Pharmacokinetics of nirmatrelvir/ritonavir and the drug-drug interaction with calcineurin inhibitor in renal transplant recipients.

OBJECTIVES: To describe the pharmacokinetic (PK) characteristics of nirmatrelvir/ritonavir in renal transplant recipients and explore the potential factors that related to the PK variance of nirmatrelvir/ritonavir and its interaction with calcineurin inhibitor (CNI). METHODS: Renal transplant recipients treated with CNI and nirmatrelvir/ritonavir were prospectively enrolled. Steady-state plasma concentrations of nirmatrelvir/ritonavir were determined by high-performance liquid chromatography-tandem mass spectrometry, and the PK parameters were calculated using non-compartmental analysis. Spearman correlation analysis was used for exploring influencing factors. RESULTS: A total of eight recipients were enrolled; for nirmatrelvir and ritonavir, AUC/dose was 0.24179 ± 0.14495 and 0.06196 ± 0.03767 µg·h·mL-1·mg-1. Red blood cell (RBC), hematocrit (Ht), hemoglobins (Hb), and creatinine clearance (Ccr) were negatively correlated with AUC/dose of nirmatrelvir, while Ccr, CYP3A5 genotype, and CYP3A4 genotype were related to the AUC/dose of ritonavir. Ccr was negatively correlated with the C0/dose of tacrolimus (TAC) after termination of nirmatrelvir/ritonavir (rs = -0.943, p = 0.008). CONCLUSIONS: The PK characteristics of nirmatrelvir/ritonavir vary greatly among renal transplant recipients. Factors including Ccr and CYP3A5 genotype were related to the in vivo exposure of nirmatrelvir/ritonavir. During the whole process before and after nirmatrelvir/ritonavir therapy, it is recommended to adjust the CNI basing on renal function to avoid CNI toxicity exposure.

Cardiac computed tomography angiography-derived pulmonary vein volumetry as a predictor for atrial fibrillation recurrence after catheter ablation.

Background: There is an increasing evidence that pulmonary vein (PV) enlargement is associated with atrial fibrillation (AF); however, the predictive value of PV enlargement in AF recurrence remains unclear. This study sought to evaluate whether PV volume quantification derived from cardiac computed tomographic angiography (CCTA) could serve as a predictive indicator of the success of the catheter ablation (CA) procedure. Methods: The data of 160 patients diagnosed with AF who underwent both CCTA and CA treatments from January to June 2020 were retrospectively examined; the CCTA was conducted before the CA surgery. The study focused on documenting the PV structure, and the volume of the PV and left atrium (LA). The clinical, CCTA, and echocardiographic predictors of the recurrence and no-recurrence groups were compared. A multivariable logistic regression analysis was performed to adjust for confounders. Receiver operating characteristic (ROC) curves were analyzed to assess the predictive performance of the predictors of AF recurrence. Results: Of the 160 patients [55.6% male, 62.00 (55.25-68.00) years, 23.1% with persistent AF], 45 (28.1%) experienced AF recurrence within a one-year period. Notably, patients with AF recurrence had elevated CHADS2 scores (P=0.020) and increased LA and PV volumes (P<0.05). Patients with persistent AF (n=37) had significantly larger LA volume indexes (P<0.001) than those with paroxysmal AF, but there was no difference between the two groups in terms of the PV maximum volume index (P=0.200). Moreover, the PV maximum volume index [odds ratio (OR): 1.244, 95% confidence interval (CI): 1.008-1.536, P=0.042] and the LA minimum volume index (OR: 1.026, 95% CI: 1.001-1.052, P=0.038) were found to be significant predictors of AF recurrence. The ROC curves revealed that the PV maximum volume index threshold for predicting AF recurrence was 7.13 mL/m2, with a sensitivity of 84.4% and a specificity of 34.8% [area under the curve (AUC): 0.635, 95% CI: 0.540-0.730, P=0.008], and the LA minimum volume index threshold for predicting AF recurrence was 46.16 mL/m2, with a sensitivity of 88.9% and a specificity of 31.3% (AUC: 0.629, 95% CI: 0.534-0.723, P=0.012). A sub-analysis of patients with a lower left atrial dimension (LAD ≤38 mm in females, LAD ≤40 mm in males, n=120) demonstrated that the PV maximum volume index was a noteworthy indicator of AF recurrence (OR: 1.443: 95% CI: 1.145-1.820, P=0.002). Conversely, no significant correlation between AF recurrence and the LA volume index was found. The AUC value for the PV maximum volume index predictive of recurrent AF was 0.680 (95% CI: 0.577-0.781, P=0.003), with a sensitivity of 75.8%, specificity of 54%, and the cut-off value of the maximum AUC was 7.89 mL/m2. Conclusions: PV volume, derived from CCTA, may help to predict the recurrence of AF after CA, and is superior to the LA size in patients with less pronounced LA enlargement.

The role of early cerebral edema and hematoma assessment in aneurysmal subarachnoid hemorrhage (a-SAH) in predicting structural brain abnormalities in cognitive impairments-- case controlled study.

BACKGROUND: Early assessment and management of cerebral edema and hematoma following aneurysmal subarachnoid hemorrhage (a-SAH) can significantly impact clinical cognitive outcomes. However, current clinical practices lack predictive models to identify early structural brain abnormalities affecting cognition. To address this gap, we propose the development of a predictive model termed the a-SAH Early Brain Edema/Hematoma Compression Neural (Structural Brain) Networks Score System (SEBE-HCNNSS). METHODS: In this study, 202 consecutive patients with spontaneous a-SAH underwent initial computed tomography (CT) or magnetic resonance imaging (MRI) scans within 24 hours of ictus with follow-up 2 months after discharge. Using logistic regression analysis (univariate and multivariate), we evaluated the association of clinically relevant factors and various traditional scale ratings with cognitive impairment (CI). Risk factors with the highest area under the curve (AUC) values were included in the multivariate analysis and least absolute shrinkage and selection operator (LASSO) analysis or Cox regression analysis. RESULTS: A total of 177 patients were enrolled in the study, and 43 patients were classified with a high SEBE-HCNNSS grade (3 to 5). After a mean follow-up of 2 months, 121 individuals (68.36%) with a-SAH and 3 control subjects developed incident CI. The CT inter-observer reliability of the SEBE-HCNNSS scale was high, with a Kappa value of 1. Furthermore, ROC analysis identified the SEBE-HCNNSS scale (OR 3.322, 95% CI 2.312-7.237, P=0.00025) as an independent predictor of edema, CI, and unfavorable prognosis. These results were also replicated in a validation cohort. CONCLUSION: Overall, the SEBE-HCNNSS scale represents a simple assessment tool with promising predictive value for CI and clinical outcomes post-a-SAH. Our findings indicate its practical utility as a prognostic instrument for risk evaluation after a-SAH, potentially facilitating early intervention and treatment.

Tonal language experience facilitates the use of spatial cues for segregating competing speech in bimodal cochlear implant listeners.

English-speaking bimodal and bilateral cochlear implant (CI) users can segregate competing speech using talker sex cues but not spatial cues. While tonal language experience allows for greater utilization of talker sex cues for listeners with normal hearing, tonal language benefits remain unclear for CI users. The present study assessed the ability of Mandarin-speaking bilateral and bimodal CI users to recognize target sentences amidst speech maskers that varied in terms of spatial cues and/or talker sex cues, relative to the target. Different from English-speaking CI users, Mandarin-speaking CI users exhibited greater utilization of spatial cues, particularly in bimodal listening.

Hydroxylation of Aryl Sulfonium Salts for Phenol Synthesis under Mild Reaction Conditions.

Hydroxylation of aryl sulfonium salts could be realized by utilizing acetohydroxamic acid and oxime as hydroxylative agents in the presence of cesium carbonate as a base, leading to a variety of structurally diverse hydroxylated arenes in 47-95% yields. In addition, the reaction exhibited broad functionality tolerance, and a range of important functional groups (e.g., cyano, nitro, sulfonyl, formyl, keto, and ester) could be well amenable to the mild reaction conditions.

Construction of strain responsive Ti-containing carboxymethyl cellulose hydrogel with transitional coordination precursor.

Due to marvelous sensitivity and flexibility, conductive hydrogels are popularly used as strain sensors in intelligent skin and wearable electronic devices fields. However, hydrogel tends to be destroyed after long-term use or in accident, leading to performance degradation. Herein, we developed an environmental-friendly Ti-containing conductive hydrogel. The hydrogel network was constructed via a simple two-step method with coordination reaction and amidation reaction based on a metal ion precursor from transitional coordination. The synergies of reversible metal coordination bonds and dynamic hydrogen bonds endowed the hydrogel with excellent self-healing properties (3 h, 93.66 %), tensile properties (136.46 kPa), compression properties (1.122 MPa), and anti-fatigue performance. At the same time, the hydrogel showed excellent self-adhesion, even underwater. Due to Ti4+, electrical conductivity of the hydrogel was visibly enhanced (σ = 25.64 mS·cm-1), which resulted in fast response (TS [time sensitivity] = 24.78 s-1) and short recovery time (153 ms). As a flexible strain sensor, the hydrogel with stable conductivity and high sensitivity could precisely detect and distinguish a series of human motions, even different letter pronunciations. These remarkable features make it a promising application in the fields of intelligent skin and wearable electronic devices.

Controllable Pyridine N-Oxidation-Nucleophilic Dechlorination Process for Enhanced Dechlorination of Chloropyridines: The Cooperation of HCO4- and HO2.

Dechlorination of chloropyridines can eliminate their detrimental environmental effects. However, traditional dechlorination technology cannot efficiently break the C-Cl bond of chloropyridines, which is restricted by the uncontrollable nonselective species. Hence, we propose the carbonate species-activated hydrogen peroxide (carbonate species/H2O2) process wherein the selective oxidant (peroxymonocarbonate ion, HCO4-) and selective reductant (hydroperoxide anion, HO2-) controllably coexist by manipulation of reaction pH. Taking 2-chloropyridine (Cl-Py) as an example, HCO4- first induces Cl-Py into pyridine N-oxidation intermediates, which then suffer from the nucleophilic dechlorination by HO2-. The obtained dechlorination efficiencies in the carbonate species/H2O2 process (32.5-84.5%) based on the cooperation of HCO4- and HO2- are significantly higher than those in the HO2--mediated sodium hydroxide/hydrogen peroxide process (0-43.8%). Theoretical calculations confirm that pyridine N-oxidation of Cl-Py can effectively lower the energy barrier of the dechlorination process. Moreover, the carbonate species/H2O2 process exhibits superior anti-interference performance and low electric energy consumption. Furthermore, Cl-Py is completely detoxified via the carbonate species/H2O2 process. More importantly, the carbonate species/H2O2 process is applicable for efficient dehalogenation of halogenated pyridines and pyrazines. This work offers a simple and useful strategy to enhance the dehalogenation efficiency of halogenated organics and sheds new insights into the application of the carbonate species/H2O2 process in practical environmental remediation.

Value of original and modified pathological scoring systems for prognostic prediction in paraffin-embedded donor kidney core biopsy.

BACKGROUND: No study has validated, compared and adapted scoring systems for prognosis prediction based on donor kidney core biopsy (CB), with less glomeruli than wedge biopsy. METHODS: A total of 185 donor kidney CB specimens were reviewed using seven scoring systems. The association between the total score, item scores, score-based grading, and allograft prognosis was investigated. In specimens with less than ten glomeruli (88/185, 47.6%), scoring systems were modified by adjusting weights of the item scores. RESULTS: The Maryland aggregate pathology index (MAPI) score-based grading and periglomerular fibrosis (PGF) associated with delayed graft function (DGF) (Grade: OR = 1.59, p < 0.001; PGF: OR = 1.06, p = 0.006). Total score, score-based grading and chronic lesion score in scoring systems associated with one-year and 3-year eGFR after transplantation. Total-score-based models had similar predictive capacities for eGFR in all scoring systems, except MAPI and Ugarte. Score of glomerulosclerosis (GS), interstitial fibrosis (IF), tubular atrophy (TA), and arteriolar hyalinosis (AH) had good eGFR predictive capacities. In specimens with less than ten glomeruli, modified scoring systems had better eGFR predictive capacities than original scoring systems. CONCLUSIONS: Scoring systems could predict allograft prognosis in paraffin-embedded CB with ten more glomeruli. A simple and pragmatic scoring system should include GS, IF, TA and AH, with weights assigned based on predictive capacity for prognosis. Replacing GS scores with tubulointerstitial scores could significantly improve the predictive capacity of eGFR. The conclusion should be further validated in frozen section.

Selective anchoring of Pt NPs on covalent triazine-based frameworks via in situ derived bridging ligands for boosting photocatalytic hydrogen evolution.

The efficient and stable production of hydrogen (H2) through Pt-containing photocatalysts remains a great challenge. Herein, we develop an effective strategy to selectively and uniformly anchor Pt NPs (∼1.2 nm) on a covalent triazine-based framework photocatalyst via in situ derived bridging ligands. Compared to Pt/CTF-1, the obtained Pt/AT-CTF-1 exhibits a considerable photocatalytic H2 evolution rate of 562.9 µmol g-1 h-1 under visible light irradiation. Additionally, the strong interaction between the Pt NPs and in situ derived bridging ligands provides remarkable stability to Pt/AT-CTF-1. Experimental investigations and photo/chemical characterization reveal the synergy of the in situ derived bridging ligands in Pt/AT-CTF-1, which can selectively anchor the Pt NPs with homogeneous sizes and efficiently improve the transmission of charge carriers. This work provides a new perspective toward stabilizing ultrasmall nanoclusters and facilitating electron transfer in photocatalytic H2 evolution materials.

An eco-friendly versatile superabsorbent hydrogel based on sodium alginate and urea for soil improvement with a synchronous chemical loading strategy.

In this paper, an eco-friendly versatile superabsorbent material was designed for soil improvement, and a synchronous chemical loading strategy was proposed. In this strategy, urea not only acted as fertilizer but also acted as a crosslinker to construct an alginate network. The microstructure, chemical structure, thermal stability and composition of the obtained SA/urea hydrogel were characterized in detail. Adsorption behavior and application performance in agriculture were evaluated. The results demonstrated that urea had two different conformations in the network. The SA/urea hydrogel had abundant pore structures with excellent water absorption performance. It could not only improve the water retention capacity of soil but also release nitrogen, phosphorus and potassium elements with degradation for as long as 9 weeks. Moreover, the hydrogel could promote plant growth, increase the nutritional composition of plants and inhibit the accumulation of harmful nitrate in plants. With advantages, including biodegradability, high water absorption, controllable degradation, excellent water retention, sustained NPK release and improved plant nutrition value, the SA/urea hydrogel has great potential for soil improvement in agriculture as an eco-friendly versatile water retention agent and can be expected to extend to more fields as a novel superabsorbent material.

Fulvic acid modified ZnO nanoparticles improve nanoparticle stability, mung bean growth, grain zinc content, and soil biodiversity.

Zinc oxide nanoparticles (ZnO NPs) have emerged as a novel solution to combat Zn deficiency in agriculture. However, challenges persist regarding their Zn utilization efficiency and environmental impact. Fulvic acid (FA), as a relatively mature modified material, is a promising candidate to enhance the environmental stability of ZnO NPs. This study investigates modifying ZnO NPs with FA to improve their stability and increase Zn content in mung bean fruit and explores their effect on plants and the soil ecosystem. We combined FA and ZnO NPs (FZ-50) at mass ratios of 1: 5, 1: 2, and 4: 5, denoted as 20 % FZ, 50 % FZ, and 80 % FZ, respectively. Initial germination tests revealed that the 50 % FZ treatment improved sprout growth and Zn content and minimized agglomeration the most. A subsequent pot experiment compared FZ-50 with ZnO, ZnO NPs, and F + Z (1: 1 FA: ZnO NPs). Notably, the FZ-50 treatment (50 % FZ applied to the soil) demonstrated superior results, exhibiting a 30.25 % increase in yield, 121 % improvement in root nodule quality, and 56.38 % increase in Zn content, with no significant changes in enzyme activities (catalase and peroxidase). Furthermore, FZ-50 increased soil available Zn content and promoted soil microorganism diversity, outperforming ZnO and ZnO NPs. This study underscores the potential of FA as a relatively mature material for modifying ZnO NPs to increase grain Zn content, presenting a novel approach to addressing Zn deficiency in agriculture.

In Situ Biosynthesis of FeS Nanoparticles Boosts Current Generation in Bioelectrochemical Systems Through Efficient Electron Transfer.

The utility of electrochemical active biofilm in bioelectrochemical systems has received considerable attention for harvesting energy and chemical products. However, the slow electron transfer between biofilms and electrodes hinders the enhancement of performance and still remains challenging. Here, using Fe3 O4 /L-Cys nanoparticles as precursors to induce biomineralization, a facile strategy for the construction of an effective electron transfer pathway through biofilm and biological/inorganic interface is proposed, and the underlying mechanisms are elucidated. Taking advantage of an on-chip interdigitated microelectrode array (IDA), the conductive current of biofilm that is related to the electron transfer process within biofilm is characterized, and a 2.10-fold increase in current output is detected. The modification of Fe3 O4 /L-Cys on the electrode surface facilitates the electron transfer between the biofilm and the electrode, as the bio/inorganic interface electron transfer resistance is only 16% compared to the control. The in-situ biosynthetic Fe-containing nanoparticles (e.g., FeS) enhance the transmembrane EET and the EET within biofilm, and the peak conductivity increases 3.4-fold compared to the control. The in-situ biosynthesis method upregulates the genes involved in energy metabolism and electron transfer from the transcriptome analysis. This study enriches the insights of biosynthetic nanoparticles on electron transfer process, holding promise in bioenergy conversion.

Behavioral and molecular response of the insect parasitic nematode Steinernema carpocapsae to plant volatiles.

Entomopathogenic nematodes (EPNs) use the chemical cues emitted by insects and insect-damaged plants to locate their hosts. Steinernema carpocapsae, a species of EPN, is an established biocontrol agent used against insect pests. Despite its promising potential, the molecular mechanisms underlying its ability to detect plant volatiles remain poorly understood. In this study, we investigated the response of S. carpocapsae infective juveniles (IJs) to 8 different plant volatiles. Among these, carvone was found to be the most attractive volatile compound. To understand the molecular basis of the response of IJs to carvone, we used RNA-Seq technology to identify gene expression changes in response to carvone treatment. Transcriptome analysis revealed 721 differentially expressed genes (DEGs) between carvone-treated and control groups, with 403 genes being significantly upregulated and 318 genes downregulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the responsive DEGs to carvone attraction were mainly involved in locomotion, localization, behavior, response to stimulus, and olfactory transduction. We also identified four upregulated genes of chemoreceptor and response to stimulus that were involved in the response of IJs to carvone attraction. Our results provide insights into the potential transcriptional mechanisms underlying the response of S. carpocapsae to carvone, which can be utilized to develop environmentally friendly strategies for attracting EPNs.

Response of current distribution in a liter-scale microbial fuel cell to variable operating conditions.

Microbial fuel cells (MFCs) are an emerging technology in renewable energy and waste treatment and the scale-up is crucial for practical applications. Undoubtedly, the analysis and comprehension of MFC operation necessitate essential information regarding the response of the current distribution to variable operating conditions, which stands as one of its significant dynamic characteristics. In this study, the dynamic responses of current distribution to external stimuli (external load, temperature, pH, and electrolyte concentration) were investigated by employing a segmented anode current collector in a liter-scale MFC. The results demonstrated that, with respect to the anodic segment close to the cathode, a major response of the segment current to changes in load, temperature and pH was observed while minor response to changes in ion concentration. It was also found that external stimuli-induced high current usually led to a worse current distribution while increasing electrolyte ion concentration could simultaneously improve the maximal power generation and current distribution. In addition, the response time of segment current to input stimulus followed the pattern of temperature ˃ pH ˃ ion concentration ˃ external load. The results and implication of this study would be helpful in enhancing the operational stability of scale-up MFCs in future practical application.

PdMo bimetallene nanozymes for photothermally enhanced antibacterial therapy and accelerated wound healing.

Although antibacterial platforms involving nanozymes have been extensively investigated, there are still problems of poor reactive oxygen species generation efficiency and obstinate bacterial biofilms. Developing a nanozyme-photothermal therapy nanoplatform with superior sterilization effects and minimal side effects would be a good alternative for completely eliminating bacteria and biofilms. Herein, an ultrathin PdMo bimetallene nanozyme with a planar topology and boosted metal utilization, exhibiting excellent photothermal and peroxidase-like activity, is designed for synergistic nanozyme-photothermal sterilization applications and accelerated wound healing. The superior catalytic activity of PdMo bimetallene nanozymes could convert a biosafe concentration of hydrogen peroxide (H2O2) into large quantities of toxic hydroxyl radicals (•OH) under laser irradiation, enhancing bacterial membrane permeability and thermal sensitivity for efficient removal of bacteria and biofilms. In addition, PdMo bimetallene presents a good wound-healing ability according to the results of fibroblast proliferation and collagen deposition with minor side effects. This work would provide an innovative avenue for developing metallene-based nanozymes for biomedical applications.

How Integrated Digital Tools Can Improve Tuberculosis Medication Adherence: A Longitudinal Study in China.

Background: Poor medication adherence remains one of the major problems in the treatment of tuberculosis (TB) patients, while digital technologies have been proven effective to improve the treatment results. However, reports on the effectiveness of comprehensive practice integrating different intervention methods and technologies are limited. The aim of this study is to evaluate the effectiveness of an integrated digital adherence intervention for TB patients. Methods: We developed a digital adherence intervention platform integrating instant WeChat message, electronic medication monitors (EMMs), and manual reminders. The primary goal of the platform was to improve the accessibility of digital adherence technologies, and thus improve treatment adherence. TB patients were newly diagnosed at 10 TB-designated hospitals and came from 220 communities, from January to June 2022. The basic characteristics and treatment adherence of TB patients in WeChat, EMM, and conventional groups were compared, and the influencing factors of high medication adherence were analyzed by logistic regression. Results: A total of 2,498 TB patients were enrolled in the study, 14.5% were managed by digital technologies, 9.5% by WeChat, and 5.0% by EMM, respectively. After intervention, the median medication rate of TB patients was significantly higher in the WeChat group (95.3%) and EMM group (95.7%) compared with that of the conventional group (83.8%). On the contrary, the median number of missed medications among patients of the conventional group (nine times) was significantly higher than that in the WeChat (three times) group and EMM (three times) group. The proportion of high adherence (adherence medication rate ≥90%) among TB patients was 64.7%, 64.5%, and 43.2% in WeChat, EMM, and conventional group, respectively. Conclusions: The application of the integrated digital adherence intervention platform could significantly improve medication adherence among TB patients. The accessibility of digital adherence technologies could be improved by integrating complementary technologies in practice.

Lycium barbarum polysaccharide alleviates DSS-induced chronic ulcerative colitis by restoring intestinal barrier function and modulating gut microbiota.

PURPOSE: This study examined the protective effects and mechanism of Lycium barbarum polysaccharides (LBP) in the context of intestinal barrier function and intestinal microbiota in mice with dextran sulfate sodium (DSS)-induced chronic ulcerative colitis (UC). METHODS: C57BL/6J male mice were assigned to a standard normal diet without DSS (control group), a normal diet with DSS (DSS group, 2% DSS given discontinuously for 3 weeks) or a normal diet supplemented with LBP (1% dry feed weight, LBP group, 2% DSS given discontinuously for 3 weeks) for a total of 8 weeks, at which point colonic tissues and caecal contents were collected. RESULTS: LBP exerted a significant effect against colitis by increasing body weight, colon length, DAI and histopathological scores. LBP inhibited proinflammatory cytokines (IL-1ß, IL-6, iNOS and TNF-α) expression, improved anti-inflammatory cytokine (IL-10) expression, promoted the expression of tight junction proteins (Occludin and ZO-1) via nuclear factor erythroid 2-related factor 2 (Nrf2) activation and decreased Claudin-2 expression to maintain the intestinal mucosal barrier. In addition, the abundances of some probiotics (Ruminococcaceae, Lactobacillus, Butyricicoccus, and Akkermansia) were decreased with DSS treatment but increased obviously with LBP treatment. And LBP reduced the abundance of conditional pathogens associated with UC (Mucispirillum and Sutterella). Furthermore, LBP improved the production of short-chain fatty acids (SCFAs), including acetic acid, propionic acid, butyric acid and isobutyric acid. CONCLUSION: LBP can alleviate DSS-induced UC by regulating inflammatory cytokines and tight junction proteins. Moreover, LBP promotes probiotics, suppresses conditional pathogens and increases SCFAs production, showing a strong prebiotic effect.

Microenvironment Regulation Strategies Facilitating High-Efficiency CO2 Electrolysis in a Zero-Gap Bipolar Membrane Electrolyzer.

In alkaline and neutral zero-gap CO2 electrolyzers, the carbon utilization efficiency of the electrocatalytic CO2 reduction to CO is less than 50% because of inherently homogeneous reactions. Utilization of the bipolar membrane (BPM) electrolyzer can effectively suppress (bi)carbonate formation and parasitic CO2 losses; however, an excessive concentration of H+ in the catalyst layer (CL) significantly hinders the activity and selectivity for CO2 reduction. Here, we report a microenvironment regulation strategy that controls the CL thickness and ionomer content to regulate local CO2 transport and the local pH within the CL. We report 80% faradaic efficiency of CO at a current density of 400 mA/cm2 without the use of a buffering layer, exceeding that of state-of-the-art catalysts with a buffering layer. A carbon utilization efficiency of 63.6% at 400 mA/cm2 is also obtained. This study demonstrates the significance of regulating the microenvironment of the CL in a BPM system.

Tumor Microenvironment-Responsive One-for-All Molecular-Engineered Nanoplatform Enables NIR-II Fluorescence Imaging-Guided Combinational Cancer Therapy.

The activable NIR-based phototheranostic nanoplatform (NP) is considered an efficient and reliable tumor treatment due to its strong targeting ability, flexible controllability, minimal side effects, and ideal therapeutic effect. This work describes the rational design of a second near-infrared (NIR-II) fluorescence imaging-guided organic phototheranostic NP (FTEP-TBFc NP). The molecular-engineered phototheranostic NP has a sensitive response to glutathione (GSH), generating hydrogen sulfide (H2S) gas, and delivering ferrocene molecules in the tumor microenvironment (TME). Under 808 nm irradiation, FTEP-TBFc could not only simultaneously generate fluorescence, heat, and singlet oxygen but also greatly enhance the generation of reactive oxygen species to improve chemodynamic therapy (CDT) and photodynamic therapy (PDT) at a biosafe laser power of 0.33 W/cm2. H2S inhibits the activity of catalase and cytochrome c oxidase (COX IV) to cause the enhancement of CDT and hypothermal photothermal therapy (HPTT). Moreover, the decreased intracellular GSH concentration further increases CDT's efficacy and downregulates glutathione peroxidase 4 (GPX4) for the accumulation of lipid hydroperoxides, thus causing the ferroptosis process. Collectively, FTEP-TBFc NPs show great potential as a versatile and efficient NP for specific tumor imaging-guided multimodal cancer therapy. This unique strategy provides new perspectives and methods for designing and applying activable biomedical phototheranostics.