Anisotropic Dual S-Scheme Heterojunctions Mimic Natural Photosynthetic System for Boosting Photoelectric Response.

The design of heterojunctions that mimic natural photosynthetic systems holds great promise for enhancing photoelectric response. However, the limited interfacial space charge layer (SCL) often fails to provide sufficient driving force for the directional migration of inner charge carriers. Drawing inspiration from the electron transport chain (ETC) in natural photosynthesis system, we developed a novel anisotropic dual S-scheme heterojunction artificial photosynthetic system composed of Bi2O3-BiOBr-AgI for the first time, with Bi2O3 and AgI selectively distributed along the bicrystal facets of BiOBr. Compared to traditional semiconductors, the anisotropic carrier migration in BiOBr overcomes the recombination resulting from thermodynamic diffusion, thereby establishing a potential ETC for the directional migration of inner charge carriers. Importantly, this pioneering bioinspired design overcomes the limitations imposed by the limited distribution of SCL in heterojunctions, resulting in a remarkable 55-fold enhancement in photoelectric performance. Leveraging the etching of thiols on Ag-based materials, this dual S-scheme heterojunction is further employed in the construction of photoelectrochemical sensors for the detection of acetylcholinesterase and organophosphorus pesticides.

One-step formation of polymorphous sperm-like microswimmers by vortex turbulence-assisted microfluidics.

Microswimmers are considered promising candidates for active cargo delivery to benefit a wide spectrum of biomedical applications. Yet, big challenges still remain in designing the microswimmers with effective propelling, desirable loading and adaptive releasing abilities all in one. Inspired by the morphology and biofunction of spermatozoa, we report a one-step formation strategy of polymorphous sperm-like magnetic microswimmers (PSMs) by developing a vortex turbulence-assisted microfluidics (VTAM) platform. The fabricated PSM is biodegradable with a core-shell head and flexible tail, and their morphology can be adjusted by vortex flow rotation speed and calcium chloride solution concentration. Benefiting from the sperm-like design, our PSM exhibits both effective motion ability under remote mag/netic actuation and protective encapsulation ability for material loading. Further, it can also realize the stable sustain release after alginate-chitosan-alginate (ACA) layer coating modification. This research proposes and verifies a new strategy for the sperm-like microswimmer construction, offering an alternative solution for the target delivery of diverse drugs and biologics for future biomedical treatment. Moreover, the proposed VTAM could also be a general method for other sophisticated polymorphous structures fabrication that isn't achievable by conventional laminar flow.

Puerarin alleviates atherosclerosis via the inhibition of Prevotella copri and its trimethylamine production.

OBJECTIVE: Puerarin (PU) is a natural compound that exhibits limited oral bioavailability but has shown promise in the treatment of atherosclerosis (AS). However, the precise mechanisms underlying its therapeutic effects remain incompletely understood. This study aimed to investigate the effects of PU and its mechanisms in mitigating AS in both mice and humans. DESIGN: The impact of PU on AS was examined in ApoE -/- mice fed a high-fat diet (HFD) and in human patients with carotid artery plaque. To explore the causal link between PU-associated gut microbiota and AS, faecal microbiota transplantation (FMT) and mono-colonisation of mice with Prevotella copri (P. copri) were employed. RESULTS: PU alleviated AS by modulating the gut microbiota, as evidenced by alterations in gut microbiota composition and the amelioration of AS following FMT from PU-treated mice into ApoE-/- mice fed HFD. Specifically, PU reduced the abundance of P. copri, which exacerbated AS by producing trimethylamine (TMA). Prolonged mono-colonisation of P. copri undermines the beneficial effects of PU on AS. In clinical, the plaque scores of AS patients were positively correlated with the abundance of P. copri and plasma trimethylamine-N-oxide (TMAO) levels. A 1-week oral intervention with PU effectively decreased P. copri levels and reduced TMAO concentrations in patients with carotid artery plaque. CONCLUSION: PU may provide therapeutic benefits in combating AS by targeting P. copri and its production of TMA. TRIAL REGISTRATION NUMBER: ChiCTR1900022488.

Carbonaceous particulate matter promotes the horizontal transfer of antibiotic resistance genes.

There is growing concern about the transfer of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in airborne particulate matter. In this study, we investigated the effects of various types of carbonaceous particulate matter (CPM) on the transfer of ARGs in vitro. The results showed that CPM promoted the transfer of ARGs, which was related to the concentration and particle size. Compared with the control group, the transfer frequency was 95.5, 74.7, 65.4, 14.7, and 3.8 times higher in G (graphene), CB (carbon black), NGP (nanographite powder), GP1.6 (graphite powder 1.6 micron), and GP45 (graphite powder 45 micron) groups, respectively. Moreover, the transfer frequency gradually increased with the increase in CPM concentration, while there was a negative relationship between the CPM particle size and conjugative transfer frequency. In addition, the results showed that CPM could promote the transfer of ARGs by increasing ROS, as well as activating the SOS response and expression of conjugative transfer-related genes (trbBp, trfAp, korA, kroB, and trbA). These findings are indicative of the potential risk of CPM for the transfer of ARGs in the environment, enriching our understanding of environmental pollution and further raising awareness of environmental protection.

SIRT2 promotes base excision repair by transcriptionally activating OGG1 in an ATM/ATR-dependent manner.

Sirtuin 2 (SIRT2) regulates the maintenance of genome integrity by targeting pathways of DNA damage response and homologous recombination repair. However, whether and how SIRT2 promotes base excision repair (BER) remain to be determined. Here, we found that independent of its catalytic activity SIRT2 interacted with the critical glycosylase OGG1 to promote OGG1 recruitment to its own promoter upon oxidative stress, thereby enhancing OGG1 promoter activity and increasing BER efficiency. Further studies revealed that SIRT2 was phosphorylated on S46 and S53 by ATM/ATR upon oxidative stress, and SIRT2 phosphorylation enhanced the SIRT2-OGG1 interaction and mediated the stimulatory effect of SIRT2 on OGG1 promoter activity. We also characterized 37 cancer-derived SIRT2 mutants and found that 5 exhibited the loss of the stimulatory effects on OGG1 transcription. Together, our data reveal that SIRT2 acts as a tumor suppressor by promoting OGG1 transcription and increasing BER efficiency in an ATM/ATR-dependent manner.

Palmitoylation is required for Sept8-204 and Sept5 to form vesicle-like structure and colocalize with synaptophysin.

Sept8 is a vesicle associated protein and there are two typical transcriptional variants (Sept8-204 and Sept8-201) expressed in mice brain. Interestingly, the coexpression of Sept8-204/Sept5 induces the formation of small sized vesicle-like structure, while that of the Sept8-201/Sept5 produces large puncta. Sept8 is previously shown to be palmitoylated. Here it was further revealed that protein palmitoylation is required for Sept8-204/Sept5 to maintain small sized vesicle-like structure and colocalize with synaptophysin, since either the expression of nonpalmitoylated Sept8-204 mutant (Sept8-204-3CA) or inhibiting Sept8-204 palmitoylation by 2-BP with Sept5 produces large puncta, which barely colocalizes with synaptophysin (SYP). Moreover, it was shown that the dynamic palmitoylation of Sept8-204 is controlled by ZDHHC17 and PPT1, loss of ZDHHC17 decreases Sept8-204 palmitoylation and induces large puncta, while loss of PPT1 increases Sept8-204 palmitoylation and induces small sized vesicle-like structure. Together, these findings suggest that palmitoylation is essential for the maintenance of the small sized vesicle-like structure for Sept8-204/Sept5, and may hint their important roles in synaptic functions.

Printed smart devices for anti-counterfeiting allowing precise identification with household equipment.

Counterfeiting has become a serious global problem, causing worldwide losses and disrupting the normal order of society. Physical unclonable functions are promising hardware-based cryptographic primitives, especially those generated by chemical processes showing a massive challenge-response pair space. However, current chemical-based physical unclonable function devices typically require complex fabrication processes or sophisticated characterization methods with only binary (bit) keys, limiting their practical applications and security properties. Here, we report a flexible laser printing method to synthesize unclonable electronics with high randomness, uniqueness, and repeatability. Hexadecimal resistive keys and binary optical keys can be obtained by the challenge with an ohmmeter and an optical microscope. These readout methods not only make the identification process available to general end users without professional expertise, but also guarantee device complexity and data capacity. An adopted open-source deep learning model guarantees precise identification with high reliability. The electrodes and connection wires are directly printed during laser writing, which allows electronics with different structures to be realized through free design. Meanwhile, the electronics exhibit excellent mechanical and thermal stability. The high physical unclonable function performance and the widely accessible readout methods, together with the flexibility and stability, make this synthesis strategy extremely attractive for practical applications.

Flash phase engineering of MoS2 nanofilms for enhanced photoelectrochemical performance.

A heterophase structure combining semiconducting 2H- and metallic 1T-MoS2 exhibits significantly enhanced photoelectrochemical performance due to the electrical coupling and synergistic effect between the phases. Therefore, site-selective effective phase engineering is crucial for the fabrication of MoS2-based photoelectrochemical devices. Here, we employed a flash phase engineering (FPE) strategy to precisely fabricate a 2H-1T heterophase structure. This technique allows simple, efficient, and precise control over the micropatterning of MoS2 nanofilms while enabling site-selective phase transition from the 1T to the 2H phase. The detection of reduced glutathione (GSH) showed an approximately 5-fold increase in sensitivity when using the electrode fabricated by FPE.

Effect of surface functionalization on DNA sequencing using MXene-based nanopores.

As one of the most promising types of label-free nanopores has great potential for DNA sequencing via fast detection of different DNA bases. As one of the most promising types of label-free nanopores, two-dimensional nanopore materials have been developed over the past two decades. However, how to detect different DNA bases efficiently and accurately is still a challenging problem. In the present work, the translocation of four homogeneous DNA strands (i.e., poly(A)20, poly(C)20, poly(G)20, and poly(T)20) through two-dimensional transition-metal carbide (MXene) membrane nanopores with different surface terminal groups is investigated via all-atom molecular dynamics simulations. Interestingly, it is found that the four types of bases can be distinguished by different ion currents and dwell times when they are transported through the Ti3C2(OH)2 nanopore. This is mainly attributed to the different orientation and position distributions of the bases, the hydrogen bonding inside the MXene nanopore, and the interaction of the ssDNA with the nanopore. The present study enhances the understanding of the interaction between DNA strands and MXene nanopores with different functional groups, which may provide useful guidelines for the design of MXene-based devices for DNA sequencing in the future.

The care needs of the elderly in China's elderly care institutions: a narrative synthesis.

China's population is ageing, affecting trends in social development and basic national conditions. More attention must be paid to the lack of care needs assessments for the elderly in China's pension institutions. This paper discusses a systematic evaluation of the care needs of the elderly in China's elderly care institutions. Literature was collected and synthesized after a search of the Web of Science, PubMed, and other databases for works published up to August 2021. Relevant content is proposed, including the name of the first author, publication date, study area, and sample size. Exactly 18 articles were included in the literature, documents that reported on a total of 7277 elderly people. The results showed a combined demand rate of primary care needs ≥50%. The top five needs included mental/psychological (76%), tranquillity/care (73%), living/environmental (71%), medical treatment (64%), and preventive healthcare (64%). The combined demand rate of secondary care needs was ≥50%. The top five needs included 79% for room/laundry/cleaning, 77% for psychological comfort and nursing, 73% for end-of-life care, 70% for disease diagnosis and treatment, and 69% for physical examination. The health needs of older people are diverse and focus mainly on mental/psychological, tranquility/care, living/environmental (71%), pharmacotherapy, and preventive healthcare.

Development of a P-tau217 Electrochemiluminescent Immunosensor Reinforced with Au-Cu Nanoparticles for Alzheimer's Disease Precaution.

To simply and rapidly detect the highly phosphorylated tau protein at threonine 217 (p-tau217) as a precautionary measure against Alzheimer's disease and distinguish it from other neurodegenerative diseases, a novel immunosensor was prepared using luminol as the electrochemiluminescent (ECL) sensing probe reinforced by Au-Cu nanoparticles (Au-Cu NPs). The Au-Cu alloy NPs were prepared via a co-reduction reaction, exhibiting excellent conductivity and catalytic activity. These properties remarkably enhanced the ECL of luminol, providing a suitable background for the sensing response. After the Au-Cu NPs were decorated on the surface of indium tin oxide glass using 3-amino-propyl trimethoxysilane, the antibody of p-tau217 was immobilized via dominant Au-N bonding to enable the biological specificity of the immunosensor. When p-tau217 specifically interacted with an antibody to form an immune complex on the sensing interface, the ECL signal of the sensor was considerably inhibited by the resulting giant biomolecular complex. This complex prevented luminol diffusion to the electrode surface and electron transfer. The resulting immunosensor showed remarkable sensitivity to p-tau217, with a wide linear detection range from 5 to 600 pg/mL. A detection limit of 0.56 pg/mL was achieved, with recoveries in human serum ranging from 92.3 to 109%. This ECL immunosensor demonstrated high sensitivity and specificity toward p-tau217, along with good reproducibility and stability, providing a new approach for clinical research on Alzheimer's disease.

Exploring the non-monotonic DNA capture behavior in a charged graphene nanopore.

Nanopore-based biomolecule detection has emerged as a promising and sought-after innovation, offering high throughput, rapidity, label-free analysis, and cost-effectiveness, with potential applications in personalized medicine. However, achieving efficient and tunable biomolecule capture into the nanopore remains a significant challenge. In this study, we employ all-atom molecular dynamics simulations to investigate the capture of double-stranded DNA (dsDNA) molecules into graphene nanopores with varying positive charges. We discover a non-monotonic relationship between the DNA capture rate and the charge of the graphene nanopore. Specifically, the capture rate initially decreases and then increases with an increase in nanopore charge. This behavior is primarily attributed to differences in the electrophoretic force, rather than the influence of electroosmosis or counterions. Furthermore, we also observe this non-monotonic trend in various ionic solutions, but not in ionless solutions. Our findings shed light on the design of novel DNA sequencing devices, offering valuable insights into enhancing biomolecule capture rates in nanopore-based sensing platforms.

Small-Molecule Probe-Induced In Situ-Sensitized Photoelectrochemical Biosensor for Monitoring α-Glucosidase Activity.

Semiconductor-based photoelectrochemical (PEC) biosensors have garnered significant attention in the field of disease diagnosis and treatment. However, the recognition units of these biosensors are mainly limited to bioactive macromolecules, which hinder the photoelectric response due to their insulating characteristics. In this study, we develop an in situ-sensitized strategy that utilizes a small-molecule probe at the interface of the photoelectrode to accurately detect α-glucosidase (α-Glu) activity. Silane, a prototype small-molecule probe, was surface-modified on graphitic carbon nitride to generate Si nanoparticles upon reacting with hydroquinone, the enzymatic product of α-Glu. The in situ formed heterojunction enhances the light-harvesting property and photoexcited carrier separation efficiency. As a result, the in situ-sensitized PEC biosensor demonstrates excellent accuracy, a low detection limit, and outstanding anti-interference ability, showing good applicability in evaluating α-Glu activity and its inhibitors in human serum samples. This novel in situ sensitization approach using small-molecule probes opens up new avenues for developing simple and efficient PEC biosensing platforms by replacing conventional biorecognition elements.

Computed tomography radiomic features and clinical factors predicting the response to first transarterial chemoembolization in intermediate-stage hepatocellular carcinoma.

BACKGROUND: According to clinical practice guidelines, transarterial chemoembolization (TACE) is the standard treatment modality for patients with intermediate-stage hepatocellular carcinoma (HCC). Early prediction of treatment response can help patients choose a reasonable treatment plan. This study aimed to investigate the value of the radiomic-clinical model in predicting the efficacy of the first TACE treatment for HCC to prolong patient survival. METHODS: A total of 164 patients with HCC who underwent the first TACE from January 2017 to September 2021 were analyzed. The tumor response was assessed by modified response evaluation criteria in solid tumors (mRECIST), and the response of the first TACE to each session and its correlation with overall survival were evaluated. The radiomic signatures associated with the treatment response were identified by the least absolute shrinkage and selection operator (LASSO), and four machine learning models were built with different types of regions of interest (ROIs) (tumor and corresponding tissues) and the model with the best performance was selected. The predictive performance was assessed with receiver operating characteristic (ROC) curves and calibration curves. RESULTS: Of all the models, the random forest (RF) model with peritumor (+10 mm) radiomic signatures had the best performance [area under ROC curve (AUC) = 0.964 in the training cohort, AUC = 0.949 in the validation cohort]. The RF model was used to calculate the radiomic score (Rad-score), and the optimal cutoff value (0.34) was calculated according to the Youden's index. Patients were then divided into a high-risk group (Rad-score > 0.34) and a low-risk group (Rad-score ≤ 0.34), and a nomogram model was successfully established to predict treatment response. The predicted treatment response also allowed for significant discrimination of Kaplan-Meier curves. Multivariate Cox regression identified six independent prognostic factors for overall survival, including male [hazard ratio (HR) = 0.500, 95% confidence interval (CI): 0.260-0.962, P = 0.038], alpha-fetoprotein (HR = 1.003, 95% CI: 1.002-1.004, P < 0.001), alanine aminotransferase (HR = 1.003, 95% CI: 1.001-1.005, P = 0.025), performance status (HR = 2.400, 95% CI: 1.200-4.800, P = 0.013), the number of TACE sessions (HR = 0.870, 95% CI: 0.780-0.970, P = 0.012) and Rad-score (HR = 3.480, 95% CI: 1.416-8.552, P = 0.007). CONCLUSIONS: The radiomic signatures and clinical factors can be well-used to predict the response of HCC patients to the first TACE and may help identify the patients most likely to benefit from TACE.

Engineering the microenvironment of electron transport layers with nickle single-atom sites for boosting photoelectrochemical performance.

Advances in the rational design of semiconductor-electrocatalyst photoelectrodes provide robust driving forces for improving energy conversion and quantitative analysis, while a deep understanding of elementary processes remains underwhelming due to the multistage interfaces involved in semiconductor/electrocatalyst/electrolyte. To address this bottleneck, we have constructed carbon-supported nickel single atoms (Ni SA@C) as an original electron transport layer with catalytic sites of Ni-N4 and Ni-N2O2. This approach illustrates the combined effect of photogenerated electron extraction and the surface electron escape ability of the electrocatalyst layer in the photocathode system. Theoretical and experimental studies reveal that Ni-N4@C, with excellent oxygen reduction reaction catalytic activity, is more beneficial for alleviating surface charge accumulation and facilitating electrode-electrolyte interfacial electron-injection efficiency under a similar built-in electric field. This instructive method enables us to engineer the microenvironment of the charge transport layer for steering the interfacial charge extract and reaction kinetics, providing a great prospect for atomic scale materials to enhance photoelectrochemical performance.

Improving Interface Matching in MOF-on-MOF S-Scheme Heterojunction through π-π Conjugation for Boosting Photoelectric Response.

Accelerating the migration of interfacial carriers in a heterojunction is of paramount importance for driving high-performance photoelectric responses. However, the inferior contact area and large resistance at the interface limit the eventual photoelectric performance. Herein, we fabricated an S-scheme heterojunction involving a 2D/2D dual-metalloporphyrin metal-organic framework with metal-center-regulated CuTCPP(Cu)/CuTCPP(Fe) through electrostatic self-assembly. The ultrathin nanosheet-like architectures reduce the carrier migration distance, while the similar porphyrin backbones promote reasonable interface matching through π-π conjugation, thereby inhibiting the recombination of photogenerated carriers. Furthermore, the metal-center-regulated S-scheme band alignments create a giant built-in electric field, which provides a huge driving force for efficient carrier separation and migration. Coupling with the biomimetic catalytic activity of CuTCPP(Fe), the resultant heterojunction was utilized to construct photoelectrochemical uric acid biosensors. This work provides a general strategy to enhance photoelectric responses by engineering the interfacial structure of heterojunctions.

Horseradish Peroxidase Immobilized in Metal Aerogels Boosts Electron Transfer and an Interfacial Reaction for Photoelectrochemical Immunoassay.

Photoelectrochemical (PEC) enzymatic biosensors have attracted widespread attention for their specificity and sensitivity, but the charge migration between an enzyme and a semiconductor remains uncertain. In this work, horseradish peroxidase (HRP) was successfully immobilized on ionic liquid-functioned Cu@Cu2O (IL-Cu@Cu2O) aerogels to boost charge transfer and an interfacial redox reaction. The photogenerated electrons flow from the conduction band of Cu2O to HRP under the assistance of Cu and are subsequently captured by [Fe(CN)6]3- in the electrolyte, which boosts the PEC response. The improved interfacial catalytic ability after the immobilization of HRP is proved by the enhanced redox ability under light irradiation. Benefiting from the excellent PEC activity and catalysis reaction of IL-Cu@Cu2O@HRP, an immunoassay platform was constructed for sensing prostate-specific antigens, which presents a wide detection range and a low limit of detection. An in-depth understanding of the direct electronic communication between a photoactive material and an enzyme for boosted charge transfer and interfacial catalysis provides a new view for the design of advanced PEC sensing platforms.

Integrating machine learning and bioinformatics analysis to m6A regulator-mediated methylation modification models for predicting glioblastoma patients' prognosis and immunotherapy response.

BACKGROUND: Epigenetic regulations of immune responses are essential for cancer development and growth. As a critical step, comprehensive and rigorous explorations of m6A methylation are important to determine its prognostic significance, tumor microenvironment (TME) infiltration characteristics and underlying relationship with glioblastoma (GBM). METHODS: To evaluate m6A modification patterns in GBM, we conducted unsupervised clustering to determine the expression levels of GBM-related m6A regulatory factors and performed differential analysis to obtain m6A-related genes. Consistent clustering was used to generate m6A regulators cluster A and B. Machine learning algorithms were implemented for identifying TME features and predicting the response of GBM patients receiving immunotherapy. RESULTS: It is found that the m6A regulatory factor significantly regulates the mutation of GBM and TME. Based on Europe, America, and China data, we established m6Ascore through the m6A model. The model accurately predicted the results of 1206 GBM patients from the discovery cohort. Additionally, a high m6A score was associated with poor prognoses. Significant TME features were found among the different m6A score groups, which demonstrated positive correlations with biological functions (i.e., EMT2) and immune checkpoints. CONCLUSIONS: m6A modification was important to characterize the tumorigenesis and TME infiltration in GBM. The m6Ascore provided GBM patients with valuable and accurate prognosis and prediction of clinical response to various treatment modalities, which could be useful to guide patient treatments.

Difference in hepatotoxicity of furan-containing components in cortex dictamni correlates the efficiency of their metabolic activation.

BACKGROUND: Cortex Dictamni (CD) has been associated with an increased risk of liver injury, which may be attributable to the metabolic activation of its furan-containing components (FCC). However, the hepatotoxic potencies of these FCCs and the mechanisms behind the differences in their toxicity intensity remain unknown. METHODS: The constituents of CD extract were determined by LC-MS/MS. Potentially toxic FCCs were screened by a previously published method. Hepatotoxicity of potentially toxic FCCs was evaluated in cultured mouse primary hepatocytes and mice. The ability to deplete hepatic glutathione (GSH), along with the formation of the corresponding GSH conjugates, resulting from the metabolic activation was determined ex vivo in mice. Intrinsic clearance rates (CLint,Vmax/Km) were assessed by a microsome-bases assay. RESULTS: A total of 18 FCCs were detected in CD extract. Among them, four FCCs, including rutaevin (RUT), limonin (LIM), obacunone (OBA) and fraxinellone (FRA) were found to be bioactivated in microsomal incubations. Only FRA displayed significant hepatotoxicity in vitro and in vivo. Similarly, FRA caused GSH depletion and GSH conjugation the most in vivo. The order of CLint for the four FCCs was FRA>>OBA>LIM>RUT. CONCLUSION: FRA is the major toxic FCC component of hepatotoxic CD extract. The hepatotoxicity of FCCs is closely related to the efficiency of their metabolic activation.