Photoacoustic Imaging-Guided Self-Adaptive Hyperthermia Supramolecular Cascade Nano-Reactor for Diabetic Periodontal Bone Regeneration.

Commencing with the breakdown of the diabetic osteoimmune microenvironment, multiple pathogenic factors, including hyperglycemia, inflammation, hypoxia, and deleterious cytokines, are conjointly involved in the progression of diabetic periodontal bone regeneration. Based on the challenge of periodontal bone regeneration treatment and the absence of real-time feedback of blood oxygen fluctuation in diabetes mellitus, a novel self-adaptive hyperthermia supramolecular cascade nano-reactor ACFDG is constructed via one-step supramolecular self-assembly strategy to address multiple factors in diabetic periodontal bone regeneration. Hyperthermia supramolecular ACFDG possesses high photothermal conversion efficiency (32.1%), and it can effectively inhibit the vicious cycle of ROS-inflammatory cascade through catalytic cascade reactions, up-regulate the expression of heat shock proteins (HSPs) under near-infrared (NIR) irradiation, which promotes periodontal bone regeneration. Remarkably, ACFDG can provide real-time non-invasive diagnosis of blood oxygen changes during periodontal bone regeneration through photoacoustic (PA) imaging, thus can timely monitor periodontal hypoxia status. In conclusion, this multifunctional supramolecular nano-reactor combined with PA imaging for real-time efficacy monitoring provides important insights into the biological mechanisms of diabetic periodontal bone regeneration and potential clinical theranostics.

Regulatory sequence-based discovery of anti-defense genes in archaeal viruses.

In silico identification of viral anti-CRISPR proteins (Acrs) has relied largely on the guilt-by-association method using known Acrs or anti-CRISPR associated proteins (Acas) as the bait. However, the low number and limited spread of the characterized archaeal Acrs and Aca hinders our ability to identify Acrs using guilt-by-association. Here, based on the observation that the few characterized archaeal Acrs and Aca are transcribed immediately post viral infection, we hypothesize that these genes, and many other unidentified anti-defense genes (ADG), are under the control of conserved regulatory sequences including a strong promoter, which can be used to predict anti-defense genes in archaeal viruses. Using this consensus sequence based method, we identify 354 potential ADGs in 57 archaeal viruses and 6 metagenome-assembled genomes. Experimental validation identified a CRISPR subtype I-A inhibitor and the first virally encoded inhibitor of an archaeal toxin-antitoxin based immune system. We also identify regulatory proteins potentially akin to Acas that can facilitate further identification of ADGs combined with the guilt-by-association approach. These results demonstrate the potential of regulatory sequence analysis for extensive identification of ADGs in viruses of archaea and bacteria.

Amorphous conversion in pyrolytic symmetric trinuclear nickel clusters trigger trifunctional electrocatalysts.

The pursuit of multifunctional electrocatalysts holds significant importance due to their comprehension of material chemistry. Amorphous materials are particularly appealing, yet they pose challenges in terms of rational design due to their structural disorder and thermal instability. Herein, we propose a strategy that entails the tandem (low-temperature/250-350 °C) pyrolysis of molecular clusters, enabling preservation of the local short-range structures of the precursor Schiff base nickel (Ni3[2(C21H24N3Ni1.5O6)]). The temperature-dependent residuals demonstrate exceptional activity and stability for at least three distinct electrocatalytic processes, including the oxygen evolution reaction (η10 = 197 mV), urea oxidation reaction (η10 = 1.339 V), and methanol oxidation reaction (1358 mA cm-2 at 0.56 V). Three distinct nickel atom motifs are discovered for three efficient electrocatalytic reactions (Ni1 and Ni1' are preferred for UOR/MOR, while Ni2 is preferred for OER). Our discoveries pave the way for the potential development of multifunctional electrocatalysts through disordered engineering in molecular clusters under tandem pyrolysis.

A Comprehensive Pyrolysis Mechanism of Binuclear Chromium-Based Complexes for Superior OER Activity.

Transition metal oxides are widely pursued as potent electrocatalysts for the oxygen evolution reaction (OER). However, single-metal chromium catalysts remain underexplored due to their intrinsic activity limitations. Herein, we successfully synthesize mixed-valence, nitrogen-doped Cr2O3/CrO3/CrN@NC nanoelectrocatalysts via one-step targeted pyrolysis techniques from a binuclear Cr-based complex (Cr2(Salophen)2(CH3OH)2), which is strategically designed as a precursor. Comprehensive pyrolysis mechanisms were thoroughly delineated by using coupled thermogravimetric analysis and mass spectrometry (TG-MS) alongside X-ray diffraction. Below 800 °C, the generation of a reducing atmosphere was noted, while continuous pyrolysis at temperatures exceeding 800 °C promoted highly oxidized CrO3 species with an elevated +6 oxidation state. The optimized catalyst pyrolyzed at 1000 °C (Cr2O3/CrO3/CrN@NCs-1000) demonstrated remarkable OER activity with a low overpotential of 290 mV in 1 M KOH and excellent stability. Further density functional theory (DFT) calculations revealed a much smaller reaction energy barrier of CrO3 than the low oxidation state species for OER reactivity. This work reveals fresh strategies for rationally engineering chromium-based electrocatalysts and overcoming intrinsic roadblocks to enable efficient OER catalysis through a deliberate oxidation state and compositional tuning.

Copper-based carbon dots modified hydrogel with osteoimmunomodulatory and osteogenesis for bone regeneration.

Biomaterials with dual functions of osteoimmunomodulation and bone repair are very promising in the field of orthopedic materials. For this purpose, we prepared copper-based carbon dots (CuCDs) and doped them into oxychondroitin sulfate/poly-acrylamide hydrogel (OPAM) to obtain a hybrid hydrogel (CuCDs/OPAM). We evaluated its osteoimmunomodulatory and bone repair properties in vitro and in vivo. The obtained CuCDs/OPAM exhibited good rBMSCs-cytocompatibility and anti-inflammatory properties in vitro. It also could effectively promote rBMSCs differentiation and the expression of osteogenic differentiation factors from rBMSCs under an inflammatory environment. Moreover, CuCDs/OPAM could induce macrophage phenotype switching (from M1-type macrophages to M2-type macrophages) in vivo, which is beneficial for anti-inflammatory action and presents good osteoimmunomodulation capability to induce a bone immune microenvironment to promote the differentiation of rBMSCs. In conclusion, CuCDs/OPAM hydrogel has dual functions of osteoimmunomodulatory and bone repair and is a promising bone filling and repair material.

Trimethyl chitosan-cysteine-based nanoparticles as an effective delivery system for portulacerebroside A in the management of hepatocellular carcinoma cells in vitro and in vivo.

Portulacerebroside A (PCA), a cerebroside compound extracted from Portulaca oleracea L., has been shown to suppress hepatocellular carcinoma (HCC) cells. This study aims to investigate the effectiveness of trimethyl chitosan-cysteine (TMC-Cys) nanocarrier in delivering PCA for HCC management and to elucidate the molecular mechanisms behind PCA's function. TMC-Cys nanocarriers notably augmented PCA's function, diminishing the proliferation, migration, and invasiveness of HCC cells in vitro, reducing hepatocellular tumorigenesis in immunocompetent mice, and impeding metastasis of xenograft tumours in nude mice. Comprehensive bioinformatics analyses, incorporating Super-PRED systems alongside pathway enrichment analysis, pinpointed toll-like receptor 4 (TLR4) and epidermal growth factor receptor (EGFR) as two promising targets of PCA, enriched in immune checkpoint pathway. PCA/nanocarrier (PCA) reduced levels of TLR4 and EGFR and their downstream proteins, including programmed cell death ligand 1, thereby increasing populations and activity of T cells co-cultured with HCC cells in vitro or in primary HCC tumours in mice. However, these effects were counteracted by additional artificial activation of TLR4 and EGFR. In conclusion, this study provides novel evidence of PCA's function in immunomodulation in addition to its direct tumour suppressive effect. TMC-Cys nanocarriers significantly enhance PCA efficacy, indicating promising application as a drug delivery system.

Four lathyrane diterpenoids from the seeds of Euphorbia lathyris.

Four new diterpenoids, including three secolathyrane diterpenoids (1-3) and one lathyrane diterpenoid (4), together with seven known diterpenoids, were obtained in the shelled seeds of Euphorbia lathyris. In particular, 1-3 possess a rare split ring structure, and currently only one compound with the same skeleton has been identified in E. lathyris. Compound 4 furnishes an unprecedented oxygen bridge structure. The structures were identified using various spectral techniques, including NMR, HR-ESI-MS, single-crystal X-ray diffraction and calculated electronic circular dichroism (ECD). The biosynthetic pathway of 1-4 was inferred. Furthermore, the cytotoxic activities of all compounds (1-11) were measured on three human tumor cells. New compounds 2 and 3 showed moderate cytotoxic activities against U937 cells with IC50 values of 22.18 and 25.41 µM, respectively.

Antibacterial, Fatigue-Resistant, and Self-Healing Dressing from Natural-Based Composite Hydrogels for Infected Wound Healing.

The treatment of infected wounds faces substantial challenges due to the high incidence and serious infection-related complications. Natural-based hydrogel dressings with favorable antibacterial properties and strong applicability are urgently needed. Herein, we developed a composite hydrogel by constructing multiple networks and loading ciprofloxacin for infected wound healing. The hydrogel was synthesized via a Schiff base reaction between carboxymethyl chitosan and oxidized sodium alginate, followed by the polymerization of the acrylamide monomer. The resultant hydrogel dressing possessed a good self-healing ability, considerable compression strength, and reliable compression fatigue resistance. In vitro assessment showed that the composite hydrogel effectively eliminated bacteria and exhibited an excellent biocompatibility. In a model of Staphylococcus aureus-infected full-thickness wounds, wound healing was significantly accelerated without scars through the composite hydrogel by reducing wound inflammation. Overall, this study opens up a new way for developing multifunctional hydrogel wound dressings to treat wound infections.

Double crosslinking decellularized bovine pericardium of dialdehyde chondroitin sulfate and zwitterionic copolymer for bioprosthetic heart valves with enhanced antithrombogenic, anti-inflammatory and anti-calcification properties.

Due to the increasing aging population and the advancements in transcatheter aortic valve replacement (TAVR), the use of bioprosthetic heart valves (BHVs) in patients diagnosed with valvular disease has increased substantially. Commercially available glutaraldehyde (GA) cross-linked biological valves suffer from reduced durability due to a combination of factors, including the high cell toxicity of GA, subacute thrombus, inflammation and calcification. In this study, oxidized chondroitin sulfate (OCS), a natural polysaccharide derivative, was used to replace GA to cross-link decellularized bovine pericardium (DBP), carrying out the first crosslinking of DBP to obtain OCS-BP. Subsequently, the zwitterion radical copolymerization system was introduced in situ to perform double cross-linking to obtain double crosslinked BHVs with biomimetic modification (P(APM/MPC)-OCS-BP). P(APM/MPC)-OCS-BP presented enhanced mechanical properties, collagen stability and enzymatic degradation resistance due to double crosslinking. The ex vivo AV-shunt assay and coagulation factors test suggested that P(APM/MPC)-OCS-BP exhibited excellent anticoagulant and antithrombotic properties due to the introduction of P(APM/MPC). P(APM/MPC)-OCS-BP also showed good HUVEC-cytocompatibility due to the substantial reduction of its residual aldehyde group. The subcutaneous implantation also demonstrated that P(APM/MPC)-OCS-BP showed a weak inflammatory response due to the anti-inflammatory effect of OCS. Finally, in vivo and in vitro results revealed that P(APM/MPC)-OCS-BP exhibited an excellent anti-calcification property. In a word, this simple cooperative crosslinking strategy provides a novel solution to obtain BHVs with good mechanical properties, and HUVEC-cytocompatibility, anti-coagulation, anti-inflammatory and anti-calcification properties. It might be a promising alternative to GA-fixed BP and exhibited good prospects in clinical applications.

DSYOLO-trash: An attention mechanism-integrated and object tracking algorithm for solid waste detection.

In a global context, the production of urban solid waste significantly varies with changes in living standards. This trend exhibits diversity across different countries and regions, reflecting shifts in lifestyles as well as varying needs and challenges in waste management strategies. However, current standards of waste recycling are too complex for the general public to follow. In this study, we propose a model called DSYOLO-Trash to identify solid waste by integrating the dual attention mechanisms convolutional block attention module (CBAM) and Contextual Transformer Networks(CotNet), which significantly enhance its ability to mine channel-related and spatial attention features while optimizing the learning process. We apply the deep simple online and realtime tracking (DeepSORT) object tracking algorithm to solid waste detection for the first time in the literature to enable the real-time identification and tracking of waste. We also develop a multi-label dataset of mixed solid waste, called MMTrash, to realistically simulate actual scenarios of waste classification. Our proposed DSYOLO-Trash delivered superior performance to classical detection algorithms on both the MMTrash and the TrashNet datasets. Our system combines the improved you only look once(YOLO) algorithm with DeepSORT technology by using industrial cameras and PLC-controlled robotic arms to intelligently sort waste. The work here constitutes an important contribution to intelligent waste management and the sustainable development of cities.

Structured 3' UTRs destabilize mRNAs in plants.

BACKGROUND: RNA secondary structure (RSS) can influence the regulation of transcription, RNA processing, and protein synthesis, among other processes. 3' untranslated regions (3' UTRs) of mRNA also hold the key for many aspects of gene regulation. However, there are often contradictory results regarding the roles of RSS in 3' UTRs in gene expression in different organisms and/or contexts. RESULTS: Here, we incidentally observe that the primary substrate of miR159a (pri-miR159a), when embedded in a 3' UTR, could promote mRNA accumulation. The enhanced expression is attributed to the earlier polyadenylation of the transcript within the hybrid pri-miR159a-3' UTR and, resultantly, a poorly structured 3' UTR. RNA decay assays indicate that poorly structured 3' UTRs could promote mRNA stability, whereas highly structured 3' UTRs destabilize mRNA in vivo. Genome-wide DMS-MaPseq also reveals the prevailing inverse relationship between 3' UTRs' RSS and transcript accumulation in the transcriptomes of Arabidopsis, rice, and even human. Mechanistically, transcripts with highly structured 3' UTRs are preferentially degraded by 3'-5' exoribonuclease SOV and 5'-3' exoribonuclease XRN4, leading to decreased expression in Arabidopsis. Finally, we engineer different structured 3' UTRs to an endogenous FT gene and alter the FT-regulated flowering time in Arabidopsis. CONCLUSIONS: We conclude that highly structured 3' UTRs typically cause reduced accumulation of the harbored transcripts in Arabidopsis. This pattern extends to rice and even mammals. Furthermore, our study provides a new strategy of engineering the 3' UTRs' RSS to modify plant traits in agricultural production and mRNA stability in biotechnology.

A Portable Self-Powered Electrochemical Sensor Based on Zinc-Air Battery for Detection of Hydrogen Sulfide.

The self-powered electrochemical sensor (SPES), an analytical sensing device without external power supply, is integrated with the dual function of power supply and detection performance, which lay the foundation for the development of intelligent and portable electrochemical sensing devices. Herein, a novel SPES based on a zinc-air battery was constructed for the detection of hydrogen sulfide (H2S) in the lysate of colon cancer cells. Typically, an Fe/Fe3C@graphene foam with oxygen reduction performance was used to construct SPES based on a zinc-air battery (ZAB-SPES), which brings the open-circuit voltage to 1.30 V. Among them, the poisoning effect of H2S causes the catalytic performance of the oxygen reduction catalyst to decrease, causing a significant decrease in the discharge voltage of ZAB. Based on this principle, ZAB-SPES was constructed for the detection of H2S using a digital multimeter. The proposed ZAB-SPES demonstrated good selectivity and reproducibility for detecting H2S compared to the results of the H2S-specific fluorescence probe. This strategy enriches the idea of constructing a self-powered sensor and a digital multimeter as detection devices, providing technical support for the portability of SPESs.

MARS an improved de novo peptide candidate selection method for non-canonical antigen target discovery in cancer.

Understanding the nature and extent of non-canonical human leukocyte antigen (HLA) presentation in tumour cells is a priority for target antigen discovery for the development of next generation immunotherapies in cancer. We here employ a de novo mass spectrometric sequencing approach with a refined, MHC-centric analysis strategy to detect non-canonical MHC-associated peptides specific to cancer without any prior knowledge of the target sequence from genomic or RNA sequencing data. Our strategy integrates MHC binding rank, Average local confidence scores, and peptide Retention time prediction for improved de novo candidate Selection; culminating in the machine learning model MARS. We benchmark our model on a large synthetic peptide library dataset and reanalysis of a published dataset of high-quality non-canonical MHC-associated peptide identifications in human cancer. We achieve almost 2-fold improvement for high quality spectral assignments in comparison to de novo sequencing alone with an estimated accuracy of above 85.7% when integrated with a stepwise peptide sequence mapping strategy. Finally, we utilize MARS to detect and validate lncRNA-derived peptides in human cervical tumour resections, demonstrating its suitability to discover novel, immunogenic, non-canonical peptide sequences in primary tumour tissue.

Modulating the default mode network: Antidepressant efficacy of transcutaneous electrical cranial-auricular acupoints stimulation targeting the insula.

BACKGROUND: Transcutaneous electrical cranial-auricular acupoint stimulation (TECAS) is a novel non-invasive therapy for major depressive disorder (MDD) that stimulates acupoints innervated by the trigeminal and auricular vagus nerves. However, there are few neuroimaging studies involving the TECAS for the treatment of MDD. Therefore, this study aimed to investigate the treatment response and neurological effects of TECAS using resting-state functional magnetic resonance imaging (rs-fMRI). METHOD: A total of 34 patients with mild-to-moderate MDD and 34 demographically matched healthy controls (HCs) were recruited. After an eight-week treatment the primary outcome was clinical response, defined as a baseline-to-endpoint ≥ 50 % reduction in the 17-item Hamilton Depression Rating Scale (HAMD-17). The low-frequency fluctuations (ALFF) method were used to investigate the brain abnormalities of MDD patients and HCs, and altered brain networks were analyzed between pre- and post-treatment using seed-based functional connectivity (FC) analysis. RESULTS: We found no significant differences in terms of gender, age, and years of education between the two groups. After treatment, the response rate was 58.82 %. Compared to HCs, MDD patients showed lower ALFF values in the left insula(t = -4.298,P < 0.005), the insula-based FC revealed in the right middle frontal gyrus (MFG)/ right superior frontal gyrus, orbital part (ORBsupmed) (t = -5.29,P < 0.005) and the right anterior cingulate gyrus (ACC)were decreased (t = -6.08,P < 0.005). Furthermore, Compared to pre-treatment, abnormal FC values in the ACC /orbital superior frontal gyrus (SFG) (t = 3.42,P < 0.005) and left superior frontal gyrus (SFG)/ supplement motor area (SMA) were enhanced (t = 3.34,P < 0.005). CONCLUSION: TECAS exhibits antidepressant efficacy, particularly influencing the insula-based functional connections within the Default Mode Network (DMN) related to emotion processing in individuals with MDD.

Crohn's disease as the intestinal manifestation of pan-lymphatic dysfunction: An exploratory proposal based on basic and clinical data.

Crohn's disease (CD) is caused by immune, environmental, and genetic factors. It can involve the entire gastrointestinal tract, and although its prevalence is rapidly increasing its etiology remains unclear. Emerging biological and small-molecule drugs have advanced the treatment of CD; however, a considerable proportion of patients are non-responsive to all known drugs. To achieve a breakthrough in this field, innovations that could guide the further development of effective therapies are of utmost urgency. In this review, we first propose the innovative concept of pan-lymphatic dysfunction for the general distribution of lymphatic dysfunction in various diseases, and suggest that CD is the intestinal manifestation of pan-lymphatic dysfunction based on basic and clinical preliminary data. The supporting evidence is fully summarized, including the existence of lymphatic system dysfunction, recognition of the inside-out model, disorders of immune cells, changes in cell plasticity, partial overlap of the underlying mechanisms, and common gut-derived fatty and bile acid metabolism. Another benefit of this novel concept is that it proposes adopting the zebrafish model for studying intestinal diseases, especially CD, as this model is good at presenting and mimicking lymphatic dysfunction. More importantly, the ensuing focus on improving lymphatic function may lead to novel and promising therapeutic strategies for CD.

Reducing Cholesterol Level in Live Macrophages Improves Delivery Performance by Enhancing Blood Shear Stress Adaptation.

In recent years, live-cell-based drug delivery systems have gained considerable attention. However, shear stress, which accompanies blood flow, may cause cell death and weaken the delivery performance. In this study, we found that reducing cholesterol in macrophage plasma membranes enhanced their tumor targeting ability by more than 2-fold. Our study demonstrates that the reduced cholesterol level deactivated the mammalian target of rapamycin (mTOR) and consequently promoted the nuclear translocation of transcription factor EB (TFEB), which in turn enhanced the expression of superoxide dismutase (SOD) to reduce reactive oxygen species (ROS) induced by shear stress. A proof-of-concept system using low cholesterol macrophages attached to MXene (e.g., l-RX) was fabricated. In a melanoma mouse model, l-RX and laser irradiation treatments eliminated tumors with no recurrences observed in mice. Therefore, cholesterol reduction is a simple and effective way to enhance the targeting performance of macrophage-based drug delivery systems.

A multicenter retrospective analysis: Factors influencing hepatic adverse events induced by immunotherapy in advanced liver cancer.

OBJECTIVES: To analyze the clinical characteristics and influencing factors of hepatotoxicity in patients with advanced hepatocellular carcinoma (HCC) treated with programmed cell death protein-1 (PD-1) inhibitors, and to provide a theoretical basis for the treatment of immune-related hepatotoxicity in patients with advanced HCC. METHODS: Retrospective analysis of clinical data of patients with advanced HCC from February 2021 to February 2023, in order to summarize and statistically analyze the influencing factors of immune-related liver adverse reactions. RESULTS: A total of 135 patients met the inclusion criteria, among whom 46 patients experienced varying degrees of immune-related liver adverse reactions, with an incidence rate of 34.1% (46/135). The time range of immune-related liver adverse reactions was 3-26 weeks, with a median time of 4 weeks. The age range of immune-related liver adverse reactions was 34-73 years, with a median age of 62 years. Statistical analysis of the influencing factors and liver adverse reactions showed that age, total bilirubin level, and Child-Pugh (C-P) grading were influencing factors for the occurrence of liver adverse reactions (p < .05), and among these three influencing factors, the proportion of males with ≥2 influencing factors was higher than that of females; liver function C-P B was an independent influencing factor for liver adverse reactions (p < .05). CONCLUSION: For male patients over 60 years old, with bilirubin levels ≥51 µmol/L and liver function C-P B, close observation of the occurrence of immune-related adverse reactions during treatment is recommended.

Targeting cAMP in D1-MSNs in the nucleus accumbens, a new rapid antidepressant strategy

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

3D Molybdenum Disulfide Nanospheres Loaded with Metformin to Enhance SCPP Scaffolds for Bone Regeneration.

Conventional strontium-doped calcium polyphosphate (SCPP) ceramics have attracted a lot of attention due to good cytocompatibility and controlled degradation. However, their poor mechanical strength, brittleness, and difficulty in eliminating unavoidable postoperative inflammation and bacterial infections in practical applications limit their further clinical application. In this study, carboxylated molybdenum disulfide nanospheres (MoS2-COOH) were first prepared via a one-step hydrothermal method. The optimal doping concentration of MoS2-COOH was then incorporated into SCPP to overcome its poor mechanical strength. To further enhance the anti-inflammatory properties of scaffolds, metformin (MET) was loaded onto MoS2-COOH through covalent bond cross-linking (MoS2-MET). Then MoS2-MET was doped into SCPP (SCPP/MoS2-MET) according to the previously obtained concentration, resulting in the controlled and sustained release of MET from the SCPP/MoS2-MET scaffolds for 21 days in vitro. The SCPP/MoS2-MET scaffolds were shown to have good biological activity in vitro to promote stem cell proliferation and the potential to promote mineralization in vitro. It also showed good osteoimmunomodulatory activity could reduce the expression of proinflammatory factors and effectively induce the differentiation of BMSCs under inflammatory conditions, upregulating the expression of relevant osteoblastic cytokines. In addition, SCPP/MoS2-MET scaffolds could effectively inhibit Staphylococcus aureus and Escherichia coli. In vivo experiments also demonstrated better osteogenic potential of SCPP/MoS2-MET scaffolds compared with the other scaffold-samples. Thus, the introduction of carboxylated molybdenum disulfide nanospheres is a promising approach to improve the properties of SCPP and may provide a new modification strategy for inert ceramic scaffolds and the construction of multifunctional composite scaffolds for bone tissue engineering.

Dopamine and cyclic adenosine monophosphate-regulated phosphoprotein with an apparent Mr of 32000 promotes colorectal cancer growth.

BACKGROUND: Dopamine and cyclic adenosine monophosphate (cAMP)-regulated phosphoprotein with an apparent Mr of 32000 (DARPP-32) is a protein that is involved in regulating dopamine and cAMP signaling pathways in the brain. However, recent studies have shown that DARPP-32 is also expressed in other tissues, including colorectal cancer (CRC), where its function is not well understood. AIM: To explore the effect of DARPP-32 on CRC progression. METHODS: The expression levels of DARPP-32 were assessed in CRC tissues using both quantitative polymerase chain reaction and immunohistochemistry assays. The proliferative capacity of CRC cell lines was evaluated with Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays, while apoptosis was measured by flow cytometry. The migratory and invasive potential of CRC cell lines were determined using wound healing and transwell chamber assays. In vivo studies involved monitoring the growth rate of xenograft tumors. Finally, the underlying molecular mechanism of DARPP-32 was investigated through RNA-sequencing and western blot analyses. RESULTS: DARPP-32 was frequently upregulated in CRC and associated with abnormal clinicopathological features in CRC. Overexpression of DARPP-32 was shown to promote cancer cell proliferation, migration, and invasion and reduce apoptosis. DARPP-32 knockdown resulted in the opposite functional effects. Mechanistically, DARPP-32 may regulate the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway in order to carry out its biological function. CONCLUSION: DARPP-32 promotes CRC progression via the PI3K/AKT signaling pathway.