Commercial Methods Research Articles

Commercial Methods for Antifungal Susceptibility Testing of Saprophytic Molds: Can They Be Used to Detect Resistance?

Commercial tests are often employed in clinical microbiology laboratories for antifungal susceptibility testing of filamentous fungi. Method-dependent epidemiological cutoff values (ECVs) have been defined in order to detect non-wild-type (NWT) isolates harboring resistance mechanisms. We reviewed the literature in order to find studies where commercial methods were used to evaluate for in vitro susceptibility of filamentous fungi and assess their ability to detect NWT isolates according to the available ECVs. Data were found for the gradient concentration strips Etest and MIC Test Strips (MTS), broth microdilution Sensititre YeastOne (SYO), Micronaut-AM and the agar dilution VIPcheck assays. Applying itraconazole, voriconazole and posaconazole Etest ECVs for A. fumigatus, Etest was able to detect 90.3% (84/93), 61.2% (90/147) and 86% (31/36) of isolates with known cyp51A mutations, respectively. Moreover, Etest also was able to detect 3/3 fks mutants using caspofungin ECVs and 2/3 micafungin mutant isolates. Applying the voriconazole and posaconazole SYO ECVs, 57.7% (67/116) and 100% (47/47) of mutants with known cyp51A substitutions were classified as NWT, respectively. VIPcheck detected 90.3% (159/176), 80.1% (141/176) and 66% (141/176)of mutants via itraconazole, voriconazole and posaconazole, respectively, whereas Micronaut-AM detected 88% (22/25). In conclusion, Etest posaconazole and itraconazole, as well as micafungin and caspofungin ECVs, detected A. fumigatus mutants. On the other hand, while the posaconazole SYO ECV was able to detect cyp51A mutants, similar data were not observed with the SYO voriconazole ECV.

Dynamic model of tissue electroporation on the basis of biological dispersion and Joule heating

Electroporation is a complex, iterative, and nonlinear phenomenon often studied through numerical simulations. In recent years, simulations of tissue electroporation have been conducted with static models. However, the results of a static model simulation are restricted to a fixed protocol signature of the pulsed electric field. In this paper, we describe a novel dynamic model of tissue electroporation that also accounts for tissue dispersion and temperature to allow time-domain simulations. We have implemented the biological dispersion of potato tubers and thermal analysis in a commercial finite-element method software. A cell electroporation model was adapted to account for the increase in tissue conductivity. The model yielded 12 parameters divided into three dynamic states of electroporation. The thermal analysis describes the dependence of tissue conductivity on temperature. The model parameters were evaluated using experiments with vegetal tissue (Solanum tuberosum) under electrochemotherapy protocols. The proposed model can accurately predict the conductivity of tissue under electroporation from 100 to 1000 V/cm. A negligible thermal effect was observed at 1000 V/cm, with a temperature increase of 0.89 °C. We believe that the proposed model is suitable to describe the electroporation at the tissue level and provides a hint of the effects on the cell membrane.

Improved DNA Extraction and Amplification Strategy for 16S rRNA Gene Amplicon-Based Microbiome Studies.

Next-generation sequencing technology has driven the rapid advancement of human microbiome studies by enabling community-level sequence profiling of microbiomes. Although all microbiome sequencing methods depend on recovering the DNA from a sample as a first critical step, lysis methods can be a major determinant of microbiome profile bias. Gentle enzyme-based DNA preparation methods preserve DNA quality but can bias the results by failing to open difficult-to-lyse bacteria. Mechanical methods like bead beating can also bias DNA recovery because the mechanical energy required to break tougher cell walls may shear the DNA of the more easily lysed microbes, and shearing can vary depending on the time and intensity of beating, influencing reproducibility. We introduce a non-mechanical, non-enzymatic, novel rapid microbial DNA extraction procedure suitable for 16S rRNA gene-based microbiome profiling applications that eliminates bead beating. The simultaneous application of alkaline, heat, and detergent ('Rapid' protocol) to milligram quantity samples provided consistent representation across the population of difficult and easily lysed bacteria equal to or better than existing protocols, producing sufficient high-quality DNA for full-length 16S rRNA gene PCR. The novel 'Rapid' method was evaluated using mock bacterial communities containing both difficult and easily lysed bacteria. Human fecal sample testing compared the novel Rapid method with a standard Human Microbiome Project (HMP) protocol for samples from lung cancer patients and controls. DNA recovered from both methods was analyzed using 16S rRNA gene sequencing of the V1V3 and V4 regions on the Illumina platform and the V1V9 region on the PacBio platform. Our findings indicate that the 'Rapid' protocol consistently yielded higher levels of Firmicutes species, which reflected the profile of the bacterial community structure more accurately, which was confirmed by mock community evaluation. The novel 'Rapid' DNA lysis protocol reduces population bias common to bead beating and enzymatic lysis methods, presenting opportunities for improved microbial community profiling, combined with the reduction in sample input to 10 milligrams or less, and it enables rapid transfer and simultaneous lysis of 96 samples in a standard plate format. This results in a 20-fold reduction in sample handling time and an overall 2-fold time advantage when compared to widely used commercial methods. We conclude that the novel 'Rapid' DNA extraction protocol offers a reliable alternative for preparing fecal specimens for 16S rRNA gene amplicon sequencing.

THE INFLUENCE OF MARKET ORIENTATION, ENTREPRENEURSHIP ORIENTATION, BUSINESS STRATEGY, AND INNOVATION ON THE PERFORMANCE

This examination aims to investigate the influence of market orientation, entrepreneurial orientation, commercial enterprise method, and innovation on the commercial enterprise performance of SMEs within the production sector in North Jakarta. The pattern selection approach in this study used a non-probability sampling technique with a convenience sampling technique. The sample on this look at is a convection business in North Jakarta with a complete of 100 respondents. data have analyzed the usage of the SEM technique with the SmartPLS utility. The consequences of this have a look at located that there may be a fine and significant effect of marketplace orientation on business performance, entrepreneurial orientation has an effective and good-sized impact on commercial enterprise overall performance, commercial enterprise method has an advantageous and vast effect on commercial enterprise performance, innovation has an insignificant high-quality effect on business performance.

Spectrophotometric estimation of curcumin in herbal face cream

Aim/Objectives: Before using plant material in cosmetics, it is important to properly identify the plant, standardize it, and use the standardized form. The prevalence of misbranded and/or spurious herbal cosmetics necessitated the regulation on their import, manufacture, sell and distribution. Hence, the study focuses on the development of a precise and reliable method for quantifying curcumin in herbal face creams. Curcumin, a frequently used phyto-constituent in these creams obtained from Curcuma longa L. (CL)belongs to the family Zingiberaceae, is known for its anti-inflammatory and wound healing properties. The proposed colorimetric method is not only accurate and reproducible, but it also has the potential to greatly contribute to the quality control and standardization of herbal cosmetics. Materials and methods: Standard methods were followed for preparation of in-house formulation and evaluation. In-house formulation was compared with four marketed samples. Results and Conclusion: Marketed samples were found to be at lower side in respect of curcumin content but comparable with in-house formulation. Although the sample number was small, the method is cost effective and gave reproducible and rapid results, hence could serve as a commercial method for standardization. The study was found to be commendable and holds great promise for the herbal cosmetics industry.

Rapid deep learning-assisted predictive diagnostics for point-of-care testing

Prominent techniques such as real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and rapid kits are currently being explored to both enhance sensitivity and reduce assay time for diagnostic tests. Existing commercial molecular methods typically take several hours, while immunoassays can range from several hours to tens of minutes. Rapid diagnostics are crucial in Point-of-Care Testing (POCT). We propose an approach that integrates a time-series deep learning architecture and AI-based verification, for the enhanced result analysis of lateral flow assays. This approach is applicable to both infectious diseases and non-infectious biomarkers. In blind tests using clinical samples, our method achieved diagnostic times as short as 2 minutes, exceeding the accuracy of human analysis at 15 minutes. Furthermore, our technique significantly reduces assay time to just 1-2 minutes in the POCT setting. This advancement has the potential to greatly enhance POCT diagnostics, enabling both healthcare professionals and non-experts to make rapid, accurate decisions.

Performance Evaluation of a Commercial Real-Time PCR Method for the Detection of Lupin Traces in Food.

In accordance with U.S. FDA Foods Program Regulatory Science Steering Committee guidelines, with this study, we optimized and validated a commercial real-time PCR method for the detection of low amounts of lupin in four classes of food matrices: chocolate cookies, ragù, Olivier salad, and barley and rice flour. DNA extracted from blank (true negative) samples artificially contaminated with lupin (Lupinus albus) flour at 1000 ppm underwent dilutions with the DNA extracted from the true negative samples up to 0.5 ppm. The limit of detection for real-time PCR was 0.5 ppm in the complex matrices (range, Ct 26-34), making this a specific, robust, and rapid method for lupin allergen detection and labeling. Our validation data support the suitability of this commercially available real-time PCR method for this purpose.

Optimized Ilmenite Leachate by Wet Mechanical Activation for the Synthesis of TiO<sub>2</sub> Nanoparticles through Sulfate Route

The extraction of ilmenite minerals using the sulfate route is one of the commercial methods for producing titanium dioxide (TiO2) materials. The sulfate process requires a high concentration of sulfuric acid to achieve high extraction yield of titanium. However, this process also results in the generation of high amounts of sulfuric acid waste. Modifying ilmenite minerals is thought to be one of approaches in reducing the consumption of highly concentrated sulfuric acid. In the current study, we investigated the effect of the ilmenite-to-water mass ratio (ITWR) on the wet-ball milling process to enhance the dissolution of titanium from the ilmenite mineral. The results revealed that increasing the water amount from 10 to 70% wt has decreased the particle size from 167.60 to 0.55 μm and increased the titanium yield from 479.36 to 1228.89 ppm. On the basis of investigation, it was shown there is a significant relationship between the ilmenite-to-water mass ratio and titanium dissolution, highlighting the importance of an optimal ratio for achieving maximum dissolving yield. The obtained TiO2 nanoparticles provide the average crystallite size of 4.16 nm, with rutile and anatase phase, and spherical morphology.

TiO2 recovered from spent selective catalytic reduction catalysts as anode material for lithium-ion batteries

Environmental protection and sustainable development are among the most severe problems in the world today. Spent selective catalytic reduction (SCR) catalysts are recognized as hazardous waste. Here, the TiO2, which accounts for nearly 80% of spent SCR catalysts, is recovered by the alkaline leaching method, and performed higher electrochemical performances than commercial TiO2 products for anode materials of Lithium-ion batteries. W, V, Si, and Al leaching rates are 40.04%, 89.59%, 61.64%, and 11.57%, respectively. A combination of density functional theory (DFT)--based calculations and experiments revealed that trace doping of Al is beneficial to the electrochemical performance of the cell, which helps us tune the Al content in the obtained materials. On this basis, the regenerated TiO2 anode materials with graphene (GR) materials are synthesized to improve the electrochemical performance, and the specific capacity of the recycled TiO2 is 188.5 mAh·g−1 after 500 cycles, and that of the regenerated TiO2/GR is the highest at 275.2 mAh·g−1. Finally, an environmental assessment of this recycling process is also carried out, human toxicity potential, CO2 gas emissions, NMVOC gas emissions, and SO2 gas emissions in this work are reduced by nearly 86.9%, 87.0%, 92.5%, and 87.0% compared with commercial sol-gel synthetic method. This work highlights the significance of recovery for preparing new energy storage materials from secondary resources.

Tribological Properties of a Sliding Joint with an a-C:H:W Coating under Lubrication Conditions with PAO8 Oil and the Addition of 2% MoS2 Nanoparticles.

One of the promising methods for improving the durability and reliability of friction joints in combustion engines is the use of thin and hard coatings, including coatings based on amorphous DLC. The a-C:H:W coating was produced using the commercial PVD method. The tested tribological joints were made of AISI 4337 steel and SAE-48 bearing alloy (conformal contact) and AISI 4337 steel and valve shims (non-conformal contact). The contact area was lubricated with SAE 5W40 engine oil and PAO8 oil + 2 wt.% MoS2 nanoparticles. The objective of this work is to explore the influence of PAO8 + MoS2 on the tribological properties of a sliding joint with an a-C:H:W coating and the change in the properties of the oils. In the conformal contact, the lubrication of the a-C:H:W coating with PAO8 + MoS2 caused a significant increase in the friction resistance (than in) as compared to the joints with a quenching and tempering surface layer and lubricated SAE 5W40, while in the non-conformal contact, the lubrication of the a-C:H:W coating with PAO8 + MoS2 caused a decrease in the friction resistance and temperature of the contact area. The joints with the a-C:H:W coating were characterized by higher wear of the SAE-48 bearing alloy, as compared to the joints with the surface layer without coating (lubricated with SAE 5W40 oil-11-fold increase, PAO8 + MoS2-46-fold increase). The wear of valve shims with the a-C:H:W coating was significantly lower as compared to the wear of the commercial version of the valve shims (the difference between joints lubricated with SAE 5W40 oil and PAO8 + MoS2 was 12%, 36% and 29% for unit pressures of 10, 15 and 20 MPa). Lubrication of the a-C:H:W coating with PAO8 oil + MoS2 protected the sliding joints against seizing in non-conformal contact.

Phyto-assisted synthesis of Silver nanoparticles using Tinospora cordifolia leaf extract and their antibacterial activity: An ecofriendly approach

To meet the increasing demands for commercial nanoparticles new eco-friendly methods of synthesis are being discovered. Plant mediated synthesis of nanoparticles offers single step, easy extracellular synthesis of nanoparticles. We report the synthesis of antibacterial Silver nanoparticles using leaf extract of the medicinal plant, Tinospora cordifolia. The leaf extract was prepared by boiling chopped leaves of Tinospora cordifolia in deionized water for 10 min and filtering the mixture with Whatman filter paper No.1. The filtrate was used as a reducing agent and stabilising agent for AgNO3. On adding 1 mM solution of Silver nitrate to the leaf extract and stirring at 75 °C for 25 min, a change in colour from yellow-brown to brown-black specified the production of Silver nanoparticles. The formation of Silver nanoparticles was monitored by UV-visible spectroscopy and further characterization of the synthesized Silver nanoparticles was done by XRD studies. The antibacterial studies were performed on Gram negative and Gram positive pathogens, Salmonella typhi, Pseudomonas aeruginosa, Enterobacter aerogenes and Staphylococcus aureus, by agar well diffusion method, on Mueller Hinton agar medium. The Silver nanoparticles synthesized from Tinospora cordifolia leaf extract were found to have antimicrobial activity against these Gram negative and Gram positive pathogenic bacteria.

Exploitation of Luminescent Lanthanide Nanoparticles for a Sensitivity-Enhanced ELISA Detection Method.

A new detection method based on the photoluminescence properties of dye-sensitized lanthanide nanoparticles (Ln NPs) was developed for enzyme-linked immunosorbent assays (ELISAs). In this method, the horseradish peroxidase (HRP) enzyme catalyzes the oxidation of phenol derivatives in the presence of hydrogen peroxide, providing dimers that are able to interact with the Ln NP surface and to efficiently photosensitize the Ln ions. Due to the very long emission lifetime of Ln, the time-gated detection of Ln NP luminescence allows the elimination of background noise due to the biological environment. After a comparison of the enzyme-catalyzed oxidation of various phenol derivatives, methyl 4-hydroxyphenyl acetate (MHPA) was selected as the most promising substrate, as the highest Ln emission intensity was observed following its HRP-catalyzed oxidation. After a meticulous optimization of the conditions of both the enzymatic reaction and the Ln sensitization (buffer, pH, concentration of the reactants, NP type, etc.), this new detection method was successfully implemented in a commercial insulin ELISA kit as a proof-of-concept, with an increased sensitivity compared to the commercial detection method.

Monitoring of Sweat Ions and Physiological Parameters via a Reconfigurable Modular System.

In recent years, wearable sensors have revolutionized health monitoring by enabling continuous, real-time tracking of human health and performance. These noninvasive devices are usually designed to monitor human physical state and biochemical markers. However, enhancing their functionalities often demands intricate customization by designers and additional expenses for users. Here, we present a strategy using assembled modular circuits to customize health monitoring wearables. The modular circuits can be effortlessly reconfigured to meet various specific requirements, facilitating the incorporation of diverse functions at a lower cost. To validate this approach, modular circuits were employed to develop four distinct systems for in vitro evaluations. These systems enabled the detection of sweat biomarkers and physical signals under various scenarios, including sedentary state, exercise, and daily activities with or without incorporating iontophoresis to induce sweat. Four key sweat markers (K+, Ca2+, Na+, and pH) and three essential physical indicators (heart rate, blood oxygen levels, and skin temperature) are selected as the detection targets. Commercial methods were also used to evaluate the potential for effective health monitoring with our technique. This reconfigurable modular wearable (ReModuWear) system promises to provide more easy-to-use and comprehensive health assessments. Additionally, it may contribute to environmental sustainability by reusing modules.

Electrode Wear Rate of RBD Palm Oil as Dielectric Fluids on Electrical Discharge Machining (EDM) at Different Peak Current and Pulse Duration of Titanium Alloys

Electrical Discharge Machining (EDM) is a widely utilized commercial method for generating a variety of forms of materials that are used as the fundamental material in a wide range of industries. Vegetable oil as the dielectric fluid is one technique for assuring EDM's long-term viability because it is ecologically benign and biodegradable. This article presents experimental investigations on the influence of electrical discharge machining (EDM) input parameters on electrode wear rate (EWR) while using EDM oil and vegetable oil as dielectric fluid. Kerosene which is known as conventional oil for EDM has been used as a benchmark to compare the feasibility of the EDM process by using a different type of dielectric fluid which is RBD palm oil. Peak currents (Ip) in the 6 to 12A range and pulse durations (ton) in the 50 to 150 µs range were chosen as the major factors for this study to improve the efficiency of EDM operation. Scanning electron microscopy (SEM) was used to observe the morphology surface characteristics of the copper electrode and the migration of workpiece material elements to the tool electrode. The EWR increases with increasing peak current, although it is inversely related to pulse duration. The lowest EWR for kerosene and RBD palm oil is 0.0416mm3/min and 0.0480mm3/min, respectively, at the same IP=6A and ton=150µs. Simultaneously, the highest EWR for both kerosene and RBD palm oil was at the same IP=12A and ton=50µs, which is 0.1725mm3/min and 0.2425mm3/min, respectively.

Multicentric evaluation of sensitivity of eight commercial anti-SARS-CoV-2 antibody assays and their correlation to virus neutralization titers in seropositive subjects

Diagnosis of SARS-CoV-2 virus is mainly based on direct detection. Determination of specific antibodies has been used mostly for epidemiological reasons. However, select immunoassays showed good correlation to plaque reduction virus neutralization test (PRNT) in smaller patient cohorts, which suggests their potential as predictors of virus neutralization titer. A total of 3,699 samples from Covid-19 patients were included in the multicentric study performed in the Czech Republic. Anti-SARS-CoV-2 antibody levels were evaluated by 8 commercial antibody assays. Simultaneously, PRNT evaluations were performed with the SARS-CoV-2 B.1.258 variant. All immunoassays showed an overall high true positive diagnostic value ranging from 79.17 to 98.04%. Several commercial EIA methods showed highly positive correlation between the assay results and PRNT levels, e.g., Liaison CoV-2 TrimericS IgG DiaSorin (Spearman r = 0.8833; Architect SASRS-CoV-2 IgG Abbott (r = 0.7298); NovaLisa SARS-CoV-2 IgG NovaTec (r = 0.7103) and Anti-SARS-CoV-2 ELISA IgG Euroimmun (r = 0.7094). While this correlation was less positive for other assays, those, conversely, presented higher true positive values. For most immunoassays, the positive percent agreement of the results was ≥ 95% in sera exhibiting PRNT levels of 1:80 and higher. The assays tested have shown variable correlation to PRNT. Those possessing high positive predictive values serve well as qualitative tests, while others can be utilised as quantitative tests highly predictive of neutralization antibody levels.

Antifungal susceptibility profile and local epidemiological cut-off values of Yarrowia (Candida) lipolytica: an emergent and rare opportunistic yeast.

Yarrowia lipolytica, also known as Candida lipolytica, is an emerging opportunistic "rare pathogenic yeast". Due to the limited data on its antifungal susceptibility, the clinical treatments become challenging. Based on the China Hospital Invasive Fungal Surveillance Network (2009-2022), we conducted a comprehensive multi-method study on clinical isolates from various central hospitals. This study is currently the largest study carried out to assess the antifungal susceptibility of Y. lipolytica. It is also the first to establish local epidemiological cut-off values (L-ECOFFs), identify its ERG11 mutations, and assess the consistency between the three prevalent commercial antifungal susceptibility testing methods and the broth microdilution method. We recommend the Sensititre YeastOne as the best option for antifungal susceptibility testing for Y. lipolytica, followed by the ATB FUNGUS 3. Nevertheless, practitioners should use the MIC test strip with discretion.

Validation of an automated sample preparation module directly connected to LC-MS/MS (CLAM-LC-MS/MS system) and comparison with conventional immunoassays for quantitation of tacrolimus and cyclosporin A in a clinical setting

BackgroundTherapeutic drug monitoring (TDM) systems generally use either liquid chromatography/tandem mass spectrometry (LC-MS/MS) or immunoassay, though both methodologies have disadvantages. In this study, we aimed to evaluate whether a CLAM-LC-MS/MS system, which consists of a sample preparation module directly connected to LC-MS/MS, could be used for clinical TDM work for immunosuppressive drugs in whole blood, which requires a hemolytic process. For this purpose, we prospectively validated this system for clinical measurement of tacrolimus and cyclosporin A in patients’ whole blood. The results were also compared with those of commercial immunoassays.MethodsWhole blood from patients treated with tacrolimus or cyclosporin A at the Department of Nephrology and Departments of Rheumatology, Kanazawa University Hospital, from May 2018 to July 2019 was collected with informed consent, and drug concentrations were measured by CLAM-LC-MS/MS and by chemiluminescence immunoassay (CLIA) for tacrolimus and affinity column-mediated immunoassay (ACMIA) for cyclosporin A. Correlations between the CLAM-LC-MS/MS and immunoassay results were analyzed.ResultsTwo hundred and twenty-four blood samples from 80 patients were used for tacrolimus measurement, and 76 samples from 21 patients were used for cyclosporin A. Intra- and inter-assay precision values of quality controls were less than 7%. There were significant correlations between CLAM-LC-MS/MS and the immunoassays for tacrolimus and cyclosporin A (Spearman rank correlation coefficients: 0.861, 0.941, P < 0.00001 in each case). The drug concentrations measured by CLAM-LC-MS/MS were about 20% lower than those obtained using the immunoassays. CLAM-LC-MS/MS maintenance requirements did not interfere with clinical operations. Compared to manual pretreatment, automated pretreatment by CLAM showed lower inter-assay precision values and greatly reduced the pretreatment time.ConclusionsThe results obtained by CLAM-LC-MS/MS were highly correlated with those of commercial immunoassay methods. CLAM-LC-MS/MS offers advantages in clinical TDM practice, including simple, automatic pretreatment, low maintenance requirement, and avoidance of interference.

Fast Simultaneous Feasibility Test for Security Constrained Unit Commitment

We present a novel fast security analysis method to perform a simultaneous feasibility test (SFT) for security constrained unit commitment (SCUC). Given an SCUC solution, SFT computes base and contingent line flows, overloads, and sensitivities for formulating the violated constraints in the SCUC solver. We use the Sherman-Morrison-Woodbury (SMW) formula to handle topology changes across hours and contingencies. We first developed this SMW-based SFT for contingencies relative to a static network as a generalization of line outage distribution factors (LODFs) achieving the speed of LODFs and modeling complex contingencies as in commercial SFTs. Speedup of the SMW method over commercial methods comes from moving computation from the solve phase to a startup phase. We now extend the SMW technique to network changes across hours and contingencies, permitting deployment on a single compute node due to speedup of the startup phase. The fast SMW-based SFT can be used in a callback, improving over the traditional SCUC-SFT iteration due to a stronger guarantee of satisfying security constraints and to overall speedup since the SCUC solver is invoked only once. The memory required by the SMW-based SFT is large but manageable, and we formulate a technique to decrease this by 80% when implemented.

A paper-based dual functional biosensor for safe and user-friendly point-of-care urine analysis.

Safe, accurate, and reliable analysis of urinary biomarkers is clinically important for early detection and monitoring of the progression of chronic kidney disease (CKD), as it has become one of the world's most prevalent non-communicable diseases. However, current technologies for measuring urinary biomarkers are either time-consuming and limited to well-equipped hospitals or lack the necessary sensitivity for quantitative analysis and post a health risk to frontline practitioners. Here we report a robust paper-based dual functional biosensor, which is integrated with the clinical urine sampling vial, for the simultaneous and quantitative analysis of pH and glucose in urine. The pH sensor was fabricated by electrochemically depositing IrOx onto a paper substrate using optimised parameters, which enabled an ultrahigh sensitivity of 71.58 mV pH-1. Glucose oxidase (GOx) was used in combination with an electrochemically deposited Prussian blue layer for the detection of glucose, and its performance was enhanced by gold nanoparticles (AuNPs), chitosan, and graphite composites, achieving a sensitivity of 1.5 μA mM-1. This dual function biosensor was validated using clinical urine samples, where a correlation coefficient of 0.96 for pH and 0.98 for glucose detection was achieved with commercial methods as references. More importantly, the urine sampling vial was kept sealed throughout the sample-to-result process, which minimised the health risk to frontline practitioners and simplified the diagnostic procedures. This diagnostic platform, therefore, holds high promise as a rapid, accurate, safe, and user-friendly point-of-care (POC) technology for the analysis of urinary biomarkers in frontline clinical settings.

Synergistic acceleration of machine learning and molecular docking for prostate-specific antigen ligand design.

Prostate-specific antigen (PSA) serves as a critical biomarker for the early detection and continuous monitoring of prostate cancer. However, commercial PSA detection methods primarily rely on antigen-antibody interactions, leading to issues such as high costs, stringent storage requirements, and potential cross-reactivity due to PSA variant sequence homology. This study is dedicated to the precise design and synthesis of molecular entities tailored for binding with PSA. By employing a million-level virtual screening to obtain potential PSA compounds and effectively guiding the synthesis using machine learning methods, the resulting lead compounds exhibit significantly improved binding affinity compared to those developed before by researchers using high-throughput screening for PSA, substantially reducing screening and development costs. Unlike antibody detection, the design of these small molecules offers promising avenues for advancing prostate cancer diagnostics. Furthermore, this study establishes a systematic framework for the rapid development of customized ligands that precisely target specific protein entities.