5-Fluorouracil (5-FU) resistance in colorectal cancer (CRC) involves oxidative stress mechanisms, but the role of epitranscriptomic regulation remains unclear. This study investigates how oxidative post-translational modifications of the N6-methyladenosine (m6A) methyltransferase METTL16 contribute to 5-FU resistance. Parental (HCT8, HCT15) and 5-FU-resistant CRC cells were compared using redox proteomics, m6A-seq, RNA-seq, and functional assays. METTL16 S-glutathionylation was assessed via streptavidin pulldown and mass spectrometry. IGF2BP3’s role was validated through knockdown/overexpression, patient-derived organoids (PDOs), and xenograft models. Clinical relevance was evaluated in 112 CRC patient tissues and data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Drug synergy was tested using isoliquiritigenin (ISO) combined with 5-FU. Resistant cells exhibited elevated global protein S-glutathionylation and reduced m6A RNA methylation. METTL16 underwent site-specific S-glutathionylation at Cys548, leading to its degradation and subsequent m6A loss. Integrative omics identified IGF2BP3 as a key METTL16 target: reduced m6A on IGF2BP3 mRNA enhanced its nuclear export, splicing, and overexpression. IGF2BP3 knockdown sensitized resistant cells to 5-FU in vitro and in vivo, while overexpression conferred resistance. Mechanistically, IGF2BP3 destabilized CFTR mRNA (an ABC transporter), reducing 5-FU uptake. Clinically, high IGF2BP3 correlated with poor survival and 5-FU resistance in CRC patients. Targeting IGF2BP3 with ISO synergized with 5-FU, overcoming resistance in cells and xenografts. Oxidative stress-induced METTL16 S-glutathionylation drives 5-FU resistance by reducing m6A modification, enabling IGF2BP3 overexpression and CFTR suppression. IGF2BP3 is a biomarker of clinical resistance, and its targeting with ISO represents a promising combinatorial strategy to restore 5-FU efficacy in CRC.

BACKGROUND:Chemotherapy-induced diarrhea (CID) is a common complication among colorectal cancer patients receiving chemotherapeutic treatment. This condition adversely affects therapeutic outcomes and potentially increases mortality risks. Acupuncture, an integral component of traditional Chinese medicine, has gained widespread use in China's clinical settings. Recent findings suggest that this non-drug approach may provide therapeutic advantages for managing CID. This warrants further research into its clinical application. METHODS:A comprehensive systematic review will be performed to find randomized controlled trials (RCTs) that examine the therapeutic effectiveness and safety of acupuncture treatments for managing CID in patients with colorectal cancer. The search strategy includes eight major electronic repositories: PubMed, Web of Science, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure (CNKI), Wanfang Data, Chinese Biomedical Database (CBM), and China Scientific Journal Database (VIP), with no language restrictions. Primary endpoints focused on clinical improvements quantified through two key parameters: alterations in diarrhea severity according to the Irritable Bowel Syndrome Severity Scoring System (IBS-SSS) classifications, and modifications in episode duration. Secondary endpoints encompassed safety assessments of acupuncture-related adverse reactions and comprehensive evaluation of quality-of-life indicators using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Two reviewers will independently assess the risk of bias for all primary outcomes via the Cochrane Risk of Bias tool (RoB2). Disagreements will be resolved through discussion or third-party adjudication. For data synthesis and meta-analysis, all statistical analyses will utilize Review Manager software version 5.3 from the Cochrane Collaboration. CONCLUSION:This systematic review will synthesize existing evidence to evaluate the therapeutic efficacy and safety of acupuncture in managing CID among colorectal cancer patients. The findings aim to inform clinical practice by assessing whether acupuncture represents a viable adjunctive therapy within evidence-based treatment protocols. SYSTEMATIC TRIAL REGISTRATION:PROSPERO CRD420251045610.

IntroductionPostoperative recurrence and metastasis of colorectal cancer (CRC) are critical factors affecting long-term survival, and how to prevent postoperative recurrence and metastasis remains an urgent clinical challenge. Studies indicate that berberine has a preventive effect against colorectal adenoma recurrence; however, no research has yet investigated its preventive efficacy against CRC. This trial aims to evaluate the clinical efficacy and safety of BBR in preventing postoperative recurrence and metastasis of CRC by comparing it with a placebo group.Methods and analysisThis trial is a multicenter, randomized, controlled, double-blind clinical study. A total of 306 eligible patients with stage IIIB, IIIC CRC who had undergone surgery will be randomly assigned in a 1:1 ratio to the placebo group and the trial group. The primary outcome is 2-year disease-free survival (DFS) rate, while secondary outcomes include 1-year and 2-year postoperative recurrence rates of CRC, as well as the incidence of adverse reactions. We expect that this randomized controlled trial (RCT) will provide high-quality evidence on BBR for the prevention of postoperative recurrence of CRC, which can achieve more significant clinical benefits to patients with stage IIIB, IIIC CRC.Ethics and disseminationThis study has been approved by the institutional review board of The Second Affiliated Hospital of Zhejiang Chinese Medical University (No. 2025-246-IH01).Clinical trial registrationwww.chictr.org.cn, identifier: ChiCTR2600117441.

Objective:Chemotherapy-induced nausea and vomiting (CINV) represents a common and debilitating side effects in cancer patients, often compromising treatment adherence and quality of life. Current management remains suboptimal, necessitating the exploration of complementary therapies. Acupuncture, as a widely used adjunctive therapy, has been attempted for the treatment of CINV. This study aims to systematically evaluate the effect and safety of acupuncture in managing CINV. Methods:We comprehensively searched seven electronic databases (EMBASE, Cochrane Library, Web of Science, PubMed, China National Knowledge Infrastructure, VIP Chinese Science and Technology Periodicals Databas, and Wanfang) and two clinical trial registries (ClinicalTrials.gov, Chinese Clinical Trial Registry) for randomized controlled trials (RCTs) comparing acupuncture with sham acupuncture or conventional treatment for CINV. The primary outcomes included complete response rate (no vomiting episodes plus no or mild nausea), the frequency of vomiting episodes, and validated scale scores. Studies quality were assessed by using the Cochrane Risk of Bias tools.The registration number of this study is CRD420251102130. Results:49 RCTs involving 4,133 participants were included in this study. The results demonstrated that compared with the control group, acupuncture significantly reduced the incidence of vomiting (RR = 0.583, 95% CI: 0.523-0.650), vomiting severity (MD = -0.839, 95% CI: -1.256 to -0.422) and vomiting episodes (MD = -3.704, 95% CI: -6.256 to -1.152). Additionally, acupuncture lowered the incidence of nausea (RR = 0.532, 95% CI: 0.432-0.655), and nausea severity (MD = -0.895, 95% CI: -1.273 to -0.516). The most utilized acupoints were Zusanli (ST36, n = 42), Neiguan (PC6, n = 38), and Zhongwan (CV12, n = 23). Conclusion:This study confirms that acupuncture is effective as an adjunctive therapy for CINV. While future large-scale, rigorously designed RCTs are warranted to further validate these findings, the current evidence provides a robust rationale for its integration into clinical practice. Systematic review registration:The registration number of this study is CRD420251102130.

Unlike hyperthermia after intratumoral injection, the method of integrated magnetic targeted hyperthermia (iMTH) guides magnetic medium to the target site and then directly performs in-situ heating, showing great potential for effective treatment of deep-seated tumors in the body. Magnetotactic bacteria (MTB), having chain-like arranged magnetic nanoparticles within its body and active movement along an external magnetic field, are considered as a very fitted material for iMTH. However, the amount of MTB concentrated on the deep-seated tumor posed a significant challenge for the successful implementation of iMTH. Herein, we aim to validate the strategy of integrating magnetic targeting and hyperthermia. An in-situ liver tumor model in mouse was developed as deep-seated tumors. After administering the polar MTB MO-1 intravenously via the tail vein, a focusing magnetic field navigated these bacteria to effectively accumulate at the deep-seated tumor site. Immediately afterwards, this targeted aggregation of MO-1 cells triggered a localized magnetic hyperthermia directly at the cancer site under an applied alternating magnetic field. Our findings demonstrated that this hyperthermia induced by the bacteria led to the death of liver cancer cells, thereby effectively curbing the progression and growth of the cancer. These promising results suggested that an iMTH approach was developed, harnessing the power of MTB. This method stands as an exciting and potential therapeutic strategy for the treatment of deep-seated tumors, offering new hope in the fight against cancer.

Magnetotactic bacteria (MTB), known for their precision in navigating along magnetic fields, also exhibit lightsensitive behaviors. In Magnetospirillum magneticum AMB-1, the photoreceptor Amb2291 is involved in phototaxis regulation and magnetosome synthesis, particularly under oxidative stress. The magnetoreceptor Amb0994 modulates flagellar activity in response to magnetic field changes. Our study used a magneto-optical system to analyze the U-turn motility of north-seeking AMB-1 wild type (WT), amb2291 and amb0994 mutants under reversed magnetic fields and controlled light conditions. The results showed that WT strains consistently executed U-turns in response to magnetic fields, regardless of light variations. The diameters of U-turn of amb0994 mutant were smaller than those of the WT control. When illuminated with blue light in a direction opposite to the magnetic field, Delta amb0994 exhibited slower U-turns with diameters similar to WT. In contrast, the Delta amb2291 strain exhibited exaggerated U-turn movements under blue light, characterized by larger movement diameters and times compared to the WT, particularly whatever the light propagation direction is the same or opposite to the magnetic field in the initial state of motility. Gene expression analysis revealed that long-term exposure to blue light and magnetic fields led to a significant upregulation of amb2291 in Delta amb0994 mutant strains and amb0994 in Delta amb2291 mutant strains. These indicate a potential cooperative role of amb2291 and amb0994 in modulating bacterial motility under blue light. This research enhances our understanding of photoreception in MTB and its impact on magnetotaxis, shedding light on how environmental factors interact with microorganisms.

Magnetotactic bacteria utilize magnetosomes to navigate along magnetic fields and employ photosensitive proteins to respond to light. However, whether a synergistic mechanism exists between phototaxis and magnetotaxis remains unclear. To investigate the cooperative roles of the magnetosensitive protein Amb0994 and the photosensitive protein Amb2291 under magnetic reversal and coupled magneto-optical conditions, we conducted a comparative analysis of Magnetospirillum magneticum AMB-1 wild-type and mutant strains (Δamb0994, Δamb2291, Δamb0994Δamb2291). Experimental results demonstrated that wild-type strains exhibited consistent magnetotaxis responses under both illuminated and control (no added light) conditions, suggesting balanced signal integration via protein synergy. The Δamb0994 mutant exhibited accelerated magnetotaxis responses, indicating that Amb0994 normally functions to moderate magnetic signal processing. In contrast, the Δamb2291 mutant showed prolonged reversal times and lacked directional selectivity after illumination, implying Amb2291 functions as a "photo-directionality sensor." The double mutant displayed the slowest responses. Further, gene expression analysis of chemotaxis and flagellar genes revealed that the Amb0994 and Amb2291 proteins act as repressors in a bidirectional inhibitory equilibrium model, which converges on shared downstream effectors to control "U-turn" behavior. Based on these findings, we extended the motion simulation model framework to provide a phenomenological explanation for the magneto-optical response. Together, these results elucidate potential mechanisms of magneto-optical signal synergy in magnetotactic bacteria and offer new insights into the evolution of microbial taxis behaviors.

Tumor heterogeneity poses numerous challenges for targeted drug therapy. Although tumor cell-derived nanovesicles (NVs) have emerged as an intriguing method for tumor targeting, how to exert the antitumor effect after targeting remains a key concern. Magnetotactic bacteria (MTB) synthesize chain-like magnetite (Fe3O4) crystals with inherent magnetic moments, which could generate significant torque under a desired magnetic field and move along the magnetic field using their own flagella. Herein, a composite of MTB AMB-1 and NVs was fabricated via electrostatic adsorption where AMB-1 could transport NVs to the tumor site by a guiding magnetic field, while NVs also assist AMB-1 in binding to tumor cells. Subsequently, under the influence of a swing magnetic field (sMF), MTB exert physical stimuli on the cells, inducing the changes of mitochondrial membrane potential and cellular reactive oxygen species (ROS). Finally, it is revealed that the NVs-loaded AMB-1 induced a decrease in cellular viability and significantly inhibited the growth of tumors in vivo under the sMF. Therefore, by remote control of the guidance and stimuli production, the NVs-loaded AMB-1 was highly promising to advance the development of targeted therapeutic strategies for tumors under the context of tumor heterogeneity.

A magneto-optical microscopic control system (MO-MCS) was developed for analyzing the magnetotaxis and phototaxis sensing in magnetotactic bacteria (MTB). The system includes a microscopic image acquisition device, a planar magnetic field generator, a multi-wavelength illumination device, and a host computer control system. The MO-MCS can accurately adjust parameters such as the magnetic field intensity, direction, and the duration and intensity of illumination. Using the system, we analyzed the motion characteristics of Magnetospirillum magneticum AMB-1 wild-type and corresponding mutant strains under various illumination conditions when the magnetic field was reversed. The experiments indicated that the photoreceptor protein Amb2291 and the magnetosensitive protein Amb0994 play complementary roles in the motion behavior of bacteria in response to magnetic field changes under blue light. The MO-MCS provides a valuable tool for investigating the response mechanisms of micro-organisms to environmental physical factors.

The widely used clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease (Cas) system is thought to have evolved from IS200/IS605 transposons. TnpB proteins, encoded by one type of IS200/IS605 transposon, are considered to be the evolutionary ancestors of Cas12 nucleases, which have been engineered to function as RNA-guided DNA endonucleases for genome editing in bacteria and human cells. TnpB nucleases, which are smaller than Cas nucleases, have been engineered for use in genome editing in animal systems, but the feasibility of this approach in plants remained unknown. Here, we obtained stably transformed genome-edited mutants in rice (Oryza sativa) by adapting three recently identified TnpB genome editing vectors, encoding distinct TnpB nucleases (ISAam1, ISDra2, and ISYmu1), for use in plants, demonstrating that the hypercompact TnpB proteins can effectively edit plant genomes. ISDra2 and ISYmu1 precisely edited their target sequences, with no off-target mutations detected, showing that TnpB transposon nucleases are suitable for development into a new genome editing tool for plants. Future modifications improving the genome-editing efficiency of the TnpB system will facilitate plant functional studies and breeding programs.

Magnetogenetics has shown great potential for cell function and neuromodulation using heat or force effects under different magnetic fields; however, there is still a contradiction between experimental effects and underlying mechanisms by theoretical computation. In this study, we aimed to investigate the role of reactive oxygen species (ROS) in mechanical force-dependent regulation from a physicochemical perspective. The transient receptor potential vanilloid 4 (TRPV4) cation channels fused to ferritin (T4F) were overexpressed in HEK293T cells and exposed to static magnetic fields (sMF, 1.4-5.0 mT; gradient: 1.62 mT/cm). An elevation of ROS levels was found under sMF in T4F-overexpressing cells, which could lead to lipid oxidation. Compared with the overexpression of TRPV4, ferritin in T4F promoted the generation of ROS under the stimulation of sMF, probably related to the release of iron ions from ferritin. Then, the resulting ROS regulated the opening of the TRPV4 channel, which was attenuated by the direct addition of ROS inhibitors or an iron ion chelator, highlighting a close relationship among iron release, ROS production, and TRPV4 channel activation. Taken together, these findings indicate that the produced ROS under sMF act on the TRPV4 channel, regulating the influx of calcium ions. The study would provide a scientific basis for the application of magnetic regulation in cellular or neural regulation and disease treatment and contribute to the development of the more sensitive regulatory technology.

Traditional Chinese medicine, specifically the Jianpi Tiaoqi (JPTQ) decoction, has been explored for its role in treating breast cancer, particularly in inhibiting lung metastasis in affected mice. Our study evaluated the effects of JPTQ on several factors, including tumour growth, apoptosis, angiogenesis, epithelial-to-mesenchymal transition (EMT) and immune microenvironment regulation. We used bioluminescence imaging to observe in situ tumour growth and potential lung metastasis. Transcriptomic analysis provided insights into gene expression, whereas flow cytometry was used to examine changes in specific immune cells, such as CD4+ T cells and myeloid-derived suppressor cells. Several essential proteins and genes, including vascular endothelial growth factor (VEGF), matrix metalloprotein-9 (MMP-9) and B-cell lymphoma 2 (Bcl-2), were assessed through quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry. Our findings showed that JPTQ treatment inhibited tumour proliferation in cancer-bearing mice. Bioluminescence imaging and pathological analysis indicated a reduction in lung metastasis. Transcriptome analysis of lung and tumour tissues indicated that the genes associated with EMT, angiogenesis, proliferation and apoptosis were regulated in the JPTQ-treated group. Kyoto Encyclopedia of Genes and Genomes analysis suggested enrichment of immune-related pathways. Flow cytometry indicated that JPTQ treatment reduced the proportion of monocyte-myeloid-derived suppressor cells in the lung and increased the number of CD4+ T cells in the peripheral blood and the number of T helper 1 (Th1) cells in the spleen (P < 0.05). E-cadherin and cleaved caspase 3 were upregulated, whereas Snail, Bcl-2, Ki67 and VEGF were downregulated in the lung and tumour tissues; moreover, the expression of MMP-9 was downregulated in the lung tissue (P < 0.05). In essence, JPTQ not only inhibits tumour growth in affected mice, but also promotes positive immune responses, reduces angiogenesis, boosts tumour cell apoptosis, reverses EMT and decreases breast cancer lung metastasis.

BACKGROUND:Alzheimer's disease (AD) is the most prevalent form of dementia, but no effective therapeutic strategy is available to date. Rhythmic magnetic stimulation is an attractive means of neuron modulation that could be beneficial for restoring learning and memory abilities. OBJECTIVE:To assess the effect of a compound pulsed rhythmic magnetic field (cPMF) on cognition during AD progression and to explore the appropriate cPMF intervention period. METHODS:Female 5xFAD mice aged 10 weeks and 18 weeks were exposed to cPMF with a carrier frequency of 40 Hz, repeated at 5 Hz for 1 h/d for 8 consecutive weeks. The Morris water maze (MWM) test was used for cognitive behavioral assessment. Furthermore, changes in molecular pathology within the brain were detected using immunofluorescence staining and real-time PCR. RESULTS:10-week-old AD mice treated with cPMF explored the target quadrant more frequently than sham-exposed AD mice in MWM test, exhibiting improved learning and memory abilities. Additionally, cPMF exposure alleviated Aβ plaque deposition and astrogliosis in the AD brain. Moreover, neurotrophic factor fibroblast growth factor 1 (FGF1) in the AD brain was upregulated by cPMF treatment. However, in 18-week-old AD mice treated with cPMF, cognitive performance and Fgf1 gene expression were not significantly improved, although Aβ plaque deposition and astrogliosis were alleviated. CONCLUSION:Early intervention via long-term rhythmic cPMF stimulation may alleviate the histopathological features and enhance neuroprotective gene Fgf1 expression, thereby improving the cognitive performance of 5xFAD mice, which should provide promising insight for the clinical treatment of patients with AD.

Background 5-Fluorouracil (5-Fu), a prominent chemotherapeutic agent for colorectal cancer (CRC) treatment, is often associated with gastrointestinal toxicities, particularly diarrhea. Our previous study demonstrated that berberine (BBR) ameliorates 5-Fu-induced intestinal mucosal injury by modulating the gut microbiota in rats. Nevertheless, the precise molecular mechanism underlying BBR's protective effect on intestinal mucosa remains elusive, and its impact on the anti-tumor efficacy of 5-Fu warrants further investigation. Methods The effect of BBR on 5-Fu-induced intestinal mucosal injury was investigated using a tumor-bearing murine model, employing H&E staining, 16 S rDNA sequencing, transcriptome sequencing, Western blot analysis, cell experiments and constructing a pseudo-germ-free tumor xenograft model. Result Our findings demonstrate that BBR alleviates intestinal mucosal damage, reduces the levels of inflammatory factors (IL-6, TNF-α, and IL-1β), and inhibits epithelial cell apoptosis in 5-Fu-treated mice without compromising 5-Fu's anti-tumor efficacy. Moreover, 16 S rDNA sequencing indicated that BBR significantly increases the abundance of Akkermansia and decreases the abundance of pathogenic bacteria Escherichia/Shigella at the genus level. Mechanistically, transcriptome sequencing and Western blot analysis confirmed that BBR upregulates PI3K/AKT/mTOR expression in the intestinal mucosa. However, this effect was not observed in tumor tissues. Notably, BBR did not demonstrate a direct protective effect on 5-Fu-treated CCD841 and SW480 cells. Additionally, BBR had no effect on the PI3K/AKT/mTOR pathway in the intestinal tissue of the 5-Fu-treated mouse model with a depleted gut microbiota. Conclusion This study indicates that BBR alleviates 5-Fu-induced intestinal mucosal injury by modulating the gut microbiota and regulating the PI3K/AKT/mTOR signaling pathway without compromising the anti-tumor efficacy of 5-Fu.

Magnetotactic bacteria (MTB), possessing chains of iron oxide nanoparticles, are potential tools for controlled therapy due to their responsiveness to weak magnetic fields. This study aims to evaluate the targeting and aggregation capabilities of axial AMB-1 and polar MO -1 MTB for therapeutic applications. A three-dimensional focusing magnetic field (fMF)-producing device was designed and established with a gradient magnetic field of 0.08 mT/mm at the central region for the guidance of MTB in vitro and in vivo . Under a unidirectional magnetic field, polar Magneto -ovoid MO -1 formed a single line in the culture dish, whereas axial Magnetospirillum magneticum AMB-1 displayed a small portion aggregated on the centerline. With simultaneous X and Y magnetic field application, MO -1 cells aggregated at a point, while AMB-1 bacteria gathered incompletely. Further, magnetic resonance imaging of breast cancer -bearing nude mice injected subcutaneously with MTB peritumorally and navigated by a fMF revealed more substantial aggregation of MO -1 cells within the tumor than AMB-1 bacteria. Prussian blue staining corroborated the penetration of MO -1 cells into the tumor tissue. These findings suggest that polar MO -1 bacteria exhibit superior targeting and aggregation properties compared to axial AMB-1, indicating their potential suitability for targeted therapeutic applications.

Ethnopharmacological relevancePrevious studies have revealed that a high-fat diet (HFD) promotes the progression of colorectal cancer (CRC) in close association with disturbances in the intestinal flora and metabolic disorders. Xianglian pill (XLP) is a well-established traditional prescription with unique advantages in controlling intestinal flora imbalance and inflammation. However, its therapeutic effects on HFD-related CRC remain largely unknown.Aim of the studyThe primary objective of this research was to investigate the anticancer mechanism of XLP in countering HFD-related CRC.Materials and methodsThe protective effect of XLP was evaluated using azoxymethane (AOM) and dextran sulfate sodium (DSS)-induced CRC model of mice exposed to a HFD. The degree of colorectal carcinogenesis, including body weight, colon length, and histopathology, was measured in mice treated with XLP and untreated mice. The effect of XLP on gut microbiota and its metabolites was detected using 16s rDNA and liquid chromatography/mass spectrometry analysis. Furthermore, a “pseudo-sterile” mouse model was constructed using antibiotics (Abx) to verify whether the gut microbiota and metabolites play a role in the pathogenesis of CRC.ResultsXLP inhibited colorectal tumorigenesis in a dose-dependent fashion. Our findings also highlighted that XLP protected the integrity of the intestinal barrier by reducing the expression of pro-inflammatory cytokines, such as IL-6 and TNF-α, as well as the infiltration of pro-inflammatory macrophages. Mechanistically, XLP inhibited the TLR4/MyD88 pathway. Notably, the XLP treatment increased the proportion of probiotics (particularly Akkermansia) and significantly reduced fecal deoxycholic acid (DCA), a microbiota-derived metabolite of bile acids (BA) closely related to Muribaculaceae. Furthermore, after Abx treatment, XLP showed no clear antitumor effects on CRC. Simultaneously, DCA-supplemented feedings promoted colorectal tumorigenesis and provoked obvious colonic inflammation, M1 macrophage infiltration, and colonic injury. In vitro, the results of RAW-264.7 macrophages and normal intestinal epithelial cells treated with DCA corroborated our in vivo findings, demonstrating consistent patterns in inflammatory responses and intestinal barrier protein expression.ConclusionOur findings suggest that XLP inhibits colorectal cancer associated with HFD via inactivating TLR4/MyD88 by remodeling gut microbiota composition and BA metabolism.

Magnetic hyperthermia is a crucial medical engineering technique for treating diseases, which usually uses alternating magnetic fields (AMF) to interplay with magnetic substances to generate heat. Recently, it has been found that in some cases, there is no detectable temperature increment after applying an AMF, which caused corresponding effects surprisingly. The mechanisms involved in this phenomenon are not yet fully understood. In this study, we aimed to explore the role of Ca2+ overload in the magnetic hyperthermia effect without a perceptible temperature rise. A cellular system expressing the fusion proteins TRPV1 and ferritin was prepared. The application of an AMF (518 kHz, 16 kA/m) could induce the fusion protein to release a large amount of iron ions, which then participates in the production of massive reactive oxygen radicals (ROS). Both ROS and its induced lipid oxidation enticed the opening of ion channels, causing intracellular Ca2+ overload, which further led to decreased cellular viability. Taken together, Ca2+ overload triggered by elevated ROS and the induced oxidation of lipids contributes to the magnetic hyperthermia effect without a perceptible temperature rise. These findings would be beneficial for expanding the application of temperature-free magnetic hyperthermia, such as in cellular and neural regulation, design of new cancer treatment methods.

Dietary fat intake is positively associated with elevated risk of colorectal cancer (CRC). Currently, clinical treatments remian inadequate bacause of the complex pathogenesis of CRC induced by a high-fat diet (HFD). Mechanistically, imbalances in gut microbiota are associated with HFD-associated colorectal tumourigenesis. Therefore, we investigated the anti-tumor activity of berberine (BBR) in modulating the dysregulated gut microbiota and related metabolites by preforming 16S rDNA sequencing and liquid chromatography/mass spectrometry. As expected, BBR treatment significantly decreased the number of colonic polyps, ameliorated gut barrier disruption, and inhibited colon inflammation and related oncogenic pathways in AOM/DSS-induced CRC model mice fed with an HFD. Furthermore, BBR alleviated gut microbiota dysbiosis and increased the abundance of beneficial gut microorganisms, including Akkermansia and Parabacteroides, in HFD-fed CRC mice. In addition, metabolomics analysis demonstrated significantly altered the glycerophospholipid metabolism during the progression of HFD-associated CRC in mice, whereas BBR treatment reverted these changes in glycerophospholipid metabolites, particularly lysophosphatidylcholine (LPC), which was confirmed to promote CRC cell proliferation and ameliorate cell junction impairment. Notably, BBR had no clear anti-tumor effects on HFD-fed CRC model mice with gut microbiota depletion, whereas transplantation of BBR-treated gut microbiota to gut microbiota-depleted CRC mice recapitulated the inhibitory effects of BBR on colorectal tumourigenesis and LPC levels. This study demonstrated that BBR inhibited HFD-associated CRC directly through modulating gut microbiota-regulated LPC levels, thereby providing a promising microbiota-modulating therapeutic strategy for the clinical prevention and treatment of Western diet-associated CRC.

Aims Magnetotactic bacteria (MTB) can use their unique intracellular magnetosome organelles to swim along the Earth's magnetic field. They play important roles in the biogeochemical cycles of iron and sulfur. Previous studies have shown that the applied magnetic fields could affect the magnetosome formation and antioxidant defense systems in MTB. However, the molecular mechanisms by which magnetic fields affect MTB cells remain unclear. We aim to better understand the dark at 28 degrees C-29 degrees C for 20 h, as shownthe interactions between magnetic fields and cells, and the mechanism of MTB adaptation to magnetic field at molecular levels.Methods and results We performed microbiological, transcriptomic, and genetic experiments to analyze the effects of a weak static magnetic field (SMF) exposure on the cell growth and magnetosome formation in the MTB strain Magnetospirillum magneticum AMB-1. The results showed that a 1.5 mT SMF significantly promoted the cell growth but reduced magnetosome formation in AMB-1, compared to the geomagnetic field. Transcriptomic analysis revealed decreased expression of genes primarily involved in the sulfate reduction pathway. Consistently, knockout mutant lacking adenylyl-sulfate kinase CysC did no more react to the SMF and the differences in growth and Cmag disappeared. Together with experimental findings of increased reactive oxidative species in the SMF-treated wild-type strain, we proposed that cysC, as a key gene, can participate in the cell growth and mineralization in AMB-1 by SMF regulation.Conclusions This study suggests that the magnetic field exposure can trigger a bacterial oxidative stress response involved in AMB-1 growth and magnetosome mineralization by regulating the sulfur metabolism pathway. CysC may serve as a pivotal enzyme in mediating sulfur metabolism to synchronize the impact of SMF on both growth and magnetization of AMB-1.