IGF-1 rs6218 polymorphisms modulate the susceptibility to age-related cataract.

Background: Single nucleotide polymorphisms (SNPs), as the most abundant form of DNA variation in the human genome, contribute to age-related cataracts (ARC) development. Apoptosis of lens epithelial cells (LECs) is closely related to ARC formation. Insulin-like growth factor 1 (IGF1) contributes to cell apoptosis regulation. Moreover, IGF1 was indicated to exhibit a close association with cataract formation. Afterward, an investigation was conducted to examine the correlation between polymorphisms in IGF1 and the susceptibility to ARC. Methods: The present investigation was a case-control study. Venous blood draws were collected from the participants for DNA genotyping. Lens capsule samples were collected to detect mRNA and apoptosis. TaqMan RT-PCR was used to detect IGF1 polymorphism genotypes and qRT PCR was used to detect IGF1 mRNA levels in LECs. LEC apoptosis was evaluated through flow cytometry. The chi-square test was used to compare differences between ARCs and controls of each SNP. Results: We found that the G allele frequency in the IGF1-rs6218 was higher in the ARCs than in the controls. Furthermore, it was observed that the rs6218 GG genotype exhibited a positive correlation to elevated levels of IGF1 mRNA in LECs. The IGF1 mRNA in the LECs and the apoptosis of LECs in nuclear type of ARCs (ARNC) was higher than the controls. Conclusion: The susceptibility to ARC was related to IGF1-rs6218 polymorphism, and this polymorphism is associated with IGF1 expression at the mRNA level. Moreover, apoptosis in LECs of ARNCs was found to be increased.

Preparation of antibacterial hydrogel from poly(aspartic hydrazide) and quaternized N-[3-(dimethylamino) propyl] methylacrylamide copolymer with antioxidant and hemostatic effects for wound repairing.

Hydrogels as wound dressing have attracted extensive attention in past decade because they can provide moist microenvironment to promote wound healing. Herein, this research designed a multifunctional hydrogel with antibacterial property and antioxidant activity fabricated from quaternary ammonium bearing light emitting quaternized TPE-P(DAA-co-DMAPMA) (QTPDD) and poly(aspartic hydrazide) (PAH). The protocatechuic aldehyde (PCA) grafted to the hydrogel through dynamic bond endowed the hydrogel with antioxidant activity and the tranexamic acid (TXA) was loaded to enhance the hemostatic performance. The hydrogel possesses preferable gelation time for injectable application, good antioxidant property and tissue adhesion, improved hemostatic performance fit for wound repairing. Furthermore, the hydrogel has excellent antimicrobial property to both E. coli and S. aureus based on quaternary ammonium structure. The hydrogel also showed good biocompatibility and the in vivo experiments proved this hydrogel can promote the wound repairing rate. This study suggests that TXA/hydrogel with quaternary ammonium structure and dynamic grafted PCA have great potential in wound healing applications.

A two-step method of cyclolinopeptide (linusorb) preparation from flaxseed cake via dry-screening.

Linusorbs (LO), cyclolinopeptides, are a group of cyclic hydrophobic peptides and considered a valuable by-product of flaxseed oil due to numerous health benefits. Currently applied acetone or methanol extraction could contaminate the feedstocks for further food-grade application. Using flaxseed cake as feedstock, this study established a practical method for preparing LO from pressed cake. Firstly, LO composition of 15 flaxseed cultivars was analyzed. Next, cold-pressed cake was milled and screened mechanically. The kernel and hull fractions were separated based on the disparity of their mechanical strength. Monitored by hyperspectral fluorescence, the LO-enriched kernel fraction separated from cold-pressed flaxseed cake was further used as feedstock for LO production. After ethanol extraction, partition, and precipitation, LOs were extracted from cold-pressed flaxseed cake with a purity of 91.4%. The proposed method could serve as feasible flaxseed cake valorization strategy and enable the preparation of other polar compounds such as flax lignan and mucilage.

Direct Oxidation of Methane to Methanol over Transition-Metal-Free Ferrierite Zeolite Catalysts.

Direct oxidation of methane to methanol was reported to be highly dependent on the transition- or noble-metal-loading catalysts in the past decades. Here, we show that the transition-metal-free aluminosilicate ferrierite (FER) zeolite effectively catalyzed methane and N2O to methanol for the first time. The distorted tetracoordinated Al in the framework and pentacoordinated Al on the extra framework formed during calcination, activation, and reaction processes were confirmed as the potential active centers. The possible reaction pathway similar to the Fe-containing zeolites was advocated based on the reaction results using different oxidants, N2O adsorption FTIR spectra, and 27Al MAS NMR spectra. The stable and efficient methanol production capacity of FER zeolite was ascribed to the two-dimensional straight channels and its distinctive Al distribution of FER zeolite (CP914C) from Zeolyst. The transition-metal-free FER zeolite performed better than the record in the literature and our recent results using transition-metal-containing catalysts in terms of selectivity and formation rate of methanol and stability. This work has great significance and prospects for utilizing CH4 and N2O as resources and will open new avenues for methane oxidation.

Decoding the influence of low temperature on biofilm development: The hidden roles of c-di-GMP.

Biofilms are widely used and play important roles in biological processes. Low temperature of wastewater inhibits the development of biofilms derived from wastewater activated sludge. However, the specific mechanism of temperature on biofilm development is still unclear. This study explored the mechanism of temperature on biofilm development and found a feasible method to enhance biofilm development at low temperature. The amount of biofilm development decreased by approximately 66 % and 55 % at 4 °C and 15 °C, respectively, as compared to 28 °C. The cyclic dimeric guanosine monophosphate (c-di-GMP) concentration also decreased at low temperature and was positively correlated with extracellular polymeric substance (EPS) content, formation, and adhesion strength. Microbial community results showed that low temperature inhibited the normal survival of most microorganisms, but promoted the growth of some psychrophile bacteria like Sporosarcina, Caldilineaceae, Gemmataceae, Anaerolineaceae and Acidobacteriota. Further analysis of functional genes demonstrated that the abundance of functional genes related to the synthesis of c-di-GMP (K18968, K18967 and K13590) decreased at low temperature. Subsequently, the addition of exogenous spermidine increased the level of intracellular c-di-GMP and alleviated the inhibition effect of low temperature on biofilm development. Therefore, the possible mechanism of low temperature on biofilm development could be the inhibition of the microorganism activity and reduction of the communication level between cells, which is the closely related to the EPS content, formation, and adhesion strength. The enhancement of c-di-GMP level through the exogenous addition of spermidine provides an alternative strategy to enhance biofilm development at low temperatures. The results of this study enhance the understanding of the influence of temperature on biofilm development and provide possible strategies for enhancing biofilm development at low temperatures.

Synergistic Strain Suppressing and Interface Engineering in Na4MnV(PO4)3/C for Wide-Temperature and Long-Calendar-Life Sodium-Ion Storage.

A Na4MnV(PO4)3 (NMVP) cathode is regarded as a promising cathode candidate for sodium-ion batteries (SIBs). However, issues such as low electronic conductivity and partial cation dissolution contribute to high polarization and structure distortion. Herein, we engineered the local electron density and reaction kinetic properties of NMVP cathodes with varying oxygen vacancies by introducing varying amounts of Zr doping and carbon coating. The optimized sample exhibited a high-rate capacity of 71.8 mAh g-1 at 30 C (83.1% capacity retention after 1000 cycles) and excellent performance over a wide temperature range (84.1 mAh g-1 at 60 °C and 61.4 mAh g-1 at -30 °C). In situ X-ray diffraction technology confirmed a redox solid solution and a two-phase reaction mechanism, revealing minor changes in cell volume and slight strain variations after Zr doping, effectively suppressing the structural distortion. Theoretical calculations illustrated that Zr doping largely shrinks the band gap of NMVP, enriches local electron density, and slightly alters the local element distribution and bond lengths. Moreover, full-cells have shown high energy density (259.9 Wh kg-1) and outstanding cycling stability (200 cycles). The work provides fresh insights into the synergistic effect of strain suppressing and interface engineering in promoting the development of wide temperature range and long-calendar-life SIBs.

Endothelial NLRP3 inflammasome regulation in atherosclerosis.

AIM: The activation of Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in endothelial cells (ECs) contributes to vascular inflammation in atherosclerosis. Considering the high glycolytic rate of ECs, we delineated whether and how glycolysis determines endothelial NLRP3 inflammasome activation in atherosclerosis. METHODS AND RESULTS: Our results demonstrated a significant upregulation of 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 3 (PFKFB3), a key regulator of glycolysis, in human and mouse atherosclerotic endothelium, which positively correlated with NLRP3 levels. Atherosclerotic stimuli upregulated endothelial PFKFB3 expression via sterol regulatory element binding protein 2 (SREBP2) transactivation. EC-selective haplodeficiency of Pfkfb3 in Apoe-/- mice resulted in reduced endothelial NLRP3 inflammasome activation and attenuation of atherogenesis. Mechanistic investigations revealed that PFKFB3-driven glycolysis increased the NADH content and induced oligomerization of C-terminal binding protein 1 (CtBP1), an NADH-sensitive transcriptional co-repressor. The monomer form, but not the oligomer form, of CtBP1 was found to associate with the transcriptional repressor Forkhead box P1 (FOXP1) and acted as a transrepressor of inflammasome components, including NLRP3, caspase-1, and interleukin-1ß (IL-1ß). Interfering with NADH-induced CtBP1 oligomerization restored its binding to FOXP1 and inhibited the glycolysis-dependent upregulation of NLRP3, Caspase-1, and IL-1ß. Additionally, EC-specific overexpression of NADH-insensitive CtBP1 alleviates atherosclerosis. CONCLUSIONS: Our findings highlight the existence of a glycolysis-dependent NADH/CtBP/FOXP1-transrepression pathway that regulates endothelial NLRP3 inflammasome activation in atherogenesis. This pathway represents a potential target for selective PFKFB3 inhibitors or strategies aimed at disrupting CtBP1 oligomerization to modulate atherosclerosis.

Composited silk fibroins ensured adhesion stability and magnetic controllability of Fe3O4-nanoparticle coating on implant for biofilm treatment.

Magnetic propulsion of nano-/micro-robots is an effective way to treat implant-associated infections by physically destroying biofilm structures to enhance antibiotic killing. However, it is hard to precisely control the propulsion in vivo. Magnetic-nanoparticle coating that can be magnetically pulled off does not need precise control, but the requirement of adhesion stability on an implant surface restricts its magnetic responsiveness. Moreover, whether the coating has been fully pulled-off or not is hard to ensure in real-time in vivo. Herein, composited silk fibroins (SFMA) are optimized to stabilize Fe3O4 nanoparticles on a titanium surface in a dry environment; while in an aqueous environment, the binding force of SFMA on titanium is significantly reduced due to hydrophilic interaction, making the coating magnetically controllable by an externally-used magnet but still stable in the absence of a magnet. The maximum working distance of the magnet can be calculated using magnetomechanical simulation in which the yielding magnetic traction force is strong enough to pull Fe3O4 nanoparticles off the surface. The pulling-off removes the biofilms that formed on the coating and enhances antibiotic killing both in vitro and in a rat sub-cutaneous implant model by up to 100 fold. This work contributes to the practical knowledge of magnetic propulsion for biofilm treatment.

[Essentials for high-quality development of fangjiomics].

The development of modern omics technology has facilitated in-depth research on many disciplines in the field of medicine. For instance, the introduction of omics-related technology has facilitated research on the mechanism of formula's action and led to the innovative development of sophisticated pharmacological analysis methods. However, in general, the previous ideas are only limited to the application level, failing to integrate with the discipline connotation of formulaology. Furthermore, they are unable to fulfill their potential role in the future evolution of formulaology and steer comprehensive research on the clinical efficacy and safety of formulas. We should not forget our origins, which are compatible with other countries, and embrace the future. Therefore, this paper proposes the three essentials of "holism, macro, and practice" to investigate the future direction of high-quality development in fangjiomics.

[Chemical constituents from Alangium chinense subsp. pauciflorum].

Chemical constituents of 70% ethanol extract of Alangium chinense subsp. pauciflorum were investigated. The 70% ethanol extract of A. chinense subsp. pauciflorum was isolated and purified by D-101 macroporous resins, silica gel, Sephadex LH-20 and other methods. As a result, nineteen compounds were isolated and identified as 4-cyclohexene-1α,2α,3α-triol-1-O-ß-D-glucoside(1), 1ß,4α,6α,13-tetrahydroxy-eudesm-11(12)-ene(2), sucrose(3), 1'-O-benzyl-α-L-rhamnopyranosyl-(1″→6')-ß-D-glucopyranoside(4), bis(2-ethylhexyl)benzene-1,2-dicarboxylate(5),(Z)-10-heneicosenoic acid(6), di-O-methylcrenati(7), methyl-α-D-fructofuranoside(8), ß-daucosterol(9), syringic acid(10), vanillicacid(11), octacosanol(12), isoarborinol(13), 2,7-dihydroxy-6-methyl-4-(1-methylethyl)-1-naphthalenecarboxylate(14),vanillin(15), coniferyl aldehyde(16), 9(11)-dehydroergosterolperoxide(17), 5α,8α-epidioxy-(22E,24R)-ergosta-6,22-dien-3ß-ol(18), ß-sitosterol(19), respectively. Compounds 1 and 2 were new compounds, compounds 5-11, 13, 15-18 were isolated from Alangium for the first time.The anti-inflammatory activity of compourd 1 was determinded by the LPS-induced RAW264.7 macrophage inflammation model. The results showed that the new compound 1 has a certain inhibitory effect on LPS-induced NO production of RAW264.7 cells, and the inhibitory rate was 54.57%.

[Network Meta-analysis of Chinese patent medicine in treatment of heart failure with preserved ejection fraction].

This study systematically evaluated the efficacy and safety of different Chinese patent medicines combined with conventional western medicine in the treatment of heart failure with preserved ejection fraction(HFpEF) and ranked for the drug selection. Randomized controlled trial(RCT) on Chinese patent medicines in treatment of HFpEF were obtained from the CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, Web of Science, and other databases from the inception to October 9, 2022. The included RCT was quantitatively analyzed using gemtc and rjags packages of R software for the network Meta-analysis. 74 RCTs were included, with a total of 7 192 patients enrolled, involving 11 different Chinese patent medicines(Shenfu Injection, Shenmai Injection, Qili Qiangxin Capsules, Shexiang Baoxin Pills, Xuezhikang Capsules, Salvia Miltiorrhiza Polyphenols Injection, Tanshinone Ⅱ_A Sulfonate Injection, Xinmailong Injection, Yangxinshi Tablets, Qishen Yiqi Dripping Pills, and Yixinshu Capsules). The results of network Meta-analysis are shown as followed.(1)In terms of improving clinical effective rate, for injection preparations, Xinmailong Injection + conventional western medicine was recommended. while for oral preparations, Shexiang Baoxin Pills + conventional western medicine, Qishen Yiqi Dripping Pills + conventional western medicine, and Qili Qiangxin Capsules + conventional western medicine were preferred.(2)In terms of improving the mitral ratio of peak early to late diastolic filling velocity(E/A), for injection preparations, Shenmai Injection + Salvia Miltiorrhiza Polyphenols Injection + conventional western medicine, Shenmai Injection + conventional western medicine, Shenfu Injection + conventional western medicine were preferred. While for oral preparations, Yixinshu Capsules + conventional western medicine was preferred.(3)In terms of reducing the ratio of early diastolic mitral inflow to early diastolic mitral annular velocity(E/e'), Shenfu Injection + conventional western medicine could be used as injection preparation, and Qili Qiangxin Capsules + conventional western medicine, Qishen Yiqi Dripping Pills + conventional western medicine for oral preparations.(4)In terms of improving 6-minute walking trail(6MWT), the injection preparations such as Shenmai Injection + conventional western medicine, Xinmailong Injection + conventional western medicine were suitable, while oral preparations like Qishen Yiqi Dripping Pills + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine were recommended.(5)In terms of reducing N-terminal pro B-type natriuretic peptide(NT-proBNP), Qili Qiangxin Capsules + conventional western medicine were preferred.(6)In terms of reducing B-type natriuretic peptide(BNP), Xinmailong Injection + conventional western medicine could be used for injection preparation and Qili Qiangxin Capsules + conventional western medicine can be used for oral preparation. In terms of adverse drug reactions, there was no significant difference between Chinese patent medicine combined with conventional western conventional and traditional western medicine alone. The results showe that Chinese patent medicine combined with conventional western medicine in treating HFpEF is superior to conventional western medicine alone in reducing clinical symptoms, improving cardiac function, and improving exercise tolerance, which also has good drug safety. However, the existing evidence is still limited by the quality and quantity of included studies, so the above conclusion requires further validation through more prospective RCT.

Pharmacokinetics, pharmacodynamics, and safety of frunexian in healthy Chinese volunteer adults: A randomized dose-escalation phase I study.

The purpose of this study was to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of frunexian (formerly known as EP-7041 and HSK36273) injection, a small molecule inhibitor of activated coagulation factor XI (FXIa), in healthy Chinese adult volunteers. This study was a randomized, placebo- and positive-controlled, sequential, ascending-dose (0.3/0.6/1.0/1.5/2.25 mg/kg/h) study of 5-day continuous intravenous infusions of frunexian. Frunexian administration exhibited an acceptable safety profile with no bleeding events. Steady state was rapidly reached with a median time ranging from 1.02 to 1.50 h. The mean half-life ranged from 1.15 to 1.43 h. Frunexian plasma concentration at a steady state and area under the concentration-time curve exhibited dose-proportional increases. The dose-escalation study of frunexian demonstrated its progressively enhanced capacities to prolong activated partial thromboplastin time (aPTT) and inhibit FXIa activity. The correlations between PK and PD biomarkers (aPTT/baseline and FXI clotting activity/baseline) were described by the two Emax models, with the EC50 values of 8940 and 1300 ng/mL, respectively. Frunexian exhibits good safety and PK/PD properties, suggesting it is a promising candidate for anticoagulant drug.

Exploration of vitamin D metabolic activity-related biological effects and corresponding therapeutic targets in prostate cancer.

BACKGROUND: Previous studies have unequivocally demonstrated that the vitamin D (VD) metabolism pathway significantly influences prognosis and sensitivity to hormone therapy in prostate cancer (PCa). However, the precise underlying mechanism remains unclear. METHODS: We performed molecular profiling of 1045 PCa patients, leveraging genes linked to VD synthesis and VD receptors. We then identified highly variable gene modules with substantial associations with patient stratification. Subsequently, we intersected these modules with differentially expressed genes between PCa and adjacent paracancerous tissues. Following a meticulous process involving single-factor regression and LASSO regression to eliminate extraneous variables and construct a prognostic model. Within the high-risk subgroup defined by the calculated risk score, we analyzed their differences in cell infiltration, immune status, mutation landscape, and drug sensitivity. Finally, we selected Apolipoprotein E (APOE), which featured prominently in this model for further experimental exploration to evaluate its potential as a therapeutic target. RESULTS: The prognostic model established in this study had commendable predictive efficacy. We observed diminished infiltration of various T-cell subtypes and reduced expression of co-stimulatory signals from antigen-presenting cells. Mutation analysis revealed that the high-risk cohort harbored a higher frequency of mutations in the TP53 and FOXA genes. Notably, drug sensitivity analysis suggested the heightened responsiveness of high-risk patients to molecular inhibitors targeting the Bcl-2 and MAPK pathways. Finally, our investigation also confirmed that APOE upregulates the proliferative and invasive capacity of PCa cells and concurrently enhances resistance to androgen receptor antagonist therapy. CONCLUSION: This comprehensive study elucidated the potential mechanisms through which this metabolic pathway orchestrates the biological behavior of PCa and findings hold promise in advancing the development of combination therapies in PCa.

Characterization of the m6A regulators' landscape highlights the clinical significance of acute myocardial infarction.

Objective: Acute myocardial infarction (AMI) is a severe cardiovascular disease that threatens human life and health globally. N6-methyladenosine (m6A) governs the fate of RNAs via m6A regulators. Nevertheless, how m6A regulators affect AMI remains to be deciphered. To solve this issue, an integrative analysis of m6A regulators in AMI was conducted. Methods: We acquired transcriptome profiles (GSE59867, GSE48060) of peripheral blood samples from AMI patients and healthy controls. Key m6A regulators were used for LASSO, and consensus clustering was conducted. Next, the m6A score was also computed. Immune cell infiltration, ferroptosis, and oxidative stress were evaluated. In-vitro and in-vivo experiments were conducted to verify the role of the m6A regulator ALKBH5 in AMI. Results: Most m6A regulators presented notable expression alterations in circulating cells of AMI patients versus those of controls. Based on key m6A regulators, we established a gene signature and a nomogram for AMI diagnosis and risk prediction. AMI patients were classified into three m6A clusters or gene clusters, respectively, and each cluster possessed the unique properties of m6A modification, immune cell infiltration, ferroptosis, and oxidative stress. Finally, the m6A score was utilized to quantify m6A modification patterns. Therapeutic targeting of ALKBH5 greatly alleviated apoptosis and intracellular ROS in H/R-induced H9C2 cells and NRCMs. Conclusion: Altogether, our findings highlight the clinical significance of m6A regulators in the diagnosis and risk prediction of AMI and indicate the critical roles of m6A modification in the regulation of immune cell infiltration, ferroptosis, and oxidative stress.

A comprehensive analysis of the prognostic characteristics of microRNAs in breast cancer.

Both overall survival (OS) and disease-specific survival (DSS) are significant when determining a patient's prognosis for breast cancer (BC). The effect of DSS-related microRNAs on BC susrvival, however, is not well understood. Here, we spotted differentially expressed miRNAs (DEMs) in the TCGA database of BC DSS, identified eight DSS-related miRNAs, and constructed a risk model. AUC values at 1, 3, and 5 years were 0.852, 0.861, and 0.868, respectively, indicating a risk model's excellent prognostic prediction ability. Then, we validated miRNA roles in BC OS and finally defined miR-551b as an independently prognostic miRNA in BC. According to function analysis, miR-551b is strongly linked with the emergence and spread of cancer, including protein ubiquitination, intracellular protein transport, metabolic pathways, and cancer pathways. Moreover, we confirmed the low expression of miR-551b in BC tissue and cells. After miR-551b inhibition or overexpression, cell function was either dramatically increased or diminished, respectively, indicating that miR-551b could regulate BC proliferation, invasion, and migration. In conclusion, we thoroughly clarified BC-related miRNAs on DSS and OS and verified miR-551b as a crucial regulator in the development and prognosis of cancer. These results can offer fresh ideas for BC therapy.

CYP3A Mediates an Unusual C(sp2)-C(sp3) Bond Cleavage via Ipso-Addition of Oxygen in Drug Metabolism.

Mammalian cytochrome P450 drug-metabolizing enzymes rarely cleave carbon-carbon (C-C) bonds and the mechanisms of such cleavages are largely unknown. We identified two unusual cleavages of non-polar, unstrained C(sp2)-C(sp3) bonds in the FDA-approved tyrosine kinase inhibitor pexidartinib that are mediated by CYP3A4/5, the major human phase I drug metabolizing enzymes. Using a synthetic ketone, we rule out the Baeyer-Villiger oxidation mechanism that is commonly invoked to address P450-mediated C-C bond cleavages. Our studies in 18O2 and H218O enriched systems reveal two unusual distinct mechanisms of C-C bond cleavage: one bond is cleaved by CYP3A-mediated ipso-addition of oxygen to a C(sp2) site of N-protected pyridin-2-amines, and the other occurs by a pseudo-retro-aldol reaction after hydroxylation of a C(sp3) site. This is the first report of CYP3A-mediated C-C bond cleavage in drug metabolism via ipso-addition of oxygen mediated mechanism. CYP3A-mediated ipso-addition is also implicated in the regioselective C-C cleavages of several pexidartinib analogs. The regiospecificity of CYP3A-catalyzed oxygen ipso-addition under environmentally friendly conditions may be attractive and inspire biomimetic or P450-engineering methods to address the challenging task of C-C bond cleavages.

Layer-Controllable "2.5D" DNA Origami Crystals Synthesized by a Hierarchical Assembly Strategy.

The finite periodic arrangement of functional nanomaterials on the two-dimensional scale enables the integration and enhancement of individual properties, making them an important research topic in the field of tuneable nanodevices. Although layer-controllable lattices such as graphene have been successfully synthesized, achieving similar control over colloidal nanoparticles remains a challenge. DNA origami technology has achieved remarkable breakthroughs in programmed nanoparticle assembly. Based on this technology, we proposed a hierarchical assembly strategy to construct a universal DNA origami platform with customized layer properties, which we called 2.5-dimensional (2.5D) DNA origami crystals. Methodologically, this strategy divides the assembly procedure into two steps: 1) array synthesis, and 2) lattice synthesis, which means that the layer properties, including layer number, interlayer distance, and surface morphology, can be flexibly customized based on the independent designs in each step. In practice, these synthesized 2.5D crystals not only pioneer the expansion of the DNA origami crystal library to a wider range of dimensions, but also highlight the technological potential for templating 2.5D colloidal nanomaterial lattices.