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Background: Emerging evidence suggests that cell deaths are involved in tumorigenesis and progression, which may be treated as a novel direction of cancers. Recently, a novel type of programmed cell death, disulfidptosis, was discovered. However, the detailed biological and clinical impact of disulfidptosis and related regulators remains largely unknown. Methods: In this work, we first enrolled pancancer datasets and performed multi-omics analysis, including gene expression, DNA methylation, copy number variation and single nucleic variation profiles. Then we deciphered the biological implication of disulfidptosis in clear cell renal cell carcinoma (ccRCC) by machine learning. Finally, a novel agent targeting at disulfidptosis in ccRCC was identified and verified. Results: We found that disulfidptosis regulators were dysregulated among cancers, which could be explained by aberrant DNA methylation and genomic mutation events. Disulfidptosis scores were depressed among cancers and negatively correlated with epithelial mesenchymal transition. Disulfidptosis regulators could satisfactorily stratify risk subgroups in ccRCC, and a novel subtype, DCS3, owning with disulfidptosis depression, insensitivity to immune therapy and aberrant genome instability were identified and verified. Moreover, treating DCS3 with NU1025 could significantly inhibit ccRCC malignancy. Conclusion: This work provided a better understanding of disulfidptosis in cancers and new insights into individual management based on disulfidptosis.

Abstract Background Preeclampsia, especially early-onset preeclampsia (EO-PE), is a pregnancy complication that has serious consequences for the health of both the mother and the fetus. Although abnormal placentation due to mitochondrial dysfunction is speculated to contribute to the development of EO-PE, the underlying mechanisms have yet to be fully elucidated. Methods The expression and localization of Siglec-6 in the placenta from normal pregnancies, preterm birth and EO-PE patients were examined by RT-qPCR, Western blot and IHC. Transwell assays were performed to evaluate the effect of Siglec-6 on trophoblast cell migration and invasion. Seahorse experiments were conducted to assess the impact of disrupting Siglec-6 expression on mitochondrial function. Co-IP assay was used to examine the interaction of Siglec-6 with SHP1/SHP2. RNA-seq was employed to investigate the mechanism by which Siglec-6 inhibits mitochondrial function in trophoblast cells. Results The expression of Siglec-6 in extravillous trophoblasts is increased in placental tissues from EO-PE patients. Siglec-6 inhibits trophoblast cell migration and invasion and impairs mitochondrial function. Mechanismly, Siglec-6 inhibits the activation of NF-κB by recruiting SHP1/SHP2, leading to increased expression of GPR20. Notably, the importance of GPR20 function downstream of Siglec-6 in trophoblasts is supported by the observation that GPR20 downregulation rescues defects caused by Siglec-6 overexpression. Finally, overexpression of Siglec-6 in the placenta induces a preeclampsia-like phenotype in a pregnant mouse model. Conclusions This study indicates that the regulatory pathway Siglec-6/GPR20 has a crucial role in regulating trophoblast mitochondrial function, and we suggest that Siglec-6 and GPR20 could serve as potential markers and targets for the clinical diagnosis and therapy of EO-PE.

Al–Nb–B refiner has been considered as an alternative to Al–Ti–B refiner for hypoeutectic Al–Si alloys due to Si-poisoning effect. In this paper, the effects of Al–Nb–B and Al–Ti–B refiner on the microstructure and mechanical properties in indirect squeeze casting Al–8Si-0.2Mg-0.5Mn alloy were compared. Results show that the grain sizes in the edge chilling layer, segregation band, and the center region of the Al–Nb–B refined alloys were refined by 13.9%, 12.5%, and 17.6% compared to Al–Ti–B refined alloys, respectively. The yield strength, tensile strength, and elongation of Al–Nb–B inoculated alloys were superior to those of the unrefined alloys and Al–Ti–B inoculated alloys. The coexistence of NbAl3 and NbB2 particles in the Al–Nb–B refiner exhibited excellent anti Si-poisoning capability. They significantly decreased the grain size and uniformly distributed the eutectic Si particles and Fe-rich phases, resulting in an increase in the yield strength of the alloy by 16.1% compared to the Al–Ti–B inoculated alloy. The distribution of iron-rich phases in the segregation band was affected by the inoculation. The size of α-Al15(Fe, Mn)3Si2 phase in Al–Ti–B inoculated alloys was refined, and the number significantly increased, resulting in a decrease in tensile strength of 12.82 MPa. In the Al–Nb–B inoculated alloys, the size and number of α-Al15(Fe, Mn)3Si2 phase decreased, and the δ-Al4FeSi2 phase increased, which effectively improved the fracture toughness and ductility. In addition, with the increase in grain refinement (from unrefined to Al–Ti–B to Al–Nb–B inoculated alloy), the fracture behavior changed from trans-granular fracture to intergranular fracture, improving the fracture toughness.

Abstract Background Equine herpesvirus (EHV) can cause respiratory, reproductive and neurological diseases in equine animals, including donkeys. The main pathogens responsible for these diseases are EHV type 1 (EHV‐1) and EHV‐4. In this study, we collected serum samples from 230 donkeys on 27 large‐scale donkey farms to detect EHV‐1 and EHV‐4 antibodies. We analyzed the presence of EHV antibodies based on region, age and season. Results Out of the 27 farms, 62.96% (17/27) tested positive for EHV. Of the 230 donkeys tested, 2.61% (6/230) were positive only for EHV‐1, 5.22% (12/230) were positive only for EHV‐4, and 4.78% (11/230) were positive for both EHV‐1 and EHV‐4. The highest percentage of positive donkeys (21.28%) was found in Dong'e County. The seropositivity rate among donkeys aged 1–4 years was significantly higher compared to the group of donkeys aged 0–1 year (p < 0.05). Additionally, the positive rate was significantly higher in fall and winter compared to spring and summer (p < 0.05). Conclusions Altogether, our findings indicate that large‐scale donkey farms in the Liaocheng area have a high prevalence of EHV antibodies. Since Liaocheng is an important donkey trading market in Shandong Province, it is crucial to consider the risk of disease transmission based on our test results. This will help in early detection and prevention of EHV outbreaks.

The emergence of novel avian influenza reassortants in wild birds in recent years is a public health concern. However, the viruses that circulate in migratory birds are not fully understood. In this study, we summarized and categorized global H11 avian influenza viruses and reported that waterfowl and shorebirds are the major reservoirs of the identified H11 viruses. The surveillance data of the 35,749 faecal samples collected from wild bird habitats in eastern China over the past seven years revealed a low prevalence of H11 viruses in birds, with a positive rate of 0.067% (24 isolates). The phylogenetic analysis of the twenty viruses indicated that H11 viruses have undergone complex reassortment with viruses circulating in waterfowl and shorebirds. These tested viruses do not acquire mammalian adaptive mutations in their genomes and preferentially bind to avian-type receptors. Experimental infection studies demonstrated that the two tested H11N9 viruses of wild bird origin replicated and transmitted more efficiently in ducks than in chickens, whereas the pigeon H11N2 virus isolated from a live poultry market was more adapted to replicate in chickens than in ducks. In addition, some H11 isolates replicated efficiently in mice and caused body weight loss but were not lethal. Our study revealed the role of waterfowl and shorebirds in the ecology and evolution of H11 viruses and the potential risk of introducing circulating H11 viruses into ducks or chickens, further emphasizing the importance of avian influenza surveillance at the interface of migratory birds and poultry.

Sparse regularization has been successfully applied to equivalent source method (ESM) in order to improve the acoustic imaging resolution. However, the application is not always feasible, especially at low frequencies. To overcome the problem, this paper proposes a high-resolution acoustic imaging method. In this method, reweighted l 1 minimization is introduced to ESM to deal with the ill-posed inverse problems. Then the obtained equivalent source strengths are used to locate the sound sources. Compared to the sparse regularization-based ESM, the proposed method can provide a low side lobe and higher spatial resolution of acoustic imaging. Meanwhile, by arranging equivalent sources in three-dimensional space, the proposed method can also realize the acoustic imaging in three-dimensional sound field with high resolution. The results of the simulation and experiment demonstrate the validations.

Microsatellites, known as simple sequence repeats (SSRs), are short tandem repeats of 1 to 6 nucleotide motifs found in all genomes, particularly eukaryotes. They are widely used as co-dominant markers in genetic analyses and molecular breeding. Triticeae, a tribe of grasses, includes major cereal crops such as bread wheat, barley, and rye, as well as abundant forage and lawn grasses, playing a crucial role in global food production and agriculture. To enhance genetic work and expedite the improvement of Triticeae crops, we have developed TriticeaeSSRdb, an integrated and user-friendly database. It contains 3,891,705 SSRs from 21 species and offers browsing options based on genomic regions, chromosomes, motif types, and repeat motif sequences. Advanced search functions allow personalized searches based on chromosome location and length of SSR. Users can also explore the genes associated with SSRs, design customized primer pairs for PCR validation, and utilize practical tools for whole-genome browsing, sequence alignment, and in silico SSR prediction from local sequences. We continually update TriticeaeSSRdb with additional species and practical utilities. We anticipate that this database will greatly facilitate trait genetic analyses and enhance molecular breeding strategies for Triticeae crops. Researchers can freely access the database at http://triticeaessrdb.com/.

Abstract Background Various anti‐parasitic drugs are used to control donkey parasitic diseases. The abuse of donkey drugs leads to the disposition of residues in the edible parts of treated donkeys. Objectives The aim of this study was to (1) analyse the pharmacokinetics of ABZSO to serve as reference for the dosage regimen in donkey; and (2) calculate the withdrawal times of the ABZSO in the tissue of the donkey. Methods The concentrations of ABZSO and its metabolites in plasma and tissues were determined using high‐performance liquid chromatography with an ultraviolet detector. Pharmacokinetic analysis was performed by the programme 3p97. Results The plasma concentrations of ABZSO and ABZSO2 concentration–time data in donkey conformed to the absorption one‐compartment open model. The t1/2ke of ABZSO was 0.67 h, whereas the t1/2ke was 12.93 h; the Cmax and the Tp were calculated as 0.58 μg mL−1 and 3.01 h. The Vd/F of ABZSO was estimated to be 10.92 L kg−1; the area under the curve (AUC) was 12.81 μg mL−1 h. The Cmax and AUC values of ABZSO were higher than those of ABZSO2; however, t1/2Ke and Vd/F were lower. Other pharmacokinetics parameters were similar between the two metabolites. Conclusions The results revealed that ABZSO2 was the main metabolite of ABZSO in donkey plasma. The concentrations of ABZSO and its chief metabolite (ABZSO2) were detected in liver, kidney, skin and muscle; however, ABZ‐SO2NH2 was only detected in liver and kidney. The results also revealed that the depletion of ABZSO and its metabolite in donkey was longer, especially in skin.

Abstract The pathogenesis of allergic asthma is similar to that of allergic rhinitis, with inflammation cells producing and releasing inflammatory mediators and cytokines closely related to CCR3.Based on the theory of "one airway, one disease", the use of CCR3 monoclonal antibody may have a similar effect on allergic rhinitis. However, there are few studies on CCR3 monoclonal antibody in allergic rhinitis. Therefore, the aim of this study was to investigate the effective concentration of CCR3 monoclonal antibody, to compare the effects of different methods of administration, and to examine the lung condition of allergic mice to investigate whether antibody treatment protects the lungs. In this study, we constructed a mouse model of allergic rhinitis and intraperitoneally injected different doses of CCR3 monoclonal antibody (5, 10, and 20 uL/mg) to observe its therapeutic effect: observing changes in tissue morphology of nasal mucosa, infiltration of inflammation, and using ELISA to detect changes in relevant inflammatory mediators and cytokines, studying the role of CCR3 mAb in inhibiting CCR3-related actions on the nasal mucosa of allergic rhinitis mice. Furthermore, In addition, the therapeutic effects of intraperitoneal injection (i.p.) and intranasal administration (i.n.) were studied on the basis of effective concentrations.

Shale oil development in the Yanchang Oilfield is characterized by rapid production decline and low productivity, and supplementing the energy requirements and enhancing the recovery of oil are major challenges for shale reservoir development. In this study, physical simulations of cyclic water flooding, CO2 immiscible huff and puff, CO2 miscible huff and puff, and gas–water alternate drive processes were conducted on Chang 7 shale reservoir samples from the Yanchang Oilfield. The mechanism behind micro-displacement was analyzed by online NMR detection technologies, which showed that the displacement should be kept above the minimum miscible pressure during CO2 huff and puff. Furthermore, our analyses showed the highest recovery rate was that of water–gas alternate flooding is due to its higher utilization of small pores. Overall, CO2–water alternating flooding or CO2 miscible huff and puff is recommended to obtain higher recovery rates, based on our results. Considering the economic benefits and construction conditions, cyclic water flooding can be used first and then converted to other modes. This study can provide theoretical support for different ways of supplementing energy and provides scientific guidance for gas injection pilot test in similar reservoirs.

ABSTRACTEquid alphaherpesvirus 8 (EqHV-8) is one of the most economically important viruses that is known to cause severe respiratory disease, abortion, and neurological syndromes in equines. However, no effective vaccines or therapeutic agents are available to control EqHV-8 infection. Heme oxygenase-1 (HO-1) is an antioxidant defense enzyme that displays significant cytoprotective effects against different viral infections. However, the literature on the function of HO-1 during EqHV-8 infection is little. We explored the effects of HO-1 on EqHV-8 infection and revealed its potential mechanisms. Our results demonstrated that HO-1 induced by cobalt-protoporphyrin (CoPP) or HO-1 overexpression inhibited EqHV-8 replication in susceptible cells. In contrast, HO-1 inhibitor (zinc protoporphyria) or siRNA targeting HO-1 reversed the anti-EqHV-8 activity. Furthermore, biliverdin, a metabolic product of HO-1, mediated the anti-EqHV-8 effect of HO-1 via both the protein kinase C (PKC)β/extracellular signal-regulated kinase (ERK)1/ERK2 and nitric oxide (NO)-dependent cyclic guanosine monophosphate (cGMP)–protein kinase G (PKG) signaling pathways. In addition, CoPP protected the mice by reducing the EqHV-8 infection in the lungs. Altogether, these results indicated that HO-1 can be developed as a promising therapeutic strategy to control EqHV-8 infection.IMPORTANCEEqHV-8 infections have threatened continuously donkey and horse industry worldwide, which induces huge economic losses every year. However, no effective vaccination strategies or drug against EqHV-8 infection until now. Our present study found that one host protien HO-1 restrict EqHV-8 replication in vitro and in vivo. Furthermore, we demonstrate that HO-1 and its metabolite biliverdin suppress EqHV-8 relication via the PKCβ/ERK1/ERK2 and NO/cGMP/PKG pathways. Hence, we believe that HO-1 can be developed as a promising therapeutic strategy to control EqHV-8 infection.

Abstract Background Premature ovarian insufficiency (POI) is an important cause of infertility characterized by the functional decline of the ovary. Granulosa cells (GCs) around oocytes are critical for folliculogenesis, and GC dysfunction is one of the important etiologies of POI. The aim of this study was to explore the potential biomarkers of POI by identifying hub genes and analyze the correlation of biomarkers with immune infiltration in POI using RNA profiling and bioinformatics analysis. Methods RNA sequencing was performed on GCs from biochemical POI (bPOI) patients and controls. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were used to explore the candidate genes. qRT‒PCR was performed to verify the expression of hub genes. Western blot, Cell Counting Kit-8, 5‐ethynyl‐2’‐deoxyuridine (EdU) assays, TUNEL (TdT-mediated dUTP Nick-End Labeling) and flow cytometry analysis were used to validate the possible role of ubiquitin-conjugating enzyme 2C (UBE2C) in POI. CIBERSORT was adopted to explore immune cell infiltration and the correlation between UBE2C and immune cells in bPOI. Results Through analysis of differentially expressed genes (DEGs) and WGCNA, we obtained 143 candidate genes. After construction of the protein‒protein interaction (PPI) network and analysis with Cytoscape, 10 hub genes, including UBE2C, PBK, BUB1, CDC20, NUSAP1, CENPA, CCNB2, TOP2A, AURKB, and FOXM1, were identified and verified by qRT‒PCR. Subsequently, UBE2C was chosen as a possible biomarker of POI because knockdown of UBE2C could inhibit the proliferation and promote the apoptosis of GCs. Immune infiltration analysis indicated that monocytes and M1 macrophages may be associated with the pathogenesis of POI. In addition, UBE2C was negatively correlated with monocytes and M1 macrophages in POI. Conclusions This study identified a hub gene in GCs that might be important in the pathogenesis of POI and revealed the key role of UBE2C in driving POI. Immune infiltration may be highly related with the onset and etiology of POI.

Wheat scab can reduce wheat yield and quality. Currently, unmanned aerial vehicles (UAVs) are widely used for monitoring field crops. However, UAV is constrained by limited computational resources on-board the platforms. In addition, compared to ground images, UAV images have complex backgrounds and smaller targets. Given the aforementioned challenges, this paper proposes a lightweight wheat scab detection network based on UAV. In addition, overlapping cropping and image contrast enhancement methods are designed to preprocess UAV remote-sensing images. Additionally, this work constructed a lightweight wheat scab detection network called LWSDNet using mixed deep convolution (MixConv) to monitor wheat scab in field environments. MixConv can significantly reduce the parameters of the LWSDNet network through depthwise convolution and pointwise convolution, and different sizes of kernels can extract rich scab features. In order to enable LWSDNet to extract more scab features, a scab feature enhancement module, which utilizes spatial attention and dilated convolution, is designed to improve the ability of the network to extract scab features. The MixConv adaptive feature fusion module is designed to accurately detect lesions of different sizes, fully utilizing the semantic and detailed information in the network to enable more accurate detection by LWSDNet. During the training process, a knowledge distillation strategy that integrates scab features and responses is employed to further improve the average precision of LWSDNet detection. Experimental results demonstrate that the average precision of LWSDNet in detecting wheat scab is 79.8%, which is higher than common object detection models and lightweight object detection models. The parameters of LWSDNet are only 3.2 million (M), generally lower than existing lightweight object detection networks.

Abstract Clear cell renal cell carcinoma (ccRCC) with venous tumor thrombus (VTT) is associated with poor prognosis. Our integrative analyses of transcriptome and proteome reveal distinctive molecular features of ccRCC with VTT, and yield the development of a prognostic classifier to facilitate ccRCC molecular subtyping and treatment. The RNA sequencing and mass spectrometry were performed in normal-tumor-thrombus tissue triples of five ccRCC patients. Statistical analysis, GO and KEGG enrichment analysis, and protein–protein interaction network construction were used to interpret the transcriptomic and proteomic data. A six-gene-based classifier was developed to predict patients’ survival using Cox regression, which was validated in an independent cohort. Transcriptomic analysis identified 1131 tumorigenesis-associated differentially expressed genes (DEGs) and 856 invasion-associated DEGs. Overexpression of transcription factor EGR2 in VTT indicated its important role in tumor invasion. Furthermore, proteomic analysis showed 597 tumorigenesis-associated differentially expressed proteins (DEPs) and 452 invasion-associated DEPs. The invasion-associated DEPs showed unique enrichment in DNA replication, lysine degradation, and PPAR signaling pathway. Integration of transcriptome and proteome reveals 142 tumorigenesis-associated proteins and 84 invasion-associated proteins displaying changes consistent with corresponding genes in transcriptomic profiling. Based on their different expression patterns among normal-tumor-thrombus triples, RAB25 and GGT5 were supposed to play a consistent role in both tumorigenesis and invasion processes, while SHMT2 and CADM4 might play the opposite roles in tumorigenesis and thrombus invasion. A prognostic classifier consisting of six DEGs (DEPTOR, DPEP1, NAT8, PLOD2, SLC7A5, SUSD2) performed satisfactorily in predicting survival of ccRCC patients (HR = 4.41, P

Rheumatoid arthritis (RA) is a multifaceted autoimmune disease characterized by systemic inflammation, affecting both articular and extra-articular structures. This condition results in inflammation of joints and synovial membranes, accompanied by the development of systemic comorbidities. Despite extensive research, the precise pathogenic mechanisms responsible for RA have yet to be completely understood. RNA methylation, a burgeoning epigenetic alteration, assumes a pivotal function in the regulation of a myriad of biological phenomena, encompassing immunity, DNA damage response, tumorigenesis, metastasis, stem cell renewal, adipocyte differentiation, circadian rhythms, cellular development and differentiation, and cell division. The N6-methyladenosine (m6A) modification is the most prevalent among the various RNA modifications found in mammalian mRNA. Recent studies have provided evidence of the significant role played by m6A modification in the pathophysiological progression of RA. This review aims to provide a comprehensive analysis of the progress made in research focused on m6A modification in the context of RA, consolidate the underlying mechanisms involved in m6A modification during the initiation of RA and discuss the potential of targeting m6A modification as a viable therapeutic approach for RA.

Chemical synthesis has become an increasing popular approach for the production of proteins because of its flexibility and convenience in changing protein sequence and/or structure. However, at present, the efficiency of protein chemical synthesis is still low due to many methodological shortcomings. Here, we used a carbohydrate binding module (CBM) as a model molecule to explore the optimization of the oxidative folding of chemically synthesized proteins. By systematically comparing the reaction results, we were able to reveal the correlation between the overall folding rate and different reaction parameters, explain the possible reason for the observed correlation and identify the optimal conditions that maximize the synthetic efficiency. Overall, the findings from this study provided new insights into protein folding mechanisms and established new guiding principles for improving the efficiency of chemical protein synthesis.

ABSTRACTThe continued evolution and emergence of novel influenza viruses in wild and domestic animals poses an increasing public health risk. Two human cases of H3N8 avian influenza virus infection in China in 2022 have caused public concern regarding the risk of transmission between birds and humans. However, the prevalence of H3N8 avian influenza viruses in their natural reservoirs and their biological characteristics are largely unknown. To elucidate the potential threat of H3N8 viruses, we analyzed five years of surveillance data obtained from an important wetland region in eastern China and evaluated the evolutionary and biological characteristics of 21 H3N8 viruses isolated from 15,899 migratory bird samples between 2017 and 2021. Genetic and phylogenetic analyses showed that the H3N8 viruses circulating in migratory birds and ducks have evolved into different branches and have undergone complicated reassortment with viruses in waterfowl. The 21 viruses belonged to 12 genotypes, and some strains induced body weight loss and pneumonia in mice. All the tested H3N8 viruses preferentially bind to avian-type receptors, although they have acquired the ability to bind human-type receptors. Infection studies in ducks, chickens and pigeons demonstrated that the currently circulating H3N8 viruses in migratory birds have a high possibility of infecting domestic waterfowl and a low possibility of infecting chickens and pigeons. Our findings imply that circulating H3N8 viruses in migratory birds continue to evolve and pose a high infection risk in domestic ducks. These results further emphasize the importance of avian influenza surveillance at the wild bird and poultry interface.

Abstract Histone modifications play critical roles in regulating gene expression and present dynamic changes during early embryo development. However, how they are reprogrammed during human prenatal germline development has not yet been elucidated. Here, we map the genome-wide profiles of three key histone modifications in human primordial germ cells (hPGCs) from weeks 8 to 23 of gestation for the first time by performing ULI-NChIP-seq. Notably, H3K4me3 exhibits a canonical promoter-enriched pattern, though with relatively lower enrichment, and is positively correlated with gene expression in globally hypomethylated hPGCs. In addition, H3K27me3 presents very low enrichment but plays an important role in not only dynamically governing specific bivalent promoters but also impeding complete X chromosome reactivation in female hPGCs. Given the activation effects of both global DNA demethylation and H3K4me3 signals, repressive H3K9me3 and H3K27me3 marks are jointly responsible for the paradoxical regulation of demethylation-resistant regions in hPGCs. Collectively, our results provide a unique roadmap of three core histone modifications during hPGC development, which helps to elucidate the architecture of germ cell reprogramming in an extremely hypomethylated DNA environment.

Germline pathogenic variants in the BRCA2 gene are strongly correlated with an elevated risk of developing breast cancer. Two specific BRCA2 variants, c.8167G>C (p.Asp2723His) and c.1583del (p.Asn528fs), have been identified from individuals with a family history of breast cancer. Here we generated two iPSC lines from breast cancer patients who are heterozygous carriers of these two variants. These iPSCs exhibit pluripotency and demonstrate the capability to differentiate into three germ layers. These iPSC lines represent a valuable resource for personalized pre-clinical research, offering new opportunities to explore the underlying mechanisms of breast cancer and develop targeted therapeutic approaches.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder that leads to death in early adulthood. Patients with DMD have null mutations leading to loss of functional dystrophin protein. Here we generated two DMD induced pluripotent stem cell (iPSC) lines, one with deletion of exon 51 and the other with a single nucleotide nonsense mutation (c.10171C > T). Both lines expressed high levels of pluripotency markers, had the capability of differentiating into derivatives of the three germ layers, and possessed normal karyotypes. These iPSC lines can serve as powerful tools to model DMD in vitro and as a platform for therapeutic development.

Down syndrome (DS) is caused by trisomy of Homo sapiens chromosome 21 (HSA21) and is by far the most common chromosomal disorder accompanied by neurodevelopmental disorders and congenital heart disease. Here, we generated two induced pluripotent stem cell (iPSC) lines from two patients with DS. These two lines exhibited normal morphology, trisomy 21 karyotype, pluripotency and differentiation capability into derivatives of three germ layers. The patient-specific iPSC lines are an invaluable resource in research to model DS-related cellular and molecular pathologies and test possible therapeutic strategies for DS.

Abstract A reduced‐dimension minimum variance distortionless response based on sub‐array optimization beamformer (SAMVDR) is proposed for large array systems or some hardware performance constrained scenarios. The SAMVDR allows to weigh between convergence rate and computational complexity by selecting the sizes of the sub‐arrays. It is worth noting that, employing a sub‐array strategy, the SAMVDR allows for computing the matrix inversion with flexibly choosing the size of the matrix. When the size of each sub‐array is 1, namely single weight optimization MVDR (SWMVDR), the SAMVDR avoids matrix inversion. So the SWMVDR is easiest to implement in system than other sizes of sub‐arrays in the SAMVDR. It is found that the SAMVDR has manageable computational complexity and fast convergence rate, which is verified by theoretical analysis and simulation results. Importantly, the output performance of the SAMVDR is very close to auxiliary vector (AV) scheme, and the SWMVDR has lower computational cost than the AV. In addition, the SAMVDR can be applied to parallel systems with higher tracking speed.

Plant architecture strongly influences rice grain yield. We report the cloning and characterization of the LTA1 gene, which simultaneously controls tiller angle and yield of rice. LTA1 encodes a chloroplast-localized protein with a conserved YbaB DNA-binding domain, and is highly expressed in photosynthetic tissues including leaves and leaf sheaths. Disrupting the function of LTA1 leads to large tiller angle and yield reduction of rice. LTA1 affects the gravity response by mediating the distribution of endogenous auxin, thereby regulating the tiller angle. An lta1 mutant showed abnormal chloroplast development and decreased chlorophyll content and photosynthetic rate, in turn leading to reduction of rice yield. Our findings shed light on the genetic basis of tiller angle and provide a potential gene resource for the improvement of plant architecture and rice yield.

Introduction: The right ventricle (RV) mechanical property is an important determinant of its function. However, compared to its elasticity, RV viscoelasticity is much less studied, and it remains unclear how pulmonary hypertension (PH) alters RV viscoelasticity. Our goal was to characterize the changes in RV free wall (RVFW) anisotropic viscoelastic properties with PH development and at varied heart rates.Methods: PH was induced in rats by monocrotaline treatment, and the RV function was quantified by echocardiography. After euthanasia, equibiaxial stress relaxation tests were performed on RVFWs from healthy and PH rats at various strain-rates and strain levels, which recapitulate physiological deformations at varied heart rates (at rest and under acute stress) and diastole phases (at early and late filling), respectively.Results and Discussion: We observed that PH increased RVFW viscoelasticity in both longitudinal (outflow tract) and circumferential directions. The tissue anisotropy was pronounced for the diseased RVs, not healthy RVs. We also examined the relative change of viscosity to elasticity by the damping capacity (ratio of dissipated energy to total energy), and we found that PH decreased RVFW damping capacity in both directions. The RV viscoelasticity was also differently altered from resting to acute stress conditions between the groups—the damping capacity was decreased only in the circumferential direction for healthy RVs, but it was reduced in both directions for diseased RVs. Lastly, we found some correlations between the damping capacity and RV function indices and there was no correlation between elasticity or viscosity and RV function. Thus, the RV damping capacity may be a better indicator of RV function than elasticity or viscosity alone. These novel findings on RV dynamic mechanical properties offer deeper insights into the role of RV biomechanics in the adaptation of RV to chronic pressure overload and acute stress.

PurposeClear cell renal cell carcinoma (ccRCC) is the most common pathology type in kidney cancer. However, the prognosis of advanced ccRCC is unsatisfactory. Thus, early diagnosis becomes one of the most important research priorities of ccRCC. However, currently available studies about ccRCC lack urine-related further studies. In this study, we applied proteomics to search urinary biomarkers to assist early diagnosis of ccRCC. In addition, we constructed a prognostic model to assist judge patients’ prognosis.Materials and methodsUrine which was used to perform 4D label-free quantitative proteomics was collected from 12 ccRCC patients and 11 non-tumor patients with no urinary system diseases. The urine of 12 patients with ccRCC confirmed by pathological examination after surgery was collected before operatoin. Bioinformatics analysis was used to describe the urinary proteomics landscape of these patients with ccRCC. The top ten proteins with the highest expression content were selected as the basis for subsequent validation. Urine from 46 ccRCC patients and 45 control patients were collected to use for verification by enzyme linked immunosorbent assay (ELISA). In order to assess the prognostic value of urine proteomics, a prognostic model was constructed by COX regression analysis on the intersection of RNA-sequencing data in The Cancer Genome Atlas (TCGA) database and our urine proteomic data.Results133 proteins differentially expressed in the urinary samples were found and 85 proteins (Fold Change, FC>1.5) were identified up-regulated while 48 down-regulated (FC

With the rapid development of deep learning, researchers are actively exploring its applications in the field of industrial anomaly detection. Deep learning methods differ significantly from traditional mathematical modeling approaches, eliminating the need for intricate mathematical derivations and offering greater flexibility. Deep learning technologies have demonstrated outstanding performance in anomaly detection problems and gained widespread recognition. However, when dealing with multivariate data anomaly detection problems, deep learning faces challenges such as large-scale data annotation and handling relationships between complex data variables. To address these challenges, this study proposes an innovative and lightweight deep learning model—the Attention-Based Deep Convolutional Autoencoding Prediction Network (AT-DCAEP). The model consists of a characterization network based on convolutional autoencoders and a prediction network based on attention mechanisms. The AT-DCAEP exhibits excellent performance in multivariate time series data anomaly detection without the need for pre-labeling large-scale datasets, making it an efficient unsupervised anomaly detection method. We extensively tested the performance of AT-DCAEP on six publicly available datasets, and the results show that compared to current state-of-the-art methods, AT-DCAEP demonstrates superior performance, achieving the optimal balance between anomaly detection performance and computational cost.

In order to promote the edible utilization of broccoli stalks and leaves, as well as solve environmental issues from broccoli residues, the whole broccoli was chosen as materials and divided into florets, stalks and leaves to analyze the nutrients and minerals contents, thermal stability and the morphology of freeze-dried broccoli flours. The chromaticity, density, swelling capacity, water-holding and oil-holding capacities of broccoli florets, stalks and leaves were also measured. The results showed that the content of flavone in broccoli leaves was 19.82±0.86 mg/g, chlorophyll of 11.35±0.65 mg/g, calcium of 11.27±0.48 mg/g, copper of 20.23±0.81 μg/g, manganese of 29.62±0.71 μg/g, which were all higher than those in stalks and florets significantly (P0.05). The leaves and florets had high swelling capacity, but stalks and florets had high water-holding and oil-holding capacities. The florets had the highest water-holding and oil-holding capacities among three samples at 140-mesh, which were 13.18±0.46 g/g and 1.77±0.13 g/g, respectively. With consideration of processing costs, 140-mesh was the optimum size for florets, stalks and leaves of broccoli flours.

BackgroundClear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT) have poor prognosis. We aimed to reveal features of ccRCC with VTT and develop a urine-based prognostic classifier to predict ccRCC prognosis through integrative analyses of transcriptomic landscape and urinary signature.MethodsRNA sequencing was performed in five patients with ccRCC thrombus-tumor-normal tissue triples, while mass spectrometry was performed for urine samples from 12 ccRCC and 11 healthy controls. A urine-based classifier consisting of three proteins was developed to predict patients’ survival and validated in an independent cohort.ResultsTranscriptomic analysis identified 856 invasion-associated differentially expressed genes (DEGs). Furthermore, proteomic analysis showed 133 differentially expressed proteins (DEPs). Integration of transcriptomic landscape and urinary signature reveals 6 urinary detectable proteins (VSIG4, C3, GAL3ST1, TGFBI, AKR1C3, P4HB) displaying abundance changes consistent with corresponding genes in transcriptomic profiling. According to TCGA database, VSIG4, TGFBI, and P4HB were significantly overexpressed in patients with shorter survival and might be independent prognostic factors for ccRCC (all p

Embryo selection in in vitro fertilization–embryo transfer (IVF-ET) mostly relies on morphological assessment using a conventional microscope or the time-lapse monitoring system, which is not comprehensive. Inappropriate levels of reactive oxygen species (ROS) in the fertilization medium may cause damage to gametes, eventually leading to adverse IVF outcomes. The present study aimed to identify the optimal oxidation–reduction level in the fertilization medium for IVF outcomes by measuring the static oxidation–reduction potential (sORP) using a highly accurate and sensitive MiOXSYS system. A total of 136 patients undergoing IVF following brief incubation were divided equally into 4 groups in this prospective cohort study. The sORP value in the fertilization medium was detected using the MiOXSYS system, and its relationship with IVF outcomes was analyzed. The primary outcome was pregnancy outcomes, including live birth rate (LBR), clinical pregnancy rate (CPR), biochemical pregnancy rate (BPR), and implantation rate (IR). The secondary outcome was embryo quality, including fertilization rate (FR), cleavage rate (CR), available embryo rate (AER), and good-quality embryo rate (GQER). Group II (sORP: 228.7–235.3 mV) showed a higher LBR, CPR, BPR, and IR compared with Group III (sORP: 235.4–242.7 mV), presented as follows: LBR (32.0% for Group II vs 3.6% for Group III, P = 0.033), CPR (32.0% for Group II vs 3.6% for Group III, P = 0.033), BPR (36.0% for Group II vs 3.6% for Group III, P = 0.019), and IR (31.3% for Group II vs 2.7% for Group III, P = 0.003). The FR in Groups I and II had lower significant differences compared with that in Groups III and IV (71.7% and 70.3% for Groups I and II vs 83.5% and 80.4% for Groups III and IV, P = 0.000). The GQER in Group I to Group IV was 32.7%, 37.4%, 26.5%, and 33.3%, respectively (P = 0.056). This study indicated that the sORP value in the fertilization medium might be a potential indicator of embryo quality and pregnancy outcome.

Abstract As the COVID‐19 pandemic evolves and new variants emerge, the development of more efficient identification approaches of variants is urgent to prevent continuous outbreaks of SARS‐CoV‐2. Field‐effect transistors (FETs) with two‐dimensional (2D) materials are viable platforms for the detection of virus nucleic acids (NAs) but cannot yet provide accurate information on NA variations. Herein, 2D Indium selenide (InSe) FETs were used to identify SARS‐CoV‐2 variants. The device's mobility and stability were ensured by atomic layer deposition (ALD) of Al2O3. The resulting FETs exhibited sub‐fM detection limits ranging from 10–14 M to 10–8 M. The recognition of single‐nucleotide variations was achieved within 15 min to enable the fast and direct identification of two core mutations (L452R, R203M) in Delta genomes (p

Abstract This paper studies the estimation problem for multisensor networked systems with mixed uncertainties, which include colored noises, same multiplicative noises in system parameter matrices, uncertain noise variances, as well as the one-step random delay (OSRD) and packet dropouts (PDs). This study utilizes the centralized fusion (CF) algorithm to combing all information received by each sensor, which improve the accuracy of the estimation. By using the augmentation method, de-randomization method and fictitious noise techniques, the original uncertain system is transformed into an augment model with only uncertain noise variances. Then, for all uncertainties within the allowable range, the robust CF steady-state Kalman estimators (predictor, filter, and smoother) are presented based on the worst-case CF system, in light of the minimax robust estimation principle. To demonstrate the robustness of the proposed CF estimators, the non-negative definite matrix decomposition method and Lyapunov equation approach are employed. It is proved that the robust accuracy of CF estimator is higher than that of each local estimator. Finally, the simulation example applied to the uninterruptible power system (UPS) with colored noises and multiple uncertainties illustrates the effectiveness of the proposed CF robust estimation algorithm.

The effects of Y on the solidification process of 7Mo super austenitic stainless steel (7MoSASS) under low cooling rate conditions (10 °C/min) were investigated using high-temperature confocal laser scanning microscopy (HT-CLSM). The in situ observation results indicate that Y samples promote an increase in austenite nucleation density. After 10 s of nucleation, the nucleation density increased by 149.53/mm2 for the Y sample. Furthermore, variance analysis indicated that Y addition improved the uniformity of the 7MoSASS solidification microstructure under low cooling rate conditions. The Johnson–Mehl–Avrami–Kolmogorov (JMAK) theory results showed that when the solid phase ratio was 0.5, the nucleation mode of the Y sample transitioned from saturation site nucleation to saturation site nucleation + Avrami nucleation. YAlO3 has a low lattice disregistry value with austenite, making it a suitable heterogeneous nucleation core for promoting the early nucleation of austenite. During the late stages of solidification, Y accumulates in the residual liquid phase, providing a greater degree of compositional undercooling. SEM-EDS analysis showed that Y contributed to the refinement of the 7MoSASS solidification microstructure, with the proportion of precipitated phases decreasing by approximately 7.5%. Cr and Mo were the main elements exhibiting positive segregation in 7MoSASS, and the Cr segregation ratio increased in the Y sample, while the Mo segregation ratio decreased.