Acceptor-donor-acceptor-type molecules with large electrostatic potential difference for effective NIR photothermal therapy.

Although acceptor-donor-acceptor (A-D-A)-type molecules offer advantages in constructing NIR absorbing photothermal agents (PTAs) due to their strong intramolecular charge transfer and molecular planarity, their applications in photothermal therapy (PTT) of tumors remain insufficiently explored. In particular, the influence of ESP distribution on the optical properties of A-D-A photosensitizers has not been investigated. Herein, we analyze and compare the difference in ESP distribution between A-D-A-type small molecules and polymers to construct NIR absorbing PTAs with a high extinction coefficient (ε) and high photothermal conversion efficiency (PCE). The calculation results of density functional theory (DFT) indicate that the large ESP difference makes A-D-A-type small molecules superior to their polymer counterparts in realizing tight molecular packing and strong NIR absorbance. Among the as-prepared nanoparticles (NPs), Y6 NPs exhibited an obvious bathochromic shift of absorption peak from 711 nm to 822 nm, with the NIR-II emission extended to 1400 nm. Moreover, a high ε value of 5.69 L g-1 cm-1 and a PCE of 66.3% were attained, making Y6 NPs suitable for PTT. With a concentration of 100 µg mL-1, Y6 NPs in aqueous dispersion yielded a death rate of 93.4% for 4T1 cells upon 808 nm laser irradiation (1 W cm-2) for 10 min, which is comparable with the best results of recently reported PTT agents.

Molecular evolution and characterization of type III polyketide synthase gene family in Aquilaria sinensis.

2-(2-Phenylethyl) chromone (PEC) and its derivatives are markers of agarwood formation and are also related to agarwood quality. However, the biosynthetic and regulatory mechanisms of PECs still remain mysterious. Several studies suggested that type III polyketide synthases (PKSs) contribute to PEC biosynthesis in Aquilaria sinensis. Furthermore, systematic studies on the evolution of PKSs in A. sinensis have rarely been reported. Herein, we comprehensively analyzed PKS genes from 12 plant genomes and characterized the AsPKSs in detail. A unique branch contained only AsPKS members was identified through evolutionary analysis, including AsPKS01 that was previously indicated to participate in PEC biosynthesis. AsPKS07 and AsPKS08, two tandem-duplicated genes of AsPKS01 and lacking orthologous genes in evolutionary models, were selected for their transient expression in the leaves of Nicotiana benthamiana. Subsequently, PECs were detected in the extracts of N. benthamiana leaves, suggesting that AsPKS07 and AsPKS08 promote PEC biosynthesis. The interaction between the promoters of AsPKS07, AsPKS08 and five basic leucine zippers (bZIPs) from the S subfamily indicated that their transcripts could be regulated by these transcription factors (TFs) and might further contribute to PECs biosynthesis in A. sinensis. Our findings provide valuable insights into the molecular evolution of the PKS gene family in A. sinensis and serve as a foundation for advancing PEC production through the bioengineering of gene clusters. Ultimately, this contribution is expected to shed light on the mechanism underlying agarwood formation.

Rational Design of Coordination Polymers Composited Hollow Multishelled Structures for Drug Delivery.

Multifunctional drug delivery systems (DDS) are in high demand for effectively targeting specific cells, necessitating excellent biocompatibility, precise release mechanisms, and sustained release capabilities. The hollow multishelled structure (HoMS) presents a promising solution, integrating structural and compositional design for efficient DDS development amidst complex cellular environments. Herein, starting from a Fe-based metal-organic framework (MOF), amorphous coordination polymers (CP) composited HoMS with controlled shell numbers are fabricated by balancing the rate of MOF decomposition and shell formation. Fe-CP HoMS loaded with DOX is utilized for synergistic chemotherapy and chemodynamic therapy, offering excellent responsive drug release capability (excellent pH-triggered drug release 82% within 72 h at pH 5.0 solution with doxorubicin (DOX) loading capacity of 284 mg g-1). In addition to its potent chemotherapy attributes, Fe-CP-HoMS possesses chemodynamic therapy potential by continuously catalyzing H2O2 to generate ·OH species within cancer cells, thus effectively inhibiting cancer cell proliferation. DOX@3S-Fe-CP-HoMS, at a concentration of 12.5 µg mL-1, demonstrates significant inhibitory effects on cancer cells while maintaining minimal cytotoxicity toward normal cells. It is envisioned that CP-HoMS could serve as an effective and biocompatible platform for the advancement of intelligent drug delivery systems in the realm of cancer therapy.

Thermophoretic glycan profiling of extracellular vesicles for triple-negative breast cancer management.

Triple-negative breast cancer (TNBC) is a highly metastatic and heterogeneous type of breast cancer with poor outcomes. Precise, non-invasive methods for diagnosis, monitoring and prognosis of TNBC are particularly challenging due to a paucity of TNBC biomarkers. Glycans on extracellular vesicles (EVs) hold the promise as valuable biomarkers, but conventional methods for glycan analysis are not feasible in clinical practice. Here, we report that a lectin-based thermophoretic assay (EVLET) streamlines vibrating membrane filtration (VMF) and thermophoretic amplification, allowing for rapid, sensitive, selective and cost-effective EV glycan profiling in TNBC plasma. A pilot cohort study shows that the EV glycan signature reaches 91% accuracy for TNBC detection and 96% accuracy for longitudinal monitoring of TNBC therapeutic response. Moreover, we demonstrate the potential of EV glycan signature for predicting TNBC progression. Our EVLET system lays the foundation for non-invasive cancer management by EV glycans.

A Novel Laryngopharyngeal Reflux Disease Model for Bama Pigs.

OBJECTIVE: To develop a novel Laryngopharyngeal Reflux Disease (LPRD) model in Bama pigs through endoscopic cricopharyngeal myotomy. METHODS: A total of eight 8-month-old Bama pigs were randomly assigned to either the control or surgery group. Prior to intervention, upper esophageal sphincter (UES) manometry and laryngopharyngeal Dx-pH monitoring were conducted to establish baseline physiological parameters for each pig. Subsequently, the surgery group underwent endoscopic cricopharyngeal myotomy, while the control group did not. Two weeks postintervention, these procedures were repeated to evaluate changes in UES contractility and the occurrence of reflux events. At week eight postsurgery, mucosal tissues from both groups were harvested for histological analysis. Hematoxylin and eosin (H&E) staining was used to assess inflammation, while transmission electron microscopy (TEM) examined alterations in intercellular spaces and desmosomes. RESULTS: The mean UES pressures in the control and surgery groups were 59 ± 9 mmHg and 68 ± 12 mmHg, respectively. In the surgery group, there was a significant decrease in UES pressure 2weeks after the operation compared to preoperative values (P = 0.005), whereas no significant change was observed in the control group (P = 0.488). Laryngopharyngeal reflux (LPR) was successfully induced in the surgery group as evidenced by reflux events with pH <5.0, which were not detected in the control group. HE staining revealed marked inflammatory cell infiltration and submucosal gland expansion in throat tissues of the surgery group Bama pigs. TEM further showed enlarged intercellular spaces and reduced desmosome numbers in the laryngopharyngeal epithelium compared to controls. CONCLUSION: Given analogous throat epithelial structures to humans, Bama pigs are an appropriate species for an LPRD animal model. Endoscopic cricopharyngeal myotomy effectively induces LPR and observable pathological changes in Bama pigs, providing a valuable platform for further research into LPRD pathophysiology.

Atomic Engineering of Single-Atom Nanozymes for Biomedical Applications.

Single-atom nanozymes (SAzymes) showcase not only uniformly dispersed active sites but also meticulously engineered coordination structures. These intricate architectures bestow upon them an exceptional catalytic prowess, thereby captivating numerous minds and heralding a new era of possibilities in the biomedical landscape. Tuning the microstructure of SAzymes on the atomic scale is a key factor in designing targeted SAzymes with desirable functions. This review first discusses and summarizes three strategies for designing SAzymes and their impact on reactivity in biocatalysis. The effects of choices of carrier, different synthesis methods, coordination modulation of first/second shell, and the type and number of metal active centers on the enzyme-like catalytic activity are unraveled. Next, a first attempt is made to summarize the biological applications of SAzymes in tumor therapy, biosensing, antimicrobial, anti-inflammatory, and other biological applications from different mechanisms. Finally, how SAzymes are designed and regulated for further realization of diverse biological applications is reviewed and prospected. It is envisaged that the comprehensive review presented within this exegesis will furnish novel perspectives and profound revelations regarding the biomedical applications of SAzymes.

Hyaluronic acid-modified mesoporous silica nanoprobes for target identification of atherosclerosis.

Rupture of vulnerable plaque and secondary thrombosis caused by atherosclerosis are one of the main causes of acute cardiovascular and cerebrovascular events, and it is urgent to develop an in-situ, noninvasive, sensitive and targeted detection method at molecular level. We chose CD44, a specific receptor highly expressed on the surface of macrophages, as the target of the molecular probe, and modified the CD44 ligand HA onto the surface of Gd2O3@MSN, constructing the MRI imaging nanoprobe HA-Gd2O3@MSN for targeted recognition of atherosclerosis. The fundamental properties of HA-Gd2O3@MSN were initially investigated. The CCK-8, hemolysis, hematoxylin-eosin staining tests and blood biochemical assays confirmed that HA-Gd2O3@MSN possessed excellent biocompatibility. Laser confocal microscopy, cellular magnetic resonance imaging, flow cytometry and immunohistochemistry were used to verify that the nanoprobes had good targeting properties. The in vivo targeting performance of the nanoprobes was further validated by employing a rabbit atherosclerosis animal model. In summary, the synthesized HA-Gd2O3@MSN nanoprobes have excellent biocompatibility properties as well as good targeting properties. It could provide a new technical tool for early identification of atherosclerosis.

Improved titer and stability of selenium nanoparticles produced by engineered Saccharomyces cerevisiae.

Selenium nanoparticles (SeNPs) have gained significant attention in the fields of medicine and healthcare products due to their various biological activities and low toxicity. In this study, we focused on genetically modifying the Saccharomyces cerevisiae strain YW16 (CICC 1406), which has the ability to efficiently reduce sodium selenite and produce red SeNPs. By overexpressing genes involved in glutathione production, we successfully increased the glutathione titer of the modified strain YJ003 from 41.0 mg/L to 212.0 mg/L. Moreover, we improved the conversion rate of 2.0 g/L sodium selenite from 49.3% to 59.6%. Furthermore, we identified three surface proteins of SeNPs, and found that overexpression of Act1, one of the identified proteins, led to increased stability of SeNPs across different acid-base and temperature conditions. Through a 135-h feed fermentation process using 5.0 g/L sodium selenite, we achieved an impressive conversion rate of 88.7% for sodium selenite, and each gram of SeNPs contained 195.7 mg of selenium. Overall, our findings present an efficient method for yeast to synthesize SeNPs with high stability. These SeNPs hold great potential for applications in nanomedicine or as nutritional supplements to address selenium deficiency.

Genetically light-enhanced immunotherapy mediated by a fluorinated reduction-sensitive delivery system.

The lack of safe and efficient therapeutic agent delivery platforms restricts combined therapy's effect, and combined cancer therapy's multi-component delivery effect needs improvement. The novel gene delivery system SS-HPT-F/pMIP-3ß-KR was proposed to construct fluorine-containing degradable cationic polymers SS-HPT-F by a mild and simple amino-epoxy ring-opening reaction. By modifying the fluorinated alkyl chain, the delivery efficiency of the plasmid was greatly improved, and the cytoplasmic transport of biomolecules was completed. At the same time, a combination plasmid (MIP-3ß-KillerRed) was innovatively designed for the independent expression of immune and photodynamic proteins. Which was efficiently transported to the tumor site by SS-HPT-F. The MIP-3ß is expressed as an immune chemokine realize the immune mobilization behavior. The photosensitive protein KillerRed expressed in the tumor killed cancer cells under irradiation and released the exocrine immune factor MIP-3ß. The immunogenic cell death (ICD) produced by photodynamic therapy (PDT) also induced the immune response of the organism. The synergistic effect of PDT and MIP-3ß mobilized the immune properties of the organism, providing light-enhanced immune combination therapy against malignant tumors. Therefore, in subcutaneous tumor-bearing and metastatic animal models, the carrier tumor growth and mobilize organism produce an immune response without systemic toxicity. This work reports the first efficient gene delivery system that achieves light-enhanced immunotherapy.

The effectiveness of the puncture channel plugging for reduction of complications after CT-guided percutaneous transthoracic needle biopsy.

The effect of plugging the puncture channel with a mixture of hemocoagulase injection on the complications of CT-guided percutaneous transthoracic need biopsy (PTNB) was discussed. The medical records of PTNB were retrospectively studied from June 2017 to May 2022. In the study, the puncture channel of 626 patients were blocked, while remain 681 patients' were not. The Mantel Haenszel method performed layered analysis and evaluated the correlation of adjusted confounding factors. The Odds Ratio and its 95% confidence interval were calculated using the Woof method. The incidence of high-level pulmonary hemorrhage was significantly reduced in patients with lesions ≤ 2 cm and different needle lengths. Patients with different pleural-needle tip angle and perineedle emphysema were blocked, and the incidence of pneumothorax and thoracic implants was significantly reduced. Through puncture channel plugging, the incidence of pulmonary hemorrhage, pneumothorax and thoracic catheterization of PTNB under CT guidance was reduced.

Photodynamic immunotherapy using ADU-S100-modified nanoparticles to treat triple-negative breast cancer.

Aim: STING agonists in immunotherapy show great promise and are currently in clinical trials. Combinations of STING agonists with other therapies remain underexplored. This study aimed to combine STING agonist-mediated immunotherapy with photodynamic therapy to treat breast cancer. Methods: STING agonist (ADU-S100)-functionalized porphyrin-based nanoparticles (NP-AS) were prepared and their antitumor properties in terms of cell apoptosis/necrosis and immune activation in triple-negative breast cancer were evaluated. Results: NP-AS induced tumor cell apoptosis/necrosis, activated the innate immune response and exhibited useful antitumor effects. Conclusion: NP-AS effectively treated breast cancer.

Novel nanoparticles prepared from isothiocyanate derivatives for phototherapy of tumor.

Phototherapy is a new method to treat tumor, including photodynamic therapy (PDT) and photothermal therapy (PTT). However, the GSH in tumor cells could deplete ROS produced by photosensitizers, resulting in inadequate PDT. Isothiocyanate not only is a new type of anti-tumor drug, but also may combine with GSH, increasing the content of intracellular ROS and improving PDT effect. Here we synthesized a kind of water-soluble nanoparticles (BN NPs) parceling BODIPY-I-35 up with mPEG-ITC and lecithin. mPEG-ITC can react with GSH in tumor cells to reduce the consumption of ROS. BN NPs can be used as vectors to deliver drugs to tumor sites. Under 808 nm laser irradiation, BN NPs solution increased 13 °C within 10 min, indicating that BN NPs had superb photothermal performance. In vitro experiments, low dose BN NPs showed satisfactory PDT and PTT effects, and the cell viability of MCF-7 cell was only 13%. In vivo, BN NPs with excellent biocompatibility showed favorable phototherapy effect and tumor was effectively inhibited. Fluorescence imaging could present the long retention effect of BN NPs in tumor locations. In conclusion, the BN NPs showed the effect of enhancing phototherapy and provided a remarkable application prospect in the phototherapy of tumor cells.

Gadolinium (III)-Chelated Deformable Mesoporous Organosilica Nanoparticles as Magnetic Resonance Imaging Contrast Agent.

Magnetic resonance imaging (MRI) contrast agents, such as Magnevist (Gd-DTPA), are routinely used for detecting tumors at an early stage. However, the rapid clearance by the kidney of Gd-DTPA leads to short blood circulation time, which limits further improvement of the contrast between tumorous and normal tissue. Inspired by the deformability of red blood cells, which improves their blood circulation, this work fabricates a novel MRI contrast agent by incorporating Gd-DTPA into deformable mesoporous organosilica nanoparticles (D-MON). In vivo distribution shows that the novel contrast agent is able to depress rapid clearance by the liver and spleen, and the mean residence time is 20 h longer than Gd-DTPA. Tumor MRI studies demonstrated that the D-MON-based contrast agent is highly enriched in the tumor tissue and achieves prolonged high-contrast imaging. D-MON significantly improves the performance of clinical contrast agent Gd-DTPA, exhibiting good potential in clinical applications.

Ascidian-Inspired Temperature-Switchable Hydrogels with Antioxidant Fullerenols for Protecting Radiation-Induced Oral Mucositis and Maintaining the Homeostasis of Oral Microbiota.

A key characteristic of radiation-induced oral mucositis (RIOM) is oxidative stress mediated by the "reactive oxygen species (ROS) storm" generated from water radiolysis, resulting in severe pathological lesions, accompanied by a disturbance of oral microbiota. Therefore, a sprayable in situ hydrogel loaded with "free radical sponge" fullerenols (FOH) is developed as antioxidant agent for RIOM radioprotection. Inspired by marine organisms, 3,4,5-trihydroxyphenylalanine (TOPA) which is enriched in ascidians is grafted to clinically approved temperature-switchable Pluronic F127 to produce gallic acid (containing the TOPA fragment)-modified Pluronic F127 (MGA) hydrogels to resist the fast loss of FOH via biomimetic adhesion during oral movement and saliva erosion. Based on this, progressive RIOM found in mice is alleviated by treatment of FOH-loaded MGA hydrogels whether pre-irradiation prophylactic administration or post-irradiation therapeutic administration, which contributes to maintaining the homeostasis of oral microbiota. Mechanistically, FOH inhibits cell apoptosis by scavenging radiation-induced excess ROS and up-regulates the inherent enzymatic antioxidants, thereby protecting the proliferation and migration of mucosal epithelial cells. In conclusion, this work not only provides proof-of-principle evidence for the oral radioprotection of FOH by blocking the "ROS storm", but also provides an effective and easy-to-use hydrogel system for mucosal in situ administration.

Response of genes related to iron and porphyrin transport in Porphyromonas gingivalis to blue light.

BACKGROUND: Antimicrobial blue light (aBL) kills a variety of bacteria, including Porphyromonas gingivalis. However, little is known about the transcriptomic response of P. gingivalis to aBL therapy. This study was designed to evaluate the selective cytotoxicity of aBL against P. gingivalis over human cells and to further investigate the genetic response of P. gingivalis to aBL at the transcriptome level. METHODS: Colony forming unit (CFU) testing, confocal laser scanning microscopy (CLSM), and scanning electron microscopy (SEM) were used to investigate the antimicrobial effectiveness of blue light against P. gingivalis. The temperatures of the irradiated targets were measured to prevent overheating. Multiple fluorescent probes were used to quantify reactive oxygen species (ROS) generation after blue-light irradiation. RNA sequencing (RNA-seq) was used to investigate the changes in global gene expression. Following the screening of target genes, real-time quantitative polymerase chain reaction (RT-qPCR) was performed to confirm the regulation of gene expression. RESULTS: A 405 nm aBL at 100 mW/cm2 significantly killed P. gingivalis within 5 min while sparing human gingival fibroblasts (HGFs). No obvious temperature changes were detected in the irradiated surface under our experimental conditions. RNA-seq showed that the transcription of multiple genes was regulated, and RT-qPCR revealed that the expression levels of the genes RgpA and RgpB, which may promote heme uptake, as well as the genes Ftn and FetB, which are related to iron homeostasis, were significantly upregulated. The expression levels of the FeoB-2 and HmuR genes, which are related to hydroxyl radical scavenging, were significantly downregulated. CONCLUSIONS: aBL strengthens the heme uptake and iron export gene pathways while reducing the ROS scavenging pathways in P. gingivalis, thus improving the accumulation of endogenous photosensitizers and enhancing oxidative damage to P. gingivalis.

Mussel-Inspired Tantalum Nanocomposite Hydrogels for In Situ Oral Cancer Treatment.

Oral squamous cell carcinoma (OSCC) is one of the most common oral malignancies. Radiotherapy is the primary noninvasive treatment of OSCC for avoiding surgery-induced facial deformities and impaired oral function. However, the specificity of in situ OSCC limits radiotherapeutic effects because of the hypoxia-induced low radiosensitivity of tumors and the low radiation tolerance of surrounding normal tissues. Here, we design a highly efficient and low-toxic radiosensitization strategy. On the one hand, biocompatible poly(vinyl pyrrolidone)-modified tantalum nanoparticles (Ta@PVP NPs) not only have strong X-ray deposition capability to upregulate oxidative stress but also have photothermal conversion efficiency to improve hypoxia for tumor radiosensitivity. On the other hand, to optimize the spatial distribution of Ta@PVP NPs within tumors, mussel-inspired catechol with bioadhesive properties is grafted on tumor microenvironment-responsive sodium alginate (DAA) to form in situ hydrogels for precision radiotherapy. On this basis, we find that Ta@PVP-DAA hydrogels effectively inhibit OSCC development in mice under photothermal-assisted radiotherapy without facial deformities and damage to surrounding normal tissues. Overall, our work not only promotes the exploration of Ta@PVP NPs as new radiosensitizers for OSCC but also develops a nanocomposite hydrogel system strategy as a promising paradigm for the precision treatment of orthotopic tumors.

The Mechanism of Houttuynia cordata Embryotoxicity Was Explored in Combination with an Experimental Model and Network Pharmacology.

Houttuynia cordata (H. cordata) is the most common herb as a food and traditional Chinese medicine. Currently, studies on its toxicity have mainly focused on hepatotoxicity. However, its potential embryotoxicity by long-term exposure is often overlooked. Objective: To investigate the effects of H. cordata on embryonic development and its toxicity mechanism by combining network pharmacology, molecular docking, and in vitro experimental methods. Methods: The effects of H. cordata on embryos were evaluated. Zebrafish embryos and embryoid bodies were administered to observe the effects of H. cordata on embryonic development. Based on network pharmacological analysis, it was found that the main active agents producing toxicity in H. cordata were oleanolic acid, lignan, and aristolactam AII. H. cordata can affect PI3K-Akt, MAPK, and Ras signaling pathways by regulating targets, such as AKT1, EGFR, CASP3, and IGF-1. RT-PCR and immunohistochemistry results showed that the expression of AKT1 and PI3K in the embryoid body was significantly reduced after drug administration (p < 0.05). Conclusions: The results of network pharmacology and in vitro experiments suggest that H. cordata may affect embryonic development by influencing the PI3K-Akt signaling pathway.

Delayed Reaction of Radiation on the Central Nervous System and Bone System in C57BL/6J Mice.

The aim of this study was to provide a suitable mouse model of radiation-induced delayed reaction and identify potential targets for drug development related to the prevention and treatment of radiation injury. C57BL/6J mice were subjected to singular (109 cGy/min, 5 Gy*1) and fractional (109 cGy/min, 5 Gy*2) total body irradiation. The behavior and activity of mice were assessed 60 days after ionizing radiation (IR) exposure. After that, the pathological changes and mechanism of the mouse brain and femoral tissues were observed by HE, Nissl, Trap staining micro-CT scanning and RNA sequencing (RNA-Seq), and Western blot. The results show that singular or fractional IR exposure led to a decrease in spatial memory ability and activity in mice, and the cognitive and motor functions gradually recovered after singular 5 Gy IR in a time-dependent manner, while the fractional 10 Gy IR group could not recover. The decrease in bone density due to the increase in osteoclast number may be relative to the down-regulation of RUNX2, sclerostin, and beta-catenin. Meanwhile, the brain injury caused by IR exposure is mainly linked to the down-regulation of BNDF and Tau. IR exposure leads to memory impairment, reduced activity, and self-recovery, which are associated with time and dose. The mechanism of cognitive and activity damage was mainly related to oxidative stress and apoptosis induced by DNA damage. The damage caused by fractional 10 Gy TBI is relatively stable and can be used as a stable multi-organ injury model for radiation mechanism research and anti-radiation medicine screening.

Application of rapid on­site evaluation in computed tomography­guided percutaneous transthoracic needle biopsy of pulmonary nodules of ≤2.0 cm in diameter.

Histopathological findings are the gold standard for diagnosing lung nodules, and Invasive diagnostic procedures such as percutaneous transthoracic needle biopsy (PTNB) are often inevitable for a confirmative diagnosis. However, the traditional biopsy method is inefficient for the diagnosis of small pulmonary nodules (diameter ≤2.0 cm). The present study aimed to investigate the application of rapid on-site evaluation (ROSE) in CT-guided PTNB of pulmonary nodules (≤2.0 cm in diameter). Data from patients undergoing PTNB in the Second Affiliated Hospital of Qiqihar Medical College between June 2018 and June 2021 were retrospectively analyzed. A total of 250 patients were included and divided into the ROSE (n=177) and the non-ROSE groups (n=73). The comparison of these two groups indicated significantly higher specimen adequacy [93.22% (165/177) vs. 71.23% (52/73)] and diagnostic accuracy [90.40% (160/177) vs. 68.49% (50/73)], as well as a significantly lower rate of secondary biopsies [5.08% (9/177) vs. 28.77% (21/73)], in the ROSE group. The coincidence rate between the diagnosis with ROSE and the final pathological results was 96.73%, indicating high consistency (κ=0.925). The results indicated that the application of ROSE in PTNB of pulmonary nodules with a diameter of ≤2.0 cm can ensure sufficient material sampling, improve the diagnostic accuracy and reduce the secondary biopsy rate, without increasing complications. ROSE can ensure high consistency with the results obtained from the pathological evaluation.

Vascular Endothelial Growth Factor Mimetic Peptide and Parathyroid Hormone (1-34) Delivered via a Blue-Light-Curable Hydrogel Synergistically Accelerate Bone Regeneration.

Safe and effective biomaterials are in urgent clinical need for tissue regeneration and bone repair. While numerous advances have been made on hydrogels promoting osteogenesis in bone formation, co-stimulation of the angiogenic pathways in this process remains to be exploited. Here, we have developed a gelatin-based blue-light-curable hydrogel system, functionalized with an angiogenic vascular endothelial growth factor (VEGF) mimetic peptide, KLTWQELYQLKYKGI (KLT), and an osteoanabolic peptide, parathyroid hormone (PTH) 1-34. We have discovered that the covalent modification of gelatin scaffold with peptides can modulate the physical properties and biological activities of the produced hydrogels. Furthermore, we have demonstrated that those two peptides orchestrate synergistically and promote bone regeneration in a rat cranial bone defect model with remarkable efficacy. This dual-peptide-functionalized hydrogel system may serve as a promising lead to functional biomaterials in bone repair and tissue engineering.