Taking SCFAs produced by Lactobacillus reuteri orally reshapes gut microbiota and elicits antitumor responses.

BACKGROUND: Colorectal cancer (CRC) incidence is increasing in recent years due to intestinal flora imbalance, making oral probiotics a hotspot for research. However, numerous studies related to intestinal flora regulation ignore its internal mechanisms without in-depth research. RESULTS: Here, we developed a probiotic microgel delivery system (L.r@(SA-CS)2) through the layer-by-layer encapsulation technology of alginate (SA) and chitosan (CS) to improve gut microbiota dysbiosis and enhance anti-tumor therapeutic effect. Short chain fatty acids (SCFAs) produced by L.r have direct anti-tumor effects. Additionally, it reduces harmful bacteria such as Proteobacteria and Fusobacteriota, and through bacteria mutualophy increases beneficial bacteria such as Bacteroidota and Firmicutes which produce butyric acid. By binding to the G protein-coupled receptor 109A (GPR109A) on the surface of colonic epithelial cells, butyric acid can induce apoptosis in abnormal cells. Due to the low expression of GPR109A in colon cancer cells, MK-6892 (MK) can be used to stimulate GPR109A. With increased production of butyrate, activated GPR109A is able to bind more butyrate, which further promotes apoptosis of cancer cells and triggers an antitumor response. CONCLUSION: It appears that the oral administration of L.r@(SA-CS)2 microgels may provide a treatment option for CRC by modifying the gut microbiota.

Comparative whole-genome resequencing to uncover selection signatures linked to litter size in Hu Sheep and five other breeds.

Hu sheep (HS), a breed of sheep carrying the FecB mutation gene, is known for its "year-round estrus and multiple births" and is an ideal model for studying the high fecundity mechanisms of livestock. Through analyzing and comparing the genomic selection features of Hu sheep and other sheep breeds, we identified a series of candidate genes that may play a role in Hu sheep's high fecundity mechanisms. In this study, we conducted whole-genome resequencing on six breeds and screened key mutations significantly correlated with high reproductive traits in sheep. Notably, the CC2D1B gene was selected by the fixation index (FST) and the cross-population composite likelihood ratio (XP-CLR) methods in HS and other five breeds. It was worth noting that the CC2D1B gene in HS was different from that in other sheep breeds, and seven missense mutations have been identified. Furthermore, the linkage disequilibrium (LD) analysis revealed a strong linkage disequilibrium in this specific gene region. Subsequently, by performing different grouping based on FecB genotypes in Hu sheep, genome-wide selective signal analysis screened several genes related to reproduction, such as BMPR1B and PPM1K. Besides, FST analysis identified functional genes related to reproductive traits, including RHEB, HSPA2, PPP1CC, HVCN1, and CCDC63. Additionally, a missense mutation was found in the CCDC63 gene and the haplotype was different between the high reproduction (HR) group and low reproduction (LR) group in HS. In summary, we discovered genetic differentiation among six distinct breeding sheep breeds at the whole genome level. Additionally, we identified a set of genes which were associated with reproductive performance in Hu sheep and visualized how these genes differed in different breeds. These findings laid a theoretical foundation for understanding genetic mechanisms behind high prolific traits in sheep.

Comprehensive review on lipid metabolism and RNA methylation: Biological mechanisms, perspectives and challenges.

Adipose tissue plays a crucial role in maintaining energy balance, regulating hormones, and promoting metabolic health. To address disorders related to obesity and develop effective therapies, it is essential to have a deep understanding of adipose tissue biology. In recent years, RNA methylation has emerged as a significant epigenetic modification involved in various cellular functions and metabolic pathways. Particularly in the realm of adipogenesis and lipid metabolism, extensive research is ongoing to uncover the mechanisms and functional importance of RNA methylation. Increasing evidence suggests that RNA methylation plays a regulatory role in adipocyte development, metabolism, and lipid utilization across different organs. This comprehensive review aims to provide an overview of common RNA methylation modifications, their occurrences, and regulatory mechanisms, focusing specifically on their intricate connections to fat metabolism. Additionally, we discuss the research methodologies used in studying RNA methylation and highlight relevant databases that can aid researchers in this rapidly advancing field.

Correction: Effect of support on hydrogen generation over iron oxides in the chemical looping process.

[This corrects the article DOI: 10.1039/D1RA07210B.].

Spatiotemporal Distributions of Acoustic Propagation in Skull During Ultrasound Neuromodulation.

There is widespread interest and concern about the evidence and hypothesis that the auditory system is involved in ultrasound neuromodulation. We have addressed this problem by performing acoustic shear wave simulations in mouse skull and behavioral experiments in deaf mice. The simulation results showed that shear waves propagating along the skull did not reach sufficient acoustic pressure in the auditory cortex to modulate neurons. Behavioral experiments were subsequently performed to awaken anesthetized mice with ultrasound targeting the motor cortex or ventral tegmental area (VTA). The experimental results showed that ultrasound stimulation (US) of the target areas significantly increased arousal scores even in deaf mice, whereas the loss of ultrasound gel abolished the effect. Immunofluorescence staining also showed that ultrasound can modulate neurons in the target area, whereas neurons in the auditory cortex required the involvement of the normal auditory system for activation. In summary, the shear waves propagating along the skull cannot reach the auditory cortex and induce neuronal activation. Ultrasound neuromodulation-induced arousal behavior needs direct action on functionally relevant stimulation targets in the absence of auditory system participation.

Soil erosion is a major drive for nano & micro-plastics to enter riverine systems from cultivated land.

Nano and micro-plastics (NMPs, particles diameter <5 mm), as emerging contaminants, have become a major concern in the aquatic environment because of their adverse consequences to aquatic life and potentially human health. Implementing mitigation strategies requires quantifying NMPs mass emissions and understanding their sources and transport pathways from land to riverine systems. Herein, to access NMPs mass input from agricultural soil to riverine system via water-driven soil erosion, we have collected soil samples from 120 cultivated land in nine drainage basins across China in 2021 and quantified the residues of six common types of plastic, including polyvinyl chloride (PVC), polymethyl methacrylate (PMMA), polypropylene (PP), polyethylene (PE), polycarbonate (PC), and polystyrene (PS). NMPs (Σ6plastics) were detected in all samples at concentrations between 3.6 and 816.6 µg/g dry weight (median, 63.3 µg/g) by thermal desorption/pyrolysis-gas chromatography-mass spectrometry. Then, based on the Revised Universal Soil Loss Equation model, we estimated that about 22,700 tonnes of NMPs may enter the Chinese riverine system in 2020 due to agricultural water-driven soil erosion, which occurs primarily from May to September. Our result suggested that over 90% of the riverine NMPs related to agricultural soil erosion in China are attributed to 36.5% of the country's total cultivated land, mainly distributed in the Yangtze River Basin, Southwest Basin, and Pearl River Basin. The migration of NMPs due to water-driven soil erosion cannot be ignored, and erosion management strategies may contribute to alleviating plastic pollution issues in aquatic systems.

The role of mitochondrial dynamics and mitophagy in skeletal muscle atrophy: from molecular mechanisms to therapeutic insights.

Skeletal muscle is the largest metabolic organ of the human body. Maintaining the best quality control and functional integrity of mitochondria is essential for the health of skeletal muscle. However, mitochondrial dysfunction characterized by mitochondrial dynamic imbalance and mitophagy disruption can lead to varying degrees of muscle atrophy, but the underlying mechanism of action is still unclear. Although mitochondrial dynamics and mitophagy are two different mitochondrial quality control mechanisms, a large amount of evidence has indicated that they are interrelated and mutually regulated. The former maintains the balance of the mitochondrial network, eliminates damaged or aged mitochondria, and enables cells to survive normally. The latter degrades damaged or aged mitochondria through the lysosomal pathway, ensuring cellular functional health and metabolic homeostasis. Skeletal muscle atrophy is considered an urgent global health issue. Understanding and gaining knowledge about muscle atrophy caused by mitochondrial dysfunction, particularly focusing on mitochondrial dynamics and mitochondrial autophagy, can greatly contribute to the prevention and treatment of muscle atrophy. In this review, we critically summarize the recent research progress on mitochondrial dynamics and mitophagy in skeletal muscle atrophy, and expound on the intrinsic molecular mechanism of skeletal muscle atrophy caused by mitochondrial dynamics and mitophagy. Importantly, we emphasize the potential of targeting mitochondrial dynamics and mitophagy as therapeutic strategies for the prevention and treatment of muscle atrophy, including pharmacological treatment and exercise therapy, and summarize effective methods for the treatment of skeletal muscle atrophy.

Acoustothermal transfection for cell therapy.

Transfected stem cells and T cells are promising in personalized cell therapy and immunotherapy against various diseases. However, existing transfection techniques face a fundamental trade-off between transfection efficiency and cell viability; achieving both simultaneously remains a substantial challenge. This study presents an acoustothermal transfection method that leverages acoustic and thermal effects on cells to enhance the permeability of both the cell membrane and nuclear envelope to achieve safe, efficient, and high-throughput transfection of primary T cells and stem cells. With this method, two types of plasmids were simultaneously delivered into the nuclei of mesenchymal stem cells (MSCs) with efficiencies of 89.6 ± 1.2%. CXCR4-transfected MSCs could efficiently target cerebral ischemia sites in vivo and reduce the infarct volume in mice. Our acoustothermal transfection method addresses a key bottleneck in balancing the transfection efficiency and cell viability, which can become a powerful tool in the future for cellular and gene therapies.

Opportunities and barriers in omics-based biomarker discovery for steatotic liver diseases.

The rising prevalence of liver diseases related to obesity and excessive use of alcohol is fuelling an increasing demand for accurate biomarkers aimed at community screening, diagnosis of steatohepatitis and significant fibrosis, monitoring, prognostication and prediction of treatment efficacy. Breakthroughs in omics methodologies and the power of bioinformatics have created an excellent opportunity to apply technological advances to clinical needs, for instance in the development of precision biomarkers for personalised medicine. Via omics technologies, biological processes from the genes to circulating protein, as well as the microbiome - including bacteria, viruses and fungi, can be investigated on an axis. However, there are important barriers to omics-based biomarker discovery and validation, including the use of semi-quantitative measurements from untargeted platforms, which may exhibit high analytical, inter- and intra-individual variance. Standardising methods and the need to validate them across diverse populations presents a challenge, partly due to disease complexity and the dynamic nature of biomarker expression at different disease stages. Lack of validity causes lost opportunities when studies fail to provide the knowledge needed for regulatory approvals, all of which contributes to a delayed translation of these discoveries into clinical practice. While no omics-based biomarkers have matured to clinical implementation, the extent of data generated has enabled the hypothesis-free discovery of a plethora of candidate biomarkers that warrant further validation. To explore the many opportunities of omics technologies, hepatologists need detailed knowledge of commonalities and differences between the various omics layers, and both the barriers to and advantages of these approaches.

Effects of antibiotics on secondary metabolism and oxidative stress in oilseed rape seeds.

Cruciferae brassica oilseed rape is the third largest oilseed crop in the world and the first in China, as well as a fertilizer-dependent crop. With the increased application of organic fertilizers from livestock manure in agricultural production in recent years, the resulting antibiotic pollution and its ecological health effects have attracted widespread attention. In this study, typical tetracycline and sulfonamide antibiotics tetracycline (TC) and sulfamethoxazole (SMZ) were used to investigate the effects of antibiotics on rapeseed quality and oxidative stress at the level of secondary metabolism on the basis of examining the effects of the two drugs on the growth of soil-cultivated rapeseed seedlings. The results showed that both plant height and biomass of rapeseed seedlings were significantly suppressed and ROS were significantly induced in rapeseed by exposure to high concentrations (2.5 mg/kg) of TC and SMZ. Carotenoids, tocopherols, and SOD enzymes were involved in the oxidative stress response to scavenge free radicals in rapeseed, but phenolic acids and flavonoids contents were decreased, which reduced the quality of the seeds to some extent.

Geometric remodeling of tricuspid valve in pulmonary hypertension and its correlation with pulmonary hypertension severity: a prospectively case-control study using four-dimensional automatic tricuspid valve quantification technology.

Background: Evaluation of the tricuspid valve (TV) is crucial for clinical decision making and post-treatment follow-up in pulmonary hypertension (PH) patients. However, little is known about 4-dimensional (4D) TV geometric remodeling in patients with PH. The aim of this study was to examine the 4D geometry of the TV in PH and its correlation with PH severity. Methods: A total of 74 PH patients with mean pulmonary arterial pressure >25 mmHg and 15 age- and gender-matched healthy individuals were consecutively included from September 2017 to December 2018 in National Center for Cardiovascular Diseases, Fuwai Hospital. All participants underwent 2-dimensional (2D) and 4D transthoracic echocardiography and PH patients underwent right heart catheterization (RHC) within 48 hours of echocardiography. TV geometry was analyzed using a dedicated 4D echocardiography from the right ventricular-focused apical view. Results: Compared with controls, PH patients had significantly larger 4D tricuspid annular (TA) and TV tenting sizes except in the 2-chamber diameter. In high-quality image cases, maximal tenting height (MTH), coaptation point height, tenting volume and 4-chamber diameter had good or moderate correlation with PH severity graded according to RHC mean pulmonary artery pressure (r=0.705, r=0.644, r=0.602, r=0.472, respectively; P<0.001 for all). In multivariable linear regression analysis, PH severity was independently associated with coaptation point height (F=18.070, P<0.001 with an R2=0.647) and MTH (F=25.576, P<0.001 with an R2=0.378). Among all 4D TV parameters, MTH had the highest area under the receiver operating characteristic (ROC) curve (AUC) in high-quality image cases [AUC =0.857, 95% confidence interval (CI): 0.743-0.972; P<0.001], comparable to echocardiographic systolic pulmonary arterial pressure (AUC =0.847, 95% CI: 0.733-0.961; P<0.001). Conclusions: In PH, TV geometric remodeling occurs mainly in TA septal-lateral dimension and TV tenting height. Worsening PH is an independent determinant of TV coaptation point height and MTH, not TA size. MTH shows a great diagnostic potential to detect severe PH.

Characterization of two CYP80 enzymes provides insights into aporphine alkaloid skeleton formation in Aristolochia contorta.

Aporphine alkaloids are a large group of natural compounds with extensive pharmaceutical application prospects. The biosynthesis of aporphine alkaloids has been paid attentions in the past decades. Here, we determined the contents of four 1-benzylisoquinoline alkaloids and five aporphine alkaloids in root, stem, leaf, and flower of Aristolochia contorta Bunge, which belongs to magnoliids. Two CYP80 enzymes were identified and characterized from A. contorta. Both of them catalyze the unusual C-C phenol coupling reactions and directly form the aporphine alkaloid skeleton. AcCYP80G7 catalyzed the formation of hexacyclic aporphine corytuberine. AcCYP80Q8 catalyzed the formation of pentacyclic proaporphine glaziovine. Kingdom-wide phylogenetic analysis of the CYP80 family suggested that CYP80 first appeared in Nymphaeales. The functional divergence of hydroxylation and C-C (or C-O) phenol coupling preceded the divergence of magnoliids and eudicots. Probable crucial residues of AcCYP80Q8 were selected through sequence alignment and molecular docking. Site-directed mutagenesis revealed two crucial residues E284 and Y106 for the catalytic reaction. Identification and characterization of two aporphine skeleton-forming enzymes provide insights into the biosynthesis of aporphine alkaloids.

Chiral ligands and photothermal synergistic effects of inorganic nanoparticles for bacteria-killing.

As the drawbacks of antibiotics in treating bacterial infections emerged, physical methods such as near-infrared-activated (NIR-activated) bacterial killing, have attracted great interests for their advantages of no resistance, short action time and few side effects. In this manuscript, NIR-activated bacteria-killing performance of chiral copper sulphide nanoparticles (L-/d-CuS NPs) was investigated using linearly polarized light (LPL) and circularly polarized light (CPL) as illumination sources, respectively. Chiral CuS NPs showed enhanced NIR-activated bacteria-killing effect compared with achiral CuS NPs under the same conditions. Moreover, these chiral CuS NPs showed obvious chirality-related antibacterial effect: the bacterial killing was more efficient under CPL activation, and L- and d-CuS NPs had higher antibacterial efficiency under left circularly polarized light (LCPL) and right circularly polarized light (RCPL), respectively. The possible mechanism of bacteria-killing performance for chiral CuS NPs was discussed in detailed. Photothermal bacteria-killing tests of chiral CuS NPs "sealed" in polydimethylsiloxane (PDMS) demonstrated the individual influence of photothermal effect. These observations in this paper could provide ideas for the potential applications of chiral nanostructures with enhanced photothermal effect in efficient bacterial killing.

Oral probiotics microgel plus Galunisertib reduced TGF-ß blockade resistance and enhanced anti-tumor immune responses in colorectal cancer.

Transforming growth factor ß (TGF-ß), a versatile immunosuppressive cytokine, has gained increasing attention as a potential target for cancer immunotherapy. However, current strategies are constrained by tumor heterogeneity and drug resistance. Therapeutic probiotics, such as Escherichia coli Nissle1917 (EcN), not only regulate the gut microbiota to increase beneficial bacteria with anti-tumor effects, but also modulate immune factors within the body, thereby enhancing immunity. In this study, we developed an oral microgel delivery system of EcN@(CS-SA)2 by electrostatic interaction between chitosan (CS) and sodium alginate (SA), aiming to enhance its bioavailability in the gastrointestinal tract (GIT). Notably, EcN@(CS-SA)2 microgel showed a synergistic enhancement of the anti-tumor efficacy of Galunisertib (Gal, a TGF-ß inhibitor) by inducing apoptosis and immunogenic cell death (ICD) in tumor cells, as well as promoting increased infiltration of CD8+ T cells into the tumor microenvironment (TME).

Ultrasound Deep Brain Stimulation Regulates Food Intake and Body Weight in Mice.

Given the widespread occurrence of obesity, new strategies are urgently needed to prevent, halt and reverse this condition. We proposed a noninvasive neurostimulation tool, ultrasound deep brain stimulation (UDBS), which can specifically modulate the hypothalamus and effectively regulate food intake and body weight in mice. Fifteen-min UDBS of hypothalamus decreased 41.4% food intake within 2 hours. Prolonged 1-hour UDBS significantly decreased daily food intake lasting 4 days. UDBS also effectively restrained body weight gain in leptin-receptor knockout mice (Sham: 96.19%, UDBS: 58.61%). High-fat diet (HFD) mice treated with 4-week UDBS (15 min / 2 days) reduced 28.70% of the body weight compared to the Sham group. Meanwhile, UDBS significantly modulated glucose-lipid metabolism and decreased the body fat. The potential mechanism is that ultrasound actives pro-opiomelanocortin (POMC) neurons in the hypothalamus for reduction of food intake and body weight. These results provide a noninvasive tool for controlling food intake, enabling systematic treatment of obesity.

Full Mass Range ΦSDM Orbitrap Mass Spectrometry for DIA Proteome Analysis.

Optimizing data-independent acquisition methods for proteomics applications often requires balancing spectral resolution and acquisition speed. Here, we describe a real-time full mass range implementation of the phase-constrained spectrum deconvolution method (ΦSDM) for Orbitrap mass spectrometry that increases mass resolving power without increasing scan time. Comparing its performance to the standard enhanced Fourier transformation signal processing revealed that the increased resolving power of ΦSDM is beneficial in areas of high peptide density and comes with a greater ability to resolve low-abundance signals. In a standard 2 h analysis of a 200 ng HeLa digest, this resulted in an increase of 16% in the number of quantified peptides. As the acquisition speed becomes even more important when using fast chromatographic gradients, we further applied ΦSDM methods to a range of shorter gradient lengths (21, 12, and 5 min). While ΦSDM improved identification rates and spectral quality in all tested gradients, it proved particularly advantageous for the 5 min gradient. Here, the number of identified protein groups and peptides increased by >15% in comparison to enhanced Fourier transformation processing. In conclusion, ΦSDM is an alternative signal processing algorithm for processing Orbitrap data that can improve spectral quality and benefit quantitative accuracy in typical proteomics experiments, especially when using short gradients.

Identification of an immune-related eRNA prognostic signature for clear cell renal cell carcinoma.

BACKGROUND: Immune-related enhancer RNAs (eRNAs) have garnered significant attention in cancer metabolism research, yet their specific roles in ccRCC have remained elusive. METHODS: We retrieved eRNA expression profiles from TCGA database and identified immune-related eRNAs (IREs) by assessing their co-expression with immune genes. Utilizing consensus clustering, we organized these IREs into two distinct clusters. The construction of an IREs signature was accomplished through the LASSO and multivariate Cox analysis. Furthermore, we performed Cell Counting Kit-8 and clonogenic assays to assess changes in the proliferative capacity of Caki-1 and 769-P cells. RESULTS: The existence of two clusters of immune-related eRNAs in ccRCC, each with distinctive prognostic and immunological attributes. Cluster B exhibited immunosuppressive properties and displayed a positive correlation with immunosuppressive cells. Functional enrichment analysis unveiled their involvement in several tumor-promoting pathways, metabolic pathways and immune pathways. The IREs signature demonstrated its potential to accurately predict patient immune and prognostic characteristics. AC003092.1, an eRNA strongly associated with patient survival, emerged as a potential oncogene significantly linked to adverse prognosis and the presence of immunosuppressive cells and checkpoints in ccRCC patients. Notably, AC003092.1 displayed marked upregulation in ccRCC tissues and cell lines, and its knockdown substantially inhibited the proliferation of Caki-1 and 769-P cells. CONCLUSION: We established a robust predictive model that played a vital role in determining the prognosis, clinicopathological characteristics and immune cell infiltration patterns of ccRCC patients. IRE, particularly AC003092.1, which was strongly associated with survival, hold promise as novel immunotherapeutic targets for ccRCC.

Specific inhibition on PAI-1 reduces the dose of Alteplase for ischemic stroke treatment.

Administration of recombinant tPA (rtPA, or trade name Alteplase®) is an FDA-approved therapy for acute ischemic stroke (AIS), but poses the risk of hemorrhagic complications. Recombinant tPA can be rapidly inactivated by the endogenous inhibitor, plasminogen activator inhibitor 1 (PAI-1). In this work, we study a novel treatment approach that combines a PAI-1 inhibitor, PAItrap4, with a reduced dose of rtPA to address the hemorrhagic concern of rtPA. PAItrap4 is a highly specific and very potent protein-based inhibitor of PAI-1, comprising of a variant of uPA serine protease domain, human serum albumin, and a cyclic RGD peptide. PAItrap4 efficiently targets and inhibits PAI-1 on activated platelets, and also possesses a long half-life in vivo. Our results demonstrate that PAItrap4 effectively counteracts the inhibitory effects of PAI-1 on rtPA, preserving rtPA activity based on amidolytic and clot lysis assays. In an in vivo murine stroke model, PAItrap4, together with low-dose rtPA, enhances the blood perfusion in the stroke-affected areas, reduces infarct size, and promotes neurological recovery in mice. Importantly, such treatment does not increase the amount of cerebral hemorrhage, thus reducing the risk of cerebral hemorrhage. In addition, PAItrap4 does not compromise the normal blood coagulation function in mice, demonstrating its safety as a therapeutic agent. These findings highlight this combination therapy as a promising alternative for the treatment of ischemic stroke, offering improved safety and efficacy.

Transthoracic Ultrasound Improves Cardiac Function in Mice.

Cardiac dysfunction is a severe complication that is associated with an increased risk of mortality in multiple diseases. Cardioprotection solution that has been researched is the electrical stimulation of the vagus nerve to exert cardio protection. This method has been shown to reduce the systemic inflammatory response and maintain the immune homeostasis of the heart. However, the invasive procedure of electrode implantation poses a risk of nerve or fiber damage. Here, we propose transthoracic ultrasound stimulation (US) of the vagus nerve to alleviate cardiac dysfunction caused by lipopolysaccharide (LPS). We developed a noninvasive transthoracic US system and exposed anesthetized mice to ultrasound protocol or sham stimulation 24 h after LPS treatment. Results showed that daily heart targeting US for 4 days significantly increased left ventricular systolic function ( p = 0.01) and improved ejection fraction ( p = 0.03) and shortening fraction ( p = 0.04). Furthermore, US significantly reduced inflammation cytokines, including IL-6 ( p = 0.03) and IL- 1ß ( p = 0.04). In addition, cervical vagotomy abrogated the effect of US, suggesting the involvement of the vagus nerve's anti-inflammatory effect. Finally, the same ultrasound treatment but for a longer period (14 days) also significantly increased cardiac function in naturally aged mice. Collectively, these findings suggest the potential of transthoracic US as a possible novel noninvasive approach in the context of cardiac dysfunction with reduced systolic function and provide new targets for rehabilitation of peripheral organ function.

Low-temperature photothermal-induced alkyl radical release facilitates dihydroartemisinin-triggered "valve-off" starvation therapy.

The high nutrient and energy demand of tumor cells compared to normal cells to sustain rapid proliferation offer a potentially auspicious avenue for implementing starvation therapy. However, conventional starvation therapy, such as glucose exhaustion and vascular thrombosis, can lead to systemic toxicity and exacerbate tumor hypoxia. Herein, we developed a new "valve-off" starvation tactic, which was accomplished by closing the valve of glucose transporter protein 1 (GLUT1). Specifically, dihydroartemisinin (DHA), 2,20-azobis [2-(2-imidazolin-2-yl) propane] dihydrochloride (AI), and Ink were co-encapsulated in a sodium alginate (ALG) hydrogel. Upon irradiation with the 1064 nm laser, AI rapidly disintegrated into alkyl radicals (R•), which exacerbated the DHA-induced mitochondrial damage through the generation of reactive oxygen species and further reduced the synthesis of adenosine triphosphate (ATP). Simultaneously, the production of R• facilitated DHA-induced starvation therapy by suppressing GLUT1, which in turn reduced glucose uptake. Systematic in vivo and in vitro results suggested that this radical-enhanced "valve-off" strategy for inducing tumor cell starvation was effective in reducing glucose uptake and ATP levels. This integrated strategy induces tumor starvation with efficient tumor suppression, creating a new avenue for controlled, precise, and concerted tumor therapy.