A Unique Approach: Biomimetic Graphdiyne-Based Nanoplatform to Treat Prostate Cancer by Combining Cuproptosis and Enhanced Chemodynamic Therapy.

Purpose: Current treatment approaches for Prostate cancer (PCa) often come with debilitating side effects and limited therapeutic outcomes. There is urgent need for an alternative effective and safe treatment for PCa. Methods: We developed a nanoplatform to target prostate cancer cells based on graphdiyne (GDY) and a copper-based metal-organic framework (GDY-CuMOF), that carries the chemotherapy drug doxorubicin (DOX) for cancer treatment. Moreover, to provide GDY-CuMOF@DOX with homotypic targeting capability, we coated the PCa cell membrane (DU145 cell membrane, DCM) onto the surface of GDY-CuMOF@DOX, thus obtaining a biomimetic nanoplatform (DCM@GDY-CuMOF@DOX). The nanoplatform was characterized by using transmission electron microscope, atomic force microscope, X-ray diffraction, etc. Drug release behavior, antitumor effects in vivo and in vitro, and biosafety of the nanoplatform were evaluated. Results: We found that GDY-CuMOF exhibited a remarkable capability to load DOX mainly through π-conjugation and pore adsorption, and it responsively released DOX and generated Cu+ in the presence of glutathione (GSH). In vivo experiments demonstrated that this nanoplatform exhibits remarkable cell-killing efficiency by generating lethal reactive oxygen species (ROS) and mediating cuproptosis. In addition, DCM@GDY-CuMOF@DOX effectively suppresses tumor growth in vivo without causing any apparent side effects. Conclusion: The constructed DCM@GDY-CuMOF@DOX nanoplatform integrates tumor targeting, drug-responsive release and combination with cuproptosis and chemodynamic therapy, offering insights for further biomedical research on efficient PCa treatment.

The chest X-ray score baseline in predicting continuous oxygen therapy failure in low-risk aged patients after thoracic surgery.

Background: Radiographic severity assessment can be instrumental in diagnosing postoperative pulmonary complications (PPCs) and guiding oxygen therapy. The radiographic assessment of lung edema (RALE) and Brixia scores correlate with disease severity, but research on low-risk elderly patients is lacking. This study aimed to assess the efficacy of two chest X-ray scores in predicting continuous oxygen therapy (COT) treatment failure in patients over 70 years of age after thoracic surgery. Methods: From January 2019 to December 2021, we searched for patients aged 70 years and above who underwent thoracic surgery and received COT treatment, with a focus on those at low risk of respiratory complications. Bedside chest X-rays, RALE, Brixia scores, and patient data were collected. Univariate, multivariate analyses, and 1:2 matching identified risk factors. Receiver operating characteristic (ROC) curves determined score sensitivity, specificity, and predictive values. Results: Among the 242 patients surviving to discharge, 19 (7.9%) patients experienced COT failure. COT failure correlated with esophageal cancer surgeries, thoracotomies (36.8% vs. 9%, P=0.003; 26.3% vs. 9.4%, P=0.004), and longer operation time (3.4 vs. 2.8 h, P=0.003). Surgical approach and RALE score were independent risk factors. The prediction model had an area under the curve (AUC) of 0.839 [95% confidence interval (CI), 0.740-0.938]. Brixia and RALE scores predicted COT failure with AUCs of 0.764 (95% CI, 0.650-0.878) with a cut-off value of 6.027 and 0.710 (95% CI, 0.588-0.832) with a cut-off value of 17.134, respectively, after 1:2 matching. Conclusions: The RALE score predict the risk of COT failure in elderly, low-risk thoracic patients better than the Brixia score. This simple, cheap, and noninvasive method helps evaluate postoperative lung damage, monitor treatment response, and provide early warning for oxygen therapy escalation. Further studies are required to confirm the validity and applicability of this model in different settings and populations.

Machine learning-assisted image label-free smartphone platform for rapid segmentation and robust multi-urinalysis.

This study presents a groundbreaking approach for the early detection of chronic kidney disease (CKD) and other urological disorders through an image-label-free, multi-dipstick identification method, eliminating the need for complex machinery, label libraries, or preset coordinates. Our research successfully identified reaction pads on 187 multi-dipsticks, each with 11 pads, leveraging machine learning algorithms trained on human urine data. This technique aims to surpass traditional colourimetric methods and concentration-colour curve fitting, offering more robust and precise community screening and home monitoring capabilities. The developed algorithms enhance the generalizability of machine learning models by extracting primary colours and correcting urine colours on each reaction pad. This method's cost-effectiveness and portability are significant, as it requires no additional equipment beyond a standard smartphone. The system's performance rivals professional medical equipment without auxiliary lighting or flash under regular indoor light conditions, effectively managing false positives and negatives across various categories with remarkable accuracy. In a controlled experimental setting, we found that random forest algorithms, based on a Bagging strategy and applied in the HSV colour space, showed optimal results in smartphone-assisted urinalysis. This study also introduces a novel urine colour correction method, significantly improving machine learning model performance. Additionally, ISO parameters were identified as crucial factors influencing the accuracy of smartphone-based urinalysis in the absence of additional lighting or optical configurations, highlighting the potential of this technology in low-resource settings.

Superhydrophobic Tipped Antimicrobial Photodynamic Therapy Device for the In Vivo Treatment of Periodontitis Using a Wistar Rat Model.

Limited options exist for treatment of periodontitis; scaling and root planing (SRP) are not sufficient to eradicate P. gingivalis and the resulting inflammatory disease. Chlorhexidine (CHX), used as an adjuvant to SRP, may reduce bacterial loads but leads to pain and staining, while evidence for its efficacy is lacking. Antibiotics are effective but can lead to drug-resistance. The rising concern of antibiotic resistance limits the future use of this treatment approach. This study evaluates the efficacy of a novel superhydrophobic (SH) antimicrobial photodynamic therapy (aPDT) device as an adjuvant to SRP for the treatment of periodontitis induced in a Wistar rat in vivo model relative to CHX. The SH-aPDT device comprises an SH silicone rubber strip coated with verteporfin photosensitizer (PS), sterilized, and secured onto a tapered plastic optical fiber tip connected to a red diode laser. The superhydrophobic polydimethylsiloxane (PDMS) strips were fabricated by using a novel soluble template method that creates a medical-grade elastomer with hierarchical surface roughness without the use of nanoparticles. Superhydrophobicity minimizes direct contact of the PS-coated surface with bacterial biofilms. Upon insertion of the device tip into the pocket and energizing the laser, the device generates singlet oxygen that effectively targets and eliminates bacteria within the periodontal pocket. SH-aPDT treatment using 125 J/cm2 of red light on three consecutive days reduced P. gingivalis significantly more than SRP-CHX controls (p < 0.05). Clinical parameters significantly improved (p < 0.05), and histology and stereometry results demonstrated SH-aPDT to be the most effective treatment for improving healing and reducing inflammation, with an increase in fibroblast cells and extracellular matrix and a reduction in vascularization, inflammatory cells, and COX-2 expression. The SH-aPDT approach resulted in complete disease clearance assessed 30 days after treatment initiation with significant reduction of the periodontal pocket and re-formation of the junctional epithelium at the enamel-cementum junction. PS isolation on a SH strip minimizes the potential for bacteria to develop resistance, where the treatment may be aided by the oxygen supply retained within the SH surface.

Swine wastewater treatment using combined up-flow anaerobic sludge blanket and anaerobic membrane bioreactor: Performance and microbial community diversity.

To address the existing economic and environmental issues associated with swine wastewater (SW) treatment, a process combining up-flow anaerobic sludge blanket (UASB) and anaerobic membrane bioreactor (AnMBR) was developed and continuously operated for 137 d. Bioreactor conversion and microbial community dynamics in reactors were analyzed. The UASB-AnMBR process yielded excellent pollutants removal efficiencies of 96% and 63% for chemical oxygen demand (COD) and total phosphorous (TP), respectively. More than 60% of Firmicutes (Terrisporobacter, Turicibacter, and Clostridium sensu stricto 1), which were dominated by Methanosaeta and Methanobacterium with relative abundances of 58.6% and 36.8% in the UASB and 22.5% and 40.3% in the AnMBR, respectively, converted complex compounds into organic acids for methanogenesis. This research presented an analysis of pollutants removal and microbial dynamics of UASB-AnMBR, which significantly affected the large-scale application of UASB-AnMBR process.

Ferrocene-Based Polymeric Nanoparticles Carrying Doxorubicin for Oncotherapeutic Combination of Chemotherapy and Ferroptosis.

Mono-chemotherapy has significant side effects and unsatisfactory efficacy, limiting its clinical application. Therefore, a combination of multiple treatments is becoming more common in oncotherapy. Chemotherapy combined with the induction of ferroptosis is a potential new oncotherapy. Furthermore, polymeric nanoparticles (NPs) can improve the antitumor efficacy and decrease the toxicity of drugs. Herein, a polymeric NP, mPEG-b-PPLGFc@Dox, is synthesized to decrease the toxicity of doxorubicin (Dox) and enhance the efficacy of chemotherapy by combining it with the induction of ferroptosis. First, mPEG-b-PPLGFc@Dox is oxidized by endogenous H2 O2 and releases Dox, which leads to an increase of H2 O2 by breaking the redox balance. The Fe(II) group of ferrocene converts H2 O2 into ·OH, inducing subsequent ferroptosis. Furthermore, glutathione peroxidase 4, a biomarker of ferroptosis, is suppressed and the lipid peroxidation level is elevated in cells incubated with mPEG-b-PPLGFc@Dox compared to those treated with Dox alone, indicating ferroptosis induction by mPEG-b-PPLGFc@Dox. In vivo, the antitumor efficacy of mPEG-b-PPLGFc@Dox is higher than that of free Dox. Moreover, the loss of body weight in mice treated mPEG-b-PPLGFc@Dox is lower than in those treated with free Dox, indicating that mPEG-b-PPLGFc@Dox is less toxic than free Dox. In conclusion, mPEG-b-PPLGFc@Dox not only has higher antitumor efficacy but it reduces the damage to normal tissue.

Evaluation of photosensitizer-containing superhydrophobic surfaces for the antibacterial treatment of periodontal biofilms.

Antimicrobial photodynamic therapy (aPDT) is a promising approach to control biofilms involved in periodontal diseases. However, certain challenges, such as staining of teeth, preferential interaction of photosensitizer (PS) with Gram-positive versus Gram-negative bacteria, and insufficient oxygen in hypoxic periodontal pockets have presented barriers to its use in the clinic. To overcome these challenges, a novel superhydrophobic (SH) film that generates airborne singlet oxygen has been developed. The SH-aPDT approach isolates the PS onto a topologically rough solid SH film on which channels allow air to diffuse to the PS surface, thus ensuring sufficient oxygen supply. Upon illumination, gas phase singlet oxygen (1O2) is produced and diffuses from the SH surface to the underlying biofilm. The killing efficacy was assessed as a function of transmitted fluence (17.9-89.5 J/cm2) and chorin e6 loading (96-1110 nmol/cm2) by counting of colony forming units, biofilm metabolism by XTT and confocal microscopy. The decrease in viability of both Gram-positive and Gram-negative bacteria in a multi-species biofilm was found to be linearly dependent on the fluence as well as the loading of the PS up to 71.6 J/cm2 when 1110 nmols/cm2 of chlorin e6 was used. A > 4.6 log bacterial reduction was observed under these conditions (p < 0.05). This novel SH-aPDT approach shows promise as an effective method to disinfect multi-species bacterial biofilms associated with periodontal disease and will be evaluated in animal models in future studies.

A postoperative comparison of high-flow nasal cannula therapy and conventional oxygen therapy for esophageal cancer patients.

BACKGROUND: Hypoxaemia in post-surgical patients of esophageal cancer (EC) is common in thoracic departments. However, few studies have investigated the role of high-flow nasal cannula (HFNC) compared with conventional oxygen therapy (COT). METHODS: A retrospective study was implemented to enroll hypoxemic patients after esophagectomy who were treated by HFNC or COT immediately after extubation between January 2019 and December 2019. We compared the effect of HFNC or COT in patients regarding the vital signs and arterial blood gases, the incidence of anastomotic leakage, postoperative pulmonary complications (PPCs), sore throat/nose, and reintubation, length of stay, and sputum production. We also 3D reconstructed the postoperative chest CT, and compared the amount of lung volume loss caused by PPCs (pneumothorax, atelectasis, pulmonary consolidation and pleural effusion) between the two groups. RESULTS: Compared to patients in COT group, sore throat/nose in HFNC group was lower, the sputum production was higher, and the total hospital stay was shorter. Compared to COT, HFNC treatment decreased systolic blood pressure (SBP) at day 1, diastolic blood pressure (DBP) at day 1-4, and heart rate (HR) at day 2-4, increased arterial partial pressure of oxygen (PaO2) at day 1-4, and arterial oxygen saturation (SaO2%) at day 1-2. In addition, the rate of PPCs and anastomotic leakage in HFNC group were lower than those in COT group. Compared to COT, HFNC treatment significantly decreased the amount of lung volume loss caused by PPCs. CONCLUSIONS: HFNC can improve the hypoxemia of patients after esophagectomy, increase the flow of sputum, reduce the incidence of PPC and anastomotic leakage.

Superhydrophobic Surfaces as a Source of Airborne Singlet Oxygen through Free Space for Photodynamic Therapy.

A superhydrophobic (SH) sandwich system has been developed to enable "contact-free" airborne singlet oxygen (1O2) delivery to a water droplet. The contact-free feature means that the sensitizer is physically separated from the droplet, which presents opportunities for photodynamic therapy (PDT). Trapping of airborne 1O2 in a H2O droplet residing on a lower SH surface was monitored with 9,10-anthracene dipropionate dianion by varying distances to an upper 1O2-generating surface. Short distances of 20 µm efficiently delivered airborne 1O2 to the droplet in single-digit picomolar steady-state concentrations. Delivery decreases linearly with distance, but 50% of the 1O2 steady-state concentration is trapped at a distance of 300 µm from the generating surface. The 1270 nm luminescence intensity was measured within the SH sandwich system, confirming the presence of airborne 1O2. Physical quenching of 1O2 to ground-state 3O2 by the water droplet itself and both physical and chemical quenching of 1O2 by the water droplet containing the trap 9,10-anthracene dipropionate dianion are observed. Unlike a majority of work in the field of PDT with dissolved sensitizers, where 1O2 diffuses short (hundreds of nanometers) distances, we show the delivery of airborne 1O2 via a superhydrophobic surface is effective through air in tenths of millimeters distances to oxidize an organic compound in water. Our results provide not only potential relevance to PDT but also surface bacterial inactivation processes.

Superhydrophobic Photosensitizers: Airborne 1O2 Killing of an in Vitro Oral Biofilm at the Plastron Interface.

Singlet oxygen is a potent agent for the selective killing of a wide range of harmful cells; however, current delivery methods pose significant obstacles to its widespread use as a treatment agent. Limitations include the need for photosensitizer proximity to tissue because of the short (3.5 µs) lifetime of singlet oxygen in contact with water; the strong optical absorption of the photosensitizer, which limits the penetration depth; and hypoxic environments that restrict the concentration of available oxygen. In this article, we describe a novel superhydrophobic singlet oxygen delivery device for the selective inactivation of bacterial biofilms. The device addresses the current limitations by: immobilizing photosensitizer molecules onto inert silica particles; embedding the photosensitizer-containing particles into the plastron (i.e. the fluid-free space within a superhydrophobic surface between the solid substrate and fluid layer); distributing the particles along an optically transparent substrate such that they can be uniformly illuminated; enabling the penetration of oxygen via the contiguous vapor space defined by the plastron; and stabilizing the superhydrophobic state while avoiding the direct contact of the sensitizer to biomaterials. In this way, singlet oxygen generated on the sensitizer-containing particles can diffuse across the plastron and kill bacteria even deep within the hypoxic periodontal pockets. For the first time, we demonstrate complete biofilm inactivation (>5 log killing) of Porphyromonas gingivalis, a bacterium implicated in periodontal disease using the superhydrophobic singlet oxygen delivery device. The biofilms were cultured on hydroxyapatite disks and exposed to active and control surfaces to assess the killing efficiency as monitored by colony counting and confocal microscopy. Two sensitizer particle types, a silicon phthalocyanine sol-gel and a chlorin e6 derivative covalently bound to fluorinated silica, were evaluated; the biofilm killing efficiency was found to correlate with the amount of singlet oxygen detected in separate trapping studies. Finally, we discuss the applications of such devices in the treatment of periodontitis.

High-Precision Dispensing of Nanoliter Biofluids on Glass Pedestal Arrays for Ultrasensitive Biomolecule Detection.

Precise dispensing of nanoliter droplets is necessary for the development of sensitive and accurate assays, especially when the availability of the source solution is limited. Conventional approaches are limited by imprecise positioning, large shear forces, surface tension effects, and high costs. To address the need for precise and economical dispensing of nanoliter volumes, we developed a new approach where the dispensed volume is dependent on the size and shape of defined surface features, thus freeing the dispensing process from pumps and fine-gauge needles requiring accurate positioning. The surface we fabricated, called a nanoliter droplet virtual well microplate (nVWP), achieves high-precision dispensing (better than ±0.5 nL or ±1.6% at 32 nL) of 20-40 nL droplets using a small source drop (3-10 µL) on isolated hydrophilic glass pedestals (500 µm on a side) bonded to arrays of polydimethylsiloxane conical posts. The sharp 90° edge of the glass pedestal pins the solid-liquid-vapor triple contact line (TCL), averting the wetting of the glass sidewalls while the fluid is prevented from receding from the edge. This edge creates a sufficiently large energy barrier such that microliter water droplets can be poised on the glass pedestals, exhibiting contact angles greater >150°. This approach relieves the stringent mechanical alignment tolerances required for conventional dispensing techniques, shifting the control of dispensed volume to the area circumscribed by the glass edge. The effects of glass surface chemistry and dispense velocity on droplet volume were studied using optical microscopy and high-speed video. Functionalization of the glass pedestal surface enabled the selective adsorption of specific peptides and proteins from synthetic and natural biomolecule mixtures, such as venom. We further demonstrate how the nVWP dispensing platform can be used for a variety of assays, including sensitive detection of proteins and peptides by fluorescence microscopy or MALDI-TOF.

Design and Fabrication of a Hybrid Superhydrophobic-Hydrophilic Surface That Exhibits Stable Dropwise Condensation.

Condensation of water vapor is an essential process in power generation, water collection, and thermal management. Dropwise condensation, where condensed droplets are removed from the surface before coalescing into a film, has been shown to increase the heat transfer efficiency and water collection ability of many surfaces. Numerous efforts have been made to create surfaces which can promote dropwise condensation, including superhydrophobic surfaces on which water droplets are highly mobile. However, the challenge with using such surfaces in condensing environments is that hydrophobic coatings can degrade and/or water droplets on superhydrophobic surfaces transition from the mobile Cassie to the wetted Wenzel state over time and condensation shifts to a less-effective filmwise mechanism. To meet the need for a heat-transfer surface that can maintain stable dropwise condensation, we designed and fabricated a hybrid superhydrophobic-hydrophilic surface. An array of hydrophilic needles, thermally connected to a heat sink, was forced through a robust superhydrophobic polymer film. Condensation occurs preferentially on the needle surface due to differences in wettability and temperature. As the droplet grows, the liquid drop on the needle remains in the Cassie state and does not wet the underlying superhydrophobic surface. The water collection rate on this surface was studied using different surface tilt angles, needle array pitch values, and needle heights. Water condensation rates on the hybrid surface were shown to be 4 times greater than for a planar copper surface and twice as large for silanized silicon or superhydrophobic surfaces without hydrophilic features. A convection-conduction heat transfer model was developed; predicted water condensation rates were in good agreement with experimental observations. This type of hybrid superhydrophobic-hydrophilic surface with a larger array of needles is low-cost, robust, and scalable and so could be used for heat transfer and water collection applications.

Catalytic, self-cleaning surface with stable superhydrophobic properties: printed polydimethylsiloxane (PDMS) arrays embedded with TiO2 nanoparticles.

Maintaining the long-term stability of superhydrophobic surfaces is challenging because of contamination from organic molecules and proteins that render the surface hydrophilic. Reactive oxygen species generated on a photocatalyst, such as TiO2, could mitigate this effect by oxidizing these contaminants. However, incorporation of such catalyst particles into a superhydrophobic surface is challenging because the particles become hydrophilic under UV exposure, causing the surface to transition to the Wenzel state. Here we show that a high concentration of hydrophilic TiO2 catalytic nanoparticles can be incorporated into a superhydrophobic surface by partially embedding the particles into a printed array of high aspect ratio polydimethylsiloxane posts. A stable Cassie state was maintained on these surfaces, even under UV irradiation, because of the significant degree of hierarchical roughness. By printing the surface on a porous support, oxygen could be flowed through the plastron, resulting in higher photooxidation rates relative to a static ambient. Rhodamine B and bovine serum albumin were photooxidized both in solution and after drying onto these TiO2-containing surfaces, and the effects of particle location and plastron gas composition were studied in static and flowing gas environments. This approach may prove useful for water purification, medical devices, and other applications where Cassie stability is required in the presence of organic compounds.

Singlet oxygen generation on porous superhydrophobic surfaces: effect of gas flow and sensitizer wetting on trapping efficiency.

We describe physical-organic studies of singlet oxygen generation and transport into an aqueous solution supported on superhydrophobic surfaces on which silicon-phthalocyanine (Pc) particles are immobilized. Singlet oxygen ((1)O2) was trapped by a water-soluble anthracene compound and monitored in situ using a UV-vis spectrometer. When oxygen flows through the porous superhydrophobic surface, singlet oxygen generated in the plastron (i.e., the gas layer beneath the liquid) is transported into the solution within gas bubbles, thereby increasing the liquid-gas surface area over which singlet oxygen can be trapped. Higher photooxidation rates were achieved in flowing oxygen, as compared to when the gas in the plastron was static. Superhydrophobic surfaces were also synthesized so that the Pc particles were located in contact with, or isolated from, the aqueous solution to evaluate the relative effectiveness of singlet oxygen generated in solution and the gas phase, respectively; singlet oxygen generated on particles wetted by the solution was trapped more efficiently than singlet oxygen generated in the plastron, even in the presence of flowing oxygen gas. A mechanism is proposed that explains how Pc particle wetting, plastron gas composition and flow rate as well as gas saturation of the aqueous solution affect singlet oxygen trapping efficiency. These stable superhydrophobic surfaces, which can physically isolate the photosensitizer particles from the solution may be of practical importance for delivering singlet oxygen for water purification and medical devices.

Superhydrophobic photosensitizers. Mechanistic studies of (1)O2 generation in the plastron and solid/liquid droplet interface.

We describe here a physical-organic study of the first triphasic superhydrophobic sensitizer for photooxidations in water droplets. Control of synthetic parameters enables the mechanistic study of "borderline" two- and three-phase superhydrophobic sensitizer surfaces where (1)O2 is generated in compartments that are wetted, partially wetted, or remain dry in the plastron (i.e., air layer beneath the droplet). The superhydrophobic surface is synthesized by partially embedding silicon phthalocyanine (Pc) sensitizing particles to specific locations on polydimethylsiloxane (PDMS) posts printed in a square array (1 mm tall posts on 0.5 mm pitch). In the presence of red light and oxygen, singlet oxygen is formed on the superhydrophobic surface and reacts with 9,10-anthracene dipropionate dianion (1) within a freestanding water droplet to produce an endoperoxide in 54-72% yields. Control of the (1)O2 chemistry was achieved by the synthesis of superhydrophobic surfaces enriched with Pc particles either at the PDMS end-tips or at PDMS post bases. Much of the (1)O2 that reacts with anthracene 1 in the droplets was generated by the sensitizer "wetted" at the Pc particle/water droplet interface and gave the highest endoperoxide yields. About 20% of the (1)O2 can be introduced into the droplet from the plastron. The results indicate that the superhydrophobic sensitizer surface offers a unique system to study (1)O2 transfer routes where a balance of gas and liquid contributions of (1)O2 is tunable within the same superhydrophobic surface.