IFNγ at the early stage induced after cryo-thermal therapy maintains CD4+ Th1-prone differentiation, leading to long-term antitumor immunity.

Introduction: Recently, more and more research illustrated the importance of inducing CD4+ T helper type (Th)-1 dominant immunity for the success of tumor immunotherapy. Our prior studies revealed the crucial role of CD4+ Th1 cells in orchestrating systemic and durable antitumor immunity, which contributes to the satisfactory outcomes of the novel cryo-thermal therapy in the B16F10 tumor model. However, the mechanism for maintaining the cryo-thermal therapy-mediated durable CD4+ Th1-dominant response remains uncovered. Additionally, cryo-thermal-induced early-stage CD4+ Th1-dominant T cell response showed a correlation with the favorable prognosis in patients with colorectal cancer liver metastasis (CRCLM). We hypothesized that CD4+ Th1-dominant differentiation induced during the early stage post cryo-thermal therapy would affect the balance of CD4+ subsets at the late phase. Methods: To understand the role of interferon (IFN)-γ, the major effector of Th1 subsets, in maintaining long-term CD4+ Th1-prone polarization, B16F10 melanoma model was established in this study and a monoclonal antibody was used at the early stage post cryo-thermal therapy for interferon (IFN)-γ signaling blockade, and the influence on the phenotypic and functional change of immune cells was evaluated. Results: IFNγ at the early stage after cryo-thermal therapy maintained long-lasting CD4+ Th1-prone immunity by directly controlling Th17, Tfh, and Tregs polarization, leading to the hyperactivation of Myeloid-derived suppressor cells (MDSCs) represented by abundant interleukin (IL)-1ß generation, and thereby further amplifying Th1 response. Discussion: Our finding emphasized the key role of early-phase IFNγ abundance post cryo-thermal therapy, which could be a biomarker for better prognosis after cryo-thermal therapy.

Freestanding Ammonium Vanadate Composite Cathodes with Lattice Self-Regulation and Ion Exchange for Long-Lasting Ca-Ion Batteries.

Calcium-ion batteries (CIBs) have emerged as a promising alternative for electrochemical energy storage. The lack of high-performance cathode materials severely limits the development of CIBs. Vanadium oxides are particularly attractive as cathode materials for CIBs, and preinsertion chemistry is often used to improve their calcium storage performance. However, the room temperature cycling lifespan of vanadium oxides in organic electrolytes still falls short of 1000 cycles. Here, based on preinsertion chemistry, the cycling life of vanadium oxides is further improved by integrated electrode and electrolyte engineering. Utilizing a tailored Ca electrolyte, the constructed freestanding (NH4)2V6O16·1.35H2O@graphene oxide@carbon nanotube (NHVO-H@GO@CNT) composite cathode achieves a 305 mAh g-1 high capacity and 10 000 cycles record-long life. Additionally, for the first time, a Ca-ion hybrid capacitor full cell is assembled and delivers a capacity of 62.8 mAh g-1. The calcium storage mechanism of NHVO-H@GO@CNT based on a two-phase reaction and the exchange of NH4 + and Ca2+ during cycling are revealed. The lattice self-regulation of V─O layers is observed and the layered vanadium oxides with Ca2+ pillars formed by ion exchange exhibit higher capacity. This work provides novel strategies to enhance the calcium storage performance of vanadium oxides via integrated structural design of electrodes and electrolyte modification.

Impaired Meningeal Lymphatics and Glymphatic Pathway in Patients with White Matter Hyperintensity.

White matter hyperintensity (WMH) represents a critical global medical concern linked to cognitive decline and dementia, yet its underlying mechanisms remain poorly understood. Here, humans are directly demonstrated that high WMH burden correlates with delayed drainage of meningeal lymphatic vessels (mLVs) and glymphatic pathway. Additionally, a longitudinal cohort study reveals that glymphatic dysfunction predicts WMH progression. Next, in a rat model of WMH, the presence of impaired lymphangiogenesis and glymphatic drainage is confirmed, followed by elevated microglial activation and white matter demyelination. Notably, enhancing meningeal lymphangiogenesis through adeno-associated virus delivery of vascular endothelial growth factor-C (VEGF-C) mitigates microglial gliosis and white matter demyelination. Conversely, blocking the growth of mLVs with a VEGF-C trap strategy exacerbates these changes. The findings highlight the role of mLVs and glymphatic pathway dysfunction in aggravating brain white matter injury, providing a potential novel strategy for WMH prevention and treatment.

Natural Killer Cells Reprogram Myeloid-Derived Suppressor Cells to Induce TNF-α Release via NKG2D-Ligand Interaction after Cryo-Thermal Therapy.

In our previous studies, a novel cryothermal therapy (CTT) was developed to induce systemic long-term anti-tumor immunity. Natural killer (NK) cells were found to play an important role in CTT-induced long-term immune-mediated tumor control at the late stage after CTT, but the underlying mechanism is unclear. Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that have potent immunosuppressive effects on T cells and weaken the long-term benefits of immunotherapy. Consequently, overcoming MDSC immunosuppression is essential for maintaining the long-term efficacy of immunotherapy. In this study, we revealed that NK cells considerably diminish MDSC accumulation at the late stage after CTT, boost T cell production, increase T cell activation, and promote MDSC maturation, culminating in Th1-dominant CD4+ T cell differentiation and enhancing NK and CD8+ T cell cytotoxicity. Additionally, NK cells activate ERK signaling in MDSCs through NKG2D-ligand interaction to increase the activity of tumor necrosis factor (TNF)-α converting enzyme (TACE)-cleaved membrane TNF-α. Furthermore, Increased TACE activity releases more soluble TNF-α from MDSCs to promote MDSC maturation. In our studies, we propose a novel mechanism by which NK cells can overcome MDSC-induced immunosuppression and maintain CTT-induced persistent anti-tumor immunity, providing a prospective therapeutic option to improve the performance of cancer immunotherapy.

Surface modifications of short quartz fibers and their influence on the physicochemical properties and in vitro cell viability of dental composites.

OBJECTIVE: Although glass fibers are more common, quartz fibers (QFs) are also considered as the ideal reinforcing material in dentistry, due to their superior mechanical strength, high purity, and good photoconductive properties. However, the relatively inert surfaces limit their further applications. Therefore, the aim of this study is to modify the fiber surface properties to improve the interfacial interactions with polymeric resins. METHODS: In this study, we systematically introduced four different surface modification strategies onto short quartz fibers (SQFs) for the preparation of dental composites. Particularly, the acid etching was a facile way to create mechanical interlocking structures. In addition, the silanization process, the sol-gel treatment, and the polymer grafting were further proposed to increase the surface roughness and the reactive sites. The effect of surface modifications on the fiber surface morphological changes, mechanical properties, water stability, and in vitro cell viability of dental composites were investigated. RESULTS: Among all surface-modified SQFs, SQFs-POSS (SQFs modified with methacrylate-POSS) exhibited the roughest surface morphology and highest grafting rates compared with other three materials. Furthermore, all these SQFs were applied as reinforcements to make dimethacrylate-based dental resin composites. Of all fillers, SQFs-POSS demonstrated the best reinforcing effect, providing significantly higher improvements of 55.7 %, 114.3 %, and 164.7 % for flexural strength, flexural modulus, and breaking energy, respectively, over those of SQFs-filled composite. The related reinforcing mechanism was further investigated. The SQFs-POSS-filled composite also exhibited the best water stability performance and in vitro cell viability. SIGNIFICANCE: This work provided valuable insights into the optimization of filler-matrix interaction through fiber surface modifications. Specifically, SQFs-POSS markedly outperformed other formulations in terms of the physicochemical performance and in vitro cytotoxicity, which offers possibilities for developing high-performance dental composites for clinical applications in restorative dentistry.

Hydronidone induces apoptosis in activated hepatic stellate cells through endoplasmic reticulum stress-associated mitochondrial apoptotic pathway.

BACKGROUND AND AIM: Hydronidone (HDD) is a novel pirfenidone derivative developed initially to reduce hepatotoxicity. Our previous studies in animals and humans have demonstrated that HDD treatment effectively attenuates liver fibrosis, yet the underlying mechanism remains unclear. This study aimed to investigate whether HDD exerts its anti-fibrotic effect by inducing apoptosis in activated hepatic stellate cells (aHSCs) through the endoplasmic reticulum stress (ERS)-associated mitochondrial apoptotic pathway. METHODS: The carbon tetrachloride (CCl4)- and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced liver fibrosis models were used for in vivo studies. In vitro studies were conducted using the human hepatic stellate cell line LX-2. The apoptotic effect of HDD on aHSCs was examined using TUNEL and flow cytometry assays. The small interfering RNA (siRNA) technique was employed to downregulate the expression of interest genes. RESULTS: HDD treatment significantly promoted apoptosis in aHSCs in both the CCl4- and DDC-induced liver fibrosis in mice and LX-2 cells. Mechanistic studies revealed that HDD triggered ERS and subsequently activated the IRE1α-ASK1-JNK pathway. Furthermore, the influx of cytochrome c from the mitochondria into the cytoplasm was increased, leading to mitochondrial dysfunction and ultimately triggering apoptosis in aHSCs. Notably, inhibition of IRE1α or ASK1 by siRNA partially abrogated the pro-apoptotic effect of HDD in aHSCs. CONCLUSIONS: The findings of both in vivo and in vitro studies suggest that HDD induces apoptosis in aHSCs via the ERS-associated mitochondrial apoptotic pathway, potentially contributing to the amelioration of liver fibrosis.

Mitochondrial targeting sequence of magnetoreceptor MagR: More than just targeting.

Iron-sulfur clusters are essential cofactors for proteins involved in various biological processes, such as electron transport, biosynthetic reactions, DNA repair, and gene expression regulation. Iron-sulfur cluster assembly protein IscA1 (or MagR) is found within the mitochondria of most eukaryotes. Magnetoreceptor (MagR) is a highly conserved A-type iron and iron-sulfur cluster-binding protein, characterized by two distinct types of iron-sulfur clusters, [2Fe-2S] and [3Fe-4S], each conferring unique magnetic properties. MagR forms a rod-like polymer structure in complex with photoreceptive cryptochrome (Cry) and serves as a putative magnetoreceptor for retrieving geomagnetic information in animal navigation. Although the N-terminal sequences of MagR vary among species, their specific function remains unknown. In the present study, we found that the N-terminal sequences of pigeon MagR, previously thought to serve as a mitochondrial targeting signal (MTS), were not cleaved following mitochondrial entry but instead modulated the efficiency with which iron-sulfur clusters and irons are bound. Moreover, the N-terminal region of MagR was required for the formation of a stable MagR/Cry complex. Thus, the N-terminal sequences in pigeon MagR fulfil more important functional roles than just mitochondrial targeting. These results further extend our understanding of the function of MagR and provide new insights into the origin of magnetoreception from an evolutionary perspective.

Acetaminophen overdose-induced acute liver injury can be alleviated by static magnetic field.

Acetaminophen (APAP), the most frequently used mild analgesic and antipyretic drug worldwide, is implicated in causing 46% of all acute liver failures in the USA and between 40% and 70% in Europe. The predominant pharmacological intervention approved for mitigating such overdose is the antioxidant N-acetylcysteine (NAC); however, its efficacy is limited in cases of advanced liver injury or when administered at a late stage. In the current study, we discovered that treatment with a moderate intensity static magnetic field (SMF) notably reduced the mortality rate in mice subjected to high-dose APAP from 40% to 0%, proving effective at both the initial liver injury stage and the subsequent recovery stage. During the early phase of liver injury, SMF markedly reduced APAP-induced oxidative stress, free radicals, and liver damage, resulting in a reduction in multiple oxidative stress markers and an increase in the antioxidant glutathione (GSH). During the later stage of liver recovery, application of vertically downward SMF increased DNA synthesis and hepatocyte proliferation. Moreover, the combination of NAC and SMF significantly mitigated liver damage induced by high-dose APAP and increased liver recovery, even 24 h post overdose, when the effectiveness of NAC alone substantially declines. Overall, this study provides a non-invasive non-pharmaceutical tool that offers dual benefits in the injury and repair stages following APAP overdose. Of note, this tool can work as an alternative to or in combination with NAC to prevent or minimize liver damage induced by APAP, and potentially other toxic overdoses.

Low Expression MCEMP1 Promoting Lung Adenocarcinoma Progression by and its Clinical Value.

BACKGROUND: Lung cancer is a highly prevalent tumor with a lack of biological markers that reflect its progression. Mast cell surface membrane protein 1 (MCEMP1, also known as C19ORF59) has not been reported in lung adenocarcinoma (LUAD). OBJECTIVE: We aimed to investigate the role of MCEMP1 in LUAD. METHODS: MCEMP1 expression in LUAD was analyzed using The Cancer Genome Atlas (TCGA) data, and conducted univariate and multivariate Cox regression analyses to evaluate the prognostic significance of MCEMP1 expression in TCGA. Tumor Immune Estimation Resource (TIMER) was used for examining the correlation between MCEMP1 expression and immune cell infiltration in LUAD. Furthermore, proliferation, migration, invasion, and colony-forming ability were investigated using LUAD cell lines. RESULTS: MCEMP1 had low expression in LUAD patient tissues and was correlated with lymph node metastasis, differentiation level, and tumor status. The Area under Curve (AUC) value of MCEMP1 for the Receiver Operating Characteristic (ROC) curve analysis was 0.984. The immune infiltration analysis revealed a correlation between MCEMP1 expression and the extent of macrophages and neutrophil infiltration in LUAD. Additionally, MCEMP1 has low expression in clinical samples, MCEMP1 overexpressed in LUAD cells substantially reduced cell growth, migration, and invasion of malignant cells. CONCLUSION: Low expression MCEMP1 promotes LUAD progression, which provides new insights and a potential biological target for future LUAD therapies.

Mucin alleviates colonic barrier dysfunction by promoting spermine accumulation through enhanced arginine metabolism in Limosilactobacillus mucosae.

Dietary fiber deprivation is linked to probiotic extinction, mucus barrier dysbiosis, and the overgrowth of mucin-degrading bacteria. However, whether and how mucin could rescue fiber deprivation-induced intestinal barrier defects remains largely unexplored. Here, we sought to investigate the potential role and mechanism by which exogenous mucin maintains the gut barrier function. The results showed that dietary mucin alleviated fiber deprivation-induced disruption of colonic barrier integrity and reduced spermine production in vivo. Importantly, we highlighted that microbial-derived spermine production, but not host-produced spermine, increased significantly after mucin supplementation, with a positive association with upgraded colonic Lactobacillus abundance. After employing an in vitro model, the microbial-derived spermine was consistently dominated by both mucin and Lactobacillus spp. Furthermore, Limosilactobacillus mucosae was identified as an essential spermine-producing Lactobacillus spp., and this isolated strain was responsible for spermine accumulation, especially after adhering to mucin in vitro. Specifically, the mucin-supplemented bacterial supernatant of Limosilactobacillus mucosae was verified to promote intestinal barrier functions through the increased spermine production with a dependence on enhanced arginine metabolism. Overall, these findings collectively provide evidence that mucin-modulated microbial arginine metabolism bridged the interplay between microbes and gut barrier function, illustrating possible implications for host gut health. IMPORTANCE: Microbial metabolites like short-chain fatty acids produced by dietary fiber fermentation have been demonstrated to have beneficial effects on intestinal health. However, it is essential to acknowledge that certain amino acids entering the colon can be metabolized by microorganisms to produce polyamines. The polyamines can promote the renewal of intestinal epithelial cell and maintain host-microbe homeostasis. Our study highlighted the specific enrichment by mucin on promoting the arginine metabolism in Limosilactobacillus mucosae to produce spermine, suggesting that microbial-derived polyamines support a significant enhancement on the goblet cell proliferation and barrier function.

Inhibition of NKCC1 Ameliorates Anxiety and Autistic Behaviors Induced by Maternal Immune Activation in Mice.

Autism spectrum disorder (ASD) is thought to result from susceptibility genotypes and environmental risk factors. The offspring of women who experience pregnancy infection have an increased risk for autism. Maternal immune activation (MIA) in pregnant animals produces offspring with autistic behaviors, making MIA a useful model for autism. However, how MIA causes autistic behaviors in offspring is not fully understood. Here, we show that NKCC1 is critical for mediating autistic behaviors in MIA offspring. We confirmed that MIA induced by poly(I:C) infection during pregnancy leads to autistic behaviors in offspring. We further demonstrated that MIA offspring showed significant microglia activation, excessive dendritic spines, and narrow postsynaptic density (PSD) in their prefrontal cortex (PFC). Then, we discovered that these abnormalities may be caused by overexpression of NKCC1 in MIA offspring's PFCs. Finally, we ameliorated the autistic behaviors using PFC microinjection of NKCC1 inhibitor bumetanide (BTN) in MIA offspring. Our findings may shed new light on the pathological mechanisms for autism caused by pregnancy infection.

Pigment epithelium­derived factor inhibits proliferation, invasion and angiogenesis, and induces ferroptosis of extravillous trophoblasts by targeting Wnt­ß­catenin/VEGF signaling in placenta accreta spectrum.

Placenta accreta spectrum (PAS) is one of the most dangerous complications in obstetrics, which can lead to severe postpartum bleeding and shock, and even necessitate uterine removal. The abnormal migration and invasion of extravillous trophoblast cells (EVTs) and enhanced neovascularization occurring in an uncontrolled manner in time and space are closely related to the abnormal expression of pro­angiogenic and anti­angiogenic factors. The pigment epithelium­derived factor (PEDF) is a multifunctional regulatory factor that participates in several important biological processes and is recognized as the most efficient inhibitor of angiogenesis. The present study aimed to explore the effects of PEDF on EVT phenotypes and the underlying mechanisms in PAS. HTR­8/SVneo cells were transfected to overexpress or knock down PEDF. Cell proliferation and invasion were assessed using Cell Counting Kit­8, 5­ethynyl­2'­deoxyuridine and Transwell assays. In vitro angiogenesis was analyzed using tube formation assays. The degree of ferroptosis was assessed by evaluating the levels of lipid reactive oxygen species, total iron, Fe2+, malondialdehyde and reduced glutathione using commercial kits. The expression levels of biomarkers of ferroptosis, angiogenesis, cell proliferation and Wnt signaling were examined by western blotting. PEDF overexpression decreased the proliferation, invasion and angiogenesis, and induced ferroptosis of EVTs. Activation of Wnt signaling with BML­284 and overexpression of vascular endothelial growth factor (VEGF) reversed the PEDF overexpression­induced suppression of cell proliferation, invasion and tube formation. PEDF overexpression­induced ferroptosis was also decreased by Wnt agonist treatment and VEGF overexpression. It was predicted that PEDF suppressed the proliferation, invasion and angiogenesis, and increased ferroptosis in EVTs by decreasing Wnt­ß­catenin/VEGF signaling. The findings of the present study suggested a novel regulatory mechanism of the phenotypes of EVTs and PAS.

Parametric analysis of the transmission dynamics during indigenous aggregated outbreaks caused by five SARS-CoV-2 strains in Nanjing, China.

Background: SARS-CoV-2 strains have been of great concern due to their high infectivity and antibody evasion. Methods: In this study, data were collected on indigenous aggregated outbreaks in Nanjing from January 2020 to December 2022, caused by five strains including the original strain, the Delta variant, and the Omicron variant (BA.2, BA.5.2, and BF.7). The basic epidemiological characteristics of infected individuals were described and then parametric analysis of transmission dynamics was performed, including the calculation of incubation period, serial interval (SI), the basic reproductive number (R0), and the household secondary attack rate (HSAR). Finally, we compared the trends of transmission dynamic parameters of different strains. Results: The incubation period for the original strain, the Delta variant, Omicron BA.2, Omicron BA.5.2, and Omicron BF.7 were 6 d (95% CI: 3.5-7.5 d), 5 d (95% CI: 4.0-6.0 d), 3 d (95% CI: 3.0-4.0 d), 3 d (95% CI: 3.0-3.0 d), and 2 d (95% CI: 2.0-3.0 d), respectively; Also, the SI of the five strains were 5.69 d, 4.79 d, 2.7 d, 2.12 d, and 2.43 d, respectively. Notably, the incubation period and SI of the five had both a progressive shortening trend (p < 0.001); Moreover, R0 of the five were 2.39 (95% CI: 1.30-4.29), 3.73 (95% CI: 2.66-5.15), 5.28 (95% CI: 3.52-8.10), 5.54 (95% CI: 2.69-11.17), 7.39 (95% CI: 2.97-18.76), with an increasing trend gradually (p < 0.01); HSAR of the five were 25.5% (95% CI: 20.1-31.7%), 27.4% (95% CI: 22.0-33.4%), 42.9% (95% CI: 34.3-51.8%), 53.1% (95% CI: 45.0-60.9%), 41.4% (95% CI, 25.5-59.3%), also with an increasing trend (p < 0.001). Conclusion: Compared to the original strain, the incubation period and SI decreased while R0 and HSAR increased, suggesting that transmission in the population was faster and the scope of the population was wider. Overall, it's crucial to keep implementing comprehensive measures like monitoring and alert systems, herd immunization plans, and outbreak control.

Diagnostic Efficacy of a Novel Rotating Brush for Endoscopic Sampling of Malignant Biliary Strictures: A Multicenter Prospective Study.

INTRODUCTION: Although cytologic examination of biliary stricture brushings obtained by endoscopic retrograde cholangiopancreatography is commonly used for diagnosing malignant biliary strictures (MBSs), it has low sensitivity. Several new brushes have capabilities that are still being debated. We have developed a novel brush working from conventional back-and-forth movement to rotation in situ (RIS) that may be more efficient for MBS sampling. We aimed to compare the MBS detection sensitivity of our RIS brush with that of the conventional brush. METHODS: In this multicenter prospective study, we enrolled patients who underwent endoscopic retrograde cholangiopancreatography for suspected MBSs involving biliary stricture brushings obtained using our RIS brush. The historical control group consisted of the 30-brushing arm of our previous randomized trial (patient inclusion, 2018-2020) that used the study design in the same centers and with the same endoscopists as were used in this study. The primary outcome was to compare the sensitivity and specificity of detecting MBSs by cytologic evaluation of biliary stricture brushings between the 2 groups. RESULTS: We enrolled 155 patients in the intent-to-treat analysis. Using the same number of brushing cycles, the RIS brush showed a higher sensitivity than the conventional brush (0.73 vs 0.56, P = 0.003). In per-protocol population, the sensitivity was also higher in the RIS brush group than in the conventional brush group (0.75 vs 0.57, P = 0.002). Multivariate analysis revealed that the RIS brush was the only predictive factor for MBS detection. No significant differences were observed in procedure-related complications between the 2 groups. DISCUSSION: The RIS brush was a promising tool for effective and safe MBS sampling and diagnosis. Further randomized studies are warranted to confirm our results (Chictr.org.cn, identifier: ChiCTR2100047270).

The RNA m6A reader IGF2BP3 regulates NFAT1/IRF1 axis-mediated anti-tumor activity in gastric cancer.

N6-methyladenosine (m6A) and its associated reader protein insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) are involved in tumor initiation and progression via regulating RNA metabolism. This study aims to investigate the biological function and clinical significance of IGF2BP3 in gastric cancer (GC). The clinical significance of IGF2BP3 was evaluated using tumor related databases and clinical tissues. The biological role and molecular mechanism of IGF2BP3 in GC progression were investigated by multi-omics analysis including Ribosome sequence (Ribo-seq), RNA sequence (RNA-seq) and m6A sequence (m6A-seq) combined with gain- and loss- of function experiments. IGF2BP3 expression is significantly elevated in GC tissues and associated with poor prognosis of GC patients. Knockdown of IGF2BP3 significantly weakens the migration and clonogenic ability, promotes the apoptosis, inhibits translation, and suppresses in vitro growth and progression of GC cells. Mechanistically, IGF2BP3 regulates the mRNA stability and translation of the nuclear factor of activated T cells 1(NFAT1) in a m6A dependent manner. Then NFAT1 induced by IGF2BP3 acts as a transcription factor (TF) to negatively regulates the promoter activities of interferon regulatory factor 1 (IRF1) to inhibit its expression. Inhibition of IGF2BP3-induced expression of IRF1 activates interferon (IFN) signaling pathway and then exerts its anti-tumor effect. Elevated IGF2BP3 promotes in vivo and in vitro GC progression via regulation of NFAT1/IRF1 pathways. Targeted inhibition of IGF2BP3 might be a potential therapeutic approach for GC treatment.

Precisely modulating the chromatin tracker via substituent engineering: reporting pathological oxidative stress during mitosis.

An in-depth understanding of cancer-cell mitosis presents unprecedented advantages for solving metastasis and proliferation of tumors, which has aroused great interest in visualizing the behavior via a luminescence tool. We developed a fluorescent molecule CBTZ-yne based on substituent engineering to acquire befitting lipophilicity and electrophilicity for anchoring lipid droplets and the nucleus, in which the low polarity environment and nucleic acids triggered a "weak-strong" fluorescence and "short-long" fluorescence-lifetime response. Meaningfully, CBTZ-yne visualized chromatin condensation, alignment, pull-push, and separation as well as lipid droplet dynamics, for the first time, precisely unveiling the asynchronous cellular mitosis processes affected by photo-generation reactive oxygen species according to the subtle change of fluorescence-lifetime. Our work suggested a new guideline for tracking the issue of the proliferation of malignant tumors in photodynamic therapy.

The application of protease in aquaculture: Prospects for enhancing the aquafeed industry.

Low-fishmeal and protein-saving diets are two prominent nutritional strategies utilized to address challenges related to the scarcity and sustainability of protein sources in aquaculture. However, these diets have been associated with adverse effects on the growth performance, feed utilization, and disease resistance of aquatic animals. To mitigate these challenges, exogenous protease has been applied to enhance the quality of diets with lower protein contents or fishmeal alternatives, thereby improving the bioavailability of nutritional ingredients. Additionally, protease preparations were also used to enzymatically hydrolyze fishmeal alternatives, thus enhancing their nutritional utilization. The present review aims to consolidate recent research progress on the use of protease in aquaculture and conclude the benefits and limitations of its application, thereby providing a comprehensive understanding of the subject and identifying opportunities for future research.

Maternal fiber-rich diet promotes early-life intestinal development in offspring through milk-derived extracellular vesicles carrying miR-146a-5p.

BACKGROUNDS: The intestinal development in early life is profoundly influenced by multiple biological components of breast milk, in which milk-derived extracellular vesicles (mEVs) contain a large amount of vertically transmitted signal from the mother. However, little is known about how maternal fiber-rich diet regulates offspring intestinal development by influencing the mEVs. RESULTS: In this study, we found that maternal resistant starch (RS) consumption during late gestation and lactation improved the growth and intestinal health of offspring. The mEVs in breast milk are the primary factor driving these beneficial effects, especially enhancing intestinal cell proliferation and migration. To be specific, administration of mEVs after maternal RS intake enhanced intestinal cell proliferation and migration in vivo (performed in mice model and indicated by intestinal histological observation, EdU assay, and the quantification of cyclin proteins) and in vitro (indicated by CCK8, MTT, EdU, and wound healing experiments). Noteworthily, miR-146a-5p was found to be highly expressed in the mEVs from maternal RS group, which also promotes intestinal cell proliferation in cells and mice models. Mechanically, miR-146a-5p target to silence the expression of ubiquitin ligase 3 gene NEDD4L, thereby inhibiting DVL2 ubiquitination, activating the Wnt pathway, and promoting intestinal development. CONCLUSION: These findings demonstrated the beneficial role of mEVs in the connection between maternal fiber rich diet and offspring intestinal growth. In addition, we identified a novel miRNA-146a-5p-NEDD4L-ß-catenin/Wnt signaling axis in regulating early intestinal development. This work provided a new perspective for studying the influence of maternal diet on offspring development.