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Abstract Background During male gametogenesis of flowering plants, sperm cell lineage (microspores, generative cells, and sperm cells) differentiated from somatic cells and acquired different cell fates. Trimethylation of histone H3 on lysine 4 (H3K4me3) epigenetically contributes to this process, however, it remained unclear how H3K4me3 influences the gene expression in each cell type. Here, we conducted chromatin immunoprecipitation sequencing (ChIP-seq) to obtain a genome-wide landscape of H3K4me3 during sperm cell lineage development in tomato (Solanum lycopersicum). Results We show that H3K4me3 peaks were mainly enriched in the promoter regions, and intergenic H3K4me3 peaks expanded as sperm cell lineage differentiated from somatic cells. H3K4me3 was generally positively associated with transcript abundance and served as a better indicator of gene expression in somatic and vegetative cells, compared to sperm cell lineage. H3K4me3 was mutually exclusive with DNA methylation at 3’ proximal of the transcription start sites. The microspore maintained the H3K4me3 features of somatic cells, while generative cells and sperm cells shared an almost identical H3K4me3 pattern which differed from that of the vegetative cell. After microspore division, significant loss of H3K4me3 in genes related to brassinosteroid and cytokinin signaling was observed in generative cells and vegetative cells, respectively. Conclusions Our results suggest the asymmetric division of the microspore significantly reshapes the genome-wide distribution of H3K4me3. Selective loss of H3K4me3 in genes related to hormone signaling may contribute to functional differentiation of sperm cell lineage. This work provides new resource data for the epigenetic studies of gametogenesis in plants.

Abstract Balkground Gobio huanghensis is a small economic fish endemic to the Yellow River at the junction of the Tibetan Plateau and the Huangtu Plateau in China. To understand the impact of environmental changes and human activities on the ecological structure of the G. huanghensis population, a comparative study was conducted on the age composition, growth characteristics, mortality rate, and exploitation rate of the G. huanghensis populations in the Gansu and Ningxia sections of the upper Yellow River. Results During the investigation, a total of 1147 individuals were collected, with 427 individuals collected from the Gansu section and 720 individuals from the Ningxia section. The results showed that G. huanghensis in the Gansu section exhibited a total length ranging from 5.00 to 22.80 cm, with an average of 12.68 ± 4.03 cm. In the Ningxia section, the total length of G. huanghensis ranged from 2.15 to 20.65 cm, with an average of 9.48 ± 3.56 cm. The age composition of G. huanghensis in the Gansu section ranged from 1 to 7 years, where female fish were observed between 1 and 7 years old, and male fish between 1 and 6 years old. In the Ningxia section, both female and male fish ranged from 1 to 5 years old. The relationships between total length and body weight were (Gansu section, R 2 = 0.9738) and (Ningxia section, R 2 = 0.9686), indicating that fish in the Gansu section exhibit positive allometric growth, while fish in the Ningxia section exhibit negative allometric growth. The von Bertalanffy growth equation revealed that G. huanghensis in the Gansu section exhibited an asymptotic total length L ∞ of 27.426 cm with a growth coefficient K of 0.225 yr−1, while in the Ningxia section, the asymptotic total length L ∞ was 26.945 cm with a growth coefficient K of 0.263 yr−1. The total mortality rate (Z) values of G. huanghensis were 0.7592 yr and 1.1529 yr in the Gansu section and Ningxia section, respectively. The average natural mortality rate (M), estimated by three different methods, in the Gansu section was 0.4432 yr, while it was 0.5366 yr in the Ningxia section. The exploitation rate (E) of G. huanghensis was 0.4163 in the Gansu section and 0.5345 in the Ningxia section, indicating that the population in the Ningxia section may have been overexploited. Conclusion Prolonged fishing pressures and environmental changes may have led to variations in the ecological parameters of the G. huanghensis population between the Gansu and Ningxia sections.

AbstractBoth bullous pemphigoid (BP) and psoriasis are common immune-related dermatological conditions in clinical practice, but the co-occurrence of these two diseases is rare. Currently, there is no consensus on the long-term safe and effective treatment for patients with both BP and psoriasis. JAK inhibitors are emerging as targeted therapeutic drugs that act by inhibiting Janus kinase activity, regulating the JAK/STAT pathway, blocking the transduction pathway of key proinflammatory cytokines, and influencing T-cell differentiation. These cytokines upstream of the JAK/STAT pathway play a pivotal role in the pathogenesis of numerous inflammatory and autoimmune disorders. Upadacitinib, a second-generation JAK inhibitor with high selectivity, demonstrates promising potential.This case report aims to provide a description of the successful treatment of bullous pemphigoid (BP) and psoriasis vulgaris by using upadacitinib, highlighting significant clinical outcomes. Additionally, we aim to analyze the underlying mechanism of upadacitinib in treating these two comorbidities by reviewing relevant literature from both domestic and international sources. Based on our clinical observations, upadacitinib appears to be a promising and well-tolerated therapeutic option for patients with concurrent BP and psoriasis, offering valuable insights for developing appropriate treatment strategies in clinical practice.

AbstractGobio huanghensis, a member of the eponymous genus within the Cyprinidae, family of the Cypriniformes order, is an endemic fish species found exclusively in the upper reaches of the Yellow River, spanning from Yinchuan to Lanzhou. This study presents the first comprehensive report of the complete mitochondrial genome sequence of G. huanghensis, encompassing 16,604 base pairs (bp) with a nucleotide composition of 26.3% cytosine (C), 17.6% guanine (G), 29.4% adenine (A), and 26.7% thymine (T). In congruence with other species in the Gobio genus, its mitochondrial genome comprises 37 genes, including two ribosomal RNA genes, 13 protein-coding genes (PCGs), and 22 transfer RNA genes. Notably, COX1 initiates with the start codon GTG, distinct from the typical ATG start codon of other PCGs. The mitogenome exhibits four types of stop codons: TAA, TAG, TA-, and T--. Phylogenetic analyses, grounded in complete mitochondrial sequences, position G. huanghensis at the forefront of one of two major clusters within the genus Gobio, corroborating existing morphological classifications. These findings offer valuable theoretical insights for the taxonomic classification, conservation, and population genetics of G. huanghensis.

Against the backdrop of hydropower development in the upper Yellow River, comprehending the spatiotemporal variation and ecological evaluation of macroinvertebrate functional feeding groups (FFGs) is paramount for the conservation and restoration of aquatic biological resources in watersheds. Detailed surveys of macroinvertebrates were conducted in the gorge and plain areas of the upper Yellow River in July 2022 and March, May, and October 2023, culminating in the identification of 65 taxonomic units (genus or species) spanning 4 phyla, 14 orders, and 35 families. Of these, 41 taxonomic units were discovered in the gorge areas and 57 in the plain areas. Among the FFGs of macroinvertebrates in the upper Yellow River, collector-gatherers were overwhelmingly dominant, followed by scrapers, collector-filterers, predators, and shredders. Concerning river section types, dominant species in the gorge areas included Gammarus sp., Limnodrilus hoffmeisteri, and Polypedilum sp. among collector-gatherers, while in the plain areas, dominant species included Ecdyonurus sp. among scrapers, Hydropsyche sp. among collector-filterers, and Gammarus sp., Limnodrilus hoffmeisteri, and Chironomus sp. among collector-gatherers. A Mantel test revealed that dissolved oxygen, conductivity, and orthophosphate were the primary environmental factors affecting the FFGs of macroinvertebrates in the upper Yellow River, with variations observed in their effects across different months. The evaluation results of the Hilsenhoff Biological Index and Shannon–Wiener Index indicate that the water quality of the upper Yellow River is at a moderate level. An assessment of the upper Yellow River ecosystem using FFG parameters demonstrated that macroinvertebrate biomass progressively increased from upstream (gorge areas) to downstream (plain areas) spatially, accompanied by increasing habitat stability, with cascade hydropower development identified as a key factor impacting habitat stability. These findings provide pertinent data and a theoretical foundation for the protection of aquatic biological resources and watershed management in the upper Yellow River.

Abstract Systems-level assessments of protein-protein interaction (PPI) network dysfunctions are currently out-of-reach because approaches enabling proteome-wide identification, analysis, and modulation of context-specific PPI changes in native (unengineered) cells and tissues are lacking. Herein, we take advantage of chemical binders of maladaptive scaffolding structures termed epichaperomes and develop an epichaperome-based ‘omics platform, epichaperomics, to identify PPI alterations in disease. We provide multiple lines of evidence, at both biochemical and functional levels, demonstrating the importance of these probes to identify and study PPI network dysfunctions and provide mechanistically and therapeutically relevant proteome-wide insights. As proof-of-principle, we derive systems-level insight into PPI dysfunctions of cancer cells which enabled the discovery of a context-dependent mechanism by which cancer cells enhance the fitness of mitotic protein networks. Importantly, our systems levels analyses support the use of epichaperome chemical binders as therapeutic strategies aimed at normalizing PPI networks.

According to characteristics of a low-grade manganese carbonate ore, it made a respective use of high gradient magnetic separation and shaker gravity separation, as well as experimental study on flotation process of the ore．Experimental results showed that wet high-intensity magnetic separation was the reasonable way to deal with the mine. The magnetic concentrate with Mn grade of 21.04% and Mn recovery of 75.55% could be obtained by adopting high intensity process of one-stage roughing, one-stage scavenging, two-stage cleaning, and regrinding magnetic separation of cleaning tailings. The experimental study provides a basis for the development of similar manganese ores.

To investigate the age composition, growth pattern, mortality, and exploitation rate of Triplophysa scleroptera in the upper reaches of the Yellow River, we measured the total length (L) and body weight (W) of 347 individuals based on three sampling surveys from 2022 to 2023. The otoliths were used in this investigation to determine age. The total length of the collected samples ranged from 5.69 cm to 18.40 cm, body weight ranged from 1.65 g to 50.22 g, and the age ranged from 1 to 7 years old. The relationship of total length and body weight was W=0.009L2.942 for the total samples, and the growth pattern observed in the study belongs to the isometric type. The von Bertalanffy growth equation revealed that the fish had an asymptotic total length L∞ of 37.536 cm, and the growth coefficient K was 0.064 yr−1. Total instantaneous mortality rate (Z) of total samples calculated by the age-based catch curve method was 1.092 yr−1. The average instantaneous rate of the natural mortality (M), estimated by three different methods, for the total samples was 0.237 yr−1. The instantaneous rate of fishing mortality (F) for the total samples was calculated as 0.855 yr−1, and the exploitation rate (E) was determined as 0.783. As a whole, compared with other Triplophysa fishes, the growth rate of T. scleroptera in the upper reaches of the Yellow River is relatively slow, and the population of T. scleroptera has been overexploited. It is crucial to establish some effective management strategies to protect this species.

T. yarkandensis is a common species of Triplophysa, and it is distributed in Shule river of Hexi Corridor, of Gansu province in China. In order to enrich gene database resources and explore the environment adaptation of T. yarkandensis, fifteen tissues were collected from three adult T. yarkandensis for transcriptome sequencing and de novo assembly. Nine major international gene annotation databases (NR, COG, egg_NOG, TrEMBL, Pfam, KOG, Swiss prot, KEGG and Gene Ontology) were utilized to annotate unigenes. A detailed study was conducted to explore the gene expression and the differentially expressed genes among five tissues (brain, heart, kidney, liver and spleen). In addition, the current study showed that candidate genes involved in salinity-alkalinity and low temperature adaptation were differentially expressed in tissues of T. yarkandensis. Precisely, mapk1, abcc1, gpx1, gpx4, cat and aqp1 genes participated in the regulation process of salinity-alkalinity adaptation, and elovl4, acaca, fasn, acaa2, acox1 and acox3 genes were involved in fatty acid metabolism and closely associated with low temperature adaptation. On the one hand, it was found that the expression of these genes varied among different tissues, and the important pathways involved in these genes were mapped. Furthermore, we analyzed mapk1 and acox1 genes in depth to obtain the predicted gene structure and important amino acid sites. The transcriptome information in this study will be conducive to provide further understanding for the molecular level research and exploration of the environmental adaptation of T. yarkandensis.

Recent studies have found that comments from teaching assistants may encourage interactions in edX-like Massive Open Online Course (xMOOC) forums. However, how concepts from these interactions are conveyed to other xMOOC participants has not received much attention. Therefore, this study focuses on a unidirectional teaching assistant-student xMOOC interaction (TS interaction), a content-related pair including one question from a student and one immediate answer from a teaching assistant. The authors particularly investigate the linguistic features (i.e., concept connectivity, concept concreteness, readability and semantic overlap) of concept conveying in TS interactions with many responses (mTS) and with few responses (fTS). In addition, a language factor (English and Chinese) is also considered. Additionally, the interaction transcripts from science lectures (SL) and political briefings (PB) were used as control groups as two opposite cases of concept conveying. At the concept level, the concept conveying in transcripts were modelled as a graph, and measured by common indicators in graph theory. At the overall level, the concept conveying in transcripts were measured by regular linguistic measuring tools. The results show that interactions with mTS and fTS demonstrate different concept conveying tendencies toward SL and PB in terms of linguistic features in both languages. The results suggest that in both languages, teaching assistants may use mixed concept-conveying strategies to stimulate more follow-up responses in xMOOC forums. These conclusions drawn from TS interactions can be even partially generalized in a larger student-student (SS) interaction dataset.

Joshi, Gomes et al. employ a chemical modulation approach of the cellular interactome to a hyperconnectivity state and show association with the increased response of pancreatic cancer cell lines to specific drugs, including those that target the MAPK-pathways and PI3K-mTOR pathway. To achieve this, the authors employ chemical modulation of the interactome via epichaperome inhibition with the small molecule PU-H71.

BackgroundRegarding the complexity of Parkinson's disease (PD), the identification of reliable biomarkers is of great significance for improving the accuracy of diagnosis and monitoring disease progression. Recently, some studies suggested that serum proline-rich protein 14 (PRR14), vascular cell adhesion molecule-1 (VCAM-1), and soluble CD163 (sCD163) factors may be associated with PD, even as potential biomarkers. However, the role of these serum factors is still unclear.ObjectivesThis study aimed to explore the alterations of serum PRR14, VCAM-1, and sCD163 levels during PD progression, and their association with disease-related variables of PD.MethodsWe performed the assessment of scale tests and the detection of serum samples in patients with PD (n = 100) and healthy controls (HCs, n = 100). Furthermore, we investigated the association between serum factors and sex, cognitive impairments, H&Y (Hohn and Yahr), age at onset (AAO), and other variables in patients with PD.ResultsPatients with PD exhibited increased PRR14 and VCAM-1 serum levels compared with HCs. No significant differences were found in serum levels of sCD163. Subgroup analysis uncovered increased VCAM-1 in the female and male subgroups (PD and HCs). Among patients with PD, decreased PRR14 and increased VCAM-1 were associated with severer cognitive impairments and severer PD (H&Y), respectively. Bivariate correlation analysis revealed that there was a positive correlation between VCAM-1 and AAO.ConclusionsIncreased serum levels of PRR14 and VCAM-1 suggest that inflammation and defective autophagy may play vital roles in the pathogenesis of PD. However, the potential mechanisms remain to be elucidated.

Artificial protrusions fabricated on metal surfaces are adequate for the mechanical interlocking to strengthen the metal/polymer joint. The morphology and its adhesion with the metal substrate of the fabricated protrusions greatly influence the joint strength and joint detachability. However, the large-sized protrusion can cause carbon fiber damage when embedded into the polymer plate, which results in the decline of the joint strength. This paper applied a diode-pumped solid-state laser system to melt stainless powders to fabricate micron-sized protrusions on metal surfaces. The effect of four impacting factors, original powder size, powder bedding thickness, laser power density, and laser irradiation time, on the formation of micro-protrusions was investigated. SEM was used to characterize the morphology and diameter of the formed micro-protrusions. The results showed that the fabricated micro-protrusions present a spherical shape under the stable manufacturing process, and the diameter ranged from 100 µm to 500 µm. The micro-protrusions size positively correlated with the original powder size and powder bedding thickness. Laser power density directly affected the forming of micro-protrusions, and the suitable process window was between 160 W/mm2 to 290 W/mm2. When the laser irradiation time was 10 s, it helped stabilize the fabrication process.

The anonymity of the Internet used to be considered as an encouraging factor that helped learners engage in online learning. However, academic studies on anonymity have found that its effect on learning is context-dependent or mixed. In this research, we focused on massive open online course (MOOC) learners’ preference for personal name disclosure in their screen names as a predictor of their final achievement levels (FALs) at the end of a course including 2606 active learners. We conducted two studies, one to examine the associations between these two variables and one to demonstrate how such associations can be utilized in MOOC FAL prediction. We found that MOOC learners who included personal names in their MOOC screen names significantly outperformed other learners in their FALs (p < 0.001). We also found that screen name preference improved FAL prediction accuracy utilizing natural language processing and proper machine learning technologies. The error rate was reduced to 4.03% by a random forest algorithm with an appropriate feature combination: the personal name disclosure indicator (PNDI), quiz scores, number of replies, and exam scores. The results are potentially useful for the development of an early intervention to provide different types of help to students who prefer to disclose personal names and those who do not. The practical effects of these interventions will be examined in the future. In addition, whether the course difficulty level or course type affects the associations between personal name disclosure and FAL will also be examined.

Abstract Background The northeastern part of the Qinghai-Tibet Plateau (QTP) presents a high number of plateau loach species. As one of the three major groups of fishes distributed on the QTP, plateau loach has high ecological value. However, the taxonomy and systematics of these fish are still controversial, and a large number of new species have been reported. The reason for this phenomenon is that the degree of morphological variation is low, the phylogenetic information provided by morphological and anatomical features used for species identification is relatively poor, and many cryptic species are observed. Based on the high-density sampling points from the biodiversity hotspots surveyed, this study aims to evaluate the biodiversity of plateau loach in the northeastern part of the QTP and reveal the hidden diversity by comparing morphological species with molecular operational taxonomic units (MOTUs). Results After careful identification and comparison of the morphology and DNA barcoding of 1630 specimens, 22 species were identified, with 20 considered valid local species and two identified as new species that had not been previously described. Based on the combination of morphological and molecular methods, a total of 24 native species were found, two of which were cryptic species: Triplophysa robusta sp1 and Triplophysa minxianensis sp1. Fourteen of the 24 species form clusters of barcodes that allow them to be reliably identified. The remaining cases involved 10 closely related species, including rapidly differentiated species and species that seemed to have experienced incomplete lineage sorting or showed introgressions. Conclusions The results highlight the need to combine traditional taxonomies with molecular methods to correctly identify species, especially closely related species, such as the plateau loach. This study provides a basis for protecting the biodiversity of plateau loach.

The welding of 8-mm thick Q235 low-carbon steel plates by keyhole tungsten inter gas welding (K-TIG), a deep penetration argon arc welding technique with tungsten electrode, is associated with many problems, including an unstable welding process and a small welding current window. To solve these prominent problems, the method of adding shielding flux on the back of the welding workpieces was proposed for the first time in this paper. This method can improve the stability of the welding process. The butt welding method was used to achieve the result of single-sided welding and double-sided forming without adding welding wire or prefabricating groove during the welding process. The results show that direct current (DC) in the range of 430–480 A is successfully used to weld the 8-mm thick Q235 low-carbon steel. The welding current window is expanded to 50 A, and the welding process stability is significantly improved. After expanding the welding current window, the microstructures and properties of welded joints obtained under different welding currents were systematically studied. The results show that the distribution of microstructures and the mechanical properties of the welded joints under different welding currents present the same states. The microstructures of the weld zone are composed of ferrite + pearlite + widmanstatten structure; the microstructures of the fusion zone are composed of Widmanstatten structure; the structures of the heat-affected zones are composed of ferrite + a small amount of pearlite. In addition, with the increase in the welding current, the fusion width of the back of the workpiece increased slightly. In the welding joint, the hardness value of the fusion zone is the highest, followed by the weld zone, and the heat-affected zone. The base material has the least hardness, and the final tensile fracture position of the welded joint is in the heat affected zone.

Alkali-salinity exerts severe osmotic, ionic, and high-pH stresses to plants. To understand the alkali-salinity responsive mechanisms underlying photosynthetic modulation and reactive oxygen species (ROS) homeostasis, physiological and diverse quantitative proteomics analyses of alkaligrass (Puccinellia tenuiflora) under Na2CO3 stress were conducted. In addition, Western blot, real-time PCR, and transgenic techniques were applied to validate the proteomic results and test the functions of the Na2CO3-responsive proteins. A total of 104 and 102 Na2CO3-responsive proteins were identified in leaves and chloroplasts, respectively. In addition, 84 Na2CO3-responsive phosphoproteins were identified, including 56 new phosphorylation sites in 56 phosphoproteins from chloroplasts, which are crucial for the regulation of photosynthesis, ion transport, signal transduction, and energy homeostasis. A full-length PtFBA encoding an alkaligrass chloroplastic fructose-bisphosphate aldolase (FBA) was overexpressed in wild-type cells of cyanobacterium Synechocystis sp. Strain PCC 6803, leading to enhanced Na2CO3 tolerance. All these results indicate that thermal dissipation, state transition, cyclic electron transport, photorespiration, repair of photosystem (PS) II, PSI activity, and ROS homeostasis were altered in response to Na2CO3 stress, which help to improve our understanding of the Na2CO3-responsive mechanisms in halophytes.

The biology of Alzheimer’s disease (AD) remains unknown. We propose AD is a protein connectivity-based dysfunction disorder whereby a switch of the chaperome into epichaperomes rewires proteome-wide connectivity, leading to brain circuitry malfunction that can be corrected by novel therapeutics.

Due to the high degree of dissimilarity in physicochemical properties between metal and carbon fiber, it presents a tremendous challenge to join them directly. In this paper, cold rolled steel (SPCC) and carbon fiber reinforced thermoplastic (CFRTP) chopped sheet hybrid joints were produced with the addition of Nylon 6 (PA6) thermoplastic film as an intermediate layer by the ultrasonic plastic welding method. The effect of ultrasonic welding energy and preheating temperature on the hybrid joint microstructure and mechanical behavior was well investigated. The suitable joining parameters could obtain a strong joint by adding the PA6 film as an intermediate layer between the SPCC and bare carbon fibers. Microstructural analysis revealed that the interface joining condition between the PA6 film and the SPCC component is the primary reason for the joint strength. The crevices generated at the interface were eliminated when the preheating temperature arrived at 200 °C, and the joint strength thus significantly increased. The lap shear test results under quasi-static loading showed that the welding energy and preheating temperature synergistically affect the joint performances. At 240 °C, the joint strength value reached the maximum. Through the analysis of the microstructure morphology, mechanical performance, and the failure mechanism of the joint, the optimized joining process window for ultrasonic plastic welding of SPCC-CFRTP by adding an intermediate layer, was obtained.

CircRNAs have been reported to play essential roles in regulating immunity and inflammation, which may be an important regulatory factor in the development of vitiligo. However, the expression profile of circRNAs and their potential biological functions in vitiligo have not been reported so far. In our study we found there are 64 dysregulated circRNAs and 14 dysregulated miRNAs in the patients with vitiligo. Through the correlation analysis, we obtained 12 dysregulated circRNAs and 5 dysregulated miRNAs, forming 48 relationships in the circRNA-miRNA-mRNA regulatory network. Gene Ontology analysis indicated dysregulated circRNAs in vitiligo is closely related to the disorder of the metabolic pathway. The KEGG pathway of dysregulation of circRNAs mainly enriched in the biological processes such as ubiquitin mediated proteolysis, endocytosis and RNA degradation, and in Jak-STAT signaling pathway. Therefore, we found the circRNA-miRNA-mRNA regulatory network are involved in the regulation of numerous melanocyte functions, and these dysregulated circRNAs may closely related to the melanocyte metabolism. Our study provides a theoretical basis for studying the vitiligo pathogenesis from the perspective of circRNA-miRNA-mRNA network.

Summary: Stresses associated with disease may pathologically remodel the proteome by both increasing interaction strength and altering interaction partners, resulting in proteome-wide connectivity dysfunctions. Chaperones play an important role in these alterations, but how these changes are executed remains largely unknown. Our study unveils a specific N-glycosylation pattern used by a chaperone, Glucose-regulated protein 94 (GRP94), to alter its conformational fitness and stabilize a state most permissive for stable interactions with proteins at the plasma membrane. This “protein assembly mutation’ remodels protein networks and properties of the cell. We show in cells, human specimens, and mouse xenografts that proteome connectivity is restorable by inhibition of the N-glycosylated GRP94 variant. In summary, we provide biochemical evidence for stressor-induced chaperone-mediated protein mis-assemblies and demonstrate how these alterations are actionable in disease.

The early molecular events that ultimately lead to neuronal cell death in pathologies such as Parkinson’s disease are poorly understood. Here the authors use pluripotent stem-cell-derived human midbrain neurons and chemical biology tools to gain molecular level insight into the events induced by toxic and genetic stresses that mimic those occurring during neurodegeneration.

Began with Computer-Assisted Language Learning (CALL) in the 1960s and extended to the widespread use of various Mobile-Assisted Language Learning (MALL) tools in education, language learning has embraced technology early on, achieved noticeable results, and found extensive practical use. However, due to the challenges in accessing user data from various language learning platforms, the measurement and assessment of language-related variables continue to rely on self-reporting and peer evaluations. This reliance hampers researchers to observe language learning from alternative perspectives, especially when it comes to analyzing raw behavioral data. To explore potential correlations between different learning modes, this study analyzed 2 million samples from Chinese students using an English language learning application. The study quantified the effectiveness of English vocabulary learning using the economic concept of return on investment (ROI) as an evaluation metric and identified four distinct learning strategies. It observed significant differences in learning ROI among learners who adopted different strategies. Based on this analysis, we recommend the following suggestions for improving language learning ROI: when memorizing new vocabulary, investing excessive amounts of time may be counterproductive; a more effective approach is to "eat less but more often," which means arranging review sessions at a reasonable pace and shortening the interval between each review.

Distant hybridization usually leads to female sterility of the hybrid but the mechanism behind this is poorly understood. Complete pistil abortion but normal male fertility was shown by one Brassica napus-Orychophragmus violaceus monosomic alien addition line (MA, AACC + 1 IO, 2n = 39) produced previously. To study the effect of a single O. violaceus chromosome addition on pistil development in different genetic backgrounds, hybrids between the MA and B. carinata (BBCC), B. juncea (AABB), and two synthetic hexaploids (AABBCC) were firstly produced in this study which show complete female sterility. A microspore culture was further performed to produce the haploid monosomic alien addition line (HMA, AC + 1 IO, 2n = 20) and disomic addition line (DA, AACC + 2 IO, 2n = 40) together with haploid (H, AC, 2n = 19) and double haploid (DH, AACC, 2n = 38) plants of B. napus from MA to investigate the dosage effect of the alien O. violaceus chromosome on pistil development and gene expression. Compared to MA, the development of the pistils of DA and HMA was completely or partially recovered, in which the pistils could swell and elongate to a normal shape after open pollination, although no seeds were produced. Comparative RNA-seq analyses revealed that the numbers of the differentially expressed genes (DEGs) were significantly different, dosage-dependent, and consistent with the phenotypic difference in pairwise comparisons of HMA vs. H, DA vs. DH, MA vs. DH, MA vs. DA, and MA vs. HMA. The gene ontology (GO) enrichment analysis of DEGs showed that a number of genes involved in the development of the gynoecium, embryo sac, ovule, and integuments. Particularly, several common DEGs for pistil development shared in HMA vs. H and DA vs. DH showed functions in genotoxic stress response, auxin transport, and signaling and adaxial/abaxial axis specification. The results provided updated information for the molecular mechanisms behind the gynoecium development of B. napus responding to the dosage of alien O. violaceus chromosomes.

In this paper, we determined the complete mitochondrial DNA (mtDNA) sequence of Gobio coriparoides and analyzed its phylogenetic position. The complete mitogenome is 16,604 bp in length. It consists of 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and 1 control region. Among the 37 genes, 28 were encoded on the heavy strand, while 9 were encoded on the light strand. The overall base composition was 28.97% for A, 18.06% for G, 26.54% for T, and 26.43% for C, with a higher A + T content (55.51%). There are some overlaps existing in G. coriparoides mitochondrial genome. The neighbor-joining (NJ) phylogenetic tree based on whole mitogenome sequences supported that G. coriparoides is the closest to G. cynocephalus. This result will provide a basic reference for understanding the genetic structure, molecular evolution, and phylogeny of G. coriparoides and related species.

Cobitoidea is one of the two superfamilies in Cypriniformes; however, few genomes have been sequenced for Cobitoidea fishes. Here, we obtained a total of 252.90 Gb of short Illumina reads and 31.60 Gb of long PacBio Sequel reads, representing approximate genome coverage of 256× and 50×, respectively. The final assembled genome is about 583.47 Mb with contig N50 sizes of 2.87 Mb, which accounts for 91.44% of the estimated genome size of 638.07 Mb. Using Hi-C–based chromatin contact maps, 99.31% of the genome assembly was placed into 25 chromosomes, and the N50 is 22.3 Mb. The gene annotation completeness was evaluated by BUSCO, and 2,470 of the 2,586 conserved genes (95.5%) could be found in our assembly. Repetitive elements were calculated to reach 33.08% of the whole genome. Moreover, we identified 25,406 protein-coding genes, of which 92.59% have been functionally annotated. This genome assembly will be a valuable genomic resource to understand the biology of the Tibetan loaches and will also set a stage for comparative analysis of the classification, diversification, and adaptation of fishes in Cobitoidea.

The molecular chaperone Hsp90 is an essential and highly abundant central node in the interactome of eukaryotic cells. Many of its large number of client proteins are relevant to cancer. A hallmark of Hsp90-dependent proteins is that their accumulation is compromised by Hsp90 inhibitors. Combined with the anecdotal observation that cancer cells may be more sensitive to Hsp90 inhibitors, this has led to clinical trials aiming to develop Hsp90 inhibitors as anti-cancer agents. However, the sensitivity to Hsp90 inhibitors has not been studied in rigorously matched normal versus cancer cells, and despite the discovery of important regulators of Hsp90 activity and inhibitor sensitivity, it has remained unclear, why cancer cells might be more sensitive. To revisit this issue more systematically, we have generated an isogenic pair of normal and oncogenically transformed NIH-3T3 cell lines. Our proteomic analysis of the impact of three chemically different Hsp90 inhibitors shows that these affect a substantial portion of the oncogenic program and that indeed, transformed cells are hypersensitive. Targeting the oncogenic signaling pathway reverses the hypersensitivity, and so do inhibitors of DNA replication, cell growth, translation and energy metabolism. Conversely, stimulating normal cells with growth factors or challenging their proteostasis by overexpressing an aggregation-prone sensitizes them to Hsp90 inhibitors. Thus, the differential sensitivity to Hsp90 inhibitors may not stem from any particular intrinsic difference between normal and cancer cells, but rather from a shift in the balance between cellular quiescence and activity.

Resonance is generally used as a metaphor to describe the manner how the information from different sources is combined. Although it is an attractive and fundamental phenomenon in human behavior studies, most studies observed semantic resonances in well-controlled experimental settings at word level. To make up the missing link between word and document level resonances, we devoted our contributions to topic resonances in a novel and natural setting: academic commentaries. Ninety-three academic commentaries from ninety-three authors, along with their references and original papers, are analyzed by a latent Dirichlet allocation based natural language processing approach. This approach can decompose a corpus written and read by an author into several topics with different weights, which can reveal the phenomena ignored at word or document level. We found that (1) topic resonances commonly exist between commenters' fundamental input and output topics; (2) output words are re-allocated by commenters to echo salient input topics; (3) commenters are more prone to associate references which focus on the non-dominant input topics; and (4) topic resonance can even be predicted by a Hebbian-like model which matches the aforementioned findings. These findings will continue to enrich our understanding on the relationship among probe, feedback and context.

The crystal structures, magnetic and optical properties of the 3d transition metals of Co or Mn doped CuInTe2 have been investigated using X-ray diffraction, magnetic measurements, ultraviolet and visible spectrophotometers. It is found that CuIn1-xTxTe2 (T=Co, Mn) crystallize in tetragonal chalcopyrite structure in a doping range of x=0-0.2. The structural analyses show that the 3d transition metal of Mn or Co prefers to occupy the 4b crystal position. Mn-doped CuIn1-xMnxTe2 (x=0-0.3) show paramagnetic characteristics at room temperature with the susceptibilities of about 10-5. However, lightly Co-doping into CuIn1-xCoxTe2 shows ferromagnetism at room temperature under a low applied field. This phenomenon is suggested to result from the spin-spin interactions between Co atoms which lead to the ferromagnetism. CuIn0.9Co0.1Te2 with ferromagnetism at room temperature under a low field revealed in this work indicates that it a good candidate for photovoltaic cells application since its bandgap matches well with that of CuIn1-xGaxSe2 with high conversion efficiency.

Pollen germination is an excellent process to study cell polarity establishment. During this process, the tip-growing pollen tube will start elongating. The plasma membrane as the selectively permeable barrier that separates the inner and outer cell environment plays crucial roles in this process. This protocol described an efficient aqueous polymer two-phase system followed by alkaline solution washing to prepare Lilium davidii or Oryza sativa plasma membrane with high purity.

Plasma membrane (PM) proteins play crucial roles in diverse biological processes. But their low abundance, alkalinity and hydrophobicity make their isolation a difficult task. This protocol describes an efficient method for PM proteins isolation, digestion and fractionation so that they can be well prepared for mass spectrometry analysis.

The surface of Q235 low carbon steel was modified by the metal inert-gas welding (MIG) method; a 304 stainless steel surfacing layer was fabricated to improve the properties of Q235 low carbon steel. For practical industry application, keyhole tungsten inter gas (K-TIG) welding was used to weld the surface-modified plates. The microstructure, elemental distribution, micro-hardness, and corrosion resistance of the surface-modified plates and the welded joints were analyzed. The corrosion tests of welded joints and surface-modified plates were carried out with the electrochemical method and hydrochloric acid immersion method, respectively, and surface morphology after corrosion was studied. The results show that the surface-modified plates and their welded joints were defect-free. The microstructure of the surfacing layer consisted of austenite, martensite, and ferrite; and the microstructure of the weld consisted mainly of martensite. The hardness and corrosion resistance of the surfacing layer was superior to that that of low carbon steel. The micro-hardness of the weld is higher than that of the stainless steel surfacing layer and the base material. The corrosion resistance of the surfacing layer is the best, and the corrosion resistance of the welding seam is better than that of the base material.

Soil salt-alkalinization is a widespread environmental stress that limits crop growth and agricultural productivity. The influence of soil alkalization caused by Na2CO3 on plants is more severe than that of soil salinization. Plants have evolved some unique mechanisms to cope with alkali stress; however, the plant alkaline-responsive signaling and molecular pathways are still unknown. In the present study, Na2CO3 responsive characteristics in leaves from 50-day-old seedlings of halophyte Puccinellia tenuiflora were investigated using physiological and proteomic approaches. Comparative proteomics revealed 43 differentially expressed proteins in P. tenuiflora leaves in response to Na2CO3 treatment for seven days. These proteins were mainly involved in photosynthesis, stress and defense, carbohydrate/energy metabolism, protein metabolism, signaling, membrane and transport. By integrating the changes of photosynthesis, ion contents, and stress-related enzyme activities, some unique Na2CO3 responsive mechanisms have been discovered in P. tenuiflora. This study provides new molecular information toward improving the alkali tolerance of cereals.

During sexual reproduction of flowering plants, the pollen tube grows fast and over a long distance within the pistil to deliver two sperms for double fertilization. Growing plant cells need to communicate constantly with external stimuli as well as monitor changes in surface tension of the cell wall and plasma membrane to coordinate these signals and internal growth machinery; however, the underlying mechanisms remain largely unknown. Here we show that the rice member of plant-specific receptor-like kinase CrRLK1Ls subfamily, Ruptured Pollen tube (RUPO), is specifically expressed in rice pollen. RUPO localizes to the apical plasma membrane and vesicle of pollen tubes and is required for male gamete transmission. K+ levels were greater in pollen of homozygous CRISPR-knockout lines than wild-type plants, and pollen tubes burst shortly after germination. We reveal the interaction of RUPO with high-affinity potassium transporters. Phosphorylation of RUPO established and dephosphorylation abolished the interaction. These results have revealed the receptor-like kinase as a regulator of high-affinity potassium transporters via phosphorylation-dependent interaction, and demonstrated a novel receptor-like kinase signaling pathway that mediates K+ homeostasis required for pollen tube growth and integrity.

Aluminum powders with different concentrations of TiC ceramic particles were applied to an AZ31B magnesium alloy by laser cladding. Due to differences in coefficients of thermal expansion, the distribution of TiC ceramic particles in the cladding layer was not uniform. The results show that the degree of TiC ceramic particle agglomeration in the cladding layer increases with increasing TiC content. The phases of cladding metal mainly consisted of Al, γ-Al12Mg17, β-Al3Mg2, and TiC. The γ-Al12Mg17 phase mainly distributed to the bottom of the cladding layer, and the β-Al3Mg2 phase distributed to the middle and surface areas. The existence of the γ-Al12Mg17 phase enhanced the hardness of the fusion zone. The microhardness of the cladding layer increased with increasing TiC ceramic particle content. An appropriate TiC content improved the wear resistance of the cladding layer. When the TiC content was excessive, the agglomeration behavior of TiC ceramic particles strongly affected the wear resistance of the coatings.

The Haihe River is the most seriously polluted river among the seven largest rivers in China. Dichloro-diphenyl-trichloroethanes (DDTs), hexachlorocyclohexanes (HCHs), and PCBs (noncoplanar polychlorinated biphenyls) in the Haihe River, Tianjin were determined using a gas chromatograph – electron capture detector (GC-ECD). Dioxin-like compounds (DLCs) were determined using Chemically Activated LUciferase gene eXpression (CALUX) bioassay. HCH and DDT levels were, respectively, 0.06–6.07 μg/L and ND (not detected) to 1.21 μg/L; PCB levels ranged from 0.12 to 5.29 μg/L; and the total DLCs in sediment were 4.78–343 pg TEQ (toxic equivalency)/g. Aquatic ecological risk assessment was performed using the joint probability curve method and the Monte Carlo-based HQ (hazard quotient) distribution method. The combined risks of similar chemicals and the total risk of dissimilar categories of chemicals were assessed based on the principles of joint toxicity. Due to the adjacent industrial activities, the risk levels of PCBs, DDTs, and HCHs were relatively high. The risk order was as follows: PCBs > DDTs ≈ HCHs > DLCs. The risk of HCHs approximated that of DDTs, which is different from the fact that risk of HCHs is usually much lower in the other Chinese rivers. The total risk caused by these pollutants was very high. Due to their high persistence and potential source from land, the high risks of such pollutants are likely to last for a long period of time.

Plant diurnal oscillation is a 24-hour period based variation. The correlation between diurnal genes and biological pathways was widely revealed by microarray analysis in different species. Rice (Oryza sativa) is the major food staple for about half of the world's population. The rice flag leaf is essential in providing photosynthates to the grain filling. However, there is still no comprehensive view about the diurnal transcriptome for rice leaves. In this study, we applied rice microarray to monitor the rhythmically expressed genes in rice seedling and flag leaves. We developed a new computational analysis approach and identified 6,266 (10.96%) diurnal probe sets in seedling leaves, 13,773 (24.08%) diurnal probe sets in flag leaves. About 65% of overall transcription factors were identified as flag leaf preferred. In seedling leaves, the peak of phase distribution was from 2:00am to 4:00am, whereas in flag leaves, the peak was from 8:00pm to 2:00am. The diurnal phase distribution analysis of gene ontology (GO) and cis-element enrichment indicated that, some important processes were waken by the light, such as photosynthesis and abiotic stimulus, while some genes related to the nuclear and ribosome involved processes were active mostly during the switch time of light to dark. The starch and sucrose metabolism pathway genes also showed diurnal phase. We conducted comparison analysis between Arabidopsis and rice leaf transcriptome throughout the diurnal cycle. In summary, our analysis approach is feasible for relatively unbiased identification of diurnal transcripts, efficiently detecting some special periodic patterns with non-sinusoidal periodic patterns. Compared to the rice flag leaves, the gene transcription levels of seedling leaves were relatively limited to the diurnal rhythm. Our comprehensive microarray analysis of seedling and flag leaves of rice provided an overview of the rice diurnal transcriptome and indicated some diurnal regulated biological processes and key functional pathways in rice.

DNA topoisomerase VI from Archaea, a heterotetrameric complex composed of two TopVIA and two TopVIB subunits, is involved in altering DNA topology during replication, transcription and chromosome segregation by catalyzing DNA strand transfer through transient double-strand breaks. The sequenced yeast and animal genomes encode only one homologue of the archaeal TopVIA subunit, namely Spo11, and no homologue of the archaeal TopVIB subunit. In yeast, Spo11 is essential for initiating meiotic recombination and this function appears conserved among other eukaryotes. In contrast to yeast and animals, studies in Arabidopsis and rice have identified three Spo11/TopVIA homologues and one TopVIB homologue in plants. Here, we further identified two novel Spo11/TopVIA homologues (named OsSpo11-4 and OsSpo11-5, respectively) that exist just in the monocot model plant Oryza sativa, indicating that at least five Spo11/TopVIA homologues are present in the rice genome. To reveal the biochemical function of the two novel Spo11/TopVIA homologues, we first examined the interactions among OsSpo11-1, OsSpo11-4, OsSpo11-5, and OsTopVIB by yeast two-hybrid assay. The results showed that OsSpo11-4 and OsTopVIB can self-interact strongly and among the 3 examined OsSpo11 proteins, only OsSpo11-4 interacted with OsTopVIB. Pull-down assay confirmed the interaction between OsSpo11-4 and OsTopVIB, which indicates that OsSpo11-4 may interact with OsTopVIB in vivo. Further in vitro enzymatic analysis revealed that among the above 4 proteins, only OsSpo11-4 exhibited double-strand DNA cleavage activity and its enzymatic activity appears dependent on Mg(2+) and independent of OsTopVIB, despite its interaction with OsTopVIB. We further analyzed the biological function of OsSpo11-4 by RNA interference and found that down-regulated expression of OsSpo11-4 led to defects in male meiosis, indicating OsSpo11-4 is required for meiosis.