Synchronously Polishing the Lead-Rich Surface and Passivating Surface Defects of CsPb(Br/I)3 Quantum Dots for High-Performance Pure-Red PeLEDs.

Mixed-halide CsPb(Br/I)3 perovskite quantum dots (QDs) are regarded as one of the most promising candidates for pure-red perovskite light-emitting diodes (PeLEDs) due to their precise spectral tuning property. However, the lead-rich surface of these QDs usually results in halide ion migration and nonradiative recombination loss, which remains a great challenge for high-performance PeLEDs. To solve the above issues, we employ a chelating agent of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid hydrate (DOTA) to polish the lead-rich surface of the QDs and meanwhile introduce a new ligand of 2,3-dimercaptosuccinic acid (DMSA) to passivate surface defects of the QDs. This synchronous post-treatment strategy results in high-quality CsPb(Br/I)3 QDs with suppressed halide ion migration and an improved photoluminescence quantum yield, which enables us to fabricate spectrally stable pure-red PeLEDs with a peak external quantum efficiency of 23.2%, representing one of the best performance pure-red PeLEDs based on mixed-halide CsPb(Br/I)3 QDs reported to date.

Exploring the impact of high-altitude de-acclimatization on renal function: The roles of oxidative and endoplasmic reticulum stress in rat models.

BACKGROUND: High-altitude de-acclimatization (HADA) significantly impacts physiological functions when individuals acclimatize to high altitudes return to lower altitudes. This study investigates HADA's effects on renal function and structure in rats, focusing on oxidative and endoplasmic reticulum stress as potential mechanisms of renal injury. OBJECTIVE: To elucidate the pathophysiological mechanisms of renal damage in HADA and evaluate the efficacy of antioxidants Vitamin C (Vit C) and tauroursodeoxycholic acid (TUDCA) in mitigating these effects. METHODS: 88 male Sprague-Dawley rats were randomly divided into a control group, a high-altitude (HA) group, a high-altitude de-acclimatization (HADA) group, and a treatment group. The control group was housed in a sea level environment (500 m), while the HA, HADA, and treatment groups were placed in a simulated high-altitude chamber (5000 m) for 90 days. After this period, the HA group completed the modeling phase; the HADA group was further subdivided into four subgroups, each continuing to be housed in a sea level environment for 3, 7, 14, and 30 days, respectively. The treatment group was split into the Vit C group, the TUDCA group, and two placebo groups, receiving medication for 3 consecutive days, once daily upon return to the sea level. The Vit C group received 100 mg/kg Vit C solution via intravenous injection, the TUDCA group received 250 mg/kg TUDCA solution via intraperitoneal injection, and the placebo groups received an equivalent volume of saline similarly. Serum, urine, and kidney tissues were collected immediately after the modeling phase. Renal function and oxidative stress levels were assessed using biochemical and ELISA methods. Renal histopathology was observed with H&E, Masson's trichrome, PAS, and PASM staining. Transmission electron microscopy was used to examine the ultrastructure of glomeruli and filtration barrier. TUNEL staining assessed cortical apoptosis in the kidneys. Metabolomics was employed for differential metabolite screening and pathway enrichment analysis. RESULTS: Compared to the control and HA groups, the HADA 3-day group (HADA-3D) exhibited elevated renal function indicators, significant pathological damage, observable ultrastructural alterations including endoplasmic reticulum expansion and apoptosis. TUNEL-positive cells significantly increased, indicating heightened oxidative stress levels. Various differential metabolites were enriched in pathways related to oxidative and endoplasmic reticulum stress. Early intervention with Vit C and TUDCA markedly alleviated renal injury in HADA rats, significantly reducing the number of apoptotic cells, mitigating endoplasmic reticulum stress, and substantially lowering oxidative stress levels. CONCLUSION: This study elucidates the pivotal roles of oxidative and endoplasmic reticulum stress in the early-stage renal injury in rats undergoing HADA. Early intervention with the Vit C and TUDCA significantly mitigates renal damage caused by HADA. These findings provide insights into the pathophysiological mechanisms of HADA and suggest potential therapeutic strategies for its future management.

Association of congenital iodine deficiency syndrome and differentiated thyroid cancer: a Mendelian randomization study.

BACKGROUND: The effect of iodine deficiency, especially during the fetal period, on thyroid cancer risk remains unclear. The evidence from observational studies is controversial because of the inevitable confounding factors. We studied the causal effect of congenital iodine deficiency on differentiated thyroid cancer (DTC) based on Mendelian randomization (MR). METHODS: Two-Sample MR analysis was performed using data from published genome-wide association studies, including congenital iodine deficiency syndrome (CIDS) (353 cases, 187,684 controls) and DTC (649 cases, 431 controls) data. RESULTS: There was a causal relationship between CIDS and DTC (P < 0.05), with CIDS increasing the DTC risk by 37.4% (OR = 1.374, 95%CI = 1.110-1.700). Heterogeneity tests and tests of multiple validities indicated that the results were solid and reliable (all P < 0.05). CONCLUSIONS: Fetal iodine deficiency increases the risk of DTC, so future clinical studies should focus on the effect of iodine supplementation during pregnancy to reduce the risk of thyroid cancer in the offspring.

Activation of the Wnt/ß-catenin signalling pathway enhances exosome production by hucMSCs and improves their capability to promote diabetic wound healing.

BACKGROUND: The use of stem cell-derived exosomes (Exos) as therapeutic vehicles is receiving increasing attention. Exosome administration has several advantages over cell transplantation, thus making exosomes promising candidates for large-scale clinical implementation and commercialization. However, exosome extraction and purification efficiencies are relatively low, and therapeutic heterogeneity is high due to differences in culture conditions and cell viability. Therefore, in this study, we investigated a priming procedure to enhance the production and therapeutic effects of exosomes from human umbilical cord mesenchymal stem cells (hucMSCs). After preconditioning hucMSCs with agonists/inhibitors that target the Wnt/ß-catenin pathway, we assessed both the production of exosomes and the therapeutic efficacy of the optimized exosomes in the context of diabetic wound healing, hoping to provide a safer, more stable and more effective option for clinical application. RESULTS: The Wnt signalling pathway agonist CHIR99021 increased exosome production by 1.5-fold without causing obvious changes in the characteristics of the hucMSCs or the size of the exosome particles. Further studies showed that CHIR99021 promoted the production of exosomes by facilitating exocytosis. This process was partly mediated by SNAP25. To further explore whether CHIR99021 changed the cargo that was loaded into the exosomes and its therapeutic effects, we performed proteomic and transcriptomic analyses of exosomes from primed and control hucMSCs. The results showed that CHIR99021 significantly upregulated the expression of proteins that are associated with cell migration and wound healing. Animal experiments confirmed that, compared to control hucMSC-derived exosomes, CHIR99021-pretreated hucMSC-derived exosomes (CHIR-Exos) significantly accelerated wound healing in diabetic mice, enhanced local collagen deposition, promoted angiogenesis, and reduced chronic inflammation. Subsequent in vitro experiments confirmed that the CHIR-Exos promoted wound healing by facilitating cell migration, inhibiting oxidative stress-induced apoptosis, and preventing cell cycle arrest. CONCLUSIONS: The Wnt agonist CHIR99021 significantly increased exosome secretion by hucMSCs, which was partly mediated by SNAP25. Notably, CHIR99021 treatment also significantly increased the exosomal levels of proteins that are associated with wound healing and cell migration, resulting in enhanced acceleration of wound healing. All of these results suggested that pretreatment of hucMSCs with CHIR99021 not only promoted exosome production but also improved the exosome therapeutic efficacy, thus providing a promising option for large-scale clinical implementation and commercialization.

Development and validation of models for predicting preterm birth and gestational latency following emergency cervical cerclage: A multicenter cohort study.

INTRODUCTION: Emergency cervical cerclage is a recognized method for preventing mid-trimester pregnancy loss and premature birth; however, its benefits remain controversial. This study aimed to establish preoperative models predicting preterm birth and gestational latency following emergency cervical cerclage in singleton pregnant patients with a high risk of preterm birth. MATERIAL AND METHODS: We retrospectively reviewed data from patients who received emergency cerclage between 2015 and 2023 in three institutions. Patients were grouped into a derivation cohort (n = 141) and an independent validation cohort (n = 61). Univariate and multivariate logistic and Cox regression analyses were used to identify independent predictive variables and establish the models. Harrell's C-index, time-dependent receiver operating characteristic curves and areas under the curves, calibration curve, and decision curve analyses were performed to assess the models. RESULTS: The models incorporated gestational weeks at cerclage placement, history of prior second-trimester loss and/or preterm birth, cervical dilation, and preoperative C-reactive protein level. The C-index of the model for predicting preterm birth before 28 weeks was 0.87 (95% CI: 0.82-0.93) in the derivation cohort and 0.82 (95% CI: 0.71-0.92) in the independent validation cohort; The C-index of the model for predicting gestational latency was 0.70 (95% CI: 0.66-0.75) and 0.78 (95% CI: 0.71-0.84), respectively. In the derivation set, the areas under the curves were 0.84, 0.81, and 0.84 for predicting 1-, 3- and 5-week pregnancy prolongation, respectively. The corresponding values for the external validation were 0.78, 0.78, and 0.79, respectively. Calibration curves showed a good homogeneity between the observed and predicted ongoing pregnant probabilities. Decision curve analyses revealed satisfactory clinical usefulness. CONCLUSIONS: These novel models provide reliable and valuable prognostic predictions for patients undergoing emergency cerclage. The models can assist clinicians and patients in making personalized clinical decisions before opting for the cervical cerclage.

Advances in the Application of AI Robots in Critical Care: Scoping Review.

BACKGROUND: In recent epochs, the field of critical medicine has experienced significant advancements due to the integration of artificial intelligence (AI). Specifically, AI robots have evolved from theoretical concepts to being actively implemented in clinical trials and applications. The intensive care unit (ICU), known for its reliance on a vast amount of medical information, presents a promising avenue for the deployment of robotic AI, anticipated to bring substantial improvements to patient care. OBJECTIVE: This review aims to comprehensively summarize the current state of AI robots in the field of critical care by searching for previous studies, developments, and applications of AI robots related to ICU wards. In addition, it seeks to address the ethical challenges arising from their use, including concerns related to safety, patient privacy, responsibility delineation, and cost-benefit analysis. METHODS: Following the scoping review framework proposed by Arksey and O'Malley and the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we conducted a scoping review to delineate the breadth of research in this field of AI robots in ICU and reported the findings. The literature search was carried out on May 1, 2023, across 3 databases: PubMed, Embase, and the IEEE Xplore Digital Library. Eligible publications were initially screened based on their titles and abstracts. Publications that passed the preliminary screening underwent a comprehensive review. Various research characteristics were extracted, summarized, and analyzed from the final publications. RESULTS: Of the 5908 publications screened, 77 (1.3%) underwent a full review. These studies collectively spanned 21 ICU robotics projects, encompassing their system development and testing, clinical trials, and approval processes. Upon an expert-reviewed classification framework, these were categorized into 5 main types: therapeutic assistance robots, nursing assistance robots, rehabilitation assistance robots, telepresence robots, and logistics and disinfection robots. Most of these are already widely deployed and commercialized in ICUs, although a select few remain under testing. All robotic systems and tools are engineered to deliver more personalized, convenient, and intelligent medical services to patients in the ICU, concurrently aiming to reduce the substantial workload on ICU medical staff and promote therapeutic and care procedures. This review further explored the prevailing challenges, particularly focusing on ethical and safety concerns, proposing viable solutions or methodologies, and illustrating the prospective capabilities and potential of AI-driven robotic technologies in the ICU environment. Ultimately, we foresee a pivotal role for robots in a future scenario of a fully automated continuum from admission to discharge within the ICU. CONCLUSIONS: This review highlights the potential of AI robots to transform ICU care by improving patient treatment, support, and rehabilitation processes. However, it also recognizes the ethical complexities and operational challenges that come with their implementation, offering possible solutions for future development and optimization.

A transcriptomics-based investigation of the mechanism of pulmonary fibrosis induced by nickel oxide nanoparticles.

Nickel oxide nanoparticles (NiONPs) are an emerging nanomaterial, which poses a huge threat to the health of workplace population. Nanoparticles induce pulmonary fibrosis, and its mechanisms are associated with noncoding RNAs (ncRNAs). However, ncRNAs and competing endogenous RNA (ceRNA) networks which involved in NiONP-induced pulmonary fibrosis are still unclear. This study aimed to identify ncRNA-related ceRNA networks and investigate the role of the Wnt/ß-catenin pathway in pulmonary fibrosis. Male Wistar rats were intratracheally instilled with 0.015, 0.06, and 0.24 mg/kg NiONPs twice a week for 9 weeks. First, we found there were 93 circularRNAs (circRNAs), 74 microRNAs (miRNAs), 124 long non-coding RNAs (lncRNAs), and 1675 messenger RNAs (mRNAs) differentially expressed through microarray analysis. Second, we constructed ceRNA networks among lncRNAs/circRNAs, miRNAs and mRNAs and identified two ceRNA networks (lncMelttl16/miR-382-5p/Hsd17b7 and circIqch/miR-181d-5p/Stat1) after real time-quantitative polymerase chain reaction (RT-qPCR) validation. Furthermore, based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, ncRNAs were found to be involved in biological processes and signaling pathways related to pulmonary fibrosis. KEGG analysis showed that NiONPs activated the Wnt/ß-catenin pathway in rats. In vitro, HFL1 cells were treated with 0, 50, 100, and 200 µg/mL NiONPs for 24 h. We found that NiONPs induced collagen deposition and Wnt/ß-catenin pathway activation. Moreover, a blockade of Wnt/ß-catenin pathway alleviated NiONP-induced collagen deposition. In conclusion, these observations suggested that ncRNAs were crucial in pulmonary fibrosis development and that the Wnt/ß-catenin pathway mediated the deposition of collagen.

Leaf grey spot caused by Arcopilus aureus on tobacco in China.

Tobacco (Nicotiana tabacum L.) is one of the most widely cultivated industrial crops worldwide. From April to July 2023, about 40% of tobacco seedlings in the greenhouse exhibited irregular taupe lesions in Zhengzhou, Henan Province, China. At an early stage of the lesion development, light grey spots with the diameter of 1-2 mm were observed, these spots gradually expanded and connected into large irregular lesions causing leaf wrinkling or withered. A total of 12 infected leaf tissues were sterilized with 75% ethanol for 45 s, rinsed three times in sterilized water and then plated on potato dextrose agar (PDA) medium for 10 days at 28°C in darkness. Seven fungal colonies that show the similar appearance were isolated and three of them (MB-1, MB-2 and MB-3) were used for subsequent identification. Colonies of these strains on PDA with loose mycelium and orange-red pigment on the underside, white aerial in the center and light yellow hyphae near the periphery, formed in the shape of a concentric ring pattern. Ascomata appeared from the 14th day, were black, spherical or ellipsoid with walls of textura angularis, and size was 53.8-101.1 µm × 50.3-104.3 µm (n=30). Terminal hairs were brown and straight, gradually tapering toward the tips. Asci clavate or fusiform, spore bearing part 16.2-29.2 × 7.3-11.4 µm (n=21), with 8 irregularly arranged ascospores, evanescent. Ascospores are brown at maturity, biapiculate, navicular or fusiform shapes with size of 8.7-12.8 µm × 4.8-6.9 µm (n=100), and more or less inaequilateral. Single spore strains derived from these strains exhibited the morphological features consistent with the original strains. The morphological characteristics of the fungus were consistent with the description of Arcopilus aureus (Chivers) X.W. Wang & Samson (= Chaetomium aureum Chivers) (Lee et al. 2019). Furthermore, the sequences of RPB2 region were amplified from these strains and the result sequences (GenBank accession no. OR513105-OR513108) all showed a 100.00% identity with A. aureus strain CBS 538.73 (GenBank accession no. KX976807.1). It was reported that the RPB2 gene was efficient in discriminating Arcopilus species (Tavares et al. 2022), thus a maximum likelihood (ML) phylogenetic tree based on the RPB2 gene sequences were constructed using MEGA 7.0 with 1000 replications of bootstrapping (Kumar et al. 2016), which revealed that these strains formed a well-supported clade with A. aureus strains of (CBS 153.52 and CBS538.73) (Wang et al. 2022). Pathogenicity analysis were performed on healthy flue-cured tobacco seedlings leaves (cv Y85) by using mycelial agar plugs (5 mm in diameter) and spore suspension (1×106 spores/mL), and the PDA plugs and sterile water were used for control group, respectively. Tobacco seedlings were incubated in a 25°C and 70% RH growth chamber. After seven days, the leaves showed obvious symptoms, with taupe lesions and yellow halos on the periphery, whereas no symptoms were found on the control leaves. The A. aureu was then reisolated from inoculated diseased leaves. Previously, A. aureus has been only reported to cause leaf black disease on Pseudostellaria heterophylla in China (Yuan et al. 2021). To our knowledge, this is the first reported of A. aureus causing tobacco leaf grey spot worldwide. Arcopilus aureus has been reported as a plant biocontrol fungus (Wang et al. 2013). However, due to the potential serious damage in tobacco seedlings caused by this fungus, the use of A. aureus as a plant biocontrol agent needs to be given more attention, and disease control measures of this pathogen should be developed.

Effect of fire and post-fire management on soil microbial communities in a lower subtropical forest ecosystem after a mountain fire.

Wildfires and post-fire management exert profound effects on soil properties and microbial communities in forest ecosystems. Understanding microbial community recovery from fire and what the best post-fire management should be is very important but needs to be sufficiently studied. In light of these gaps in our understanding, this study aimed to assess the short-term effects of wildfire and post-fire management on both bacteria and fungi community composition, diversity, structure, and co-occurrence networks, and to identify the principal determinants of soil processes influencing the restoration of these communities. Specifically, we investigated soil bacterial and fungal community composition, diversity, structure, and co-occurrence networks in lower subtropical forests during a short-term (<3 years) post-fire recovery period at four main sites in Guangdong Province, southern China. Our results revealed significant effects of wildfires on fungal community composition, diversity, and co-occurrence patterns. Network analysis indicated reduced bacterial network complexity and connectivity post-fire, while the same features were enhanced in fungal networks. However, post-fire management effects on microbial communities were negligible. Bacterial diversity correlated positively with soil microbial biomass nitrogen, soil organic carbon, and soil total nitrogen. Conversely, based on the best random forest model, fungal community dynamics were negatively linked to nitrate-nitrogen and soil water content. Spearman's correlation analysis suggested positive associations between bacterial networks and soil factors, whereas fungal networks exhibited predominantly negative associations. This study elucidates the pivotal role of post-fire management in shaping ecological outcomes. Additionally, it accentuates the discernible distinctions between bacterial and fungal responses to fire throughout a short-term recovery period. These findings contribute novel insights that bear significance in evaluating the efficacy of environmental management strategies.

High-Performance and Polarization-Sensitive Imaging Photodetector Based on WS2 /Te Tunneling Heterostructure.

Next-generation imaging systems require photodetectors with high sensitivity, polarization sensitivity, miniaturization, and integration. By virtue of their intriguing attributes, emerging 2D materials offer innovative avenues to meet these requirements. However, the current performance of 2D photodetectors is still below the requirements for practical application owing to the severe interfacial recombination, the lack of photoconductive gain, and insufficient photocarrier collection. Here, a tunneling dominant imaging photodetector based on WS2 /Te heterostructure is reported. This device demonstrates competitive performance, including a remarkable responsivity of 402 A W-1 , an outstanding detectivity of 9.28 × 1013 Jones, a fast rise/decay time of 1.7/3.2 ms, and a high photocurrent anisotropic ratio of 2.5. These outstanding performances can be attributed to the type-I band alignment with carrier transmission barriers and photoinduced tunneling mechanism, allowing reduced interfacial trapping effect, effective photoconductive gains, and anisotropic collection of photocarriers. Significantly, the constructed photodetector is successfully integrated into a polarized light imaging system and an ultra-weak light imaging system to illustrate the imaging capability. These results suggest the promising application prospect of the device in future imaging systems.

Broadband Polarization-Sensitive Photodetection of Magnetic Semiconducting MnTe Nanoribbons.

2D materials with low symmetry are explored in recent years because of their anisotropic advantage in polarization-sensitive photodetection. Herein the controllably grown hexagonal magnetic semiconducting α-MnTe nanoribbons are reported with a highly anisotropic (100) surface and their high sensitivity to polarization in a broadband photodetection, whereas the hexagonal structure is highly symmetric. The outstanding photoresponse of α-MnTe nanoribbons occurs in a broadband range from ultraviolet (UV, 360 nm) to near infrared (NIR, 914 nm) with short response times of 46 ms (rise) and 37 ms (fall), excellent environmental stability, and repeatability. Furthermore, due to highly anisotropic (100) surface, the α-MnTe nanoribbons as photodetector exhibit attractive sensitivity to polarization and high dichroic ratios of up to 2.8 under light illumination of UV-to-NIR wavelengths. These results demonstrate that 2D magnetic semiconducting α-MnTe nanoribbons provide a promising platform to design the next-generation polarization-sensitive photodetectors in a broadband range.

Didymin alleviates metabolic dysfunction-associated fatty liver disease (MAFLD) via the stimulation of Sirt1-mediated lipophagy and mitochondrial biogenesis.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is one of the most prevalent metabolic syndromes worldwide. However, no approved pharmacological treatments are available for MAFLD. Chenpi, one kind of dried peel of citrus fruits, has traditionally been utilized as a medicinal herb for liver diseases. Didymin is a newly identified oral bioactive dietary flavonoid glycoside derived from Chenpi. In this study, we investigated the therapeutic potential of Didymin as an anti-MAFLD drug and elucidated its underlying mechanisms. METHODS: High-fat diet (HFD)-induced MAFLD mice and alpha mouse liver 12 (AML12) cells were utilized to evaluate the effects and mechanisms of Didymin in the treatment of MAFLD. Liver weight, serum biochemical parameters, and liver morphology were examined to demonstrate the therapeutic efficacy of Didymin in MAFLD treatment. RNA-seq analysis was performed to identify potential pathways that could be affected by Didymin. The impact of Didymin on Sirt1 was corroborated through western blot, molecular docking analysis, microscale thermophoresis (MST), and deacetylase activity assay. Then, a Sirt1 inhibitor (EX-527) was utilized to confirm that Didymin alleviates MAFLD via Sirt1. Western blot and additional assays were used to investigate the underlying mechanisms. RESULTS: Our results suggested that Didymin may possess therapeutic potential against MAFLD in vitro and in vivo. By promoting Sirt1 expression as well as directly binding to and activating Sirt1, Didymin triggers downstream pathways that enhance mitochondrial biogenesis and function while reducing apoptosis and enhancing lipophagy. CONCLUSIONS: These suggest that Didymin could be a promising medication for MAFLD treatment. Furthermore, its therapeutic effects are mediated by Sirt1.

Polarization-sensitive UV photodetector based on ReSe2/GaN mixed-dimensional heterojunction.

Polarization-sensitive photodetectors in the ultraviolet (UV) region have been favored for their great meaning in the field of military and civilian. UV photodetectors based on GaN have aroused much attention due to high photocurrent and high sensitivity. However, the dependence on external power sources and the limited sensitivity to polarized UV light significantly impede the practical application of these photodetectors in UV-polarized photodetection. Herein, a polarization-sensitive UV photodetector based on ReSe2/GaN mixed-dimensional van der Waals (vdWs) heterojunction is proposed. Owing to the high-quality junction and type-II band alignment, the responsivity and specific detectivity reach values of 870 mA/W and 6.8 × 1011 Jones, under 325 nm illumination, respectively. Furthermore, thanks to the strong in-plane anisotropy of ReSe2, the device is highly sensitive to polarized UV light with a photocurrent anisotropic ratio up to 6.67. The findings are expected to bring new opportunities for the development of highly sensitive, high-speed and energy-efficient polarization-sensitive photodetectors.

Exosomes derived from mesenchymal stem cells attenuate diabetic kidney disease by inhibiting cell apoptosis and epithelial-to-mesenchymal transition via miR-424-5p.

Diabetic kidney disease (DKD) is well-acknowledged as one of the most common complications in diabetes mellitus. Recent studies have demonstrated the promising role of mesenchymal stem cell-derived exosomes (MSC-exos) as a cell-free treatment strategy for DKD. The present study sought to investigate the therapeutic potential and the underlying mechanisms of MSC-exos in DKD. The authentication of MSC-exos was validated by western blot, transmission electron microscope (TEM), and nanosight tracking analysis (NTA). Apoptosis was detected by western blot, TUNEL staining, and flow cytometry. Epithelial-to-mesenchymal transition (EMT) was evaluated by western blot and immunofluorescence. The relationship between miR-424-5p and Yes-associated protein 1 (YAP1) was revealed by dual luciferase reporter assay. We observed that MSC-exos could attenuate DKD by decreasing cell apoptosis and inhibiting epithelial-to-mesenchymal transition (EMT) in diabetic kidneys in db/db mice. Besides, we documented that MSC-exos could reverse high glucose-induced apoptosis and EMT in HK2 cells. Interestingly, miR-424-5p derived from MSC-exos could inhibit YAP1 activation in HK2 cells, resulting in alleviation of high glucose-induced cell apoptosis and EMT. Our study provides novel insights into MSC-exos-mediated protective effect in DKD. MSC-exos could inhibit high glucose-induced apoptosis and EMT through miR-424-5p targeting of YAP1.

cGAS-STING mediates cytoplasmic mitochondrial-DNA-induced inflammatory signal transduction during accelerated senescence of pancreatic ß-cells induced by metabolic stress.

Type 2 diabetes mellitus (T2DM) is an age-related disease characterized by impaired pancreatic ß cell function and insulin resistance. Recent studies have shown that the accumulation of senescent ß cells under metabolic stress conditions leads to the progression of T2DM, while senolysis can improve the prognosis. However, the specific mechanism of ß cell senescence is still unclear. In this study, we found that the increased load of senescence pancreatic ß cells in both older mice and obese mice induced by high-fat diet (HFD) (DIO mice) was accompanied by activation of the Cyclic GMP-AMP synthase (cGAS) - stimulator of interferon genes (STING) pathway and using cGAS or STING small interfering RNA or STING inhibitor C176 to downregulate this pathway reduced the senescence-associated secretion profile (SASP) and senescence of Min6 cells treated with palmitic acid or hydrogen peroxide. C176 intervention in DIO mice also significantly reduced the inflammation and senescence of the islets, thereby protecting the function of pancreatic ß cell and glucose metabolism. Our study further revealed that mitochondrial DNA (mtDNA) leakage under metabolic stress conditions was critical for the activation of the cGAS-STING pathway, which can be reversed by the mtDNA depleting agent ethidium bromide. Consistently, mtDNA leakage was more severe in older mice and was accelerated by a chronic HFD. In conclusion, we demonstrate that cytoplasmic mtDNA activates the cGAS-STING pathway to mediate SASP during the accelerated senescence of pancreatic ß-cells induced by metabolic stress, and this process can be downregulated by the STING inhibitor C176.

Molecularly Imprinted Polymers with Shape-Memorable Imprint Cavities for Efficient Separation of Hemoglobin from Blood.

Efficient separation and purification of hemoglobin from blood and other complicated biological fluids still remains a big challenge. Molecularly imprinted polymers (MIPs) of hemoglobin are potential choices; however, they suffer from severe problems including difficult template removal and low imprinting efficiency like other protein-imprinted polymers. Herein, a novel MIP of bovine hemoglobin (BHb) was designed in which a peptide crosslinker (PC), instead of the commonly used crosslinkers, was used. The PC, a random copolymer of lysine and alanine, adopts an α-helical conformation at pH 10 but transits to a random coil conformation at pH 5. The introduction of alanine residues lowers the pH range at which the PC undergoes helix-coil transition. The imprint cavities in the polymers are shape-memorable due to the reversible and precise helix-coil transition of the peptide segments in the polymers. They can be enlarged by lowering pH from 10 to 5, thus allowing complete removal of the template protein under mild conditions. When the pH is adjusted back to 10, their original size and shape will be recovered. Therefore, the MIP binds the template protein BHb with high affinity. Compared with the MIP crosslinked with the commonly used crosslinker, the imprinting efficiency of the PC-crosslinked MIP is significantly improved. In addition, both the maximum adsorption capacity (641.9 mg/g) and imprinting factor (7.2) are much higher than the BHb MIPs reported previously. The new BHb MIP also exhibits high selectivity toward BHb and good reusability. Thanks to the high adsorption capacity and high selectivity of the MIP, when it was applied to extract BHb from bovine blood, BHb in the blood sample was extracted almost completely, and high purity product was obtained.

Two decades of capacity building to support global malaria control and elimination: retrospective and prospective international trainings in Jiangsu Institute of Parasitic Diseases, China, 2002-2021.

BACKGROUND: Malaria is still one of the major infectious diseases affecting human health, and the World Health Organization (WHO) has attached special importance to malaria-related technical training for its global elimination efforts. The Jiangsu Institute of Parasitic Diseases (JIPD), designated as a WHO Collaborating Centre for Research and Training on Malaria Elimination, has conducted numerous international malaria training programmes during the last 2 decades. METHODS: A retrospective analysis of international training programmes organized and facilitated by JIPD in China since 2002 was conducted. A web-based questionnaire was designed to gather respondents' basic information, evaluation of course topics, methodology, trainers, and facilitators, course impact, and suggestions for future trainings. Individuals who participated in the training courses from 2017 to 2019 were invited to participate in this assessment. RESULTS: Since 2002, JIPD has conducted 62 malaria-related international trainings attended by 1935 participants from 85 countries, covering 73% of malaria endemic countries. Of 752 participants enrolled, 170 responded to the online survey. A majority of respondents (160/170, 94.12%) gave a high evaluation of the training, with an average score of 4.52 (5 maximum score). Also, survey respondents gave a 4.28 score on "knowledge and skills gained in the training useful for the national malaria programme", 4.52 on "topics appropriate to their professional needs", and 4.52 on "knowledge and skills gained in the training useful to their career". Surveillance and response was the most important topic discussed and field visit was the most effective method of training. For future training programmes, with increasing length of training, more field visits and demonstration, improving language barrier, and sharing experience were what the respondents requested most. CONCLUSION: JIPD, as a professional institute for malaria control, has conducted a great quantity of training in the past 20 years, providing training opportunities to both malaria and non-malaria endemic countries globally. For future training, survey respondents' suggestions will be considered to provide a more effective capacity building activity to better contribute to global malaria elimination.

Regulatory mechanism of interaction between Y-box-binding protein 1 and heterogenous nuclear ribonucleoprotein K in cell division cycle 25a signal pathway and lung cancer metastasis.

The research aimed to the influences of the interaction between Y-box-binding protein 1 (YBX1) and heterogeneous nuclear ribonucleoprotein K (HNRNPK) on cell division cycle protein 25 phosphatase A (CDC25a) signal pathway and the regulatory mechanism of lung cancer (LC) metastasis. A total of 34 patients diagnosed with LC pathologically were selected as the research objects, and the expression levels of YBX1, HNRNP and CDC25a in LC non-metastasis tissues and LC metastasis tissues were detected by immunohistochemistry and Western blot (WB). High-expression stable cell lines including YBX1/A549 and HNRNPK /A549 were established in the LC A549 cell strain. The expression levels of YBX1 and HNRNP in YBX1/A549 and HNRNPK /A549 were tested by RT-PCR and WB. Besides, the number of migratory cells YBX1/A549 and HNRNPK /A549 was detected by cell migration experiment, and the influences of the interaction between YBX1 and HNRNP on the expression level of CDC25a were analyzed by co-immunoprecipitation (co-IP). The results showed that the expression level of YBX1 protein in LC metastasis tissues was higher than that in LC non-metastasis tissues (P<0.001). The expression level of HNRNPK protein in LC metastasis tissues was higher than that in LC non-metastasis tissues (P<0.01). The expression level of CDC25a protein in LC metastasis tissues was higher than that in LC non-metastasis tissues (P<0.05). Compared with the Control Group of A549 cell strain and transfected blank plasmid, mRNA levels and relative protein expression levels of YBX1 and HNRNPK in YBX1/A549 and HNRNPK/A549 cell lines were both increased (P<0.001). The number of migratory cells YBX1/A549 and HNRNPK/A549 was increased compared with A549 cells and those in Control Group (P<0.001), and cell migration rate of YBX1/A549 and HNRNPK/A549 was also enhanced compared with A549 cells and those in Control Group (P<0.001). The mRNA and protein levels of YBX1 in YBX1/A549 cell line were increased compared with those in Control Group (P<0.01), and the comparison of mRNA level and protein expression level of HNRNPK in YBX1/A549 cell line with the in Control Group showed no differences (P>0.05). The mRNA level and protein expression level of HNRNPK in HNRNPK/A549 cell line were enhanced compared with those in Control Group (P<0.01), and the comparison of YBX1 level and protein expression level in HNRNPK/A549 cell line with the in Control Group demonstrated no differences (P>0.05). YBX1 antibody adopted in co-IP was coated with magnetic beads, and numerous HNRNPK protein was abundant in YBX1/HNRNPK composite. The mRNA level and protein expression level of YBX1 and HNRNPK in YBX1/A549 and HNRNPK/A549 cell lines were enhanced compared with those in Control Group (P<0.001), and the comparison of mRNA level and protein expression level of CDC25 with those in Control Group showed no differences (P>0.05). The mRNA level and protein expression level of CDC25a in YBX1/HNRNPK/A549 were both higher than those in YBX1/A549 cell line and HNRNPK/A549 (P<0.001). With being induced by YBX1 or HNRNPK, the number of migratory cells CDC25/A549 was increased compared with that in Control Group (P<0.05). The mRNA level and protein expression level of CDC25a in YBX1/HNRNPK/A549 were both significantly higher than those in YBX1/A549 cell line and HNRNPK/A549 (P<0.001). All the above results indicated that the interaction between YBX1 and HNRNP regulated the expression of CDC25a, and further got involved in LC metastasis.

Puerarin ameliorates metabolic dysfunction-associated fatty liver disease by inhibiting ferroptosis and inflammation.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is frequently linked to type 2 diabetes mellitus (T2DM), and both conditions exacerbate the progression of the other. However, there is currently no standardized treatment or drug for MAFLD. In this study, A MAFLD animal model through a high-fat diet (HFD) along with administration of streptozotocin (STZ), and palmitic acid (PA)-induced AML12 cells were treated by puerarin. The objective of this study was to assess the therapeutic effect of puerarin, a flavonoid substance that possesses various pharmacological properties, on MAFLD. The results showed that puerarin administration enhanced glucose tolerance and insulin sensitivity, while also mitigating liver dysfunction and hyperlipidemia in MAFLD mice. Moreover, puerarin attenuated oxidative stress levels and inflammation in the liver. Transmission electron microscopy and Western blot analysis indicated that puerarin inhibited ferroptosis in vivo. Further mechanistic investigations revealed that puerarin upregulated SIRT1 expression, increased nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels, and facilitated translocation into the nucleus. The protective effect of puerarin on PA-induced AML12 cells was diminished by the utilization of EX-527 (a SIRT1 inhibitor) and Nrf2 siRNA. Overall, the results demonstrate that puerarin ameliorates MAFLD by suppressing ferroptosis and inflammation via the SIRT1/Nrf2 signaling pathway. The results emphasize the possible medicinal application of puerarin for managing MAFLD.

HDAC3 Contributes to Ischemic Stroke by Regulating Interferon Pathway.

BACKGROUND: The inflammation and immune response contribute to ischemic stroke pathology. Damaged brain cells release inflammatory substances to activate the immune system in the acute phase of stroke, including altering the interferon signaling pathway. However, the involvement of histone deacetylation in stroke remains unclear. METHODS: To investigate whether histone deacetylation modulation could regulate the interferon signaling pathway and mediate the pathogenic changes after stroke, the middle cerebral artery occlusion (MCAO) mouse model was treated with histone deacetylase 3 (HDAC3) inhibitor and RGFP966. Additionally, a series of approaches, including middle cerebral artery occlusion (MCAO), real-time polymerase chain reaction (PCR), western blot, 2,3,5-triphenyltetrazolium chloride (TTC) staining, behavioral experiments, and confocal imaging were utilized. RESULTS: It is observed that RGFP966 pretreatment could lead to better outcomes in the MCAO mouse model, including the decrease of infarction volumes, the amelioration of post-stroke anxiety-like behavior, and the relief of inflammatory responses. Furthermore, we found that RGFP966 could counteract the hyperactivation of the interferon signaling pathway and the excessive expression of Z-DNA Binding Protein 1 (ZBP1) in microglia. CONCLUSIONS: We demonstrated a novel mechanism that HDAC3 inhibition could ameliorate the pathological injury after ischemic stroke by downregulating the ZBP1/phosphorylated Interferon Regulatory Factor 3 (p-IRF3) pathway. Thus, these data provide a new promising target for therapies for ischemic stroke.