Injectable Chitosan Hydrogels Doped with 2D Peptide Nanosheet-Drug Conjugates for Glutathione-Responsive Sustained Drug Delivery.

The development of novel and effective drug delivery systems aimed at enhancing therapeutic profile and efficacy of therapeutic agents is a critical challenge in modern medicine. This study presents an intelligent drug delivery system based on self-assembled two-dimensional peptide nanosheets (2D PNSs). Leveraging the tunable properties of amino acid structures and sequences, we design a peptide with the sequence of Fmoc-FKKGSHC, which self-assembles into 2D PNSs with uniform structure, high biocompatibility, and excellent degradability. Covalent attachment of thiol-modified doxorubicin (DOX) drugs to 2D PNSs via disulfide bond results in the peptide-drug conjugates (PDCs), which is denoted as PNS-SS-DOX. Subsequently, the PDCs are encapsulated within the injectable, thermosensitive chitosan (CS) hydrogels for drug delivery. The designed drug delivery system demonstrates outstanding pH-responsiveness and sustained drug release capabilities, which are facilitated by the characteristics of the CS hydrogels. Meanwhile, the covalently linked disulfide bond within the PNS-SS-DOX is responsive to intracellular glutathione (GSH) within tumor cells, enabling controlled drug release and significantly inhibiting the cancer cell growth. This responsive peptide-drug conjugate based on a 2D peptide nanoplatform paves the way for the development of smart drug delivery systems and has bright prospects in the future biomedicine field.

Dual-Functional Eu-Metal-Organic Framework with Ratiometric Fluorescent Broad-Spectrum Sensing of Benzophenone-like Ultraviolet Filters and High Proton Conduction.

The construction of attractive dual-functional lanthanide-based metal-organic frameworks (Ln-MOFs) with ratiometric fluorescent detection and proton conductivity is significant and challenging. Herein, a three-dimensional (3D) Eu-MOF, namely, [Eu4(HL)2(SBA)4(H2O)6]·9H2O, has been hydrothermally synthesized with a dual-ligand strategy, using (4-carboxypiperidyl)-N-methylenephosphonic acid (H3L = H2O3PCH2-NC5H9-COOH) and 4-sulfobenzoic acid monopotassium salt (KHSBA = KO3SC6H4COOH) as organic linkers. Eu-MOF showed ratiometric fluorescent broad-spectrum sensing of benzophenone-like ultraviolet filters (BP-like UVFs) with satisfactory sensitivity, selectivity, and low limits of detection in water/ethanol (1:1, v/v) solutions and real urine systems. A portable test paper was prepared for the convenience of actual detection. The potential sensing mechanisms were thoroughly analyzed by diversified experiments. The synergistic effect of the forbidden energy transfer from the ligand to Eu3+, the internal filtration effect (IFE), the formation of a complex, and weak interactions between the KHSBA ligand and BP-like UVFs is responsible for the ratiometric sensing effect. Meanwhile, Eu-MOF displayed relatively high proton conductivity of 2.60 × 10-4 S cm-1 at 368 K and 95% relative humidity (RH), making it a potential material for proton conduction. This work provides valuable guidance for the facile and effective design and construction of multifunctional Ln-MOFs with promising performance.

Recent advance in bioactive hydrogels for repairing spinal cord injury: material design, biofunctional regulation, and applications.

Functional hydrogels show potential application in repairing spinal cord injury (SCI) due to their unique chemical, physical, and biological properties and functions. In this comprehensive review, we present recent advance in the material design, functional regulation, and SCI repair applications of bioactive hydrogels. Different from previously released reviews on hydrogels and three-dimensional scaffolds for the SCI repair, this work focuses on the strategies for material design and biologically functional regulation of hydrogels, specifically aiming to show how these significant efforts can promoting the repairing performance of SCI. We demonstrate various methods and techniques for the fabrication of bioactive hydrogels with the biological components such as DNA, proteins, peptides, biomass polysaccharides, and biopolymers to obtain unique biological properties of hydrogels, including the cell biocompatibility, self-healing, anti-bacterial activity, injectability, bio-adhesion, bio-degradation, and other multi-functions for repairing SCI. The functional regulation of bioactive hydrogels with drugs/growth factors, polymers, nanoparticles, one-dimensional materials, and two-dimensional materials for highly effective treating SCI are introduced and discussed in detail. This work shows new viewpoints and ideas on the design and synthesis of bioactive hydrogels with the state-of-the-art knowledges of materials science and nanotechnology, and will bridge the connection of materials science and biomedicine, and further inspire clinical potential of bioactive hydrogels in biomedical fields.

Two Stable Cd-MOFs as Dual-Functional Materials with Luminescent Sensing of Antibiotics and Proton Conduction.

Construction and investigation of dual-functional metal-organic frameworks (MOFs) with luminescent sensing and proton conduction provide widespread applications in clean energy and environmental monitoring fields. By selecting a phosphonic acid ligand 4-pyridyl-CH2N(CH2PO3H2)2 (H4L) and coligand 2,2'-biimidazole (H2biim), two cadmium-based MOFs [Cd1.5(HL)(H2biim)0.5] (1) and (H4biim)0.5·[Cd2(L)(H2biim)Cl] (2) with different structures and properties have been hydrothermally synthesized by controlling reaction temperature. Based on the excellent thermal and chemical stabilities, and good luminescent stabilities in water solution, 1 and 2 can serve as luminescent sensors of chloramphenicol (CAP) with different quenching constant (KSV) values and detection limits (LODs) in water, simulated environmental system, and real fish water system. Meanwhile, different sensing effects and possible sensing mechanisms are analyzed in detail. Moreover, 1 and 2 can also serve as good proton-conducting materials. The proton conductivities can reach up to 1.41 × 10-4 S cm-1 for 1 and 1.02 × 10-3 S cm-1 for 2 at 368 K and 95% relative humidity (RH). Among them, 2 shows better luminescent sensing and proton conduction performance than 1, which indicates that different crystal structures have a great impact on the properties of MOFs. Through the discussion of the relationship between structures and properties in detail, the possible reasons for the differences in properties are obtained, which can provide theoretical guidance for the rational design of this kind of dual-functional MOFs in the future.

Comparative analysis of absorbed ingredients and metabolites, and pharmacokinetic studies of Zhimu-Huangbai herb pair in the plasma of normal and type 2 diabetes mellitus rats by UHPLC-linear trap quadrupole-orbitrap MS and LC-MS/MS.

A new rapid ultra-high-performance liquid chromatography coupled with linear trap quadrupole orbitrap mass spectrometry method was established for the qualitative analysis of absorbed ingredients and metabolites of Zhimu-Huangbai herb pair, which is used to treat type 2 diabetes mellitus. A total of 16 absorbed ingredients and 11 metabolites were identified in normal and type 2 diabetes mellitus rats, respectively. Such findings indicated that the diabetic model had no effect on the type of components in plasma. Seven absorbed ingredients and 11 metabolites were first identified after the oral administration of Zhimu-Huangbai herb pair. Thereafter, ultra-high-performance liquid chromatography coupled with linear trap quadrupole orbitrap mass spectrometry and liquid chromatography-API4000+ triple quadrupole mass spectrometer methods were established and validated for pharmacokinetic comparative studies of seven major bioactive components in normal and type 2 diabetes mellitus rats. Partial pharmacokinetic parameters in the plasma of type 2 diabetes mellitus rats were significantly different from those in normal rats. To our knowledge, this is the first comparison of absorbed ingredients and metabolites of Zhimu-Huangbai herb pair, and its use in pharmacokinetic studies between normal and type 2 diabetes mellitus rats. Ultimately, our findings provide insights into the clinical usage of Zhimu-Huangbai herb pair.

Dual-Functional Metal-Organic Framework for Luminescent Detection of Carcinoid Biomarkers and High Proton Conduction.

It remains a challenge to exploit dual-functional metal-organic frameworks (MOFs) for applications, including luminescence detection and proton conduction. With the deliberate selection of the bifunctional organic ligand 5-sulfoisophthalic acid monosodium salt (NaH2bts), and the phosphonic acid ligand N,N'-piperazine (bismethylenephosphonic acid; H4L), a robust three-dimensional (3D) noninterpenetrating dual-functional MOF, [Tb(H2L)(H2bts)(H2O)]·H2O (1), has been synthesized hydrothermally. On the basis of the excellent thermal and chemical as well as superior luminescence stabilities in water and solutions with different pHs, 1 can serve as the simple, rapid, and highly selective and sensitive luminescence detection of the carcinoid biomarkers 5-hydroxytryptamine (HT) and its metabolite 5-hydroxyindole-3-acetic acid (HIAA) with detection limits of nanomolar magnitude in water and in simulated blood plasma and urine systems. Due to the change in the signals that could be readily differentiated by the naked eye under a UV lamp, a portable test paper has been developed. The probable quenching mechanisms are discussed in detail. In addition, a great number of hydrogen-bonding networks are formed among the uncoordinated carboxylic oxygen atoms, sulfonate oxygen atoms, protonated nitrogen atoms, and water molecules, which provide potential proton-hopping sites for proton conduction, leading to a maximum proton conductivity of 2.3 × 10-4 S cm-1 at 368 K and 95% relative humidity. The above results suggest that rationally designed dual-functional MOFs can open an avenue for the development of occupational diagnostic tools and alternative energy technology.

Study on Omentin-1 and miR-502-3p in osteoporotic fracture.

OBJECTIVES: To explore the expression and correlation of Omentin-1 and miR-502-3p in serum of patients with osteoporotic fracture (OPF). METHODS: Sixty OPF patients diagnosed and treated in our hospital from June 2018 to December 2019 were included in group A. Fifty-six osteoporosis patients without fractures were included in group B. Omentin-1 and miR-502-3p levels were detected by enzyme-linked immunosorbent assay (ELISA) and real-time quantitative PCR (qRT-PCR). Their predictive value for diagnostic efficiency was assessed by ROC curve. Spearman's rank correlation test was used for correlation analysis. The risk factors related to the prognosis of OPF were analyzed by Logistic univariate and multivariate analysis. RESULTS: The expression of Omentin-1 and miR-502-3p in group A was markedly lower than in group B (P<0.001). Spearman correlation analysis showed that in OPF, there was a negative correlation between serum Omentin-1 and TNF-α (r=0.8579, P<0.001), a negative correlation between serum miR-502-3p and TNF-α (r= 0.8653, P<0.001), and a positive correlation between serum Omentin-1 and miR-502-3p (r= 0.8764, P<0.001). CONCLUSIONS: Omentin-1 and miR-502-3p were down-regulated in serum of patients with OPF, both of which could be used as potential biomarkers for the diagnosis and disease evaluation of OPF.

LINC01018 confers a novel tumor suppressor role in hepatocellular carcinoma through sponging microRNA-182-5p.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality. Emerging evidence has demonstrated that some long noncoding RNAs (lncRNAs) are involved in the development and progression of HCC. Herein, the current study aimed to explore the potential mechanism of LINC01018 in regulating the progression of HCC. Initially, the expression of LINC01018, microRNA-182-5p (miR-182-5p), and forkhead box protein O1 (FOXO1) was quantified in 72 paired HCC and adjacent normal tissue samples as well as HCC cells, followed by identification of the interaction among them. To define the contributory role of LINC01018 in the progression of HCC, the expression of LINC01018, miR-182-5p, or FOXO1 was altered in HCC cells, followed by evaluation of cell proliferation, cell cycle distribution, and cell apoptosis. Finally, in vivo tests were performed to further verify the role of LINC01018 in HCC. It was observed that LINC01018 and FOXO1 were poorly expressed but miR-182-5p was highly expressed in HCC tissues and cells. The upregulation of LINC01018 was shown to decrease proliferation while promoting apoptosis of HCC cells. LINC01018 acted as a sponge of miR-182-5p, which targeted FOXO1. Last, mice injected with Hep3B overexpressing FOXO1 displayed suppressed xenograft tumor formation. Collectively, overexpression of LINC01018 represses proliferation and promotes apoptosis of HCC cells via upregulation of FOXO1 by sponging miR-182-5p, which highlights overexpression of LINC01018 as a candidate suppressor of HCC.NEW & NOTEWORTHY This study provides evidence for understanding the molecular mechanism involved in the progression of hepatocellular carcinoma and identifies a novel network of LINC01018/miR-182-5p/FOXO1. We also conducted in vivo experiments in nude mice to validate the anti-tumor effect of LINC01018.

Synthesis and Photoluminescent Properties of Eu²âº-Doped BaSiF6 Nanoparticles.

By adjusting the molar ratio of oleic acid (OA), oleylamine (OM), and 1-octadecene (OD) ligands in reaction solution, Eu²âº-doped BaSiF6 nanoparticles were synthesized using a thermal decomposition synthesis route. Eu²âº ions have been successfully doped into BaSiF6 host lattice and strong 4f-4f line emission of the Eu²âº in BaSiF6 matrix is observed. Meanwhile, the photoluminescent (PL) properties of BaSiF6:Eu²âº nanoparticles doping Eu²âº ions at different concentrations were also studied.

Bioconjugation of poly(acrylic acid)-capped BaYF5:Yb3+/Er3+ up-conversion nanoparticles to bovine serum albumin: synthesis and photoluminescent properties.

Water-soluble BaYF5:Yb3+/Er3+ nanoparticles with the surface functionalized by a layer of poly(acrylic acid) (PAA) were synthesized via a facile one-step PAA-assisted hydrothermal method. Bovine serum albumin (BSA) protein was conjugated with BaYF5:Yb3+/Er3+ upconversion nanoparticles via free carboxylic acid groups on the surface of nanoparticles. The final products were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), infrared (IR) spectrophotometry, ultraviolet (UV) spectrophotometry and photoluminescence spectroscopy (PL). The XRD results showed that PAA-capped BaYF5:Yb3+/Er3+ upconversion nanoparticles could be obtained via a PAA assisted hydrothermal process with the pH value of 8 at 200 degrees C for 24 h. The TEM results showed that the morphology of BaYF5:Yb3+/Er3+ nanoparticles was spherical particles with an average diameter of about 4 nm. The IR and UV spectra showed that BSA has been conjugated with BaYF5:Yb3+/Er3+ up-conversion nanoparticles. The luminescence properties of BaYF5:Yb3+/Er3+ up-conversion nanoparticles were also studied. The luminescence properties of the products suggest that BaYF5:Yb3+/Er3+ upconversion nanoparticles have promising applications for labels in biological assays.

Assembling Ag2S quantum dots onto peptide nanosheet as a biomimetic two-dimensional nanoplatform for synergistic near infrared-II fluorescent imaging and photothermal therapy of tumor.

Fluorescent bioimaging and photothermal therapy (PTT) techniques have potential significance in cancer diagnosis and treatment and have been widely applied in biomedical and practical clinical trials. This study proposes the molecular design and biofabrication of a two-dimensional (2D) nanoplatform, exhibiting promising prospects for synergistic bioimaging and PTT of tumors. First, biocompatible 2D peptide nanosheets (PNSs) were designed and prepared through peptide self-assembly. These served as a support matrix for assembling polyethylene glycol-modified Ag2S quantum dots (PEG-Ag2SQDs) to form a 2D nanoplatform (PNS/PEG-Ag2SQDs) with unique fluorescent and photothermal properties. The designed 2D nanoplatform not only showed improved photothermal efficacy and an elevated photothermal conversion efficiency of 52.46 %, but also demonstrated significant lethality against tumors in both in vitro and in vivo cases. Additionally, it displays excellent imaging effects in the near-infrared II region, making it suitable for synergistic fluorescent imaging-guided PTT of tumors. This study not only provides a facile approach for devising and synthesizing 2D peptide assemblies but also presents new biomimetic strategies to create functional 2D organic/inorganic nanoplatforms for biomedical applications.

Recent advances in peptide-based bioactive hydrogels for nerve repair and regeneration: from material design to fabrication, functional tailoring and applications.

The injury of both central and peripheral nervous systems can result in neurological disorders and severe nervous diseases, which has been one of the challenges in the medical field. The use of peptide-based hydrogels for nerve repair and regeneration (NRR) provides a promising way for treating these problems, but the effects of the functions of peptide hydrogels on the NRR efficiency have been not understood clearly. In this review, we present recent advances in the material design, matrix fabrication, functional tailoring, and NRR applications of three types of peptide-based hydrogels, including pure peptide hydrogels, other component-functionalized peptide hydrogels, and peptide-modified polymer hydrogels. The case studies on the utilization of various peptide-based hydrogels for NRR are introduced and analyzed, in which the effects and mechanisms of the functions of hydrogels on NRR are illustrated specifically. In addition, the fabrication of medical NRR scaffolds and devices for pre-clinical application is demonstrated. Finally, we provide potential directions on the development of this promising topic. This comprehensive review could be valuable for readers to know the design and synthesis strategies of bioactive peptide hydrogels, as well as their functional tailoring, in order to promote their practical applications in tissue engineering, biomedical engineering, and materials science.

A stable Mn(II) coordination polymer demonstrating proton conductivity and quantitative sensing of oxytetracycline in aquaculture.

The construction and investigation of dual-functional coordination polymers (CPs) with proton conduction and luminescence sensing is of great significance in clean energy and agricultural monitoring fields. In this work, an Mn-based coordination polymer (Mn-CP), namely, [Mn0.5(HL)] (H2L = HOOCC6H4C6H4CH2PO(OH)OCH3), was hydrothermally synthesized. Mn-CP has a one-dimensional (1D) chain structure, in which uncoordinated -COOH groups can serve as potential sites for fluorescence sensing. Moreover, Mn-CP shows good water and pH stabilities, offering the feasibility for proton conduction and sensing applications. Mn-CP displays comparatively high proton conductivity of 1.07 × 10-4 S cm-1 at 368 K and 95% relative humidity (RH), which is promising for proton conduction materials. Moreover, it can serve as a repeatable, highly selective, and visualized fluorescence sensor for detecting oxytetracycline (OTC). More importantly, Mn-CP reveals an amazing quantitative sensing of OTC in actual samples such as seawater, aquaculture freshwater, soil infiltration solutions, and tap water. This work proves the excellent application potential of dual-functional CPs in the field of clean energy and environmental protection, especially for the fluorescence detection of antibiotics in aquaculture systems.

Skimmianine attenuates liver ischemia/reperfusion injury by regulating PI3K-AKT signaling pathway-mediated inflammation, apoptosis and oxidative stress.

Liver ischemia/reperfusion (I/R) injury is a common injury after liver transplantation and hepatectomy. Skimmianine (Ski) has antibacterial, antiviral pharmacological effects. However, it is not clear whether Ski has a protective effect against liver I/R injury. In the present study, we established a mouse liver I/R model and an AML12 cell hypoxia-reoxygenation (H/R) model, both pretreated with different concentrations of Ski. Serum transaminase levels, necrotic liver area, cell viability, inflammatory factors, oxidative stress and apoptosis-related levels were measured to assess the protective effect of Ski against liver I/R injury. Western blotting was used to detect apoptosis-related proteins and PI3K-AKT pathway-related proteins. Mice and cells were also treated with PI3K inhibitor LY294002 to assess changes in indicators of liver injury. The results showed that Ski significantly reduced transaminase levels, liver necrosis area, oxidative stress, and apoptosis levels in mice with I/R. Ski also inhibited cell injury and apoptosis after H/R. Moreover, Ski activated phosphorylation of PI3K-AKT pathway-related proteins after liver I/R and cell H/R. Importantly, the PI3K inhibitor LY294002 effectively reversed the alleviation of I/R injury caused by Ski. These results confirm that Ski exerts a protective effect against liver I/R injury through activation of the PI3K-AKT pathway.

Prognostic Model of D2 Radical Gastrectomy Combined with Neoadjuvant Chemotherapy for Gastric Cancer.

Purpose: The AJCC (the American Joint Committee on Cancer) ypTNM (post-neoadjuvant pathologic stage group) staging was established based on patients with lymphadenectomy scope less than D2 and did not include ypT0N0 patients with pathologically complete response (PCR). The purpose of this study was to construct a survival predictive model for gastric cancer patients after neoadjuvant chemotherapy and gastrectomy combined with D2 lymphadenectomy. Patients and Methods: The multicenter data of 838 gastric cancer patients who received neoadjuvant chemotherapy and gastrectomy combined with D2 lymphadenectomy were analyzed retrospectively. These dual center patients were divided into training (n = 671, the Affiliated Hospital of Qingdao University) and validation (n = 167, Qingdao West Coast New Area Central Hospital) cohorts. Based on training cohort, univariate and multivariable COX regression analyses were performed to select the clinicopathological characteristics significantly correlating with overall survival and construct a nomogram. Based on training and validation cohorts, the distinguishing and calibrating capabilities of nomogram was evaluated by the receiver operating characteristic (ROC) curve, Harrell's concordance index (C-index), decision curve analysis (DCA) curve and calibration curve. Results: Platelet-to-lymphocyte ratio (PLR), pathologic stage after neoadjuvant treatment: ypT and ypN stage, tumor regression grade (TRG) became independent variables intimately related to the prognosis and was used to construct nomograms of 3/5-year prognosis. The nomograms showed an accuracy in predicting OS (overall survival) rate, with area under the ROC curve (AUC) of 0.818 (95% CI = 0.753~0.883) and C-index of 0.801 (95% CI = 0.744~0.858) in validation cohort. Calibration curves showed satisfactory agreement between nomogram prediction and actual result, and DCA curves indicated the large positive net benefit and excellent clinical usefulness of nomogram. Conclusion: This study successfully developed a nomogram to predict overall survival of gastric cancer patients after neoadjuvant chemotherapy and gastrectomy combined with D2 lymphadenectomy, which might have excellent predictive performance and clinical application value.

Highly pH-stable lanthanide MOFs: a tunable luminescence and ratiometric luminescent probe for sulfamethazine.

By selecting a bisphosphonic ligand H4L (H4L = 4-F-C6H4CH2N(CH2PO3H2)2) and a coligand oxalate (H2C2O4), three isostructural lanthanide metal-organic frameworks (Ln-MOFs) with a 2D layer structure, [Ln(H3L)(C2O4)]·2H2O (Ln = Eu (1), Gd (2), or Tb (3)), were hydrothermally prepared. By tuning the molar ratio of Eu3+, Gd3+, and Tb3+ in the above reactions, six bimetallic or trimetallic doped Ln-MOFs (EuxTb1-x (x = 0.02 (4), 0.04 (5), and 0.06 (6)), Gd0.94Eu0.06 (7), Gd0.96Tb0.04 (8) and Gd0.95Tb0.03Eu0.02 (9)) were obtained. The powder X-ray diffraction (PXRD) patterns of doped Ln-MOFs 4-9 show that they are isomorphous with 1-3. The bimetallic doped Ln-MOFs show a gradual variation of luminous colors between yellow-green, yellow, orange, pink, and light blue. Meanwhile, the trimetallic doped Gd0.95Tb0.03Eu0.02 Ln-MOF (9) displays near white-light emission with a quantum yield of 11.39%. Interestingly, the luminous inks of 1-9 are invisible and color tunable, which makes it possible to promote their anti-counterfeiting applications. Additionally, 3 displays good thermal, water, and pH stabilities, which provides the feasibility for its sensing application. The luminescence sensing experiments show that 3 can serve as a highly selective, reusable, and ratiometric luminescent sensor of sulfamethazine (SMZ). Moreover, 3 shows an excellent SMZ detection performance in real samples, such as mariculture water and real urine. Owing to the visible variation of the response signal under a UV lamp, portable SMZ test paper was prepared.

Post-synthetic functionalization of Zn-CP by Tb3+ ions: a ratiometric luminescent sensor for the ultraviolet filter benzophenone.

Developing high-accuracy luminescent sensors for detecting emerging environmental pollutants is of great importance and is still a challenge. Utilizing a 4-carboxyphenylphosphonic acid (H3pbc) ligand, a novel one-dimensional (1D) Zn-based coordination polymer with the formula [Zn2(Hpbc)2(2,2'-bipy)(H2O)]·H2O (Zn-CP, H3pbc = 4-HOOCC6H4PO3H2, 2,2'-bipy = 2,2'-bipyridine) has been hydrothermally synthesized. Each of the 1D chains was linked via π-π stacking interactions and formed a supramolecular framework. Furthermore, due to the existence of uncoordinated -COOH groups, the terbium-functionalized hybrid (Tb3+@Zn-CP) was prepared by introducing Tb3+ ions into the structure through coordinated postsynthetic modification (PSM). Tb3+@Zn-CP shows the characteristic emission of Tb3+ ions due to the "antenna effect" of the H3pbc ligand. Based on the excellent luminescence properties and structural stabilities of Zn-CP and Tb3+@Zn-CP, they can be used as highly sensitive and selective luminescent probes of the UV filter BP (benzophenone) depending on multiquenching effects. In addition, their obvious color change can be easily distinguished by the naked eye under ultraviolet light, which was successfully used in the preparation of portable BP test paper. More importantly, Tb3+@Zn-CP is the first example of CPs as a ratiometric luminescent sensor for BP. This work provides a novel strategy for the construction of ratiometric luminescent probes of BP-type UVFs through coordinated postsynthetic modification.

A comprehensive analysis of gasdermin family gene as therapeutic targets in pan-cancer.

Six members of the gasdermin family are involved in various biological functions in malignant tumors. The present study aimed to perform a comprehensive analysis of gasdermin family genes in pan-cancer. Raw data was acquired from the genotype-tissue expression (GTEx) and the Cancer Genome Atlas. High inter-tumor heterogeneity in the expression between paracancerous and tumor tissues was observed across cancers. Survival analysis confirmed that the risk or protective effects of gasdermin family members on prognosis depended on the cancer types. The mutation frequency appeared to be high, and the mutation group had a worse prognosis. Besides, gasdermin family genes were associated with immune infiltrate subtypes, stromal and immune cell infiltration levels, TMB, MSI, immune checkpoint gene expression, and tumor stemness scores. Moreover, gasdermin family gene expressions affected the expressions of MMR genes and methyltransferases and could predict cancer cells sensitivity to chemotherapeutic drugs. Subsequently, the findings were double-checked in LIHC and PAAD. GSEA results indicated the gasdermin family genes mainly involved in tumor metabolism and immune microenvironment remodeling related signaling pathways. In conclusion, our findings confirmed that gasdermin family genes were potential therapeutic cancer targets in pan-cancer.

Single Impact Injury of Vertebral Endplates Without Structural Disruption, Initiates Disc Degeneration Through Piezo1 Mediated Inflammation and Metabolism Dysfunction.

STUDY DESIGN: In vitro experimental study. OBJECTIVE: To establish an axial impact injury model of intervertebral disc (IVD) and to investigate if a single impact injury without endplate structural disruption could initiate intervertebral disc degeneration (IDD), and what is the roles of Piezo1 in this process. SUMMARY OF BACKGROUND DATA: Although IDD process has been confirmed to be associated with structural failures such as endplate fractures, whether a single impact injury of the endplates without structural disruption could initiate IDD remains controversial. Previous studies reported that Piezo1 mediated inflammation participated in the progression of IDD induced by mechanical stretch; however, the roles of Piezo1 in IVD impact injury remain unknown. METHODS: Rats spinal segments were randomly assigned into Control, Low, and High Impact groups, which were subjected to pure axial impact loading using a custom-made apparatus, and cultured for 14 days. The degenerative process was investigated by using histomorphology, real-time Polymerase Chain Reaction(PCR), western-blot, immunofluorescence, and energy metabolism of IVD cell. The effects of Piezo1 were investigated by using siRNA transfection, real-time PCR, western-blot, and immunofluorescence. RESULTS: The discs in both of the impact groups presented degenerative changes after 14 days, which showed significant up-regulation of Piezo1, NLRP3 inflammasome, the catabolic (MMP-9, MMP-13), and pro-inflammatory gene (IL-1ß) expression than that of the control group (P < 0.05), accompanied by significantly increased release of ATP, lactate, nitric oxide (NO), and glucose consumption of IVD cells at first 7 days. Silencing Piezo1 reduced the activation of NLRP3 inflammasome and IL-1ß expression in the nucleus pulposus induced by impact injury. CONCLUSION: It demonstrated that not only fracture of the endplate but also a single impact injury without structural impairment could also initiate IDD, which might be mediated by activation of Piezo1 induced inflammation and abnormal energy metabolism of IVD cells.Level of Evidence: N/A.

Development and Validation of a Prognostic Signature Associated With Tumor Microenvironment Based on Autophagy-Related lncRNA Analysis in Hepatocellular Carcinoma.

Objective: The present study aimed to establish a prognostic signature based on the autophagy-related long non-coding RNAs (lncRNAs) analysis in patients with hepatocellular carcinoma (HCC). Methods: Patients with HCC from The Cancer Genome Atlas (TCGA) were taken as the training cohort, and patients from the International Cancer Genome Consortium (ICGC) were treated as the validation cohort. Autophagy-related lncRNAs were obtained via a co-expression network analysis. According to univariate and multivariate analyses, a multigene prognostic signature was constructed in the training cohort. The predictive power of the signature was confirmed in both cohorts. The detailed functions were investigated using functional analysis. The single-sample gene set enrichment analysis (ssGSEA) score was used to evaluate the tumor microenvironment. The expression levels of immunotherapy and targeted therapy targets between the two risk groups were compared. Finally, a nomogram was constructed by integrating clinicopathological parameters with independently predictive value and the risk score. Results: Four autophagy-related lncRNAs were identified to establish a prognostic signature, which separated patients into high- and low-risk groups. Survival analysis showed that patients in the high-risk group had a shorter survival time in both cohorts. A time-independent receiver-operating characteristic (ROC) curve and principal component analysis (PCA) confirmed that the prognostic signature had a robust predictive power and reliability in both cohorts. Functional analysis indicated that the expressed genes in the high-risk group are mainly enriched in autophagy- and cancer-related pathways. ssGSEA revealed that the different risk groups were associated with the tumor microenvironment. Moreover, the different risk groups had positive correlations with the expressions of specific mutant genes. Multivariate analysis showed that the risk score also exhibited excellent predictive power irrespective of clinicopathological characteristics in both cohorts. A nomogram was established. The nomogram showed good discrimination, with Harrell's concordance index (C-index) of 0.739 and good calibration. Conclusion: The four autophagy-related lncRNAs could be used as biological biomarkers and therapeutic targets. The prognostic signature and nomogram might aid clinicians in individual treatment optimization and clinical decision-making for patients with HCC.