The emerging role of regulated cell death in ischemia and reperfusion-induced acute kidney injury: current evidence and future perspectives.

Renal ischemia‒reperfusion injury (IRI) is one of the main causes of acute kidney injury (AKI), which is a potentially life-threatening condition with a high mortality rate. IRI is a complex process involving multiple underlying mechanisms and pathways of cell injury and dysfunction. Additionally, various types of cell death have been linked to IRI, including necroptosis, apoptosis, pyroptosis, and ferroptosis. These processes operate differently and to varying degrees in different patients, but each plays a role in the various pathological conditions of AKI. Advances in understanding the underlying pathophysiology will lead to the development of new therapeutic approaches that hold promise for improving outcomes for patients with AKI. This review provides an overview of the recent research on the molecular mechanisms and pathways underlying IRI-AKI, with a focus on regulated cell death (RCD) forms such as necroptosis, pyroptosis, and ferroptosis. Overall, targeting RCD shows promise as a potential approach to treating IRI-AKI.

Unilateral pulmonary edema after minimally-invasive bentall procedure - Case report.

Introduction: Unilateral pulmonary edema (UPE), a life-threatening complication of cardiac surgery, often occurs after prolonged cardiopulmonary bypass and lung collapse, especially in minimally-invasive cardiac surgery (MICS). The present study reported a young patient with severe UPE after the surgery as well as corresponding clinical treatments. In addition to the supportive treatment of extracorporeal membrane oxygenation (ECMO), monitoring changes in cardiopulmonary function and early clinical interventions are crucial. Conclusion: By weighing the beneficial and detrimental effects of the treatment, it calls for early diagnosis and new therapeutic strategies for the complication.

Enhanced MRI Radiomics Based Model for Predicting Recurrence or Metastasis of Nasopharyngeal Cancer (NC) Undergoing Concurrent Chemoradiotherapy: A Retrospective Study.

Nasopharyngeal Carcinoma (NC) refers to the malignant tumor that occurs at the top and side walls of the nasopharyngeal cavity. The NC incidence rate always dominates the first among the malignant tumors of the ear, nose and throat, and mainly occurs in Asia. NC cases are mainly concentrated in southern provinces in China, with about 4 million existing NC. With the pollution of environment and pickled diet, and the increase of life pressure, the domestic NC incidence rate has reached 4.5-6.5/100000 and is increasing year by year. It was reported that the known main causes of NC include hereditary factor, genetic mutations, and EB virus infection, common clinical symptoms of NC include nasal congestion, bloody mucus, etc. About 90% of NC is highly sensitive to radiotherapy which is regard as the preferred treatment method; However, for NC with lower differentiation, larger volume, and recurrence after treatment, surgical resection and local protons and heavy ions therapy are also indispensable means. According to reports, the subtle heterogeneity and diversity exists in some NC, with about 80% of NC undergone radiotherapy and about 25% experienced recurrence and death within five years after radiotherapy in China. Therefore, screening the NC population with suspected recurrence after concurrent chemoradiotherapy may improve survival rates in current clinical decision-making.

NC is one of the prevalent malignancies of the head and neck region with poor prognosis. The aim of this study is to establish a predictive model for assessing NC prognosis using clinical and MR radiomics data.

Fungal fermentation of Fuzhuan brick tea: A comprehensive evaluation of sensory properties using chemometrics, visible near-infrared spectroscopy, and electronic nose.

Fuzhuan brick tea (FBT) fungal fermentation is a key factor in achieving its unique dark color, aroma, and taste. Therefore, it is essential to develop a rapid and reliable method that could assess its quality during FBT fermentation process. This study focused on using electronic nose (e-nose) and spectroscopy combination with sensory evaluations and physicochemical measurements for building machine learning (ML) models of FBT. The results showed that the fused data achieved 100 % accuracy in classifying the FBT fermentation process. The SPA-MLR method was the best prediction model for FBT quality (R2 = 0.95, RMSEP = 0.07, RPD = 4.23), and the fermentation process was visualized. Where, it was effectively detecting the degree of fermentation relationship with the quality characteristics. In conclusion, the current study's novelty comes from the established real-time method that could sensitively detect the unique post-fermentation quality components based on the integration of spectral, and e-nose and ML approaches.

The regulation and potential role of interleukin-32 in tuberculous pleural effusion.

The possible protective effect of interleukin-32 (IL-32) in Mycobacterium tuberculosis (Mtb) infection has been indicated. However, few studies have been focused on IL-32 in tuberculosis patients. Additionally, the regulation of IL-32 production has rarely been reported. In the present study, the production, regulation, and role of IL-32 in tuberculous pleurisy (TBP) were investigated. We found that the content of IL-32 in tuberculous pleural effusion (TPE) was higher than the level in the malignant pleural effusion and transudative pleural effusion. The level of IL-32 mRNA in pleural fluid mononuclear cells (PFMCs) was higher than that in peripheral blood mononuclear cells (PBMCs) of patients with TBP, and this difference was mainly reflected in the splice variants of IL-32α, IL-32ß, and IL-32γ. Compared with the PBMCs, PFMCs featured higher IL-32ß/IL-32γ and IL-32α/IL-32γ ratios. In addition, lipopolysaccharide (LPS), Bacillus Calmette-Guérin (BCG), and H37Ra stimulation could induce IL-32 production in the PFMCs. IL-32 production was positively correlated with the TNF-α, IFN-γ, and IL-1Ra levels in TPE, whereas IFN-γ, but not TNF-α or IL-1Ra, could induce the production of IL-32 in PFMCs. Furthermore, IL-32γ could induce the TNF-α production in PFMCs. Monocytes and macrophages were the main sources of IL-32 in PFMCs. Nevertheless, direct cell-cell contact between lymphocytes and monocytes/macrophages plays an important role in enhancing IL-32 production by monocyte/macrophage cells. Finally, compared with the non-tuberculous pleural effusion, the purified CD4+ and CD8+ T cells in TPE expressed higher levels of intracellular IL-32. Our results suggested that, as a potential biomarker, IL-32 may play an essential role in the protection against Mtb infection in patients with TBP. However, further studies need to be carried out to clarify the functions and mechanisms of the IFN-γ/IL-32/TNF-α axis in patients with TBP.

SARS-CoV-2 Antibodies in Human Milk After mRNA and Adenovector-Based Vaccination: A Systematic Review and Meta-Analysis.

BACKGROUND: SARS-CoV-2 specific antibodies exist in human milk expressed by lactating parents after vaccination. In the existing research, the effects of vaccine types on human milk are inconsistent. RESEARCH AIM: This study aims to perform a systematic review and meta-analysis of the existing observational studies to compare the positive rates of SARS-CoV-2 specific antibodies in human milk according to mRNA and adenovector-based vaccination. METHODS: PubMed, Web of Science, Elsevier Science Direct and Cochrane Library databases were systematically searched for relevant articles published from December 30, 2019 to February 15, 2023. Observational studies were considered eligible provided they reported data on SARS-CoV-2 specific antibodies in human milk. The risk of bias in non-randomized studies of interventions (ROBINS-I) tool, the Newcastle-Ottawa Scale (NOS), and the Agency for Healthcare Research and Quality (AHRQ) were used to assess risk of bias. Seven studies, including 511 lactating participants, were included in this review and meta-analysis. RESULTS: The positive rate of SARS-CoV-2 IgA is higher in mRNA vaccine groups than in adenovector-based vaccine groups (OR = 4.80, 95% CI [3.04, 7.58], p < 0.001). The positive rate of SARS-CoV-2 IgG was higher in mRNA vaccines than in adenovector-based vaccines. CONCLUSIONS: Compared to adenovector-based vaccines, mRNA vaccines present a higher positivity rate of IgA and IgG in human milk after vaccination. In other words, mRNA vaccinations may offer breastfed children a higher level of protection than adenovector-based vaccinations. Further high-quality data is still required to substantiate these findings.

Evaluation of MeltPro Assay in Identification of Second-Line Injectable Drug Resistance in Multidrug-Resistant Tuberculosis Isolates.

Objective: We compared the MeltPro assay to whole-genome sequencing (WGS) to investigate the molecular characterization of second-line injectable drug (SLID) resistance in multidrug-resistant tuberculosis (MDR-TB) isolates in Chongqing, China. Methods: A total of 122 MDR-TB patient isolates were collected between March 2019 and June 2020 from Chongqing Municipality, China. Conventional drug-susceptibility testing was performed using the proportion method, followed to generate minimum inhibitory concentrations (MICs) of SLIDs determined by microplate alamarblue assay. All strains were subjected to both MeltPro and WGS assays. Results: Among 122 MDR-TB isolates, 30 (24.6%), 22 (18.0%), and 14 (11.5%) were resistant to kanamycin (KM), amikacin (AM), and capreomycin (CM), respectively. Of the 31 SLID-resistant isolates, 24 (77.4%, 24/31) isolates harbored mutations in the rrs gene, with the most prevalent mutations in rrs A1401G (22/24, 91.7%). Mutation in rrs A1401G was associated with high levels of resistance to KM (MIC, ≥40 µg/mL) and AM (MIC, ≥64 µg/mL), but disparities in CM-resistance levels. Using phenotypic drug-susceptibility testing as gold standard, we found that the overall sensitivity of MeltPro and WGS was 87.1% and 90.32% and specificity 100% and 97.8%, respectively. Seven isolates had discordant results between phenotypic and genotypic resistance of SLIDs. Conclusion: MeltPro is a promising diagnostic tool for accurate identification of SLID-resistant MTB isolates with mutations in the rrs and eis genes. There was a disparity between MeltPro with WGS results in the proportion of heterogeneous drug-resistant bacteria with rrs mutation and limited probes. Resistance mechanisms other than genetic mutations will affect the consistency of MeltPro and WGS with phenotypic drug-susceptibility results.

MyD88 and Its Inhibitors in Cancer: Prospects and Challenges.

The interplay between the immune system and cancer underscores the central role of immunotherapy in cancer treatment. In this context, the innate immune system plays a critical role in preventing tumor invasion. Myeloid differentiation factor 88 (MyD88) is crucial for innate immunity, and activation of MyD88 promotes the production of inflammatory cytokines and induces infiltration, polarization, and immune escape of immune cells in the tumor microenvironment. Additionally, abnormal MyD88 signaling induces tumor cell proliferation and metastasis, which are closely associated with poor prognosis. Therefore, MyD88 could serve as a novel tumor biomarker and is a promising target for cancer therapy. Current strategies targeting MyD88 including inhibition of signaling pathways and protein multimerization, have made substantial progress, especially in inflammatory diseases and chronic inflammation-induced cancers. However, the specific role of MyD88 in regulating tumor immunity and tumorigenic mechanisms remains unclear. Therefore, this review describes the involvement of MyD88 in tumor immune escape and disease therapy. In addition, classical and non-classical MyD88 inhibitors were collated to provide insights into potential cancer treatment strategies. Despite several challenges and complexities, targeting MyD88 is a promising avenue for improving cancer treatment and has the potential to revolutionize patient outcomes.

Genomic insights into local adaptation of upland cotton in China and Pakistan.

KEY MESSAGE: Different kinship and resistance to cotton leaf curl disease (CLCuD) and heat were found between upland cotton cultivars from China and Pakistan. 175 SNPs and 82 InDels loci related to yield, fiber quality, CLCuD, and heat resistance were identified. Elite alleles found in Pakistani accessions aided local adaptation to climatic condition of two countries. Adaptation of upland cotton (Gossypium hirsutum) beyond its center of origin is expected to be driven by tailoring of the genome and genes to enhance yield and quality in new ecological niches. Here, resequencing of 456 upland cotton accessions revealed two distinct kinships according to the associated country. Fiber quality and lint percentage were consistent across kinships, but resistance to cotton leaf curl disease (CLCuD) and heat was distinctly exhibited by accessions from Pakistan, illustrating highly local adaption. A total of 175 SNP and 82 InDel loci related to yield, fiber quality, CLCuD and heat resistance were identified; among them, only two overlapped between Pakistani and Chinese accessions underscoring the divergent domestication and improvement targets in each country. Loci associated with resistance alleles to leaf curl disease and high temperature were largely found in Pakistani accessions to counter these stresses prevalent in Pakistan. These results revealed that breeding activities led to the accumulation of unique alleles and helped upland cotton become adapted to the respective climatic conditions, which will contribute to elucidating the genetic mechanisms that underlie resilience traits and help develop climate-resilient cotton cultivars for use worldwide.

Streptomyces virginiae XDS1-5, an antagonistic actinomycete, as a biocontrol to peach brown rot caused by Monilinia fructicola.

BACKGROUND: Peach brown rot, caused by the pathogen Monilinia fructicola, represents a significant postharvest infectious disease affecting peach fruit. This disease is responsible for a substantial increase in fruit decay rates, leading to significant economic losses, often exceeding 50%. Currently, there is a growing interest in identifying biocontrol agents to mitigate peach brown rot, with a predominant interest in Bacillus species. RESULTS: In this investigation, we isolated 410 isolates of actinomycetes from non-farmland ecosystem soil samples. Subsequently, 27 isolates exhibiting superior inhibitory capabilities were selected. Among these, strain XDS1-5 demonstrated the most robust fungistatic effect against brown rot disease, achieving an 80% inhibition rate in vitro and a 66% inhibition rate in vivo. XDS1-5 was identified as belonging to the Streptomyces virginiae species. Furthermore, a fermentation filtrate of XDS1-5 exhibited the ability to metabolize 34.21% of the tested carbon sources and 7.37% of the tested nitrogen sources. Particularly noteworthy was its capacity to disrupt the cell membrane structure directly, leading to increased cell membrane permeability and cytoplasmic leakage. Additionally, our investigation indicated that indoline, a metabolite produced by XDS1-5, played a pivotal role in inhibiting the growth of M. fructicola. CONCLUSION: In summary, our study has identified a biocontrol actinomycete, XDS1-5, with the potential to effectively inhibit postharvest brown rot disease in peaches. This finding holds great significance for the biological control of peach brown rot, offering promising prospects for mitigating the economic losses associated with this devastating disease. © 2024 Society of Chemical Industry.

UDP-glucosyltransferase 71C4 controls the flux of phenylpropanoid metabolism to shape cotton seed development.

Seeds play a crucial role in plant reproduction, making it essential to identify genes that affect seed development. In this study, we focused on UDP-glucosyltransferase 71C4 (UGT71C4) in cotton, a member of the glycosyltransferase family that shapes seed width, length, and therefore, seed index and seed cotton yield. Overexpression of UGT71C4 results in seed enlargement due to its glycosyltransferase activity on flavonoids, which redirects metabolic flux from lignin to flavonoid metabolism. This shift promotes cell proliferation of ovule via accumulation of flavonoid glycoside, significantly enhancing seed cotton yield with the seed index increasing from 10.66 g to 11.91 g. In contrast, knockout of UGT71C4 leads to smaller seeds owing to activation of the lignin metabolism pathway, and redirection of metabolic flux back to lignin synthesis. This redirection leads to increased ectopic lignin deposition in the ovule, inhibiting ovule growth and development, and alters yield component, increasing the lint percentage from 41.42% to 43.40% but reducing the seed index from 10.66 g to 8.60 g. Our research sheds new light on seed size development and opens potential pathways for enhancing plant seed yield.

A hybrid deep learning scheme for MRI-based preliminary multiclassification diagnosis of primary brain tumors.

Objectives: The diagnosis and treatment of brain tumors have greatly benefited from extensive research in traditional radiomics, leading to improved efficiency for clinicians. With the rapid development of cutting-edge technologies, especially deep learning, further improvements in accuracy and automation are expected. In this study, we explored a hybrid deep learning scheme that integrates several advanced techniques to achieve reliable diagnosis of primary brain tumors with enhanced classification performance and interpretability. Methods: This study retrospectively included 230 patients with primary brain tumors, including 97 meningiomas, 66 gliomas and 67 pituitary tumors, from the First Affiliated Hospital of Yangtze University. The effectiveness of the proposed scheme was validated by the included data and a commonly used data. Based on super-resolution reconstruction and dynamic learning rate annealing strategies, we compared the classification results of several deep learning models. The multi-classification performance was further improved by combining feature transfer and machine learning. Classification performance metrics included accuracy (ACC), area under the curve (AUC), sensitivity (SEN), and specificity (SPE). Results: In the deep learning tests conducted on two datasets, the DenseNet121 model achieved the highest classification performance, with five-test accuracies of 0.989 ± 0.006 and 0.967 ± 0.013, and AUCs of 0.999 ± 0.001 and 0.994 ± 0.005, respectively. In the hybrid deep learning tests, LightGBM, a promising classifier, achieved accuracies of 0.989 and 0.984, which were improved from the original deep learning scheme of 0.987 and 0.965. Sensitivities for both datasets were 0.985, specificities were 0.988 and 0.984, respectively, and relatively desirable receiver operating characteristic (ROC) curves were obtained. In addition, model visualization studies further verified the reliability and interpretability of the results. Conclusions: These results illustrated that deep learning models combining several advanced technologies can reliably improve the performance, automation, and interpretability of primary brain tumor diagnosis, which is crucial for further brain tumor diagnostic research and individualized treatment.

Comparative transcriptomic analysis provides insights into the genetic networks regulating oil differential production in oil crops.

BACKGROUND: Plants differ more than threefold in seed oil contents (SOCs). Soybean (Glycine max), cotton (Gossypium hirsutum), rapeseed (Brassica napus), and sesame (Sesamum indicum) are four important oil crops with markedly different SOCs and fatty acid compositions. RESULTS: Compared to grain crops like maize and rice, expanded acyl-lipid metabolism genes and relatively higher expression levels of genes involved in seed oil synthesis (SOS) in the oil crops contributed to the oil accumulation in seeds. Here, we conducted comparative transcriptomics on oil crops with two different SOC materials. In common, DIHYDROLIPOAMIDE DEHYDROGENASE, STEAROYL-ACYL CARRIER PROTEIN DESATURASE, PHOSPHOLIPID:DIACYLGLYCEROL ACYLTRANSFERASE, and oil-body protein genes were both differentially expressed between the high- and low-oil materials of each crop. By comparing functional components of SOS networks, we found that the strong correlations between genes in "glycolysis/gluconeogenesis" and "fatty acid synthesis" were conserved in both grain and oil crops, with PYRUVATE KINASE being the common factor affecting starch and lipid accumulation. Network alignment also found a conserved clique among oil crops affecting seed oil accumulation, which has been validated in Arabidopsis. Differently, secondary and protein metabolism affected oil synthesis to different degrees in different crops, and high SOC was due to less competition of the same precursors. The comparison of Arabidopsis mutants and wild type showed that CINNAMYL ALCOHOL DEHYDROGENASE 9, the conserved regulator we identified, was a factor resulting in different relative contents of lignins to oil in seeds. The interconnection of lipids and proteins was common but in different ways among crops, which partly led to differential oil production. CONCLUSIONS: This study goes beyond the observations made in studies of individual species to provide new insights into which genes and networks may be fundamental to seed oil accumulation from a multispecies perspective.

Visualizing Motion Trail via Phosphorescence Carbon Nanodots-Based Delay Display Array.

A scene that contains both old and instant events with a clear motion trail is visually intriguing and dynamic, which can convey a sense of change, transition, or evolution. Developing an eco-friendly delay display system offers a powerful tool for fusing old and instant events, which can be used for visualizing motion trails. Herein, we brighten triplet excitons of carbon nanodots (CNDs) and increase their emission yield by a multidimensional confinement strategy, and the CND-based delay display array is demonstrated. The intense confinement effects via multidimensional confinement strategy suppress nonradiative transitions, and 240% enhancement in the phosphorescence efficiency and 260% enhancement in the lifetime of the CNDs are thus realized. Considering their distinctive phosphorescence performances, a delay display array containing a 4 × 4 CND-based delay lighting device is demonstrated, which can provide ultralong phosphorescence over 7 s, and the motion that occurred in different timelines is recorded clearly. This finding will motivate the investigation of phosphorescent CNDs in motion trail recognition.

Spectroscopic Techniques and Hydrogen-Sensitive Compounds: A New Horizon in Hydrogen Detection.

Detecting hydrogen leaks remains a pivotal challenge demanding robust solutions. Among diverse detection techniques, the fiber-optic method distinguishes itself through unique benefits, such as its distributed measurement properties. The adoption of hydrogen-sensitive materials coated on fibers has gained significant traction in research circles, credited to its operational simplicity and exceptional adaptability across varied conditions. This manuscript offers an exhaustive investigation into hydrogen-sensitive materials and their incorporation into fiber-optic hydrogen sensors. The research profoundly analyzes the sensor architectures, performance indicators, and the spectrum of sensing materials. A detailed understanding of these sensors' potentials and constraints emerges through rigorous examination, juxtaposition, and holistic discourse. Furthermore, this analysis judiciously assesses the inherent challenges tied to these systems, simultaneously highlighting potential pathways for future innovation. By spotlighting the hurdles and opportunities, this paper furnishes a view on hydrogen sensing technology, particularly related to optical fiber-based applications.

Strategies for the Enhancement of Secondary Metabolite Production via Biosynthesis Gene Cluster Regulation in Aspergillus oryzae.

The filamentous fungus Aspergillus oryzae (A. oryzae) has been extensively used for the biosynthesis of numerous secondary metabolites with significant applications in agriculture and food and medical industries, among others. However, the identification and functional prediction of metabolites through genome mining in A. oryzae are hindered by the complex regulatory mechanisms of secondary metabolite biosynthesis and the inactivity of most of the biosynthetic gene clusters involved. The global regulatory factors, pathway-specific regulatory factors, epigenetics, and environmental signals significantly impact the production of secondary metabolites, indicating that appropriate gene-level modulations are expected to promote the biosynthesis of secondary metabolites in A. oryzae. This review mainly focuses on illuminating the molecular regulatory mechanisms for the activation of potentially unexpressed pathways, possibly revealing the effects of transcriptional, epigenetic, and environmental signal regulation. By gaining a comprehensive understanding of the regulatory mechanisms of secondary metabolite biosynthesis, strategies can be developed to enhance the production and utilization of these metabolites, and potential functions can be fully exploited.

Activation of Nrf2/HO-1 signaling pathway exacerbates cholestatic liver injury.

Nuclear factor erythroid 2-related factor-2 (Nrf2) antioxidant signaling is involved in liver protection, but this generalization overlooks conflicting studies indicating that Nrf2 effects are not necessarily hepatoprotective. The role of Nrf2/heme oxygenase-1 (HO-1) in cholestatic liver injury (CLI) remains poorly defined. Here, we report that Nrf2/HO-1 activation exacerbates liver injury rather than exerting a protective effect in CLI. Inhibiting HO-1 or ameliorating bilirubin transport alleviates liver injury in CLI models. Nrf2 knockout confers hepatoprotection in CLI mice, whereas in non-CLI mice, Nrf2 knockout aggravates liver damage. In the CLI setting, oxidative stress activates Nrf2/HO-1, leads to bilirubin accumulation, and impairs mitochondrial function. High levels of bilirubin reciprocally upregulate the activation of Nrf2 and HO-1, while antioxidant and mitochondrial-targeted SOD2 overexpression attenuate bilirubin toxicity. The expression of Nrf2 and HO-1 is elevated in serum of patients with CLI. These results reveal an unrecognized function of Nrf2 signaling in exacerbating liver injury in cholestatic disease.

Mo4+-Doped CuS Nanosheet-Assembled Hollow Spheres for CO2 Electroreduction to Ethanol in a Flow Cell.

Electrocatalytic CO2 reduction reaction (CO2RR) to ethanol has been widely researched for potential commercial application. However, it still faces limited selectivity at a large current density. Herein, Mo4+-doped CuS nanosheet-assembled hollow spheres are constructed to address this issue. Mo4+ ion doping modifies the local electronic environments and diversifies the binding sites of CuS, which increases the coverage of linear *COL and produces bridge *COB for subsequent *COL-*COH coupling toward ethanol production. The optimal Mo9.0%-CuS can electrocatalyze CO2 to ethanol with a faradaic efficiency of 67.5% and a partial current density of 186.5 mA cm-2 at -0.6 V in a flow cell. This work clarifies that doping high valence transition metal ions into Cu-based sulfides can regulate the coverage and configuration of related intermediates for ethanol production during the CO2RR in a flow cell.

Cell of origin epigenetic priming determines susceptibility to Tet2 mutation.

Hematopoietic stem cell (HSC) mutations can result in clonal hematopoiesis (CH) with heterogeneous clinical outcomes. Here, we investigate how the cell state preceding Tet2 mutation impacts the pre-malignant phenotype. Using an inducible system for clonal analysis of myeloid progenitors, we find that the epigenetic features of clones at similar differentiation status are highly heterogeneous and functionally respond differently to Tet2 mutation. Cell differentiation stage also influences Tet2 mutation response indicating that the cell of origin's epigenome modulates clone-specific behaviors in CH. Molecular features associated with higher risk outcomes include Sox4 that sensitizes cells to Tet2 inactivation, inducing dedifferentiation, altered metabolism and increasing the in vivo clonal output of mutant cells, as confirmed in primary GMP and HSC models. Our findings validate the hypothesis that epigenetic features can predispose specific clones for dominance, explaining why identical genetic mutations can result in different phenotypes.

Preparation of near-infrared photoacoustic imaging and photothermal treatment agent for cancer using a modifiable acid-triggered molecular platform.

Ratiometric near-infrared fluorescent pH probes with various pKa values were innovatively designed and synthesized based on cyanine with a diamine moiety. The photochemical properties of these probes were thoroughly evaluated. Among the series, IR-PHA exhibited an optimal pKa value of approximately 6.40, closely matching the pH of cancerous tissues. This feature is particularly valuable for real-time pH monitoring in both living cells and living mice. Moreover, when administered intravenously to tumor-bearing mice, IR-PHA demonstrated rapid and significant enhancement of near-infrared fluorescence and photoacoustic signals within the tumor region. This outcome underscores the probe's exceptional capability for dual-modal cancer imaging utilizing near-infrared fluorescence (NIRF) and photoacoustic (PA) modalities. Concurrently, the application of a continuous-wave near-infrared laser efficiently ablated cancer cells in vivo, attributed to the photothermal effect induced by IR-PHA. The results strongly indicate that IR-PHA is well-suited for NIRF/PA dual-modality imaging and photothermal therapy of tumors. This makes it a promising candidate for theranostic applications involving small molecules.