Self-distillation framework for document-level relation extraction in low-resource environments.

The objective of document-level relation extraction is to retrieve the relations existing between entities within a document. Currently, deep learning methods have demonstrated superior performance in document-level relation extraction tasks. However, to enhance the model's performance, various methods directly introduce additional modules into the backbone model, which often increases the number of parameters in the overall model. Consequently, deploying these deep models in resource-limited environments presents a challenge. In this article, we introduce a self-distillation framework for document-level relational extraction. We partition the document-level relation extraction model into two distinct modules, namely, the entity embedding representation module and the entity pair embedding representation module. Subsequently, we apply separate distillation techniques to each module to reduce the model's size. In order to evaluate the proposed framework's performance, two benchmark datasets for document-level relation extraction, namely GDA and DocRED are used in this study. The results demonstrate that our model effectively enhances performance and significantly reduces the model's size.

A nanocomposite hydrogel loaded with Ag nanoparticles reduced by aloe vera polysaccharides as an antimicrobial multifunctional sensor.

Developing high-performance hydrogels with anti-freeze, and antimicrobial properties is crucial for the practical application of flexible sensors. In this study, we prepared silver nanoparticles (AgNPs) with aloe polysaccharide (AP) as a reducing agent. Then, the AP/AgNPs were added to a system of polyvinyl alcohol and borax crosslinked in water/glycerol to obtain a multifunctional conductive hydrogel. The incorporated AgNPs improved the conductivity (0.39 S/m) and mechanical properties (elongation at break: 732.9 %, fracture strength: 1267.6 kPa) of the hydrogel. In addition, resultant hydrogel exhibited potential for sensing strain, temperature, and humidity. When used as a strain sensor, the hydrogel system exhibited low detection limit (0.1 %), and fast response (0.08 s). The resistance of the hydrogel decreased with an increase in the absorbed moisture content, enabling humidity detection (25-95 %) to monitor breathing status. As a temperature sensor, the hydrogel supported a wide detection range (-50 to +90 °C) and sensitivity (-30-0 °C, temperature coefficient of resistance (TCR) = -5.64 %/°C) to detect changes in the ambient temperature. This study proposes a simple method for manufacturing multifunctional hydrogel sensors, which broadens their application prospects in wearable sensing and electronic products.

Treatment algorithms of relapsing multiple sclerosis: an exploration based on the available disease-modifying therapies in China.

Multiple sclerosis (MS) was defined as a rare disease in China due to its low prevalence. For a long time, interferon ß was the only approved disease-modifying therapy (DMT). Since the first oral DMT was approved in 2018, DMT approval accelerated, and seven DMTs were approved within 5 years. With an increasing number of DMTs being prescribed in clinical practice, it is necessary to discuss the standardized MS treatment algorithms depending on the disease activity and DMT availability. In this review paper, more than 20 Chinese experts in MS have reviewed the therapeutic progress of MS in China and worldwide and discussed algorithms for treating relapsing MS (RMS) based on the available DMTs in China, providing insights for establishing the standardized RMS treatment algorithms in this country.

Treatment algorithms of relapsing multiple sclerosis in China In this review paper, more than 20 Chinese experts in MS have reviewed the therapeutic progress of MS in China and worldwide and discussed algorithms for treating relapsing MS (RMS) based on the available DMTs in China, providing insights for establishing the standardized RMS treatment algorithms in this country: 1) CIS and RRMS account for more than 90% of the MS patients and most of them are mild to moderate; 2) MS patients should initiate DMT treatments as soon as the disease has been diagnosed in order to reduce the risk of disease progression; 3) Patients who have been diagnosed with MS should start treatment with fundamental DMTs unless the disease course has been highly active; 4) MAGNIMS score may be a suitable and simplified assessment tool for measuring treatment response to DMTs; 5) Patients treated with corticosteroids and NSIS should be switched to the standardized DMT treatment during remission in accordance with disease activity.

Efficient generation of cloned cats with altered coat colour by editing of the KIT gene.

Coat colour largely determines the market demand for several cat breeds. The KIT proto-oncogene (KIT) gene is a key gene controlling melanoblast differentiation and melanogenesis. KIT mutations usually cause varied changes in coat colour in mammalian species. In this study, we used a pair of single-guide RNAs (sgRNAs) to delete exon 17 of KIT in somatic cells isolated from two different Chinese Li Hua feline foetuses. Edited cells were used as donor nuclei for somatic cell nuclear transfer (SCNT) to generate cloned embryos presenting an average cleavage rate exceeding 85%, and an average blastocyst formation rate exceeding 9.5%. 131 cloned embryos were transplanted into four surrogates, and all surrogates carried their pregnancies to term, and delivered 4.58% (6/131) alive cloned kittens, with 1.53% (2/131) being KIT-edited heterozygotes (KITD17/+). The KITD17/+ cats presented an obvious darkness reduction in the mackerel tabby coat. Immunohistochemical analysis (IHC) of skin tissues indicated impaired proliferation and differentiation of melanoblasts caused by the lack of exon17 in feline KIT. To our knowledge, this is the first report on coat colour modification of cats through gene editing. The findings could facilitate further understanding of the regulatory role of KIT on feline coat colour and provide a basis for the breeding of cats with commercially desired coat colour.

Preparation of Mesophase Pitch with Fine-Flow Texture from Ethylene Tar/Naphthalene by Catalytic Synthesis for High-Thermal-Conductivity Carbon Fibers.

Mesophase pitch is usually prepared by radical polymerization or catalytic polymerization from coal tar, petroleum, and aromatic compounds, and the catalytic synthesis of mesophase pitch from pure aromatic compounds is more controllable in the preparation of high-quality mesophase pitch. However, the corrosive and highly toxic nature of the catalyst has limited the further development of this method. In this study, mesophase pitch was synthetized using ethylene tar and naphthalene as raw materials and boron trifluoride diethyl etherate as a catalyst. The effect of the catalytic reaction on the structure and properties of the mesophase pitch was investigated. The results show that naphthalene plays an important role in the mesophase content and reaction pressure (from above 6 MPa to 2.35 MPa). Mesophase pitch with fine-flow texture can be prepared by introducing more methylene groups, naphthenic structures, and aliphatic hydrocarbons during synthesis. Carbon fibers prepared from mesophase pitch show a split structure, and the thermal conductivity is 730 W/(m·K). This work provides theoretical support for lower toxicity and causticity and for reaction-controlled technology for the synthesis of high-purity mesophase pitch.

Current perspectives on the regulatory mechanisms of sucrose accumulation in sugarcane.

Sugars transported from leaves (source) to stems (sink) energize cell growth, elongation, and maintenance. which are regulated by a variety of genes. This review reflects progress and prospects in the regulatory mechanism for maximum sucrose accumulation, including the role of sucrose metabolizing enzymes, sugar transporters and the elucidation of post-transcriptional control of sucrose-induced regulation of translation (SIRT) in the accumulation of sucrose. The current review suggests that SIRT is emerging as a significant mechanism controlling Scbzip44 activities in response to endogenous sugar signals (via the negative feedback mechanism). Sucrose-controlled upstream open reading frame (SC-uORF) exists at the 5' leader region of Scbzip44's main ORF, which inhibits sucrose accumulation through post-transcriptional regulatory mechanisms. Sucrose transporters (SWEET1a/4a/4b/13c, TST, SUT1, SUT4 and SUT5) are crucial for sucrose translocation from source to sink. Particularly, SWEET13c was found to be a major contributor to the efflux in the transportation of stems. Tonoplast sugar transporters (TSTs), which import sucrose into the vacuole, suggest their tissue-specific role from source to sink. Sucrose cleavage has generally been linked with invertase isozymes, whereas sucrose synthase (SuSy)-catalyzed metabolism has been associated with biosynthetic processes such as UDP-Glc, cellulose, hemicellulose and other polymers. However, other two key sucrose-metabolizing enzymes, such as sucrose-6-phosphate phosphohydrolase (S6PP) and sucrose phosphate synthase (SPS) isoforms, have been linked with sucrose biosynthesis. These findings suggest that manipulation of genes, such as overexpression of SPS genes and sucrose transporter genes, silencing of the SC-uORF of Scbzip44 (removing the 5' leader region of the main ORF that is called SIRT-Insensitive) and downregulation of the invertase genes, may lead to maximum sucrose accumulation. This review provides an overview of sugarcane sucrose-regulating systems and baseline information for the development of cultivars with higher sucrose accumulation.

HDAC2 counteracts vascular calcification by activating autophagy in chronic kidney disease.

Vascular calcification is a major risk factor for cardiovascular disease mortality, with a significant prevalence in chronic kidney disease (CKD). Pharmacological inhibition of histone acetyltransferase has been proven to protect against from vascular calcification. However, the role of Histone Deacetylase 2 (HDAC2) and molecular mechanisms in vascular calcification of CKD remains unknown. An in vivo model of CKD was established using mouse fed with a high adenine and phosphate diet, and an in vitro model was produced using human aortic vascular smooth muscle cells (VSMCs) stimulated with ß-glycerophosphate (ß-GP). HDAC2 expression was found to be reduced in medial artery of CKD mice and ß-GP-induced VSMCs. Overexpression of HDAC2 attenuated OPN and OCN upregulation, α-SMA and SM22α downregulation, and calcium deposition in aortas of CKD. The in vitro results also demonstrated that ß-GP-induced osteogenic differentiation was inhibited by HDAC2. Furthermore, we found that HDAC2 overexpression caused an increase in LC3II/I, a decrease in p62, and an induction of autophagic flux. Inhibition of autophagy using its specific inhibitor 3-MA blocked HDAC2's protective effect on osteogenic differentiation in ß-GP-treated VSMCs. Taken together, these results suggest that HDAC2 may protect against vascular calcification by the activation of autophagy, laying out a novel insight for the molecular mechanism in vascular calcification of CKD.

Minocycline attenuates the bilirubin-induced developmental neurotoxicity through the regulation of innate immunity and oxidative stress in zebrafish embryos.

When liver or intestinal function is impaired, bilirubin accumulates in the body and leads to neonatal jaundice. However, the potential negative effects caused by excessive accumulation of bilirubin such as developmental immunotoxicity and neurotoxicity remain unclear. We used a zebrafish model to establish bilirubin-induced jaundice symptoms and evaluated the toxic effects of bilirubin in aquatic organisms. Firstly, our results suggested that bilirubin exposure markedly decreased the survival rate, induced the developmental toxicity and increased the yellow pigment deposited in the zebrafish tail. Meanwhile, the number of macrophages and neutrophils was substantially reduced in a concentration-dependent manner. Besides, the antioxidant enzyme activities were greatly elevated while the inflammatory genes were significantly decreased after bilirubin exposure. Secondly, transcriptome analysis identified 708 genes were differentially expressed after bilirubin exposure, which animal organ morphogenesis, chemical synaptic transmission, and MAPK / mTOR signaling pathways were significantly enriched. Thirdly, bilirubin exposure leads to a significant decrease in the motility of zebrafish, including a dose-dependent decrease in the travelled distance, movement time, and average velocity. Moreover, the innate immune genes and apoptosis-related genes such as TLR4, NF-κB p65, STAT3 and p53 were elevated at a concentration of 10 µg/mL of bilirubin. Finally, our results further revealed that the anti-inflammatory and neuroprotective minocycline could partially rescue the bilirubin-induced neurobehavioral disorders in zebrafish embryos. In conclusion, our study explored the bilirubin-induced immunotoxicity and neurotoxicity in aquatic organisms, which will provide a theoretical basis for the treatment of neonatal jaundice in clinical practice.

Correction: Nian et al. Coping Strategies for Pertussis Resurgence. Vaccines 2023, 11, 889.

The authors would like to make the following corrections to this published paper [...].

lncRNA-MIAT rs9625066 polymorphism could be a potential biomarker for ischemic stroke.

BACKGROUND: Ischemic stroke (IS) is a common and serious neurological condition that is highly fatal but so far no early diagnostic markers are available. Myocardial infarction-associated transcript (MIAT) is a long non-coding RNA (lncRNA) that could lead to IS by inducing autophagy and apoptosis in neuronal cells. However, there has been no report on the link between susceptibility to IS and the single-nucleotide polymorphisms (SNPs) of MIAT. This study aimed to investigate the association between MIAT gene polymorphisms and IS risk. METHODS: A total of 320 IS patients and 310 age-, sex- and race-matched controls were included in this study. Four polymorphisms (rs2157598, rs5761664, rs1894720, and rs9625066) were genotyped by using SNPscan technique. RESULTS: Among the 4 polymorphisms of MIAT, only rs9625066 was associated with IS risk (CA vs. CC: adjusted OR = 0.55, 95% CI, 0.37-0.85, P = 0.006; AA vs. CC: adjusted OR = 0.39, 95% CI, 0.16-0.94, P = 0.036; (AA + CA vs. CC: adjusted OR = 0.53, 95% CI, 0.35-0.80, P = 0.002; A vs. C adjusted OR = 0.59, 95% CI, 0.42-0.82, P = 0.002). Haplotype analysis showed a 1.32-fold increase (95% CI, 1.05-1.67, P = 0.017) in IS risk for rs2157598-rs5761664-rs1894720-rs9625066 (A-C-G-C). Logistic regression analysis identified some independent impact factors for IS including rs9625066 AA/AC, TC, TG, HDL-C (P < 0.05). CONCLUSION: The rs9625066 polymorphism of MIAT might be associated with IS susceptibility in Chinese population, in which AA/CA plays a protective role in IS, whereas the CC genotype increases the risk of developing IS, suggesting it might be a marker predictive of IS risk.

It starts at home: non-economic factors influencing consumer acceptance of battery storage in Australia.

Homeowners play a critical role in the uptake of low-carbon technologies, yet little is known about the factors that underlie market acceptance of residential battery storage. This research integrates social-psychological, demographic and behavioural factors into a holistic model that predicts market acceptance. Previous research has indicated that social factors play a crucial role in the adoption of rooftop solar. Still, the influence of subjective norms on battery storage, a relatively invisible technology, has yet to be fully understood. An online survey from homeowners in Australia, a mature renewable energy market, is used to provide insights into market acceptance that are relevant to international energy markets. A two-step econometric model, using factor analysis and ordered logistic regression, was used for data analysis. The results show that subjective norms, moral emotions and an environmental self-identity are positively associated with market acceptance. Demographic factors, such as younger age and higher levels of education, predict market acceptance. Motives such as technical interest, autarky and load-shifting behaviours are also relevant. Several recommendations for policymakers and practitioners are offered to improve the acceptance of battery storage, including interventions that exploit social parameters and appeal to consumer psychology.

Changes in muscle strength and risk of cardiovascular disease among middle-aged and older adults in China: Evidence from a prospective cohort study.

BACKGROUND: Evidence indicates that low muscle strength is associated with an increased cardiovascular diseases (CVDs) risk. However, the association between muscle strength changes based on repeated measurements and CVD incidence remains unclear. METHODS: The study used data from the China Health and Retirement Longitudinal Study in 2011 (Wave 1), 2013 (Wave 2), 2015 (Wave 3), and 2018 (Wave 4). Low muscle strength was defined as handgrip strength <28 kg for men or <18 kg for women, or chair-rising time ≥12 s. Based on changes in muscle strength from Waves 1 to 2, participants were categorized into four groups of Normal-Normal, Low-Normal, Normal-Low, and Low-Low. CVD events, including heart disease and stroke, were recorded using a self-reported questionnaire during Waves 3 and 4 visits. Cox proportional hazards models were used to investigate the association between muscle strength changes and CVD incidence after multivariable adjustments. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated with the Normal-Normal group as the reference. RESULTS: A total of 1164 CVD cases were identified among 6608 participants. Compared to participants with sustained normal muscle strength, the CVD risks increased progressively across groups of the Low-Normal (HR = 1.20, 95% CI: 1.01-1.43), the Normal-Low (HR = 1.35, 95% CI: 1.14-1.60), and the Low-Low (HR = 1.76, 95% CI: 1.49-2.07). Similar patterns were observed for the significant associations between muscle strength status and the incidence risks of heart disease and stroke. Subgroup analyses showed that the significant associations between CVD and muscle strength changes were consistent across age, sex, and body mass index (BMI) categories. CONCLUSIONS: The study found that muscle strength changes were associated with CVD risk. This suggests that continuous tracking of muscle status may be helpful in screening cardiovascular risk.

Genetic Studies Highlight the Role of TET2 and INO80 in DNA Damage Response and Kidney Disease Pathogenesis.

Genome-wide association studies (GWAS) have identified over 800 loci associated with kidney function, yet the specific genes, variants, and pathways involved remain elusive. By integrating kidney function GWAS, human kidney expression and methylation quantitative trait analyses, we identified Ten-Eleven Translocation (TET) DNA demethylase 2: TET2 as a novel kidney disease risk gene. Utilizing single-cell chromatin accessibility and CRISPR-based genome editing, we highlight GWAS variants that influence TET2 expression in kidney proximal tubule cells. Experiments using kidney-tubule-specific Tet2 knockout mice indicated its protective role in cisplatin-induced acute kidney injury, as well as chronic kidney disease and fibrosis, induced by unilateral ureteral obstruction or adenine diet. Single-cell gene profiling of kidneys from Tet2 knockout mice and TET2- knock-down tubule cells revealed the altered expression of DNA damage repair and chromosome segregation genes, notably including INO80 , another kidney function GWAS target gene itself. Remarkably both TET2- null and INO80- null cells exhibited an increased accumulation of micronuclei after injury, leading to the activation of cytosolic nucleotide sensor cGAS-STING. Genetic deletion of cGAS or STING in kidney tubules or pharmacological inhibition of STING protected TET2 null mice from disease development. In conclusion, our findings highlight TET2 and INO80 as key genes in the pathogenesis of kidney diseases, indicating the importance of DNA damage repair mechanisms.

Dynamic metabolite QTL analyses provide novel biochemical insights into kernel development and nutritional quality improvement in common wheat.

Despite recent advances in crop metabolomics, the genetic control and molecular basis of the wheat kernel metabolome at different developmental stages remain largely unknown. Here, we performed widely targeted metabolite profiling of kernels from three developmental stages (grain-filling kernels [FKs], mature kernels [MKs], and germinating kernels [GKs]) using a population of 159 recombinant inbred lines. We detected 625 annotated metabolites and mapped 3173, 3143, and 2644 metabolite quantitative trait loci (mQTLs) in FKs, MKs, and GKs, respectively. Only 52 mQTLs were mapped at all three stages, indicating the high stage specificity of the wheat kernel metabolome. Four candidate genes were functionally validated by in vitro enzymatic reactions and/or transgenic approaches in wheat, three of which mediated the tricin metabolic pathway. Metabolite flux efficiencies within the tricin pathway were evaluated, and superior candidate haplotypes were identified, comprehensively delineating the tricin metabolism pathway in wheat. Finally, additional wheat metabolic pathways were re-constructed by updating them to incorporate the 177 candidate genes identified in this study. Our work provides new information on variations in the wheat kernel metabolome and important molecular resources for improvement of wheat nutritional quality.

Unraveling the epigenetic code: human kidney DNA methylation and chromatin dynamics in renal disease development.

Epigenetic changes may fill a critical gap in our understanding of kidney disease development, as they not only reflect metabolic changes but are also preserved and transmitted during cell division. We conducted a genome-wide cytosine methylation analysis of 399 human kidney samples, along with single-nuclear open chromatin analysis on over 60,000 cells from 14 subjects, including controls, and diabetes and hypertension attributed chronic kidney disease (CKD) patients. We identified and validated differentially methylated positions associated with disease states, and discovered that nearly 30% of these alterations were influenced by underlying genetic variations, including variants known to be associated with kidney disease in genome-wide association studies. We also identified regions showing both methylation and open chromatin changes. These changes in methylation and open chromatin significantly associated gene expression changes, most notably those playing role in metabolism and expressed in proximal tubules. Our study further demonstrated that methylation risk scores (MRS) can improve disease state annotation and prediction of kidney disease development. Collectively, our results suggest a causal relationship between epigenetic changes and kidney disease pathogenesis, thereby providing potential pathways for the development of novel risk stratification methods.

Precisely Control Relationship between Sulfur Vacancy and H Absorption for Boosting Hydrogen Evolution Reaction.

Effective and robust catalyst is the core of water splitting to produce hydrogen. Here, we report an anionic etching method to tailor the sulfur vacancy (VS) of NiS2 to further enhance the electrocatalytic performance for hydrogen evolution reaction (HER). With the VS concentration change from 2.4% to 8.5%, the H* adsorption strength on S sites changed and NiS2-VS 5.9% shows the most optimized H* adsorption for HER with an ultralow onset potential (68 mV) and has long-term stability for 100 h in 1 M KOH media. In situ attenuated-total-reflection Fourier transform infrared spectroscopy (ATR-FTIRS) measurements are usually used to monitor the adsorption of intermediates. The S- H* peak of the NiS2-VS 5.9% appears at a very low voltage, which is favorable for the HER in alkaline media. Density functional theory calculations also demonstrate the NiS2-VS 5.9% has the optimal |ΔGH*| of 0.17 eV. This work offers a simple and promising pathway to enhance catalytic activity via precise vacancies strategy.

[Retracted] Intracisternal administration of an interleukin­6 receptor antagonist attenuates surgery­induced cognitive impairment by inhibition of neuroinflammatory responses in aged rats.

[This retracts the article DOI: 10.3892/etm.2014.2149.].

The functional divergence of homologous GPAT9 genes contributes to the erucic acid content of Brassica napus seeds.

BACKGROUND: The early allopolyploid Brassica napus was a hybrid of two Brassica species, that had undergone a whole genome duplication event followed by genome restructuring, including deletions and small scale duplications. A large number of homologous genes appeared functional divergence during species domestication. Due to the high conservation of de novo glycerolipid biosynthesis, multiple homologues of glycerol-3-phosphate acyltransferases (GPATs) have been found in B. napus. Moreover, the functional variances among these homologous GPAT-encoding genes are unclear. RESULTS: In this study, four B. napus homologous genes encoding glycerol-3-phosphate acyltransferase 9 (BnaGPAT9) were characterized. Although a bioinformatics analysis indicated high protein sequence similarity, the homologues demonstrated tissue-specific expression patterns and functional divergence. Yeast genetic complementation assays revealed that BnaGPAT9-A1/C1 homologues but not BnaGPAT9-A10/C9 homologues encoded functional GPAT enzymes. Furthermore, a single nucleotide polymorphism of BnaGPAT9-C1 that occurred during the domestication process was associated with enzyme activity and contributed to the fatty acid composition. The seed-specific expression of BnGPAT9-C11124A increased the erucic acid content in the transformant seeds. CONCLUSIONS: This study revealed that BnaGPAT9 gene homologues evolved into functionally divergent forms with important roles in erucic acid biosynthesis.

Copper Stress Causes Shell Morphology Changes in Early Juvenile Anodonta woodiana Based on Geometric-Morphometric Analysis.

In this study, the morphological characteristics of early juvenile shells of Anodonta woodiana, which were exposed to different concentrations of aqueous copper, were analyzed using 10 landmarks to determine morphological changes in the shells. Morphological changes mainly occurred at the top of the shell and front and back ends of the central axis. Stepwise discriminant analysis proved shape differences among experimental and control groups. The results of this study demonstrate for the first time that environmentally relevant copper concentrations cause stress-related morphological changes in A. woodiana in the vulnerable early juvenile stage.