Breaking the Activity-Selectivity Trade-off for CH4-to-C2H6 Photoconversion.

Photocatalytic conversion of methane (CH4) to ethane (C2H6) has attracted extensive attention from academia and industry. Typically, the traditional oxidative coupling of CH4 (OCM) reaches a high C2H6 productivity, yet the inevitable overoxidation limits the target product selectivity. Although the traditional nonoxidative coupling of CH4 (NOCM) can improve the product selectivity, it still encounters unsatisfied activity, arising from being thermodynamically unfavorable. To break the activity-selectivity trade-off, we propose a conceptually new mechanism of H2O2-triggered CH4 coupling, where the H2O2-derived ·OH radicals are rapidly consumed for activating CH4 into ·CH3 radicals exothermically, which bypasses the endothermic steps of the direct CH4 activation by photoholes and the interaction between ·CH3 and ·OH radicals, affirmed by in situ characterization techniques, femtosecond transient absorption spectroscopy, and density-functional theory calculation. By this pathway, the designed Au-WO3 nanosheets achieve unprecedented C2H6 productivity of 76.3 mol molAu-1 h-1 with 95.2% selectivity, and TON of 1542.7 (TOF = 77.1 h-1) in a self-designed flow reactor, outperforming previously reported photocatalysts regardless of OCM and NOCM pathways. Also, under outdoor natural sunlight irradiation, the Au-WO3 nanosheets exhibit similar activity and selectivity toward C2H6 production, showing the possibility for practical applications. Interestingly, this strategy can be applied to other various photocatalysts (Au-WO3, Au-TiO2, Au-CeO2, Pd-WO3, and Ag-WO3), showing a certain universality. It is expected that the proposed mechanism adds another layer to our understanding of CH4-to-C2H6 conversion.

Rapid, Micron-Resolution 3D Printing of Nd:YAG Ceramic with Optical Gain.

Polycrystalline yttrium aluminum garnet (YAG) ceramic doped with neodymium (Nd), referred to as Nd:YAG, is widely used in solid-state lasers. However, conventional powder metallurgy methods suffer from expenses, time consumption, and limitations in customizing structures. This study introduces a novel approach for creating Nd:YAG ceramics with 3D free-form structures from micron (∼70 µm) to centimeter scales. Firstly, sol-gel synthesis is employed to form photocurable colloidal solutions. Subsequently, by utilizing a home-built micro-continuous liquid interface printing process, precursors are printed into 3D poly(acrylic acid) hydrogels containing yttrium, aluminum, and neodymium hydroxides, with a resolution of 5.8 µm pixel-1 at a speed of 10 µm s-1. After the hydrogels undergo thermal dehydration, debinding, and sintering, polycrystalline Nd:YAG ceramics featuring distinguishable grains are successfully produced. By optimizing the concentrations of the sintering aids (tetraethyl orthosilicate) and neodymium trichloride (NdCl3), the resultant samples exhibit satisfactory photoluminescence, emitting light concentrated at 1064 nm when stimulated by a 532 nm laser. Additionally, Nd:YAG ceramics with various 3D geometries (e.g., cone, spiral, and angled pillar) are printed and characterized, which demonstrates the potential for applications, such as laser and amplifier fibers, couplers, and splitters in optical circuits, as well as gain metamaterials or metasurfaces.

Versatile Patterning of Liquid Metal via Multiphase 3D Printing.

This paper presents a scalable and straightforward technique for the immediate patterning of liquid metal/polymer composites via multiphase 3D printing. Capitalizing on the polymer's capacity to confine liquid metal (LM) into diverse patterns. The interplay between distinctive fluidic properties of liquid metal and its self-passivating oxide layer within an oxidative environment ensures a resilient interface with the polymer matrix. This study introduces an inventive approach for achieving versatile patterns in eutectic gallium indium (EGaIn), a gallium alloy. The efficacy of pattern formation hinges on nozzle's design and internal geometry, which govern multiphase interaction. The interplay between EGaIn and polymer within the nozzle channels, regulated by variables such as traverse speed and material flow pressure, leads to periodic patterns. These patterns, when encapsulated within a dielectric polymer polyvinyl alcohol (PVA), exhibit an augmented inherent capacitance in capacitor assemblies. This discovery not only unveils the potential for cost-effective and highly sensitive capacitive pressure sensors but also underscores prospective applications of these novel patterns in precise motion detection, including heart rate monitoring, and comprehensive analysis of gait profiles. The amalgamation of advanced materials and intricate patterning techniques presents a transformative prospect in the domains of wearable sensing and comprehensive human motion analysis.

Identification and function analysis of BCL2 in immune response of Pteria penguin.

B-cell lymphoma/leukemia-2 (BCL2), an anti-apoptotic factor in the mitochondrial regulatory pathway of apoptosis, is critically important in immune defenses. In this study, a novel BCL2 gene was characterized from Pteria penguin (P. penguin). The PpBCL2 was 1482 bp long, containing an open reading frame (ORF) of 588 bp encoding 195 amino acids. Four highly conserved BCL-2 homology (BH) domains were found in PpBCL2. Amino acid alignment and phylogenetic tree showed that PpBCL2 had the highest similarity with BCL2 of Crassostrea gigas at 65.24 %. Tissue expression analysis showed that PpBCL2 had high constitutive expression in gill, digestive diverticulum and mantle, and was significantly increased 72 h of Vibrio parahaemolyticus (V. parahaemolyticus) challenge in these immune tissues. Furthermore, PpBCL2 silencing significantly inhibited antimicrobial activity of hemolymph supernatant by 1.4-fold, and significantly reduced the survival rate by 51.7 % at 72 h post infection in P. penguin. These data indicated that PpBCL2 played an important role in immune response of P. penguin against V. parahaemolyticus infection.

Chlorogenic acid improves common carp (Cyprinus carpio) liver and intestinal health through Keap-1/Nrf2 and NF-κB signaling pathways: Growth performance, immune response and antioxidant capacity.

In this experiment, we investigated the effects of adding chlorogenic acid (CGA) to the diet on growth performance, immune function, inflammation response, antioxidant capacity and its related mechanisms of common carp (Cyprinus carpio). A total of 600 fish were selected and randomly divided into five treatment groups and fed with CGA containing 0 mg/kg (CK), 100 mg/kg (L100), 200 mg/kg (L200), 400 mg/kg (L400) and 800 mg/kg (L800) for 56 days. The results of the experiment were as follows: addition of CGA significantly increased the WGR, SGR, FER, and PER of common carp (P < 0.05). The addition of 400-800 mg/kg of CGA significantly increased the serum levels of LZM, AKP activity, C3 and C4 concentration, and increased immune function of common carp (P < 0.05). Regarding antioxidant enzyme activities, adding CGA significantly increased SOD, CAT, and GsH-Px activities, while decreasing MDA content (P < 0.05). Compared with the CK group, the mRNA expression levels of NF-κB, TNF-α, and IL-1ß were decreased. The IL-10 and TGF-ß were increased in the liver and intestines of the CGA supplemented group. Meanwhile, the addition of CGA also significantly up-regulated the mRNA expression levels of Nrf2, HO-1, SOD, CAT, and GPX (P < 0.05). CGA also positively contributed to the development of the carp intestinal tract, as demonstrated by decreased serum levels of DAO, D-LA, and ET-1. And the mucosal fold height was increased significantly with increasing levels of CGA. In conclusion, the addition of CGA in the feed can enhance the growth performance, immune function and antioxidant capacity of common carp, and improve the health of the intestine and liver. According to the results of this experiment, the optimal addition amount in common carp diets was 400 mg/kg.

Nomogram predictive model for in-hospital mortality risk in elderly ICU patients with urosepsis.

BACKGROUND: Urinary tract infection (UTI) is a common cause of sepsis. Elderly patients with urosepsis in intensive care unit (ICU) have more severe conditions and higher mortality rates owing to factors such as advanced age, immunosenescence, and persistent host inflammatory responses. However, comprehensive studies on nomograms to predict the in-hospital mortality risk in elderly patients with urosepsis are lacking. This study aimed to construct a nomogram predictive model to accurately assess the prognosis of elderly patients with urosepsis and provide therapeutic recommendations. METHODS: Data of elderly patients with urosepsis were extracted from the Medical Information Mart for Intensive Care (MIMIC) IV 2.2 database. Patients were randomly divided into training and validation cohorts. A predictive nomogram model was constructed from the training set using logistic regression analysis, followed by internal validation and sensitivity analysis. RESULTS: This study included 1,251 patients. LASSO regression analysis revealed that the Glasgow Coma Scale (GCS) score, red cell distribution width (RDW), white blood count (WBC), and invasive ventilation were independent risk factors identified from a total of 43 variables studied. We then created and verified a nomogram. The area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA) of the nomogram were superior to those of the traditional SAPS-II, APACHE-II, and SOFA scoring systems. The Hosmer-Lemeshow test results and calibration curves suggested good nomogram calibration. The IDI and NRI values showed that our nomogram scoring tool performed better than the other scoring systems. The DCA curves showed good clinical applicability of the nomogram. CONCLUSIONS: The nomogram constructed in this study is a convenient tool for accurately predicting in-hospital mortality in elderly patients with urosepsis in ICU. Improving the treatment strategies for factors related to the model could improve the in-hospital survival rates of these patients.

Effects of rural hospital closures on nurse staffing levels and health care utilization at nearby hospitals.

Our study examines the causal effect of rural hospital closures on nearby hospitals' nurse staffing levels and health care utilization. We use data from the 2014-2019 American Hospital Association Survey on nurse staffing level outcomes including licensed practical or vocational nurses (LPNs), registered nurses (RNs), and advanced practice nurses (APNs); and health care utilization outcomes, including inpatient and outpatient surgical operations and emergency department (ED) visits. Using propensity score matching and difference-in-differences (DID) methods, we find that rural hospital closures lead to an average increase of 37.3% in the number of nurses in nearby rural hospitals during the 4 years following the closure. This increase is found across all categories of nurses, including LPNs, RNs, and APNs. We also find a substantial increase in the provision of inpatient and outpatient surgical operations but there is no change in ED visits. We do not find any effects for nearby urban hospitals. Our study suggests that a large proportion of the nursing workforce relocates to nearby hospitals after a rural hospital closure, which mitigates the negative consequences of such closures and allows these nearby hospitals to provide a larger volume of highly profitable services.

MSC-derived exosomes protect auditory hair cells from neomycin-induced damage via autophagy regulation.

BACKGROUND: Sensorineural hearing loss (SNHL) poses a major threat to both physical and mental health; however, there is still a lack of effective drugs to treat the disease. Recently, novel biological therapies, such as mesenchymal stem cells (MSCs) and their products, namely, exosomes, are showing promising therapeutic potential due to their low immunogenicity, few ethical concerns, and easy accessibility. Nevertheless, the precise mechanisms underlying the therapeutic effects of MSC-derived exosomes remain unclear. RESULTS: Exosomes derived from MSCs reduced hearing and hair cell loss caused by neomycin-induced damage in models in vivo and in vitro. In addition, MSC-derived exosomes modulated autophagy in hair cells to exert a protective effect. Mechanistically, exogenously administered exosomes were internalized by hair cells and subsequently upregulated endocytic gene expression and endosome formation, ultimately leading to autophagy activation. This increased autophagic activity promoted cell survival, decreased the mitochondrial oxidative stress level and the apoptosis rate in hair cells, and ameliorated neomycin-induced ototoxicity. CONCLUSIONS: In summary, our findings reveal the otoprotective capacity of exogenous exosome-mediated autophagy activation in hair cells in an endocytosis-dependent manner, suggesting possibilities for deafness treatment.

Willingness to receive mpox vaccine among men who have sex with men: a systematic review and meta-analysis.

BACKGROUND: Since May 2022, mpox outbreaks have been occurring in non-mpox endemic areas, with the main population affected being men who have sex with men (MSM). Outbreak prevention and control depend not only on the effectiveness of vaccines but also on people's willingness to receive these vaccines. Currently, there is lack of synthesis on the overall rates and influence factors of MSMs' willingness to vaccinate against mpox. Therefore, we systematically reviewed studies that assessed the willingness of MSM to receive mpox vaccine. METHODS: Studies reporting mpox vaccination intentions among MSM were included by searching five databases (PubMed, Web of Science, EMBASE, CINAHL, and SCOPUS) from inception to May 12, 2024. The quality of the included literature was assessed using Joanna Briggs Institute's critical appraisal tool. The data analysis software is Stata17. The systematic review has been registered with Prospero (registration ID: CRD42023452357). RESULTS: Twenty cross-sectional studies were included in the review. Meta-analysis results showed that the pooled willingness rate of vaccinate against mpox was 77.0% (95% CI: 73-81%, I2 = 99.4%). According to subgroup analysis, study countries (P = 0.002), research sample size (P = 0.001), and whether participants were infected with HIV (P = 0.002) may be sources of heterogeneity. The results of the meta-analysis of influencing factors showed that more number of sexual partners (OR: 2.24, 95%CI: 1.86-2.69), pre-exposure prophylaxis use (OR: 6.04, 95%CI: 4.80-7.61), history of sexually transmitted infections (OR: 2.96, 95%CI: 2.33-3.76), confidence in the vaccine's effectiveness (OR: 2.79, 95%CI: 2.04-3.80) and safety (OR: 10.89, 95%CI: 5.22-22.72), fear of mpox infection (OR: 2.47, 95%CI: 2.11-2.89) and epidemics (OR: 2.87, 95%CI: 2.22-3.70), high mpox knowledge (OR: 2.35, 95%CI: 1.51-3.66), and the belief that people at high risk should be prioritized for vaccination (OR: 3.09, 95%CI: 1.40-6.84) were the facilitators of vaccine willingness. In addition, as a secondary outcome, meta-analysis results showed a pooled unwillingness rate of 16% (95% CI: 13-20%, I2 = 98.1%, 9 studies). CONCLUSION: Willingness to vaccinate mpox was high among MSM, but some participants still had negative attitudes towards vaccination. Therefore, the Ministry of Public Health should develop targeted and effective strategies against those influencing factors to prevent and manage mpox outbreaks.

The Association Between Rumination and Craving in Chinese Methamphetamine-Dependent Patients: The Masking Effect of Depression.

BACKGROUND: Craving is a core feature of addiction. Rumination and depression play a crucial role in the process of methamphetamine addiction. The aim of this study was to examine the relationship between rumination, depression and craving in methamphetamine patients, which has not been explored yet. METHODS: A total of 778 patients with methamphetamine user disorder (MUD) at the Xinhua Drug Rehabilitation Center, located in Mianyang City, Sichuan Province, China. We used a set of self-administered questionnaires that included socio-demographic, detailed drug use history, rumination, depression and craving information. The Rumination Response Scale (RRS) was used to measure rumination, the Beck Depression Inventory (BDI) to measure depression and the Visual Analogue Scale (VAS) to measure craving. RESULTS: There was a significant positive correlation between rumination and craving, or depression, and between depression and craving. Furthermore, depression mediated between rumination and craving, with a mediation effect of 160%. CONCLUSIONS: Our findings suggest that there is a close interrelationship between rumination, craving and depression in MUD patients, and that depression may play a mediating role between rumination and craving.

This is the first study to investigate the relationship between rumination and craving during withdrawal in methamphetamine dependent patients and the mediating role of depression.Among methamphetamine patients, it was found that reflection was positively correlated with rumination and depression, depression and craving, rumination and craving, and depression plays the mediating role between rumination and craving.These findings suggest that interventions to reduce depression and rumination may also be effective for withdrawal and relapse reduction in methamphetamine patients, providing further rationale for the treatment of methamphetamine patients.

Potential protective effects of sodium butyrate on glycinin-induced oxidative stress, inflammatory response, and growth inhibition in Cyprinus carpio.

Investigated mitigating effects of sodium butyrate (SB) on the inflammatory response, oxidative stress, and growth inhibition of common carp (Cyprinus carpio) (2.94 ± 0.2 g) are caused by glycinin. Six isonitrogenous and isoenergetic diets were prepared, in which the basal diet was the control diet and the Gly group diet contained 80 g/kg glycinin, while the remaining 4 diets were supplemented with 0.75, 1.50, 2.25, and 3.00 g/kg SB, respectively. The feeding trial lasted for 8 weeks, and the results indicated that supplementing the diet with 1.50-2.25 g/kg of SB significantly improved feed efficiency and alleviated the growth inhibition induced by glycinin. Hepatopancreas and intestinal protease activities and the content of muscle crude protein were significantly decreased by dietary glycinin, but supplement 1.50-2.25 g/kg SB partially reversed this result. SB (1.50-2.25 g/kg) increased the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the hepatopancreas and reduced the activities of AST and ALT in the serum. Glycinin significantly reduced immune and antioxidant enzyme activities, whereas 1.50-2.25 g/kg SB reversed these adverse effects. Furthermore, compared with the Gly group, supplement 1.50-2.25 g/kg SB eminently up-regulated the TGF-ß and IL-10 mRNA, and down-regulated the IL-1ß, TNF-α, and NF-κB mRNA in hepatopancreas, mid-intestine (MI), and distal intestine (DI). Meanwhile, supplement 1.50-2.25 g/kg SB activated the Keap1-Nrf2-ARE signaling pathway and upregulate CAT, SOD, and HO-1 mRNA expression in hepatopancreas, MI, and DI. Summarily, glycinin induced inflammatory response, and oxidative stress of common carp ultimately decreased the digestive function and growth performance. SB partially mitigated these adverse effects by activating the Keap1-Nrf2-ARE signaling pathway and inhibiting the NF-κB signaling pathway.

The effect of masks on infants' ability to fast-map and generalize new words.

Young children today are exposed to masks on a regular basis. However, there is limited empirical evidence on how masks may affect word learning. The study explored the effect of masks on infants' abilities to fast-map and generalize new words. Seventy-two Chinese infants (43 males, Mage = 18.26 months) were taught two novel word-object pairs by a speaker with or without a mask. They then heard the words and had to visually identify the correct objects and also generalize words to a different speaker and objects from the same category. Eye-tracking results indicate that infants looked longer at the target regardless of whether a speaker wore a mask. They also looked longer at the speaker's eyes than at the mouth only when words were taught through a mask. Thus, fast-mapping and generalization occur in both masked and not masked conditions as infants can flexibly access different visual cues during word-learning.

Novel GNAI3 mutation in a Chinese family with auriculocondylar syndrome and treatment of severe dentofacial deformities: a 5-year follow-up case report.

BACKGROUND: Auriculocondylar syndrome (ARCND) is an extremely rare autosomal dominant or recessive condition that typically manifests as question mark ears (QMEs), mandibular condyle hypoplasia, and micrognathia. Severe dental and maxillofacial malformations present considerable challenges in patients' lives and clinical treatment. Currently, only a few ARCND cases have been reported worldwide, but most of them are related to genetic mutations, clinical symptoms, and ear correction; there are few reports concerning the treatment of dentofacial deformities. CASE PRESENTATION: Here, we report a rare case of ARCND in a Chinese family. A novel insertional mutation in the guanine nucleotide-binding protein alpha-inhibiting activity polypeptide 3 (GNAI3) was identified in the patient and their brother using whole-exome sequencing. After a multidisciplinary consultation and examination, sequential orthodontic treatment and craniofacial surgery, including distraction osteogenesis and orthognathic surgery, were performed using three-dimensional (3D) digital technology to treat the patient's dentofacial deformity. A good prognosis was achieved at the 5-year follow-up, and the patient returned to normal life. CONCLUSIONS: ARCND is a monogenic and rare condition that can be diagnosed based on its clinical triad of core features. Molecular diagnosis plays a crucial role in the diagnosis of patients with inconspicuous clinical features. We present a novel insertion variation in GNAI3, which was identified in exon 2 of chromosome 110116384 in a Chinese family. Sequential therapy with preoperative orthodontic treatment combined with distraction osteogenesis and orthognathic surgery guided by 3D digital technology may be a practical and effective method for treating ARCND.

Single-shot Fourier ptychographic microscopy with isotropic lateral resolution via polarization-multiplexed LED illumination.

Fourier ptychographic microscopy (FPM) has emerged as a new wide-field and high-resolution computational imaging technique in recent years. To ensure data redundancy for a stable convergence solution, conventional FPM requires dozens or hundreds of raw images, increasing the time cost for both data collection and computation. Here, we propose a single-shot Fourier ptychographic microscopy with isotropic lateral resolution via polarization-multiplexed LED illumination, termed SIFPM. Three LED elements covered with 0°/45°/135° polarization films, respectively, are used to provide numerical aperture-matched illumination for the sample simultaneously. Meanwhile, a polarization camera is utilized to record the light field distribution transmitted through the sample. Based on weak object transfer functions, we first obtain the amplitude and phase estimations of the sample by deconvolution, and then we use them as the initial guesses of the FPM algorithm to refine the accuracy of reconstruction. We validate the complex sample imaging performance of the proposed method on quantitative phase target, unstained and stained bio-samples. These results show that SIFPM can realize quantitative imaging for general samples with the resolution of the incoherent diffraction limit, permitting high-speed quantitative characterization for cells and tissues.

An overview of aptamer: Design strategy, prominent applications, and potential challenge in plants.

Aptamers, serving as highly efficient molecular recognition and biotechnology tools, have garnered increasing interest in the realm of plant science in recent years. Aptamers are synthetic single-stranded short nucleotides or peptides, that bind targets with high specificity and affinity, triggering precise biological responses. As an alternative to antibodies, aptamers present promising avenues for advancement in biological researches. Aptamers function in a range of fields, encompassing cell signaling, drug development, biosensor technology, as well as botany, agricultural and forestry sciences. In this review, we introduce classifications and screening methods of aptamers, as well as aptamer-based technologies, highlighting their significant contributions to recent advancements. With their powerful functionality and ability to bind targets with high specificity and affinity, aptamers offer promising opportunities for breakthroughs in plant research.

Vitamin E Intake and Prevalence Rates of Thyroid Dysfunction and Autoimmune Thyroiditis: A Cross-Sectional Analysis of NHANES Data.

Background: Thyroid disorders are associated with various dietary factors and nutritional elements. The aim of this study was to investigate the relationships between dietary vitamin E intake and the prevalence of thyroid dysfunction and thyroid antibody positivity using data from the National Health and Nutrition Examination Survey (NHANES) database. Methods: Data from the NHANES database collected between 2007 and 2012 were analyzed. A total of 7,773 nonpregnant adults without preexisting thyroid diseases and possessing complete thyroid and vitamin E data were included in the study. The participants were categorized into tertiles based on their dietary vitamin E intake: the lowest group (T1: ≤4.53 mg), the intermediate group (T2: 4.54-8.10 mg), and the highest group (T3: ≥8.11 mg). We used a complex multistage probability sampling design in conjunction with R software. We compared thyroid indices, the prevalence of overt and subclinical hyperthyroidism or hypothyroidism, and the occurrence of thyroid antibody positivity among the three groups based on vitamin E intake. Weighted multinomial logistic regression was used to assess the association between dietary vitamin E intake and thyroid disorders. Restricted cubic splines (RCSs) were used to explore potential nonlinear associations. Results: The prevalence rates of subclinical hypothyroidism (SCH) were 3.63%, 3.07%, and 1.85% in T1, T2, and T3, respectively, indicating a decreasing trend (P-trend = 0.013). In the general population, high vitamin E intake (T3) was significantly associated with a lower prevalence of SCH (OR = 0.28, CI = 0.15-0.54, p < 0.001). Subgroup analysis revealed a more pronounced protective effect in males, with both moderate (T2, OR = 0.45, CI = 0.23-0.87, p = 0.020) and high (T3, OR = 0.19, CI = 0.09-0.39, p < 0.001) dietary vitamin E intake being associated with a lower prevalence of SCH. In addition, moderate (T2, OR = 0.59, CI = 0.37-0.93, p = 0.024) and high (T3, OR = 0.52, CI = 0.36-0.75, p < 0.001) dietary vitamin E intake was associated with a lower prevalence of autoimmune thyroiditis (AIT) in males. However, no significant association was observed among females. Conclusion: The findings of this study suggest that a higher intake of vitamin E is associated with lower prevalence rates of SCH and autoimmune thyroiditis among males.

Genetic Analysis of Two Novel GPI Variants Disrupting H Bonds and Localization Characteristics of 55 Gene Variants Associated with Glucose-6-phosphate Isomerase Deficiency.

OBJECTIVE: Glucose-6-phosphate isomerase (GPI) deficiency is a rare hereditary nonspherocytic hemolytic anemia caused by GPI gene variants. This disorder exhibits wide heterogeneity in its clinical manifestations and molecular characteristics, often posing challenges for precise diagnoses using conventional methods. To this end, this study aimed to identify the novel variants responsible for GPI deficiency in a Chinese family. METHODS: The clinical manifestations of the patient were summarized and analyzed for GPI deficiency phenotype diagnosis. Novel compound heterozygous variants of the GPI gene, c.174C>A (p.Asn58Lys) and c.1538G>T (p.Trp513Leu), were identified using whole-exome and Sanger sequencing. The AlphaFold program and Chimera software were used to analyze the effects of compound heterozygous variants on GPI structure. RESULTS: By characterizing 53 GPI missense/nonsense variants from previous literature and two novel missense variants identified in this study, we found that most variants were located in exons 3, 4, 12, and 18, with a few localized in exons 8, 9, and 14. This study identified novel compound heterozygous variants associated with GPI deficiency. These pathogenic variants disrupt hydrogen bonds formed by highly conserved GPI amino acids. CONCLUSION: Early family-based sequencing analyses, especially for patients with congenital anemia, can help increase diagnostic accuracy for GPI deficiency, improve child healthcare, and enable genetic counseling.

Construction and validation of a nomogram prediction model for the progression to septic shock in elderly patients with urosepsis.

Background: Septic shock is a clinical syndrome characterized by the progression of sepsis to a severe stage. Elderly patients with urosepsis in the intensive care unit (ICU) are more likely to progress to septic shock. This study aimed to establish and validate a nomogram model for predicting the risk of progression to septic shock in elderly patients with urosepsis. Methods: We extracted data from the Medical Information Mart for Intensive Care (MIMIC-IV) and the eICU Collaborative Research Database (eICU-CRD). The MIMIC-IV dataset was split into a training set for model development and an internal validation set to assess model performance. Further external validation was performed using a distinct dataset sourced from the eICU-CRD. Predictors were screened using least absolute shrinkage and selection operator (LASSO) regression and multivariable logistic regression analyses. The evaluation of model performance included discrimination, calibration, and clinical usefulness. Results: The study demonstrated that the Glasgow Coma Scale (GCS), white blood count (WBC), platelet, blood urea nitrogen (BUN), calcium, albumin, congestive heart failure (CHF), and invasive ventilation were closely associated with septic shock in the training cohort. Nomogram prediction, utilizing eight parameters, demonstrated strong predictive accuracy with area under the curve (AUC) values of 0.809 (95 % CI 0.786-0.834), 0.794 (95 % CI 0.756-0.831), and 0.723 (95 % CI 0.647-0.801) in the training, internal validation, and external validation sets, respectively. Additionally, the nomogram demonstrated a promising calibration performance and significant clinical usefulness in both the training and validation sets. Conclusion: The constructed nomogram is a reliable and practical tool for predicting the risk of progression to septic shock in elderly patients with urosepsis. Its implementation in clinical practice may enhance the early identification of high-risk patients, facilitate timely and targeted interventions to mitigate the risk of septic shock, and improve patient outcomes.

diABZI and poly(I:C) inhibit osteoclastic bone resorption by inducing IRF7 and IFIT3.

Type I interferons (IFN-I) are pleiotropic factors endowed with multiple activities that play important roles in innate and adaptive immunity. Although many studies indicate that IFN-I inducers exert favorable effects on broad-spectrum antivirus, immunomodulation, and anti-tumor activities by inducing endogenous IFN-I and IFN-stimulated genes, their function in bone homeostasis still needs further exploration. Here, our study demonstrates 2 distinct IFN-I inducers, diABZI and poly(I:C), as potential therapeutics to alleviate osteolysis and osteoporosis. First, IFN-I inducers suppress the genes that control osteoclast (OC) differentiation and activity in vitro. Moreover, diABZI alleviates bone loss in Ti particle-induced osteolysis and ovariectomized -induced osteoporosis in vivo by inhibiting OC differentiation and function. In addition, the inhibitory effects of IFN-I inducers on OC differentiation are not observed in macrophages derived from Ifnar1-/-mice, which indicate that the suppressive effect of IFN-I inducers on OC is IFNAR-dependent. Mechanistically, RNAi-mediated silencing of IRF7 and IFIT3 in OC precursors impairs the suppressive effect of the IFN-I inducers on OC differentiation. Taken together, these results demonstrate that IFN-I inducers play a protective role in bone turnover by limiting osteoclastogenesis and bone resorption through the induction of OC-specific mediators via the IFN-I signaling pathway.

OCs are responsible for bone resorption, and their excessive differentiation and enhanced activity will lead to bone resorption diseases such as osteoporosis and osteolysis. Here, our study demonstrates 2 distinct IFN-I inducers, diABZI and poly(I:C), as potential therapeutics to alleviate osteolysis and osteoporosis. IFN-I inducers suppress OC differentiation, and particularly diABZI alleviates bone loss in osteolysis and osteoporosis mouse models. Taken together, IFN-I inducers play a protective role in bone turnover by limiting osteoclastogenesis and bone resorption through the induction of OC-specific mediators via the IFN-I signaling pathway. Our in-depth and comprehensive discovery of the IFN-I inducer would provide new insight into OC biology and therapeutic targets for osteoclastic bone resorption diseases.

Apoptotic Extracellular Vesicles Induced Endothelial Cell-Mediated Autologous Stem Cell Recruitment Dominates Allogeneic Stem Cell Therapeutic Mechanism for Bone Repair.

Although stem cell therapy is proved to be a promising strategy for bone repair and regeneration, transplanted allogeneic stem cells generally suffer from unfavorable apoptosis instead of differentiation into osteocytes. How the apoptotic stem cells promote bone regeneration still needs to be uncovered. In this work, we found that apoptotic extracellular vesicles released by allogeneic stem cells are critical mediators for promoting bone regeneration. Based on the results of in vivo experiments, a mechanism of apoptotic stem cells determined autologous stem cell recruitment and enhance osteogenesis was proposed. The nanoscaled apoptotic extracellular vesicles released from transplanted stem cells were endocytosed by vascular endothelial cells and preferentially distribute at endoplasmic reticular region. The oxidized phosphatidylcholine enriched in the vesicles activated the endoplasmic reticulum stress and triggered the reflective elevation of adhesion molecules, which induced the recruitment of autologous stem cells located in the blood vessels, transported them into the defect region, and promoted osteogenesis and bone repair. These findings not only reveal the mechanism of stem cell therapy of bone defects but also provide a cue for investigation of the biological process of stem cell therapy for other diseases and develop stem cell therapeutic strategies.