Surgical tumor-derived nanoplatform targets tumor-associated macrophage for personalized postsurgical cancer immunotherapy.

Directly activating CD8+ T cells within the tumor through antigen-presenting cells (APCs) hold promise for tumor elimination. However, M2-like tumor-associated macrophages (TAMs), the most abundant APCs in tumors, hinder CD8+ T cell activation due to inefficient antigen cross-presentation. Here, we demonstrated a personalized nanotherapeutic platform using surgical tumor-derived galactose ligand-modified cancer cell membrane (CM)-coated cysteine protease inhibitor (E64)-loaded mesoporous silica nanoparticles for postsurgical cancer immunotherapy. The platform targeted M2-like TAMs and released E64 within lysosomes, which reshaped antigen cross-presentation and directly activated CD8+ T cells, thus suppressing B16-OVA melanoma growth. Furthermore, this platform, in combination with anti-PD-L1 antibodies, enhanced the therapeutic efficacy and substantially inhibited 4T1 tumor growth. CMs obtained from surgically resected tumors were used to construct a personalized nanotherapeutic platform, which, in synergy with immune checkpoint blockade (ICB), effectively inhibited postsurgical tumor recurrence in 4T1 tumor. Our work offered a robust, safe strategy for cancer immunotherapy and prevention of postsurgical tumor recurrence.

A nano-bioconjugate modified with anti-SIRPα antibodies and antisense oligonucleotides of mTOR for anti-atherosclerosis therapy.

Atherosclerosis is the main cause of a series of fatal cardiovascular diseases, characterized by pathological accumulation of apoptotic cells and lipids. Pro-phagocytic antibody-based or pro-autophagy gene-based therapies are currently being explored to stimulate the phagocytic clearance of apoptotic cells and lipid metabolism; however, monotherapies are only moderately effective or require high doses with unacceptable side effects. Herein, we engineered a specific nano-bioconjugate loaded with antisense oligonucleotides (ASOs) of mammalian target of rapamycin (mTOR) and modified with anti-signal-regulated protein-α antibody (aSIRPα) for macrophage-mediated atherosclerosis therapy. The specific nano-bioconjugate utilized acid-responsive calcium phosphate (CaP) as a carrier to load mTOR ASOs, coated with lipid on the surface of CaP nanoparticles (ASOs@CaP), and subsequently modified with aSIRPα. The resulting nano-bioconjugates could accumulate within atherosclerotic plaques, target to macrophages and reactivate lesional phagocytosis through blocking the CD47-SIRPα signaling axis. In addition, efficient delivery of mTOR ASOs inhibited mTOR expression, which significantly restored impaired autophagy. The combined action of mTOR ASOs and aSIRPα reduced apoptotic cells and lipids accumulation. This nanotherapy significantly reduced plaque burden and inhibited progression of atherosclerotic lesions. These results show the potential of specific nano-bioconjugates for the prevention of atherosclerotic cardiovascular disease. STATEMENT OF SIGNIFICANCE: Atherosclerosis is the main cause of a series of fatal cardiovascular diseases. Pro-phagocytic antibody-based or pro-autophagy gene-based therapies are currently being explored to stimulate the phagocytic clearance of apoptotic cells and lipid metabolism; however, monotherapies are only moderately effective or require high doses with unacceptable side effects. Herein, we engineered a specific nano-bioconjugate loaded with antisense oligonucleotides (ASOs) of mammalian target of rapamycin (mTOR) and modified with anti-signal-regulated protein-α antibody (aSIRPα) for macrophage-mediated atherosclerosis therapy. Our study demonstrated that the combined action of mTOR ASOs and aSIRPα reduced apoptotic cells and lipids accumulation. This nanotherapy significantly reduced plaque burden and inhibited progression of atherosclerotic lesions. These results show the potential of specific nano-bioconjugates for the prevention of atherosclerotic cardiovascular disease.

A DNA Logic Circuit Equipped with a Biological Amplifier Loaded into Biomimetic ZIF-8 Nanoparticles Enables Accurate Identification of Specific Cancers In Vivo.

DNA logic circuits (DLC) enable the accurate identification of specific cell types, such as cancer cells, but they face the challenges of weak output signals and a lack of competent platforms that can efficiently deliver DLC components to the target site in the living body. To address these issues, we rationally introduced a cascaded biological amplifier module based on the Primer Exchange Reaction inspired by electronic circuit amplifier devices. As a paradigm, three abnormally expressed Hela cell microRNAs (-30a, -17, and -21) were chosen as "AND" gate inputs. DLC response to these inputs was boosted by the amplifier markedly enhancing the output signal. More importantly, the encapsulation of DLC and amplifier components into ZIF-8 nanoparticles resulted in their efficient delivery to the target site, successfully distinguishing the Hela tumor subtype from other tumors in vivo. Thus, we envision that this strategy has great potential for clinical cancer diagnosis.

Classroom walkthroughs as an effective strategy for preschool improvement during the COVID-19 lockdowns: a Chinese model.

Classroom walkthroughs are a widely used strategy for school improvement, varying over contexts and times. This study aims to explore the Chinese model of classroom walkthroughs in early childhood settings (ECS) during the COVID-19 lockdowns through a triangulated qualitative study. First, a group of ECS leaders (N = 15; Myear of teaching experience = 18.87, SD = 7.74, range = 6-33 years) and a group of teachers (N = 15; Myear of teaching experience = 8.40, SD = 3.96, range = 3-19 years) were interviewed in early 2022, and leaders' observations notes were reviewed. The interview data were transcribed, recoded, and analyzed using an inductive approach, and the walkthrough documents were examined as a triangulation. Four themes and 13 subthemes emerged from the interview data: content, pedagogical skills, tasks, and challenges pertaining to classroom walk-throughs. Two major challenges against efficient classroom walkthroughs during the COVID-19 lockdowns were found: building community and feeding forward. Based on the results, a Chinese model of classroom walkthrough was proposed. Implications for quality improvement were also addressed.

Intrinsic and extrinsic dopings in epitaxial films MnBi2Te4.

The intrinsic antiferromagnetic topological insulator MnBi2Te4and members of its family have been the subject of theoretical and experimental research, which has revealed the presence of a variety of defects and disorders that are crucial in determining the topological and magnetic properties. This also brings about challenges in realizing the quantum states like the quantum anomalous Hall and the axion insulator states. Here, utilizing cryogenic magnetoelectric transport and magnetic measurements, we systematically investigate the effects arising from intrinsic doping by antisite defects and extrinsic doping by Sb in MnBi2Te4epitaxial films grown by molecular beam epitaxy. We demonstrate that the nonequilibrium condition in epitaxy allows a wide growth window for optimizing the crystalline quality and defect engineering. While the intrinsic antisite defects caused by the intermixing between Bi and Mn can be utilized to tune the Fermi level position as evidenced by a p-to-n conductivity transition, the extrinsic Sb-doping not only compensates for this doping effect but also modifies the magnetism and topology of the film, during which a topological phase transition is developed. Conflicting reports from the theoretical calculations and experimental measurements in bulk crystals versus epitaxial films are addressed, which highlights the intimate correlation between the magnetism and topology as well as the balance between the Fermi-level positioning and defect control. The present study provides an experimental support for the epitaxial growth of the intrinsic topological insulator and underlines that the topology, magnetism, and defect engineering should be revisited for enabling a steady and reliable film production.

Neutrophil-Membrane-Coated Biomineralized Metal-Organic Framework Nanoparticles for Atherosclerosis Treatment by Targeting Gene Silencing.

Antisense oligonucleotides (ASOs) are promising tools for gene silencing and have been exploited as therapeutics for human disease. However, delivery of therapeutic ASOs to diseased tissues or cells and subsequent escape from the endosomes and release of ASO in the cytosol remain a challenge. Here, we reported a neutrophil-membrane-coated zeolitic imidazolate framework-8 (ZIF-8) nanodelivery platform (AM@ZIF@NM) for the targeted transportation of ASOs against microRNA-155 (anti-miRNA-155) to the endothelial cells in atherosclerotic lesions. Neutrophil membrane could improve plaque endothelial cells targeting through the interaction between neutrophil membrane protein CD18 and endothelial cell membrane protein intercellular adhesion molecule-1 (ICAM-1). The ZIF-8 "core" provided high loading capacity and efficient endolysosomal escaping ability. Delivery of anti-miR-155 effectively downregulated miR-155 expression and also saved the expression of its target gene BCL6. Moreover, RELA expression and the expression of its downstream target genes CCL2 and ICAM-1 were correspondingly reduced. Consequently, this anti-miR-155 nanotherapy can inhibit the inflammation of atherosclerotic lesions and alleviate atherosclerosis. Our study shows that the designed biomimetic nanodelivery system has great application prospects in the treatment of other chronic diseases.

A xylan assisted surface-enhanced Raman scattering substrate for rapid food safety detection.

Cellulose fiber/paper-based surface-enhanced Raman scattering (SERS) is considered as a promising food safety detection technology due to its non-toxicity, low cost, flexibility, and hygroscopicity for possible rapid on-site agricultural product contaminant detection. However, it faces the problems of poor noble metal adhesion and toxic noble metal reducing agent. In this study, a natural macromolecule-xylan was used as both a reducing agent and a stabilizing agent to prepare stable Au-Ag bimetal nanoparticles, which were anchored on the paper surface by xylans in order to fabricate a paper-based Au-Ag bimetallic SERS substrate. The results show that the SERS substrate has a high Raman enhancement performance and reproductively. The substrate can effectively detect trace pesticide, i.e., thiram, and the limit of detection is as low as 1 × 10-6 mol/L (0.24 ppm). In addition, the paper-based SERS substrate can be used for direct detection of pesticide residues on the surface of fruit. The paper-based SERS substrate developed in this study has great potential in applications for rapid food safety detection.

An environment-friendly dip-catalyst with xylan-based catalytic paper coatings.

Replacing catalyst supports with sustainable and degradable materials is an urgent task. Xylan is a type of abundant natural polymers with potential applications in dispersing, anchoring, and coating materials, but its material values have always been underestimated. In this study, polyethyleneimine modified dialdehyde xylan (DAX-PEI) was used as a dispersing and anchoring agent to bind Pd nanoparticles onto paper surface to produce a DAX-PEI-Pd coated paper, which was used to catalyze Suzuki-Miyaura reactions. The catalytic coated paper exhibited a good catalytic activity with a yield of 91% and a high turnover frequency (TOF) of 3300 h-1. Besides, it showed an excellent recyclability with the same catalytic coated paper being used 15 times and still having a yield of nearly 90%. This environment-friendly catalytic coated paper owns its great prospect in organic synthesis.

Erythrocyte-Membrane-Enveloped Biomineralized Metal-Organic Framework Nanoparticles Enable Intravenous Glucose-Responsive Insulin Delivery.

A "closed-loop" insulin delivery system that can mimic the dynamic and glucose-responsive insulin secretion as islet ß-cells is desirable for the therapy of type 1 and advanced type 2 diabetes mellitus (T1DM and T2DM). Herein, we introduced a kind of "core-shell"-structured glucose-responsive nanoplatform to achieve intravenous "smart" insulin delivery. A finely controlled one-pot biomimetic mineralization method was utilized to coencapsulate insulin, glucose oxidase (GOx), and catalase (CAT) into the ZIF-8 nanoparticles (NPs) to construct the "inner core", where an efficient enzyme cascade system (GOx/CAT group) served as an optimized glucose-responsive module that could rapidly catalyze glucose to yield gluconic acid to lower the local pH and effectively consume the harmful byproduct hydrogen peroxide (H2O2), inducing the collapse of pH-sensitive ZIF-8 NPs to release insulin. The erythrocyte membrane, a sort of natural biological derived lipid bilayer membrane which has intrinsic biocompatibility, was enveloped onto the surface of the "inner core" as the "outer shell" to protect them from elimination by the immune system, thus making the NPs intravenously injectable and could stably maintain a long-term existence in blood circulation. The in vitro and in vivo results indicate that our well-designed nanoplatform possesses an excellent glucose-responsive property and can maintain the blood glucose levels of the streptozocin (STZ)-induced type 1 diabetic mice at the normoglycemic state for up to 24 h after being intravenously administrated, confirming an intravenous insulin delivery strategy to overcome the deficits of conventional daily multiple subcutaneous insulin administration and offering a potential candidate for long-term T1DM treatment.

mRNA-Activated Multifunctional DNAzyme Nanotweezer for Intracellular mRNA Sensing and Gene Therapy.

Deoxyribozyme (DNAzyme) is regarded as a promising gene therapy drug. However, poor cellular uptake efficacy and low biological stability limit the utilization of DNAzyme in gene therapy. Here, we report a well-known programmable DNAzyme-based nanotweezer (DZNT) that provides a new strategy for the detection of TK1 mRNA and survivin mRNA-targeted gene silencing therapy. At the end of the DZNT arm, there are two functionalized single-stranded DNA and each consists of two parts: the segment complementary to TK1 mRNA and the split-DNAzyme segment. The hybridization with intracellular TK1 mRNA enables the imaging of TK1 mRNA. Meanwhile, the hybridization draws the split-DNAzyme close to each other and activates DNAzyme to cleave the survivin mRNA to realize gene silencing therapy. The results demonstrate that the DZNT nanocarrier has excellent cell penetration, good biocompatibility, and noncytotoxicity. DZNT can image intracellular biomolecule TK1 mRNA with a high contrast. Furthermore, the split-DNAzyme can efficiently cleave the survivin mRNA with the aid of TK1 mRNA commonly present in cancer cells, accordingly can selectively kill cancer cells, and has no harm to normal cells. Taken together, the multifunctional programmable DZNT provides a promising platform for the early diagnosis of tumors and gene therapy.

Biomineralized metal-organic framework nanoparticles enable a primer exchange reaction-based DNA machine to work in living cells for imaging and gene therapy.

Sensitive tumor imaging and precise tumor therapy play critical roles in the cancer combat. Herein, we build a DNA machine based on a primer exchange reaction (PER) for mRNA imaging and gene therapy. By using zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) to co-deliver the components including a primer, hairpin and strand displacing polymerase to the living cells, the PER-based DNA machine can be initiated by intracellular survivin mRNA and continuously produce Bcl-2 antisense DNA (ASD), which enables the DNA machine not only to image survivin mRNA but also to implement gene therapy. The results demonstrate that ZIF-8 NPs can protect the polymerases and nucleic acid probes from protease attack and nuclease degradation. After internalization, pH-responsive ZIF-8 NPs can efficiently release cargos from endo-lysosomes due to the protonation effect. The intracellular PER-based DNA machine has been demonstrated to be able to sensitively image survivin mRNA expression levels and selectively kill the cancer cells and has no effect on the normal cells. The PER-based DNA machine may provide a promising platform for early stage tumor diagnosis and more precise tumor therapy.

A photocontrolled and self-powered bipedal DNA walking machine for intracellular microRNA imaging.

In this work, we report a photocontrolled and self-powered DNA walking machine with bipedal DNAzyme walkers for intracellular microRNA imaging.

Aptamer-Functionalized DNA Origami for Targeted Codelivery of Antisense Oligonucleotides and Doxorubicin to Enhance Therapy in Drug-Resistant Cancer Cells.

Drug resistance is a major obstacle to the efficient therapy of drug-resistant cancer. To overcome this problem, we constructed a multifunctional DNA origami-based nanocarrier for codelivery of a chemotherapeutic drug (doxorubicin, Dox) and two different antisense oligonucleotides (ASOs; B-cell lymphoma 2 (Bcl2) and P-glycoprotein (P-gp)) into drug-resistant cancer cells for enhanced therapy. To increase the targeting ability of origami, staple strands with 5'-end extended MUC1 sequences were used in the preparation of aptamer-functionalized origami carrying ASOs (Apt-origami-ASO). Dox-loaded Apt-origami-ASO (Apt-Dox-origami-ASO) was prepared by electrostatic adsorption of Dox in origami. Atomic force microscopy (AFM) images demonstrated the successful preparation of Apt-origami-ASO. In vitro studies showed that the Apt-Dox-origami-ASO (Apt-DOA) could controllably release Dox in pH 5.0 phosphate-buffered saline (PBS) buffer and release ASOs in response to glutathione. Further experiments revealed that the origami could protect ASOs against nuclease degradation in 10% FBS. Confocal imaging showed that the Apt-DOA nanocarrier could efficiently enter the Hela/adriamycin (ADR) cells and escape from lysosomes for codelivery of Dox and ASOs into the cytoplasm. The quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot assays testified the efficient silencing of Bcl2 and P-gp mRNA and downregulation of the corresponding protein expressions by Apt-DOA in Hela/ADR cells. Moreover, with the synergetic effect by codelivery of multi-ASOs and Dox, the anticancer assay showed that Apt-DOA could circumvent multidrug resistance and significantly enhance cancer therapy in Hela/ADR and MCF-7/ADR cells. Hence, this multifunctional origami-based codelivery nanocarrier presents a new strategy for efficient therapy of drug-resistant cancer.

A spatial-confinement hairpin cascade reaction-based DNA tetrahedral amplifier for mRNA imaging in live cells.

The three-dimensional (3D) DNA nanostructure has been got much attention due to its excellent biocompatibility, enhanced structural stability, highly programmable and perfect cell-delivery performance. Here, a novel 3D DNA tetrahedron amplifier (DTA) has been developed for rapid and efficient mRNA imaging in living cells using target catalyzing spatial-confinement hairpin DNA assembly cascade reaction inside the DNA nanostructure. The DTA was constructed by assembling a DNA tetrahedron with four DNA strands at first, and then by assembling two metastable DNA hairpins H1 (Cy5) and H2 (Cy3) at specific locations of the DNA tetrahedron. In the presence of target mRNA, the catalyzed hairpin assembly (CHA) reaction on the DTA could be triggered and a H1-H2 duplexes nanostructure could be formed, which would obtain a significant fluorescence resonance energy transfer (FRET) signal, and release the target mRNA could trigger next H1-H2 duplexes formation. Due to the 3D DNA tetrahedral spatial-confinement effect, the circular reaction of DTA could achieve rapid and efficient amplification detection of target mRNA in living cells. Moreover, the DTA show excellent structural stability and non-cytotoxicity. This strategy presents a versatile method for the ultrasensitive detection of biomarkers in living system and gains a deeper development of the DNA nanostructures in biomedical functions.

Engineering a Biodegradable Nanocarrier for Enhancing the Response of T98G Cells to Temozolomide.

Temozolomide (TMZ), the most common DNA alkylating agent, is predominantly mediated by O6-methylguanine DNA lesions for the treatment of glioblastoma (GBM). When O6-methylguanine-DNA methyltransferase (MGMT) is present, TMZ-induced O6-methylguanine lesions are repaired, resulting in the emergence of resistance to chemotherapy. Herein, we attempted to enhance the response of T98G cells to TMZ by gene silencing of MGMT. In this work, we developed transition metal manganese (Mn)-doped mesoporous silica nanoparticles (MSNs) as a carrier system for the co-delivery of TMZ and 10-23 DNAzyme, and realized gene silencing to enhance the TMZ sensitivity in T98G cells. The intelligent theranostic platform based on manganese-doped mesoporous silica nanoparticles (Mn-MSNs) can be decomposed and release chemotherapy drugs under acidic pH and reducing conditions. Meanwhile, the produced Mn2+ could act as a cofactor of 10-23 DNAzyme to effectively cleave MGMT mRNA, knock down MGMT protein, and sensitize T98G cells to TMZ-induced apoptosis. By co-delivering TMZ and 10-23 DNAzyme employing Mn-MSNs, the concentrations of TMZ that needed to inhibit cell growth by 50% (IC50 values) decreased (by more than 3.8-fold) compared with free TMZ. This work shows that the designed platform holds great promise for advancing the treatment of drug-resistant cancer.

Biomineralized Metal-Organic Framework Nanoparticles Enable Enzymatic Rolling Circle Amplification in Living Cells for Ultrasensitive MicroRNA Imaging.

The enzymatic amplification strategy in living cells faces challenges of highly efficient intracellular codelivery of amplification reagents including DNA polymerase. In this work, we develop biomineralized metal-organic framework nanoparticles (MOF NPs) as a carrier system for intracellular codelivery of ϕ29 DNA polymerase (ϕ29DP) and nucleic acid probes and realize a polymerization amplification reaction in living cells. A pH-sensitive biodegradable MOF NP of zeolitic imidazolate framework-8 (ZIF-8) is utilized to encapsulate ϕ29DP and adsorb nucleic acid probes. After uptake into cells, the encapsulated ϕ29DP and surface-adsorbed DNA probes are released and escaped from endolysosomes. In the presence of ϕ29DP and deoxyribonucleotide triphosphates (dNTPs), the intracellular miRNA-21 triggers a rolling circle amplification (RCA) reaction and the autonomous synthesized Mg2+-dependent DNAzyme cleaves the fluorogenic substrate, providing a readout fluorescence signal for the monitoring of miRNA-21. This is the first example of the intracellular RCA reaction in living cells. Therefore, the proposed method provides new opportunities for achieving enzymatic amplification reaction in living cells.

A microRNA-triggered self-powered DNAzyme walker operating in living cells.

DNA-based nanomachines have received increasing attention due to their great potential to mimic natural biological motors and create novel modes of motion. Here, we report a DNAzyme-based walking machine, which can operate in living cells after triggered by intracellular miRNA-21. The walking machine is constructed by assembling DNAzyme walking strands and FAM-labeled substrate strands on a single gold nanoparticle (AuNP). The DNAzyme walking strand is first silenced by a blocker strand. After cellular uptake, DNAzyme-based walker can be triggered by intracellular miRNA-21 and autonomously walk along the AuNP-based 3D track fueled by DNAzyme-catalyzed substrate cleavage. Each walking step results in the cleavage of a substrate strand and the release of a FAM-labeled DNA strand, allowing real-time monitoring of the operation of the machine. The DNAzyme-based walking machine has been successfully applied to image and monitor miRNA-21 expression levels in living cells with excellent specificity and reliability. This walking machine would hold great potential in the miRNA associated biological research and disease diagnostics.

Comparative pharmacokinetic investigation on baicalin and wogonoside in type 2 diabetic and normal rats after oral administration of traditional Chinese medicine Huanglian Jiedu decoction.

ETHNOPHARMACOLOGICAL RELEVANCE: Huanglian Jiedu decoction (HLJDD) is used traditionally in China for the treatment of diabetes mellitus in clinical practice, which has been proved to be effective. The purpose of this study was to investigate the pharmacokinetic characteristics (especially the area under the curve, AUC) of baicalin and wogonoside in type 2 diabetic rats after oral administration of HLJDD extract and to explore its possible mechanism. MATERIALS AND METHODS: HLJDD extract and Radix scutellariae extract were prepared and the contents of baicalin and wogonoside contained in two extracts were assayed with high performance liquid chromatography (HPLC). Type 2 diabetic rats were induced by high fat diet and intraperitoneal injection of streptozotocin. Pharmacokinetics of baicalin and wogonoside in type 2 diabetic and normal control rats after oral administration of HLJDD extract or Radix scutellariae extract were investigated. Pharmacokinetics of baicalin in type 2 diabetic and normal rats after oral administration of pure baicalin was also investigated. RESULTS: The pharmacokinetic parameters (especially AUCs) of baicalin and wogonoside in type 2 diabetic rats after oral administration of HLJDD extract were remarkably different from those in normal rats. And the alterations of the AUCs of baicalin and wogonoside in type 2 diabetic rats after oral administration of Radix scutellariae extract were similar to those after oral administration of HLJDD extract. Moreover, the increase of the AUC of baicalin in type 2 diabetic rats after oral administration of pure baicalin was similar to that after oral administration of HLJDD extract or Radix scutellariae extract. CONCLUSION: The pharmacokinetic behaviors of baicalin and wogonoside (especially the systemic exposure [AUCs] of baicalin and wogonoside) were significantly altered in type 2 diabetic rats after orally administrated HLJDD extract. And the increased AUCs of baicalin and wogonoside in type 2 diabetic rats after oral administration of HLJDD extract resulted from neither the effects of other herbs contained in HLJDD nor the effects of other components contained in Radix scutellariae. It might result from the effects of the pathological status of type 2 diabetes mellitus.

Hypolipidemic effect of the Chinese polyherbal Huanglian Jiedu decoction in type 2 diabetic rats and its possible mechanism.

Huanglian Jiedu Decoction (HLJDD) is used traditionally in China for the treatment of diabetes mellitus in clinical practice, which has been proved to be effective. In present investigation, the 3D-HPLC fingerprint of HLJDD and the contents of main components (namely berberine, baicalin and geniposide) contained in the extract of HLJDD were assayed with high performance liquid chromatography (HPLC). Type 2 diabetic rats were induced by high fat diet and streptozotocin. Type 2 diabetic rats were treated with HLJDD extract for 30d, while blood glucose and body weight were monitored during the experiment. At the end of experiment, the levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were assayed. Intestinal mucosa homogenate was prepared and the activity of pancreatic lipase was analyzed. Moreover, the olive oil loading test (OOLT) was performed and the inhibitory effect of HLJDD extract on the pancreatic lipase in vitro was evaluated. The results showed that, after the treatment of HLJDD extract, the final body weight and the levels of fasting plasma glucose, TC, TG and LDL-C were significantly reduced while the HDL-C level was increased in type 2 diabetic rats. The OOLT showed that HLJDD extract could lower the postprandial plasma TG level of type 2 diabetic rats. The activity of pancreatic lipase in type 2 diabetic rats was decreased after the treatment of HLJDD extract. Moreover, HLJDD extract could inhibit the activity of pancreatic lipase in vitro. In conclusion, the TCM prescription HLJDD possessed potent lipid-modulating effect on type 2 diabetic rats. And HLJDD extract exerted hypolipidemic effects partly via inhibiting the increased activity of intestinal pancreatic lipase in type 2 diabetic rats.