Protein biomarkers have great significance for the early diagnosis of diseases. However, the discovery and validation of novel biomarkers in mass spectrometry-based proteomics remain challenging due to the inherently low abundance of glycoproteins and the presence of interfering substances. Efficient glycopeptide enrichment strategies enable the identification of glycoproteins from complex biological samples, thereby laying the foundation for biomarker discovery. This research proposed concise pre-treatment and two types of associated data processing methods for identifying potential protein biomarkers, leveraging glycopeptide enrichment using nanomaterials with different enrichment specificities obtained through diverse material design strategies. As the foundation for implementing this method, the microporous structured nanomaterial Fe3O4@PDA@MOF-IDA and the mesoporous structured nanomaterial mM-TiO2@Cys are synthesized to acquire comprehensive protein information with varying orientation. The synthesized nanomaterials both demonstrate excellent enriching performances, including a high enrichment capacity, a spectacular selectivity, and an excellent spatial confinement ability. After the acquired raw data were subjected to database searches using two software platforms, relevant protein information was obtained. By applying two data processing methods to analyze the search results from the two software platforms, respectively, 2 glycoproteins were successfully identified as novel potential quality-expressed proteins for nasopharyngeal carcinoma.

Resistance to PARP inhibitors (PARPi) remains a major clinical challenge in ovarian cancer (OC), emphasizing the need for novel strategies to enhance therapeutic efficiency. Our previous work revealed that the antimalarial drug quinacrine (QC) can be repurposed to induce cell death in OC by promoting lysosomal release of active cathepsin L (CTSL). Building on these outcomes, we investigated whether QC-activated CTSL influences DNA damage and homologous recombination (HR) repair in OC cells. Our experimental evidence shows that QC-activated CTSL downregulates key DNA repair proteins RAD51 and 53BP1, leading to impaired HR repair and increased DNA damage. Importantly, genetic knockdown of CTSL significantly reduced QC-induced DNA damage, confirming the CTSL plays a direct functional role in this process. We also found out that the response of combined QC and PARPi differs in models. CTSL was translocated to the nucleus (nCTSL) in responsive patient-derived ascitic (PDA) and patient-derived xenograft (PDX) spheroids. Contrarily, non-responsive models did not have nuclear CTSL. Mechanically, QC could not suppress CRM1/XPO1 nuclear export receptor in non-responsive cells, leading to continued export of CTSL from the nucleus. To address this, we have used the CRM1 inhibitor KPT-8602, which restored nuclear retention of CTSL. This led to enhanced therapeutic synergy with PARPi and overcame resistance in QC-treated PDA 3D-spheroids. Consistent with these findings, QC reduced tumor burden in both the cell-derived OVCAR-5 xenograft and PDX-PH070 models that showed QC-induced nCTSL, but not in the non-responsive PDX-PH095 model. However, in additional non-responsive PDX models (PH747 and PH081), treatment with QC and KPT-8602 substantially reduced tumor burden. Collectively, our results confirm a critical role for nuclear CTSL in QC-induced DNA damage and identify nCTSL as a possible predictive biomarker of therapeutic response. These results suggest that combining QC with PARPi or CRM1 inhibitors represents a promising strategy to overcome PARPi resistance in OC.

Reliable detection of low-abundance rabies viral RNA (RABV RNA) requires sensitive readouts that tolerate interfacial and matrix-associated signal variation. We developed a DNA tetrahedron-confined G4-nanotweezer biosensor combining electrochemiluminescence (ECL) and surface-enhanced Raman scattering (SERS). A Ti3C2/CsPbBr3@PDA@AuNPs nanocomposite (PAM) provided the dual-mode transducing interface, with hemin serving as both an ECL-modulating species and a SERS reporter. CsPbBr3 served as the ECL emitter, PDA improved interfacial stability, AuNPs provided SERS hotspots and DNA anchoring sites, and Ti3C2 acted as a conductive scaffold. Without target RNA, the bridging strand (ST) promoted a closed G4/hemin configuration, producing high SERS and low ECL signals. RABV RNA-triggered binding-induced isothermal amplification generated single-stranded DNA activators for CRISPR-Cas12a. Subsequent ST cleavage prevented nanotweezer closure and reduced interfacial hemin enrichment, producing an ECL-on/SERS-off response. Control experiments linked hemin-associated ECL modulation to the interfacial configuration without establishing a unique microscopic quenching pathway. The ratiometric signal R = IECL/ISERS enabled quantification over 1 aM to 50 fM. Additional low-concentration calibration yielded an estimated detection limit of 0.0675 aM by blank-threshold inverse prediction, extrapolated below the lowest measured nonzero standard of 0.10 aM. At 10 fM, matched-channel comparisons gave ratiometric relative standard deviations of 2.49% for ten successive readings and 2.87% across six independently prepared electrodes. In tenfold-diluted human serum at 10 fM, the ratio showed an 8.20% absolute deviation from phosphate-buffered saline, indicating partial matrix-effect compensation. This shared-reporter architecture links programmable DNA switching to complementary optical readouts for sensitive ratiometric viral RNA analysis.

Endovascular Coarctoplasty (CoAP) with stenting is the treatment of choice in Coarctation of Aorta (CoA). Literature on the harms or benefits of CoAP in Eisenmenger's syndrome (ES) is scarce. There is the hypothetical possibility of an increase in right-to-left intracardiac shunting once the coarctation is relieved. We report a 17-year-old male adolescent who presented with secondary hypertension, cyanosis, and lower limb claudication. He was diagnosed as a case of ventricular septal defect (VSD), patent ductus arteriosus (PDA), and CoA with associated ES. He underwent successful balloon CoAP with no clinical or invasive hemodynamic deterioration. At one-year follow-up, there was no clinical or echocardiographic evidence of complications from ES or restenosis. This case highlights that CoA with ES can be safely managed by CoAP with good long-term results. The proposed pathophysiology for the uneventful procedure is an extension of our understanding of the 'shunt dynamics' in cyanotic spells in patients with congenital cyanotic heart diseases.

A macroconidial synanamorph, namely a phragmosporous phialidic morph of Kendrickiella phycomyces (Pezizomycotina incertae sedis), was newly observed in authentic cultures isolated from the Kitora and Takamatsuzuka Tumuli in Japan. The synanamorph was sparsely produced throughout of the colonies on PDA after a few days at room temperature in cultures revived from lyophiles or in streak cultures, both derived from germinated Kendrickiella-type aseptate microconidia. After 1-2 wk, the microconidial synanamorph (the Kendrickiella-type synanamorph) and creeping hyphae completely overgrew the macroconidial morph produced on the colony surface. This sparsely produced morph appears to be a common cultural character in K. phycomyces with pleomorphic conidiation. The morphology of the macroconidial morph is described and the taxonomy of K. phycomyces is briefly reviewed and discussed.

The removal of template proteins by proteases is a viable strategy to improve the structural stability of imprinted cavities in molecularly imprinted polymers (MIPs). Human serum albumin (HSA), the most abundant serum protein, can mask trace biomarker signals and hinder their detection. In this study, HSA was covalently immobilized on Fe3O4@SiO2 via glutaraldehyde, and a thin polydopamine (PDA) layer was formed by dopamine (DA) self-polymerization, yielding magnetic molecularly imprinted polymers (MMIPs). The template was then removed with trypsin and chymotrypsin, and this enzymatic approach was compared with acid elution. The MMIPs reached adsorption equilibrium within 40 min, with a maximum capacity of 63.28 mg·g[-1] and an imprinting factor of 4.06. Sips analysis indicated heterogeneous monolayer adsorption, and the MMIPs exhibited selective HSA adsorption in complex biological matrices. After six cycles, acid-eluted MMIPs retained 94.5% of their initial capacity, whereas enzymatically eluted MMIPs retained 96.9% and showed better preservation of PDA functional groups. These results indicate that the developed material is highly promising for repeated selective removal of target proteins.

In the present study, an efficient reverse-phase high-performance liquid chromatography method was developed for the quantification of impurities of icatibant (IBT) injection in finished formulations. The stationary phase employed is Kromasil 100 C18 with dimension of (150 × 4.6) mm, 3.5 µm. A 0.05 M KH2PO4 (pH 2.5) and methanol in the ratio of (90:10%v/v) was used as eluent A and 0.05 M KH2PO4 (pH 2.5) and methanol in the ratio of (70:30%v/v) was used as eluent B pumped through 1.0 mL/min flow rate using photodiode array detector at 210 nm. The IBT injection was analyzed under various degradation conditions, including acid, base, peroxide, photolytic, and thermal, were evaluated using a present proposed developed method. The method validation was carried out based on International Conference on Harmonization guidelines, by evaluating several key parameters. The observed limit of detection values were 0.066, 0.165, 0.165, 0.197, 0.134, and 0.493 μg/mL, the observed limit of quantification values were 0.201, 0.501, 0.500, 0.598, 0.406, and 1.495 μg/mL for icatibant (7-10), Des-Pro-Impurity, Des-Arg-impurity, Des-D-Arg-impurity, D-Tic (O) 8-10 icatibant and icatibant (1-6), respectively. The average recovery percentages of impurities of IBT injection were found to be 87.4% to 108.2%. The established methodology demonstrated linearity across a concentration interval of 0.020 to 34.73μg/mL for IBT and its impurities. Specific unidentified "Impurity at RRT about 0.92" (D-Tic (O) 8-10 Icatibant), "Impurity at RRT about 1.15," "Impurity at RRT about 1.24," and "Impurity at RRT about 0.57" were identified and liquid chromatography-high resolution mass spectrometry technique was used for their characterization. This method was assessed and confirmed to be more reliable for quantifying impurities of IBT injections.

We present the case of a symptomatic 6 month old infant with a very rare form of complete vascular ring caused by a right aortic arch with abnormal branching pattern and a large left-sided patent ductus arteriosus (PDA). The large left sided PDA connected between the main pulmonary artery and the descending thoracic aorta. This configuration in combination with the right aortic arch caused tracheoesophageal compression. In addition, the left subclavian artery (LSA) and left vertebral artery (LVA) were originating from the PDA (Isolated left subclavian and left vertebral artery). This anomaly closely parallels the characteristics observed in a double aortic arch. Successful management was achieved by division of the PDA with re-implantation of the isolated LSA and LVA into the left common carotid artery.

The C-X-C motif chemokine receptor 4 (CXCR4)/C-X-C motif chemokine ligand 12 (CXCL12) axis drives immune exclusion in pancreatic ductal adenocarcinoma (PDA). Building on our preclinical data, we conducted the first stage of an open-label, single-arm phase 2 clinical trial combining CXCR4 inhibition (motixafortide), PD-1 blockade (cemiplimab), and chemotherapy (gemcitabine/nab-paclitaxel [GN]; MCGN) in 11 treatment-naïve patients with metastatic PDA (NCT04543071). The primary endpoint, objective response rate, was 64% partial response and 55% confirmed partial response per Response Evaluation Criteria in Solid Tumors. Secondary endpoints include median progression-free survival of 9.7 months (95% confidence interval [CI]: 5.9-not reached [NR]), overall survival of 10.1 months (95% CI: 9.3-NR), duration of response of 8.2 months, and 91% disease control rate. One patient achieved a pathological complete response after pancreatoduodenectomy and hepatectomy, remaining disease-free for 18 months without adjuvant therapy. Exploratory single-nucleus RNA-sequencing of serial biopsies showed reduced tumor heterogeneity, depletion of epithelial-to-mesenchymal transitional states, and enrichment of CXCL12+ cancer-associated fibroblasts in responders relative to resistant patients. MCGN also induced tumor inflammation as confirmed by tissue staining and T cell rescue. A multicenter randomized phase 2 trial comparing MCGN to GN in patients with treatment-naïve metastatic PDA is ongoing.

Achieving stable and efficient nitrite accumulation in integrated partial denitrification/anammox (PD/A) processes is typically constrained by substrate competition among microorganisms, posing a significant challenge for large-scale engineering applications. This study proposes a novel strategy for regulating nitrogen transformation pathways using chlorite (ClO2[-]) as a bioregulator, by inducing denitrification to remain at the nitrite stage and thereby providing a stable substrate supply for the anammox process. In the continuous-flow PD/A biofilter, the increase of ClO2[-] concentration from 0 to 1.0 mg/L was associated with an increase in total nitrogen removal efficiency (Re.TN) from 62.74% to a peak value of 85.27%, accompanied by an increase in effluent nitrite accumulation rate (NAR) from 62.24% to 81.77%. [15]N stable isotope tracing further confirmed that the anammox pathway dominated the system, contributing up to 98.9% of the total N2 production and serving as the primary functional support for deep nitrogen removal. The system demonstrated exceptional process robustness across a wide hydraulic retention time (HRT) range of 5-12 h, with Re.TN consistently maintained above 80%. In addition, the system exhibited good conversion capacity for ClO2[-], with the residual concentration in the effluent maintained within the safety limits, thereby reducing the potential risk of secondary pollution. Microbial community analysis indicated that ClO2[-] regulation was associated with changes in the functional microbial community structure, accompanied by increased relative abundances of the core autotrophic anammox bacteria (Candidatus Brocadia and Candidatus Jettenia) and the succession of heterotrophic Thauera populations toward nitrite-producing subgroups. Metagenomic functional profiling revealed that the functional potential of core nitrogen metabolism changed under ClO2[-] regulation, with increased relative abundances of nitrate reduction-related genes (narG/H/I) and decreased relative abundance of the nitrite reduction-related gene (nirS), while the relative abundance of the Anammox-related marker gene hdh increased by 27.5%. This study provides new insights into optimizing the stability of the PD/A system and offers new perspectives for the further engineering application of efficient nitrogen removal processes.

In this work, we have developed a photoelectrochemical-electrochemical (PEC-EC) dual-mode sensing platform consisting of a polydopamine (PDA)-poly(sulfobetaine methacrylate) (PSBMA) anti-fouling zwitterionic interface equipped with a photocurrent-polarity-switching strategy. The PSBMA-PDA copolymer anti-fouling layer was attached to a hydrogen bonded organic framework-101 (HOF-101)-Sb2S3 modified indium titanium oxide (ITO) electrode surface using a dopamine mediated coupling reaction. The attachment of the aptamer of the model analyte prostate specific antigen (PSA) was designed to trigger a hybridisation chain reaction that linked the bifunctional factor of thionine-modified hairpin H1 and hairpin H2 to the anti-fouling electrode surface. Thionine then induced a switch from a cathodic to an anodic photocurrent at the PSBMA-PDA-HOF-101-Sb2S3/ITO, while generating a large differential pulse voltammetric current. This PSBMA-PDA interface-based anti-fouling thus acts as a dual-mode sensing platform that not only offers good anti-fouling capability by reducing non-specific adsorption, but also sensitively detects PSA over a 10 fg mL[-1] - 100 ng mL[-1] linear range and a detection limit of 5.0 fg mL[-1] PSA in the PEC mode, and a 50 fg mL[-1] - 100 ng mL[-1] linear range and a detection limit of 24.6 fg mL[-1] in the EC mode. This anti-fouling PEC-EC dual-mode sensing platform is readily applicable to the highly sensitive and selective detection of various disease biomarkers by simply attaching the corresponding DNA aptamer, thereby offering a promising pathway for early clinical diagnosis and point-of-care testing.

Deformable materials permit spatiotemporally precise on-demand drug delivery via responsive morphological or structural changes, yet limited deformation mechanisms hinder their advancement. Herein, we present a photothermal-triggered deformable system engineered through liquid metal (LM) dealloying, enabling controlled multi-drug release and combined antibacterial therapy. This system features eutectic gallium-indium (EGaIn) nanoparticles (NPs) encapsulated within a polydopamine (PDA) coating, which confers stability and drug-loading capacity to the LMNPs. Additionally, this PDA coating amplifies the photothermal response, critically facilitating the dealloying and structural reconfiguration of EGaIn LMNPs under near-infrared (NIR) irradiation. The separation of In and Ga generates an In-rich core and a gallium oxide shell aggregate, inducing expansion of LMNPs that ruptures the PDA coating to trigger payload release. The results demonstrate that photosensitizer (IR820) and antibiotics levofloxacin (Lev) loaded in this system achieve on-demand release via this photothermal-triggered dealloying process. This approach achieved 6.7-log (99.99998%) reductions in Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) burdens in vitro, and a ∼5.6-log (99.999%) decrease in bacterial load in an E. coli-infected superficial wound model, via combined photothermal, photodynamic, and chemotherapeutic effects. This work pioneers the integration of LM dealloying dynamics with controlled drug release, offering a transformative strategy for precision and multimodal therapy.

Veterinary drug residues in milk represent an important food safety concern, particularly under conditions of co-administration where transporter-mediated drug-drug interactions may alter residue profiles. Marbofloxacin, a fluoroquinolone antimicrobial, is actively secreted into milk through the ATP-binding cassette transporter ABCG2 (BCRP), whereas ivermectin has been reported to interact with ABC transporters. The present study integrated in silico and in vivo approaches to investigate whether ivermectin may influence marbofloxacin secretion into sheep milk through transporter-mediated mechanisms. A homology model of ovine ABCG2 was constructed using the human cryo-electron microscopy structure as a template. Molecular docking and molecular dynamics simulations were subsequently performed to evaluate ligand-transporter interactions and complex stability. Docking analysis demonstrated that ivermectin exhibited a broader and more favorable interaction profile within the ABCG2 transmembrane cavity compared with marbofloxacin, with partial overlap at residues associated with substrate recognition, particularly within the Asp129-Asp130 region. Molecular dynamics simulations confirmed stable accommodation of ivermectin within the transporter throughout the simulation period without structural destabilization of the protein. The in vivo component included lactating dairy ewes receiving marbofloxacin alone or in combination with ivermectin under routine field conditions. Milk samples collected at the predicted peak milk concentration were analyzed using a validated HPLC-PDA/MS method. Marbofloxacin was detected in all milk samples with high analytical specificity. Ewes treated with ivermectin exhibited significantly lower marbofloxacin concentrations in milk compared with animals receiving marbofloxacin alone, while significant within-animal variability between udder halves was also observed.

The long-term success of titanium (Ti) implants in dental and orthopedic applications is frequently undermined by the dual challenges of interfacial infection and inadequate osseointegration. Consequently, there is an imperative need for multifunctional coatings that simultaneously exert antibacterial and osteoinductive activities. In this study, photothermal agent polydopamine (PDA) and photosensitizer rose bengal (RB) were facilely co-immobilized onto the titanium dioxide nanotube (TNT) arrays via mussel-inspired chemistry and amide coupling. This integrated platform enables highly efficient synergistic photothermal (PTT) and photodynamic (PDT) bacterial inactivation. The resulting TNT-PDA-RB nanocoating exhibited exceptional photobactericidal efficacy (>99.99%) against both Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA) in vitro under dual-wavelength irradiation (808 nm + 532 nm) for only 3 min. Furthermore, the coating demonstrated excellent cytocompatibility with preosteoblasts and negligible hemotoxicity against erythrocytes. In vivo rat subcutaneous infection model confirms its robust anti-infective performance, achieving a bacterial load reduction of 2.49 log (>99%) compared with pristine Ti implants. Concurrently, the nanocoating significantly promoted the alkaline phosphatase (ALP) activity and the extracellular matrix (ECM) mineralization of preosteoblasts, indicating enhanced osteoinductive properties. This multifunctional TNT-PDA-RB nanocoating offers a robust and versatile strategy for augmenting the clinical performance of Ti implants.