micronoma, has equity, and is a scientific advisory board member. The terms of these arrangements have been reviewed and approved by the University of California, San Diego, in accordance with its conflict of interest policies. Linda Brubaker received editorial stipends from JAMA and UptoDate. The rest of the authors reported no disclosures., (Copyright © 2024 American Urogynecologic Society. All rights reserved.)

Purpose: The aims of the present study were (a) to compare the scanning time and image count to complete optical scans of a typodont between augmented-reality-assisted intraoral scanning (ARIOS) and intraoral scanning (IOS); (b) to compare the accuracy of the digital casts derived from ARIOS and IOS; (c) to compare participant-related outcomes between ARIOS and IOS., Materials and Methods: A multi-session within-subject experiment was conducted to compare ARIOS and IOS. Thirty-one dental students participated in the study. Following a trial session, each participant obtained optical scans under ARIOS and IOS conditions. The time required to complete the scan, and the number of images taken were recorded. Participant feedback was collected using entry, exit, and NASA-Task Load Index (TLX) surveys. The accuracy of the digital casts derived from the optical scans was measured in root mean square error (RMSE)., Results: The present study found a 6.8% increase in preference for ARIOS from entry to exit survey. Slightly more participants favored the ARIOS setup compared to IOS; 54.8% of participants favored ARIOS, 9.7% were indifferent, and 35.5% favored IOS. NASA-TLX subscale ratings were higher for IOS in general apart from mental demand. The accuracy of the digital casts between ARIOS and IOS was comparable in RMSE., Conclusion: ARIOS was advantageous compared to IOS in ergonomics, improved scanner tracking, and ease of scanner orientation. However additional trials, increased field of view, and better superimposition of scanning status to the target site were improvements desired by the study participants., (© 2024 by the American College of Prosthodontists.)

A phytochemical study of the ethanol extract from Ailanthus altissima (Mill.) Swingle leaves resulted in the isolation of four new monoterpenoids (1-3, 5). The structures were elucidated using HRESIMS data, NMR spectroscopic data, quantum chemical calculations for NMR and ECD, and custom DP4+ probability analysis. Additionally, the absolute configuration of sugar was determined by acid hydrolysis. Compounds 1-4 are cyclogeraniane monocyclic monoterpenes, while compound 5 contains an acyclic mycrane monoterpenes skeleton. Anti-tyrosinase, anti-acetylcholinesterase, and anti-butyrylcholinesterase activities were tested. Compound 1 showed notable anti-acetylcholinesterase activity, and compound 3 exhibited significant inhibitory effects on anti-tyrosinase activity. Furthermore, the potential binding sites of compounds 1 and 3 were predicted by molecular docking., Competing Interests: Declaration of competing interest Qi Song, Zhi-Kang Duan, Ya-Nuo Tan, Zhi-Heng Gao, Dai Liu, Jin-Le Hao, Bin Lin, Xiao-Xiao Huang, and Shao-Jiang Song declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In managing metabolic dysfunction-associated steatotic liver disease, which affects over 30% of the general population, effective noninvasive biomarkers for assessing disease severity, monitoring disease progression, predicting the development of liver-related complications, and assessing treatment response are crucial. The advantage of simple fibrosis scores lies in their widespread accessibility through routinely performed blood tests and extensive validation in different clinical settings. They have shown reasonable accuracy in diagnosing advanced fibrosis and good performance in excluding the majority of patients with a low risk of liver-related complications. Among patients with elevated serum fibrosis scores, a more specific fibrosis and imaging biomarker has proved useful to accurately identify patients at risk of liver-related complications. Among specific fibrosis blood biomarkers, enhanced liver fibrosis is the most widely utilized and has been approved in the United States as a prognostic biomarker. For imaging biomarkers, the availability of vibration-controlled transient elastography has been largely improved over the past years, enabling the use of liver stiffness measurement (LSM) for accurate assessment of significant and advanced fibrosis, and cirrhosis. Combining LSM with other routinely available blood tests enhances the ability to diagnose at-risk metabolic dysfunction-associated steatohepatitis; and predict liver-related complications, some reaching an accuracy comparable to that of liver biopsy. Magnetic resonance imaging-based modalities provide the most accurate quantification of liver fibrosis, though the current utilization is limited to research settings. Expanding their future use in clinical practice depends on factors such as cost and facility availability.

Ultra-widefield (UWF) retinal imaging stands as a pivotal modality for detecting major eye diseases such as diabetic retinopathy and retinal detachment. However, UWF exhibits a well-documented limitation in terms of low resolution and artifacts in the macular area, thereby constraining its clinical diagnostic accuracy, particularly for macular diseases like age-related macular degeneration. Conventional supervised super-resolution techniques aim to address this limitation by enhancing the resolution of the macular region through the utilization of meticulously paired and aligned fundus image ground truths. However, obtaining such refined paired ground truths is a formidable challenge. To tackle this issue, we propose an unpaired, degradation-aware, super-resolution technique for enhancing UWF retinal images. Our approach leverages recent advancements in deep learning: specifically, by employing generative adversarial networks and attention mechanisms. Notably, our method excels at enhancing and super-resolving UWF images without relying on paired, clean ground truths. Through extensive experimentation and evaluation, we demonstrate that our approach not only produces visually pleasing results but also establishes state-of-the-art performance in enhancing and super-resolving UWF retinal images. We anticipate that our method will contribute to improving the accuracy of clinical assessments and treatments, ultimately leading to better patient outcomes.

Purpose: Chronic kidney disease (CKD) may elevate susceptibility to age-related macular degeneration (AMD) because of shared risk factors, pathogenic mechanisms, and genetic polymorphisms. Given the inconclusive findings in prior studies, we investigated this association using extensive datasets in the Asian Eye Epidemiology Consortium., Design: Cross-sectional study., Participants: Fifty-one thousand two hundred fifty-three participants from 10 distinct population-based Asian studies., Methods: Age-related macular degeneration was defined using the Wisconsin Age-Related Maculopathy Grading System, the International Age-Related Maculopathy Epidemiological Study Group Classification, or the Beckman Clinical Classification. Chronic kidney disease was defined as estimated glomerular filtration rate (eGFR) of less than 60 ml/min per 1.73 m 2 . A pooled analysis using individual-level participant data was performed to examine the associations between CKD and eGFR with AMD (early and late), adjusting for age, sex, hypertension, diabetes, body mass index, smoking status, total cholesterol, and study groups., Main Outcome Measures: Odds ratio (OR) of early and late AMD., Results: Among 51 253 participants (mean age, 54.1 ± 14.5 years), 5079 had CKD (9.9%). The prevalence of early AMD was 9.0%, and that of late AMD was 0.71%. After adjusting for confounders, individuals with CKD were associated with higher odds of late AMD (OR, 1.46; 95% confidence interval [CI], 1.11-1.93; P = 0.008). Similarly, poorer kidney function (per 10-unit eGFR decrease) was associated with late AMD (OR, 1.12; 95% CI, 1.05-1.19; P = 0.001). Nevertheless, CKD and eGFR were not associated significantly with early AMD (all P ≥ 0.149)., Conclusions: Pooled analysis from 10 distinct Asian population-based studies revealed that CKD and compromised kidney function are associated significantly with late AMD. This finding further underscores the importance of ocular examinations in patients with CKD., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Employing an MS/MS-based molecular networking-guided strategy, three new eudesmane-type sesquiterpenes (1-3) and one undescribed pseudoguaianolide sesquiterpene (8), along with four known eudesmane-type sesquiterpene lactones (4-7) were extracted and purified from the herbs of Carpesium abrotanoides L. Structural elucidation encompassed comprehensive spectroscopic analysis, NMR calculations, DP4+ analysis, and ECD calculations. The cytotoxicity activity of all isolates was evaluated against two human hepatoma carcinoma cells (HepG2 and Hep3B) in vitro. It was demonstrated that compounds 2 and 4 showed moderate cytotoxic against HepG2 and Hep3B cells. Furthermore, all compounds were evaluated for their acetylcholinesterase (AChE) inhibitory activity. Particularly noteworthy is that, in comparison to the positive control, compound 1 demonstrated significant AChE inhibition with an inhibition rate of 77.86%. In addition, the inhibitory mechanism of compound 1 were investigated by in silico docking analyze and molecular dynamic simulation., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

1,2-diarylpropanes are a kind of abundant natural products formed by radical coupling. On account of molecular flexibility, it was challenged in the identifications of relative and absolute configurations of the 1,2-diarylpropanes. In this research, fourteen pairs of enantiomeric 1,2-diarylpropanes (1a/1b-14a/14b), comprising twelve previously undescribed pairs (1a/1b-4a/4b, 6a/6b-10a/10b, and 12a/12b-14a/14b), were isolated from the fruit of Crataegus pinnatifida. Their structures were determined through multiple NMR spectral analyses, empirical NMR rules, X-ray crystallography, and the comparison of experimental ECD spectra with calculated data. In addition, the analysis of ECD spectra revealed that substituent effects could generate an inverted chiroptical response, exhibiting in mirror-image ECD signals. This phenomenon was investigated by conformational analysis, molecular orbital analysis, the transition density matrix and hole/electron distributions. Moreover, a potential experimental rule was proposed for the rapid determination of the absolute configurations of the 1,2-diarylpropanes., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest to this work., (Copyright © 2024. Published by Elsevier Ltd.)

Diabetic retinopathy (DR) is a major complication of diabetes mellitus and is a leading cause of vision loss globally. A prompt and accurate diagnosis is crucial for ensuring favorable visual outcomes, highlighting the need for increased access to medical care. The recent remarkable advancements in artificial intelligence (AI) have raised high expectations for its role in disease diagnosis and prognosis prediction across various medical fields. In addition to achieving high precision comparable to that of ophthalmologists, AI-based diagnosis of DR has the potential to improve medical accessibility, especially through telemedicine. In this review paper, we aim to examine the current role of AI in the diagnosis of DR and explore future directions.

Lung cancer is the leading cause of cancer deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancers. Euphorbia kansui yielded 13-oxyingenol-dodecanoate (13OD), an ingenane-type diterpenoid, which had a strong cytotoxic effect on NSCLC cells. The underlying mechanism and potential target, however, remained unknown. The study found that 13OD effectively inhibited the cell proliferation and colony formation of NSCLC cells (A549 and H460 cells), with less toxicity in normal human lung epithelial BEAS-2B cells. Moreover, 13OD can cause mitochondrial dysfunction, and apoptosis in NSCLC cells. Mechanistically, the transcriptomics results showed that differential genes were mainly enriched in the mTOR and AMPK signaling pathways, which are closely related to cellular autophagy, the related indicators were subsequently validated. Additionally, bafilomycin A1 (Baf A1), an autophagy inhibitor, reversed the mitochondrial damage caused by 13OD. Furthermore, the Omics and Text-based Target Enrichment and Ranking (OTTER) method predicted ULK1 as a potential target of 13OD against NSCLC cells. This hypothesis was further confirmed using molecular docking, the cellular thermal shift assay (CETSA), and Western blot analysis. Remarkably, ULK1 siRNA inhibited 13OD's toxic activity in NSCLC cells. In line with these findings, 13OD was potent and non-toxic in the tumor xenograft model. Our findings suggested a possible mechanism for 13OD's role as a tumor suppressor and laid the groundwork for identifying targets for ingenane-type diterpenoids., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Demand for the exploration of botanical pesticides continues to increase due to the detrimental effects of synthetic chemicals on human health and the environment and the development of resistance by pests. Under the guidance of a bioactivity-guided approach and HSQC-based DeepSAT, 16 coumarin derivatives were discovered from the leaves of Ailanthus altissima (Mill.) Swingle, including seven undescribed monoterpenoid coumarins, three undescribed monoterpenoid phenylpropanoids, and two new coumarin derivatives. The structure and configurations of these compounds were established and validated via extensive spectroscopic analysis, acetonide analysis, and quantum chemical calculations. Biologically, 5 exhibited significant antifeedant activity toward the Plutella xylostella . Moreover, tyrosinase being closely related to the growth and development of larva, the inhibitory potentials of 5 against tyrosinase was evaluated in vitro and in silico . The bioactivity evaluation results highlight the prospect of 5 as a novel category of botanical insecticide.

The role of ferroptosis-associated gene SLC7A11 in esophageal cancer progression is largely unknown, therefore, the effects of blocking SLC7A11 on esophageal squamous cell carcinoma (ESCC) cells are evaluated. Results showed that SLC7A11 was overexpressed in ESCC tissues both in mRNA and protein levels. Blocking SLC7A11 using Erastin suppressed the proliferation and colony formation of ESCC cells, decreased cellular ATP levels, and improved ROS production. Sixty-three SLC7A11-binding proteins were identified using the IP-MS method, and these proteins were enriched in four signaling pathways, including spliceosome, ribosome, huntington disease, and diabetic cardiomyopathy. The deubiquitinase inhibitors PR-619, GRL0617, and P 22077 could reduce at least 40% protein expression level of SLC7A11 in ESCC cells, and PR-619 and GRL0617 exhibited suppressive effects on the cell viability and colony formation ability of KYSE30 cells, respectively. Erastin downregulated GPX4 and DHODH and also reduced the levels of β-catenin, p-STAT3, and IL-6 in ESCC cells. In conclusion, SLC7A11 was overexpressed in ESCC, and blocking SLC7A11 using Erastin mitigated malignant phenotypes of ESCC cells and downregulated key ferroptosis-associated molecules GPX4 and DHODH. The therapeutic potential of targeting SLC7A11 should be further evaluated in the future., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background & Aims: FibroScan® Expert 630 and FibroScan® Mini+430 are novel vibration-controlled transient elastography devices equipped with the same SmartExam software, which allows continuous measurement of controlled attenuation parameter (CAP) during the entire examination. This study aims to compare the CAP variabilities and the quantification for liver fibrosis and steatosis between the conventional FibroScan and the SmartExam-equipped machines in patients with metabolic dysfunction-associated steatotic liver disease (MASLD)., Methods: This retrospective study included 118 patients with biopsy-proven MASLD who underwent liver biopsy at two tertiary centres between 2021 and 2023. Liver stiffness and steatosis measurements were performed using both FibroScan machines and M and XL probes for each individual. Liver histology was used as the reference standard for liver fibrosis and steatosis staging., Results: Standard deviations of continuous CAP (cCAP) were significantly lower than those of CAP for all probes (p < .0001). CAP variability was significantly associated with body mass index (p < .01), probe selection (p < .001) as well as the random effect of centre. Only the effect of probe selection (p < .001) was significantly associated with cCAP variability. No significant difference was found in the performance of staging liver fibrosis and steatosis between two types of machines at the same cut-offs., Conclusions: The SmartExam-based VCTE reduces the variability of CAP measurement and achieves a similar accuracy as the FibroScan 502 device for the estimation of both hepatic steatosis and fibrosis. Future studies should determine if cCAP is a better tool to monitor changes in steatosis than the original CAP., (© 2024 The Authors. Liver International published by John Wiley & Sons Ltd.)