Reciprocal communication between FAPs and muscle cells via distinct extracellular vesicle miRNAs in muscle regeneration.

Muscle regeneration is a complex process relying on precise teamwork between multiple cell types, including muscle stem cells (MuSCs) and fibroadipogenic progenitors (FAPs). FAPs are also the main source of intramuscular adipose tissue (IMAT). Muscles without FAPs exhibit decreased IMAT infiltration but also deficient muscle regeneration, indicating the importance of FAPs in the repair process. Here, we demonstrate the presence of bidirectional crosstalk between FAPs and MuSCs via their secretion of extracellular vesicles (EVs) containing distinct clusters of miRNAs that is crucial for normal muscle regeneration. Thus, after acute muscle injury, there is activation of FAPs leading to a transient rise in IMAT. These FAPs also release EVs enriched with a selected group of miRNAs, a number of which come from an imprinted region on chromosome 12. The most abundant of these is miR-127-3p, which targets the sphingosine-1-phosphate receptor S1pr3 and activates myogenesis. Indeed, intramuscular injection of EVs from immortalized FAPs speeds regeneration of injured muscle. In late stages of muscle repair, in a feedback loop, MuSCs and their derived myoblasts/myotubes secrete EVs enriched in miR-206-3p and miR-27a/b-3p. The miRNAs repress FAP adipogenesis, allowing full muscle regeneration. Together, the reciprocal communication between FAPs and muscle cells via miRNAs in their secreted EVs plays a critical role in limiting IMAT infiltration while stimulating muscle regeneration, hence providing an important mechanism for skeletal muscle repair and homeostasis.

Recent developments in the fabrication of food microparticles and nanoparticles using microfluidic systems.

Microfluidics is revolutionizing the production of microparticles and nanoparticles, offering precise control over dimensions and internal structure. This technology facilitates the creation of colloidal delivery systems capable of encapsulating and releasing nutraceuticals. Nutraceuticals, often derived from food-grade ingredients, can be used for developing functional foods. This review focuses on the principles and applications of microfluidic systems in crafting colloidal delivery systems for nutraceuticals. It explores the foundational principles behind the development of microfluidic devices for nutraceutical encapsulation and delivery. Additionally, it examines the prospects and challenges with using microfluidics for functional food development. Microfluidic systems can be employed to form emulsions, liposomes, microgels and microspheres, by manipulating minute volumes of fluids flowing within microchannels. This versatility can enhance the dispersibility, stability, and bioavailability of nutraceuticals. However, challenges as scaling up production, fabrication complexity, and microchannel clogging hinder the widespread application of microfluidic technologies. In conclusion, this review highlights the potential role of microfluidics in design and fabrication of nutraceutical delivery systems. At present, this technology is most suitable for exploring the role of specific delivery system features (such as particle size, composition and morphology) on the stability and bioavailability of nutraceuticals, rather than for large-scale production of nutraceutical delivery systems.

Associations between digital literacy, health literacy, and digital health behaviors among rural residents: evidence from Zhejiang, China.

OBJECTIVE: Within the digital society, the limited proficiency in digital health behaviors among rural residents has emerged as a significant factor intensifying health disparities between urban and rural areas. Addressing this issue, enhancing the digital literacy and health literacy of rural residents stands out as a crucial strategy. This study aims to investigate the relationship between digital literacy, health literacy, and the digital health behaviors of rural residents. METHODS: Initially, we developed measurement instruments aimed at assessing the levels of digital literacy and health literacy among rural residents. Subsequently, leveraging micro survey data, we conducted assessments on the digital literacy and health literacy of 968 residents in five administrative villages in Zhejiang Province, China. Building upon this foundation, we employed Probit and Poisson models to empirically scrutinize the influence of digital literacy, health literacy, and their interaction on the manifestation of digital health behaviors within the rural population. This analysis was conducted from a dual perspective, evaluating the participation of digital health behaviors among rural residents and the diversity to which they participate in such behaviors. RESULTS: Digital literacy exhibited a notably positive influence on both the participation and diversity of digital health behaviors among rural residents. While health literacy did not emerge as a predictor for the occurrence of digital health behavior, it exerted a substantial positive impact on the diversity of digital health behaviors in the rural population. There were significant interaction effects between digital literacy and health literacy concerning the participation and diversity of digital health behaviors among rural residents. These findings remained robust even after implementing the instrumental variable method to address endogeneity issues. Furthermore, the outcomes of robust analysis and heterogeneity analysis further fortify the steadfastness of the aforementioned conclusions. CONCLUSION: The findings suggest that policymakers should implement targeted measures aimed at enhancing digital literacy and health literacy among rural residents. This approach is crucial for improving rural residents' access to digital health services, thereby mitigating urban-rural health inequality.

An Integrated Strategy Based on 10-DAB Extraction and In Situ Whole-Cell Biotransformation of Renewable Taxus Needles to Produce Baccatin III.

Baccatin III is a crucial precursor in the biosynthesis pathway of paclitaxel. Its main sources are extraction from Taxus or chemical synthesis using 10-deacetylbaccatin III (10-DAB) as substrate. However, these preparation approaches exhibit serious limitations, including the low content of baccatin III in Taxus and the complicated steps of chemical synthesis. Heterologous expression of 10-deacetylbaccatin III-10-O-acetyltransferase (TcDBAT) in microbial strains for biotransformation of 10-DAB is a promising alternative strategy for baccatin III production. Here, the promotion effects of glycerol supply and slightly acidic conditions with a low-temperature on the catalysis of recombinant TcDBAT strain were clarified using 10-DAB as substrate. Taxus needles is renewable and the content of 10-DAB is relatively high, it can be used as an effective source of the catalytic substrate 10-DAB. Baccatin III was synthesized by integrating the extraction of 10-DAB from renewable Taxus needles and in situ whole-cell catalysis in this study. 40 g/L needles were converted into 20.66 mg/L baccatin III by optimizing and establishing a whole-cell catalytic bioprocess. The method used in this study can shorten the production process of Taxus extraction for baccatin III synthesis and provide a reliable strategy for the efficient production of baccatin III by recombinant strains and the improvement of resource utilization rate of Taxus needles.

High-Throughput Host-Microbe Single-Cell RNA Sequencing Reveals Ferroptosis-Associated Heterogeneity during Acinetobacter baumannii Infection.

Interactions between host and bacterial cells are integral to human physiology. The complexity of host-microbe interactions extends to different cell types, spatial aspects, and phenotypic heterogeneity, requiring high-resolution approaches to capture their full complexity. The latest breakthroughs in single-cell RNA sequencing (scRNA-seq) have opened up a new era of studies in host-pathogen interactions. Here, we first report a high-throughput cross-species dual scRNA-seq technology by using random primers to simultaneously capture both eukaryotic and bacterial RNAs (scRandom-seq). Using reference cells, scRandom-seq can detect individual eukaryotic and bacterial cells with high throughput and high specificity. Acinetobacter baumannii (A.b) is a highly opportunistic and nosocomial pathogen that displays resistance to many antibiotics, posing a significant threat to human health, calling for discoveries and treatment. In the A.b infection model, scRandom-seq witnessed polarization of THP-1 derived-macrophages and the intracellular A.b-induced ferroptosis-stress in host cells. The inhibition of ferroptosis by Ferrostatin-1 (Fer-1) resulted in the improvement of cell vitality and resistance to A.b infection, indicating the potential to resist related infections. scRandom-seq provides a high-throughput cross-species dual single-cell RNA profiling tool that will facilitate future discoveries in unraveling the complex interactions of host-microbe interactions in infection systems and tumor micro-environments.

Light-Triggered Signal Enhancement Strategy Integrated with a CRISPR/Cas13a-Based Assay for Ultrasensitive and Specific miRNA Detection.

The development of facile, accurate, and affordable assays for microRNAs (miRNAs) in early cancer is greatly desirable but encounters an obstacle due to low cellular abundance in biofuids. In this study, we present a novel approach called a light-triggered exponential amplification strategy coupled with a CRISPR/Cas13a-based diagnostic system (LEXPA-CRISPR), which directly transduces rare miRNA targets into photocontrolled signal enhancement response. This innovative platform leverages trans-cleavage of CRISPR/Cas13a, activated by the miRNA target, to cleave specific RNA fragments within the MB@PC-NAC assembly, thus releasing free PC-single-stranded DNA (PC-ssDNA) that is modified by a photocleavable linker (PC linker). UV irradiation is further employed toward the photoresponsive PC-ssDNA, resulting in instantaneous generation of oligo with a new 5' phosphate group (Pho-ssDNA). The Pho-ssDNA serves as a trigger for rolling circle amplification (RCA) reaction, which generates thousands of long ssDNA repeats of diverse lengths with a strong fluorescence signal. Through optimization, we achieved a detection limit of 1 fM for miR21 without the need for target amplification. Moreover, the programmable versatility of LEXPA-CRISPR is also demonstrated for miR17 determination only with simple modification of CRISPR RNA (crRNA) sequences. This proposed biosensor successfully monitored the levels of miR21 and miR17 in tumor cells, showing a satisfactory consistency with the standard qRT-PCR method. Conclusively, LEXPA-CRISPR represents a promising strategy for ultrasensitive miRNA detection. It combines the advantages of light-triggered signal amplification and robust collateral cleavage activity of Cas13a, making it an attractive tool for practical CRISPR-based diagnostics.

A novel function by cathepsin D in degradation of nucleic acids.

Cathepsin D (CTSD) is an aspartic endopeptidase, however, we found that it was also capable of enzymatic digestion of nucleic acids (NAs). The purpose of this study was to investigate the basic properties of CTSD enzymatic activity on NAs, and explore the degradation mechanism. The results showed that NAs were efficiently digested between pH 3.0 and 5.0, and the optimum pH was 3.5. CTSD exhibited optimum activity at the temperature of 50°C. The degradation rate was improved with an increased CTSD concentration, and NAs were digested to an enzyme concentration of 0.001%, at which point, NAs were no longer digested. Ca2+ and Mg2+ at low concentrations of 5 mM promoted the digestion remarkably. As the protein substrate for CTSD, both Hb and BSA had no effect on DNA degradation, even when the molar ratio of protein:DNA was 104:1. Kinetic parameters of Km and kcat/Km value were (42 ± 1) µM and (1.62 ± 0.1) × 10-2 s-1mM-1 respectively, using real-time quantitative PCR (RT-PCR). Specially, pepstatin A which is the specific aspartic protease inhibitor exhibited inhibitory effect on NA digestion by CTSD as well, suggesting that the catalytic active site of CTSD for NAs might be the same as protein. A brief degradation mechanism is discussed. The present study may change the cognition of CTSD specificity for substrate and contribute greatly to enzymology of CTSD.

RNF217 regulates iron homeostasis through its E3 ubiquitin ligase activity by modulating ferroportin degradation.

Ferroportin (FPN), the body's sole iron exporter, is essential for maintaining systemic iron homeostasis. In response to either increased iron or inflammation, hepatocyte-secreted hepcidin binds to FPN, inducing its internalization and subsequent degradation. However, the E3 ubiquitin ligase that underlies FPN degradation has not been identified. Here, we report the identification and characterization of a novel mechanism involving the RNF217-mediated degradation of FPN. A combination of 2 different E3 screens revealed that the Rnf217 gene is a target of Tet1, mediating the ubiquitination and subsequent degradation of FPN. Interestingly, loss of Tet1 expression causes an accumulation of FPN and an impaired response to iron overload, manifested by increased iron accumulation in the liver together with decreased iron in the spleen and duodenum. Moreover, we found that the degradation and ubiquitination of FPN could be attenuated by mutating RNF217. Finally, using 2 conditional knockout mouse lines, we found that knocking out Rnf217 in macrophages increases splenic iron export by stabilizing FPN, whereas knocking out Rnf217 in intestinal cells appears to increase iron absorption. These findings suggest that the Tet1-RNF217-FPN axis regulates iron homeostasis, revealing new therapeutic targets for FPN-related diseases.

Electromagnetic characteristics of antisymmetric toroidal dipole array of plasmonic metasurfaces.

An antisymmetric toroidal dipole array of plasmonic metasurfaces, whose unit cell consisted of a pair of physically connected asymmetric split-ring resonators, is presented in this study. Moreover, a new paradigm was established to control toroidal electric dipole properties. Toroidal electric dipoles and electric and magnetic hybrid pseudo-anapole states are excited owing to imperfect and perfect destructive interference, respectively, which leads to the spatial separation of the electric and magnetic fields and a distinct asymmetric Fano line shape in the transmission spectrum. The imperfect destructive interference was further modified by adjusting the relative position between the even and odd layers of the metasurfaces. The scattered power of the toroidal electric dipole is tuned continuously and linearly, which enables the tailoring of the electromagnetic response. The displacement sensitivity is approximately 0.13 GHz/mm over the range 0-8 mm. The modulation depth of the scattered power of the toroidal electric dipole can reach 740%, realising a toroidal electric-dipole-to-electric-dipole transition. The proposed plasmonic metasurfaces provide a platform to efficiently control near-field enhancement, far-field radiation, and electric-magnetic separation and find potential applications in frequency-selective surfaces, sensors, filters, spectroscopic tests, and many other areas.

Triptolide injection reduces Alzheimer's disease-like pathology in mice.

Triptolide is an epoxidized diterpene lactone isolated from Tripterygium wilfordii. Studies have shown that triptolide exerts organ-protective effects. However, it remains unknown whether triptolide improves Alzheimer's disease (AD)-like presentations. Thirty healthy 8-week-old male C57BL/6J mice were randomly divided into control (n = 10), model (n = 10), and triptolide (n = 10) groups. Amyloid-ß (Aß)42 was injected bilaterally into the ventricles of mice in the model group. Triptolide was injected intraperitoneally daily after injecting Aß42 (a total of 30 days) in the triptolide group. Learning and memory were tested using the Morris water maze test. The deposition of Aß42 in the hippocampus was detected using immunohistochemical staining. In the hippocampus, three synaptic-associated proteins-gephyrin, collybistin, and GABRA1 -were detected by western blotting. Furthermore, we used ELISA to detect proinflammatory cytokines, including TNF-α and IL-1ß, in the blood and hippocampus. Moreover, superoxide dismutase (SOD), malondialdehyde (MDA), and GSH levels were measured using the corresponding kits. We found that triptolide improved spatial learning and memory in AD-like mice. Additionally, triptolide maintained the expression of gephyrin, collybistin, and GABRA1 and reduced Aß in these mice. Additionally, triptolide reduced the expression of inflammatory cytokines and decreased oxidative damage in AD-like mice. Our study suggests that triptolide attenuates AD-like changes in the mouse brain.

The differences in drug resistance between drug-resistant tuberculosis patients with and without diabetes mellitus in northeast China: a retrospective study.

BACKGROUND: Diabetes mellitus (DM) and drug-resistant tuberculosis (DR-TB) are serious global public health problems. This study aimed to explore the differences in drug resistance between DR-TB patients with and without DM. Risk factors for developing multidrug-resistant tuberculosis (MDR-TB) were also investigated among DR-TB patients. METHODS: The patient's basic demographic,　clinical characteristics, and drug susceptibility testing (DST) data were collected from the Chinese Disease Control Information System. Descriptive statistics were used to estimate the frequency and proportion of included variables. Categorical variables were compared using the Chi-square test or Fisher's exact test. Chi-square tests for trends were used to determine changes and trends in MDR-TB and pre-extensively drug-resistantTB (pre-XDR-TB) patterns over time. Univariate and multivariate logistic regression analysis was used to explore the risk factors of MDR-TB. RESULTS: Compared with DR-TB patients with DM, DR-TB patients without DM had significantly higher rates of mono-resistant streptomycin (SM) and any resistance to kanamycin (KM), but significantly lower rates of any resistance to protionamide (PTO) and mono-resistance to levofloxacin (LFX), and pre-XDR-TB (P<0.05). The proportion of resistance to other anti-TB drugs was not statistically different between the DR-TB with and without DM. Among DR-TB patients without and with DM, the proportion of patients with MDR-TB and pre-XDR-TB patterns showed a significant downward trend from 2016 to 2021 (P<0.05). Among DR-TB patients without DM, male, previously treated DR-TB cases, and immigration were risk factors for MDR-TB (P<0.05). In DR-TB patients with DM, a negative sputum smear is a risk factor for MDR-TB (P<0.05). CONCLUSION: There was no statistical difference in resistance patterns between DR-TB with and without DM, except in arbitrary resistance to PTO and KM, mono-resistant SM and LFX, and pre-XDR-TB. Great progress has been made in the prevention and control of MDR-TB and pre-XDR-TB. However, DR-TB patients with and without DM differ in their risk factors for developing MDR-TB.

Tris(2-chloroethyl) Phosphate Exerts Hepatotoxic Impacts on Zebrafish by Disrupting Hypothalamic-Pituitary-Thyroid and Gut-Liver Axes.

The ubiquitous environmental presence of tris(2-chloroethyl) phosphate (TCEP) poses a potential threat to animals; however, little is known about its hepatotoxicity. In this study, the effects of TCEP exposure (0.5 and 5.0 µg/L for 28 days) on liver health and the potential underlying toxification mechanisms were investigated in zebrafish. Our results demonstrated that TCEP exposure led to hepatic tissue lesions and resulted in significant alterations in liver-injury-specific markers. Moreover, TCEP-exposed fish had significantly lower levels of thyrotropin-releasing hormone and thyroid-stimulating hormone in the brain, evidently less triiodothyronine whereas more thyroxine in plasma, and markedly altered expressions of genes from the hypothalamic-pituitary-thyroid (HPT) axis in the brain or liver. In addition, a significantly higher proportion of Bacteroidetes in the gut microbiota, an elevated bacterial source endotoxin lipopolysaccharide (LPS) in the plasma, upregulated expression of LPS-binding protein and Toll-like receptor 4 in the liver, and higher levels of proinflammatory cytokines in the liver were detected in TCEP-exposed zebrafish. Furthermore, TCEP-exposed fish also suffered severe oxidative damage, possibly due to disruption of the antioxidant system. These findings suggest that TCEP may exert hepatotoxic effects on zebrafish by disrupting the HPT and gut-liver axes and thereafter inducing hepatic inflammation and oxidative stress.

Mouse4mC-BGRU: Deep learning for predicting DNA N4-methylcytosine sites in mouse genome.

DNA N4-methylcytosine (4mC) is an important DNA modification and plays a crucial role in a variety of biological processes. Accurate 4mC site identification is fundamental to improving the understanding of 4mC biological functions and mechanisms. However, lots of identification approaches are limited to traditional machine learning, which leads to weak learning ability and a complex feature extraction process. Here, we propose Mouse4mC-BGRU, an advanced deep learning model that utilizes adaptive embedding based on bidirectional gated recurrent units (BGRU). Benchmark results show that our model performs better than the state-of-the-art methods in the prediction of 4mC sites in the mouse genome. By using adaptive features to extract representation, Mouse4mC-BGRU can capture the latent biology information of input sequence, which effectively enhances model representation ability. In addition, we visualize the training process of Mouse4mC-BGRU with dim reduction tools and intuitively show the effectiveness of our model, demonstrating that Mouse4mC-BGRU has great potential to be a powerful and practically useful tool to accurately identify 4mC sites.

Substituting Fish Meal with Tubiechong (Eupolyphaga sinensis) By-Product in the Diets of Largemouth Bass (Micropterus salmoides): Effects on Growth, Meat Quality, and Liver Health.

A feeding trial was conducted to evaluate the effect of replacing 0% (control), 10% (T10), 20% (T20), 30% (T30), and 40% (T40) fish meal with a Tubiechong (Eupolyphaga sinensis) by-product in largemouth bass (Micropterus salmoides). Triplicate groups of 30 fish (5.36 ± 0.01 g) were fed two times daily to apparent satiation for 60 days. The experimental results showed that the Tubiechong by-product could improve the growth performance of largemouth bass by increasing the FBW, WGR, and SGR until the replacement ratio was 40%. The quadratic regression analysis showed that the proportion of the Tubiechong by-product was 20.79% and 20.91%, respectively, when WGR and SGR were the best. Concurrently, the meat quality in the replacement groups was higher, specifically, the lightness and white values were higher, and the water loss rates were lower (P < 0.05) than that in the control group. Moreover, the changes of the activities of CAT and GSH in the liver and T-AOC and GSH in serum could reveal the antioxidant capacity improvement of fish by the Tubiechong by-product. In the study, the replacement groups had lower T-CHO and HDL-C in serum (P < 0.05), indicating that the Tubiechong by-product had an active role in improving blood lipid and regulating lipid metabolism. Simultaneously, the replacement groups had a normal structure with central hepatocytes' nuclei and deviated from the center partly, while most of the hepatocytes were swollen in the control group with nuclear degeneration. The results showed that the Tubiechong by-product had a positive effect on the liver health of fish. Conclusively, the present study indicated that the partial dietary replacement of fish meal using the Tubiechong by-product (for up to 40% replacement level) in the diet of largemouth bass not only caused no adverse effects on fish health but also improved the growth performance, meat quality, antioxidant capacity, and hepatic health and is conducive to supplying nutritious, high-quality, and healthy aquatic products.

Potential of Chinese Yam (Dioscorea polystachya Turczaninow) By-Product as a Feed Additive in Largemouth Bass (Micropterus salmoides): Turning Waste into Valuable Resources.

Chinese yam (Dioscorea polystachya Turczaninow) by-product produced in the water extraction process is commonly directly discarded resulting in a waste of resources and environmental pollution. However, the value of Chinese yam by-product which still contains effective ingredients is far from being fully realized; hence, it has the potential to be a safe and effective feed additive in aquaculture. To investigate the impacts of Chinese yam by-product on growth performance, antioxidant ability, histomorphology, and intestinal microbiota of Micropterus salmoides, juvenile fish (initial weight 13.16 ± 0.05 g) were fed diets supplemented with 0% (control), 0.1% (S1), 0.4% (S2), and 1.6% (S3) of Chinese yam by-product for 60 days. The results showed that no significant difference was found in weight gain, specific growth rate, and survival among all the experimental groups (P > 0.05). Feed conversion ratios of the S1 and S3 groups were significantly lower than those in the control group (P < 0.05). SOD activity of the S3 group and GSH contents of Chinese yam by-product groups were significantly higher than those in the control group (P < 0.05). MDA levels of the S2 and S3 groups were significantly lower than those in the control group and the S1 group (P < 0.05). Besides, Chinese yam by-product could protect liver and intestine health, as well as increase the abundance of beneficial bacteria and decrease the abundance of potential pathogens. This study suggests that Chinese yam by-product has the potential to be used as a functional feed additive in aquaculture, providing a reference for efficient recovery and utilization of by-products from plant sources during processing and culturing high-quality aquatic products.

Effect of polyhydroxy-terminated PAMAM dendrimer on dentin matrix metalloproteinases within the hybrid layers.

BACKGROUND: Intrafibrillar remineralization within the hybrid layers (HLs) has recently attracted extensive attention in achieving durable resin-dentin bonds. The polyhydroxy-terminated poly(amidoamine) dendrimer (PAMAM-OH) at fourth generation becomes a desirable candidate to induce intrafibrillar remineralization to protect exposed collagen fibrils within HLs based on the size exclusion effect of fibrillar collagen. However, the remineralization process in vivo is time-consuming, during which the exposed collagen fibrils are vulnerable to enzymatic degradation, resulting in unsatisfactory remineralization. Thereby, if PAMAM-OH itself possesses concomitant anti-proteolytic activity during the induction of remineralization, it would be very beneficial to obtain satisfactory remineralization. METHODS: Binding capacity tests using adsorption isotherm and confocal laser scanning microscopy (CLSM) were performed to assess if the PAMAM-OH had adsorption capacity on dentin. Anti-proteolytic testings were detected by MMPs assay kit, in-situ zymography and ICTP assay. Adhesive infiltration of resin-dentin interface and tensile bond strength before and after thermomechanical cycling were implemented to assess if the PAMAM-OH adversely affected resin-dentin bonds. RESULTS: Anti-proteolytic testings performed using MMPs assay kit, in-situ zymography and ICTP assay indicated that PAMAM-OH inhibited exogenous soluble MMP-9 as well as had inhibitory effect on the endogenous proteases. Adhesive infiltration of resin-dentin interface and tensile bond strength before and after thermomechanical cycling were implemented to indicate that the PAMAM-OH pretreatment had no adverse effects on immediate dentin bonding and prolonged the durability of resin-dentin bonds. CONCLUSIONS: PAMAM-OH possesses anti-proteolytic activity and prevents exposed collagen fibrils within HLs from degradation, which lays the foundation for the satisfactory intrafibrillar remineralization induced by PAMAM-OH within HLs to achieve durable resin-dentin bonds in the next work.

The mechanism for thermal-enhanced chaperone-like activity of α-crystallin against UV irradiation-induced aggregation of γD-crystallin.

Exposure to solar UV irradiation damages γ-crystallin, leading to cataract formation via aggregation. α-Crystallin, as a small heat shock protein, efficiently suppresses this irreversible aggregation by selectively binding the denatured γ-crystallin monomer. In this study, liquid chromatography tandem mass spectrometry was used to evaluate UV-325 nm irradiation-induced photodamage of human γD-crystallin in the presence of bovine α-crystallin, atomic force microscope (AFM) and dynamic light scattering (DLS) techniques were used to detect the quaternary structure changes of the α-crystallin oligomer, and Fourier transform infrared spectroscopy and temperature-jump nanosecond time-resolved IR absorbance difference spectroscopy were used to probe the secondary structure changes of bovine α-crystallin. We find that the thermal-induced subunit dissociation of the α-crystallin oligomer involves the breaking of hydrogen bonds at the dimeric interface, leading to three different spectral components at varied temperature regions as resolved from temperature-dependent IR spectra. Under UV-325 nm irradiation, unfolded γD-crystallin binds to the dissociated α-crystallin subunit to form an αγ-complex, then follows the reassociation of the αγ-complex to the partially dissociated α-crystallin oligomer. This prevents the aggregation of denatured γD-crystallin. The formation of the γD-bound α-crystallin oligomer is further confirmed by AFM and DLS analysis, which reveals an obvious size expansion in the reassociated αγ-oligomers. In addition, UV-325 nm irradiation causes a peptide bond cleavage of γD-crystallin at Ala158 in the presence of α-crystallin. Our results suggest a very effective protection mechanism for subunits dissociated from α-crystallin oligomers against UV irradiation-induced aggregation of γD-crystallin, at the expense of a loss of a short C-terminal peptide in γD-crystallin.

iDNA-ABT: advanced deep learning model for detecting DNA methylation with adaptive features and transductive information maximization.

MOTIVATION: DNA methylation plays an important role in epigenetic modification, the occurrence, and the development of diseases. Therefore, identification of DNA methylation sites is critical for better understanding and revealing their functional mechanisms. To date, several machine learning and deep learning methods have been developed for the prediction of different DNA methylation types. However, they still highly rely on manual features, which can largely limit the high-latent information extraction. Moreover, most of them are designed for one specific DNA methylation type, and therefore cannot predict multiple methylation sites in multiple species simultaneously. In this study, we propose iDNA-ABT, an advanced deep learning model that utilizes adaptive embedding based on Bidirectional Encoder Representations from Transformers (BERT) together with transductive information maximization (TIM). RESULTS: Benchmark results show that our proposed iDNA-ABT can automatically and adaptively learn the distinguishing features of biological sequences from multiple species, and thus perform significantly better than the state-of-the-art methods in predicting three different DNA methylation types. In addition, TIM loss is proven to be effective in dichotomous tasks via the comparison experiment. Furthermore, we verify that our features have strong adaptability and robustness to different species through comparison of adaptive embedding and six handcrafted feature encodings. Importantly, our model shows great generalization ability in different species, demonstrating that our model can adaptively capture the cross-species differences and improve the predictive performance. For the convenient use of our method, we further established an online webserver as the implementation of the proposed iDNA-ABT. AVAILABILITY AND IMPLEMENTATION: Our proposed iDNA-ABT and data are freely accessible via http://server.wei-group.net/iDNA_ABT and our source codes are available for downloading in the GitHub repository (https://github.com/YUYING07/iDNA_ABT). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Hepatic transferrin plays a role in systemic iron homeostasis and liver ferroptosis.

Although the serum-abundant metal-binding protein transferrin (encoded by the Trf gene) is synthesized primarily in the liver, its function in the liver is largely unknown. Here, we generated hepatocyte-specific Trf knockout mice (Trf-LKO), which are viable and fertile but have impaired erythropoiesis and altered iron metabolism. Moreover, feeding Trf-LKO mice a high-iron diet increased their susceptibility to developing ferroptosis-induced liver fibrosis. Importantly, we found that treating Trf-LKO mice with the ferroptosis inhibitor ferrostatin-1 potently rescued liver fibrosis induced by either high dietary iron or carbon tetrachloride (CCl4) injections. In addition, deleting hepatic Slc39a14 expression in Trf-LKO mice significantly reduced hepatic iron accumulation, thereby reducing ferroptosis-mediated liver fibrosis induced by either a high-iron diet or CCl4 injections. Finally, we found that patients with liver cirrhosis have significantly lower levels of serum transferrin and hepatic transferrin, as well as higher levels of hepatic iron and lipid peroxidation, compared with healthy control subjects. Taken together, these data indicate that hepatic transferrin plays a protective role in maintaining liver function, providing a possible therapeutic target for preventing ferroptosis-induced liver fibrosis.

Actively tunable toroidal response in microwave metamaterials.

Toroidal dipole moment has attracted much attention in recent years due to their novel electromagnetic response such as non-reciprocal interactions and unusual low-radiating manifestations. However, most of the previously reported toroidal dipole moment are incapable of real-time control of direction and intensity. In this paper, an actively tunable toroidal metamaterials are proposed to achieve programmable toroidal dipole manipulations with electric control. The intensity and direction of toroidal dipole can be sensitively regulated by electrically controlling the loaded diodes. Our proof-of-concept experiments show that the toroidal dipole could be dynamically switched to the electric and magnetic dipole. Meantime, the direction of toroidal dipole also could be controlled. Experimental and numerical results, in good agreement, demonstrate good performance of the proposed toroidal metamaterials, with potential applications in modulators, sensors, and filters.