The growth factor content as an indicator of platelet counts in platelet-rich plasma.

BACKGROUND: Platelet contains growth factors that enhance tissue repair mechanisms, including epidermal growth factor (EGF), platelet-derived growth factor (PDGF-AA and -AB), and transforming growth factor (TGF)-ß. Autologous platelet-rich plasma (PRP) has been shown to significantly improve the treatment of tendon injuries compared with hyaluronic acid and placebo. The topic of agreement between platelet concentrations and growth factors has been covered in some previous studies, but growth factor levels did not correlate well with platelet concentrations. METHOD: In this study, autologous PRP was prepared by concentrating platelets through a J6-MI centrifuge. The automatic hematology analyzer Sysmex XN-20 was used to analyze the platelet concentration in PRP, and the PRP growth factors were determined by ELISA, including PDGF, transforming growth factor- ß1 (TGF-ß1), and EGF. Statistical analysis was conducted on data from 107 patients who received autologous PRP using Pearson correlation analysis. RESULTS: Pearson correlation analysis revealed PDGF, TGF, and EGF had a strong positive correlation with the platelet concentration of the final PRP product (r = 0.697, p < 0.0001; r = 0.488, p < 0.0001; r = 0.572, p < 0.0001, respectively) CONCLUSIONS: There was a strong positive correlation between the concentration of platelets in the final PRP product and the levels of PDGF-AB, TGF-ß, and EGF. These results suggested straightforward and cost-effective growth factor tests can provide valuable information about platelet content in PRP.

Evaluating artificial intelligence's role in lung nodule diagnostics: A survey of radiologists in two pilot tertiary hospitals in China.

Objectives: This study assesses the perceptions and attitudes of Chinese radiologists concerning the application of artificial intelligence (AI) in the diagnosis of lung nodules. Material and Methods: An anonymous questionnaire, consisting of 26 questions addressing the usability of AI systems and comprehensive evaluation of AI technology, was distributed to all radiologists affiliated with Beijing Anzhen Hospital and Beijing Tsinghua Changgung Hospital. The data collection was conducted between July 19, and 21, 2023. Results: Of the 90 respondents, the majority favored the AI system's convenience and usability, reflected in "good" system usability scale (SUS) scores (Mean ± standard deviation [SD]: 74.3 ± 11.9). General usability was similarly well-received (Mean ± SD: 76.0 ± 11.5), while learnability was rated as "acceptable" (Mean ± SD: 67.5 ± 26.4). Most radiologists noted increased work efficiency (Mean Likert scale score: 4.6 ± 0.6) and diagnostic accuracy (Mean Likert scale score: 4.2 ± 0.8) with the AI system. Views on AI's future impact on radiology careers varied (Mean ± SD: 3.2 ± 1.4), with a consensus that AI is unlikely to replace radiologists entirely in the foreseeable future (Mean ± SD: 2.5 ± 1.1). Conclusion: Radiologists at two leading Beijing hospitals generally perceive the AI-assisted lung nodule diagnostic system positively, citing its user-friendliness and effectiveness. However, the system's learnability requires enhancement. While AI is seen as beneficial for work efficiency and diagnostic accuracy, its long-term career implications remain a topic of debate.

Gradient conducting polymer surfaces with netrin-1-conjugation promote axon guidance and neuron transmission of human iPSC-derived retinal ganglion cells.

Major advances have been made in utilizing human-induced pluripotent stem cells (hiPSCs) for regenerative medicine. Nevertheless, the delivery and integration of hiPSCs into target tissues remain significant challenges, particularly in the context of retinal ganglion cell (RGC) restoration. In this study, we introduce a promising avenue for providing directional guidance to regenerated cells in the retina. First, we developed a technique for construction of gradient interfaces based on functionalized conductive polymers, which could be applied with various functionalized ehthylenedioxythiophene (EDOT) monomers. Using a tree-shaped channel encapsulated with a thin PDMS and a specially designed electrochemical chamber, gradient flow generation could be converted into a functionalized-PEDOT gradient film by cyclic voltammetry. The characteristics of the successfully fabricated gradient flow and surface were analyzed using fluorescent labels, time of flight secondary ion mass spectrometry (TOF-SIMS), and X-ray photoelectron spectroscopy (XPS). Remarkably, hiPSC-RGCs seeded on PEDOT exhibited improvements in neurite outgrowth, axon guidance and neuronal electrophysiology measurements. These results suggest that our novel gradient PEDOT may be used with hiPSC-based technologies as a potential biomedical engineering scaffold for functional restoration of RGCs in retinal degenerative diseases and optic neuropathies.

Semi-supervised meta-learning elucidates understudied molecular interactions.

Many biological problems are understudied due to experimental limitations and human biases. Although deep learning is promising in accelerating scientific discovery, its power compromises when applied to problems with scarcely labeled data and data distribution shifts. We develop a deep learning framework-Meta Model Agnostic Pseudo Label Learning (MMAPLE)-to address these challenges by effectively exploring out-of-distribution (OOD) unlabeled data when conventional transfer learning fails. The uniqueness of MMAPLE is to integrate the concept of meta-learning, transfer learning and semi-supervised learning into a unified framework. The power of MMAPLE is demonstrated in three applications in an OOD setting where chemicals or proteins in unseen data are dramatically different from those in training data: predicting drug-target interactions, hidden human metabolite-enzyme interactions, and understudied interspecies microbiome metabolite-human receptor interactions. MMAPLE achieves 11% to 242% improvement in the prediction-recall on multiple OOD benchmarks over various base models. Using MMAPLE, we reveal novel interspecies metabolite-protein interactions that are validated by activity assays and fill in missing links in microbiome-human interactions. MMAPLE is a general framework to explore previously unrecognized biological domains beyond the reach of present experimental and computational techniques.

The impact of energy poverty on the health and welfare of the middle-aged and older adults.

Drawing upon data from the 2018 CHARLS, this paper utilizes MEPI and a 10% threshold indicator to, respectively, assess the energy poverty (EP) status among middle-aged and older adults in China, focusing on the unavailability and unaffordability of energy services. Additionally, an econometric model is constructed to investigate the effects of EP on the health and welfare of middle-aged and older adults. Regression results indicate that EP exerts a significant negative impact on the health and welfare of middle-aged and older adults. This conclusion remains robust after conducting endogeneity and robustness tests, demonstrating its validity. Finally, based on the calculation results, we propose relevant policy recommendations including enhancing energy services for older adults in rural areas, integrating household energy alternatives with targeted poverty alleviation, enhancing monitoring mechanisms, and conducting energy education activities to alleviate EP and improve the quality of life of middle-aged and older adults.

Patient, family, and community factors associated with medication adherence among people with hypertension or diabetes: A cross-sectional analysis.

Background: While suboptimal medication adherence remains an obstacle to the management of hypertension and diabetes in China, few studies have investigated associated factors with medication adherence on different dimensions simultaneously. Objective: To systematically examine associated patient, family, and community factors with suboptimal medication adherence among people with hypertension and/or type 2 diabetes in China. Methods: The study stratified a random sample of 622 adults aged 45 years or older with hypertension and/or type 2 diabetes from three southeast cities in China in 2019. Trained interviewers used the Morisky Green Levine Medication Adherence Scale, Self-Efficacy to Manage Chronic Disease (SEMCD) Scale, and the Family Adaptability, Partnership, Growth, Affection, and Resolve (APGAR) Scale to assess medication adherence, self-efficacy, and family function, respectively. Participants also reported their perceived satisfaction with community health services (quantity, quality, affordability, and overall acceptance). The study used the multivariable logistic regression to assess the association of patient, family, and community factors with suboptimal medication adherence. Results: Among the participants, 42.9% reported suboptimal medication adherence. In the multivariable logistic regression model, male participants (odds ratio [OR] = 0.55, p = 0.001) had higher medication adherence compared to females. Having a self-efficacy score that was lower than or equal to the sample mean was significantly associated with lower adherence (OR = 1.44, p = 0.039). Participants unsatisfied with the affordability of community health services and medicine had lower adherence (OR = 2.18, p = 0.028) than those neutral or satisfied. There were no significant associations between family function and medication adherence. Conclusions: Sex, self-efficacy, and perceived affordability of community health services were important factors associated with medication adherence. Healthcare professionals are recommended to consider multiple factors and leverage services and resources in community health centers when promoting medication adherence.

Apoptosis mediated by crosstalk between mitochondria and endoplasmic reticulum: A possible cause of citrinin disruption of the intestinal barrier.

Citrinin (CTN) is a mycotoxin commonly found in contaminated foods and feed, posing health risks to both humans and animals. However, the mechanism by which CTN damages the intestine remains unclear. In this study, a model of intestinal injury was induced by administering 1.25 mg/kg and 5 mg/kg of CTN via gavage for 28 consecutive days in 6-week-old Kunming mice, aiming to explore the potential mechanisms underlying intestinal injury. The results demonstrate that CTN can cause structural damage to the mouse jejunum. Additionally, CTN reduces the protein expression of Claudin-1, Occludin, ZO-1, and MUC2, thereby disrupting the physical and chemical barriers of the intestine. Furthermore, exposure to CTN alters the structure of the intestinal microbiota in mice, thus compromising the intestinal microbial barrier. Meanwhile, the results showed that CTN exposure could induce excessive apoptosis in intestinal cells by altering the expression of proteins such as CHOP and GRP78 in the endoplasmic reticulum and Bax and Cyt c in mitochondria. The mitochondria and endoplasmic reticulum are connected through the mitochondria-associated endoplasmic reticulum membrane (MAM), which regulates the membrane. We found that the expression of bridging proteins Fis1 and BAP31 on the membrane was increased after CTN treatment, which would exacerbate the endoplasmic reticulum dysfunction, and could activate proteins such as Caspase-8 and Bid, thus further inducing apoptosis via the mitochondrial pathway. Taken together, these results suggest that CTN exposure can cause intestinal damage by disrupting the intestinal barrier and inducing excessive apoptosis in intestinal cells.

Clinicopathological factors of ovarian clear cell carcinoma: A single institutional analysis of 247 cases in China.

Ovarian clear cell carcinoma (OCCC) is a subtype of ovarian cancer with a poor prognosis that often shows resistance to chemotherapy. This study retrospectively analyzed 247 patients with OCCC who were admitted to the Cancer Hospital of the Chinese Academy of Medical Sciences (CAMS) between August 2007 and August 2023. Univariate and multivariate Cox regression analyses were used to identify clinicopathological factors associated with OCCC, and a nomogram prediction model was developed to predict OCCC patient survival outcomes. Kaplan‒Meier survival analysis was used to compare survival outcomes among patients with recurrent disease. Compared with systemic therapy, secondary debulking surgery significantly improved the postrecurrence survival (PRS) rate (P = 0.006). Subgroup analysis revealed that the survival benefit was more pronounced in patients with recurrence and satisfactory tumor shrinkage (PPRS = 0.01, PPFS2 = 0.047). The multivariate analysis revealed that positive preoperative ascites, incomplete remission following initial treatment, and undergoing more than six cycles of postoperative chemotherapy were independent prognostic factors affecting overall survival (OS). Additionally, patients with a positive PD-L1 test who received immunotherapy did not experience relapse during the follow-up period. In conclusion, the secondary clearance procedure offers significant benefits for patients with recurrent OCCC, and patients may experience a survival benefit from supplemental immune or targeted therapy at the end of chemotherapy. The development of a personalized treatment plan can help achieve precise treatment, improve prognosis, and enhance patients' quality of life.

Glucose-responsive, self-healing, wet adhesive and multi-biofunctional hydrogels for diabetic wound healing.

Diabetic wounds are serious clinical complications which manifest wet condition due to the mass exudate, along with disturbed regulation of inflammation, severe oxidative stress and repetitive bacterial infection. Existing treatments for diabetic wounds remain unsatisfactory due to the lack of ideal dressings that encompass mechanical performance, adherence to moist tissue surfaces, quick repair, and diverse therapeutic benefits. Herein, we fabricated a wet adhesive, self-healing, glucose-responsive drug releasing hydrogel with efficient antimicrobial and pro-healing properties for diabetic wound treatment. PAE hydrogel was constructed with poly(acrylic acid-co-acrylamide) (AA-Am) integrated with a dynamic E-F crosslinker, which consisted of epigallocatechin gallate (EGCG) and 4-(2-acrylamidoethylcarbamoyl)-3-fluorophenylboronic acid (AFPBA). Due to the dynamic crosslinking nature of boronate esters, abundant catechol groups and hydrogen bonding, PAE hydrogel demonstrated excellent mechanical properties with about 1000 % elongation, robust adhesion to moist tissues, fast self-healing, and absorption of biofluids of 10 times of its own weight. Importantly, PAE hydrogel exhibited sustained and glucose-responsive release of EGCG. Together, the bioactive PAE hydrogel had effective antibacterial, antioxidative, and anti-inflammatory properties in vitro, and accelerated diabetic wound healing in rats via reducing tissue-inflammatory response, enhancing angiogenesis, and reprogramming of macrophages. Overall, this versatile hydrogel provides a straightforward solution for the treatment of diabetic wound, and shows potential for other wound-related application scenarios.

Plant-based and planetary-health diets, environmental burden, and risk of mortality: a prospective cohort study of middle-aged and older adults in China.

BACKGROUND: Plant-based diets (PBDs) and planetary-health diets (PHDs) are recommended for their potential health and environmental benefits, but population-based evidence in diverse cultures is scarce. METHODS: We included 9364 adults aged 45 years and older (52·3% female, 47·7% male) from the open cohort of the China Health and Nutrition Survey. Dietary intake was assessed using 3-day 24 h dietary recalls combined with weighing methods from 1997 to 2011, and mortality was documented from 1997 to 2015. We calculated the overall PBD index (PDI), healthful PBD index (hPDI), and unhealthful PBD index (uPDI; ranges 18-90), and the PHD score (range 0-140). We also estimated the related greenhouse gas emissions, land appropriation, and total water footprint and examined their associations with mortality. FINDINGS: PBD indices were inversely related to greenhouse gas emissions, land appropriation, and total water footprint, whereas higher PHD score was related to higher environmental burdens (p<0·0001). During follow-up (mean 9·2 years), 792 (8·5%) death cases were documented. PDI (HR 1·08 [95% CI 0·88-1·32]) and hPDI (0·98 [0·80-1·21]) were not significantly associated with mortality, whereas higher uPDI was related to a higher mortality risk (1·55 [1·26-1·91]). In contrast, higher PHD score was associated with lower mortality risk (0·79 [0·63-0·99]). INTERPRETATION: The PBDs showed environmental benefits, but are not necessarily associated with lower mortality risk. The PHD, developed mainly in western populations, was related to lower mortality risk but higher environmental burdens in the Chinese population. FUNDING: Fundamental Research Funds for the Central Universities, Zhejiang University Global Partnership Fund, and National Natural Science Foundation of China.

Burden of cancers in six female organs in China and worldwide.

BACKGROUND: Cancers in female organs remain a substantial burden in China and worldwide. GLOBOCAN 2022 has recently updated the estimates of cancer burden. This study aims to depict the profiles of disease burden and to compare the age-specific rates of cancers in female organs in China with those in other countries. METHODS: The latest estimates of incidence and mortality of cancers in female organs from various regions and countries were extracted from the GLOBOCAN 2022 database. We compared the proportion of total cases or deaths for cancers affecting six female organs and other tumor types in China and globally. Correlation analysis was conducted to evaluate the relationship between age-standardized incidence rate (ASIR) or age-standardized mortality rate (ASMR) and the Human Development Index (HDI). Additionally, age-specific rate curves were plotted for ten exemplary countries with different income levels. RESULTS: Globally, there are varying burdens of female organ cancers, with higher incidence rates in Northern America and elevated rates of cervical cancer in Africa. Female organ cancers in China remain a significant burden due to their large proportion of the six tumors. A positive correlation between socioeconomic development and the incidence of breast, uterine corpus, ovarian, and vulvar cancers was noted, whereas a negative association between the HDI tiers and mortality rates was found for cervical and vaginal cancers. In 2022, Chinese women aged 50-54 years are experiencing high incidence rates of breast, cervix uteri, corpus uteri, and ovarian cancers. CONCLUSIONS: Cancers in female organs continue to be a significant health concern for women in China and worldwide. It is crucial to implement comprehensive prevention strategies tailored to address the increasing trend among younger individuals and reduce regional disparities.

Endoplasmic reticulum stress promotes oxidative stress, inflammation, and apoptosis: A novel mechanism of citrinin-induced renal injury and dysfunction.

Citrinin (CTN) has been reported to induce renal failure and structural damage, but its nephrotoxic effects and mechanisms are not fully understood. Therefore, we established a model by orally administering CTN (0, 1.25, 5, or 20 mg/kg) to mice for 21 consecutive days. Histological and biochemical analyses revealed that CTN caused structural damage to renal tubules, increased inflammatory cell infiltration, and elevated levels of serum markers of renal function (creatinine, urea, and uric acid). Moreover, mRNA transcript levels of the inflammatory factors TNF-α, IL-1ß, and IL-6 were increased, indicating the occurrence of an inflammatory response. Furthermore, exposure to CTN induced renal oxidative stress by decreasing antioxidant GSH levels, antioxidant enzyme (SOD, CAT) activities, and increasing oxidative products (ROS, MDA). In addition, CTN increased the expression of proteins associated with endoplasmic reticulum (ER)stress and apoptotic pathways. ER stress has been shown to be involved in regulating various models of kidney disease, but its role in CTN-induced renal injury has not been reported. We found that pretreatment with the ER stress inhibitor 4-PBA (240 mg/kg, ip) alleviated CTN-induced oxidative stress, NF-κB pathway mediated inflammatory response, and apoptosis. Interestingly, 4-PBA also partially alleviated renal structural damage and dysfunction. Thus, ER stress may be a novel target for the prevention and treatment of CTN-induced renal injury.

The Off-Treatment Effects of Olpasiran on Lipoprotein(a) Lowering: OCEAN(a)-DOSE Extension Period Results.

BACKGROUND: Olpasiran, a small interfering RNA (siRNA), blocks lipoprotein(a) (Lp(a)) production by preventing translation of apolipoprotein(a) mRNA. In phase 2, higher doses of olpasiran every 12 weeks (Q12W) reduced circulating Lp(a) by >95%. OBJECTIVES: This study sought to assess the timing of return of Lp(a) to baseline after discontinuation of olpasiran, as well as longer-term safety. METHODS: OCEAN(a)-DOSE (Olpasiran Trials of Cardiovascular Events And LipoproteiN[a] Reduction-DOSE Finding Study) was a phase 2, dose-finding trial that enrolled 281 participants with atherosclerotic cardiovascular disease and Lp(a) >150 nmol/L to 1 of 4 active doses of olpasiran vs placebo (10 mg, 75 mg, 225 mg Q12W, or an exploratory dose of 225 mg Q24W given subcutaneously). The last dose of olpasiran was administered at week 36; after week 48, there was an extended off-treatment follow-up period for a minimum of 24 weeks. RESULTS: A total of 276 (98.2%) participants entered the off-treatment follow-up period. The median study exposure (treatment combined with off-treatment phases) was 86 weeks (Q1-Q3: 79-99 weeks). For the 75 mg Q12W dose, the off-treatment placebo-adjusted mean percent change from baseline in Lp(a) was -76.2%, -53.0%, -44.0%, and -27.9% at 60, 72, 84, and 96 weeks, respectively (all P < 0.001). The respective off-treatment changes in Lp(a) for the 225 mg Q12W dose were -84.4%, -61.6%, -52.2%, and -36.4% (all P < 0.001). During the extension follow-up phase, no new safety concerns were identified. CONCLUSIONS: Olpasiran is a potent siRNA with prolonged effects on Lp(a) lowering. Participants receiving doses ≥75 mg Q12W sustained a ∼40% to 50% reduction in Lp(a) levels close to 1 year after the last dose. (Olpasiran Trials of Cardiovascular Events And LipoproteiN[a] Reduction-DOSE Finding Study [OCEAN(a)-DOSE]; NCT04270760).

Caffeic acid modulates intestinal microbiota, alleviates inflammatory response, and enhances barrier function in a piglet model challenged with lipopolysaccharide.

Young animals are highly susceptible to intestinal damage due to incomplete intestinal development, making them vulnerable to external stimuli. Weaning stress in piglets, for instance, disrupts the balance of intestinal microbiota and metabolism, triggering intestinal inflammation and resulting in gut damage. Caffeic acid (CA), a plant polyphenol, can potentially improve intestinal health. Here, we evaluated the effects of dietary CA on the intestinal barrier and microbiota using a lipopolysaccharide (LPS)-induced intestinal damage model. Eighteen piglets were divided into three groups: control group (CON), LPS group (LPS), and CA + LPS group (CAL). On the 21st and 28th day, six piglets in each group were administered either LPS (80 µg/kg body weight; Escherichia coli O55:B5) or saline. The results showed that dietary CA improved the intestinal morphology and barrier function, and alleviated the inflammatory response. Moreover, dietary CA also improved the diversity and composition of the intestinal microbiota by increasing Lactobacillus and Terrisporobacter while reducing Romboutsia. Furthermore, the LPS challenge resulted in a decreased abundance of 14 different bile acids and acetate, which were restored to normal levels by dietary CA. Lastly, correlation analysis further revealed the potential relationship between intestinal microbiota, metabolites, and barrier function. These findings suggest that dietary CA could enhance intestinal barrier function and positively influence intestinal microbiota and its metabolites to mitigate intestinal damage in piglets. Consuming foods rich in CA may effectively reduce the incidence of intestinal diseases and promote intestinal health in piglets.

Our study focuses on a major issue affecting young animals. After weaning, piglets are particularly vulnerable to severe intestinal infections due to their immature intestinal systems, leading to damaged barriers and financial losses for the pig industry. We explore the possibility of using caffeic acid (CA), a natural compound found in plants, to promote intestinal health. Our research shows that adding CA to the diet can reduce intestinal inflammation and improve barrier function in weaned piglets challenged by lipopolysaccharide. CA positively affects ileal microbiota by increasing beneficial bacteria like Lactobacillus and Terrisporobacter and decreasing Romboutsia. We also observed differing regulatory effects of CA between the ileum and colon, with opposite changes in primary bile acids. Our findings emphasize the potential of CA as a dietary supplement to improve intestinal barrier function and modulate the inflammatory response by targeting gut microbiota and metabolites. To our knowledge, this is the first to demonstrate the effects of CA on ileal barrier function and microbiota in piglets. Our findings could significantly benefit the pig industry by mitigating financial losses from serious intestinal infections. Additionally, this research may offer key insights into the health of human infants' intestines.

Glycolytic dysregulation in Alzheimer's disease: unveiling new avenues for understanding pathogenesis and improving therapy.

Alzheimer's disease poses a significant global health challenge owing to the progressive cognitive decline of patients and absence of curative treatments. The current therapeutic strategies, primarily based on cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists, offer limited symptomatic relief without halting disease progression, highlighting an urgent need for novel research directions that address the key mechanisms underlying Alzheimer's disease. Recent studies have provided insights into the critical role of glycolysis, a fundamental energy metabolism pathway in the brain, in the pathogenesis of Alzheimer's disease. Alterations in glycolytic processes within neurons and glial cells, including microglia, astrocytes, and oligodendrocytes, have been identified as significant contributors to the pathological landscape of Alzheimer's disease. Glycolytic changes impact neuronal health and function, thus offering promising targets for therapeutic intervention. The purpose of this review is to consolidate current knowledge on the modifications in glycolysis associated with Alzheimer's disease and explore the mechanisms by which these abnormalities contribute to disease onset and progression. Comprehensive focus on the pathways through which glycolytic dysfunction influences Alzheimer's disease pathology should provide insights into potential therapeutic targets and strategies that pave the way for groundbreaking treatments, emphasizing the importance of understanding metabolic processes in the quest for clarification and management of Alzheimer's disease.

Molecular composition limits the reaction kinetics of riverine dissolved organic matter decomposition.

The bioavailability and degradation of riverine dissolved organic matter (DOM) play crucial roles in greenhouse gas emissions; however, studies on the kinetic decomposition of fluvial DOM remain scarce. In this study, the decomposition kinetics of dissolved organic carbon (DOC) were characterized using the reactivity continuum model through 28-day bio-incubation experiments with water samples from the Yangtze River. The relationship between DOM composition and decomposition kinetics was analyzed using optical and molecular characterization combined with apparent decay coefficients. Our results revealed that DOM compounds rich in nitrogen and sulfur were predominantly removed, exhibiting a transition from an unsaturated to a saturated state following microbial degradation. These heteroatomic compounds, which constituted 75.61 % of the DOM compounds positively correlated with the decay coefficient k0, underwent preferential degradation in the early stages of bio-incubation due to their higher bioavailability. Additionally, we observed that S-containing fractions with high molecular weight values (MW > 400 Da) may be associated with larger reactivity grades. This study underscored the complex interplay between DOM composition and its kinetic decomposition in river ecosystems, providing further support for the significance of molecular composition in large river DOM as crucial factors affecting decomposition.

Latest developments of generative artificial intelligence and applications in ophthalmology.

The emergence of generative artificial intelligence (AI) has revolutionized various fields. In ophthalmology, generative AI has the potential to enhance efficiency, accuracy, personalization and innovation in clinical practice and medical research, through processing data, streamlining medical documentation, facilitating patient-doctor communication, aiding in clinical decision-making, and simulating clinical trials. This review focuses on the development and integration of generative AI models into clinical workflows and scientific research of ophthalmology. It outlines the need for development of a standard framework for comprehensive assessments, robust evidence, and exploration of the potential of multimodal capabilities and intelligent agents. Additionally, the review addresses the risks in AI model development and application in clinical service and research of ophthalmology, including data privacy, data bias, adaptation friction, over interdependence, and job replacement, based on which we summarized a risk management framework to mitigate these concerns. This review highlights the transformative potential of generative AI in enhancing patient care, improving operational efficiency in the clinical service and research in ophthalmology. It also advocates for a balanced approach to its adoption.

Nesprin-2 coordinates opposing microtubule motors during nuclear migration in neurons.

Nuclear migration is critical for the proper positioning of neurons in the developing brain. It is known that bidirectional microtubule motors are required for nuclear transport, yet the mechanism of the coordination of opposing motors is still under debate. Using mouse cerebellar granule cells, we demonstrate that Nesprin-2 serves as a nucleus-motor adaptor, coordinating the interplay of kinesin-1 and dynein. Nesprin-2 recruits dynein-dynactin-BicD2 independently of the nearby kinesin-binding LEWD motif. Both motor binding sites are required to rescue nuclear migration defects caused by the loss of function of Nesprin-2. In an intracellular cargo transport assay, the Nesprin-2 fragment encompassing the motor binding sites generates persistent movements toward both microtubule minus and plus ends. Nesprin-2 drives bidirectional cargo movements over a prolonged period along perinuclear microtubules, which advance during the migration of neurons. We propose that Nesprin-2 keeps the nucleus mobile by coordinating opposing motors, enabling continuous nuclear transport along advancing microtubules in migrating cells.

RNA m6A modification regulates cell fate transition between pluripotent stem cells and 2-cell-like cells.

N6-methyladenosine (m6A) exerts essential roles in early embryos, especially in the maternal-to-zygotic transition stage. However, the landscape and roles of RNA m6A modification during the transition between pluripotent stem cells and 2-cell-like (2C-like) cells remain elusive. Here, we utilised ultralow-input RNA m6A immunoprecipitation to depict the dynamic picture of transcriptome-wide m6A modifications during 2C-like transitions. We found that RNA m6A modification was preferentially enriched in zygotic genome activation (ZGA) transcripts and MERVL with high expression levels in 2C-like cells. During the exit of the 2C-like state, m6A facilitated the silencing of ZGA genes and MERVL. Notably, inhibition of m6A methyltransferase METTL3 and m6A reader protein IGF2BP2 is capable of significantly delaying 2C-like state exit and expanding 2C-like cells population. Together, our study reveals the critical roles of RNA m6A modification in the transition between 2C-like and pluripotent states, facilitating the study of totipotency and cell fate decision in the future.

Furin Egress from the TGN is Regulated by Membrane-Associated RING-CH Finger (MARCHF) Proteins and Ubiquitin-Specific Protease 32 (USP32) via Nondegradable K33-Polyubiquitination.

Furin primarily localizes to the trans-Golgi network (TGN), where it cleaves and activates a broad range of immature proproteins that play critical roles in cellular homeostasis, disease progression, and infection. Furin is retrieved from endosomes to the TGN after being phosphorylated, but it is still unclear how furin exits the TGN to initiate the post-Golgi trafficking and how its activity is regulated in the TGN. Here three membrane-associated RING-CH finger (MARCHF) proteins (2, 8, 9) are identified as furin E3 ubiquitin ligases, which catalyze furin K33-polyubiquitination. Polyubiquitination prevents furin from maturation by blocking its ectodomain cleavage inside cells but promotes its egress from the TGN and shedding. Further ubiquitin-specific protease 32 (USP32) is identified as the furin deubiquitinase in the TGN that counteracts the MARCHF inhibitory activity on furin. Thus, the furin post-Golgi trafficking is regulated by an interplay between polyubiquitination and phosphorylation. Polyubiquitination is required for furin anterograde transport but inhibits its proprotein convertase activity, and phosphorylation is required for furin retrograde transport to produce fully active furin inside cells.