HIF1A-dependent overexpression of MTFP1 promotes lung squamous cell carcinoma development by activating the glycolysis pathway.

Introduction: Mitochondrial fission process 1 (MTFP1) is an inner mitochondrial membrane (IMM) protein implicated in the development and progression of various tumors, particularly lung squamous cell carcinoma (LUSC). This study aims to provide a more theoretical basis for the treatment of LUSC. Methods: Through bioinformatics analysis, MTFP1 was identified as a novel target gene of HIF1A. MTFP1 expression in LUSC was examined using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Proteomics Data Commons (PDC) databases. The Kaplan-Meier plotter (KM plotter) database was utilized to evaluate its correlation with patient survival. Western blot and chromatin immunoprecipitation (ChIP) assays were employed to confirm the regulatory relationship between MTFP1 and HIF1A. Additionally, cell proliferation, colony formation, and migration assays were conducted to investigate the mechanism by which MTFP1 enhances LUSC cell proliferation and metastasis. Results: Our findings revealed that MTFP1 overexpression correlated with poor prognosis in LUSC patients(P < 0.05). Moreover, MTFP1 was closely associated with hypoxia and glycolysis in LUSC (R = 0.203; P < 0.001, R = 0.391; P < 0.001). HIF1A was identified as a positive regulator of MTFP1. Functional enrichment analysis demonstrated that MTFP1 played a role in controlling LUSC cell proliferation. Cell proliferation, colony formation, and migration assays indicated that MTFP1 promoted LUSC cell proliferation and metastasis by activating the glycolytic pathway (P < 0.05). Conclusions: This study establishes MTFP1 as a novel HIF1A target gene that promotes LUSC growth by activating the glycolytic pathway. Investigating MTFP1 may contribute to the development of effective therapies for LUSC patients, particularly those lacking targeted oncogene therapies.

FOXP4-mediated induction of PTK7 activates the Wnt/ß-catenin pathway and promotes ovarian cancer development.

Ovarian cancer (OV) poses a significant challenge in clinical settings due to its difficulty in early diagnosis and treatment resistance. FOXP4, belonging to the FOXP subfamily, plays a pivotal role in various biological processes including cancer, cell cycle regulation, and embryonic development. However, the specific role and importance of FOXP4 in OV have remained unclear. Our research showed that FOXP4 is highly expressed in OV tissues, with its elevated levels correlating with poor prognosis. We further explored FOXP4's function through RNA sequencing and functional analysis in FOXP4-deficient cells, revealing its critical role in activating the Wnt signaling pathway. This activation exacerbates the malignant phenotype in OV. Mechanistically, FOXP4 directly induces the expression of protein tyrosine kinase 7 (PTK7), a Wnt-binding receptor tyrosine pseudokinase, which causes abnormal activation of the Wnt signaling pathway. Disrupting the FOXP4-Wnt feedback loop by inactivating the Wnt signaling pathway or reducing FOXP4 expression resulted in the reduction of the malignant phenotype of OV cells, while restoring PTK7 expression reversed this effect. In conclusion, our findings underscore the significance of the FOXP4-induced Wnt pathway activation in OV, suggesting the therapeutic potential of targeting this pathway in OV treatment.

The R2R3-MYB transcription factor ZeMYB32 negatively regulates anthocyanin biosynthesis in Zinnia elegans.

KEY MESSAGE: This study identified an R2R3-MYB from Zinnia elegans, ZeMYB32, which negatively regulates anthocyanin biosynthesis.

SnO2/Au Microelectromechanical Systems Modified by Oxygen Vacancies for Enhanced Sensing of Dioctyl Phthalate.

Dioctyl phthalate (DOP) serves as a characteristic gas utilized in early electrical fire detection, its detection offers promising prospects for the prevention of electrical fires. In this study, we employed a modified photodeposition method to prepare Tin dioxide (SnO2) materials co-modified with Au and oxygen vacancies. Subsequently, microelectromechanical systems (MEMS) gas sensor for DOP detection were fabricated, utilizing 0.5 %Au/SnO2-I as the sensing material. Characterization results reveal the presence of abundant oxygen vacancies in 0.5 %Au/SnO2-I. The synergistic interplay of Au and oxygen vacancies resulted in a remarkable response of 9.98 to 20 ppm of DOP at operational temperature of 250 °C. This represents a significant 96 % enhancement in comparison to the response value of 4.50 exhibited by pure SnO2 at 300 °C. Notably, this gas sensor boasts low power consumption and demonstrates a quick response in the detection of overheating polyvinyl chloride (PVC) cables under simulated conditions.

FBXO5-mediated RNF183 degradation prevents endoplasmic reticulum stress-induced apoptosis and promotes colon cancer progression.

Endoplasmic reticulum (ER) stress induces the unfolded protein response (UPR), and prolonged ER stress leads to cell apoptosis. Despite increasing research in this area, the underlying molecular mechanisms remain unclear. Here, we discover that ER stress upregulates the UPR signaling pathway while downregulating E2F target gene expression and inhibiting the G2/M phase transition. Prolonged ER stress decreases the mRNA levels of E2F2, which specifically regulates the expression of F-Box Protein 5(FBXO5), an F-box protein that functions as an inhibitor of the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase complex. Depletion of FBXO5 results in increased ER stress-induced apoptosis and decreased expression of proteins related to PERK/IRE1α/ATF6 signaling. Overexpression of FBXO5 wild-type (not its ΔF-box mutant) alleviates apoptosis and the expression of the C/EBP Homologous Protein (CHOP)/ATF. Mechanistically, we find that FBXO5 directly binds to and promotes the ubiquitin-dependent degradation of RNF183, which acts as a ubiquitin E3 ligase in regulating ER stress-induced apoptosis. Reversal of the apoptosis defects caused by FBXO5 deficiency in colorectal cancer cells can be achieved by knocking down RNF183 in FBXO5-deficient cells. Functionally, we observed significant upregulation of FBXO5 in colon cancer tissues, and its silencing suppresses tumor occurrence in vivo. Therefore, our study highlights the critical role of the FBXO5/RNF183 axis in ER stress regulation and identifies a potential therapeutic target for colon cancer treatment.

Classification of oolong tea varieties based on computer vision and convolutional neural networks.

BACKGROUND: In the contemporary food industry, accurate and rapid differentiation of oolong tea varieties holds paramount importance for traceability and quality control. However, achieving this remains a formidable challenge. This study addresses this lacuna by employing machine learning algorithms - namely support vector machines (SVMs) and convolutional neural networks (CNNs) - alongside computer vision techniques for the automated classification of oolong tea leaves based on visual attributes. RESULTS: An array of 13 distinct characteristics, encompassing color and texture, were identified from five unique oolong tea varieties. To fortify the robustness of the predictive models, data augmentation and image cropping methods were employed. A comparative analysis of SVM- and CNN-based models revealed that the ResNet50 model achieved a high Top-1 accuracy rate exceeding 93%. This robust performance substantiates the efficacy of the implemented methodology for rapid and precise oolong tea classification. CONCLUSION: The study elucidates that the integration of computer vision with machine learning algorithms constitutes a promising, non-invasive approach for the quick and accurate categorization of oolong tea varieties. The findings have significant ramifications for process monitoring, quality assurance, authenticity validation and adulteration detection within the tea industry. © 2023 Society of Chemical Industry.

Self-Cross-Linked Chitosan/Albumin-Bound Nanoparticle Hydrogel for Inhibition of Postsurgery Malignant Glioma Recurrence.

The development of chemoimmunotherapy with reduced systemic toxicity using local formulations is an effective strategy for combating tumor recurrence. Herein, we reported a localized hydrogel system for antitumor chemoimmunotherapy, formed by doxorubicin (DXR)-loaded bovine serum albumin (BSA) nanoparticles self-cross-linked with natural polysaccharide chitosan (CS). The drug-loaded hydrogel (DXR-CBGel) with antiswelling performance and prolonged drug-release profile was combined with antiprogrammed cell death protein 1 (aPD-1) as an in situ vaccine for treating glioblastoma multiforme (GBM) lesions. The antiswelling hydrogel system shows excellent biosafety for volume-sensitive GBM lesions. Both the albumin-bound formulation and the in situ gelation design facilitate the local retention and sustained release of DXR to generate long-term chemoimmunotherapy with reduced systemic toxicity. The chemotherapy-induced immunogenic cell death of DXR with the assistance of immunotherapeutic CS can trigger tumor-specific immune responses, which are further amplified by an immune checkpoint blockade to effectively inhibit cancer recurrence. The strategy of combining albumin-bound drug formulation and biocompatible polymer-based hydrogel for localized chemoimmunotherapy shows great potential against postsurgery glioblastoma recurrence.

Yantiao Formula intervention in Rats with Sepsis: Network Pharmacology and Experimental Analysis.

AIM AND OBJECTIVE: Traditional Chinese Medicine prescribes Yantiao Formula (YTF; peach kernel, mirabilite, Angelica sinensis, Radix Scrophulariae, raw rhubarb, Radix Paeoniae, Flos Lonicerae, Forsythia, and Ophiopogon japonicus) to treat sepsis. Clinically, it reduced the inflammatory response of sepsis. It also reduced lung damage by decreasing the level of TNF-α in septic rats' serum. Using network pharmacology analysis, we investigated the efficacy network and mechanism of YTF in treating sepsis. MATERIALS AND METHODS: We used the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and a Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine (BATMAN-TCM) combined with literature to collect the main components in YTF and their targets. DisGeNET and GENECARDS databases were used for sepsis-related targets. Cytoscape 3.7.1 software was used to construct the herbcomponent- target and ingredient-target-disease interaction protein-protein interaction networks of YTF. The jvenn was used to perform the intersection of YTF targets and sepsis targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed． We also created a sepsis rat model using cecal ligation and perforation and stimulated alveolar macrophages (NR8383) with endotoxin to investigate the mechanisms of YTF. RESULTS: GO, and KEGG enrichment analysis revealed that these targets involved mineralocorticoid secretion, aldosterone secretion, active regulation of chronic inflammatory response, the exogenous coagulation pathway, and other pathophysiology. It was linked to various inflammatory factors and the MAPK pathway. YTF inhibits the p38MAPK pathway and decreases TNF- α, IL-6, and CXCL8 levels. CONCLUSION: YTF has a multi-component, multi-target, and multi-channel role in treating sepsis. The primary mechanisms may involve inhibiting the p38MAPK pathway to reduce the inflammatory response.

A systematic characterization of soil/dust ingestion for typical subpopulations in China.

An accurate assessment of human exposure to pollutants through the ingestion of dust and/or soil particles depends on a thorough understanding their rate of human ingestion. To this end, we investigated the load and size distribution patterns of dust/soil particles on the hands of three typical subpopulations, including preschoolers, college students, and security guards (outdoor workers). The geometric mean diameter of dust/soil particles on hands was observed to be 38.7 ± 11.2, 40.0 ± 12.1, and 36.8 ± 10.4 µm for preschoolers, college students, and security guards, respectively. The particle size distribution differed between subpopulations: Preschoolers were more exposed to fine particles, whereas security guards were exposed to more coarse particles. The geometric means of dust/soil particle loading on the hands were 0.126, 0.0163, and 0.0377 mg/cm2 for preschoolers, college students, and security guards, respectively. Males had statistically higher dust/soil particle loadings on hands than females, notably for preschoolers and college students; preschoolers with frequent hand contact with the bare ground had higher dust/soil particle loadings compared to those of peers in contact with commercial and residential grounds. The mean total dust/soil particle ingestion rate was estimated to be 245, 19.7, and 33.1 mg/day for preschoolers, college students, and security guards, respectively. Our estimates for college students and security guards are close to the consensus central-tendency values recommended by the U.S. EPA's Exposure Factor Handbook for American adults, whereas the estimates for children are much higher than the upper percentile values recommended for American children.

USP14 regulates heme metabolism and ovarian cancer invasion through BACH1 deubiquitination and stabilization.

The deubiquitinating enzyme USP14 has been established as a crucial regulator in various diseases, including tumors, neurodegenerative diseases, and metabolic diseases, through its ability to stabilize its substrate proteins. Our group has utilized proteomic techniques to identify new potential substrate proteins for USP14, however, the underlying signaling pathways regulated by USP14 remain largely unknown. Here, we demonstrate the key role of USP14 in both heme metabolism and tumor invasion by stabilizing the protein BACH1. The cellular oxidative stress response factor NRF2 regulates antioxidant protein expression through binding to the antioxidant response element (ARE). BACH1 can compete with NRF2 for ARE binding, leading to the inhibition of the expression of antioxidant genes, including HMOX-1. Activated NRF2 also inhibits the degradation of BACH1, promoting cancer cell invasion and metastasis. Our findings showed a positive correlation between USP14 expression and NRF2 expression in various cancer tissues from the TCGA database and normal tissues from the GTEx database. Furthermore, activated NRF2 was found to increase USP14 expression in ovarian cancer (OV) cells. The overexpression of USP14 was observed to inhibit HMOX1 expression, while USP14 knockdown had the opposite effect, suggesting a role for USP14 in regulating heme metabolism. The depletion of BACH1 or inhibition of heme oxygenase 1 (coded by HMOX-1) was also found to significantly impair USP14-dependent OV cell invasion. In conclusion, our results highlight the importance of the NRF2-USP14-BACH1 axis in regulating OV cell invasion and heme metabolism, providing evidence for its potential as a therapeutic target in related diseases.

Multifunctional theragnostic ultrasmall gold nanodot-encapsuled perfluorocarbon nanodroplets for laser-focused ultrasound sequence irradiation (LFSI)-based enhanced tumor ablation.

Despite the substantial potential of focused ultrasound therapy, its efficacy in cancer therapy has been limited due to the high cavitation threshold and safety concerns regarding the use of high-intensity energy pulses. Here, ultrasmall Au nanodot-loaded PEG-modified perfluorocarbon nanodroplets (Au-PFCnDs) were prepared and used as a therapeutic enhancer. A LFSI method was designed to achieve enhanced tumor ablation at a mild focused ultrasound (FUS) energy pulse with the assistance of the instinct photothermal effect of intratumor-permeable ultrasmall Au nanodots under 808 nm NIR laser irradiation. In addition to their therapeutic function, Au-PFCnDs can also generate multimodal images to provide information for tumor surveillance and treatment guidance. The experimental results also showed that the cRGD-targeted Au-PFCnDs could be more efficiently delivered into the tumor and selectively destroy tumors with no observable side effects on normal tissue under LFSI treatment.

ZeMYB9 regulates cyanidin synthesis by activating the expression of flavonoid 3'-hydroxylase gene in Zinnia elegans.

Petal color in Zinnia elegans is characterized mainly by anthocyanin accumulation. The difference in the content of anthocyanins, especially cyanidins, affects petal coloration in Z. elegans, but the underlying regulatory mechanism remains elusive. Here, we report one R2R3-MYB transcription factor from subgroup 6, ZeMYB9, acting as a positive regulator of anthocyanin accumulation in Z. elegans. Up-regulated expression of ZeMYB9 and flavonoid 3'-hydroxylase gene (ZeF3'H) was detected in the cultivar with higher cyanidin content. ZeMYB9 could specifically activate the promoter of ZeF3'H, and over-expression of ZeMYB9 induces much greater anthocyanin accumulation and higher expression level of anthocyanin biosynthetic genes in both petunia and tobacco. And then, ZeMYB9 was demonstrated to interact with ZeGL3, a bHLH transcription factor belonging to IIIf subgroup. Promoter activity of ZeF3'H was significantly promoted by co-expressing ZeMYB9 and ZeGL3 compared with expressing ZeMYB9 alone. Moreover, transient co-expression of ZeMYB9 and ZeGL3 induced anthocyanin accumulation in tobacco leaves. Our results suggest that ZeMYB9 could enhance cyanidin synthesis and regulate petal color in Z. elegans though activating the expression of ZeF3'H, by itself or interacting with ZeGL3.

TOCN/copper calcium titanate composite aerogel films as high-performance triboelectric materials for energy harvesting.

The development of high-performance cellulose-based triboelectric nanogenerators (TENG) has been a subject widely concerned by researchers. Here, we prepared a composite aerogel film based on TEMPO-oxidized cellulose nanofiber (TOCN) and copper calcium titanate (CaCu3Ti4O12, CCTO) nanoparticles. Under their comprehensive effects of the enhanced dielectric performance, the TOCN/CCTO-20 composite film with 20 % CCTO content based TENG device showed the best output performance of an open circuit voltage of 152 V, a short circuit current of 33.8 µA and a power density of 483 mW/m2, which were 3.37, 4.07 and 3.71 times higher than that of the pure TOCN based TENG device, respectively. In addition, effects of external force conditions, aerogel film size parameters and the agglomeration state of high filler content on the output performance were also studied. These results indicated that the TOCN/CCTO composite aerogel films can be used as efficient and low-cost cellulose-based triboelectric positive materials for energy harvesting.

Distribution of flame retardants among indoor dust, airborne particles and vapour phase from Beijing: spatial-temporal variation and human exposure characteristics.

The occurrence and distribution of 10 brominated flame retardants (BFRs) and 10 organophosphate flame retardants (OPFRs) were investigated in indoor dust, total suspended particles (TSP), and vapour phase from offices (n = 10), homes (n = 9), and day-care centres (n = 10) in Beijing, China. Three types of samples were collected biweekly from one office and one home over a year to examine temporal trends. BFRs in dust significantly correlated with those in TSP, while OPFRs significantly correlated among all three matrices. In addition, BFRs in dust (ng/g) and TSP (pg/m3) exhibited similar temporal trends with higher levels in the cold season, whereas OPFRs in TSP and vapour phase (pg/m3) showed similar temporal trends with higher levels in the warm season. The geometric mean concentrations of BFRs and OPFRs in the three matrices from the above mentioned three types of indoor microenvironments were used for exposure and health risk estimation, and ∑7OPFRs showed much higher hazard index (HI) values than ∑10BFRs for all subpopulations, and inhalation of OPFRs was a major risk source. With the volatility of flame retardants (FRs) decreasing, the contribution of dust ingestion and dermal absorption showed an increasing trend, and the contribution of inhalation exhibited a gradual decreasing trend, which implied the dominant exposure pathway to FRs is strongly related to the vapour pressure (25 °C, Pa) of these substances. Using a single type of microenvironment or the collection of samples at a single point in time can lead to overestimation or underestimation of overall exposure and risk for people to some extent. The correlations of FRs in dust, TSP, and vapour phase from indoor microenvironments, as well as their temporal trends were first reported in this study, which will provide a basis for more accurate FR exposure assessments in the future.

Porous cellulose composite aerogel films with super piezoelectric properties for energy harvesting.

The piezoelectric effect is one of the most promising electromechanical coupling processes for mechanical energy conversion and energy harvesting. However, natural polymer based piezoelectric materials are of poor piezoelectric performance. we developed flexible porous piezoelectric aerogel films based on TEMPO-oxidized cellulose nanofibrils (TOCN) and MoS2 nanosheets. Those aerogel films possessed large specific surface areas and abundant mesopores. Moreover, they exhibited very good piezoelectric properties when a field strength of 20 MV/m was used to polarize MoS2 nanosheets and air in the mesopores. When assembled to piezoelectric nanogenerators (PENGs), a TOCN/MoS2 aerogel film PENG containing 6 wt% of MoS2 exhibited the best output performance. It generated an open circuit voltage of 42 V and a short-circuit current of 1.1 µA, a maximum area power density of 1.29 µW/cm2 and a maximum volume power density of 0.143 µW/cm3. These features enable them to be promising piezoelectric materials for energy harvesting.

Transforming Passive into Active: Multimodal Pheophytin-Based Carbon Dots Customize Protein Corona to Target Metastatic Breast Cancer.

Formation of protein corona on nanomaterials surface in vivo is usually considered as an unpredictable event for a predefined targeted delivery system for malignant cancers. In most situations, these protein coronas substantially change targeting efficiency or even cause adverse reactions which both hinder the clinical translation of the cargo-delivery systems. Active customization of protein corona onto nanomaterials surfaces can benefit their biomedical performances and open up new opportunities in construction of targeted delivery systems. Herein, lipid-PEG/pheophytin carbon dots (LPCDs) are prepared from natural chlorophyll and integrate seamlessly with positron emission tomography imaging, near-infrared fluorescence imaging, and photodynamic therapy capacity. In vitro measurements demonstrate that the LPCDs can actively absorb apolipoproteins into the protein corona to enhance their uptakes in breast cancer cells. In vivo studies confirm that LPCDs can give accurate delineation of metastatic breast cancer foci from surrounding normal tissues with multimodal biomedical functions. The feasibility of using LPCDs as a multimodal imaging and cancer-targeting nanoplatform may provide impetus for developing precise yet facile protein corona-targeted delivery systems for future clinical practice.

A novel mutation in PCK2 gene causes primary angle-closure glaucoma.

Primary angle-closure glaucoma (PACG) is an ophthalmic genetic disease characterized by direct contact between the iris and trabecular meshwork, resulting in an obstructed outflow of aqueous humor from the eye. However, it is unclear as to what role genetics plays in the development of PACG. The present study investigated the disease-causing mutation in a five-generation Chinese PACG family using whole-genome sequencing. A novel heterozygous missense mutation c.977C>T in PCK2 gene was identified in five affected family members, but not in any unaffected and 86 unrelated healthy individuals. This nucleotide substitute is predicted to result in a proline to leucine substitution p.Pro326Leu. Furthermore, the function of this mutation was analyzed through various in vitro assays using the RGC-5 cell line. Our results demonstrate that the p.Pro326Leu mutation induces RGC-5 cell cycle arrest and apoptosis with a decreased BcL-XL. The increasing P53, P27, P21, AKT, and P-GSK3α were also detected in the cells transfected with c.977C>T mutation, suggesting that this mutation within PCK2 gene cause PACG through impairment of AKT/GSK3α signaling pathway.

In vitro immunomodulation of magnesium on monocytic cell toward anti-inflammatory macrophages.

Biodegradable magnesium (Mg) has shown great potential advantages over current bone fixation devices and vascular scaffold technologies; however, there are few reports on the immunomodulation of corrosive Mg products, the micron-sized Mg particles (MgMPs). Human monocytic leukemia cell line THP-1 was set as the in vitro cell model to estimate the immunomodulation of MgMPs on cell proliferation, apoptosis, polarization and inflammatory reaction. Our results indicated high-concentration of Mg2+ demoted the proliferation of the THP-1 cells and, especially, THP-1-derived macrophages, which was a potential factor that could affect cell function, but meanwhile, cell apoptosis was almost not affected by Mg2+. In particular, the inflammation regulatory effects of MgMPs were investigated. Macrophages exposed to Mg2+ exhibited down-regulated expressions of M1 subtype markers and secretions of pro-inflammatory cytokines, up-regulated expression of M2 subtype marker and secretion of anti-inflammatory cytokine. These results indicated Mg2+ could convert macrophages from M0 to M2 phenotype, and the bioeffects of MgMPs on human inflammatory cells were most likely due to the Mg2+-induced NF-κB activation reduction. Together, our results proved Mg2+ could be used as a new anti-inflammatory agent to suppress inflammation in clinical applications, which may provide new ideas for studying the immunomodulation of Mg-based implants on human immune system.

Racquet Sports Recognition Using a Hybrid Clustering Model Learned from Integrated Wearable Sensor.

Racquet sports can provide positive benefits for human healthcare. A reliable detection device that can effectively distinguish movement with similar sub-features is therefore needed. In this paper, a racquet sports recognition wristband system and a multilayer hybrid clustering model are proposed to achieve reliable activity recognition and perform number counting. Additionally, a Bluetooth mesh network enables communication between a phone and wristband, and sets-up the connection between multiple devices. This allows users to track their exercise through the phone and share information with other players and referees. Considering the complexity of the classification algorithm and the user-friendliness of the measurement system, the improved multi-layer hybrid clustering model applies three-level K-means clustering to optimize feature extraction and segmentation and then uses the density-based spatial clustering of applications with noise (DBSCAN) algorithm to determine the feature center of different movements. The model can identify unlabeled and noisy data without data calibration and is suitable for smartwatches to recognize multiple racquet sports. The proposed system shows better recognition results and is verified in practical experiments.

Highly aligned hierarchical intrafibrillar mineralization of collagen induced by periodic fluid shear stress.

Periodic fluid shear stress (FSS) is one of the main mechanical microenvironments in mineralization of bone matrix. To elucidate the mechanism of periodic FSS in collagen mineralization, a mechanical loading induced mineralization system is developed and compared with traditional polyacrylic acid (PAA) induced mineralization. Fourier transform infrared (FTIR) spectroscopy, calcium-to-phosphorus molar ratio and transmission electron microscopy (TEM) demonstrate that both periodic FSS and PAA can control the size of amorphous calcium phosphate (ACP) to avoid aggregation and help the formation of intrafibrillar mineralization. Differently, periodic FSS under a proper cycle and range can accelerate the conversion of ACP to apatite crystals and alleviate the reduced transformation caused by PAA. Under the action of template analogues, periodic FSS can also promote the formation of highly oriented hierarchical intrafibrillar mineralized (HIM) collagen. These findings are helpful for understanding the mechanism of collagen mineralization in natural bone matrix and contribute to the design of novel bone substitute materials with hierarchical structures.