Role of indocyanine green-guided near-infrared fluorescence imaging in identification of the cause of neonatal cholestasis.

To evaluate the efficacy and safety of indocyanine green (ICG)-guided near-infrared fluorescence (NIRF) imaging during surgery to diagnose the cause of neonatal cholestasis (NC). Data on NC patients who underwent both NIRF with ICG and conventional laparoscopic bile duct exploration (the gold standard) at our institute from January 2022 to December 2022 were retrospectively analyzed. The patients' baseline characteristics and liver function outcomes were collected and analyzed, and the diagnostic consistency was compared between the 2 methods. In total, 16 NC patients were included in the study, comprising 8 (50%) male and 8 (50%) female patients, ranging in age from 42 to 93 days, with a median age of 54.4 ±â€…21 days. During surgery, all the patients underwent NIRF with ICG, followed by conventional laparoscopic bile duct exploration. Finally, 15 of the patients were diagnosed with biliary atresia (BA) (1 with type-I BA, and 14 with type-II BA). The other patient was diagnosed with cholestasis. The diagnostic results from fluorescence imaging with ICG were consistent with those from conventional laparoscopic bile duct exploration. ICG-guided NIRF is associated with an easy operation, less trauma, and good safety. Also, its diagnostic accuracy is similar to conventional laparoscopic bile duct exploration.

Associations between Preschool Teachers' Food-Based Learning Frequency, Level of Personal Priority and Identified Resources and Challenges: A Needs Assessment.

Food-based learning (FBL) is the use of food as a teaching tool in the classroom, which can expose children to healthy foods to improve preference and consumption. However, more research is needed on the use and perception of FBL in the Head Start (HS) preschool classroom. In an online survey, we explored associations between North Carolina HS teachers' (n = 168) experiences (e.g., resources, challenges, needs, and preferences) with FBL, how frequently teachers implemented it, and how much they prioritized it. We used frequencies and chi-square tests of independence to assess associations between study variables. Teachers reported using FBL regularly with access to FBL resources (e.g., books and center play materials) and experiencing challenges (e.g., lack of funding and material resources). Teachers partnered with parents and farmers markets and expressed a need for additional FBL professional development. Our needs assessment findings revealed specific resources, challenges, and perceptions significantly associated with how often teachers used FBL and their priority level. Additional research should investigate how to alleviate FBL challenges and strategies to create policy and environmental changes that facilitate early FBL.

Theoretical study of the structural and thermodynamic properties of U-He compounds under high pressure.

Uranium is considered as a very important nuclear energy material because of the huge amount of energy it releases. As the main product of the spontaneous decay of uranium, it is difficult for helium to react with uranium because of its chemical inertness. Therefore, bubbles will be formed inside uranium, which could greatly reduce the performance of uranium or cause safety problems. Additionally, nuclear materials are usually operated in an environment of high-temperature and high-pressure, so it is necessary to figure out the exact state of helium inside uranium under extreme conditions. Here, we explored the structural stability of the U-He system under high pressure and high temperature by using density functional theory calculations. Two metastable phases are found between 50 and 400 GPa: U4He with space group Fmmm and U6He with space group P1̄. Both are metallic and adopt layered structures. Electron localization function calculation combined with charge density difference analysis indicates that there are covalent bonds between U and U atoms in both Fmmm-U4He and P1̄-U6He. Regarding the elastic modulus of α-U, the addition of helium has certain influence on the mechanical properties of uranium. Besides, first-principles molecular dynamics simulations were carried out to study the dynamical behavior of Fmmm-U4He and P1̄-U6He at high-temperature. It was found that Fmmm-U4He and P1̄-U6He undergo one-dimensional superionic phase transitions at 150 GPa. Our study revealed the exotic structure of U-He compounds beyond the formation of bubbles under high-pressure and high-temperature, which might be relevant to the performance and safety issues of nuclear materials under extreme conditions.

Membrane protein MHZ3 regulates the on-off switch of ethylene signaling in rice.

Ethylene regulates plant growth, development, and stress adaptation. However, the early signaling events following ethylene perception, particularly in the regulation of ethylene receptor/CTRs (CONSTITUTIVE TRIPLE RESPONSE) complex, remains less understood. Here, utilizing the rapid phospho-shift of rice OsCTR2 in response to ethylene as a sensitive readout for signal activation, we revealed that MHZ3, previously identified as a stabilizer of ETHYLENE INSENSITIVE 2 (OsEIN2), is crucial for maintaining OsCTR2 phosphorylation. Genetically, both functional MHZ3 and ethylene receptors prove essential for OsCTR2 phosphorylation. MHZ3 physically interacts with both subfamily I and II ethylene receptors, e.g., OsERS2 and OsETR2 respectively, stabilizing their association with OsCTR2 and thereby maintaining OsCTR2 activity. Ethylene treatment disrupts the interactions within the protein complex MHZ3/receptors/OsCTR2, reducing OsCTR2 phosphorylation and initiating downstream signaling. Our study unveils the dual role of MHZ3 in fine-tuning ethylene signaling activation, providing insights into the initial stages of the ethylene signaling cascade.

Amphipathic Surfactant on Reconstructed Bismuth Enables Industrial-Level Electroreduction of CO2 to Formate.

Developing efficient electrocatalysts for selective formate production via the electrochemical CO2 reduction reaction (CO2RR) is challenged by high overpotential, a narrow potential window of high Faradaic efficiency (FEformate), and limited current density (Jformate). Herein, we report a hierarchical BiOBr (CT/h-BiOBr) with surface-anchored cetyltrimethylammonium bromide (CTAB) for formate-selective large-scale CO2RR electrocatalysis. CT/h-BiOBr achieves over 90% FEformate across a wide potential range (-0.5 to -1.1 V) and an industrial-level Jformate surpassing 100 mA·cm-2 at -0.7 V. In situ investigations uncover the reconstructed Bi(110) surface as the active phase, with CTAB playing a dual role: its hydrophobic alkyl chains create a CO2-enriching microenvironment, while its polar head groups fine-tune the electronic structure, fostering a highly active phase. This work provides valuable insights into the role of surfactants in electrocatalysis and guides the design of electrocatalysts for the large-scale CO2RR.

Self-enhanced localized alkalinity at the encapsulated Cu catalyst for superb electrocatalytic nitrate/nitrite reduction to NH3 in neutral electrolyte.

The electrocatalytic nitrate/nitrite reduction reaction (eNOx-RR) to ammonia (NH3) is thermodynamically more favorable than the eye-catching nitrogen (N2) electroreduction. To date, the high eNOx-RR-to-NH3 activity is limited to strong alkaline electrolytes but cannot be achieved in economic and sustainable neutral/near-neutral electrolytes. Here, we construct a copper (Cu) catalyst encapsulated inside the hydrophilic hierarchical nitrogen-doped carbon nanocages (Cu@hNCNC). During eNOx-RR, the hNCNC shell hinders the diffusion of generated OH- ions outward, thus creating a self-enhanced local high pH environment around the inside Cu nanoparticles. Consequently, the Cu@hNCNC catalyst exhibits an excellent eNOx-RR-to-NH3 activity in the neutral electrolyte, equivalent to the Cu catalyst immobilized on the outer surface of hNCNC (Cu/hNCNC) in strong alkaline electrolyte, with much better stability for the former. The optimal NH3 yield rate reaches 4.0 moles per hour per gram with a high Faradaic efficiency of 99.7%. The strong-alkalinity-free advantage facilitates the practicability of Cu@hNCNC catalyst as demonstrated in a coupled plasma-driven N2 oxidization with eNOx-RR-to-NH3.

Yishen Jiangzhuo decoction attenuates cisplatin­induced acute kidney injury by inhibiting inflammation, oxidative stress and apoptosis through the TNF signal pathway.

The present study aimed to investigate the therapeutic effects and mechanisms of Yishen Jiangzhuo decoction (YSJZD) in a mouse model of cisplatin-induced acute kidney injury (AKI). The mice were divided into the NC, cisplatin and cisplatin + YSJZD groups. A concentration-dependent effect of YSJZD on cisplatin-induced AKI was observed and the optimal concentration for intervention was calculated. Changes in blood urea nitrogen and serum creatinine levels combined with hematoxylin and eosin and periodic acid-Schiff staining and transmission electron microscopy observations indicated that YSJZD enhanced renal function, reduced pathological injury and protected renal tubular epithelial cells in cisplatin-induced AKI mice. The results of the transcriptomic and enrichment analyses showed that the mechanisms of YSJZD may be associated with inflammation, oxidation, apoptosis and the TNF signal pathway. Immunofluorescence, oxidative stress index, terminal deoxynucleotidyl transferase dUTP nick end labeling assay and western blotting revealed that YSJZD downregulated apoptosis in the renal tissues of AKI mice and further decreased the expression levels of p-p65, p-p38 MAPK, TNF-α, cleaved-caspase-3 and malondialdehyde, while increasing the levels of NAD-dependent protein deacetylase sirtuin-3, glutathione and superoxide dismutase. Overall, the results showed that YSJZD could effectively abrogate cisplatin-induced AKI in mice through mechanisms primarily related to its anti-inflammatory, antioxidative and antiapoptotic effects by inhibited the TNF signal pathway. YSJZD warrants further investigation as a clinical empirical prescription.

ß-catenin mediates endodermal commitment of human ES cells via distinct transactivation functions.

BACKGROUND: ß-catenin, acting as the core effector of canonical Wnt signaling pathway, plays a pivotal role in controlling lineage commitment and the formation of definitive endoderm (DE) during early embryonic development. Despite extensive studies using various animal and cell models, the ß-catenin-centered regulatory mechanisms underlying DE formation remain incompletely understood, partly due to the rapid and complex cell fate transitions during early differentiation. RESULTS: In this study, we generated new CTNNB1-/- human ES cells (hESCs) using CRISPR-based insertional gene disruption approach and systematically rescued the DE defect in these cells by introducing various truncated or mutant forms of ß-catenin. Our analysis showed that a truncated ß-catenin lacking both N- and C-terminal domains (ΔN148C) could robustly rescue the DE formation, whereas hyperactive ß-catenin mutants with S33Y mutation or N-terminal deletion (ΔN90) had limited ability to induce DE lineage. Notably, the ΔN148C mutant exhibited significant nuclear translocation that was positively correlated with successful DE rescue. Transcriptomic analysis further uncovered that two weak ß-catenin mutants lacking the C-terminal transactivation domain (CTD) activated primitive streak (PS) genes, whereas the hyperactive ß-catenin mutants activated mesoderm genes. CONCLUSION: Our study uncovered an unconventional regulatory function of ß-catenin through weak transactivation, indicating that the levels of ß-catenin activity determine the lineage bifurcation from mesendoderm into endoderm and mesoderm.

Household Food Sourcing Patterns and Their Associations with Food Insecurity in Appalachian Ohio.

BACKGROUND: Households experiencing food insecurity may use dynamic strategies to meet food needs. Yet, the relationship between household food sourcing behaviors and food security, particularly in rural settings, is understudied. OBJECTIVE: To identify food sourcing patterns and their associations with food insecurity among households in rural Appalachian Ohio during the COVID-19 pandemic. DESIGN: Survey data were collected from a cohort of households in Athens County, Ohio in July 2020, October 2020, January 2021, and April 2021. PARTICIPANTS/SETTING: The sample included 663 households with household food sourcing and food security information for ≥1 survey wave. MAIN OUTCOME MEASURES: Household food sourcing patterns. Households reported the frequency with which they obtained food from various retailers and charitable sources, classified as supercenters, supermarkets, convenience stores, farmers' markets, or charitable sources. STATISTICAL ANALYSES: Principal component analysis was used to identify food sourcing patterns. Linear mixed models were used to assess changes in food sourcing behaviors over the study period and to determine whether food sourcing behaviors differed according to food security status. RESULTS: Two patterns were identified: 1) Convenience Stores and Charitable Food, 2) Supermarkets and Farmers' Markets, not Supercenters. Relative to July 2020, alignment of households' food sourcing behaviors with the "Supermarkets and Farmers' Markets, not Supercenters" pattern was higher in October 2020 (ß=0.07; 95% CI: 0.02, 0.12) and alignment with the "Convenience Stores and Charitable Food" pattern was lower in April 2021 (ß=-0.06; 95% CI: -0.11, -0.02). Compared to food-secure households, food sourcing behaviors of food-insecure households were more closely aligned with the "Convenience Stores and Charitable Food" pattern (ß=0.07; 95% CI: 0.00, 0.13); no statistically significant difference in scores was observed for the "Supermarkets and Farmers' Markets, not Supercenters" pattern (ß=-0.07; 95% CI: -0.15, 0.02). CONCLUSIONS: These findings support efforts to increase access to healthy, affordable options at venues where food-insecure households may be likely to obtain food, such as convenience stores and charitable sources.

High-sensitivity narrow­band T-shaped cantilever Fabry-perot acoustic sensor for photoacoustic spectroscopy.

Photoacoustic spectroscopy (PAS) has been rapidly developed and applied to different detection scenarios. The acoustic pressure detection is an important part in the PAS system. In this paper, an ultrahigh sensitivity Fabry-Perot acoustic sensor with a T-shaped cantilever was proposed. To achieve the best acoustic pressure effect, the dimension of the cantilever structure was designed and optimized by finite element analysis using COMSOL Multiphysics. Simulation results showed that the sensitivity of such T-shaped cantilever was 1.5 times higher than that based on a rectangular cantilever, and the resonance frequency of T-shaped cantilever were able to modulate from 800 Hz to 1500 Hz by adjusting the multi-parameter characteristics. Experimental sensing results showed that the resonance frequency of T-shaped Fabry-Perot acoustic sensor was 1080 Hz, yielding a high sensitivity of 1.428 µm/Pa, with a signal-to-noise ratio (SNR) of 84.8 dB and a detectable pressure limit of 1.9 µPa/Hz1/2@1 kHz. We successfully used such acoustic sensor to measure acetylene (C2H2) concentration in the PAS. The sensitivity of PAS for C2H2 gas was 3.22 pm/ppm with a concentration range of 50 ppm ∼100 ppm, and the minimum detection limit was 24.91ppb.

Blade-Coating (100)-Oriented α-FAPbI3 Perovskite Films via Crystal Surface Energy Regulation for Efficient and Stable Inverted Perovskite Photovoltaics.

Photoactive formamidinium lead triiodide (α-FAPbI3) perovskite has dominated the prevailing high-performance perovskite solar cells (PSCs), normally for those spin-coated, conventional n-i-p structured devices. Unfortunately, α-FAPbI3 has not been made full use of its advantages in inverted p-i-n structured PSCs fabricated via blade-coating techniques owing to uncontrollable crystallization kinetics and complicated phase evolution of FAPbI3 perovskites. Herein, a customized crystal surface energy regulation strategy has been innovatively developed by incorporating 0.5 mol% of N-aminoethylpiperazine hydroiodide (NAPI) additive into α-FAPbI3 crystal-derived perovskite ink, which enabled the formation of phase-pure, highly-oriented α-FAPbI3 films. We deciphered the phase transformation mechanisms and crystallization kinetics of blade-coated α-FAPbI3 perovskite films via combining a series of in-situ characterizations. Interestingly, the strong chemical interactions between the NAPI and inorganic Pb-I framework help to reduce the surface energy of (100) crystal plane by 42%, retard the crystallization rate and lower the formation energy of α-FAPbI3. The resultant blade-coated inverted PSCs based on (100)-oriented α-FAPbI3 perovskite films realized promising efficiencies up to 24.16% (~26.5% higher than that of the randomly-oriented counterparts), accompanied by improved operational stability. This result represented one of the best performances reported to date for FAPbI3-based inverted PSCs fabricated via scalable deposition methods.

Photothermal Iron-Based Riboflavin Microneedles for the Treatment of Bacterial Keratitis via Ion Therapy and Immunomodulation.

Bacterial biofilm formation protects bacteria from antibiotics and the immune system, excessive inflammation further complicates treatment. Here, iron-based metal-organic framework (MIL-101)-loaded riboflavin nanoparticles are designed for the therapeutic challenge of biofilm infection and hyperinflammation in bacterial keratitis. Specifically, MIL-101 produces a thermal effect under exogenous near-infrared light irradiation, which synergizes with ferroptosis-like bacterial death induced by iron ions to exert an effective biofilm infection eradication effect. On the other hand, the disintegration of MIL-101 sustains the release of riboflavin, which inhibits the pro-inflammatory response of macrophage over-activation by modulating their phenotypic switch. In addition, to solve the problems of short residence time, poor permeability, and low bioavailability of corneal medication, the MR@MN microneedle patch is further prepared by loading nanoparticles into SilMA hydrogel, which ultimately achieves painless, transepithelial, and highly efficient drug delivery. In vivo and ex vivo experiments demonstrate the effectiveness of this approach in eliminating bacterial infection and promoting corneal healing. Therefore, the MRMN patch, acting as an ocular drug delivery system with the ability of rapid corneal healing, promises a cost-effective solution for the treatment of bacterial keratitis, which may also lead to a new approach for treating bacterial keratitis in clinics.

Antibiotics suppress the expression of antimicrobial peptides and increase sensitivity of Cydia pomonella to granulosis virus.

Cydia pomonella granulovirus (CpGV) is a highly specific and environmentally friendly pathogenic virus successfully used as a biological insecticide against codling moth larvae. Continuous application of CpGV has led to high levels of resistance in codling moth, Cydia pomonella (C. pomonella). Nevertheless, the specific molecular mechanisms underlying the development of resistance in codling moths to CpGV have been rarely investigated. This study explored the potential antiviral immune roles of codling moth antimicrobial peptides (AMPs) against CpGV. A total of 11 AMP genes classified in cecropin, defensin, gloverin, and attacin subfamilies, were identified in the codling moth genome. The cecropin and gloverin subfamilies were found to be the ancestral genes of the AMP gene family. The expression of two AMP genes (CmGlo1 and CmAtt1) significantly increased following CpGV challenge, and CmGlo1 and CmAtt1 gene silencing resulted in a significant increase in CpGV replication in codling moth larvae. The hemolymph and fat body serve as major viral immune functional tissues in codling moth larvae. Moreover, zhongshengmycin significantly reduced the diversity and abundance of codling moth larvae gut microbiota, thereby suppressing the expression of CmAtt1 AMP gene. We also found that the combination of the virus with zhongshengmycin would enhance the insecticidal effects of CpGV. This study provides the first explanation of the molecular mechanisms driving CpGV immune function development in codling moths, approached from the perspective of the codling moth itself. Additionally, we introduced an alternative approach to combat codling moth in the field by combining antibiotics with biopesticides to amplify the insecticidal effects of the latter.

Analysis of Efficacy and Safety of Laparoscopy Plus Choledochoscopy Combined With Holmium Laser Lithotripsy for Choledocholithiasis and Hepatolithiasis.

Background: With the advancement of laparoscopic technology, the combination of laparoscopy, choledochoscopy, and holmium laser lithotripsy has emerged as an effective treatment modality for both choledocholithiasis and hepatolithiasis. This study aimed to assess the efficacy and safety of this approach. Methods: Retrospective analysis was conducted on the medical records of 76 patients diagnosed with choledocholithiasis and hepatolithiasis between April 2021 and March 2023. Patients were divided into two groups based on the treatment plan: the control group, which underwent traditional laparotomy and choledochoscopy lithotripsy (n = 38), and the experimental group, which underwent laparoscopy combined with choledochoscopy and holmium laser lithotripsy (n = 38). Comparative analysis was performed on various operation-related parameters, stone-free rate, complication rates, and changes in biochemical, liver function, inflammatory, stress response indicators, and pain scores between the two groups. Results: The experimental group demonstrated significantly shorter stone removal time, reduced intraoperative bleeding, and shorter hospital stay compared to the control group (P < 0.05). Moreover, the experimental group exhibited lower incidence of postoperative complications and lower pain scores at 2 weeks to 3 months post-operation (P < 0.05). Biochemical indicators including total bile acid (TBA), total bilirubin (TBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and glutamyl transpeptidase (GGT) were significantly lower in the observation group compared to the control group (P < 0.05). Additionally, stress and inflammation indicators were also lower in the experimental group (P < 0.05). Conclusions: The combination of laparoscopy, choledochoscopy, and holmium laser lithotripsy presents favorable therapeutic outcomes in the management of choledocholithiasis and hepatolithiasis, indicating its potential for widespread clinical application.

BET Bromodomain Inhibition Potentiates Ocular Melanoma Therapy by Inducing Cell Cycle Arrest.

Purpose: Ocular melanoma is a common primary malignant ocular tumor in adults with limited effective treatments. Epigenetic regulation plays an important role in tumor development. The switching/sucrose nonfermentation (SWI/SNF) chromatin remodeling complex and bromodomain and extraterminal domain family proteins are epigenetic regulators involved in several cancers. We aimed to screen a candidate small molecule inhibitor targeting these regulators and investigate its effect and mechanism in ocular melanoma. Methods: We observed phenotypes caused by knockdown of the corresponding gene and synergistic effects with BRD inhibitor treatment and SWI/SNF complex knockdown. The effect of JQ-1 on ocular melanoma cell cycle and apoptosis was analyzed with flow cytometry. Via RNA sequencing, we also explored the mechanism of BRD4. Results: The best tumor inhibitory effect was observed for the BRD4 inhibitor (JQ-1), although there were no statistically obvious changes in the shBRD4 and shBRD9 groups. Interestingly, the inhibitory effect of JQ-1 was decrease in the shBRD4 group. JQ-1 inhibits the growth of melanoma in various cell lines and in tumor-bearing mice. We found 17 of these 28 common differentially expressed genes were downregulated after MEL270 and MEL290 cells treated with JQ-1. Four of these 17 genes, TP53I11, SH2D5, SEMA5A, and MDGA1, were positively correlated with BRD4. In TCGA database, low expression of TP53I11, SH2D5, SEMA5A, and MDGA1 improved the overall survival rate of patients. Furthermore, the disease-free survival rate was increased in the groups with low expression of TP53I11, SH2D5, and SEMA5A. Conclusions: JQ-1 may act downstream of BRD4 and suppress ocular melanoma growth by inducing G1 cell cycle arrest.

Valtrate suppresses TNFSF14-mediated arrhythmia after myocardial ischemia-reperfusion via inducing N-linked glycosylation of LTßR to regulate MGA/MAX/c-Myc/Cx43.

Myocardial ischemia-reperfusion (MIR)-induced arrhythmia remains a major cause of death in patients with cardiovascular diseases. The reduction of Cx43 has been known as a major inducer of arrhythmias after MIR, but the reason for the reduction of Cx43 remain largely unknown. This study aimed to find the key mechanism underlying the reduction of Cx43 after MIR and to screen out a herbal extract to attenuate arrhythmia after MIR. The differential expressed genes in peripheral blood mononuclear cell (PBMC) after MIR was analyzed using the data from several GEO datasets, followed by the identification in the PBMC and the serum of patients with myocardial infarction. Tumour necrosis factor superfamily protein 14 (TNFSF14) was increased in the the PBMC and the serum of patients, which might be associated to the injury after MIR. The toxic effects of TNFSF14 on cardiomyocytes was investigated in vitro. Valtrate was screened out from several herbal extracts. Its protection against TNFSF14-induced injury was evaluated in cardiomyocytes and animal models with MIR. Recombinant TNFSF14 protein not only suppressed the viability of cardiomyocytes, but also decreased Cx43 by stimulating the receptor LTßR. LTßR induces the competitive binding of MAX to MGA rather than the transcriptional factor c-Myc, thereby suppressing c-Myc-mediated transcription of Cx43. Valtrate promoted the N-linked glycosylation modification of LTßR, which reversed TNFSF14-induced reduction of Cx43 and attenuated arrhythmia after MIR. In all, Valtrate suppresses TNFSF14-induced reduction of Cx43 thereby attenuating arrhythmia after MIR.

Integrated image-based deep learning and language models for primary diabetes care.

Primary diabetes care and diabetic retinopathy (DR) screening persist as major public health challenges due to a shortage of trained primary care physicians (PCPs), particularly in low-resource settings. Here, to bridge the gaps, we developed an integrated image-language system (DeepDR-LLM), combining a large language model (LLM module) and image-based deep learning (DeepDR-Transformer), to provide individualized diabetes management recommendations to PCPs. In a retrospective evaluation, the LLM module demonstrated comparable performance to PCPs and endocrinology residents when tested in English and outperformed PCPs and had comparable performance to endocrinology residents in Chinese. For identifying referable DR, the average PCP's accuracy was 81.0% unassisted and 92.3% assisted by DeepDR-Transformer. Furthermore, we performed a single-center real-world prospective study, deploying DeepDR-LLM. We compared diabetes management adherence of patients under the unassisted PCP arm (n = 397) with those under the PCP+DeepDR-LLM arm (n = 372). Patients with newly diagnosed diabetes in the PCP+DeepDR-LLM arm showed better self-management behaviors throughout follow-up (P < 0.05). For patients with referral DR, those in the PCP+DeepDR-LLM arm were more likely to adhere to DR referrals (P < 0.01). Additionally, DeepDR-LLM deployment improved the quality and empathy level of management recommendations. Given its multifaceted performance, DeepDR-LLM holds promise as a digital solution for enhancing primary diabetes care and DR screening.

Silencing of CircTRIM25/miR-138-5p/CREB1 axis promotes chondrogenesis in osteoarthritis.

BACKGROUND: Dysregulated circular RNAs (circRNAs) are involved in osteoarthritis (OA) progression. OBJECTIVE: We aimed to explore the effect of hsa_circ_0044719 (circTRIM25) on the ferroptosis of chondrocytes. METHODS: Chondrocytes were treated with interleukin (IL)-1ß to generate cell model. Cellular behaviours were measured using cell counting kit-8, enzyme-linked immunosorbent assay, relevant kits, propidium iodide staining, and immunofluorescence assay. Quantitative real-time polymerase chain reaction was performed to examine the expression of circTRIM25, miR-138-5p, and cAMP responsive element binding protein 1 (CREB1), and their interactions were assessed using luciferase reporter analysis and RNA pull-down assay. RESULTS: CircTRIM25 was upregulated in OA tissues and IL-1ß-stimulated chondrocytes. Knockdown of circTRIM25 facilitated the viability and suppressed ferroptosis and inflammation of IL-1ß-induced cells. CircTRIM25 served as a sponge of miR-138-5p, which directly targets CREB1. Downregulation of miR-138-5p abrogated the effect induced by knockdown of circTRIM25. Furthermore, enforced CREB1 reversed the miR-138-5p induced effect. Moreover, knockdown of circTRIM25 attenuated cartilage injury in vivo. CONCLUSION: Silencing of circTRIM25 inhibited ferroptosis of chondrocytes via the miR-138-5p/CREB axis and thus attenuated OA progression.

The mechanism of arbuscular mycorrhizal fungi-alleviated manganese toxicity in plants: A review.

The development of the mining industry and the overuse of inorganic fertilizers have led to an excess of manganese (Mn) in the soil, thereby, contaminating the soil environment and people's health. On heavy metal-contaminated soils, the combined arbuscular mycorrhizal fungi (AMF)-phytoremediation technique becomes a hotspot because of its environmentally friendly, in situ remediation. AMF inoculation often leads to a decrease in host Mn acquisition, which provides a basis for its application in phytoremediation of contaminated soils. Moreover, the utilization value of native AMF is greater than that of exotic AMF, because native AMF can adapt better to Mn-contaminated soils. In addition to the fact that AMF enhance plant Mn tolerance responses such as regionalization, organic matter chelation, limiting uptake and efflux, and so on, AMF also develop plant-independent fungal pathways such as direct biosorption of Mn by mycorrhizal hyphae, fungal Mn transporter genes, and sequestration of Mn by mycorrhizal hyphae, glomalin, and arbuscule-containing root cortical cells, which together mitigate excessive Mn toxicity to plants. Clarifying AMF-plant interactions under Mn stress will provide support for utilizing AMF as a phytoremediation in Mn-contaminated soils. The review reveals in detail how AMF develop its own mechanisms for responding to excess Mn and how AMF enhance plant Mn tolerance, accompanied by perspectives for future research.

Schistosoma japonicum cystatin alleviates paraquat poisoning caused acute lung injury in mice through activating regulatory macrophages.

BACKGROUND: Paraquat (PQ) is a widely used herbicide that poisons human by accident or intentional ingestion. PQ poisoning causes systemic inflammatory response syndrome (SIRS) resulting in acute lung injury (ALI) with an extremely high mortality rate. Blood trematode Schistosoma japonicum-produced cystatin (Sj-Cys) is a strong immunomodulatory protein that has been experimentally used to treat inflammation related diseases. In this study, Sj-Cys recombinant protein (rSj-Cys) was used to treat PQ-induced lung injury and the immunological mechanism underlying the therapeutic effect was investigated. METHODS: PQ-induced acute lung injury mouse model was established by intraperitoneally injection of 20 mg/kg of paraquat. The poisoned mice were treated with rSj-Cys and the survival rate was observed up to 7 days compared with the group without treatment. The pathological changes of PQ-induced lung injury were observed by examining the histochemical sections of affected lung tissue and the wet to dry ratio of lung as a parameter for inflammation and edema. The levels of the inflammation related cytokines IL-6 and TNF-α and regulatory cytokines IL-10 and TGF-ß were measured in sera and in affected lung tissue using ELISA and their mRNA levels in lung tissue using RT-PCR. The macrophages expressing iNOS were determined as M1 and those expressing Arg-1 as M2 macrophages. The effect of rSj-Cys on the transformation of inflammatory M1 to regulatory M2 macrophages was measured in affected lung tissue in vivo (EKISA and RT-PCR) and in MH-S cell line in vitro (flow cytometry). The expression levels of TLR2 and MyD88 in affected lung tissue were also measured to determine their role in the therapy of rSj-Cys on PQ-induced lung injury. RESULT: We identified that treatment with rSj-Cys significantly improved the survival rate of mice with PQ-induced lung injury from 30 % (untreated) to 80 %, reduced the pathological damage of poisoning lung tissue, associated with significantly reduced levels of proinflammatory cytokines (IL-6 from 1490 to 590 pg/ml, TNF-α from 260 to 150 pg/ml) and increased regulatory cytokines (IL-10 from360 to 550 pg/ml, and TGF-ß from 220 to 410 pg/ml) in both sera (proteins) and affected lung tissue (proteins and mRNAs). The polarization of macrophages from M1to M2 type was found to be involved in the therapeutic effect of rSj-Cys on the PQ-induced acute lung injury, possibly through inhibiting TLR2/MyD88 signaling pathway. CONCLUSIONS: Our study demonstrated the therapeutic effect of rSj-Cys on PQ poisoning caused acute lung injury by inducing M2 macrophage polarization through inhibiting TLR2/MyD88 signaling pathway. The finding in this study provides an alternative approach for the treatment of PQ poisoning and other inflammatory diseases.