CaMK II in Cardiovascular Diseases, Especially CaMK II-δ: Friends or Enemies.

Cardiovascular diseases (CVDs) tend to affect the young population and are associated with a significant economic burden and psychological distress to the society and families. The physiological and pathological processes underlying CVDs are complex. Ca2+/calmodulin-dependent kinase II (CaMK II), a protein kinase, has multiple biological functions. It participates in multiple pathological processes and plays a central role in the development of CVDs. Based on this, this paper analyzes the structural characteristics and distribution of CaMK II, the mechanism of action of CaMK II, and the relationship between CaMK II and CVDs, including ion channels, ischemia-reperfusion injury, arrhythmias, myocardial hypertrophy, cardiotoxicity, hypertension, and dilated cardiomyopathy. Given the different regulatory mechanisms of different isoforms of CaMK II, the clinical use of specific targeted inhibitors or novel compounds should be evaluated in future research to provide new directions.

Laboratory animal ethics education improves medical students' awareness of laboratory animal ethics.

OBJECTIVE: In this study, we added laboratory animal ethics education into both didactic sessions and practical sessions the general surgery laboratory course, with the didactic sessions focus on teaching the fundamental principles of laboratory animal ethics, while the practical sessions emphasize the application of these principles in laboratory classes and have assessed the changes in medical students' perception of laboratory animal ethics following medical students exposure to such education. METHODS: One hundred and eighty-nine third-year medical students from Wuhan University's Second Clinical College completed a laboratory animal ethics awareness questionnaire and a laboratory animal ethics written examination before and after laboratory animal ethics education. RESULTS: After receiving laboratory animal ethics education, the percentage of students who supported euthanasia for the execution of animals and humane treatment of laboratory animals were 95.2% and 98.8%, respectively, which did not differ from the 94.9% and 96.4% observed before the education. Moreover, there was a notable increase in the proportion of students who knew about regulations related to laboratory animals (from 39.9% to 57.1%), welfare issues (from 31.9% to 50.0%), and the 3R principle (from 30.4% to 58.9%) post-education, all statistically significant at P < 0.05. Test scores also showed improvement, with students scoring (93.02 ± 11.65) after education compared to (67.83 ± 8.08) before, a statistically significant difference. CONCLUSIONS: This research helps to provide information for the good practices of laboratory animal ethics education. After receiving laboratory animal ethics education, students are better able to treat laboratory animals in a correct animal ethical manner. Laboratory animal ethics education helps improve students' knowledge of laboratory animal ethics. Students' perception towards how the laboratory animal ethics course should be delivered may vary. Still, new courses or better organized courses on laboratory animal ethics education are required in order to provide students an in-depth understanding.

Dynamics of polarization-tuned mirror symmetry breaking in a rotationally symmetric system.

Lateral momentum conservation is typically kept in a non-absorptive rotationally symmetric system through mirror symmetry via Noether's theorem when illuminated by a homogeneous light wave. Therefore, it is still very challenging to break the mirror symmetry and generate a lateral optical force (LOF) in the rotationally symmetric system. Here, we report a general dynamic action in the SO(2) rotationally symmetric system, originating from the polarization-tuned mirror symmetry breaking (MSB) of the light scattering. We demonstrate theoretically and experimentally that MSB can be generally applied to the SO(2) rotationally symmetric system and tuned sinusoidally by polarization orientation, leading to a highly tunable and highly efficient LOF (9.22 pN/mW/µm-2) perpendicular to the propagation direction. The proposed MSB mechanism and LOF not only complete the sets of MSB of light-matter interaction and non-conservative force only using a plane wave but also provide extra polarization manipulation freedom.

Late-onset sepsis in newborns caused by Bacillus Cereus: a case report and literature review.

Bacillus cereus is a bacterium capable of causing late-onset neonatal sepsis. By analyzing 11 cases, this study investigates the diagnosis, treatment, and prognosis of Bacillus cereus infections, aiming to provide insights into clinical diagnosis and therapy. The study scrutinized 11 instances of late-onset neonatal sepsis, including two fatalities attributable to Bacillus cereus, one accompanied by cerebral hemorrhage. An examination and analysis of these cases' symptoms, signs, laboratory tests, and treatment processes, along with a review of related literature from 2010 to 2020, revealed a high mortality rate of 41.38% in non-gastrointestinal infections caused by Bacillus cereus. Our findings underscore the critical importance of rapid diagnosis and effective antimicrobial therapy in reducing mortality rates. Once the source of infection is identified, implementing effective infection control measures is essential.

Vanadium as a Ti-like mediator boosting electronic transmission in Fe-based MOFs for photocatalytic sterilization.

Efficient metal-organic frameworks (MOFs) photocatalytic bactericidal catalysts are urgently needed in water purification. Herein, a Fe-MOF (MIL-88B-NH2(V1Fe5) with promoted electron transport was achieved by vanadium (V) ions doping and V/Fe ratio optimization, showing excellent photocatalytic bactericidal activity againstE. coliunder visible light irradiation (99.92%). The efficient antibacterial mechanism, V as a Ti-like mediator boosting electronic transmission in MIL-88B-NH2(V1Fe5), was revealed by its band structure, transient photocurrent, electrochemical impedance spectroscopy, and scavenger quenching experiments. The enhancement of photocatalytic bactericidal performance of Fe-MOFs by V-ion-doping was confirmed by two other Fe-MOFs, MIL-53-NH2(V1Fe5) and MIL-101-NH2(V1Fe5), with the same metal ions and ligands, both of which have higher performance than the corresponding undoped MOFs. Among them, MIL-88B-NH2(V1Fe5) exhibits the highest photocatalytic bactericidal activity due to its suitable metal clusters ([M(µ3-O)] cluster) and topological structure (three-dimensional rhomboid network structure). This work demonstrated the amplification effect of V ion doping on electron transport in Fe-MOFs photocatalysts.

Engineering valence-mismatched Ti4+ into Fe-based metal-organic-frameworks for enhanced photocatalytic CO2 reduction.

A series of low-dose high-valence Ti4+ doped MIL-53-NH2(Fe) photocatalysts were synthesized for visible-light-driven CO2 reduction. The highest CO2-to-CO conversion rate of Ti4+ doped MIL-53-NH2(Fe) was 7.24 mmol g-1 h-1 and the highest CO selectivity was 94% in acetonitrile solvent using [Ru(bpy)3]2+ and triethanolamine.

Sandwich-structured continuous ZIF-8/Ti3C2 MXene/ZIF-8 for efficient sterilization: Enhanced photocatalytic activity, photothermal effect, and environmental safety.

The development of effective water purification systems is crucial for controlling and remediating environmental pollution, especially in terms of sterilization. Herein, we demonstrate elaborately designed composite nanosheets with a sandwich structure, composed of two-dimensional (2D) Ti3C2 MXene nanosheet core and conformal ZIF-8 ultrathin outer layers, and their potential applications in photocatalytic sterilization. The study results indicate that the conformal ZIF-8-MXene nanosheet exhibits an expanded light absorption range (826 nm), improved photothermal conversion efficiency (6.2 °C s-1), and photocurrent response, thus boosting photocatalytic sterilization efficiency (6.63 log10 CFU mL-1) against Escherichia coli under simulated sunlight within 90 min. Interestingly, 2D ZIF-8 layers exhibit positive zeta potential (19 mV), good hydrophilicity (40.6°), and local photogenerated-hole accumulation, possessing efficient bacteria-trapping efficiency. Membrane filters fabricated from optimized composite nanosheets exhibit an outstanding bacteria-trapping and sterilization efficiency (almost 100 %) against Escherichia coli under simulated sunlight within 30 min of the flow photocatalytic experiments. This work not only presents a rational structural design of the conformal and ultrathin anchoring of ZIF-8 onto a 2D conductive material for bacteria-trapping and sterilization, but also opens new opportunities for using metal-organic frameworks in photocatalytic disinfection of drinking water.

Dialogue between mitochondria and endoplasmic reticulum-potential therapeutic targets for age-related cardiovascular diseases.

Mitochondria-associated endoplasmic reticulum membranes (MAMs) act as physical membrane contact sites facilitating material exchange and signal transmission between mitochondria and endoplasmic reticulum (ER), thereby regulating processes such as Ca2+/lipid transport, mitochondrial dynamics, autophagy, ER stress, inflammation, and apoptosis, among other pathological mechanisms. Emerging evidence underscores the pivotal role of MAMs in cardiovascular diseases (CVDs), particularly in aging-related pathologies. Aging significantly influences the structure and function of the heart and the arterial system, possibly due to the accumulation of reactive oxygen species (ROS) resulting from reduced antioxidant capacity and the age-related decline in organelle function, including mitochondria. Therefore, this paper begins by describing the composition, structure, and function of MAMs, followed by an exploration of the degenerative changes in MAMs and the cardiovascular system during aging. Subsequently, it discusses the regulatory pathways and approaches targeting MAMs in aging-related CVDs, to provide novel treatment strategies for managing CVDs in aging populations.

Carboxymethylated Lycium barbarum seed dreg dietary fiber alleviates high fat diet-induced hyperlipidemia in mice via intestinal regulation.

In this study, we investigated the ameliorative gut modulatory effect of carboxymethylated Lycium barbarum seed dreg insoluble dietary fiber (LBSDIDF) on hyperlipidemic mice. After seven weeks of insoluble dietary fiber (IDF) intervention, the results demonstrated that IDFs effectively inhibited body weight gain, with slimming and hypolipidemic effects, and improved liver histopathology by decreasing ALT, AST, TNF-α and IL-6, and increasing short-chain fatty acid (SCFA) levels in hyperlipidemic mice. With the increasing diversity and abundance of intestinal bacteria and decreasing ratio of Firmicutes to Bacteroidetes, intestinal flora facilitated cholesterol lowering effects in hyperlipidemic mice. Our research offers a novel concept for the use of LBSDIDF as a prebiotic to improve intestinal dysbiosis or as a preventive measure against obesity and dyslipidemia.

Development of Indocyanine Green/Methyl-ß-cyclodextrin Complex-Loaded Liposomes for Enhanced Photothermal Cancer Therapy.

Photothermal therapy (PTT) is a promising cancer therapeutic approach due to its spatial selectivity and high potency. Indocyanine green (ICG) has been considered a biocompatible PTT agent. However, ICG has several challenges to hinder its clinical use including rapid blood clearance and instability to heat, light, and solvent, leading to a loss of photoactivation property and PTT efficacy. Herein, we leveraged stabilizing components, methyl-ß-cyclodextrin and liposomes, in one nanoplatform (ICD lipo) to enhance ICG stability and the photothermal therapeutic effect against cancer. Compared to ICG, ICD lipo displayed a 4.8-fold reduction in degradation in PBS solvent after 30 days and a 3.4-fold reduction in photobleaching after near-infrared laser irradiation. Moreover, in tumor-bearing mice, ICD lipo presented a 2.7-fold increase in tumor targetability and inhibited tumor growth 9.6 times more effectively than did ICG without any serious toxicity. We believe that ICD lipo could be a potential PTT agent for cancer therapeutics.

Effect of κ-carrageenan on the quality of crayfish surimi gels.

The demand for crayfish surimi products has grown recently due to its high protein content. This study examined the effects of varying κ-carrageenan (CAR) and crayfish surimi (CSM) concentrations on the gelling properties of CAR-CSM composite gel and its intrinsic formation process. Our findings demonstrated that with the increasing concentration of carrageenan, the quality of CAR-CSM exhibited rising trend followed by subsequently fall. Based on the textural qualities, the highest quality CAR-CSM was achieved at 0.3% carrageenan addition. With the exception of chewiness, and the cooking loss of the gel system was 1.62%, whiteness was 82.35%, and the percentage of ß-sheets increased to 57.18%. Further increase in CAR (0.4-0.5%) addition resulted in internal build-up of LCAR-CSM, conversion of intermolecular forces into disulfide bonds and gel breakage. This study exudes timely recommendations for extending the CAR application for the continuous development of crayfish surimi and its derivatives and its overall economic worth.

Transgenic expression of artificial microRNA targeting soybean mosaic virus P1 gene confers virus resistance in plant.

RNA silencing is an innate immune mechanism of plants against invasion by viral pathogens. Artificial microRNA (amiRNA) can be engineered to specifically induce RNA silencing against viruses in transgenic plants and has great potential for disease control. Here, we describe the development and application of amiRNA-based technology to induce resistance to soybean mosaic virus (SMV), a plant virus with a positive-sense single-stranded RNA genome. We have shown that the amiRNA targeting the SMV P1 coding region has the highest antiviral activity than those targeting other SMV genes in a transient amiRNA expression assay. We transformed the gene encoding the P1-targeting amiRNA and obtained stable transgenic Nicotiana benthamiana lines (amiR-P1-3-1-2-1 and amiR-P1-4-1-2-1). Our results have demonstrated the efficient suppression of SMV infection in the P1-targeting amiRNA transgenic plants in an expression level-dependent manner. In particular, the amiR-P1-3-1-2-1 transgenic plant showed high expression of amiR-P1 and low SMV accumulation after being challenged with SMV. Thus, a transgenic approach utilizing the amiRNA technology appears to be effective in generating resistance to SMV.

Deficiency of SECTM1 impairs corneal wound healing in aging.

The corneal epithelium is the outermost transparent barrier of the eyeball and undergoes continuous self-renewal by limbal stem cells (LSCs) during its lifetime; however, the impact of aging on LSCs remains largely unknown. Here, we showed that the healing ability of the cornea in elderly macaques (Macaca fascicularis) was significantly decreased compared to that of younger macaques. This delayed wound closure accompanied a disordered cell arrangement and corneal opacity. A novel cytokine, Secreted and Transmembrane 1 (SECTM1), was found to facilitate corneal healing and was upregulated in young macaques upon wounding. Mechanistically, SECTM1 is essential for LSC migration and proliferation, and may partially function through Cell Division Cycle Associated 7 (CDCA7). Notably, the topical application of SECTM1 to aged wounded corneas dramatically promoted re-epithelialization and improved corneal transparency in both mice and macaques. Our work suggests that aging may impair the expression of healing response factors and injury repair in non-human primate corneas, and that SECTM1 application could potentially benefit corneal wound healing in clinical treatment.

Digital ischemic necrosis in a patient with systematic lupus erythematosus patient after severe acute respiratory syndrome coronavirus 2 infection: a case report.

BACKGROUND: Patients with coronavirus disease 2019 have a high incidence of thrombosis that decreases after recovery. When coronavirus disease 2019 is accompanied by diseases prone to thrombosis, risk of post-infection thrombotic events may increase. CASE PRESENTATION: We report a case of digital ischemic gangrene in a 24-year-old Chinese female with systemic lupus erythematosus after recovery from coronavirus disease 2019. The pathogenesis was related to clinical characteristics of systemic lupus erythematosus, hypercoagulability caused by coronavirus disease 2019, and second-hit due to viral infection. CONCLUSION: Patients with autoimmune diseases should remain alert to autoimmune system disorders induced by severe acute respiratory syndrome coronavirus 2 and other viruses. Treatment for these patients should be strictly standardized, and appropriate anticoagulation methods should be selected to prevent thrombosis.

The Effectiveness of Polyhexanide in Treating Wound Infections Due to Methicillin-Resistant Staphylococcus Aureus: A Prospective Analysis.

Purpose: Polyhexanide is a safe and effective wound care antiseptic commonly used in clinics as wound rinsing solution and gel. However, the efficacy of Polyhexanide in treatment of wound infected with MRSA (methicillin-resistant Staphylococcus aureus) is unknown. The aim of this study is to assess the effectiveness of polyhexanide with povidone iodine in treating wound infected with MRSA. Patients and Methods: A prospective analysis of 62 patients with wound infections, who were admitted to our department from 2016 to 2020, was conducted in order to assess the efficacy of different treatment approaches. The patients were divided into two groups: the experimental group and the control group. In the experimental group, 30 patients underwent treatment with a combination of diluted povidone iodine and polyhexanide immersion. Conversely, in the control group, 32 patients received treatment with diluted povidone iodine along with systemic antibiotic therapy. The time required for dressing changes, bacterial clearance rates, and the Bates-Jasen wound assessment tool (BWAT) scores were utilized as indicators to evaluate the effectiveness of the treatments. Results: In our study, the findings indicated that the experimental group exhibited a lesser number of days for the bacteria culture to turn negative compared to the control group, with statistical significance (p<0.05). Furthermore, the decline in the BWAT score was significantly greater in the experimental group than in the control group (p<0.05). However, no significant differences were observed in terms of dressing times and wound coverage between the two groups (p>0.05). Conclusion: Polyhexanide combined with povidone iodine can effectively remove MRSA infection in wounds and reduce antibiotic dosages.

Dry environment on the expression of lacrimal gland S100A9, Anxa1, and Clu in rats via proteomics.

AIM: To investigate the underlying mechanism of dry environment (autumn dryness) affecting the lacrimal glands in rats. METHODS: Twenty Sprague-Dawley rats were randomly divided into two groups. The rats were fed in specific pathogen free environment as the control group (n=10), and the rats fed in dry environment as the dryness group (n=10). After 24d, lacrimal glands were collected from the rats. The tissues morphology was observed by hematoxylin-eosin (HE) staining. Tandem mass tags (TMT) quantitative proteomics analysis technology was used to screen the differential expressed proteins of lacrimal glands between the two groups, then bioinformatics analysis was performed. Further, the immunohistochemical (IHC) method was used to verify the target proteins. RESULTS: In dryness group, the lacrimal glands lobule atrophied, the glandular cavities enlarged, the sparse nuclear distribution and scattered inflammatory infiltration between the acinus were observed. The proteomics exhibited that a total of 195 up-regulated and 236 down-regulated differential expressed proteins screened from the lacrimal glands of rats. It was indicated that the biological processes (BP) of differential expressed proteins mainly included cell processes and single BP. The cellular compositions of differential expressed proteins mainly located in cells, organelles. The molecular functions of differential expressed proteins mainly included binding, catalytic activity. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the differential expressed proteins mainly involved lysosome, complement and coagulation cascade, and ribosome pathway. The IHC result verified that the up-regulated expression proteins of Protein S100A9 (S100A9), Annexin A1 (Anxa1), and Clusterin (Clu) in lacrimal glands of rats in dryness group were higher than control group. CONCLUSION: The up-regulated expression proteins of S100A9, Anxa1, and Clu may be the potential mechanisms of dry eye symptoms caused by dry environment. This study provides clues of dry environments causing eye-related diseases for further studies.

Linear Electro-Optic Effect in 2D Ferroelectric for Electrically Tunable Metalens.

The advent of 2D ferroelectrics, characterized by their spontaneous polarization states in layer-by-layer domains without the limitation of a finite size effect, brings enormous promise for applications in integrated optoelectronic devices. Comparing with semiconductor/insulator devices, ferroelectric devices show natural advantages such as non-volatility, low energy consumption and high response speed. Several 2D ferroelectric materials have been reported, however, the device implementation particularly for optoelectronic application remains largely hypothetical. Here, the linear electro-optic effect in 2D ferroelectrics is discovered and electrically tunable 2D ferroelectric metalens is demonstrated. The linear electric-field modulation of light is verified in 2D ferroelectric CuInP2S6. The in-plane phase retardation can be continuously tuned by a transverse DC electric field, yielding an effective electro-optic coefficient rc of 20.28 pm V-1. The CuInP2S6 crystal exhibits birefringence with the fast axis oriented along its (010) plane. The 2D ferroelectric Fresnel metalens shows efficacious focusing ability with an electrical modulation efficiency of the focusing exceeding 34%. The theoretical analysis uncovers the origin of the birefringence and unveil its ultralow light absorption across a wide wavelength range in this non-excitonic system. The van der Waals ferroelectrics enable room-temperature electrical modulation of light and offer the freedom of heterogeneous integration with silicon and another material system for highly compact and tunable photonics and metaoptics.

Age-dependent distribution of IgA and IgG antibody-secreting cells in the pharyngeal tonsil of the Bactrian camel.

The pharyngeal tonsil, located in the nasopharynx, can effectively defend against pathogens invading the body from the upper respiratory tract and play a crucial role in mucosal immunity of the respiratory tract. Immunoglobulin A (IgA) and Immunoglobulin G (IgG) serve as key effector molecules in mucosal immunity, exhibiting multiple immune functions. This study aimed to investigate the distribution patterns and age-related alterations of IgA and IgG antibody-secreting cells (ASCs) in the pharyngeal tonsils of Bactrian camels. Twelve Alashan Bactrian camels were categorized into four age groups: young (1-2 years, n=3), pubertal (3-5 years, n=3), middle-aged (6-16 years, n=3) and old (17-20 years, n=3). The distribution patterns of IgA and IgG ASCs in the pharyngeal tonsils of Bactrian camels of different ages were meticulously observed, analyzed and compared using immunohistochemical and statistical methods. The results revealed that IgA ASCs in the pharyngeal tonsils of all age groups were primarily clustered or diffusely distributed in the reticular epithelium and its subepithelial regions (region A) and around the glands (region C), scattered in the subepithelial regions of non-reticular epithelium (region B), and sporadically distributed in the interfollicular regions (region D). Interestingly, the distribution pattern of IgG ASCs in the pharyngeal tonsils closely mirrored that of IgA ASCs. The distribution densities of IgA and IgG ASCs in these four regions were significantly decreased in turn (P<0.05). However, IgA ASCs exhibited significantly higher densities than IgG ASCs in the same region (P<0.05). Age-related alterations indicated that the distribution densities of IgA and IgG ASCs in each region of the pharyngeal tonsils exhibited a trend of initially increasing and subsequently decreasing from young to old camels, reaching a peak in the pubertal group. As camels age, there was a significant decrease in the densities of IgA and IgG ASCs in all regions of the pharyngeal tonsils (P<0.05). The results demonstrate that the reticular epithelium and its subepithelial regions in the pharyngeal tonsils of Bactrian camels are the primary regions where IgA and IgG ASCs colonize and exert their immune functions. These regions play a pivotal role in inducing immune responses and defending against pathogen invasions in the pharyngeal tonsils. IgA ASCs may be the principal effector cells of the mucosal immune response in the pharyngeal tonsils of Bactrian camels. Aging significantly reduces the densities of IgA and IgG ASCs, while leaving their distribution patterns unaffected. These findings will provide valuable insights for further investigations into the immunomorphology, immunosenescence, and response mechanisms of the pharyngeal tonsils in Bactrian camels.

The efficacy and safety of adding PD-1 blockade to induction chemotherapy and concurrent chemoradiotherapy (IC-CCRT) for locoregionally advanced nasopharyngeal carcinoma: an observational, propensity score-matched analysis.

BACKGROUND: Despite the success of PD-1 blockade in recurrent/metastatic nasopharyngeal carcinoma (NPC), its effect for locoregionally advanced NPC (LANPC) remains unclear. This study aimed to evaluate the benefit of adding PD-1 blockade to the current standard treatment (gemcitabine and cisplatin IC  plus cisplatin CCRT ) for LANPC patients. METHODS: From January 2020 to November 2022, 347 patients with non-metastatic high-risk LANPC (stage III-IVA, excluding T3-4N0) were included. Of the 347 patients, 268 patients were treated with standard treatment (IC-CCRT), and 79 received PD-1 blockade plus IC-CCRT (PD-1 group). For the PD-1 group, PD-1 blockade was given intravenously once every 3 weeks for up to 9 cycles (3 induction and 6 adjuvant). The primary endpoint was disease-free survival (DFS) (i.e. freedom from local/regional/distant failure or death). The propensity score matching (PSM) with the ratio of 1:2 was performed to control confounding factors. RESULTS: After PSM analysis, 150 patients receiving standard treatment and 75 patients receiving additional PD-1 blockade remained in the current analysis. After three cycles of IC, the PD-1 group had significantly higher rates of complete response (defined as disappearance of all target lesions; 24% vs. 9%; P = 0.006) and complete biological response (defined as undetectable cell-free Epstein-Barr virus DNA, cfEBV DNA; 79% vs. 65%; P = 0.046) than that in the standard group. And the incidence of grade 3-4 toxicity during IC was 47% in the PD-1 group and 41% in the standard group, with no significant difference (P = 0.396). During follow-up period, additional PD-1 blockade to standard treatment improved 3-year DFS from 84 to 95%, with marginal statistical significance (HR, 0.28; 95%CI, 0.06-1.19; P = 0.064). CONCLUSION: Additiaonl PD-1 blockade to gemcitabine and cisplatin IC and adjuvant treatment results in significant improvement in tumor regression, cfEBV DNA clearance, superior DFS, and comparable toxicity profiles in high-risk LANPC patients.

Enhanced hyaline cartilage formation and continuous osteochondral regeneration via 3D-Printed heterogeneous hydrogel with multi-crosslinking inks.

The unique gradient structure and complex composition of osteochondral tissue pose significant challenges in defect regeneration. Restoration of tissue heterogeneity while maintaining hyaline cartilage components has been a difficulty of an osteochondral tissue graft. A novel class of multi-crosslinked polysaccharide-based three-dimensional (3D) printing inks, including decellularized natural cartilage (dNC) and nano-hydroxyapatite, was designed to create a gradient scaffold with a robust interface-binding force. Herein, we report combining a dual-nozzle cross-printing technology and a gradient crosslinking method to create the scaffolds, demonstrating stable mechanical properties and heterogeneous bilayer structures. Biofunctional assessments revealed the remarkable regenerative effects of the scaffold, manifesting three orders of magnitude of mRNA upregulation during chondrogenesis and the formation of pure hyaline cartilage. Transcriptomics of the regeneration site in vivo and scaffold cell interaction tests in vitro showed that printed porous multilayer scaffolds could form the correct tissue structure for cell migration. More importantly, polysaccharides with dNC provided a hydrophilic microenvironment. The microenvironment is crucial in osteochondral regeneration because it could guide the regenerated cartilage to ensure the hyaline phenotype.