A Universal Electronic Structure Modulation Strategy: Is Strong Adsorption Always Correlated with High Catalysis?

Unveiling the inherent link between polysulfide adsorption and catalytic activity is key to achieving optimal performance in Lithium-sulfur (Li-S) batteries. Current research on the sulfur reaction process mainly relies on the strong adsorption of catalysts to confine lithium polysulfides (LiPSs) to the cathode side, effectively suppressing the shuttle effect of polysulfides. However, is strong adsorption always correlated with high catalysis? The inherent relationship between adsorption and catalytic activity remains unclear, limiting the in-depth exploration and rational design of catalysts. Herein, the correlation between "d-band center-adsorption strength-catalytic activity" in porous carbon nanofiber catalysts embedded with different transition metals (M-PCNF-3, M = Fe, Co, Ni, Cu) is systematically investigated, combining the d-band center theory and the Sabatier principle. Theoretical calculations and experimental analysis results indicate that Co-PCNF-3 electrocatalyst with appropriate d-band center positions exhibits moderate adsorption capability and the highest catalytic conversion activity for LiPSs, validating the Sabatier relationship in Li-S battery electrocatalysts. These findings provide indispensable guidelines for the rational design of more durable cathode catalysts for Li-S batteries.

Multi-dimensional evaluation of pain response in low day-age calves to two types of dehorning.

Introduction: Dehorning calves is necessary to minimize injury because intensive raising circumstances make horned cows more aggressive. However, acute pain is commonly perceived by farm animals when undergoing painful practices such as dehorning, affecting their health status and quality of life. By quantifying the magnitude of pain and discomfort associated with dehorning, we aim to contribute to a more humane and sustainable cattle farming industry. Methods: The objective of this study was to evaluate the behavioral, physiological, and emotional effects of acute dehorning pain in calves using two methods: dehorning cream and dehorning hot-iron.30 Holstein calves aged 4 days were selected for the study. These calves were randomly assigned to two experimental groups based on the method of disbudding: dehorning cream (n = 15) and hot-iron dehorning (n = 15). Before and after dehorning, we evaluated their physiological indicators of infrared eye temperature, concentrations of substance P, IL-6, cortisol, haptoglobin, as well as emotional state, and pain-related behavioral reactions. Results: Post-dehorning, the duration of lying down decreased significantly in both groups (DI and DC: 0-4 h) after dehorning (p < 0.05). Both groups exhibited increased frequencies of pain-related behaviors such as head shaking (DI: 1-7 h, DC: 1-6 h), ear flicking (DI: 2-7 h, DC: 2-7 h), head scratching (DI: 2-3 h, DC: 1-7 h), and top scuffing (DI: 2 h, DC: 2-7 h) compared to pre-dehorning (p < 0.05). The DC group demonstrated a higher frequency of head-shaking, ear-flicking, head-scratching, and top-rubbing behaviors, along with a longer duration of lying down (0-4 h), compared to the DI group (p < 0.05). Post-dehorning, play behavior reduced significantly in both groups (6-8 h) (p < 0.05), whereas judgment bias and fear levels showed no significant change (p > 0.05). Physiological measures including eye temperature, and blood levels of substance P and IL-6, did not differ significantly between the groups before and after dehorning (p > 0.05). However, 48 h after dehorning, calves in the DC group had significantly higher haptoglobin levels compared to the DI group (p = 0.015). Additionally, salivary cortisol levels in the DC group increased significantly at 3.5 h and 7 h post-dehorning (p = 0.018, p = 0.043). Discussion: Both hot-iron and cream dehorning induced pain in calves, as evidenced by increased pain-related behaviors, elevated salivary cortisol, and higher haptoglobin levels, alongside reduced positive behaviors. Notably, these effects were more pronounced in the DC group than in the DI group, suggesting that dehorning hot-iron may be a comparatively less stressful dehorning method for young calves. Moreover, the brief duration of pain response and weaker response to dehorning observed in 13-day-age calves in this study suggests that dehorning at younger ages may be more advisable and warrants further research.

A 4D-Printable Photocurable Resin Derived from Waste Cooking Oil with Enhanced Tensile Strength.

In pursuit of enhancing the mechanical properties, especially the tensile strength, of 4D-printable consumables derived from waste cooking oil (WCO), we initiated the production of acrylate-modified WCO, which encompasses epoxy waste oil methacrylate (EWOMA) and epoxy waste oil acrylate (EWOA). Subsequently, a series of WCO-based 4D-printable photocurable resins were obtained by introducing a suitable diacrylate molecule as the second monomer, coupled with a composite photoinitiator system comprising Irgacure 819 and p-dimethylaminobenzaldehyde (DMAB). These materials were amenable to molding using an LCD light-curing 3D printer. Our findings underscored the pivotal role of triethylene glycol dimethacrylate (TEGDMA) among the array of diacrylate molecules in enhancing the mechanical properties of WCO-based 4D-printable resins. Notably, the 4D-printable material, composed of EWOA and TEGDMA in an equal mass ratio, exhibited nice mechanical strength comparable to that of mainstream petroleum-based 4D-printable materials, boasting a tensile strength of 9.17 MPa and an elongation at break of 15.39%. These figures significantly outperformed the mechanical characteristics of pure EWOA or TEGDMA resins. Furthermore, the EWOA-TEGDMA resin demonstrated impressive thermally induced shape memory performance, enabling deformation and recovery at room temperature and retaining its shape at -60 °C. This resin also demonstrated favorable biodegradability, with an 8.34% weight loss after 45 days of soil degradation. As a result, this 4D-printable photocurable resin derived from WCO holds immense potential for the creation of a wide spectrum of high-performance intelligent devices, brackets, mold, folding structures, and personalized products.

Achieving High Ionic Conductivity and Mechanical Strength by a Leather Gel Electrolyte for Flexible Zinc-Ion Batteries.

The continuous advancement in the field of flexible and wearable electronics has led to increased research interest in safe, low-cost, and flexible zinc-ion batteries, particularly with a focus on flexible electrolytes. In this study, we present a leather gel electrolyte (LGE) that offers robust mechanical properties and an excellent electrochemical performance. LGE exhibits an ionic conductivity of 1.36 × 10-2 S cm-1 and achieves a capacity of 303.7 mAh g-1 in flexible zinc-manganese dioxide batteries. Even after 1000 cycles, the capacity retention remains above 90%, demonstrating outstanding performance in protecting the zinc anode. Furthermore, such a flexible battery shows good resistance to damage due to the strong mechanical strength originating from leather. Notably, LGE utilizes green and sustainable leather as a raw material, making it a promising option for sustainable flexible devices.

Early signs of neurodegenerative diseases: Possible mechanisms and targets for Golgi stress.

The Golgi apparatus plays a crucial role in mediating the modification, transport, and sorting of intracellular proteins and lipids. The morphological changes occurring in the Golgi apparatus are exceptionally important for maintaining its function. When exposed to external pressure or environmental stimulation, the Golgi apparatus undergoes adaptive changes in both structure and function, which are known as Golgi stress. Although certain signal pathway responses or post-translational modifications have been observed following Golgi stress, further research is needed to comprehensively summarize and understand the related mechanisms. Currently, there is evidence linking Golgi stress to neurodegenerative diseases; however, the role of Golgi stress in the progression of neurodegenerative diseases such as Alzheimer's disease remains largely unexplored. This review focuses on the structural and functional alterations of the Golgi apparatus during stress, elucidating potential mechanisms underlying the involvement of Golgi stress in regulating immunity, autophagy, and metabolic processes. Additionally, it highlights the pivotal role of Golgi stress as an early signaling event implicated in the pathogenesis and progression of neurodegenerative diseases. Furthermore, this study summarizes prospective targets that can be therapeutically exploited to mitigate neurodegenerative diseases by targeting Golgi stress. These findings provide a theoretical foundation for identifying novel breakthroughs in preventing and treating neurodegenerative diseases.

Chirality-Dependent Valley Polarization in Magnetic van der Waals Heterostructures via Spin-Selective Charge Transfer.

Magnetic proximity interaction provides a promising route to manipulate the spin and valley degrees of freedom in van der Waals heterostructures. Here, we report a control of valley pseudospin in the WS2/MoSe2 heterostructure by utilizing the magnetic proximity effect of few-layered CrBr3 and, for the first time, observe a substantial difference in valley polarization of intra/interlayer excitons under different circularly polarized laser excitations, referred to as chirality-dependent valley polarization. Theoretical and experimental results reveal that the spin-selective charge transfer between MoSe2 and CrBr3, as well as between MoSe2 and WS2, is mostly responsible for the chiral feature of valley polarization in comparison with the proximity exchange field. This means that a long-distance manipulation of exciton behaviors in multilayer heterostructures can be achieved through spin-selective charge transfer. This work marks a significant advancement in the control of spin and valley pseudospin in multilayer structures.

Circulating micrornas as potential diagnostic biomarkers for cervical intraepithelial neoplasia and cervical cancer: a systematic review and meta-analysis.

BACKGROUND: Cervical cancer is a prevalent malignancy of the female reproductive system. Cervical intraepithelial neoplasia (CIN) is a precursor lesion for CC. Various studies have examined circulating microRNAs (miRNAs) as potential early diagnostic markers for CC and CIN. However, the findings have been inconclusive. Therefore, it is necessary to evaluate the diagnostic accuracy and identify potential sources of variability among these studies. METHODS: The PubMed, Cochrane Library, Embase, and Web of Science databases were searched to identify relevant literature. Then, Stata 14.0 was utilized to calculate summary estimates for diagnostic parameters, including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic (ROC). To scrutinize the heterogeneity, the Cochran-Q test and I2 statistic were utilized. As significant heterogeneity was observed, the random effects model was chosen. To explore potential sources of the heterogeneity, subgroup and regression analyses were conducted. RESULTS: We analysed 12 articles reporting on 24 studies involving 1817 patients and 1731 healthy controls. The pooled sensitivity was 0.77 (95% CI 0.73-0.81), the specificity was 0.81 (95% CI 0.73-0.86), the PLR was 3.99 (95% CI 2.81-5.65), the NLR was 0.28 (95% CI 0.23-0.35), the DOR was 14.18 (95% CI 8.47-23.73), and the area under the curve (AUC) was 0.85 (95% CI 0.81-0.87). Subgroup analysis revealed that multiple miRNAs can improve diagnostic performance; the pooled sensitivity of multiple miRNAs was 0.78 (95% CI 0.68-0.86), the specificity was 0.85 (95% CI 0.78-0.90), and the AUC was 0.89 (95% CI 0.86-0.91). CONCLUSION: This study suggested that circulating microRNAs may be biomarkers for early CC diagnosis.

Functional properties, structural characteristics, and anti-complementary activities of two degraded polysaccharides from strawberry fruits.

Two low-molecular-weight polysaccharides (DPSP50 and DPSP70) were obtained using hydrogen peroxide-vitamin C (H2O2-Vc) treatment at 50 °C and 70 °C, respectively. Both DPSP50 and DPSP70 comprised the same six monosaccharides in different ratios, and their molecular weights (Mws) were 640 kDa and 346 kDa, respectively. Functional properties analyses demonstrated that DPSP50 and DPSP70 each had an excellent water holding capacity, oil absorption capacity, and emulsion properties, as well as shear-thinning characteristics and viscoelastic properties. Fourier transform infrared (FT-IR) and nuclear magnetic resonance (NMR) spectroscopic assays confirmed the existence of α-, ß-pyranose rings and the same six sugar residues in DPSP50 and DPSP70. The results of Congo red test, scanning electron microscopy (SEM), and X-ray diffraction (XRD) demonstrated that DPSP50 and DPSP70 did not contain triple-helix conformations, but were amorphous aggregates with flake-like shape and rough surface. Additionally, both DPSP50 and DPSP70 showed strong anti-complementary activities through the classical pathway and the alternative pathway. The results support the potential utility of these degraded polysaccharides from strawberry fruits in functional foods and medicines.

Multi-omic analyses reveal key sectors of jasmonate-mediated defense responses in rice.

The phytohormone jasmonate (JA) plays a central role in plant defenses against biotic stressors. However, our knowledge of the JA signaling pathway in rice (Oryza sativa) remains incomplete. Here, we integrated multi-omic data from three tissues to characterize the functional modules involved in organizing JA-responsive genes. In the core regulatory sector, MYC2 transcription factor transcriptional cascades are conserved. in different species but with distinct regulators (e.g. bHLH6 in rice)., in which genes are early expressed across all tissues. In the feedback sector, MYC2 also regulates the expression of JA repressor and catabolic genes, providing negative feedback that truncates the duration of JA responses. For example, the MYC2-regulated NAC (NAM, ATAF1/2 and CUC2) transcription factor genes NAC1, NAC3, and NAC4 encode proteins that repress JA signaling and herbivore resistance. In the tissue-specific sector, many late-expressed genes are associated with the biosynthesis of specialized metabolites that mediate particular defensive functions. For example, the terpene synthase gene TPS35 is specifically induced in the leaf sheath and TPS35 functions in defense against oviposition by brown planthoppers and the attraction of this herbivore's natural enemies. Thus, by characterizing core, tissue-specific, and feedback sectors of JA-elicited defense responses, this work provides a valuable resource for future discoveries of key JA components in this important crop.

NRDE2 deficiency impairs homologous recombination repair and sensitizes hepatocellular carcinoma to PARP inhibitors.

To identify novel susceptibility genes for hepatocellular carcinoma (HCC), we performed a rare-variant association study in Chinese populations consisting of 2,750 cases and 4,153 controls. We identified four HCC-associated genes, including NRDE2, RANBP17, RTEL1, and STEAP3. Using NRDE2 (index rs199890497 [p.N377I], p = 1.19 × 10-9) as an exemplary candidate, we demonstrated that it promotes homologous recombination (HR) repair and suppresses HCC. Mechanistically, NRDE2 binds to the subunits of casein kinase 2 (CK2) and facilitates the assembly and activity of the CK2 holoenzyme. This NRDE2-mediated enhancement of CK2 activity increases the phosphorylation of MDC1 and then facilitates the HR repair. These functions are eliminated almost completely by the NRDE2-p.N377I variant, which sensitizes the HCC cells to poly(ADP-ribose) polymerase (PARP) inhibitors, especially when combined with chemotherapy. Collectively, our findings highlight the relevance of the rare variants to genetic susceptibility to HCC, which would be helpful for the precise treatment of this malignancy.

Prediction of Cognitive Impairment Risk among Older Adults: A Machine-Learning Based Comparative Study and Model Development.

Detecting cognitive decline early in the older adults is crucial for effective intervention. This study, part of the Ma'anshan Healthy Aging Cohort Study, examined 2,288 participants with normal cognitive function. Forty-two potential predictors, including demographics, chronic diseases, lifestyle factors, and baseline cognitive function, were selected. The dataset was divided into training, validation, and test sets (60%, 20%, and 20%, respectively). Recursive feature elimination (RFE) and six machine learning algorithms were used for model development. Model performance was assessed using area under the curve (AUC), specificity, sensitivity, and accuracy. SHapley Additive exPlanations (SHAP) was applied for interpretability, revealing the top ten influential features: baseline MMSE, education, economic status, social activities, PSQI, BMI, SBP, DBP, IADL, and age. The Naïve Bayes (NB) algorithm-based model achieved an AUC of 0.820 (95% CI 0.773-0.887) on the test set, outperforming other algorithms. This model can help primary healthcare staff in community settings identify individuals at higher risk of cognitive impairment within three years among older adults.

Enhanced Magnetoimpedance Effect in Co-Based Micron Composite CoFeNiSiB Ribbon Strips Coated by Carbon and FeCoGa Nanofilms for Sensing Applications.

Quenched Co-based ribbon strips are widely used in the fields of magnetic amplifier, magnetic head material, magnetic shield, electric reactor, inductance core, sensor core, anti-theft system label, and so on. In this study, Co-based composite CoFeNiSiB ribbon strips with a micron width were fabricated by micro-electro-mechanical systems (MEMS) technology. The carbon and FeCoGa nanofilms were deposited for surface modification. The effect of carbon and FeCoGa nanofilm coatings on the crystal structure, surface morphology, magnetic properties, and magnetoimpedance (MI) effect of composite ribbon strips were systematically investigated. The results show that the surface roughness and coercivity of the composite ribbon strips are minimum at a thickness of the carbon coating of 60 nm. The maximum value of MI effect is 41% at 2 MHz, which is approximately 2.4 times greater than plain ribbon and 1.6 times greater than FeCoGa-coated composite ribbon strip. The addition of a carbon layer provides a conductive path for high frequency currents, which effectively reduces the characteristic frequency of the composite ribbon strip. The FeCoGa coating is able to close the flux path and reduce the coercivity, which, in turn, increases the transverse permeability and improves the MI effect. The findings indicate that a successful combination of carbon layer and magnetostrictive FeCoGa nanofilm layer can improve the MI effect and magnetic field sensitivity of the ribbon strips, demonstrating the potential of the composite strips for local and micro area field sensing applications.

[Cadmium Phytoremediation Effect of Sweet Sorghum Assisted with Citric Acid on Typical Parent Soil in Southern China].

Sweet sorghum has a large biomass and strong cadmium (Cd) absorption capacity, which has the potential for phytoremediation of Cd-contaminated soil. In order to study the Cd phytoremediation effect of sweet sorghum assisted with citric acid on the typical parent materials in southern China, a field experiment was carried out in two typical parent material farmland areas (neutral purple mud field and jute sand mud field) with Cd pollution in Hunan Province. The results showed that:① Citric acid had no inhibitory effect on the growth of sweet sorghum. After the application of citric acid, the aboveground biomass of sweet sorghum at the maturity stage increased by 10.1%-24.7%. ② Both sweet sorghum planting and citric acid application reduced the soil pH value, and the application of citric acid further reduced the soil pH value at each growth stage of sweet sorghum; this decrease was greater in the neutral purple mud field, which decreased by 0.24-0.72 units. ③ Both sweet sorghum planting and citric acid application reduced the total amount of soil Cd, and the decreases in the neutral purple mud field and jute sand mud field were 23.8%-52.2% and 17.1%-31.8%, respectively. The acid-extractable percentage of soil Cd in both places increased by 38.6%-147.7% and 4.8%-22.7%, respectively. ④ The application of citric acid could significantly increase the Cd content in various tissues of sweet sorghum. The Cd content in the aboveground part of the plant in the neutral purple mud field was higher than that in the jute sand mud field, and the Cd content in stems and leaves was 0.25-1.90 mg·kg-1 and 0.21-0.64 mg·kg-1, respectively. ⑤ After applying citric acid, the Cd extraction amount of sweet sorghum in neutral purple mud soil in the mature stage reached 47.56 g·hm-2. In summary, citric acid could enhance the efficiency of sweet sorghum in the phytoremediation of Cd-contaminated soil, and the effect was better in neutral purple mud fields. This technology has the potential for remediation coupled with agro-production for heavy metal-contaminated farmland.

Prussian blue analogue derived from leather waste as a bifunctional catalyst in zinc-air batteries.

A Prussian blue analogue was synthesized using biomass leather waste as a precursor by doping with Co2+ ions. This material, demonstrates good performance in both the oxygen reduction reaction and oxygen evolution reaction, and exhibits excellent charge-discharge performance and stability in zinc-air batteries.

Effectiveness of a standardized quality control management procedure for COVID-19 RT-PCR testing: a large-scale diagnostic accuracy study in China.

BACKGROUND: The study aimed to construct a standardized quality control management procedure (QCMP) and access its accuracy in the quality control of COVID-19 reverse transcriptase-polymerase chain reaction (RT-PCR). METHODS: Considering the initial RT-PCR results without applying QCMP as the gold standard, a large-scale diagnostic accuracy study including 4,385,925 participants at three COVID-19 RT-PCR testing sites in China, Foshan (as a pilot test), Guangzhou and Shenyang (as validation sites), was conducted from May 21, 2021, to December 15, 2022. RESULTS: In the pilot test, the RT-PCR with QCMP had a high accuracy of 99.18% with 100% specificity, 100% positive predictive value (PPV), and 99.17% negative predictive value (NPV). The rate of retesting was reduced from 1.98% to 1.16%. Its accuracy was then consistently validated in Guangzhou and Shenyang. CONCLUSIONS: The RT-PCR with QCMP showed excellent accuracy in identifying true negative COVID-19 and relieved the labor and time spent on retesting.

Advancing glioblastoma treatment by targeting metabolism.

Alterations in cellular metabolism are important hallmarks of glioblastoma(GBM). Metabolic reprogramming is a critical feature as it meets the higher nutritional demand of tumor cells, including proliferation, growth, and survival. Many genes, proteins, and metabolites associated with GBM metabolism reprogramming have been found to be aberrantly expressed, which may provide potential targets for cancer treatment. Therefore, it is becoming increasingly important to explore the role of internal and external factors in metabolic regulation in order to identify more precise therapeutic targets and diagnostic markers for GBM. In this review, we define the metabolic characteristics of GBM, investigate metabolic specificities such as targetable vulnerabilities and therapeutic resistance, as well as present current efforts to target GBM metabolism to improve the standard of care.

Core microbiota for nutrient digestion remained and ammonia utilization increased after continuous batch culture of rumen microbiota in vitro.

Introduction: This study aimed to investigate the digestive function, urea utilization ability, and bacterial composition changes in rumen microbiota under high urea (5% urea in diet) over 23 days of continuous batch culture in vitro. Methods: The gas production, dry matter digestibility, and bacterial counts were determined for the continuously batch-cultured rumen fluid (CRF). The changes in fermentation parameters, NH3-N utilization efficiency, and microbial taxa were analyzed in CRF and were compared with that of fresh rumen fluid (RF), frozen rumen fluid (FRF, frozen rumen fluid at -80°C for 1 month), and the mixed rumen fluid (MRF, 3/4 RF mixed with 1/4 CRF) with in vitro rumen fermentation. Results: The results showed that the dry matter digestibility remained stable while both the microbial counts and diversity significantly decreased over the 23 days of continuous batch culture. However, the NH3-N utilization efficiency of the CRF group was significantly higher than that of RF, FRF, and MRF groups (p < 0.05), while five core genera including Succinivibrio, Prevotella, Streptococcus, F082, and Megasphaera were retained after 23 days of continuous batch culture. The NH3-N utilization efficiency was effectively improved after continuous batch culture in vitro, and Streptococcus, Succinivibrio, Clostridium_sensu_stricto_1, p.251.o5, Oxalobacter, Bacteroidales_UCG.001, and p.1088.a5_gut_group were identified to explain 75.72% of the variation in NH3-N utilization efficiency with the RandomForest model. Conclusion: Thus, core bacterial composition and function retained under high urea (5% urea in diet) over 23 days of continuous batch culture in vitro, and bacterial biomarkers for ammonia utilization were illustrated in this study. These findings might provide potential applications in improving the efficiency and safety of non-protein nitrogen utilization in ruminants.

Physicochemical properties of a novel chestnut porous starch nanoparticle.

A novel chestnut porous starch nanoparticle (PSNP) was successfully synthesized, combining the properties of starch nanoparticle (SNP) and porous starch. The SNP obtained through ultrasonic and acid hydrolysis, exhibited a smaller particle size (173.9 nm) and a higher specific surface area (SSA) compared to native starch. After the synergistic hydrolysis by α-amylase and glucoamylase, the porous structure appeared on the surface of SNP. The prepared PSNP had a size of 286.3 nm and the highest SSA. In the adsorption experiments, PSNP showed higher capacities for adsorbing water, oil and methylene blue (MB) compared to other samples. The acid and enzymatic treatments resulted in a decrease in the levels of total starch content and amylose ratio. Furthermore, the treatments increased the levels of relative crystallinity (RC) and solubility, while decreasing the short-range ordered structure and swelling ratio at high temperatures. It was observed that the SSA of starch granules positively correlated with the MB and water adsorption capacity (WAC), solubility, and RC. These findings highlight the potential of the novel PSNP as an efficient adsorbent for bioactive substances and dyes.

MicroRNA-204-5p Ameliorates Renal Injury via Regulating Keap1/Nrf2 Pathway in Diabetic Kidney Disease.

Background: Diabetic kidney disease (DKD) is characterized by renal fibrosis, and the pathogenesis of renal fibrosis is still not definitely confirmed. MiR-204-5p plays an important role in the regulation of fibrosis, autophagy and oxidative stress. In this study, we aimed to investigate the role of miR-204-5p on renal damage in diabetic kidneys and the underlying mechanisms involved. Methods: In vivo, AAV-Ksp-miR-204-5p mimics were injected into mice via tail vein. In vitro, high glucose-induced HK-2 cells were treated with miR-204-5p inhibitor, miR-204-5p mimics, ATG5 siRNA, tertiary butyl hydroquinone (TBHQ), ML385, or 3-Methyladenine (3-MA). FISH and qRT-PCR were used to detect miR-204-5p expression. The expressions of protein and mRNA were detected by Western blotting, immunofluorescence, immunohistochemistry and qRT-PCR. The concentration of fibronectin in HK-2 cells culture medium was detected by ELISA. Results: The expression of miR-204-5p in diabetic kidneys was significantly inhibited than that in control group. Delivering miR-204-5p mimics increased miR-204-5p expression, improved renal function, inhibited renal fibrosis and oxidative stress, and restored autophagy in db/db mice. In vitro, the expression of miR-204-5p was inhibited by HG treatment in HK-2 cells. MiR-204-5p mimics effectively increased miR-204-5p expression and reduced fibronectin and collagen I expression, restored autophagy dysfunction, and increased Nrf2 expression, whereas these alterations were abrogated by Nrf2 inhibitor ML385, autophagy inhibitor 3-methyladenine (3-MA, 5 mM) treatment or ATG5 siRNA transfection in HG-induced HK-2 cells. In addition, miR-204-5p inhibitor significantly inhibited miR-204-5p expression and aggravated HG-induced fibronectin and collagen I expression, autophagy dysfunction, and decreased Nrf2 expression, while these alterations were abolished by Nrf2 activator TBHQ. Furthermore, the binding of miR-204-5p with Keap1 was confirmed by luciferase reporter assay and miR-204-5p negatively regulated Keap1 expression, resulting in the activation of Nrf2 pathway. Conclusion: MicroRNA-204-5p protects against the progression of diabetic renal fibrosis by restoring autophagy via regulating Keap1/Nrf2 pathway.

Prediction of positive pulmonary nodules based on machine learning algorithm combined with central carbon metabolism data.

BACKGROUND: Lung cancer causes a huge disease burden, and early detection of positive pulmonary nodules (PPNs) as an early sign of lung cancer is extremely important for effective intervention. It is necessary to develop PPNs risk recognizer based on machine learning algorithm combined with central carbon metabolomics. METHODS: The study included 2248 participants at high risk for lung cancer from the Ma'anshan Community Lung Cancer Screening cohort. The Least Absolute Shrinkage and Selection Operator (LASSO) was used to screen 18 central carbon-related metabolites in plasma, recursive feature elimination (RFE) was used to select all 42 features, followed by five machine learning algorithms for model development. The performance of the model was evaluated using area under the receiver operator characteristic curve (AUC), accuracy, precision, recall, and F1 scores. In addition, SHapley Additive exPlanations (SHAP) was performed to assess the interpretability of the final selected model and to gain insight into the impact of features on the predicted results. RESULTS: Finally, the two prediction models based on the random forest (RF) algorithm performed best, with AUC values of 0.87 and 0.83, respectively, better than other models. We found that homogentisic acid, fumaric acid, maleic acid, hippuric acid, gluconic acid, and succinic acid played a significant role in both PPNs prediction model and NPNs vs PPNs model, while 2-oxadipic acid only played a role in the former model and phosphopyruvate only played a role in the NPNs vs PPNs model. This model demonstrates the potential of central carbon metabolism for PPNs risk prediction and identification. CONCLUSION: We developed a series of predictive models for PPNs, which can help in the early detection of PPNs and thus reduce the risk of lung cancer.