Target-Induced Photocurrent-Polarity-Switching PEC Sensing Platform Based on In Situ Generation of Oxygen Vacancy-Modulated Energy Band Structures.

The polarity of the photocurrent can be modulated by tunable bipolar photoelectrochemical (PEC) behavior, which is anticipated to address the issues of high background signal caused by traditional unidirectional increasing/decreasing response and false-positive/false-negative problems. Here, a new approach is suggested for the first time, which employs a target-induced enzyme-catalyzed reaction and in situ oxygen vacancy (OV) generation to achieve heterojunction photocurrent switching for highly sensitive detection of alkaline phosphatase (ALP). Among them, the ALP can catalyze the decomposition of ascorbic acid phosphate to produce ascorbic acid, which not only acts as an electron donor to change the redox environment but also acts as a reducing agent to introduce OVs into BiOBr semiconductors in cooperation with illumination. The introduction of vacancies can effectively modulate the energy band structure of BiOBr, while with the change of redox conditions, the transfer path of photogenerated carriers is changed, thus realizing the switching of photocurrents, which leads to its use in the construction of a negative-background anti-interference PEC sensing platform, achieving a wide linear range from 0.005 to 500 U·L-1 with a low detection limit of 0.0017 U·L-1. In conclusion, the photocurrent switching operation of this system is jointly regulated by chemistry, optics, and carrier motion, which provides a new idea for the construction of a PEC sensing platform based on photocurrent polarity switching.

Selective removal of Pb(II) from yellow rice wine using magnetic carbon-based adsorbent.

BACKGROUND: The non-distilled property and prolonged production period of yellow rice wine have significantly increased the metal residue problem, posing a threat to human health. In this study, a magnetic carbon-based adsorbent, named magnetic nitrogen-doped carbon (M-NC), was developed for the selective removal of lead(II) (Pb(II)) from yellow rice wine. RESULTS: The results showed that the uniformly structured M-NC could be easily separated from the solution, exhibiting a high Pb(II) adsorption capacity of 121.86 mg g-1 . The proposed adsorption treatment showed significant Pb(II) removal efficiencies (91.42-98.90%) for yellow rice wines in 15 min without affecting their taste, odor, and physicochemical characteristics of the wines. The adsorption mechanism studied by X-ray photoelectron spectroscopy (XPS) and Fourier-transform infrared (FTIR) analyses indicated that the selective removal of Pb(II) could be attributed to the electrostatic interaction and covalent interaction between the empty orbital of Pb(II) and the π electrons of the N species on M-NC. Additionally, the M-NC showed no significant cytotoxicity on the Caco-2 cell lines. CONCLUSION: Selective removal of Pb(II) from yellow rice wine was achieved using magnetic carbon-based adsorbent. This facile and recyclable adsorption operation could potentially address the challenge of toxic metal pollution in liquid foods. © 2023 Society of Chemical Industry.

[Intestinal and pharyngeal microbiota in early neonates: an analysis based on high-throughput sequencing]. / åŸºäºŽé«˜é€šé‡æµ‹åºåˆ†æžæ—©æœŸæ–°ç”Ÿå„¿è‚ é“å’Œå’½éƒ¨å¾®ç”Ÿç‰©èŒç¾¤.

OBJECTIVES: To investigate the distribution characteristics and correlation of intestinal and pharyngeal microbiota in early neonates. METHODS: Full-term healthy neonates who were born in Shanghai Pudong New Area Maternal and Child Health Hospital from September 2021 to January 2022 and were given mixed feeding were enrolled. The 16S rRNA sequencing technique was used to analyze the stool and pharyngeal swab samples collected on the day of birth and days 5-7 after birth, and the composition and function of intestinal and pharyngeal microbiota were analyzed and compared. RESULTS: The diversity analysis showed that the diversity of pharyngeal microbiota was higher than that of intestinal microbiota in early neonates, but the difference was not statistically significant (P>0.05). On the day of birth, the relative abundance of Proteobacteria in the intestine was significantly higher than that in the pharynx (P<0.05). On days 5-7 after birth, the relative abundance of Actinobacteria and Proteobacteria in the intestine was significantly higher than that in the pharynx (P<0.05), and the relative abundance of Firmicutes in the intestine was significantly lower than that in the pharynx (P<0.05). At the genus level, there was no significant difference in the composition of dominant bacteria between the intestine and the pharynx on the day of birth (P>0.05), while on days 5-7 after birth, there were significant differences in the symbiotic bacteria of Streptococcus, Staphylococcus, Rothia, Bifidobacterium, and Escherichia-Shigella between the intestine and the pharynx (P<0.05). The analysis based on the database of Clusters of Orthologous Groups of proteins showed that pharyngeal microbiota was more concentrated on chromatin structure and dynamics and cytoskeleton, while intestinal microbiota was more abundant in RNA processing and modification, energy production and conversion, amino acid transport and metabolism, carbohydrate transport and metabolism, coenzyme transport and metabolism, and others (P<0.05). The Kyoto Encyclopedia of Genes and Genomes analysis showed that compared with pharyngeal microbiota, intestinal microbiota was more predictive of cell motility, cellular processes and signal transduction, endocrine system, excretory system, immune system, metabolic diseases, nervous system, and transcription parameters (P<0.05). CONCLUSIONS: The composition and diversity of intestinal and pharyngeal microbiota of neonates are not significantly different at birth. The microbiota of these two ecological niches begin to differentiate and gradually exhibit distinct functions over time.

Combination of transcatheter arterial chemoembolization and portal vein embolization for patients with hepatocellular carcinoma: a review.

BACKGROUND: Transcatheter arterial chemoembolization has been widely used in patients with hepatocellular carcinoma. However, double blood supply and the existence of portal vein tumor thrombus influence the efficacy of transcatheter arterial chemoembolization. MAIN BODY: Theoretically, portal vein embolization combined with transcatheter arterial chemoembolization may bring a breakthrough in the therapeutic effect of hepatocellular carcinoma. The feasibility, efficacy, long-term survival benefits, and side effects of the combined treatment have been explored in previous studies. Chemotherapeutic agents may also be added in the portal vein embolization procedure to further improve the treatment response. CONCLUSION: In this study, we review the existing data and studies on the combined treatment in patients with hepatocellular carcinoma and provide an overall view of the strategy.

Folate-targeted nanoparticle delivery of androgen receptor shRNA enhances the sensitivity of hormone-independent prostate cancer to radiotherapy.

Androgen receptor (AR) plays a crucial role in the development and progression of prostate cancer (PCa). PCa patients typically receive androgen deprivation therapy; nonetheless, these patients eventually develop castration and radiation resistance. We hypothesized that we could further improve radiotherapeutic efficacy of hormone-independent PCa (HIPC) by silencing AR. In this study, nanoparticle (NP) AR-shRNA was formulated using folate-targeted H1 nanopolymer. We demonstrated that NP AR-shRNA enhances PCa radiosensitivity as indicated by the inhibition of cell growth, increased apoptosis, and increased cell cycle arrest in AR-dependent HIPC in vitro. The radiosensitizing effect of NP AR-shRNA could be validated in vivo, as NP AR-shRNA significantly suppressed tumor growth and prolonged the survival of HIPC tumor-bearing mice. Analysis at the molecular level revealed that NP AR-shRNA inhibits DNA damage repair signaling pathways. Our study supports further investigation of NP AR-shRNA for the improvement of radiotherapy efficacy in HIPC.

Nanoparticle formulation of small DNA molecules, Dbait, improves the sensitivity of hormone-independent prostate cancer to radiotherapy.

Intensification of radiotherapy has been shown to improve prostate cancer (PCa) outcomes. We hypothesized that we could further improve radiotherapy efficacy through the use DNA repair inhibitors. In this study, we evaluated the use of a new class of DNA damage repair inhibitor, nanoparticle (NP) Dbait, in radiosensitization of PCa. NP Dbait was formulated using H1 nanopolymer (folate-polyethylenimine600-cyclodextrin). We demonstrated that NP Dbait was a potent radiosensitizer in vitro by colony forming assay using PCa cell lines. The result was validated in vivo using mouse xenograft models of PCa and we showed that NP Dbait significantly suppressed tumor growth and prolonged survival. Western blot, immunofluorescence and immunohistochemistry showed that NP Dbait inhibited DNA damage repair signaling pathways by mimicking DNA double-strand breaks. Our study supports further investigations of NP Dbait in improving the therapeutic efficacy of cancer radiotherapy.

NAP1L1 Promotes Endometrial Cancer Progression via EP300-Mediated DDX5 Promoter Acetylation.

Endometrial cancer (EC) is one of the predominant tumors of the female reproductive system. In this current study, we investigated the functions and related mechanisms of NAP1L1/DDX5 in EC. This retrospective study analyzed the medical records of EC patients, collected tissue samples for NAP1L1 and DDX5 staining, and conducted survival analysis using the Kaplan-Meier method. To evaluate the impact of NAP1L1 and/or DDX5 on cellular processes in EC cells, several techniques were employed. These included CCK-8 assay, wound healing assay, Transwell assay, as well as overexpression or knockdown of target gene expression. Additionally, ChIP, dual luciferase reporter gene, Co-IP assay were utilized to confirm the interaction between NAP1L1, EP300 and DDX5. Furthermore, qRT-PCR, western blot and Co-IP assay were performed to analyze the modulation of NAP1L1/DDX5 in Wnt/ß-catenin. NAP1L1 and DDX5 expression were upregulated in EC tissues, and correlated with poor prognosis. NAP1L1/DDX5 promoted EC cell proliferation, migration and invasion. NAP1L1 promotes acetylation and transcription by recruiting EP300 to the DDX5 promoter. DDX5 could activate Wnt/ß-catenin signal by binding to ß-catenin. In animal models, knockdown of NAP1L1 inhibits EC tumor growth and lung metastasis. To sum up, our study demonstrated that NAP1L1 promoted the malignant phenotypes of EC cells via recruiting EP300 to promote DDX5 acetylation, thus activating the Wnt/ß-catenin signaling pathway. Implications: Our research findings indicate that targeting the NAP1L1/EP300/DX5 axis might be a new potential treatment option for endometrial cancer.

A portable polymeric electrochromism-based visual biosensing device with distance readout.

A distance-based visual electrochromic biosensing device is proposed. With this device, the naked eye is capable of discerning the distance of discoloration, which exhibits a positive correlation with the concentration of the detected substance.

Highly selective detection and removal of mercury ions in the aquatic environment based on magnetic ZIF-71 multifunctional composites with sufficient chlorine functional groups.

The development of both detection and removal technologies for heavy metal ions is of great importance. Most of the existing adsorbents that contain oxygen, nitrogen or sulfur functional groups can remove heavy metals, but achieving both selective detection and removal of a single metal ion is difficult because they bind to a wide range of heavy metal ions. Herein, we selected zeolite imidazolium hydrochloride framework-71 (ZIF-71) with sufficient chlorine functional groups to fabricate magnetic ZIF-71 multifunctional composites (M-ZIF-71). M-ZIF-71 had a large specific surface area, excellent water stability, and good magnetic properties, which made M-ZIF-71 conducive to the separation and recovery of adsorbents and the assembly of electrodes. M-ZIF-71 exhibited high selectivity, wide linear range (1-500 µg/L), and low detection limit (0.32 µg/L) for electrochemical detection of mercury ions (Hg2+). Meanwhile, M-ZIF-71 demonstrated rapid Hg2+ adsorption with a high capacity of 571.2 mg/g and excellent recyclability. The high selectivity for Hg2+ was attributed to the powerful affinity of highly electronegative chlorine and Hg2+. Moreover, XPS spectra demonstrated the interaction between chlorine and Hg2+. This work provides a new inspiration for applications in the targeted monitoring and removal of heavy metal pollution.

Nano­selenium functionalized chitosan gel beads for Hg(II) removal from apple juice.

The presence of potentially toxic elements and compounds poses threats to the quality and safety of fruit juices. Among these, Hg(II) is considered as one of the most poisonous heavy metals to human health. Traditional chitosan-based and selenide-based adsorbents face challenges such as poor adsorption capacity and inconvenient separation in juice applications. In this study, we prepared nano­selenium functionalized chitosan gel beads (nanoSe@CBs) and illustrated the synergistic promotions between chitosan and nanoSe in removing Hg(II) from apple juice. The preparation conditions, adsorption behaviors, and adsorption mechanism of nanoSe@CBs were systematically investigated. The results revealed that the adsorption process was primarily controlled by chemical adsorption. At the 0.1 % dosage, the adsorbent exhibited high uptake, and the maximum adsorption capacity from the Langmuir isotherm model could reach 376.5 mg/g at room temperature. The adsorbent maintained high adsorption efficiency (> 90 %) across a wide range of Hg(II) concentrations (0.01 to 10 mg/L) and was unaffected by organic acids present in apple juice. Additionally, nanoSe@CBs showed negligible effects on the quality of apple juice. Overall, nanoSe@CBs open up possibilities to be used as a safe, low-cost and highly-efficient adsorbent for the removal of Hg(II) from juices and other liquid foods.

Phosphorylated FOXQ1, a novel substrate of JNK1, inhibits sorafenib-induced ferroptosis by activating ETHE1 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly heterogeneous and malignant cancer with poor overall survival. The application of sorafenib is a major breakthrough in the treatment of HCC. In our study, FOXQ1 was significantly overexpressed in sorafenib-resistant HCC cells and suppressed sorafenib-induced ferroptosis. We found that phosphorylation of FOXQ1 at serine 248 is critical for the suppression of sorafenib-induced ferroptosis. Furthermore, as the upstream phosphorylation kinase of FOXQ1, JNK1, which is activated by sorafenib, can directly phosphorylate the serine 248 site of FOXQ1. Then, the phosphorylated FOXQ1 got a high affinity for the promoter of ETHE1 and activates its transcription. Further flow cytometry results showed that ETHE1 reduced intracellular lipid peroxidation and iron levels. Collectively, our study implicated the JNK1-FOXQ1-ETHE1 axis in HCC ferroptosis induced by sorafenib, providing mechanistic insight into sensitivity to sorafenib therapy of HCC.

A bioetching-induced visualized-organic photoelectrochemical transistor dual-signal mode sensor for alkaline phosphatase detection.

A study of an integrated OPECT biosensor gate and the EC color-changing region on the same chip was carried out, achieving sensitive detection through bioetching-induced signal changes. Enzymatic bioetching enables specific alkaline phosphatase (ALP) detection by catalyzing the production of CdS, which modulates the channel current and generates a visual signal.

The role of USP7-YY1 interaction in promoting colorectal cancer growth and metastasis.

Colorectal cancer (CRC) remains a significant global health issue with high incidence and mortality. Yin Yang 1 (YY1) is a powerful transcription factor that acts dual roles in gene activation and repression. High expression level of YY1 has been reported in CRC, indicating the existence of stable factors of YY1 in CRC cells. We aimed to identify the key molecules and underlying mechanisms responsible for stabilizing YY1 expression in CRC. Mass spectrometry analysis was utilized to identify USP7 as a potential molecule that interacted with YY1. Mechanically, USP7 stabilizes YY1 expression at the protein level by interfering its K63 linkage ubiquitination. YY1 exerts its oncogenic function through transcriptionally activating TRIAP1 but suppressing LC3B. In addition, at the pathological level, there is a positive correlation between the expression of YY1 and the budding of CRC. This study has revealed the intricate interplay between YY1 and USP7 in CRC, suggesting that they could serve as novel therapeutic targets or predictive biomarkers for CRC patients.

The correlation of the intestinal with pharyngeal microbiota in early neonates.

Introduction: The gut-lung axis has long been recognized as an important mechanism affecting intestinal and lung immunity. Still, few studies have examined the correlation between the intestinal and pharyngeal microbiota in early neonates, especially when feeding patterns are one of the main drivers of microbiota development. Methods: To explore the composition and function of intestinal and pharyngeal microbiota and to analyze the effect of limited formula feeding on the initial microbiota colonization in early full-term neonates, we characterized the stool and oropharyngeal microbiota of 20 healthy full-term newborns sampled on days 0 and 5-7 after birth using 16S rRNA gene sequencing. Based on the sequencing results, a comparison was made of the compositions and functions of the intestinal and oropharyngeal microbiota for analysis. Results and discussion: At the phylum level, Firmicutes, Actinobacteria, Proteobacteria, and Bacteroidetes were the most abundant in both niches. At the genus level, the species of pioneer bacteria were rich in the intestine and oropharynx but low in abundance on day 0. On days 5-7, Bifidobacterium (25.40%) and Escherichia-Shigella (22.16%) were dominant in the intestine, while Streptococcus (38.40%) and Staphylococcus (23.13%) were dominant in the oropharynx. There were eight core bacteria genera in the intestine and oropharynx on days 5-7, which were Bifidobacterium, Escherichia-Shigella, Staphylococcus, Streptococcus, Bacteroides, Parabacteroides, Rothia, and Acinetobacter. As indicated by PICRUSt analysis, on days 5-7, the intestinal microbiota was more predictive than the oropharyngeal microbiota in transcription, metabolism, cell motility, cellular processes and signaling, and organismal system function in the KEGG pathway. Compared to exclusive breastfeeding, limited formula feeding (40-60%) had no significant effect on the neonatal intestinal and oropharyngeal microbiota composition during the initial colonization period. Our results suggest that the initial colonization of microbiota is closely related to the ecological niche environment in the intestine and oropharynx, with their core microbiota being closely correlated. We found that early limited formula feeding could not significantly affect the initial colonization of microbiota in the intestine and oropharynx.

Copper transporter gene ATP7A: A predictive biomarker for immunotherapy and targeted therapy in hepatocellular carcinoma.

BACKGROUND: ATP7A is an important copper transporter that regulates numerous cellular biological processes. However, the role of ATP7A in immunotherapy and targeted therapy, especially for hepatocellular carcinoma (HCC), remains unknown. METHODS: We analyzed ATP7A expression and its effect on digestive system tumor prognoses, assessed its expression in tissue microarrays from 319 HCC patients, and investigated the relationship between ATP7A expression and tumor immunity. Specifically, we evaluated the possible association between ATP7A and programmed death ligand 1 (PD-L1) expression in human HCC tissues. Finally, we analyzed the effect of ATP7A on sorafenib efficacy in HCC. RESULTS: ATP7A is generally highly expressed in digestive system tumors but related to poor prognosis only in HCC. ATP7A levels are positively associated with immune cell infiltration and immune checkpoint expression (especially PD-L1). HCC patients coexpressing APT7A and PD-L1 demonstrate poor prognoses. Moreover, HCC patients with high ATP7A levels were more sensitive to sorafenib and demonstrated higher survival rates after sorafenib treatment. CONCLUSIONS: This study provides insights into the correlation between ATP7A levels and tumor immune infiltration and immune checkpoint function in HCC, sheds light on the significance of ATP7A in cancer progression, and provides guidance for more effective and general therapeutic strategies.

Facile synthesis of chitosan-tartaric acid biosorbents for removal of Cu(II) and Cd(II) from water and tea beverages.

Consumption of water and tea beverages leads to the intake of heavy metals by humans. Development of technology for decontamination greatly reduces the risks of the heavy metal exposure. In this study, environment-friendly chitosan-tartaric acid biosorbents (CTBs) were synthesized by a facile one-step cross-linking strategy to mitigate the Cu(II) and Cd(II) contamination in water and tea beverages. The cross linkage of tartaric acid and chitosan endowed CTBs with excellent properties in aspects of surface roughness, mechanical strength, and acid resistance. Adsorption performance and mechanism of CTBs were studied, and the Langmuir isotherm model and pseudo-second-order kinetic model were adhered during adsorption. Up to 90 % removal efficiencies of Cu(II) and Cd(II) from water and tea beverages by CTBs were achieved. Moreover, the adsorption showed only a slight reduction in the quality of tea beverages. This study offers a new insight for reduction of heavy metals-pollution in beverages.

Efferocytosis: An accomplice of cancer immune escape.

The clearance of apoptotic cells by efferocytes such as macrophages and dendritic cells is termed as "efferocytosis", it plays critical roles in maintaining tissue homeostasis in multicellular organisms. Currently, available studies indicate that efferocytosis-related molecules and pathways are tightly associated with cancer development, metastasis and treatment resistance, efferocytosis also induces an immunosuppressive tumor microenvironment and assists cancer cells escape from immune surveillance. In this study, we reviewed the underlying mechanisms of efferocytosis in mediating the occurrence of cancer immune escape, and then emphatically summarized the strategies of using efferocytosis as therapeutic target to enhance the anti-tumor efficacies of immune checkpoint inhibitors, hoping to provide powerful evidences for more effective therapeutic regimens of malignant tumors.

The role of transcription factor Yin Yang-1 in colorectal cancer.

BACKGROUND: Yin Yang-1 (YY1) is identified as a transcription factor with multiple functions. However, the role of YY1 in tumorigenesis remains controversial and its regulatory effects may depend upon not only cancer types, but also its interacting partners, chromatin structure, and the context in which it acts. It has been detected that YY1 was highly expressed in colorectal cancer (CRC). Intriguingly, many YY1-repressed genes exhibit tumor suppressive potential while YY1 silencing is related to chemotherapy resistance. Therefore, it is crucial to meticulously explore YY1 protein structure and the dynamic alteration of its interactome in each cancer type. This review attempts to describe the structure of YY1, summarize the mechanism that influence the expression level of YY1 and also highlight the recent advances in our understanding of regulatory insights of YY1 functions in CRC. METHODS: Related studies were identified through scoping search of PubMed, Web of science, Scopus and Emhase concerning the terms of "colorectal cancer", colorectal carcinoma" or CRC with "YY1". The retrieval strategy included title, abstract, and keywords with no language limitations. All the included articles were categorized depending on the mechanisms they explored. RESULTS: In total, 170 articles were identified for further screening. After removing the duplication, not relevant outcomes and review articles, 34 were finally included in the review. Among them, 10 articles revealed the reasons of YY1 high expression in CRC, 13 articles explored YY1 function in CRC, and 11 articles fell into both aspects. In addition, we also summarized 10 clinical trials concerning the expression and activity of YY1 in various diseases, which offers a hint for future application. CONCLUSIONS: YY1 is highly expressed in CRC and broadly recognized as an oncogenic factor during the whole course of CRC. Sporadic controversial views are raised in term of CRC treatment, reminding us that future studies should take the influence of therapeutic regimens into concern.

Beer-derived nitrogen, phosphorus co-doped carbon quantum dots: Highly selective on-off-on fluorescent probes for the detection of ascorbic acid in fruits.

A rapid, facile and ultrasensitive fluorescence sensing system based on beer-derived nitrogen, phosphorus co-doped carbon quantum dots (N, P-CQDs) for the detection of ascorbic acid (AA) in fruits was proposed. N, P-CQDs were successfully synthesized by one-step hydrothermal method, which afforded a high quantum yield (21.7 %), and showed the fluorescence with a maximum emission wavelength of 450 nm at an excitation wavelength of 370 nm. Further, N, P-CQDs were employed as an efficient sensor for ultrasensitive Fe3+-detection at concentrations ranging from 1-20 µM and 100-300 µM, respectively. N, P-CQDs@Fe3+ showed a high sensitivity and selectivity for AA detection. A linear response range for AA was obtained from 1 to 200 µM with limit of detection of 0.84 µM was obtained for AA. The result of MTT test showed that N, P-CQDs exhibit low toxicity, providing fast, accurate and less toxic route for testing AA in the food analysis fields.

Pyrotinib and chrysin synergistically potentiate autophagy in HER2-positive breast cancer.

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) has been the most challenging subtype of BC, consisting of 20% of BC with an apparent correlation with poor prognosis. Despite that pyrotinib, a new HER2 inhibitor, has led to dramatic improvements in prognosis, the efficacy of pyrotinib monotherapy remains largely restricted due to its acquired resistance. Therefore, identifying a new potential antitumor drug in combination with pyrotinib to amplify therapeutic efficacy is a pressing necessity. Here, we reported a novel combination of pyrotinib with chrysin and explored its antitumor efficacy and the underlying mechanism in HER2-positive BC. We determined that pyrotinib combined with chrysin yielded a potent synergistic effect to induce more evident cell cycle arrest, inhibit the proliferation of BT-474 and SK-BR-3 BC cells, and repress in vivo tumor growth in xenograft mice models. This may be attributed to enhanced autophagy induced by endoplasmic reticulum stress. Furthermore, the combined treatment of pyrotinib and chrysin induced ubiquitination and glucose-6-phosphate dehydrogenase (G6PD) degradation by upregulating zinc finger and BTB/POZ domain-containing family protein 16 (ZBTB16) in tumorigenesis of BC. Mechanistically, we identified that miR-16-5p was a potential upstream regulator of ZBTB16, and it showed a significant inverse correlation with ZBTB16. Inhibition of miR-16-5p overexpression by restoring ZBTB16 significantly potentiated the overall antitumor efficacy of pyrotinib combined with chrysin against HER2-positive BC. Together, these findings demonstrate that the combined treatment of pyrotinib and chrysin enhances autophagy in HER2-positive BC through an unrecognized miR-16-5p/ZBTB16/G6PD axis.