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Abstract Purpose To characterize the phenotype and genotype of a Chinese family with autosomal‐dominant retinitis pigmentosa (RP) accompanied by iris coloboma. Methods The proband, a 34‐year‐old male, was examined with his family by using fundus photography, optical coherence tomography (OCT), autofluorescence, and full‐field electroretinography (ffERG). Genetic analyses were conducted through whole‐exome sequencing (WES) to screen for variations. Results Three members of this Chinese family were shown to be bilateral iris coloboma. The male proband and his mother exhibited typical RP feature. The proband's late grandfather had been documented manifestation of iris coloboma. The mode of inheritance was confirmed to be autosomal dominance. Through linkage analysis and WES, a heterozygous variation in the miR‐204 gene (n.37C>T), a noncoding RNA gene, was identified in these three members. Conclusions In this third independent and the first Asian family, the existence of a miR‐204 variant associated with RP accompanied by iris coloboma was confirmed. Our findings reinforce the significance of miR‐204 as an important factor influencing visual function in the retina. When phenotypes like RP accompanied by iris coloboma in an autosomal‐dominant pattern, including in Chinese patients, miR‐204 aberrations should be considered.

After a coal seam is mined, the oxidized coal left in its goaf is prone to water immersion, and spontaneous combustion accidents involving water-immersed coal may easily occur when mining the underlying coal seam. Using scanning electron microscopy and nitrogen adsorption experimental methods, the physical structure of high-temperature pre-oxidized water-immersed coal samples was characterized. By means of infrared spectroscopy, electron spin resonance (ESR) and simultaneous thermal analysis, the microscopic characteristics of the coal samples and the endothermic and exothermic characteristics of the oxidative combustion process were studied. The results showed that a specific pre-oxidation soaking time generated more oxidation pores in the coal sample, causing more water to become trapped in the pores and increasing the secondary oxidation heat absorption. High-temperature oxidation promoted the conversion of coal sample functional groups (FG) and free radical active sites, Water immersion led to the formation and loss of FG, and the longer the water immersion time was, the greater the loss. The larger average pore size of the pre-oxidized water-immersed coal sample provided more coal-oxygen contact sites, and the breaking of chemical bonds in the FG during the secondary oxidation process accelerated the heat release and promoted the oxidative re-ignition of the coal sample. The spontaneous combustion of water-immersed coal in the goaf can be prevented by controlling the high oxidation temperature and water immersion time. [ABSTRACT FROM AUTHOR]

Aim: To assess mesenchymal stem cells (MSCs) as carriers for HIF-1α siRNA-loaded nanoparticles (NPs) for targeted therapy of experimental choroidal neovascularization (CNV). Materials & methods: A poly (lactic-co-glycolic acid) (PLGA)-core/lipid-shell hybrid NP was designed. The transfection efficacy of MSCs with the hybrid NPs was assessed. Mice were intravenously injected with MSCs after laser photocoagulation and CNV was assessed at 7 days post-injection. Results & conclusion: The transfection efficiency of hybrid NPs into MSCs was 72.7%. HIF-1α mRNA expression in 661w cells co-cultured with MSC-hybrid-siRNA NPs was significantly lower. Intravenous delivery of MSC-hybrid-siRNA NPs greatly reduced CNV area and length. Intravenous injection of MSC-hybrid-siRNA NPs achieved therapeutic efficacy in reducing CNV area. The MSC-mediated homing enabled targeted inhibition of ocular angiogenesis. Article highlights A HIF-1α siRNA-loaded PLGA@lipid hybrid nanoparticles system was designed. An MSC-mediated biodegradable hybrid nanoparticle system for targeted delivery of HIF-1α siRNA was developed. The MSC-mediated homing enabled targeted ocular angiogenesis. MSCs can be potentially exploited as an ideal drug delivery system, a so-called Trojan horse strategy. Systemic administration of MSCs loaded with nanoparticles inhibited pathological angiogenesis. Integration of advanced nanomaterials with cell-based platforms can amplify the overall therapeutic impact. MSCs can be safely delivered without triggering a major immune reaction. The ability of MSCs to specifically migrate to CNV without accrual in other organs. [ABSTRACT FROM AUTHOR]

Background and objective: The aim of this study was to investigate potential hub genes for dilated cardiomyopathy (DCM). Methods: Five DCM-related microarray datasets were downloaded from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were used for identification. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, disease ontology, gene ontology annotation and protein-protein interaction (PPI) network analysis were then performed, while a random forest was constructed to explore central genes. Artificial neural networks were used to compare with known genes and to develop new diagnostic models. 240 population blood samples were collected and expression of hub genes was verified in these samples using RT-PCR and demonstrated by Nomogram. Results: After differential analysis, 33 genes were statistically significant (adjusted P < 0.05). Functional enrichment of these differential genes resulted in 85 Gene Ontology (GO) functions identified and 6 pathways enriched for the KEGG pathway. PPI networks and molecular complex assays identified 10 hub genes (adjusted P < 0.05). Random forest identified SMOC2 and SFRP4 as the most important, followed by FCER1G and FRZB. NeuraHF models (SMOC2, SFRP4, FCER1G and FRZB) were selected by artificial neural network model and had better diagnostic efficacy for the onset of DCM, compared with the traditional KG-DCM models (MYH7, ACTC1, TTN and LMNA). Finally, SFRP4 and FRZB were expressed higher in DCM verified by RT-PCR and as a factor for DCM identified by Nomogram. Conclusions: We performed an integrated analysis and identified SFRP4 and FRZB as a new factor for DCM. But the exact mechanism still needs further experimental verification. [ABSTRACT FROM AUTHOR]

The Central Asian Orogenic Belt (CAOB) was formed by the aggregation and collage of numerous Paleozoic subduction‐accretion assemblages and Precambrian microcontinental blocks. However, the tectonic nature of the southeastern CAOB remains controversial, which complicates the reconstruction of the Paleo‐Asian Ocean. To address this issue, a deep seismic reflection survey was initiated across the southeastern CAOB and reveals broad gentle sub‐horizontal reflectors in the middle‐lower crust and a relatively transparent zone in the upper crust. Combining with the Precambrian geological outcrops and other geophysical features, we support a microcontinental block, the Xilinhot Block, existed in the Paleo‐Asian domain. Thus, the Paleo‐Asian Ocean was separated into two branches that underwent north‐dipping and double‐dipping oceanic plate subduction, respectively, to form the Hegenshan‐Heihe and Solonker sutures. Multiple relics beneath Hegenshan‐Heihe Suture indicate that multiple sets of unidirectional oceanic subduction‐accretion and magmatism were important mechanisms of continental growth. Plain Language Summary: During the consumption of the Paleo‐Asian Ocean, a great number of Paleozoic subduction‐related accretionary complexes were developed and combined with pre‐existing Precambrian continental fragments to form the Central Asian Orogenic Belt (CAOB). However, research on the tectonic evolution of this area has been limited, and the tectonic nature of the southeastern CAOB remains controversial. A deep seismic reflection survey along the southeastern CAOB shows the crustal architecture in detail. The broad gentle sub‐horizontal reflectors and a relatively transparent zone in the profile reveal a Precambrian continental fragment existed in the North Orogenic Belt of CAOB. The Paleo‐Asian Ocean was further separated into two parts, the fossil subduction zones of which show northward and bidirectional dipping characteristics beneath the Hegenshan‐Heihe and Solonker sutures, respectively. Several relics of the unidirectional subduction beneath the Hegenshan‐Heihe Suture indicate that multiple sets of unidirectional oceanic subduction‐accretion and magmatism were important mechanisms of continental growth. Key Points: A preserved microcontinental block has been revealed in the North Orogenic Belt of Central Asian Orogenic BeltThe Paleo‐Asian Ocean was separated into two branches, which were closed respectively by north‐dipping and double‐dipping subductionMultiple unidirectional subduction‐accretion and oceanic magmatism may contribute to continental growth [ABSTRACT FROM AUTHOR]

Background: The present study aimed to dissect the cellular complexity of Crohn's disease (CD) using single‐cell RNA sequencing, focusing on identifying key cell populations and their transcriptional profiles in inflamed tissue. Methods: We applied scRNA‐sequencing to compare the cellular composition of CD patients with healthy controls, utilizing Seurat for clustering and annotation. Differential gene expression analysis and protein–protein interaction networks were constructed to identify crucial genes and pathways. Results: Our study identified eight distinct cell types in CD, highlighting crucial fibroblast and T cell interactions. The analysis revealed key cellular communications and identified significant genes and pathways involved in the disease's pathology. The role of fibroblasts was underscored by elevated expression in diseased samples, offering insights into disease mechanisms and potential therapeutic targets, including responses to ustekinumab treatment, thus enriching our understanding of CD at a molecular level. Conclusions: Our findings highlight the complex cellular and molecular interplay in CD, suggesting new biomarkers and therapeutic targets, offering insights into disease mechanisms and treatment implications. [ABSTRACT FROM AUTHOR]

With the gradual expansion of aquaculture industry in China, the frequent occurrence of diseases in aquatic animal aquaculture and the pollution of aquatic water are becoming more and more serious. The long-term use of antibiotics and traditional vaccines in aquaculture has caused water pollution, drug-resistant strains, antibiotic residues, and other problems, which restricts the healthy development of aquaculture industry. Plant polysaccharides play an important role in replacing antibiotics. Plant polysaccharides exist in the leaves, flowers, roots, stems, and fruits of plants. They are macromolecular polymers that connect various monosaccharides by glycosidic bonds. Plant polysaccharides have the advantages of safety, high efficiency, low residue and no drug resistance. Plant polysaccharides have many biological functions, such as regulating immunity, anti-oxidation, lowering blood sugar, anti-tumor, and improving intestinal health. The application of plant polysaccharides in animal production can improve body health, enhance immunity and antioxidant capacity, and improve production performance. Therefore, this paper mainly reviewed the physicochemical properties, biological functions of plant polysaccharides and their application in aquaculture, so as to provide a reference for their further promotion and application in aquaculture. [ABSTRACT FROM AUTHOR]

Caoyuanheimo-1 (Agaricus sp.) is a delectable mushroom native to Inner Mongolia, China, belonging to the Agaricus genus and valued for both its edible and medicinal properties. Although it has been cultivated to a certain extent, the molecular mechanisms regulating its development remain poorly understood. Building on our understanding of its growth and development conditions at various stages, we conducted transcriptomic and metabolomic studies to identify the differentially expressed genes (DEGs) and metabolites throughout its growth cycle. Simultaneously, we analyzed the synthesis pathways and identified several key genes involved in the production of terpenoids, which are secondary metabolites with medicinal value widely found in mushrooms. A total of 6843 unigenes were annotated, and 449 metabolites were detected in our study. Many of these metabolites and differentially expressed genes (DEGs) are involved in the synthesis and metabolism of amino acids, such as arginine, cysteine, methionine, and other amino acids, which indicates that the genes related to amino acid metabolism may play an important role in the fruiting body development of Caoyuanheimo-1. Succinic acid also showed a significant positive correlation with the transcriptional level changes of nine genes, including laccase-1 (TRINITY_DN5510_c0_g1), fruiting body protein SC3 (TRINITY_DN3577_c0_g1), and zinc-binding dihydrogenase (TRINITY_DN2099_c0_g1), etc. Additionally, seventeen terpenoids and terpenoid-related substances were identified, comprising five terpenoid glycosides, three monoterpenoids, two diterpenoids, one sesquiterpenoid, one sesterterpenoid, two terpenoid lactones, and three triterpenoids. The expression levels of the genes related to terpenoid synthesis varied across the three developmental stages. [ABSTRACT FROM AUTHOR]

Background: Previous studies of maternal iron and birth outcomes have been limited to single indicators that do not reflect the comprehensive relationship with birth outcomes. We aimed to investigate the relationship between maternal iron metabolism and neonatal anthropometric indicators using comprehensive iron-related indicators. Methods: A total of 914 Chinese mother-child dyads were enrolled in this prospective study. Subjects' blood samples were collected at ≤ 14 weeks of gestation. Serum concentrations of iron-related indicators were measured by enzyme-linked immunosorbent assay (ELISA). Femur length was measured by B-ultrasound nearest delivery. Neonatal anthropometric indicators were collected from medical records. Results: After adjustment for potential covariates, higher iron (per one standard deviation, SD increase) was detrimentally associated with − 0.22 mm lower femur length, whereas higher transferrin (per one SD increase) was associated with 0.20 mm higher femur length. Compared with normal subjects (10th-90th percentiles), subjects with extremely high (> 90th percentile) iron concentration were detrimentally associated with lower femur length, birth weight, and chest circumference, and a higher risk of low birth weight, LBW (HR: 3.92, 95%CI: 1.28, 12.0). Subjects with high concentration of soluble transferrin receptor, sTFR and transferrin (> 90th percentile) were associated with higher femur length. Subjects with low concentration of iron and ferritin concentrations (< 10th percentile) were associated with a higher risk of LBW (HR: 4.10, 95%CI: 1.17, 14.3) and macrosomia (HR: 2.79, 95%CI: 1.06, 7.35), respectively. Conclusions: Maternal iron overload in early pregnancy may be detrimentally associated with neonatal anthropometric indicators and adverse birth outcomes. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What is the mechanism behind cryoinjury in human sperm, particularly concerning the interplay between reactive oxygen species (ROS) and autophagy, and how does it subsequently affect sperm fate? SUMMARY ANSWER The freeze-thaw operation induces oxidative stress by generating abundant ROS, which impairs sperm motility and activates autophagy, ultimately guiding the sperm toward programmed cell death such as apoptosis and necrosis, as well as triggering premature capacitation. WHAT IS KNOWN ALREADY Both ROS-induced oxidative stress and autophagy are thought to exert an influence on the quality of frozen-thawed sperm. STUDY DESIGN, SIZE, DURATION Overall, 84 semen specimens were collected from young healthy fertile males, with careful quality evaluation. The specimens were split into three groups to investigate the ROS-induced cryoinjury: normal control without any treatment, sperm treated with 0.5 mM hydrogen peroxide (H2O2) for 1 h, and sperm thawed following cryopreservation. Samples from 48 individuals underwent computer-assisted human sperm analysis (CASA) to evaluate sperm quality in response to the treatments. Semen samples from three donors were analyzed for changes in the sperm proteome after H2O2 treatment, and another set of samples from three donors were analyzed for changes following the freeze-thaw process. The other 30 samples were used for fluorescence-staining and western blotting. PARTICIPANTS/MATERIALS, SETTING, METHODS Sperm motility parameters, including progressive motility (PR %) and total motility (PR + NP %), were evaluated using the CASA system on a minimum of 200 spermatozoa. The proteomic profiles were determined with label-free mass spectrometry (MS/MS) and protein identification was performed via ion search against the NCBI human database. Subsequently, comprehensive bioinformatics was applied to detect significant proteomic changes and functional enrichment. Fluorescence-staining and western blot analyses were also conducted to confirm the proteomic changes on selected key proteins. The ROS level was measured using 2′,7′-dichlorodihydrofluorescein diacetate labeling and the abundance of bioactive mitochondria was determined by evaluating the inner mitochondrial membrane potential (MMP) level. Molecular behaviors of sequestosome-1 (p62 or SQSTM1) and microtubule-associated proteins 1A/1B light chain 3 (LC3) were monitored to evaluate the state of apoptosis in human sperm. Fluorescent probes oxazole yellow (YO-PRO-1) and propidium iodide (PI) were utilized to monitor programmed cell death, namely apoptosis and necrosis. Additionally, gradient concentrations of antioxidant coenzyme Q10 (CoQ10) were introduced to suppress ROS impacts on sperm. MAIN RESULTS AND THE ROLE OF CHANCE The CASA analysis revealed a significant decrease in sperm motility for both the H2O2-treatment and freeze-thaw groups. Fluorescence staining showed that high ROS levels were produced in the treated sperm and the MMPs were largely reduced. The introduction of CoQ10 at concentrations of 20 and 30 μM resulted in a significant rescue of progressive motility (P  < 0.05). The result suggested that excessive ROS could be the major cause of sperm motility impairment, likely by damaging mitochondrial energy generation. Autophagy was significantly activated in sperm when they were under oxidative stress, as evidenced by the upregulation of p62 and the increased conversion of LC3 as well as the upregulation of several autophagy-related proteins, such as charged multivesicular body protein 2a, mitochondrial import receptor subunit TOM22 homolog, and WD repeat domain phosphoinositide-interacting protein 2. Additionally, fluorescent staining indicated the occurrence of apoptosis and necrosis in both H2O2-treated sperm and post-thaw sperm. The cell death process can be suppressed when CoQ10 is introduced, which consolidates the view that ROS could be the major contributor to sperm cryoinjury. The freeze-thaw process could also initiate sperm premature capacitation, demonstrated by the prominent increase in tyrosine phosphorylated proteins, verified with anti-phosphotyrosine antibody and immunofluorescence assays. The upregulation of capacitation-related proteins, such as hyaluronidase 3 and Folate receptor alpha, supported this finding. LARGE SCALE DATA The data underlying this article are available in the article and its online supplementary material. LIMITATIONS, REASONS FOR CAUTION The semen samples were obtained exclusively from young, healthy, and fertile males with progressive motility exceeding 60%, which might overemphasize the positive effects while possibly neglecting the negative impacts of cryoinjury. Additionally, the H2O2 treatment conditions in this study may not precisely mimic the oxidative stress experienced by sperm after thawing from cryopreservation, potentially resulting in the omission of certain molecular alterations. WIDER IMPLICATIONS OF THE FINDINGS This study provides substantial proteomic data for a comprehensive and deeper understanding of the impact of cryopreservation on sperm quality. It will facilitate the design of optimal protocols for utilizing cryopreserved sperm to improve applications, such as ART, and help resolve various adverse situations caused by chemotherapy, radiotherapy, and surgery. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by grants from the Major Innovation Project of Research Institute of National Health Commission (#2022GJZD01-3) and the National Key R&D Program of China (#2018YFC1003600). All authors declare no competing interests. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Photoreceptor cell death, primarily through apoptosis, related to retinal disorders like retinitis pigmentosa (RP), would result in vision loss. The pathological processes and crucial mutant conditions preceding photoreceptor cell demise are not well understood. This study aims to conduct an in-depth examination of early-stage changes in the widely utilized Pde6brd1/rd1 (rd1) mouse model, which has Pde6b gene mutations representing autosomal recessive RP disorder. We investigated the morphology and ultrastructure of retinal cells, including second-order neurons, during the initial phase of disease progression. Our findings revealed that mitochondrial alterations in rod photoreceptors were present as a predeath mutant state as early as postnatal day 3 (P3). The bipolar and horizontal cells from the rd1 mouse retina exhibited significant morphological changes in response to loss of photoreceptor cells, indicating that second-order neurons rely on these cells for their structures. Subsequent oral administration of idebenone, a mitochondria-protective agent, enhanced retinal function and promoted both photoreceptor cell survival and inner retinal second-order synaptogenesis in rd1 mice at P14. Our findings offer a mechanistic framework, suggesting that mitochondrial damage acts as an early driver for photoreceptor cell death in retinal degeneration. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a chronic inflammatory disease that affects arteries and is the main cause of cardiovascular disease. Atherosclerotic plaque formation is usually asymptomatic and does not manifest until the occurrence of clinical events. Therefore, early diagnosis and treatment of atherosclerotic plaques is particularly important. Here, a series of NIR‐II fluorescent dyes (RBT‐NH) are developed for three photoresponsive NO prodrugs (RBT‐NO), which can be controllably triggered by 808 nm laser to release NO and turn on the NIR‐II emission in the clinical medicine "therapeutic window". Notably, RBT3‐NO is selected for its exhibited high NO releasing efficiency and superior fluorescence signal enhancement. Subsequently, a platelet‐mimicking nano‐prodrug system (RBT3‐NO‐PEG@PM) is constructed by DSPE‐mPEG5k and platelet membrane (PM) for effectively targeted diagnosis and therapy of atherosclerosis in mice. The results indicate that this platelet‐mimicking NO nano‐prodrug system can reduce the accumulation of lipids at the sites of atherosclerotic plaques, improve the inflammatory response at the lesion sites, and promote endothelial cell migration, thereby slowing the progression of plaques. [ABSTRACT FROM AUTHOR]

Optical encryption technology attracts considerable attention in the field of information encryption, information storage, and anti‐counterfeiting. However, optical encryption based on conventional on/off mode still faces issues such as low scalability, ease of cracking, and poor storage capacity; multi‐dimensional and high storage capacity information encryption systems are thus needed. Herein, a programmable information encryption circuit system is demonstrated by constructing a delay light‐emitting diode (LED) array using multi‐color phosphorescent carbon nanodots (CNDs) with versatile lifetimes. The CNDs show adjustable luminescence wavelength and lifetime from 192 to 1148 ms. The programmable delay luminescent circuit provides an intricate framework for meticulously integrating an LED array, enabling the creation of intricate patterns or alphanumeric codes. These intricate designs are engineered to serve as a component of an encryption system, which can be deciphered and unveiled under a specific delay time range. This study demonstrates the feasibility and superiority of the system as a new type of information anti‐counterfeiting encryption technology, providing a new concept for exploring the field of integrated circuit anti‐counterfeiting and encryption. [ABSTRACT FROM AUTHOR]

With the advancement of coal mining, the pre‐mining stress on the coal seam increases. After mining, the coal seam fractures and unloads, leaving granular coal in the goaf with a high risk of spontaneous combustion. To investigate the oxidation behavior and underlying mechanisms of granular coal in goafs at various depths, fresh coal was subjected to static stresses ranging from 4 to 16 MPa and then underwent unloading treatment to generate granular coal with varying initial stresses. Subsequently, simulations of granular coal in goafs at various depths were conducted. Structural characteristics (pores and functional groups) and oxidation heat production performance of the granular coal after unloading were analyzed using a low‐temperature nitrogen adsorption instrument, a Fourier infrared spectrometer, and a simultaneous thermal analysis system. The findings suggest that as the initial loading stress increases, the number of micropores and mesopores within the unloaded bulk coal decreases, while the number of macropores increases. Furthermore, important oxidation‐active structures, including ‐OH, ‐CH3, ‐CH2‐, C=O, and ‐COOH, gradually increase, with a slight decrease observed after exceeding 8 MPa. The pressure‐unloading process leads to a gradual decrease in the characteristic temperature of the bulk coal, with the characteristic temperature increasing after exceeding 8 MPa, although it still remains lower than that of the raw coal. As the burial depth of the goaf increases, the oxidation behavior of the unloaded granular coal becomes more pronounced, leading to an increased tendency and risk of spontaneous combustion. If the initial loading stress on deep coal seams is excessive, the oxidation heat production capacity of the resulting unloaded granular coal may be slightly diminished, yet it still poses a significant disaster risk. The research results can provide valuable insights for mitigating and managing spontaneous combustion risks in coal seam mining operations conducted at different depths. [ABSTRACT FROM AUTHOR]