Maintaining moderate levels of hypochlorous acid promotes neural stem cell proliferation and differentiation in the recovery phase of stroke.

JOURNAL/nrgr/04.03/01300535-202503000-00029/figure1/v/2024-06-17T092413Z/r/image-tiff It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late stroke. Indeed, previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain tissue. Our previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke, but its specific role and mechanism are currently unclear. To simulate stroke in vivo, a middle cerebral artery occlusion rat model was established, with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic stroke. We found that in the early stage (within 24 hours) of ischemic stroke, neutrophils produced a large amount of hypochlorous acid, while in the recovery phase (10 days after stroke), microglia were activated and produced a small amount of hypochlorous acid. Further, in acute stroke in rats, hypochlorous acid production was prevented using a hypochlorous acid scavenger, taurine, or myeloperoxidase inhibitor, 4-aminobenzoic acid hydrazide. Our results showed that high levels of hypochlorous acid (200 µM) induced neuronal apoptosis after oxygen/glucose deprivation/reoxygenation. However, in the recovery phase of the middle cerebral artery occlusion model, a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and astrocytes. This suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion injury. Lower levels of hypochlorous acid (5 and 100 µM) promoted nuclear translocation of ß-catenin. By transfection of single-site mutation plasmids, we found that hypochlorous acid induced chlorination of the ß-catenin tyrosine 30 residue, which promoted nuclear translocation. Altogether, our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.

UBE2C-induced crosstalk between mono- and polyubiquitination of SNAT2 promotes lymphatic metastasis in bladder cancer.

Ubiquitination plays an essential role in protein stability, subcellular localization, and interactions. Crosstalk between different types of ubiquitination results in distinct biological outcomes for proteins. However, the role of ubiquitination-related crosstalk in lymph node (LN) metastasis and the key regulatory factors controlling this process have not been determined. Using high-throughput sequencing, we found that ubiquitin-conjugating enzyme E2 C (UBE2C) was overexpressed in bladder cancer (BCa) and was strongly associated with an unfavorable prognosis. Overexpression of UBE2C increased BCa lymphangiogenesis and promoted LN metastasis both in vitro and in vivo. Mechanistically, UBE2C mediated sodium-coupled neutral amino acid transporter 2 (SNAT2) monoubiquitination at lysine 59 to inhibit K63-linked polyubiquitination at lysine 33 of SNAT2. Crosstalk between monoubiquitination and K63-linked polyubiquitination increased SNAT2 membrane protein levels by suppressing epsin 1-mediated (EPN1-mediated) endocytosis. SNAT2 facilitated glutamine uptake and metabolism to promote VEGFC secretion, ultimately leading to lymphangiogenesis and LN metastasis in patients with BCa. Importantly, inhibition of UBE2C significantly attenuated BCa lymphangiogenesis in a patient-derived xenograft model. Our results reveal the mechanism by which UBE2C mediates crosstalk between the monoubiquitination and K63-linked polyubiquitination of SNAT2 to promote BCa metastasis and identify UBE2C as a promising target for treating LN-metastatic BCa.

Application of neutrophil-lymphocyte ratio and red blood cell distribution width in diabetes mellitus complicated with heart failure.

BACKGROUND: Accumulating clinical evidence has shown that diabetes mellitus (DM) is a serious risk factor for cardiovascular disorders and an important factor for adverse cardiovascular events. AIM: To explore the value of the combined determination of the neutrophil-lymphocyte ratio (NLR) and red blood cell distribution width (RDW) in the early diagnosis and prognosis evaluation of DM complicated with heart failure (HF). METHODS: We retrospectively analyzed clinical data on 65 patients with type 2 DM (T2DM) complicated with HF (research group, Res) and 60 concurrent patients with uncomplicated T2DM (control group, Con) diagnosed at Zhejiang Provincial People's Hospital between January 2019 and December 2021. The NLR and RDW values were determined and comparatively analyzed, and their levels in T2DM + HF patients with different cardiac function grades were recorded. The receiver operating characteristic (ROC) curves were plotted to determine the NLR and RDW values (alone and in combination) for the early diagnosis of HF. The correlation between NLR and RDW with the presence or absence of cardiac events was also investigated. RESULTS: Higher NLR and RDW levels were identified in the Res vs the Con groups (P < 0.05). The NLR and RDW increased gradually and synchronously with the deterioration of cardiac function in the Res group, with marked differences in their levels among patients with grade II, III, and IV HF (P < 0.05). ROC curve analysis revealed that NLR combined with RDW detection had an area under the curve of 0.915, a sensitivity of 76.9%, and a specificity of 100% for the early diagnosis of HF. Furthermore, HF patients with cardiac events showed higher NLR and RDW values compared with HF patients without cardiac events. CONCLUSION: NLR and RDW were useful laboratory indicators for the early diagnosis of DM complicated with HF, and their joint detection was beneficial for improving diagnostic efficiency. Additionally, NLR and RDW values were directly proportional to patient outcomes.

The role of cytolethal distending toxin in Glaesserella parasuis JS0135 strain infection: Cytotoxicity, phagocytic resistance and pathogenicity.

Glaesserella parasuis is an important porcine pathogen that commonly colonizes the upper respiratory tract of pigs and is prone to causing Glässer's disease under complex conditions. As yet, the disease has led to serious economic losses to the swine industry worldwide. Studies so far have found that several virulence factors are associated with the pathogenicity of G. parasuis, but the pathogenic mechanism is still not fully understood. Cytolethal distending toxin (CDT), a potential virulence factor in G. parasuis, is involved in cytotoxicity, serum resistance, adherence to and invasion of host cells in vitro. Here, to further investigate the pathogenic role of CDT during G. parasuis infection in vitro and in vivo, a double cdt1 and cdt2 deletion mutant (Δcdt1Δcdt2) without selectable marker was first generated in G. parasuis JS0135 strain by continuous natural transformations and replica plating. Morphological observation and lactate dehydrogenase assay showed that the Δcdt1Δcdt2 mutant was defective in cytotoxicity. Additionally, the Δcdt1Δcdt2 mutant was more susceptible to phagocytosis caused by 3D4/2 macrophages compared to the wild-type JS0135 strain. Moreover, by focusing on clinical signs, necropsy, bacterial recovery and pathological observation, we found that the deletion of cdt1 and cdt2 genes led to a significant attenuation of virulence in G. parasuis. Taken together, these findings suggest that as an important virulence factor, CDT can significantly affect the pathogenicity of G. parasuis.

Application of Weak-Beam Dark-Field STEM for Dislocation Loop Analysis †.

Nanoscale dislocation loops formed by irradiation can significantly contribute to both irradiation hardening and embrittlement of materials when subjected to extreme nuclear reactor environments. This study explores the application of weak-beam dark-field (WBDF) scanning transmission electron microscopy (STEM) methods for quantitative irradiation-induced defect analysis in crystalline materials, with a specific focus on dislocation loop imaging and analysis. A high-purity Fe-5 wt% Cr model alloy was irradiated with 8 MeV Fe2+ ions at 450°C to a fluence of 8.8 × 1019 m-2, inducing dislocation loops for analysis. While transmission electron microscopy (TEM) has traditionally been the primary tool for dislocation imaging, recent advancements in STEM technology have reignited interest in using STEM for defect imaging. This study introduces and compares three WBDF STEM methods, demonstrating their effectiveness in suppressing background contrasts, isolating defect information for dislocation loop type classification, providing finer dislocation line images for small loop analysis, and presenting inside-outside contrast for identifying loop nature. Experimental findings indicate that WBDF STEM methods surpass traditional TEM approaches, yielding clearer and more detailed images of dislocation loops. The study concludes by discussing the potential applications of WBDF STEM techniques in defect analysis, emphasizing their adaptability across various material systems beyond nuclear materials.

A-to-I RNA co-editing predicts clinical outcomes and is associated with immune cells infiltration in hepatocellular carcinoma.

Aberrant RNA editing has emerged as a pivotal factor in the pathogenesis of hepatocellular carcinoma (HCC), but the impact of RNA co-editing within HCC remains underexplored. We used a multi-step algorithm to construct an RNA co-editing network in HCC, and found that HCC-related RNA editings are predominantly centralized within the network. Furthermore, five pairs of risk RNA co-editing events were significantly correlated with the overall survival in HCC. Based on presence of risk RNA co-editings resulted in the categorization of HCC patients into high-risk and low-risk groups. Disparities in immune cell infiltrations were observed between the two groups, with the high-risk group exhibiting a greater abundance of exhausted T cells. Additionally, seven genes associated with risk RNA co-editing pairs were identified, whose expression effectively differentiates HCC tumor samples from normal ones. Our research offers an innovative perspective on the etiology and potential therapeutics for HCC.

Performance evaluation of influenza a rapid antigen test and PCR among nasopharyngeal and oropharyngeal samples.

Objectives: Rapid antigen test (RAT) and polymerase chain reaction (PCR) using nasopharyngeal (NP) or oropharyngeal (OP) swab specimens are the two main testing techniques used for laboratory diagnosis of influenza in clinical practice. However, performance variations have been observed not only between techniques, but also between different specimens. This study evaluated the differences in performance between specimens and testing techniques to identify the best combination in clinical practice. Methods: Both NP and OP samples from suspected influenza patients collected in the 2023/4-2023/5 Flu-season in Xiamen, China, were tested for RAT and quantitative PCR. The testing performance of the different specimens and testing techniques were recorded and evaluated. Results: Compared to PCR, RAT showed 58.9 % and 10.3 % sensitivity for NP and OP swabs, respectively. The Limit of Detection (LoD) was 28.71 the Median Tissue Culture Infectious Dose (TCID50)/mL. Compared with PCR using NP swabs, PCR with OP swabs showed 89.5 % sensitivity and 95.4 % specificity. Conclusions: There were no significant differences in performance between the specimens when PCR was used to test for influenza. However, a decrease in sensitivity was observed when the RAT was used, regardless of the specimen type. Therefore, to avoid false-negative results, PCR may be a better choice when OP swabs are used as specimens. In contrast, NP swabs should be the recommended specimens for RAT.

Gubra Amylin-NASH Diet Induced Nonalcoholic Fatty Liver Disease Associated with Histological Damage, Oxidative Stress, Immune Disorders, Gut Microbiota, and Its Metabolic Dysbiosis in Colon.

SCOPE: The overall changes of colon under nonalcoholic fatty liver disease (NAFLD) remain to be further elucidated. METHODS AND RESULTS: This study establishes a mouse model of NAFLD through a long-term Gubra Amylin-nonalcoholic steatohepatitis (NASH) diet (GAN diet). The results show that GAN diet significantly induces weight gain, liver steatosis, colonic oxidative stress, and lipid accumulation in blood, liver, and adipose tissue in mice. GAN feeding reduces the diversity of the gut microbiota, alters the composition and abundance of the gut microbiota, and leads to an increase in microbial metabolites such as long-chain fatty acids (LCFAs) and secondary bile acids (BAs), as well as a decrease in short-chain fatty acids (SCFAs). The RNA-seq and immunofluorescence results reveal that the GAN diet alters the expression of proteins and their coding genes involved in oxidative stress, immune response, and barrier function in colon tissue, such as lipocalin-2 (Lcn2, p < 0.05), heme oxygenase-1 (HO-1/Hmox1, p < 0.05), interferon-gamma (IFN-γ), and claudin-3/7. In addition, correlation analysis indicates a strong correlation between the changes in gut microbiota and lipid biomarkers. Additionally, the expression of immune related genes in colon tissue is related to the LCFAs produced by microbial metabolism. CONCLUSION: GAN-induced NAFLD is related to microbiota and its metabolic imbalance, oxidative stress, immune disorders, and impaired barrier function in colon.

Optimization of extended Kozak elements enhances recombinant proteins expression in CHO cells.

In eukaryotes, the localization of small ribosomal subunits to mRNA transcripts requires the translation of Kozak elements at the starting site. The sequence of Kozak elements affects the translation efficiency of protein synthesis. However, whether the upstream nucleotide of Kozak sequence affects the expression of recombinant proteins in Chinese hamster ovary (CHO) cells remains unclear. In order to find the optimal sequence to enhance recombinant proteins expression in CHO cells, -10 to +4 sequences around ATG in 100 CHO genes were compared, and the extended Kozak elements with different translation intensities were constructed. Using the classic Kozak element as control, the effects of optimized extended Kozak elements on the secreted alkaline phosphatase (SEAP) and human serum albumin (HSA) gene were studied. The results showed that the optimized extended Kozak sequence can enhance the stable expression level of recombinant proteins in CHO cells. Furthermore, it was found that the increased expression level of the recombinant protein was not related with higher transcription level. In summary, optimizing extended Kozak elements can enhance the expression of recombinant proteins in CHO cells, which contributes to the construction of an efficient expression system for CHO cells.

Dynamic Structural Fluxionality in a Planar Tetracoordinate Carbon Cluster Stabilized by Boron Ligands.

The design of boron-based molecular rotors stems from boron-carbon binary clusters containing multiple planar hypercoordinate carbons (phCs, such as C2B8). However, the design of boron-coordinated phCs is challenging due to boron's tendency to occupy hypercoordinate centers more than carbon. Although this challenge has been addressed, the designed clusters of interest have not exhibited dynamic fluxionality similar to that of the initial C2B8. To address this issue, we report a σ/π doubly aromatic CB2H5+ cluster, the first global minimum containing a boron-coordinated planar tetracoordinate carbon atom with dynamic fluxionality. Dynamics simulations show that two ligand H atoms exhibit alternate rotation, resulting in an intriguing dynamic fluxionality in this cluster. Electronic structure analysis reveals the flexible bonding positions of the ligand H atoms because they do not participate in π delocalized bonding nor bond to any other non-carbon atom, highlighting this rotational fluxionality. Unprecedentedly, the fluxional process involves not only the usual conversion of the number of bonding atoms, but also the type of bonding (3c π bonds ↔ 4c σ bonds), which is an uncommon fluxional mechanism. The cluster represents an effort to apply phC species to molecular machines.

CVD Grown CNTs-Modified Electrodes for Vanadium Redox Flow Batteries.

Vanadium redox flow batteries (VRFBs) are of considerable importance in large-scale energy storage systems due to their high efficiency, long cycle life and easy scalability. In this work, chemical vapor deposition (CVD) grown carbon nanotubes (CNTs)-modified electrodes and Nafion 117 membrane are utilised for formulating a vanadium redox flow battery (VRFB). In a CVD chamber, the growth of CNTs is carried out on an acid-treated graphite felt surface. Cyclic voltammetry of CNT-modified electrode and acid-treated electrode revealed that CNTs presence improve the reaction kinetics of V3+/V2+ and VO2+/VO2+ redox pairs. Battery performance is recorded for analysing, the effect of modified electrodes, varying electrolyte flow rates, varying current densities and effect of removing the current collector plates. CNTs presence enhance the battery performance and offered 96.30% of Coulombic efficiency, 79.33% of voltage efficiency and 76.39% of energy efficiency. In comparison with pristine electrodes, a battery consisting CNTs grown electrodes shows a 14% and 15% increase in voltage efficiency and energy efficiency, respectively. Battery configured without current collector plates performs better as compared to with current collector plates which is possibly due to decrease in battery resistance.

NAT10 Phase Separation Regulates YTHDF1 Splicing to Promote Gastric Cancer Progression.

Gastric cancer (GC) is an aggressive malignancy with poor patient outcomes. NAT10 is an acetyltransferase that has been reported to contribute to GC progression. In-depth investigation into the underlying molecular mechanisms driven by NAT10 could help identify therapeutic targets to improve GC treatment. Here, we found that NAT10 forms condensates to regulate RNA dynamics and promote GC progression. In GC patient samples, elevated NAT10 expression correlated with an unfavorable prognosis, advanced disease stage, and metastasis. NAT10 enhanced proliferation, migration, and invasion of GC cells, supported growth of patient-derived organoids, and accelerated tumor development. A C-terminal intrinsically disordered region mediated liquid-liquid phase separation (LLPS) of NAT10 and was essential for its tumor-promoting function in GC. Moreover, NAT10 interacted with the splicing factor SRSF2, leading to its acetylation and increased stability. Acetylated SRSF2 directly bound to the pre-mRNA of the m6A reader YTHDF1, resulting in enhanced YTHDF1 exon 4 skipping and upregulation of a short YTHDF1 transcript that could stimulate GC cell proliferation and migration. Furthermore, YTHDF1 exon 4 skipping correlated with NAT10 and SRSF2 expression and was associated with a more aggressive phenotype in GC patient samples. Together, this study uncovers the role of NAT10 LLPS in modulating YTHDF1 splicing through SRSF2 acetylation to drive GC progression, providing insights into the oncogenic mechanism of NAT10.

Preoperative magnetic resonance imaging-radiomics in cervical cancer: a systematic review and meta-analysis.

Background: The purpose of this systematic review and meta-analysis is to evaluate the potential significance of radiomics, derived from preoperative magnetic resonance imaging (MRI), in detecting deep stromal invasion (DOI), lymphatic vascular space invasion (LVSI) and lymph node metastasis (LNM) in cervical cancer (CC). Methods: A rigorous and systematic evaluation was conducted on radiomics studies pertaining to CC, published in the PubMed database prior to March 2024. The area under the curve (AUC), sensitivity, and specificity of each study were separately extracted to evaluate the performance of preoperative MRI radiomics in predicting DOI, LVSI, and LNM of CC. Results: A total of 4, 7, and 12 studies were included in the meta-analysis of DOI, LVSI, and LNM, respectively. The overall AUC, sensitivity, and specificity of preoperative MRI models in predicting DOI, LVSI, and LNM were 0.90, 0.83 (95% confidence interval [CI], 0.75-0.89) and 0.83 (95% CI, 0.74-0.90); 0.85, 0.80 (95% CI, 0.73-0.86) and 0.75 (95% CI, 0.66-0.82); 0.86, 0.79 (95% CI, 0.74-0.83) and 0.80 (95% CI, 0.77-0.83), respectively. Conclusion: MRI radiomics has demonstrated considerable potential in predicting DOI, LVSI, and LNM in CC, positioning it as a valuable tool for preoperative precision evaluation in CC patients.

Probiotic Lactobacillus rhamnosus GG improves insulin sensitivity and offspring survival via modulation of gut microbiota and serum metabolite in a sow model.

BACKGROUND: Sows commonly experience insulin resistance in late gestation and lactation, causing lower feed intake and milk production, which can lead to higher mortality rates in newborn piglets. The probiotic Lactobacillus rhamnosus GG (LGG) is known to improve insulin resistance. However, whether supplementing LGG can improve insulin sensitivity in sows and enhance lactation performance, particularly the early survival of offspring remains unclear. Hence, we explored the effects and mechanisms of supplementing LGG during late gestation and lactation on sow insulin sensitivity, lactation performance, and offspring survival. In total, 20 sows were randomly allocated to an LGG (n = 10) and control group (n = 10). RESULTS: In sows, LGG supplementation significantly improved insulin sensitivity during late gestation and lactation, increased feed intake, milk production and colostrum lactose levels in early lactation, and enhanced newborn piglet survival. Moreover, LGG treatment significantly reshaped the gut microbiota in sows, notably increasing microbiota diversity and enriching the relative abundance of insulin sensitivity-associated probiotics such as Lactobacillus, Bifidobacterium, and Bacteroides. Serum metabolite and amino acid profiling in late-gestation sows also revealed decreased branched-chain amino acid and kynurenine serum levels following LGG supplementation. Further analyses highlighted a correlation between mitigated insulin resistance in late pregnancy and lactation by LGG and gut microbiota reshaping and changes in serum amino acid metabolism. Furthermore, maternal LGG enhanced immunity in newborn piglets, reduced inflammation, and facilitated the establishment of a gut microbiota. CONCLUSIONS: We provide the first evidence that LGG mitigates insulin resistance in sows and enhances offspring survival by modulating the gut microbiota and amino acid metabolism.

Ginkgolide C attenuated Western diet-induced non-alcoholic fatty liver disease via increasing AMPK activation.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a metabolic dysregulation-related disorder that is generally characterized by lipid metabolism dysfunction and an excessive inflammatory response. Currently, there are no authorized pharmacological interventions specifically designed to manage NASH. It has been reported that Ginkgolide C exhibits anti-inflammatory effects and modulates lipid metabolism. However, the impact and function of Ginkgolide C in diet-induced NASH are unclear. METHODS: In this study, mice were induced by a Western Diet (WD) with different doses of Ginkgolide C with or without Compound C (adenosine 5 '-monophosphate (AMP)-activated protein kinase (AMPK) inhibitor). The effects of Ginkgolide C were evaluated by assessing liver damage, steatosis, fibrosis, and AMPK expression. RESULTS: The results showed that Ginkgolide C significantly alleviated liver damage, steatosis, and fibrosis in the WD-induced mice. In addition, Ginkgolide C markedly improved insulin resistance and attenuated hepatic inflammation. Importantly, Ginkgolide C exerted protective effects by activating the AMPK signaling pathway, which was reversed by AMPK inhibition. CONCLUSION: Ginkgolide C alleviated NASH induced by WD in mice, potentially via activating the AMPK signaling pathway.

Effect of a comprehensive geriatric assessment nursing intervention model on older patients with diabetes and hypertension.

BACKGROUND: The Comprehensive Geriatric Assessment (CGA) was introduced late in China and is primarily used for investigating and evaluating health problems in older adults in outpatient and community settings. However, there are few reports on its application in hospitalized patients, especially older patients with diabetes and hypertension. AIM: To explore the nursing effect of CGA in hospitalized older patients with diabetes and hypertension. METHODS: We performed a retrospective single-center analysis of patients with comorbid diabetes mellitus and hypertension who were hospitalized and treated in the Jiangyin Hospital of Traditional Chinese Medicine between September 2020 and June 2022. Among the 80 patients included, 40 received CGA nursing interventions (study group), while the remaining 40 received routine nursing care (control group). The study group's comprehensive approach included creating personalized CGA profiles, multidisciplinary assessments, and targeted interventions in areas, such as nutrition, medication adherence, exercise, and mental health. However, the control group received standard nursing care, including general and medical history collection, fall prevention measures, and regular patient monitoring. After 6 months of nursing care implementation, we evaluated the effectiveness of the interventions, including assessments of blood glucose levels fasting blood glucose, 2-h postprandial blood glucose, and glycated hemoglobin, type A1c (HbA1c); blood pressure indicators such as diastolic blood pressure (DBP) and systolic blood pressure (SBP); quality of life as measured by the 36-item Short Form Survey (SF-36) questionnaire; and treatment adherence. RESULTS: After 6 months, the nursing outcomes indicated that patients who underwent CGA nursing interventions experienced a significant decrease in blood glucose indicators, such as fasting blood glucose, 2-h postprandial blood glucose, and HbA1c, as well as blood pressure indicators, including DBP and SBP, compared with the control group (P < 0.05). Quality of life assessments, including physical health, emotion, physical function, overall health, and mental health, showed marked improvements compared to the control group (P < 0.05). In the study group, 38 patients adhered to the clinical treatment requirements, whereas only 32 in the control group adhered to the clinical treatment requirements. The probability of treatment adherence among patients receiving CGA nursing interventions was higher than that among patients receiving standard care (95% vs 80%, P < 0.05). CONCLUSION: The CGA nursing intervention significantly improved glycemic control, blood pressure management, and quality of life in hospitalized older patients with diabetes and hypertension, compared to routine care.

Improving iPSC Differentiation Using a Nanodot Platform.

Differentiation of induced pluripotent stem cells (iPSCs) is an extremely complex process that has proven difficult to study. In this research, we utilized nanotopography to elucidate details regarding iPSC differentiation by developing a nanodot platform consisting of nanodot arrays of increasing diameter. Subjecting iPSCs cultured on the nanodot platform to a cardiomyocyte (CM) differentiation protocol revealed several significant gene expression profiles that were associated with poor differentiation. The observed expression trends were used to select existing small-molecule drugs capable of modulating differentiation efficiency. BRD K98 was repurposed to inhibit CM differentiation, while iPSCs treated with NSC-663284, carmofur, and KPT-330 all exhibited significant increases in not only CM marker expression but also spontaneous beating, suggesting improved CM differentiation. In addition, quantitative polymerase chain reaction was performed to determine the gene regulation responsible for modulating differentiation efficiency. Multiple genes involved in extracellular matrix remodeling were correlated with a CM differentiation efficiency, while genes involved in the cell cycle exhibited contrasting expression trends that warrant further studies. The results suggest that expression profiles determined via short time-series expression miner analysis of nanodot-cultured iPSC differentiation can not only reveal drugs capable of enhancing differentiation efficiency but also highlight crucial sets of genes related to processes such as extracellular matrix remodeling and the cell cycle that can be targeted for further investigation. Our findings confirm that the nanodot platform can be used to reveal complex mechanisms behind iPSC differentiation and could be an indispensable tool for optimizing iPSC technology for clinical applications.

Dual-Vacancy-Engineered ZnIn2S4 Nanosheets for Harnessing Low-Frequency Vibration Induced Piezoelectric Polarization Coupled with Static Dipole Field to Enhance Photocatalytic H2 Evolution.

This study investigates the impact of In- and S-vacancy concentrations on the photocatalytic activity of non-centrosymmetric zinc indium sulfide (ZIS) nanosheets for the hydrogen evolution reaction (HER). A positive correlation between the concentrations of dual In and S vacancies and the photocatalytic HER rate over ZIS nanosheets is observed. The piezoelectric polarization, stimulated by low-frequency vortex vibration to ensure the well-dispersion of ZIS nanosheets in solution, plays a crucial role in enhancing photocatalytic HER over the dual-vacancy engineered ZIS nanosheets. The piezoelectric characteristic of the defective ZIS nanosheets is confirmed through the piezopotential response measured using piezoelectric force microscopy. Piezophotocatalytic H2 evolution over the ZIS nanosheets is boosted under accelerated vortex vibrations. The research explores how vacancies alter ZIS's dipole moment and piezoelectric properties, thereby increasing electric potential gradient and improving charge-separation efficiency, through multi-scale simulations, including Density Functional Theory and Finite Element Analysis, and a machine-learning interatomic potential for defect identification. Increased In and S vacancies lead to higher electric potential gradients in ZIS along [100] and [010] directions, attributing to dipole moment and the piezoelectric effect. This research provides a comprehensive exploration of vacancy engineering in ZIS nanosheets, leveraging the piezopotential and dipole field to enhance photocatalytic performances.

Interference of ATP-Adenosine Axis by Engineered Biohybrid for Amplifying Immunogenic Cell Death-Mediated Antitumor Immunotherapy.

Immunogenic cell death (ICD) often results in the production and accumulation of adenosine (ADO), a byproduct that negatively impacts the therapeutic effect as well as facilitates tumor development and metastasis. Here, an innovative strategy is elaborately developed to effectively activate ICD while avoiding the generation of immunosuppressive adenosine. Specifically, ZIF-90, an ATP-responsive consumer, is synthesized as the core carrier to encapsulate AB680 (CD73 inhibitor) and then coated with an iron-polyphenol layer to prepare the ICD inducer (AZTF), which is further grafted onto prebiotic bacteria via the esterification reaction to obtain the engineered biohybrid (Bc@AZTF). Particularly, the designed Bc@AZTF can actively enrich in tumor sites and respond to the acidic tumor microenvironment to offload AZTF nanoparticles, which can consume intracellular ATP (iATP) content and simultaneously inhibit the ATP-adenosine axis to reduce the accumulation of adenosine, thereby alleviating adenosine-mediated immunosuppression and strikingly amplifying ICD effect. Importantly, the synergy of anti-PD-1 (αPD-1) with Bc@AZTF not only establishes a collaborative antitumor immune network to potentiate effective tumoricidal immunity but also activates long-lasting immune memory effects to manage tumor recurrence and rechallenge, presenting a new paradigm for ICD treatment combined with adenosine metabolism.

[Research Progress of Functional Materials for Conversion of Agricultural Biomass Wastes].

Excess agricultural biomass waste is increasing rapidly, leading to many environmental and governance issues. Therefore, increased attention has been paid to the recycling and value-added application of agricultural biomass waste. In recent years, the research of agricultural biomass waste utilization and derived functional materials has mainly included the following two aspects： ① the extraction of natural polymers and value-added applications and ② the direct preparation of new carbon-based materials, including adsorption, catalysis, energy storage electrode, and composite functional materials. The conversion of agricultural biomass waste into functional materials has been gradually realized and widely used. To enable industrial-scale production and the quality and safety of agricultural biomass waste derivatives and to develop highly feasible and cost-effective biomass waste conversion methods should be the focus of future studies.