An analysis of AURKB's prognostic and immunological roles across various cancers.

Aurora kinase B (AURKB), an essential regulator in the process of mitosis, has been revealed through various studies to have a significant role in cancer development and progression. However, the specific mechanisms remain poorly understood. This study, therefore, seeks to elucidate the multifaceted role of AURKB in diverse cancer types. This study utilized bioinformatics techniques to examine the transcript, protein, promoter methylation and mutation levels of AURKB. The study further analysed associations between AURKB and factors such as prognosis, pathological stage, biological function, immune infiltration, tumour mutational burden (TMB) and microsatellite instability (MSI). In addition, immunohistochemical staining data of 50 cases of renal clear cell carcinoma and its adjacent normal tissues were collected to verify the difference in protein expression of AURKB in the two tissues. The results show that AURKB is highly expressed in most cancers, and the protein level of AURKB and the methylation level of its promoter vary among cancer types. Survival analysis showed that AURKB was associated with overall survival in 12 cancer types and progression-free survival in 11 cancer types. Elevated levels of AURKB were detected in the advanced stages of 10 different cancers. AURKB has a potential impact on cancer progression through its effects on cell cycle regulation as well as inflammatory and immune-related pathways. We observed a strong association between AURKB and immune cell infiltration, immunomodulatory factors, TMB and MSI. Importantly, we confirmed that the AURKB protein is highly expressed in kidney renal clear cell carcinoma (KIRC). Our study reveals that AURKB may be a potential biomarker for pan-cancer and KIRC.

Autoimmune diseases and the risk of bladder cancer: A Mendelian randomization analysis.

OBJECTIVE: To investigate the association between autoimmune diseases (AIDs) and bladder cancer (BC) at the genetic level using Mendelian randomization (MR). METHODS: Single nucleotide polymorphisms (SNPs) associated with the seven AIDs were extracted from the IEU GWAS database, and the SNPs were quality-controlled using strict screening criteria. The association between AIDs and BC risk was assessed by inverse-variance weighted (IVW), MR-Egger regression and Weighted median method. The heterogeneity of SNPs was evaluated by Cochran Q test. MR-Egger intercept test and MR-PRESSO global test were used to test the horizontal pleiotropy of SNPs. Both sides with potential causal associations were validated using the validation set. RESULTS: Our result showed that genetically predicted RA was significantly associated with an increased risk of BC (IVW OR = 1.214, 95 % CI = 1.062-1.388, P = 0.005). MS nominally increased the risk of BC (IVW OR = 1.095, 95 % CI = 1.005-1.193, P = 0.037), consistent with the results of the MR analysis of the BC validation cohort. However SLE, T1D, UC, CD, and MG were not causally associated with BC risk (P > 0.05). The sensitivity analyses showed that there was no heterogeneity or horizontal pleiotropy in our findings. CONCLUSION: This study provides evidence of a causal relationship between AIDs and BC risk at the genetic level, confirming a causal relationship between RA and MS in increasing the risk of BC.

Vascular smooth muscle-specific LRRC8A knockout ameliorates angiotensin II-induced cerebrovascular remodeling by inhibiting the WNK1/FOXO3a/MMP signaling pathway.

Hypertensive cerebrovascular remodeling involves the enlargement of vascular smooth muscle cells (VSMCs), which activates volume-regulated Cl- channels (VRCCs). The leucine-rich repeat-containing family 8 A (LRRC8A) has been shown to be the molecular identity of VRCCs. However, its role in vascular remodeling during hypertension is unclear. In this study, we used vascular smooth muscle-specific LRRC8A knockout (CKO) mice and an angiotensin II (Ang II)-induced hypertension model. The results showed that cerebrovascular remodeling during hypertension was ameliorated in CKO mice, and extracellular matrix (ECM) deposition was reduced. Based on the RNA-sequencing analysis of aortic tissues, the level of matrix metalloproteinases (MMPs), such as MMP-9 and MMP-14, were reduced in CKO mice with hypertension, which was further verified in vivo by qPCR and immunofluorescence analysis. Knockdown of LRRC8A in VSMCs inhibited the Ang II-induced upregulation of collagen I, fibronectin, and matrix metalloproteinases (MMPs), and overexpression of LRRC8A had the opposite effect. Further experiments revealed an interaction between with-no-lysine (K)-1 (WNK1), which is a "Cl--sensitive kinase", and Forkhead transcription factor O3a (FOXO3a), which is a transcription factor that regulates MMP expression. Ang II induced the phosphorylation of WNK1 and downstream FOXO3a, which then increased the expression of MMP-2 and MMP-9. This process was inhibited or potentiated when LRRC8A was knocked down or overexpressed, respectively. Overall, these results demonstrate that LRRC8A knockout in vascular smooth muscle protects against cerebrovascular remodeling during hypertension by reducing ECM deposition and inhibiting the WNK1/FOXO3a/MMP signaling pathway, demonstrating that LRRC8A is a potential therapeutic target for vascular remodeling-associated diseases such as stroke.

Scoparone suppresses mitophagy-mediated NLRP3 inflammasome activation in inflammatory diseases.

Recent evidence shows that targeting NLRP3 inflammasome activation is an important means to treat inflammasome-driven diseases. Scoparone, a natural compound isolated from the Chinese herb Artemisia capillaris Thunb, has anti-inflammatory activity. In this study we investigated the effect of scoparone on NLRP3 inflammasome activation in inflammatory diseases. In LPS-primed, ATP or nigericin-stimulated mouse macrophage J774A.1 cells and bone marrow-derived macrophages (BMDMs), pretreatment with scoparone (50 µM) markedly restrained canonical and noncanonical NLRP3 inflammasome activation, evidenced by suppressed caspase-1 cleavage, GSDMD-mediated pyroptosis, mature IL-1ß secretion and the formation of ASC specks. We then conducted a transcriptome analysis in scoparone-pretreated BMDMs, and found that the differentially expressed genes were significantly enriched in mitochondrial reactive oxygen species (ROS) metabolic process, mitochondrial translation and assembly process, as well as in inflammatory response. We demonstrated in J774A.1 cells and BMDMs that scoparone promoted mitophagy, a well-characterized mechanism to control mitochondrial quality and reduce ROS production and subsequent NLRP3 inflammasome activation. Mitophagy blockade by 3-methyladenine (3-MA, 5 mM) reversed the protective effects of scoparone on mitochondrial damage and inflammation in the murine macrophages. Moreover, administration of scoparone (50 mg/kg) exerted significant preventive effects via inhibition of NLRP3 activation in mouse models of bacterial enteritis and septic shock. Collectively, scoparone displays potent anti-inflammatory effects via blocking NLRP3 inflammasome activation through enhancing mitophagy, highlighting a potential action mechanism in treating inflammasome-related diseases for further clinical investigation.

Capsaicin functions as a selective degrader of STAT3 to enhance host resistance to viral infection.

Although STAT3 has been reported as a negative regulator of type I interferon (IFN) signaling, the effects of pharmacologically inhibiting STAT3 on innate antiviral immunity are not well known. Capsaicin, approved for the treatment of postherpetic neuralgia and diabetic peripheral nerve pain, is an agonist of transient receptor potential vanilloid subtype 1 (TRPV1), with additional recognized potencies in anticancer, anti-inflammatory, and metabolic diseases. We investigated the effects of capsaicin on viral replication and innate antiviral immune response and discovered that capsaicin dose-dependently inhibited the replication of VSV, EMCV, and H1N1. In VSV-infected mice, pretreatment with capsaicin improved the survival rate and suppressed inflammatory responses accompanied by attenuated VSV replication in the liver, lung, and spleen. The inhibition of viral replication by capsaicin was independent of TRPV1 and occurred mainly at postviral entry steps. We further revealed that capsaicin directly bound to STAT3 protein and selectively promoted its lysosomal degradation. As a result, the negative regulation of STAT3 on the type I IFN response was attenuated, and host resistance to viral infection was enhanced. Our results suggest that capsaicin is a promising small-molecule drug candidate, and offer a feasible pharmacological strategy for strengthening host resistance to viral infection.

Dual Targeted Nanoparticles for the Codelivery of Doxorubicin and siRNA Cocktails to Overcome Ovarian Cancer Stem Cells.

Most anticancer treatments only induce the death of ordinary cancer cells, while cancer stem cells (CSCs) in the quiescent phase of cell division are difficult to kill, which eventually leads to cancer drug resistance, metastasis, and relapse. Therefore, CSCs are also important in targeted cancer therapy. Herein, we developed dual-targeted and glutathione (GSH)-responsive novel nanoparticles (SSBPEI-DOX@siRNAs/iRGD-PEG-HA) to efficiently and specifically deliver both doxorubicin and small interfering RNA cocktails (siRNAs) (survivin siRNA, Bcl-2 siRNA and ABCG2 siRNA) to ovarian CSCs. They are fabricated via electrostatic assembly of anionic siRNAs and cationic disulfide bond crosslinking-branched polyethyleneimine-doxorubicin (SSBPEI-DOX) as a core. Interestingly, the SSBPEI-DOX could be degraded into low-cytotoxic polyethyleneimine (PEI). Because of the enrichment of glutathione reductase in the tumor microenvironment, the disulfide bond (-SS-) in SSBPEI-DOX can be specifically reduced to promote the controlled release of siRNA and doxorubicin (DOX) in the CSCs. siRNA cocktails could specifically silence three key genes in CSCs, which, in combination with the traditional chemotherapy drug DOX, induces apoptosis or necrosis of CSCs. iRGD peptides and "sheddable" hyaluronic acid (HA) wrapped around the core could mediate CSC targeting by binding with neuropilin-1 (NRP1) and CD44 to enhance delivery. In summary, the multifunctional delivery system SSBPEI-DOX@siRNAs/iRGD-PEG-HA nanoparticles displays excellent biocompatibility, accurate CSC-targeting ability, and powerful anti-CSC ability, which demonstrates its potential value in future treatments to overcome ovarian cancer metastasis and relapse. To support this work, as exhaustive search was conducted for the literature on nanoparticle drug delivery research conducted in the last 17 years (2007-2023) using PubMed, Web of Science, and Google Scholar.

OrMKK3 Influences Morphology and Grain Size in Rice.

Although morphology and grain size are important to rice growth and yield, the identity of abundant natural allelic variations that determine agronomically important differences in crops is unknown. Here, we characterized the function of mitogen-activated protein kinase 3 from Oryza officinalis Wall. ex Watt encoded by OrMKK3. Different alternative splicing variants occurred in OrMKK3. Green fluorescent protein (GFP)-OrMKK3 fusion proteins localized to the cell membrane and nuclei of rice protoplasts. Overexpression of OrMKK3 influenced the expression levels of the grain size-related genes SMG1, GW8, GL3, GW2, and DEP3. Phylogenetic analysis showed that OrMKK3 is well conserved in plants while showing large amounts of variation between indica, japonica, and wild rice. In addition, OrMKK3 slightly influenced brassinosteroid (BR) responses and the expression levels of BR-related genes. Our findings thus identify a new gene, OrMKK3, influencing morphology and grain size and that represents a possible link between mitogen-activated protein kinase and BR response pathways in grain growth. Supplementary Information: The online version contains supplementary material available at 10.1007/s12374-020-09290-2.

Study protocol for artificial intelligence-assisted sponge cytology as pre-endoscopy screening for early esophegeal squmaous epithelial lesions in China.

BACKGROUND: Endoscopic screening is the widely accepted screening strategy for esophageal squmaous cell carcinoma (ESCC). However, massive endoscopic screening is expensive and not cost-efficient, and novel pre-endoscopy detection used as a preliminary screening method arouses new concerns. We are planning to launch an artificial intelligence (AI) assisted sponge cytology for detecting esophageal squmaous high-grade intraepithelial neoplasia (HGIN) and above lesions. The aim of this trail is to investigate the efficiency of AI-assisted sponge cytology in population-based screening of early esophageal squmaous epithelial lesions. METHODS: The study will be prospectively conducted in five regions with a high prevalence of ESCC. AI-assisted sponge cytology and endoscopic examination will be sequentially performed. Based on our previous data, at least 864 patients with esophageal HGIN and above lesions are needed to achieve enough statistical power. And, a calculated 112,500 individuals with high risks of ESCC will be recruited. In the first stage, each 24,000 participants who meet the inclusion criteria will be recruited on a voluntary basis. Setting pathological results as standard reference, diagnostic threshold and according performance of AI-assisted detection will be evaluated. A prediction model will be constructed by co-analyzing cytological results and relevant risk factors. Then, an external validation cohort will be used for validation of the model efficiency. Also, cost-efficiency analysis will be performed. This study protocol was registered on chineseclinicaltrial.gov (ChiCTR1900028524). DISCUSSION: Our study will determine whether this AI-assisted sponge cytology can be used as an effective pre-endoscopy detection tool for large-scale screening for ESCC in high-risk areas.

Viral Nanoparticle System: An Effective Platform for Photodynamic Therapy.

Photodynamic therapy (PDT) is a promising therapy due to its efficiency and accuracy. The photosensitizer is delivered to the target lesion and locally activated. Viral nanoparticles (VNPs) have been explored as delivery vehicles for PDT in recent years because of their favorable properties, including simple manufacture and good safety profile. They have great potential as drug delivery carriers in medicine. Here, we review the development of PDT photosensitizers and discuss applications of VNP-mediated photodynamic therapies and the performance of VNPs in the treatment of tumor cells and antimicrobial therapy. Furthermore, future perspectives are discussed for further developing novel viral nanocarriers or improving existing viral vectors.

Research Progress on Synthesis and Application of Cyclodextrin Polymers.

Cyclodextrins (CDs) are a series of cyclic oligosaccharides formed by amylose under the action of CD glucosyltransferase that is produced by Bacillus. After being modified by polymerization, substitution and grafting, high molecular weight cyclodextrin polymers (pCDs) containing multiple CD units can be obtained. pCDs retain the internal hydrophobic-external hydrophilic cavity structure characteristic of CDs, while also possessing the stability of polymer. They are a class of functional polymer materials with strong development potential and have been applied in many fields. This review introduces the research progress of pCDs, including the synthesis of pCDs and their applications in analytical separation science, materials science, and biomedicine.

SGK1 mediates the hypotonic protective effect against H2O2-induced apoptosis of rat basilar artery smooth muscle cells by inhibiting the FOXO3a/Bim signaling pathway.

Serum- and glucocorticoid-inducible kinease-1 (SGK1) is a serine/threonine kinase regulated by hypotonic stimuli, which is involved in regulation of cell cycle and apoptosis. Our previous study shows that activation of volume-regulated Cl- channels (VRCCs) protects rat basilar artery smooth muscle cells (BASMCs) against hydrogen peroxide (H2O2)-induced apoptosis. In the present study, we investigated whether SGK1 was involved in the protective effect of VRCCs in BASMCs. We showed that hypotonic challenge significantly reduced H2O2-induced apoptosis, and increased SGK1 phosphorylation, but did not affect SGK1 protein expression. The protective effect of hypotonic challenge against H2O2-induced apoptosis was mediated through inhibiting mitochondria-dependent apoptotic pathway, evidenced by increased Bcl-2/Bax ratio, stabilizing mitochondrial membrane potential (MMP), decreased cytochrome c release from the mitochondria to the cytoplasm, and inhibition of the activation of caspase-9 and caspase-3. These protective effects of hypotonic challenge against H2O2-induced apoptosis was diminished and enhanced, respectively, by SGK1 knockdown and overexpression. We further revealed that SGK1 activation significantly increased forkhead box O3a (FOXO3a) phosphorylation, and then inhibited the translocation of FOXO3a into nucleus and the subsequent expression of Bcl-2 interacting mediator of cell death (Bim). In conclusion, SGK1 mediates the protective effect of VRCCs against H2O2-induced apoptosis in BASMCs via inhibiting FOXO3a/Bim signaling pathway. Our results provide compelling evidences that SGK1 is a critical link between VRCCs and apoptosis, and shed a new light on the treatment of vascular apoptosis-associated diseases, such as vascular remodeling, angiogenesis, and atherosclerosis.

The Structural Characteristics of Seaweed Polysaccharides and Their Application in Gel Drug Delivery Systems.

In recent years, researchers across various fields have shown a keen interest in the exploitation of biocompatible natural polymer materials, especially the development and application of seaweed polysaccharides. Seaweed polysaccharides are a multi-component mixture composed of one or more monosaccharides, which have the functions of being anti-virus, anti-tumor, anti-mutation, anti-radiation and enhancing immunity. These biological activities allow them to be applied in various controllable and sustained anti-inflammatory and anticancer drug delivery systems, such as seaweed polysaccharide-based nanoparticles, microspheres and gels, etc. This review summarizes the advantages of alginic acid, carrageenan and other seaweed polysaccharides, and focuses on their application in gel drug delivery systems (such as nanogels, microgels and hydrogels). In addition, recent literature reports and applications of seaweed polysaccharides are also discussed.

The Application of Prussian Blue Nanoparticles in Tumor Diagnosis and Treatment.

Prussian blue nanoparticles (PBNPs) have attracted increasing research interest in immunosensors, bioimaging, drug delivery, and application as therapeutic agents due to their large internal pore volume, tunable size, easy synthesis and surface modification, good thermal stability, and favorable biocompatibility. This review first outlines the effect of tumor markers using PBNPs-based immunosensors which have a sandwich-type architecture and competitive-type structure. Metal ion doped PBNPs which were used as T1-weight magnetic resonance and photoacoustic imaging agents to improve image quality and surface modified PBNPs which were used as drug carriers to decrease side effects via passive or active targeting to tumor sites are also summarized. Moreover, the PBNPs with high photothermal efficiency and excellent catalase-like activity were promising for photothermal therapy and O2 self-supplied photodynamic therapy of tumors. Hence, PBNPs-based multimodal imaging-guided combinational tumor therapies (such as chemo, photothermal, and photodynamic therapies) were finally reviewed. This review aims to inspire broad interest in the rational design and application of PBNPs for detecting and treating tumors in clinical research.

Imine Bond- and Coordinate Bond-Linked pH-Sensitive Cisplatin Complex Nanoparticles for Active Targeting to Tumor Cells.

Aldehyde hyaluronic acid-cisplatin (A-HA-CDDP) complex nanoparticles were readily prepared, and CDDP was stably loaded into the core of the NPs through imine bond and coordinate bond linkages. The results show that the NPs were prepared successfully by a chemical complexation reaction rather than by physical mixing. Compared to many CDDP and HA complex nanoparticles evaluated in other studies, A-HA-CDDP NPs with imine and coordinate bonds between the A-HA and CDDP displayed better sustained release behavior and pH sensitivity. Therefore, the acidic tumor environment could accelerate the release of CDDP from the NPs. MTT and AO/EB staining assays showed that A-HA-CDDP NPs had comparable cell inhibition with CDDP in HeLa cells as well as little toxicity to NIH3T3 cells. This result indicates that the chemical reaction between A-HA and CDDP had little effect on the antitumor activity of CDDP and that the NPs actively targeted CD44-rich tumor cells. Both a hemolysis test and a protein adsorption assay demonstrated that A-HA-CDDP NPs had good biocompatibility and blood circulation in vivo. Therefore, the NPs have the potential to be used for targeted CDDP delivery in vivo. A subsequent publication will describe the circulation, targeting and tumor inhibition experiments of these NPs in vivo.

pH responsible and fluorescent Cy5.5-PEG-g-A-HA/CDDP complex nanoparticles: synthesis, characterization, and application for targeted drug delivery.

Clinical application of cisplatin (CDDP) against various solid tumors is often limited due to its poor selectivity and severe side effect. Considering this, in our study, CDDP was incorporated in fluorescent PEG amine grafted aldehyde hyaluronic acid by imine bond and metal ion coordination bond linking and formed a complex, the complex was then self-assembled into nanoparticles in water simply. FT-IR, XRD, DLS and SEM analysis demonstrated that the nanoparticles were prepared successfully and exhibited a spherical structure with size ranged from 216.4 to 372.3 nm in diameter. CDDP releasing from the nanoparticles was in a controlled manner, and had faster release rate at lower pH, indicating the nanoparticles were responsive to tumor micro-acid environment. Since fluorescent Cy5.5 and targeting hyaluronic acid existed on the surface of the nanoparticles, CLSM images clearly showed that the nanoparticles could target and internalize into HeLa cells, and then inhibited the growth of HeLa cells. In addition, MTT, AO-EB staining, and hemolysis assay showed that the nanoparticles had good cyto-/hemo-compatibility. Hence, the nanoparticles had the potential to be used for cancer therapy and diagnosis. The further in vivo experiment will be shown in the next work. pH responsible and fluorescent Cy5.5-PEG-g-A-HA/CDDP complex nanoparticles were facilely fabricated for controlled and targeted delivery of CDDP.

Multiresponsive and biocompatible self-healing hydrogel: its facile synthesis in water, characterization and properties.

Multiresponsive and biocompatible self-healing ε-PL/A-Pul/BPEI hydrogels were prepared in aqueous solution by Schiff base reaction with aldehyded pullulan (A-Pul), ε-poly-l-lysine (ε-PL) and branched polyethyleneimine (BPEI) as materials. The imine bonds were rapidly cross-linked into a hydrogel network within 80 s. Scanning electron microscopy images showed that the hydrogels exhibited a cross-linked structure with the average pore size from 58 to 82 µm. Rheology tests indicated that the hydrogels maintained good mechanical properties. Water contact angles and swelling studies suggested that the hydrogels could swell in water, with a max swell ratio of 1559%, and pH and temperature had an influence on the equilibrium swelling ratio. The hydrogels could be injected either before or after gelation, and they displayed a self-healing process in ddH2O at room temperature based on the dynamic uncoupling and recoupling of the imine bonds. The MTT assays implied that the hydrogels were non-cytotoxic on mice bone marrow mesenchymal stem cells. Therefore, the hydrogels showed potential application in biomedical fields, and consequently further work was performed using the self-healing hydrogels as drug carriers in in vitro/vivo antitumor studies.

Rapid Thermochromic and Highly Thermally Conductive Nanocomposite Based on Silicone Rubber for Temperature Visualization Thermal Management in Electronic Devices.

Effective heat dissipation and real-time temperature monitoring are crucial for ensuring the long-term stable operation of modern, high-performance electronic products. This study proposes a silicon rubber polydimethylsiloxane (PDMS)-based nanocomposite with a rapid thermal response and high thermal conductivity. This nanocomposite enables both rapid heat dissipation and real-time temperature monitoring for high-performance electronic products. The reported material primarily consists of a thermally conductive layer (Al2O3/PDMS composites) and a reversible thermochromic layer (organic thermochromic material, graphene oxide, and PDMS nanocoating; OTM-GO/PDMS). The thermal conductivity of OTM-GO/Al2O3/PDMS nanocomposites reached 4.14 W m-1 K-1, reflecting an increase of 2200% relative to that of pure PDMS. When the operating temperature reached 35, 45, and 65 °C, the surface of OTM-GO/Al2O3/PDMS nanocomposites turned green, yellow, and red, respectively, and the thermal response time was only 30 s. The OTM-GO/Al2O3/PDMS nanocomposites also exhibited outstanding repeatability and maintained excellent color stability over 20 repeated applications.

Inspired by game theory: Multi-signal output photoelectrochemical point-of-care immunoassay based on target-triggered organic electronic barriers.

This work presents an integrated photoelectrochemical, impedance and colorimetric biosensing platform for flexible detection of cancer markers based on the targeted response by combining liposome amplification strategies and target-induced non-in situ formation of electronic barriers as the signal transduction modality on carbon-modified CdS photoanodes. Inspired by game theory, the carbon layer modified CdS hyperbranched structure with low impedance and high photocurrent response was firstly obtained by surface modification of CdS nanomaterials. Through a liposome-mediated enzymatic reaction amplification strategy, a large number of organic electron barriers were formed by a biocatalytic precipitation (BCP) reaction triggered by horseradish peroxidase released from cleaved liposomes after the introduction of the target molecule, thereby increasing the impedance characteristics of the photoanode as well as attenuating the photocurrent. The BCP reaction in the microplate was accompanied by a significant color change, which opened up a new window for point-of-care testing. Taking carcinoembryonic antigen (CEA) as a proof of concept, the multi-signal output sensing platform showed a satisfactory sensitive response to CEA with an optimal linear range of 20 pg mL-1-100 ng mL-1. The detection limit was as low as 8.4 pg mL-1. Meanwhile, with the assistance of a portable smartphone and a miniature electrochemical workstation, the electrical signal obtained was synchronized with the colorimetric signal to correct the actual target concentration in the sample, further reducing the occurrence of false reports. Importantly, this protocol provides a new idea for the sensitive detection of cancer markers and the construction of a multi-signal output platform.

Multifunctional chondroitin sulfate based hydrogels for promoting infected diabetic wounds healing by chemo-photothermal antibacterial and cytokine modulation.

Diabetic foot (DF) is difficult to heal due to the formation of drug-resistant bacterial biofilms and dysregulation of the wound microenvironment. To solve this problem, multifunctional hydrogels were prepared by in situ or spraying with 3-aminophenylboronic acid modified oxidized chondroitin sulfate (APBA-g-OCS), polyvinyl alcohol (PVA) and black phosphorus/bismuth oxide/ε-polylysine (BP/Bi2O3/ε-PL) as precursors for promoting infected diabetic wounds healing. The hydrogels display multiple stimulus responsiveness, strong adhesion and rapid self-healing ability owing to the dynamic borate ester bonds, hydrogen bonds and π-π conjugation cross-link points, remain synergistic chemo-photothermal antibacterial effect and anti-biofilm formation ability due to the doping of BP/ Bi2O3/ε-PL into the hydrogel by dynamic imine bonds crosslinking and possess anti-oxidation and inflammatory chemokine adsorption ability attributing to the presence of APBA-g-OCS. Most importantly, as a result of the above functions, the hydrogels can not only respond to the wound microenvironment to conduct combined PTT and chemotherapy for efficient anti-inflammation, but also improve the wound microenvironment by scavenging ROS and regulating the expression of cytokines, thus further accelerating collagen deposition, promoting granulation tissue formation and angiogenesis, finally promoting the healing of infected wounds in diabetic rats.

Clinical diagnostic biomarker "circulating tumor cells" in breast cancer - a meta-analysis.

Objective: Using meta-analysis, we evaluate circulating tumor cells(CTCs) as a potential diagnostic tool for breast cancer. Methods: A document search was conducted using publicly available databases up to May 2021. Specific inclusion and exclusion criteria were formulated and summarize relevant data through literature types, research types, case populations, samples, etc. Subgroup analysis of documents based on regions, enrichment methods, and detection methods. The included research projects were evaluated using DeeKs' bias, and evaluation indicators such as specificity (SPE), sensitivity (SEN), diagnosis odds ratio (DOR) were used as evaluation indicators. Results: 16 studies on the use of circulating tumor cells to diagnose breast cancer were included in our meta-analysis. Overall sensitivity value was 0.50 (95%CI:0.48-0.52), specificity value was 0.93 (95%CI:0.92- 0.95), DOR value was 33.41 (95%CI:12.47-89.51), and AUC value was 0.8129. Conclusion: In meta-regressions and subgroup analysis, potential heterogeneity factors were analyzed, but the source of heterogeneity is still unclear. CTCs, as a novel tumor marker, have a good diagnostic value, but its enrichment and detection methods still need to continue to be developed to improve detection accuracy. Therefore, CTCs can be used as an auxiliary means of early detection, which is helpful to the diagnosis and screening of breast cancer.